Pediatric Emergency Medicine

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PEDIATRIC EMERGENCY MEDICINE Copyright © 2008 by Saunders, an imprint of Elsevier Inc.

ISBN: 978-1-4160-0087-7

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Notice Knowledge and best practice in this field are constantly changing. As new research and experience broaden our knowledge, changes in practice, treatment and drug therapy may become necessary or appropriate. Readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of the practitioner, relying on their own experience and knowledge of the patient, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the Editors assumes any liability for any injury and/or damage to persons or property arising out or related to any use of the material contained in this book. The Publisher Library of Congress Cataloging-in-Publication Data Pediatric emergency medicine / [edited by] Jill M. Baren . . . [et al.]. p. ; cm. Includes bibliographical references and index. ISBN-13: 978-1-4160-0087-7 ISBN-10: 1-4160-0087-9 1. Pediatric emergencies. I. Baren, Jill M. [DNLM: 1. Emergencies. 2. Child. 3. Critical Care—methods. 205 P3712 2007] RJ370.P45153 2007 618.92′0025—dc22

4. Infant.

WS 2007018571

Acquisitions Editor: Maria Lorusso Developmental Editor: Joanie Milnes Project Manager: David Saltzberg Design Direction: Steven Stave

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To my husband Kenneth—I am truly grateful for your endless love, support of our family life, and pride in my career, for without those things, this book and all of my work would not exist. To my sons Noah and Andrew—I am continually amazed by your gifts of love, patience, and wisdom beyond your years. You have made every minute of my life worthwhile. To my parents—you gave me the right start and never stopped encouraging me to be what I wanted to be. To an extraordinary mentor, James S. Seidel, MD, PhD, who opened many doors in the world of pediatric emergency medicine and encouraged me to go through them. To my co-editors John, Lance, and Steve—thank you for your friendship, creativity, humor, persistence, high standards, and the countless hours you spent making this a reality. Jill Baren

I dedicate this work to the two loves of my life—my wife Angela, and my daughter Ava. It is my hope that this text serves to help protect, repair and sustain the health and lives of children and parents everywhere. Steve Rothrock

To my wife, Mary Beth, and our children, Kelly, Matthew and Colleen for all their help, love and patience. To my friends and colleagues for all the support and mentoring they have given me over the past 25 years. Especially to all the children and parents who, in a time of crisis, put their faith and confidence in our care. John A. Brennan

To acutely ill and injured children and the professionals who care for them. Lance Brown

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Contributors Fredrick M. Abrahamian, DO, FACEP Assistant Professor of Medicine, UCLA School of Medicine, Los Angeles; Director of Education, Department of Emergency Medicine, Olive View-UCLA Medical Center, Sylmar, California Tetanus Prophylaxis; Rabies Postexposure Prophylaxis Thomas J. Abramo, MD, FAAP, FACEP Professor of Emergency Medicine and Pediatrics, Director, Pediatric Emergency Department, Medical Director of Pediatric Transport, and Pediatric Emergency Phyisician-in-Chief, Department of Emergency Medicine, Vanderbilt University Medical Center, Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville, Tennessee Monitoring in Critically Ill Children Robert Acosta, MD Assistant Professor, Department of Pediatrics, Albert Einstein College of Medicine; Attending Physician, Department of Pediatric Emergency Medicine, Jacobi Medical Center, Bronx, New York Rhinosinusitis Paula Agosto, RN, MHA Director of Nursing, Emergency, Critical Care, and Transport, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania Burns Coburn Allen, MD Assistant Professor of Pediatrics, Baylor College of Medicine; Attending Physician, Texas Children’s Hospital, Houston, Texas Bone, Joint, and Spine Infections Elizabeth R. Alpern, MD, MSCE Assistant Professor, Department of Pediatrics, University of Pennsylvania School of Medicine; Attending Physician, Division of Emergency Medicine, Department of Pediatrics, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania Bacteremia Jesus M. Arroyo, MD Assistant Professor of Emergency Medicine, Department of Emergency Medicine, University of Texas Medical School at Houston, Houston, Texas Sepsis

Miriam Aschkenasy, MD, MPH Assistant Professor, Boston University School of Medicine; Attending Physician, Boston Medical Center, Boston, Massachusetts Ear Diseases Peter S. Auerbach, MD, FAAEM, FAAP Attending Physician, Department of Emergency Medicine, Inova Fairfax Hospital and Inova Fairfax Hospital for Children, Falls Church, Virginia Pelvic and Genitourinary Trauma Franz E. Babl, MD, MPH Clinical Associate Professor, University of Melbourne; Pediatric Emergency Physician, Royal Children’s Hospital, Melbourne, Victoria, Australia Central Nervous System Vascular Disorders; VaccinationRelated Complaints and Side Effects Michael C. Bachman, MD, MBA Assistant Medical Director, Department of Pediatric Emergency Medicine, and Pediatric Emergency Medicine Fellowship Director, Newark Beth Israel Medical Center, Newark, New Jersey Eye Disorders Megan H. Bair-Merritt, MD, MSCE Assistant Professor, Division of General Pediatrics and Adolescent Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland Interpersonal and Intimate Partner Violence Roger A. Band, MD Department of Emergency Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania Penile and Testicular Disorders Isabel Barata, MD Assistant Professor of Pediatrics, New York University Medical School, New York; Director of Pediatric Emergency Medicine, North Shore University Hospital, Manhasset, New York Neurovascular Injuries Besh Barcega, MD, MBA Assistant Professor, Emergency Medicine and Pediatrics, Loma Linda University School of Medicine; Medical Director, Pediatric Emergency Department, Loma Linda University Children’s Hospital and Medical Center, Loma Linda, California Lower Extremity Trauma vii

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Contributors

Jill M. Baren, MD, MBE, FACEP, FAAP Associate Professor of Emergency Medicine and Pediatrics, University of Pennsylvania School of Medicine; Department of Emergency Medicine, Hospital of the University of Pennsylvania; Division of Emergency Medicine, Department of Pediatrics, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania End-of-Life Issues Beverly H. Bauman, MD Department of Emergency Medicine, Oregon Health and Sciences University, Portland, Oregon Ovarian Disorders; Vaginal and Urethral Disorders Lee S. Benjamin, MD Assistant Professor, Division of Emergency Medicine, Department of Surgery, and Division of Pediatric Emergency Medicine, Department of Pediatrics, Duke University School of Medicine; Interim Associate Medical Director of Pediatric Emergency Medicine, Duke University Medical Center, Durham, North Carolina Serum Sickness Suzanne M. Beno, MD Assistant Professor, Faculty of Medicine and Dentistry, University of Alberta; Faculty, Division of Pediatric Emergency Medicine, The Stollery Children’s Hospital, Edmonton, Alberta, Canada; Formerly Clinical Instructor, University of Pennsylvania School of Medicine; Fellow, Pediatric Emergency Medicine, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania Anaphylaxis; Renal Disorders Deena Berkowitz, MD, MPH Adjunct Professor, Department of Pediatrics, George Washington University of Medicine; Attending, Emergency Department, Children’s National Medical Center, Washington, DC Lumbar Puncture Jason E. Bernad, MD Attending Physician—Emergency Medicine, Saratoga Hospital, Saratoga Springs, New York Wound Management Daan Biesbroeck, MD Attending Emergency Department Staff, OLVG Hospital, Amsterdam, The Netherlands Urinary Tract Infections in Children and Adolescents

Boura’a Bou Aram, MD Department of Pediatrics, State University of New York Upstate Medical University, Syracuse, New York Hemolytic-Uremic Syndrome; Utilizing Blood Bank Resources/Transfusion Reactions and Complications John C. Brancato, MD Assistant Professor of Pediatrics and Emergency Medicine, University of Connecticut School of Medicine, Farmington; Attending Physician, Division of Emergency Medicine, Connecticut Children’s Medical Center, Hartford, Connecticut Abdominal Hernias; Metabolic Acidosis; Metabolic Alkalosis Daniel F. Brennan, MD Clinical Associate Professor, Department of Emergency Medicine, University of Florida College of Medicine, Gainesville; Clinical Associate Professor, Department of Clinical Sciences, Florida State University College of Medicine, Orlando Campus, Tallahassee; Attending Physician, Department of Emergency Medicine, Emergency Medicine Residency Program, Orlando Regional Medical Center, Orlando, Florida Ectopic Pregnancy John A. Brennan, MD, FACEP, FAAP Executive Director, Newark Beth Israel Medical Center and the Children’s Hospital of New Jersey, Newark, New Jersey; Senior Vice President for Clinical and Emergency Services, and Director, Pediatric Emergency Medicine, Saint Barnabas Health Care System, West Orange, New Jersey The Sick or Injured Child in a Community Hospital Emergency Department; Patient Safety, Medical Errors, and Quality of Care; Hernia Reduction Allison V. Brewer, MD Attending Physician, Mercy Hospital, Portland, Maine Musculoskeletal Disorders in Systemic Disease Kenneth B. Briskin, MD, FACS Associate Clinical Professor, Temple University, Philadelphia; Assistant Clinical Professor, University of Pennsylvania, Philadelphia, Pennsylvania; Chief, Division of Otolaryngology, Crozer-Chester Medical Center, Upland, Pennsylvania Epistaxis; Epistaxis Control

Jeffrey S. Blake, MD Pediatric Emergency Medicine Fellow, Division of Emergency Medicine, Children’s National Medical Center, Washington, DC Gastrointestinal Bleeding

Kathleen Brown, MD Assistant Professor of Pediatrics and Emergency Medicine, George Washington University School of Medicine; Medical Unit Director, Pediatric Emergency Medicine, Children’s National Medical Center, Washington, DC Lumbar Puncture

Frederick C. Blum, MD, FACEP Associate Professor of Emergency Medicine and Pediatrics, West Virginia University School of Medicine, Department of Emergency Medicine, Ruby Memorial Hospital, Morgantown, West Virginia Abdominal Trauma

Lance Brown, MD, MPH, FACEP, FAAP Chief, Division of Pediatric Emergency Medicine, and Associate Professor of Emergency Medicine and Pediatrics, Loma Linda University Medical Center and Children’s Hospital, Loma Linda, California Approach to Multisystem Trauma; Excessive Crying

Contributors

Linda L. Brown, MD, MSCE Assistant Professor of Pediatrics, Yale University School of Medicine; Attending, Pediatric Emergency Medicine, Yale-New Haven Children’s Hospital, New Haven, Connecticut Dental Disorders

Marina Catallozzi, MD Assistant Professor of Clinical Pediatrics and Population and Family Health, Columbia University—College of Physicians and Surgeons, Mailman School of Public Health, New York, New York Human Immunodeficiency Virus Infection and Other Immunosuppressive Conditions

Michael D. Burg, MD, FACEP Assistant Clinical Professor of Emergency Medicine, Department of Emergency Medicine, University of California, San Francisco-Fresno, University Medical Center, Fresno, California Upper Extremity Trauma

Esther H. Chen, MD Assistant Professor, University of Pennsylvania; Attending Physician, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania Postexposure Prophylaxis

Sean P. Bush, MD, FACEP Professor of Emergency Medicine, Department of Emergency Medicine, Loma Linda University School of Medicine; Director, Fellowship of Envenomation Medicine, Department of Emergency Medicine, Loma Linda University Medical Center, Loma Linda, California Snake and Spider Envenomations James M. Callahan, MD Associate Professor of Clinical Pediatrics, Department of Pediatrics, Division of Emergency Medicine, University of Pennsylvania School of Medicine; Director, Medical Education, Emergency Department, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania Wound Management Richard M. Cantor, MD Associate Professor of Emergency Medicine and Pediatrics, Upstate Medical University; Director, Pediatric Emergency Services, University Hospital, Syracuse, New York Neonatal Resuscitation; Common Pediatric Overdoses Nicole P. Carbonell, MD Resident, School of Medicine, University of Alabama at Birmingham; Resident, Department of Emergency Medicine, University Hospital, University of Alabama at Birmingham, Birmingham, Alabama Thoracostomy Eric T. Carter, MD Assistant Medical Director, Emergency Department, South Lake Hospital, Clermont, Florida Hypokalemia; Hyperkalemia; Hypocalcemia David D. Cassidy, MD Clinical Assistant Professor, Department of Emergency Medicine, University of Florida College of Medicine, Gainesville; Clinical Assistant Professor, Department of Clinical Sciences, Florida State University College of Medicine, Tallahassee; Assistant Director, Department of Emergency Medicine, and Attending and Ultrasound Director, Emergency Medicine Residency Program, Orlando Regional Medical Center, Orlando, Florida Pyloric Stenosis; Constipation

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Richard E. Chinnock, MD Professor and Chair of Pediatrics, Loma Linda University School of Medicine; Physician-in-Chief, and Director, Pediatric Heart Transplant Program, Loma Linda University Children’s Hospital, Loma Linda, California Postsurgical Cardiac Conditions and Transplantation Christine S. Cho, MD, MPH Assistant Clinical Professor, Department of Pediatrics, University of California San Francisco, San Francisco; Attending Physician, Children’s Hospital and Research Center, Oakland, California Circulatory Emergencies: Shock Thomas H. Chun, MD Assistant Professor, Departments of Emergency Medicine and Pediatrics, Brown University; Attending Physician, Emergency Department, Hasbro Children’s Hospital, Providence, Rhode Island Psychobehavioral Disorders Mark C. Clark, MD, FACEP, FAAP Clinical Associate Professor, Department of Emergency Medicine, University of Florida College of Medicine, Gainesville; Medical Director, Department of Emergency Medicine, Arnold Palmer Hospital for Children, Orlando; Clinical Associate Professor, Department of Clinical Sciences, Florida State University College of Medicine, Tallahassee, Florida Hernia Reduction Robert L. Cloutier, MD Assistant Professor, Department of Emergency Medicine & Pediatrics, Oregon Health & Science University, Portland, Oregon Ovarian Disorders; Vaginal and Urethral Disorders Teresa J. Coco, MD Assistant Professor of Pediatric Emergency Medicine, University of Alabama at Birmingham School of Medicine; Administrator, After Hours Clinic Children’s South, Children’s Hospital of Alabama, Birmingham, Alabama General Approach to Poisoning Arthur Cooper, MD, MS Professor of Surgery, Columbia University College of Physicians & Surgeons; Director of Trauma & Pediatric Surgical Services, Harlem Hospital Center, New York, New York Thoracic Trauma; Abdominal Trauma

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Contributors

James D’Agostino, MD Assistant Professor of Emergency Medicine and Pediatrics, Department of Emergency Medicine, Upstate Medical University, Syracuse, New York Malrotation and Midgut Volvulus Elizabeth M. Datner, MD Associate Professor, University of Pennsylvania School of Medicine; Medical Director, Department of Emergency Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania Pregnancy-Related Complications Sergio V. Delgado, MD Associate Professor, Child and Adolescent Psychiatry, Department of Psychiatry, University of Cincinnati School of Medicine; Medical Director, Outpatient Services, Department of Psychiatry, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio Major Depression and Suicidality T. Kent Denmark, MD Associate Professor of Emergency Medicine and Pediatrics, and Medical Director, Medical Simulation Center, Loma Linda University School of Medicine; Program Director, Pediatric Emergency Medicine, Attending Physician, Pediatric Emergency Department, Loma Linda University Medical Center and Children’s Hospital, Loma Linda, California Inborn Errors of Metabolism; Near Drowning and Submersion Injuries Andrew DePiero, MD Assistant Professor of Pediatrics, Jefferson Medical College, Philadelphia, Pennsylvania; Attending Physician, Division of Emergency Medicine, A.I. duPont Hospital for Children, Wilmington, Delaware Apparent Life-Threatening Events Stephanie J. Doniger, MD, FAAP Pediatric Emergency Medicine Fellow, Children’s Hospital and Health Center/University of California, San Diego, San Diego, California Dysrhythmias Aaron J. Donoghue, MD, MSCE Assistant Professor of Pediatrics and Anesthesia, University of Pennsylvania School of Medicine; Attending Physician, Division of Emergency Medicine and Critical Care Medicine, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania Intubation, Rescue Devices, and Airway Adjuncts Gregory M. Enns, MB, ChB Associate Professor of Pediatrics, and Director, Biomedical Genetics Program, Division of Medical Genetics, Stanford University, Stanford, California Hypoglycemia Mirna M. Farah, MD Assistant Professor, Division of Emergency Medicine, Department of Pediatrics, University of Pennsylvania School of Medicine; Attending Physician, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania Family Presence

Joel A. Fein, MD, MPH Associate Professor of Pediatrics and Emergency Medicine, University of Pennsylvania School of Medicine; Attending Physician, Emergency Department, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania Interpersonal and Intimate Partner Violence George L. Foltin, MD Associate Professor of Pediatrics and Emergency Medicine, New York University School of Medicine; Director, Center for Pediatric Emergency Medicine, Bellevue Hospital Center, New York, New York Thoracic Trauma; Abdominal Trauma; Emergency Medical Services and Transport Eron Y. Friedlaender, MD, MPH Assistant Professor of Clinical Pediatrics, University of Pennsylvania School of Medicine; Attending Physician, Division of Emergency Medicine, Department of Pediatrics, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania Cystic Fibrosis Susan Fuchs, MD Professor of Pediatrics, Feinberg School of Medicine, Northwestern University; Associate Director, Division of Pediatric Emergency Medicine, Children’s Memorial Hospital, Chicago, Illinois The Child-Friendly Emergency Department: Practices, Policies, and Procedures Gregory Garra, DO Assistant Clinical Professor of Emergency Medicine, Stony Brook University School of Medicine; Emergency Medicine Residency Program Director, Stony Brook University Hospital, Stony Brook, New York Removal of Ocular Foreign Bodies; Fracture Reduction and Splinting Techniques Marianne Gausche-Hill, MD Professor of Clinical Medicine, David Geffen School of Medicine at UCLA, Los Angeles; Director, EMS and Pediatric Emergency Medicine Fellowships, HarborUCLA Medical Center, Torrance, California Respiratory Distress and Respiratory Failure Barry G. Gilmore, MD, MSW Associate Professor of Pediatrics, Department of Pediatrics, University of Tennessee Health Sciences Center College of Medicine; Attending Physician, and Director of Emergency Services, Division of Emergency Services, LeBonheur Children’s Medical Center, Memphis, Tennessee Disorders of Movement; Ultrasonography Timothy G. Givens, MD Associate Professor, Emergency Medicine and Pediatrics, Vanderbilt University Medical Center; Associate Medical Director, and Fellowship Director, Pediatric Emergency Medicine, Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville, Tennessee Sickle Cell Disease

Contributors

Nicole Glaser, MD Associate Professor of Pediatrics, University of California, Davis, School of Medicine; Department of Pediatrics, University of California, Davis, Medical Center, Sacramento, California Diabetic Ketoacidosis; Hypoglycemia Theodore E. Glynn, MD Department of Emergency Medicine, Ingham Regional Medical Center, Lansing; Assistant Clinical Professor, Michigan State University, East Lansing, Michigan Syncope Ran D. Goldman, MD Division Head and Medical Director, Division of Pediatric Emergency Medicine, BC Children’s Hospital; Associate Professor, Department of Pediatrics, University of British Columbia; Senior Associate Clinician Scientist, Child & Family Research Institute (CFRI), Vancouver, British Columbia, Canada Oral, Ocular, and Maxillofacial Trauma Marc H. Gorelick, MD, MSCE Professor of Pediatrics and Population Health, Medical College of Wisconsin; Jon E. Vice Chair in Emergency Medicine, Children’s Hospital of Wisconsin, Milwaukee, Wisconsin Urinary Tract Infection in Infants Vincent J. Grant, MD, FRCP(C), FAAP Assistant Professor, Division of Pediatric Emergency Medicine, Department of Pediatrics, University of Ottawa; Medical Director, Trauma Program, Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada Head Trauma Steven M. Green, MD Professor of Emergency Medicine and Pediatrics, Loma Linda University, Loma Linda, California Procedural Sedation and Analgesia Victoria S. Gregg, MD Assistant Professor of Pediatrics, Baylor College of Medicine; Attending Physician, Emergency Department, Texas Children’s Hospital, Houston, Texas Overuse Syndromes and Inflammatory Conditions Jacqueline Grupp-Phelan, MD, MPH Associate Professor of Clinical Pediatrics, University of Cincinnati College of Medicine; Assistant Professor of Clinical Pediatrics, Division of Emergency Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio Major Depression and Suicidality Martin I. Herman, MD Professor of Pediatrics, University of Tennessee Health Sciences Center College of Medicine; Attending Physician, Director of Urgent Care Services, and Assistant Director, Emergency Services, LeBonheur Children’s Medical Center, Memphis, Tennessee Disorders of Movement; Testicular Torsion

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Marilyn P. Hicks, MD* Director of Pediatric Emergency Medicine Education, Department of Emergency Medicine, WakeMed Health Systems, Raleigh; Adjunct Assistant Professor of Emergency Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina Excessive Crying Nancy E. Holecek, RN Senior Vice President for Patient Care Services, Saint Barnabas Health Care System, West Orange New Jersey Patient Safety, Medical Errors, and Quality of Care Mark A. Hostetler, MD, MPH, FACEP, FAAP Associate Professor, Department of Pediatrics, and Chief, Section of Pediatric Emergency Medicine, The University of Chicago, Pritzker School of Medicine; Medical Director, Pediatric Emergency Department, The University of Chicago Comer Children’s Hospital, Chicago, Illinois Inhalation Exposures Vivian Hwang, MD Assistant Clinical Professor of Emergency Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC; Attending Physician, Inova Fairfax Hospital, Falls Church, Virginia Muscle and Connective Tissue Disorders Alson S. Inaba, MD, PALS-NF Associate Professor of Pediatrics, University of Hawaii John A. Burns School of Medicine; Pediatric Emergency Medicine Attending Physician and Course Director, Kapiolani Medical Center for Women and Children; Course Director, Pediatric Advanced Life Support, The Queen’s Medical Center; Pediatric Advanced Life Support National Faculty and PROAD Subcommittee, American Heart Association National ECC Committee, Honolulu, Hawaii Congenital Heart Disease Sean F. Isaak, MD Clinical Assistant Professor, Department of Clinical Sciences, Florida State University College of Medicine, Tallahassee; Attending Emergency Medicine, Department of Emergency Medicine, Orlando Regional Healthcare, Orlando, Florida Incision and Drainage Paul Ishimine, MD Assistant Clinical Professor, Departments of Medicine and Pediatrics, University of California, San Diego, School of Medicine; Director, Pediatric Emergency Medicine, Department of Emergency Medicine, University of California, San Diego, Medical Center; Associate Fellowship Director, Division of Pediatric Emergency Medicine, Rady Children’s Hospital—San Diego, San Diego, California Hyperthermia; Hypothermia

*Deceased

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Contributors

Cynthia R. Jacobstein, MD, MSCE Clinical Assistant Professor of Pediatrics, University of Pennsylvania School of Medicine; Attending Physician, Emergency Department, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania Issues of Consent, Confidentiality and Minor Status

Christopher R. King, MD, FACEP Associate Professor of Emergency Medicine and Pediatrics, University of Pittsburgh School of Medicine, UPMC Presbyterian Hospital, Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania Local and Regional Anesthesia

Gloria Cecelia C. Jacome, MD Emergency Medical Associates, Long Branch, New Jersey Digital Injuries and Infections

Niranjan Kissoon, MD, FRCP(C), FAAP, FCCM, FACPE Professor and Associate Head, Department of Pediatrics, Faculty of Medicine, University of British Columbia; Senior Medical Director, Acute and Critical Care Program, BC Children’s Hospital, Vancouver, British Columbia, Canada Jaundice

David M. Jaffe, MD Dana Brown Professor of Pediatrics, and Director, Division of Emergency Medicine, Washington University, and St. Louis Children’s Hospital, St. Louis, Missouri Fever in the Well-Appearing Young Infant David P. John, MD Director of Quality and Risk Management, Department of Emergency Medicine, Middlesex Healthcare System, Middletown, Connecticut Patient Safety, Medical Errors, and Quality of Care Madeline Matar Joseph, MD Associate Professor of Emergency Medicine and Pediatrics, Chief, Pediatric Emergency Medicine Department, and Medical Director, Pediatric Emergency Department, University of Florida Health Science Center, Jacksonville, Florida Gastrointestinal Foreign Bodies; Hepatitis; Pancreatitis Kelly A. Keogh, MD Assistant Professor of Paediatrics, University of Toronto; Division of Pediatric Emergency Medicine, Hospital for Sick Children Toronto, Ontario, Canada Enterostomy Tubes Nazeema Khan, MD Pediatric Emergency Medicine Attending, Joe DiMaggio Children’s Hospital, Hollywood, Florida Hypertensive Emergencies; Valvular Heart Disease Grace J. Kim, MD Assistant Professor of Emergency Medicine, Loma Linda University School of Medicine; Assistant Program Director, Pediatric Emergency Medicine Fellowship, Loma Linda University Medical Center, Loma Linda, California Postsurgical Cardiac Conditions and Transplantation Tommy Y. Kim, MD Assistant Professor, Department of Pediatric Emergency Medicine, Loma Linda University Medical Center, Loma Linda, California Headaches; Conditions Causing Increased Intracranial Pressure Brent R. King, MD Professor of Emergency Medicine and Pediatrics, and Chairman, Department of Emergency Medicine, The University of Texas Medical School at Houston; Chief of Emergency Services, Memorial Hermann Hospital; Attending Physician, Department of Emergency Medicine, Lyndon B. Johnson General Hospital, Houston, Texas Sepsis

Craig A. Kizewic, DO Pediatric Emergency Medicine Fellow, Department of Emergency Medicine, University of Florida Health Science Center—Shands Jacksonville, Jacksonville, Florida Gastrointestinal Foreign Bodies Ann Klasner, MD, MPH Associate Professor of Pediatrics, University of Alabama at Birmingham; Co-Director, Pediatric Emergency Fellowship Program, and Attending Physician, Emergency Department, The Children’s Hospital of Alabama, Birmingham, Alabama Brain Tumor Terry P. Klassen, MD, MSc, FRCPC Professor and Chair, Department of Pediatrics, University of Alberta; Regional Program Clinical Director, Department of Child Health, Stollery Children’s Hospital, Capital Health, Edmonton, Alberta, Canada Upper Airway Disorders Stephen R. Knazik, DO, MBA Clinical Associate Professor of Pediatrics and Emergency Medicine, Wayne State University School of Medicine; E.D. Medical Director and Chief of Pediatric Emergency Medicine, Children’s Hospital of Michigan, Detroit, Michigan Chest Pain Paul Kolecki, MD, FACEP Associate Professor, Department of Emergency Medicine, Thomas Jefferson University; Consultant, Philadelphia Poison Control Center, Philadelphia, Pennsylvania Adverse Effects of Anticonvulsants and Psychotropic Agents Baruch Krauss, MD, EdM Assistant Professor of Pediatrics, Harvard Medical School and Children’s Hospital, Boston, Massachusetts Procedural Sedation and Analgesia Kelly L. Kriwanek, MD Attending Physician, Children’s Hospital Central California, Madera, California Peripheral Neuromuscular Disorders Nathan Kuppermann, MD, MPH Professor of Emergency Medicine and Pediatrics, University of California, Davis, School of Medicine, Sacramento, California Diabetic Ketoacidosis

Contributors

Kenneth T. Kwon, MD, FACEP, FAAP Associate Clinical Professor, Department of Emergency Medicine, University of California, Irvine, School of Medicine, Irvine; Director of Pediatric Emergency Medicine, Department of Emergency Medicine, University of California, Irvine, Medical Center, Orange, California Electrical Injury Steve Levi, MD Assistant Clinical Professor of Medicine, Robert Wood Johnson School of Medicine; Chief, Electrophysiology, Our Lady of Lourdes Medical Center, Camden, New Jersey Pacemakers and Internal Defibrillators Deborah A. Levine, MD Clinical Assistant Professor of Pediatrics and Emergency Medicine, New York University School of Medicine; Attending Physician, Bellevue Hospital Center, New York, New York Bronchiolitis Stuart Lewena, MBBS, BMedSci, FRACP Honorary Fellow, Department of Pediatrics, Melbourne University, Melbourne; Pediatric Emergency Physician, Royal Children’s Hospital, Victoria, Australia Central Nervous System Vascular Disorders; VaccinationRelated Complaints and Side Effects Erica L. Liebelt, MD Associate Professor of Pediatrics and Emergency Medicine, University of Alabama at Birmingham School of Medicine; Director, Medical Toxicology Services, Children’s Hospital and University of Alabama at Birmingham Hospital, Birmingham, Alabama General Approach to Poisoning Marc Y. R. Linares, MD Director, Pediatric Emergency Fellowship Program, and Attending Physician, Emergency Department, Miami Children’s Hospital, Miami, Florida Gallbladder Disorders Robert Luten, MD Professor of Pediatrics and Emergency Medicine, Department of Emergency Medicine, University of Florida School of Medicine, Shands Hospital, Jacksonville, Florida Approach to Resuscitation and Advanced Life Support for Infants and Children Sharon E. Mace, MD Associate Professor, Department of Emergency Medicine, The Ohio State University School of Medicine, Columbus; Faculty, and Emergency Medicine Residency, MetroHealth Medical Center, Cleveland; Director, Pediatric Education/Quality Improvement, and Director, Observation Unit, Cleveland Clinic, Cleveland, Ohio Triage

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Charles G. Macias, MD, MPH Associate Professor of Pediatrics, Baylor College of Medicine; Attending Physician, Emergency Department, Texas Children’s Hospital, Houston, Texas Bone, Joint, and Spine Infections; Overuse Syndromes and Inflammatory Conditions Ian Maconochie, MBBS, FRCPCH, FCEM Honorary Senior Lecturer, Imperial College; Lead Clinician, Paediatric Emergency Department, St. Mary’s Hospital, St. Mary’s Trust, London, United Kingdom Dehydration and Disorders of Sodium Balance William K. Mallon, MD, FACEP, FAASM Associate Professor of Clinical Emergency Medicine, Keck School of Medicine of University of Southern California; Director, Division of International Emergency Medicine, Department of Emergency Medicine, Los Angeles County + University of Southern California Medical Center, Los Angeles, California Neck Trauma Courtney H. Mann, MD Adjunct Instructor, University of North Carolina at Chapel Hill, Chapel Hill; Medical Director, Pediatric Emergency Department, WakeMed Health and Hospitals, Raleigh, North Carolina Vomiting and Diarrhea Deborah J. Mann, MD Assistant Professor, Emergency Medicine, State University of New York Upstate Medical University, Syracuse, New York Common Pediatric Overdoses Jonathan Marr, MD Pediatric Emergency Medicine Fellow, University of Texas Southwestern Medical School, and Children’s Medical Center Dallas, Dallas, Texas Monitoring in Critically Ill Children; Seizures Nestor Martinez, MD Fellow, Pediatric Emergency Medicine, Miami Children’s Hospital, Miami, Florida Gallbladder Disorders Andrew D. Mason, MD Division of Pediatric Emergency Medicine, Hospital for Sick Children, Toronto, Ontario, Canada Enterostomy Tubes Todd A. Mastrovitch, MD Instructor of Emergency Medicine in Clinical Pediatrics, Weill Medical College of Cornell University, New York; Academic Pediatric Emergency Medicine Attending, and Director, Pediatric Education, Department of Emergency Medicine, New York Hospital Queens, Flushing, New York Failure to Thrive Thom A. Mayer, MD Chairman of Emergency Medicine, Fairfax Medical Center, Fairfax, Virginia Triage

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Contributors

James J. McCarthy, MD, FACEP Assistant Professor, Department of Emergency Medicine, University of Texas at Houston Medical School; Medical Director, Emergency Center, Memorial Hermann Hospital, Houston, Texas Sepsis Maureen McCollough, MD, FACEP Associate Professor of Emergency Medicine and Pediatrics, Keck School of Medicine of University of Southern California; Medical Director, Department of Emergency Medicine, and Director, Pediatric Emergency Department, Los Angeles County + University of Southern California Medical Center, Los Angeles, California The Critically Ill Neonate Ryan S. McCormick, BS, EMT-P Director, Office of Emergency Management, and Director, Center for Healthcare Preparedness, Saint Barnabas Health Care System, West Orange, New Jersey Disaster Preparedness for Children Barbara E. McDevitt, MD Director of Pediatric Emergency Services, Saint Barnabas Medical Center, Livingston, New Jersey Thoracic Trauma; Vomiting, Spitting Up, and Feeding Disorders William M. McDonnell, MD, JD Assistant Professor of Pediatrics, Division of Pediatric Emergency Medicine, University of Utah School of Medicine; Primary Children’s Medical Center, Salt Lake City, Utah High Altitude–Associated Illnesses Mark S. McIntosh, MD, MPH, FAAP, FACEP Clinical Assistant Professor, Department of Emergency Medicine, University of Florida, Jacksonville, Florida Valvular Heart Disease Francis Mencl, MD, MS, FACEP Associate Professor of Emergency Medicine, Northeastern Ohio Universities College of Medicine, Rootstown; Director of EMS, and Attending Emergency Department Staff, Summa Health Systems, Akron, Ohio Urinary Tract Infections in Children and Adolescents Russell Migita, MD Clinical Assistant Professor, Division of Emergency Medicine, Department of Pediatrics, University of Washington School of Medicine; Clinical Director, Emergency Services, Children’s Hospital and Regional Medical Center, Seattle, Washington Ventriculoperitoneal and Other Intracranial Shunts Angela M. Mills, MD, FACEP Assistant Professor, University of Pennsylvania School of Medicine; Attending Physician, Department of Emergency Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania Pregnancy-Related Complications

Lilit Minasyan, MD Fellow, Pediatric Emergency Medicine, Loma Linda University Children’s Hospital and Medical Center, Loma Linda, California Lower Extremity Trauma Rakesh D. Mistry, MD, MS Assistant Professor of Pediatrics, University of Pennsylvania School of Medicine; Attending Physician, Division of Emergency Medicine, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania Urinary Tract Infection in Infants Ameer P. Mody, MD, MPH Assistant Professor of Emergency Medicine and Pediatrics, Loma Linda University School of Medicine, Loma Linda; Clinical Director, Pediatric Emergency Medicine, Emergency Medicine Specialists of Orange County, Children’s Hospital of Orange County, Orange, California Trauma in Infants; The Steroid-Dependent Child; Addisonian Crisis; Thyrotoxicosis Cynthia J. Mollen, MD, MSCE Assistant Professor, Pediatrics, University of Pennsylvania; Attending Physician, Emergency Medicine, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania Sexually Transmitted Infections James A. Moynihan, MS, DO, FAAP Assistant Residency Director for Pediatric Emergency Medicine Fellowship, and Assistant Professor of Emergency Medicine, Division of Pediatric Emergency Medicine, Department of Emergency Medicine, Loma Linda University School of Medicine; Assistant Medical Director, Department of Emergency Medicine, Loma Linda University Medical Center and Children’s Hospital, Loma Linda, California Snake and Spider Envenomations Antonio E. Muñiz, MD, FACEP, FAAP, FAAEM Associate Professor of Emergency Medicine and Pediatrics, The University of Texas Medical School at Houston; Medical Director of Pediatric Emergency Medicine, Children’s Memorial Hermann Hospital, Houston, Texas Stridor in Infancy; Neonatal Skin Disorders; Erythema Multiforme Major and Minor; Henoch-Schönlein Purpura; Classic Viral Exanthems; Dermatitis; Infestations; Other Important Rashes Stacey Murray-Taylor, MD Associate Director, Adult Emergency Department, Newark Beth Israel Medical Center, Newark, New Jersey Access of Ports and Catheters and Management of Obstruction Michael J. Muszynski, MD Professor of Clinical Sciences, and Orlando Regional Campus Dean, Florida State University College of Medicine, Tallahassee, Florida Skin and Soft Tissue Infections

Contributors

Frances M. Nadel, MD, MSCE Assistant Professor of Clinical Pediatrics, University of Pennsylvania School of Medicine; Attending Physician, Division of Emergency Medicine, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania Vascular Access

Ronald I. Paul, MD Professor of Pediatrics, and Chief, Division of Pediatric Emergency Medicine, University of Louisville; Chief, Pediatric Emergency Medicine, Kosair Children’s Hospital, Louisville, Kentucky Diseases of the Hip

Alan L. Nager, MD Assistant Professor of Pediatrics, Department of Pediatrics, Keck School of Medicine of University of Southern California; Director, Department of Emergency and Transport Medicine, Children’s Hospital Los Angeles, Los Angeles, California Dehydration and Disorders of Sodium Balance

Barbara M. Garcia Peña, MD, MPH Research Director, Assistant Fellowship Director, Emergency Department, Miami Children’s Hospital, Miami, Florida Inflammatory Bowel Disease

John F. O’Brien, MD, FACEP Associate Clinical Professor, Department of Emergency Medicine, University of Florida Gainesville, Gainesville; Orlando Regional Medical Center, Associate Residency Director, Department of Emergency Medicine, Orlando Regional Medical Center, Orlando, Florida Incision and Drainage Pamela J. Okada, MD Associate Professor of Pediatrics, University of Texas Southwestern Medical Center at Dallas; Attending Physician, Emergency Department, Children’s Medical Center Dallas, Dallas, Texas Seizures Robert P. Olympia, MD Assistant Professor of Emergency Medicine and Pediatrics, Penn State College of Medicine; Attending Physician, Department of Emergency Medicine, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania Selected Infectious Diseases Kevin C. Osterhoudt, MD, MSCE Associate Professor of Pediatrics, University of Pennsylvania School of Medicine; Medical Director, The Poison Control Center, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania Toxic Alcohols Patricia S. Padlipsky, MD Fellow in Pediatric Emergency Medicine, Harbor-UCLA Medical Center, Torrance, California Respiratory Distress and Respiratory Failure Joe Pagane, MD Department of Emergency Medicine, Orlando Regional Medical Center, Orlando, Florida Foreign Body Removal Ruth Ann Pannell, MD Resident, Emergency Medicine, Orlando Regional Medical Center, Orlando, Florida Foreign Body Removal Norman A. Paradis, MD Senior Medical Director, Emergency Medicine, and Professor of Surgery and Medicine, University of Colorado Health Sciences Center, Denver, Colorado Cerebral Resuscitation

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Jay Pershad, MD, FAAP Associate Professor of Pediatrics, and Co-Director, Pediatric Emergency Fellowship Program, University of Tennessee Health Sciences Center; Attending Physician, Emergency Department, and Associate Medical Director, EMSC Education, and Sedationist, Radiology Department, LeBonheur Children’s Medical Center, Memphis, Tennessee Peripheral Neuromuscular Disorders; Ultrasonography Shari L. Platt, MD, FAAP Associate Professor of Clinical Pediatrics, Weill Cornell College of Medicine; Director, Pediatric Emergency Service, New York Presbyterian Hospital, New York, New York Pneumonia Jill C. Posner, MD, MSCE Assistant Professor of Pediatrics, University of Pennsylvania School of Medicine, University of Pennsylvania; Attending Physician, Pediatric Emergency Medicine, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania Menstrual Disorders; Replacing a Tracheostomy Tube Amy L. Puchalski, MD Assistant Professor of Pediatrics and Emergency Medicine, Medical College of Georgia; Attending Physician, Children’s Medical Center, Augusta, Georgia Neck Infections; Neck Masses Earl J. Reisdorff, MD Director of Medical Education, Department of Emergency Medicine, Ingham Regional Medical Center, Lansing; Associate Professor, Michigan State University, East Lansing, Michigan Syncope; Chest Pain Mark G. Roback, MD Professor of Pediatrics, and Associate Director, Division of Emergency Medicine, University of Minnesota Medical School, Minneapolis, Minnesota High Altitude–Associated Illnesses Steven C. Rogers, MD Fellow, Pediatric Emergency Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah Near Drowning and Submersion Injuries

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Contributors

Genie E. Roosevelt, MD, MPH Assistant Professor, Section of Emergency Medicine, Department of Pediatrics, University of Colorado at Denver and Health Sciences Center; Attending Physician, Emergency Department, The Children’s Hospital, Denver, Colorado Cerebral Resuscitation

Neil Schamban, MD Associate Clinical Professor, Emergency Medicine, Mount Sinai School of Medicine, New York, New York; Vice Chairman, Department of Emergency Medicine, Newark Beth Israel Medical Center, Newark, New Jersey Eye Disorders; The Sick or Injured Child in a Community Hospital Emergency Department; Access of Ports and Catheters and Management of Obstruction

Lazaro G. Rosales, MD Department of Pathology, State University of New York Upstate Medical University, Syracuse, New York Utilizing Blood Bank Resources/Transfusion Reactions and Complications

Carl H. Schultz, MD, FACEP Professor of Clinical Emergency Medicine, and CoDirector, EMS and Disaster Medical Sciences Fellowship, Department of Emergency Medicine, University of California, Irvine, School of Medicine, Irvine; Director, Disaster Medical Services, Department of Emergency Medicine, University of California, Irvine, Medical Center, Orange, California Electrical Injury

Kimberly R. Roth, MD Assistant Professor, Division of Pediatric Emergency Medicine, University of Pittsburgh School of Medicine, Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania Local and Regional Anesthesia Steven G. Rothrock, MD, FACEP, FAAP Professor of Emergency Medicine, University of Florida; Associate Professor of Clinical Sciences, Florida State University, Orlando Regional Healthcare System, Orlando, Florida Approach to Resuscitation and Advanced Life Support for Infants and Children; Rapid Sequence Intubation; Neonatal Resuscitation; The Critically Ill Neonate; Circulatory Emergencies: Shock; Oral, Ocular, and Maxillofacial Trauma; Appendicitis Alfred Sacchetti, MD Assistant Clinical Professor, Emergency Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania; Chief, Emergency Services, Our Lady of Lourdes Medical Center, Camden, New Jersey The Sick or Injured Child in a Community Hospital Emergency Department; Pacemakers and Internal Defibrillators Peter D. Sadowitz, MD Associate Professor of Pediatric Emergency Medicine and Associate Professor of Medicine, State University of New York, Syracuse, New York Cancer and Cancer-Related Complications in Children; Acute Childhood Immune Thrombocytopenic Purpura and Related Platelet Disorders Esther Maria Sampayo, MD Assistant Professor of Pediatrics and Pediatric Emergency Medicine, University of Pennsylvania; Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania Oral Lesions John P. Santamaria, MD Affi liate Professor, Department of Pediatrics, University of South Florida School of Medicine, Tampa, Florida Dysbarism

Sandra H. Schwab, MD Assistant Professor, Department of General Pediatrics, University of Pennsylvania; Attending Physician, Department of General Pediatrics, Division of Emergency Medicine, The Childrens Hospital of Philadelphia, Philadelphia, Pennsylvania Menstrual Disorders Fred Schwartz, MD Attending Physician, Pediatric Emergency Medicine, Saint Barnabas Medical Center, Livingston, New Jersey Paraphimosis Reduction Deborah Scott, RN, ARNP Nurse Examiner, Arnold Palmer Hospital Child Advocacy Center, Orlando, Florida Sexual Abuse Matthew A. Seibel, MD Clinical Professor, Florida State University; Pediatric Hospitalist, Arnold Palmer Hospital for Children, Orlando, Florida Sexual Abuse Samir S. Shah, MD Assistant Professor of Pediatrics and Epidemiology, University of Pennsylvania School of Medicine; Attending Physician, Divisions of Infectious Diseases and General Pediatrics, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania Post-Liver Transplantation Complications Ghazala Q. Sharieff, MD, FACEP, FAAEM, FAAP Associate Clinical Professor, Children’s Hospital and Health Center, University of California, San Diego; Director of Pediatric Emergency Medicine, PalomarPomerado Hospitals, California Emergency Physicians, San Diego, California Dysrhythmias; Pericarditis, Myocarditis, and Endocarditis Richard D. Shih, MD, FAAEM, FACEP Associate Professor of Surgery, New Jersey Medical School, UMDNJ, Newark; Residency Director, Emergency Medicine, Morristown Memorial Hospital, Morristown, New Jersey Adverse Effects of Anticonvulsants and Psychotropic Agents

Contributors

Jan M. Shoenberger, MD, FACEP, FAAEM Assistant Professor of Clinical Emergency Medicine, Keck School of Medicine of University of Southern California; Associate Residency Director, Department of Emergency Medicine, Los Angeles County + University of Southern California Medical Center, Los Angeles, California Neck Trauma Ian Shrier, MD, PhD, Dip Sport Med (FACSM) Associate Professor, Department of Family Medicine, SMBD-Jewish General Hospital, McGill University; Investigator, Centre for Clinical Epidemiology and Community Studies, Montréal, Québec, Canada Compartment Syndrome Jonathan I. Singer, MD, FAAP, FACEP Professor of Emergency Medicine and Pediatrics, Vice Chair, and Associate Program Director, Department of Emergency Medicine, Boonshoft School of Medicine, Wright State University; Staff Physician, Children’s Medical Center, Dayton, Ohio Intussusception Sharon R. Smith, MD Associate Professor of Pediatrics, Department of Pediatrics, University of Connecticut Health Center, Farmington; Associate Professor of Pediatrics, Department of Emergency Medicine, Connecticut Children’s Medical Center, Hartford, Connecticut Management of Acute Asthma Abdul-Kader Souid, MD, PhD Professor of Pediatrics and Biochemistry, State University of New York Upstate Medical University, Syracuse, New York Cancer and Cancer-Related Complications in Children; Acute Childhood Immune Thrombocytopenic Purpura and Related Platelet Disorders; Disorders of Coagulation; Hemolytic-Uremic Syndrome; Utilizing Blood Bank Resources/Transfusion Reactions and Complications Blake Spirko, MD, FACEP, FAAP Pediatric Emergency Medicine Fellowship Director, and Assistant Professor, Department of Emergency Medicine, Tufts University School of Medicine, Boston; Pediatric Emergency Medicine Fellowship Director, and Assistant Professor, Department of Emergency Medicine, Baystate Medical Center, Springfield, Massachusetts Musculoskeletal Disorders in Systemic Disease Nicole S. Sroufe, MD, MPH Pediatric Emergency Medicine Fellow, Department of Emergency Medicine, University of Michigan, Ann Arbor, Michigan Rhabdomyolysis Rachel M. Stanley, MD, MHSA Assistant Professor, University of Michigan; Department of Emergency Medicine, University of Michigan Health Center, Ann Arbor, Michigan Rhabdomyolysis

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Robert Steele, MD, FACEP Associate Professor, Loma Linda University Medical School; Interim Medical Director, Department of Emergency Medicine, Loma Linda University Medical Center, Loma Linda, California Pericardiocentesis Mardi Steere, MBBS, FAAP Staff Specialist, Pediatric Emergency, Women’s and Children’s Hospital, North Adelaide, South Australia, Australia Pancreatitis Gail M. Stewart, DO, FAAP Associate Professor of Emergency Medicine and Pediatrics, Loma Linda University School of Medicine; Attending Physician, Pediatric Emergency Department, Loma Linda University Medical Center and Children’s Hospital, Loma Linda, California Trauma in Infants; Conditions Causing Increased Intracranial Pressure Patricia Sweeney-McMahon, RN, MS Assistant Vice President, Clinical and Emergency Services, Saint Barnabas Health Care System, West Orange, New Jersey Patient Safety, Medical Errors, and Quality of Care; Digital Injuries and Infections David A. Talan, MD, FACEP, FIDSA Professor of Medicine, UCLA School of Medicine, Los Angeles; Chairman, Department of Emergency Medicine, and Faculty, Division of Infectious Diseases, Olive View-UCLA Medical Center, Sylmar, California Tetanus Prophylaxis; Rabies Postexposure Prophylaxis Todd B. Taylor, MD Adjunct Associate Professor, Department of Emergency Medicine, Vanderbilt University School of Medicine, Vanderbilt University, Nashville, Tennessee Emergency Medical Treatment and Labor Act (EMTALA) Stephen J. Teach, MD, MPH Professor of Pediatrics and Emergency Medicine, Department of Pediatrics, George Washington University School of Medicine and Health Sciences; Associate Chief, Division of Emergency Medicine, Children’s National Medical Center; Associate Director, Center for Clinical and Community Research, Children’s National Medical Center, Washington, DC Gastrointestinal Bleeding Sieuwert-Jan C. ten Napel, MD Resident, Emergency Medicine, Emergency Department, Onze lieve Vrouwe Gasthuis-Hospital, Amsterdam, The Netherlands Upper Extremity Trauma Thomas E. Terndrup, MD, FACEP, FAAEM Professor and Chair, Emergency Medicine, and Associate Dean for Clinical Research, Penn State Milton S. Hershey Medical Center, Penn State College of Medicine, Hershey, Pennsylvania Thoracostomy

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Contributors

Tonya M. Thompson, MD, MA Assistant Professor, Departments of Pediatrics and Emergency Medicine, University of Arkansas for Medical Sciences; Associate Pediatric Emergency Medicine Fellowship Director, Department of Pediatrics, Arkansas Children’s Hospital, Little Rock, Arkansas Headaches Andrea Thorp, MD Fellow in Pediatric Emergency Medicine, Loma Linda University Medical Center and Children’s Hospital, Loma Linda, California Pericardiocentesis Irene Tien, MD, MSc Assistant Professor, Boston University School of Medicine, Boston; Staff Physician, Newton-Wellesley Hospital, Newton, Massachusetts Ear Diseases; Physical Abuse and Child Neglect

Andrew Wackett, MD Assistant Clinical Professor of Emergency Medicine, Stony Brook University Medical Center, Stony Brook, New York Spinal Trauma Ron M. Walls, MD Professor of Medicine, Department of Emergency Medicine, Harvard Medical School; Chairman, Department of Emergency Medicine, Brigham and Women’s Hospital, Boston, Massachusetts Intubation, Rescue Devices, and Airway Adjuncts Jennifer L. Waxler, DO Emergency Medical Associates, Long Branch, New Jersey Digital Injuries and Infections

John A. Tilelli, MD Clinical Assistant Professor, Florida State University, Tallahassee; Intensivist, Division of Pediatric Critical Care Medicine, Arnold Palmer Children’s Hospital, Orlando Regional Healthcare System, Orlando, Florida Drugs of Abuse; Cardiovascular Agents; Ventilator Considerations

Evan J. Weiner, MD, FAAP Fellow, Pediatric Emergency Medicine, University of Florida Health Science Center; Physician, Pediatric Emergency Medicine, Wolfson Children’s Hospital, Jacksonville, Florida Hepatitis

Nicholas Tsarouhas, MD Associate Professor of Clinical Pediatrics, Department of Pediatrics, University of Pennsylvania School of Medicine; Medical Director, Emergency Transport Services, and Attending Physician, Emergency Department, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania Burns

Stuart B. Weiss, MD Partner, MedPrep Consulting Group, LLC, New York, New York Disaster Preparedness for Children

Michael G. Tunik, MD Associate Professor of Pediatrics and Emergency Medicine, New York University School of Medicine; Research Director, and Associate Director, Pediatric Emergency Medicine, Bellevue Hospital Center, New York, New York Emergency Medical Services and Transport Christian Vaillancourt, MD, MSc, FRCPC Assistant Professor, Department of Emergency Medicine, The Ottawa Hospital, University of Ottawa; Associate Scientist, Ottawa Health Research Institute, Ottawa, Ontario, Canada Compartment Syndrome Jonathan H. Valente, MD, FACEP Assistant Professor, Departments of Emergency Medicine and Pediatrics, Brown Medical School, Brown University; Attending Physician, Rhode Island Hospital and Hasbro Children’s Hospital, Providence, Rhode Island Minor Infant Problems Peter Viccellio, MD Clinical Professor of Emergency Medicine, Stony Brook University Medical Center, Stony Brook, New York Spinal Trauma

James A. Wilde, MD, FAAP Associate Professor of Emergency Medicine and Pediatrics, and Director, Pediatric Emergency Medicine, Medical College of Georgia, Augusta, Georgia Central Nervous System Infections Kristine G. Williams, MD, MPH Instructor, Pediatrics, Washington University School of Medicine; Instructor, Pediatrics, Division of Emergency Medicine, St. Louis Children’s Hospital, St. Louis, Missouri Fever in the Well-Appearing Young Infant Michael Witt, MD, MPH Instructor in Pediatrics, Harvard Medical School; Attending Physician, Children’s Hospital, Boston, Massachusetts Abdominal Hernias Aaron Wohl, MD Clinical Assistant Professor, Department of Emergency Medicine, University of Florida College of Medicine, Gainesville; Attending Physician, Department of Emergency Medicine, Lee Memorial Hospital, Fort Myers, Florida Constipation

Contributors

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Tony Woodward, MD, MBA Professor, Division of Emergency Medicine, Department of Pediatrics, University of Washington School of Medicine; Director, Emergency Services, Children’s Hospital and Regional Medical Center, Seattle, Washington Ventriculoperitoneal and Other Intracranial Shunts

Kelly D. Young, MD, MS Associate Clinical Professor of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles; Director, Pediatric Emergency and Pain Management Education, Department of Emergency Medicine, Harbor-UCLA Medical Center, Torrance, California Approach to Pain Management

Robert Bruce Wright, MD, FAAP, FRCPC Assistant Professor, Division of Pediatric Emergency Medicine, Department of Pediatrics, University of Alberta; Assistant Director, Division of Pediatric Emergency Medicine, Stollery Children’s Hospital, Edmonton, Alberta, Canada Upper Airway Disorders

Joseph J. Zorc, MD Associate Professor of Pediatrics and Emergency Medicine, University of Pennsylvania School of Medicine; Attending Physician, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania Altered Mental Status/Coma

Todd Wylie, MD, MPH Assistant Professor, Program Director Pediatric Emergency Medicine Fellowship, Department of Emergency Medicine, University of Florida, Jacksonville, Florida Pericarditis, Myocarditis, and Endocarditis; Hypertensive Emergencies

Alexander Zouros, MD, FRCS(C) Assistant Professor, Department of Neurosurgery, Loma Linda University Medical Center, Loma Linda, California Conditions Causing Increased Intracranial Pressure

Preface Societies are often judged by the care they provide for the young and the weak. The quality of care for injured and ill children has grown tremendously since the formation and growth of pediatric emergency medicine as a subspecialty within the pediatric and emergency medicine communities. The body of knowledge that defines pediatric emergency medicine is deep in breadth and wide in scope. Those who practice it are energetic, intelligent, and caring. They come from diverse backgrounds and share the common goal of providing safe, comprehensive, high quality, cost-effective care. Because children are treated in many venues ranging from the prehospital setting, to urgent care clinics, community hospital emergency departments, academic medical centers and pediatric specialty care hospitals, the provision of excellent pediatric emergency care is of great interest to many. This text is designed to meet the needs of anyone who cares for childhood emergencies. It is a highly practical and clinically useful reference organized in a logical fashion – according to the way one would think and problem solve when confronted with any emergency in a child. The emphasis is on information that has an impact in real-time care at the bedside and therefore helps the emergency practitioner at the moment help is most required. The book includes 200 chapters replete with clinical algorithms, tables, photos, figures, and expert commentary. The information is presented in a format which highlights key points, important clinical features, potential pitfalls, and delineates the diagnostic approach and specific management for a myriad of pediatric emergency problems. The sections of the book are divided according to the typical way that one experiences patients in an emergency department – by level of acuity, type of disease, and patient characteristics. Section I: Immediate Approach to the Critical Patient addresses life-threatening presentations of medical and surgical disease and contains crucial information on providing immediate and life-saving therapies. Section II: Approach to the Trauma Patient, provides similar information when dealing with acute injury as well as definitive management recommendations for a wide range of traumatic conditions. Section III: Approach to Unique Problems of Infancy highlights important clinical features and critical management information for conditions which specifically affect this high-risk population of emergency patients. Sections IV and V: Approach to the Acutely Ill Patient and Approach to Envi-

ronmental Illness and Injury cover the wide spectrum of conditions encountered on a regular basis in the emergency care of children. Section VII: Procedures, Sedation, Pain Management and Devices, provides step by step techniques, important clinical considerations, and helpful illustrations for performing procedures and managing devices in children in the emergency department. Several unique features of this text will prove invaluable to busy clinicians. Section VI: The Practice Environment, explicitly discusses difficult issues such as triage, the care of minors, end of life care, and family presence during resuscitation and offers practical and workable solutions. Section VIII: Quick Looks, offers an immediate differential diagnosis to common pediatric emergency department symptomoriented complaints ranging from abdominal pain and cyanosis to jaundice and lymphadenopathy. The text is extensively cross referenced to provide the most rapid and useful assistance to the reader. The creation of the first edition of Pediatric Emergency Medicine was borne out of the desire to synthesize and disseminate the evidence based practice of emergency care for children, where such evidence exists. There has been an explosive amount of research in the last several years on many aspects of pediatric emergency medicine, with findings that challenge current practices on a regular basis. Much is still to be learned, however, each year therapies based on anecdotal evidence or opinion are replaced with evidence based guidelines and validated decision rules. When evidence to support a particular diagnostic strategy or treatment could not be found, this text makes the best possible recommendation based on current literature and expert opinion or consensus, referencing statements in text for our readers’ convenience. It also highlights controversies, cutting edge developments and areas that are in need of further study. Our goal is to assure that a scientifically sound rationale is used as the basis for the management of ill and injured children. We hope to further such care on a regular basis in emergency departments everywhere to individuals of all backgrounds who provide pediatric emergency care. It is our intention that this first edition of Pediatric Emergency Medicine will become an invaluable resource in this capacity. With the knowledge and insight gained from the experts who have written on these pages, we sincerely hope that this text will promote and advance excellent emergency care to the young and vulnerable.

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We gratefully acknowledge the work of Joanie Milnes, our developmental editor. Joanie was the ultimate professional, gently guiding us through every stage of publication. She was tough and persistent when we needed her to be but always kind, and remarkably hard working. We also appreciate the guidance and assistance of other Elsevier staff, particularly Todd Hummel who gave us a great start, and Maria Lorusso who gave us a great fi nish. Ran D. Goldman, our pharmacology editor, did us a tremendous service and we are indebted to him for providing an efficient and thorough review of our chapters and for checking every medication dose and reference contained within. Ran, we thank you for that extra reassurance and for your tremendous hard work. We pay tribute to all our contributors who authored chapters and put up with many requests and deadlines. Their level of excitement about the project as well as their knowledge and commitment to creating a high quality, thoroughly referenced work was unsurpassed. Several colleagues volunteered above and beyond the call of duty to author multiple chapters and we are indebted to them for the volume of work they embraced in a short period of time. We especially thank our colleagues at The Children’s Hospital of Philadelphia, the Hospital of the University of Pennsylvania, Saint Barnabas Health Care System, Loma Linda University Medical Center and Children’s Hospital, and Orlando Regional Healthcare for their willingness to become authors and for the daily privilege of working with them in our respective emergency departments. And finally, the motivation to create this book comes in large part, from our patients. They are a constant source of learning and inspiration and we thank them for the opportunity to care for them. It is our intention and hope that this text will improve the health and well being of those we are privileged to serve.

Jill M. Baren, MD, MBE, FACEP, FAAP Steven G. Rothrock, MD, FACEP, FAAP John A. Brennan, MD, FACEP, FAAP Lance Brown, MD, MPH, FACEP, FAAP

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Chapter 1 Approach to Resuscitation and Advanced Life Support for Infants and Children Robert Luten, MD and Steven G. Rothrock, MD

Key Points Both shock and respiratory failure can be diagnosed and treated in a timely fashion utilizing simple bedside clinical parameters. With the exception of infants with cardiac failure, clinicians are most likely to under-resuscitate infants and children with shock (i.e., they do not administer enough fluids in a timely manner). A clear understanding of technique and equipment for BVM ventilation before, and maintenance of endotracheal tube position after, intubation is crucial. Eliminate unnecessary mental activity so that time can be used for assessing the priorities of resuscitation. Use printed material or cards to facilitate dosing and equipment selection and age-specific algorithms to improve management of resuscitation and evaluation of critically ill infants and children. The practice of fundamental mock scenarios and treatment modalities can provide confidence when addressing the rare critically ill child.

failure and shock as its principal resuscitative thrust. The treatment of pediatric cardiac arrest, although included, needs to be seen in perspective relative to the larger picture, the priority for recognition of and resuscitation from shock and respiratory failure. Although the science of resuscitation therapy is continually evolving and requires periodic review, management of a pediatric resuscitation is a skill that changes little over time. Certain practical issues that are inherent in the treatment of respiratory failure, shock, and cardiac arrest in children are discussed in this chapter. Survival with normal neurologic function following inhospital cardiac arrest is 14% to 15% and less than 3% after out-of-hospital pediatric cardiac arrest.1-5 Studies have delineated markers for poor outcome and no survival. It is helpful to know these probability markers to guide appropriateness of ongoing resuscitation and to quickly prepare and console parents in dealing with the death of their child. Also, in an effort to prevent cardiac survival in the presence of probable devastating neurologic outcome, it is helpful to have guidelines for termination of resuscitative efforts. Most authors agree that, in the absence of extenuating circumstances such as profound hypothermia, resuscitative efforts beyond two to three doses of epinephrine are unlikely to be successful.3,6,7 Other markers for poor probability of survival include drowning requiring chest compressions and advanced life support medications at the scene, lack of cardiac activity on arrival to the emergency department (ED), and prolonged (>30 minutes) resuscitation.3,6,7

Introduction and Background

Approach

Survival following cardiac arrest in children is poor. As opposed to adults, in whom cardiac arrest is frequently a primary event brought on by ischemic heart disease, in children cardiac arrest is a secondary phenomenon, usually the result of profound metabolic disturbances from untreated shock or respiratory failure. In the early 1980s, the American Heart Association, through the creation of the Pediatric Advanced Life Support (PALS) course, aimed its educational emphasis at the recognition and treatment of respiratory

A recent review of the pediatric resuscitation process attempted to define elements of the mental (cognitive) burden of providers when dealing with critically ill children.8 An increase in logistical time is inherent in pediatric resuscitation compared to adult resuscitation. One of the reasons for this increased logistical time is the age- and size-related variations unique to children, which introduce the need for more complex, “nonautomatic” mental activities, such as calculating drug doses and selecting equipment. These activities 3

4

SECTION I — Immediate Approach to the Critical Patient

may subtract from other important mental activities such as assessment, evaluation, prioritization, and synthesis of information, which can be referred to in the resuscitative process as “critical thinking activity.” Summation of these logistical difficulties leads to inevitable time delays, and a corresponding increase in the potential for decision-making errors in the pediatric resuscitative process. This is in sharp contrast to adult resuscitation. One way of understanding this differences is to examine the adult resuscitation process. Medications used frequently (e.g., epinephrine, atropine, glucose, bicarbonate, and lidocaine) are packaged in prefi lled syringes containing the exact adult dose, making their ordering and administration “automatic” (i.e., not requiring mental effort beyond the decision to order one ampule or one unit dose of the drug). The same concept is seen in equipment selection, where the usual necessary equipment is laid out for immediate access and use. It is also common to have preprinted algorithms readily available to guide drug selection, drug dosing, equipment selection, and administration decisions, even though the provider frequently has a good working knowledge of these issues. The end result is that the adult provider’s time is freed up for critical thinking, and is not occupied with these other decisions. The use of resuscitation aids in pediatric resuscitation can significantly reduce the cognitive load caused by obligatory calculations of dosage and equipment selection. These aids relegate these activities to a lower order of mental function. In other words, the use of resuscitation aids in pediatric resuscitation transforms nonautomatic activities into automatic activities, decreasing logistical time, thereby increasing critical thinking time. An example is the Broselow-Luten system that codifies children to a color by a single length measurement. The color then serves as a code for preselected equipment, precalculated medications, and other age/ size-related variables such as fluids and ventilator settings (Fig. 1–1).

Evaluation and Management The ABCs Standard preliminary treatment is usually initiated prior to arrival of critically ill or arrested children in the ED. Laypeople and emergency medical services (EMS) providers have been shown inaccurate at detecting breathlessness and the presence of a pulse in patients with cardiac arrest.9 For this reason, a complete cardiopulmonary re-evaluation is essential upon patient arrival in the ED. Head tilt and chin lift (jaw thrust without head tilt if cervical spine injury is possible) are initiated to open an obstructed airway while rescue breaths are given for apneic patients. Upon ED arrival, more advanced airway techniques, subsequently described, are applied. As respiratory failure is the most common precipitating event in childhood cardiac arrest, attention to properly opening the airway, adequate ventilation, and oxygenation are key resuscitation techniques. Clinicians should be aware that the infant’s heart is below the lower third of the sternum in 88% of cases.10 For this reason, chest compressions over the lower third of the sternum generate a higher mean arterial pressure compared to the midsternum11 (Fig. 1–2). Additionally, using both hand to encircle the chest while applying chest compressions to

infants (1 year old

• Resume CPR • Give epinephrinec IV or IO at 0.01 mg/kg (0.1 mL/kg of 1:10,000) or endotrachealy at 0.1 mg/kg (0.1 mL/kg of 1:1,000)

After 5 cycles of CPR, recheck rhythm

If VF/Pulseless VT persist • Shock once at 4J/kg or • Use AED>1 year old • Consider one of the following medications • Amiodarone 5mg/kg IV or IO • Lidocaine 1 mg/kg IV or IO • Magnesium 25–50 mg/kg IV or IO (max 2 grams) if Torsades de pointes is present

FIGURE 1–5. Pulseless cardiac arrest management.

in children 1 to 8 years old. Subsequently, ventilation and cardiac compressions are initiated and medications, including epinephrine and antiarrhythmics, are given. As for asystole and PEA, adult arrest protocols are recommended for children over 8 years old with VF/pulseless VT, the primary

During CPR • Give 15 compressions then 2 breaths (if 2 person CPR) • Secure airway and confirm placement (e.g. visualization followed by capnographic waveform analysis) • After intubation, cycles are no longer delivered. Instead, give continuous CPR without pauses for breaths. Give 8–10 breaths per minute via endotracheal tube

• Change persons performing compressions every 2 min.

Search for and treat underlying causes of cardiac arrest Hypovolemia, Hypoxia, Hydrogen ions (acidosis), Hypo-Hyperkalemia, Hypoglycemia, Hypothermia, Toxins, Tamponade, Tension pneumothorax, Trauma, Thrombosis (coronary or pulmonary)

• Resume CPR • Give epinephrine IV or IO at 0.01 mg/kg (0.1 mL/kg of 1:10,000) or endotrachealy at 0.1 mg/kg (0.1 mL/kg of 1:1,000) • Repeat q 3–5 minc

• Resume CPR for 5 cycles (2 minutes) • If pulseless VT or VF occur, see VT/VF algorithm above.

aVF–

ventricular fibrillation, VT– ventricular tachycardia bPEA – pulseless electrical activity cGive epinephrine q 3–5 min. Consider higher dose (0.1mg/kg administered IV or IO) only in exceptional circumstances (e.g. β blocker overdose)

After medications, continue CPR for 5 cyles (2 minutes) and recheck rhythm. If VF/Pulseless VF persist, resume CPR for 2 minute cycles, rechecking rhythm every 2 minutes followed by shock while administering epinephrine q 3–5 minutes and antiarrhythmics. If asystole/PEA occur, treat as per PEA/asystole algorithm.

difference being the use of vasopressin for these arrest rhythms instead of or in addition to epinephrine. Following drug administration, repeat defibrillation at 4 joules/kg is followed by CPR and further drug administration (see Fig. 1–5). Clinicians need to be aware of prehospital provider

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SECTION I — Immediate Approach to the Critical Patient

recommendations for use of AEDs in cardiac arrest in children 1 year of age or older. AEDs are 96% sensitive and 100% specific at identifying VF/VT at this age.34 In general, delivery of adult defibrillator doses to children over 1 year old has been shown safe, although use of pediatric algorithms, pads, and cables for adult AEDs is preferred.33 In the postarrest state, besides careful attention to ETT positioning and maintenance, frequent monitoring of vital signs is essential. Vasoactive medications are frequently required, at least transiently, to maintain perfusion as myocardial depression as well poor vascular tone are common in this scenario. The use of these drugs requires careful monitoring as clinical response is very patient specific and can also vary at different infusion rates.

Summary Therapy for pediatric cardiopulmonary arrest has changed little in the past decade. As a result, outcome for cardiac arrest has not improved. Currently, studies are underway to evaluate preventative techniques for at-risk infants and children, earlier prehospital interventions (e.g., specific pediatric AEDs), and postresuscitation neurologic preservation (e.g., therapeutic hypothermia). Recognition of disorders leading to respiratory and cardiac arrest and prompt aggressive management have the potential to minimize morbidity and mortality in critically ill infants and children. The decision tree for simultaneous recognition, differentiation and management is clinical, requiring minimal ancillary studies. Once cardiac arrest occurs, CPR and advanced life support techniques are employed using standard algorithms. Drug dosing, equipment selection, and patient management is enhanced by use of length-based cognitive resuscitation aids (e.g., Broselow-Luten system) and printed management guides. Newer techniques of US and ETCO2 may aid in rapid diagnosis and management of patients with viable arrest rhythms and may predict return of spontaneous circulation. REFERENCES 1. Ronco R, King W, Donley DK, et al: Outcome and cost at a children’s hospital following resuscitation for out-of-hospital cardiopulmonary arrest. Arch Pediatr Adolesc Med 149:210, 1995. 2. Schindler MB, Bohn D, Cox PN, et al: Outcome of out-of-hospital cardiac or respiratory arrest in children. N Engl J Med 335:1473, 1996. 3. Young KD, Gasuche-Hill M, McClung CD, Lewis RJ: A prospective, population based study of the epidemiology and outcome of out of hospital pediatric cardiopulmonary arrest. Pediatrics 114:157–164, 2004. 4. Gills J, Dickson D, Rieder M, et al: Results of inpatient pediatric resuscitation. Crit Care Med 14:469–471, 1986. 5. Reis AG, Nadkarni V, Perondi MB, et al: A prospective investigation into the epidemiology of in hospital pediatric cardiopulmonary arrest using the Utstein style. Pediatrics 109:200–209, 2002. 6. Zarirsky A, Nadkarni V, Getson P, Kuehl K: CPR in children. Ann Emerg Med 16:1107–1111, 1998. *7. Young KD, Seidel JS: Pediatric cardiopulmonary resuscitation: a collective review. Ann Emerg Med 33:195, 1999. *8. Luten R, Wears R, Broselow J, et al: Managing the unique size related issues of pediatric resuscitation: reducing cognitive load with resuscitation aids. Acad Emerg Med 9:840–847, 2002. *Selected readings.

9. Ruppert M, Reith MW, Widmann JH, et al: Checking for breathing: evaluation of the diagnostic capability of emergency medical services personnel, physicians, medical students, and medical laypersons. Ann Emerg Med 34:720–729, 1999. 10. Phillips GW, Zideman DA: Relationship of infant to sternum: its significance in cardiopulmonary resuscitation. Pediatrics 114:157–164, 2004. 11. Orlowski JP: Optimum position for external cardiac compression in infants and young children. Ann Emerg Med 15:667–673, 1986. 12. Dorfsman ML, Menegazzi JJ, Wadas RJ, Auble TE: Two fi nger vs. two thumb compression in an infant model of prolonged cardiopulmonary resuscitation. Acad Emerg Med 7:1077–1082, 2000. *13. American Heart Association: Pediatric basic and advanced life support. Circulation 112(Suppl III):III-73–III-90, 2005. 14. Ward KR, Menegazzi JJ, Zelenak RR, et al: A comparison of chest compressions between mechanical and manual CPR by monitoring end-tidal CO2 during human cardiac arrest. Ann Emerg Med 22: 669–674, 1993. 15. Kern KB: Cardiopulmonary resuscitation without ventilation. Crit Care Med 28:N186–N189, 2000. 16. Swenson RD, Weaver WD, Niskanen RA, et al: Hemodynamics in humans during conventional and experimental methods of cardiopulmonary resuscitation. Circulation 78:630–639, 1988. 17. Maier GW, Newton JR, Wolfe JA, et al: The influence of manual cardiac compression rate on hemodynamic support during cardiac arrest: high impulse cardiopulmonary resuscitation. Circulation 74(Suppl IV):IV51–IV-59, 1986. 18. Callaham M, Barton C: Prediction of outcome of cardiopulmonary resuscitation from end-tidal carbon dioxide concentration. Crit Care Med 18:358–362, 1990. 19. Wayne MA, Levine RL, Miller CC: Use of end tidal CO2 to predict outcome in prehospital cardiopulmonary arrest. Ann Emerg Med 25:762–767, 1995. 20. Ward KR, Yealy DM: End tidal carbon dioxide monitoring in emergency medicine: clinical applications. Acad Emerg Med 5:637–646, 1998. 21. Salen PO, O’Connor R, Sierzenski P, et al: Can cardiac sonography and capnography be used independently and in combination to predict resuscitation outcomes? Acad Emerg Med 8:610–615, 2001. 22. Amaya SC, Langsam A: Ultrasound detection of ventricular fibrillation disguised as asystole. Ann Emerg Med 33:344–346, 1999. 23. Hirschman AM, Krauath RE: Venting vs. ventilating: a danger of manual resuscitation. Chest 82:369–370, 1982. 24. Sugiyama K, Yokoyama K: Displacement of the endotracheal tube caused by change of head position in pediatric anesthesia: evaluation by fiberoptic bronchoscopy. Anesth Analg 82:251–253, 1996. 25. Olufolabi AJ, Charlton GA, Spargo PM: Effect of head posture on tracheal tube position in children. Anaesthesia 59:1069–1072, 2004. 26. Chameides L (ed): Textbook of Pediatric Life Support. Dallas, TX: American Heart Association, 1987. 27. Carcillo JA, Davis AL, Zaritsky A: Role of early fluid resuscitation in pediatric septic shock. JAMA 266:1242–1245, 1991. 28. Carcillo J: Pediatric septic shock and multiple organ failure. Crit Care Clin 19:413–440, 2003. 28. Seigler RS, Tecklenburg F, Shealy R: Prehospital intraosseus infusions by emergency medical services personnnel: a prospective study. Pediatrics 84:173–177, 1989. 30. Olsen D, Packer BE, Perrett J, et al: Evaluation of the bone injection gun as a method for intraosseous cannula placement for fluid therapy in adult dogs. Vet Surg 31:533–540, 2002. 31. Sirbaugh PE, Pepe PE, Shook JE, et al: A prospective, population-based study of the demographics, epidemiology, management, and outcome of out-of-hospital pediatric cardiopulmonary arrest. Ann Emerg Med 33:174–184, 1999. *32. American Heart Association: Pediatric advanced life support. Circulation 102(Suppl I):I-291–I-342, 2000. 33. Samson RA, Berg RA, Bingham R, et al: Use of automated external defibrillators for children: an update. An advisory statement from the Pediatric Advanced Life Support Task Force, International Liaison Committee on Resuscitation. Circulation 107:3250–3255, 2003. 34. Ceechin F, Jorgenson JB, Berul CI, et al: Is arrhythmia detection by automatic external defibrillator accurate for children? Sensitivity and specificity of an automatic external defibrillator algorithm in 696 pediatric arrhythmias. Circulation 103:2483–2488, 2001.

Chapter 2 Respiratory Distress and Respiratory Failure Patricia S. Padlipsky, MD and Marianne Gausche-Hill, MD

Key Points Pediatric airway differences are most pronounced in infants. By 8 years of age the pediatric airway is anatomically like the adult airway. Respiratory distress is a state of increased work of breathing, whereas respiratory failure is a state of inadequate oxygenation or ventilation. Respiratory failure may or may not be preceded by respiratory distress.

Recognition and Approach There are anatomic, physiologic, and behavioral differences between the adult and pediatric airway that affect the risk of airway obstruction, the risk of the development of respiratory compromise, and the approach to management. The transition from neonatal to adult airway anatomy is completed by 8 to 10 years of age. By this time the airway is similar to that of the adult, only smaller. Anatomic, physiologic, and behavioral differences with their impact on patient care are summarized in Table 2–1. Anatomic Differences

Assessment of the respiratory status of an infant or child begins with the Pediatric Assessment Triangle. A rapid general impression directs immediate airway management. Infants and children have unique clinical scenarios and conditions that may lead to a difficult airway.

Introduction and Background Respiratory problems or complaints are one of the most common reasons for infants and children seeking medical care in an emergency department (ED). Children represent about 10% of all prehospital care transports, and of these about 10% are due to respiratory complaints.1-3 In the ED, respiratory complaints account for approximately 10% to 20% of the pediatric visits.4 Respiratory compromise is the leading cause of death in children less than 1 year of age. Children often go through a period of respiratory distress prior to respiratory failure, but respiratory failure may exist without signs of respiratory distress. The survival of children from cardiopulmonary arrest (9%) is dismal compared to those in respiratory failure alone (80%); therefore, it is imperative that the emergency physician anticipate and recognize early signs and symptoms of respiratory failure and intervene quickly to prevent further deterioration to cardiopulmonary failure/arrest.5,6

Neonates (defined as < 1 month of age) have large heads in relation to their body size. The relatively large occiput can result in natural flexion of the neck when lying supine, which can lead to airway obstruction. A towel roll placed under the infant’s shoulders will elevate the patient’s torso and result in a neutral position (Fig. 2–1). The neonate’s chest muscles are not well developed, and the diaphragm and abdominal muscles are the main muscles of respiration. Abdominal breathing is normal in infants, but it often becomes exaggerated and faster as the infant has increasing respiratory difficulty. With increasing respiratory distress, the abdominal muscles may become fatigued, leading to seesawing respirations that may precede respiratory failure. Also, factors that impede diaphragmatic excursion, such as a distended gastric air bubble, severe pneumoperitoneum, or ascites, can also result in respiratory failure. The differences in anatomy of the upper airway in infants and children versus adults result in increased susceptibility to respiratory distress and failure. For example, children have a relatively larger volume of tongue intraorally, which can lead to airway obstruction especially if there is loss of muscle tone and the tongue relaxes in a posterior position, obstructing the upper airway. This obstruction can be overcome by making sure that the head is repositioned to the midline and in the sniffing position. If necessary, an airway adjunct (oropharyngeal or nasopharyngeal) can be inserted. The narrow upper airway passage can also be obstructed by a foreign body or an infection that may cause inflammation and excess secretions. The large mass of tonsilar and adenoidal tissue can result in trauma to these tissues during nasotracheal 13

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SECTION I — Immediate Approach to the Critical Patient

Tracheal axis Pharyngeal axis

Oral axis

A

Tracheal axis Pharyngeal axis

Oral axis

B

Oral axis

Tracheal axis Pharyngeal axis

C

intubation or nasopharyngeal airway placement. Therefore, emergency nasotracheal intubation is rarely performed in infants and children, and caution must be exercised in placing a nasopharyngeal airway in an infant. Other airway differences that can result in additional challenges to successful endotracheal intubation include the following: 1) the pediatric epiglottis is floppy, soft, and omega or U-shaped as compared to the adult epiglottis, and 2) the larynx is higher and more cephalad (the glottis is located at C3-4 in the newborn, at C4-5 by 2 years of age, and at C5-6

FIGURE 2–1. Alignment of the tracheal, pharyngeal, and oral axes. A, Alignment of airway axes with neck flexion. B, Alignment of airway axes with head extension and neck flexion—the “sniffing position.” C, Alignment of airway axes in supine position. (From Hazinski MF [ed]: PALS Provider Manual. Dallas: American Heart Association, 2002, p 95.)

for an adult) (Fig. 2–2). Use of a Miller or Wis-Hipple laryngoscope blade is often helpful in these situations. A straight laryngoscope blade is used in young children during laryngoscopy because of the acute epiglottic angle and shallow vallecula (Fig. 2–3). The straight blade is recommended for use until approximately 3 to 5 years of age but may be used in any age child or adolescent. Also, placing a towel under the patient’s shoulders until age 2 years and under the head in older children (with head in the sniffing position) will help align the tracheal, pharyngeal, and oral axes, facilitating

Chapter 2 — Respiratory Distress and Respiratory Failure

15

Palate Tongue Epiglottis Vocal cords

FIGURE 2–2. Comparison of adult and pediatric airway structures. (Modified from Riazzi J: The difficult pediatric airway. In Benumof JL [ed]: Airway Management: Principles and Practice. St. Louis: Mosby Year Book, 1996, p 587.)

Table 2–1

Anatomic and Physiologic Airway Differences between Children and Adults That Impact Emergency Airway Management

Anatomic Differences Large occiput Large tongue Larger adenoids and tonsils Floppy and long epiglottis Larynx cephalad and anterior Narrowest portion of larynx at the cricoid ring Narrower tracheal diameter, shorter distance between rings Shorter tracheal length

Impact

Action

Flexion of the neck with possible airway obstruction Airway obstruction, especially with loss of muscle tone May obstruct airway, hemorrhage into the airway if injured Visualization of vocal cords difficult Vocal cords more difficult to visualize Use of cuffed tubes may cause pressure damage to cartilage Needle cricothyrotomy preferred surgical airway in infants and small children Intubation of the right mainstem; dislodgement

Reposition head, towel under shoulders

Narrower airway

Greater airway resistance

Fewer alveoli

Increase respiratory rate to increase minute ventilation Easy fatigability, increased abdominal breathing, increased respiratory rate

Underdeveloped chest and abdominal muscles Physiologic Differences Preferential nose breathers Increased metabolism and reduced FRC* Immature immune system

Mucus or blood may obstruct nares, causing respiratory distress Shortened period of protection from hypoxia At greater risk for respiratory infections

Behavioral Differences Inability to verbalize distress or pain

Practitioner must rely on signs based on developmental milestones

Reposition head, sniffing position, towel under shoulders, airway adjuncts Caution with use of nasopharyngeal airway; reposition head Use straight blade to intubate Positioning and use of straight blade Use uncuffed tubes until about 8 years of age or, if cuffed tube used, do not overinflate cuff Consider needle cricothyrotomy if cannot bagmask ventilate, intubate, or use LMA Use length-based resuscitation tape for ETT size and depth of ETT placement, or estimate by 3 times the ETT size; reassess frequently Suction liberally; remove foreign material; use bronchodilators for lower airway obstruction Provide supplemental oxygen; assist ventilation when respiratory rates too slow Early oxygen with signs/symptoms of respiratory distress, bag-mask ventilation with poor tidal volume or respiratory failure Suction nares liberally Oxygenate; bag-mask ventilation and cricoid pressure may be necessary prior to intubation Assess for infections with fever or signs of respiratory illness Recognize signs of respiratory distress and failure

*Functional residual capacity is the lung volume at the end of a normal expiration, when the muscles of respiration are completely relaxed; at FRC, and at FRC only, the tendency of the lungs to collapse is exactly balanced by the tendency of the chest wall to expand (see Johns Hopkins School of Medicine Interactive Respiratory Physiology website at http://oac.med.jhmi.edu/res_phys/Dictionary.html). Abbreviations: ETT, endotracheal tube; LMA, laryngeal mask airway.

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SECTION I — Immediate Approach to the Critical Patient

FIGURE 2–3. Proper use of and blade position for laryngoscope. (Modified from Gausche-Hill M, Henderson DP, Goodrich SM, et al [eds]: Pediatric Airway Management for the Prehospital Professional. Sudbury, MA: Jones & Bartlett, 2004, p 84.)

visualization of the glottis with intubation (Fig. 2–1). The pediatric larynx is funnel shaped, with the narrowest portion at the cricoid ring (below the vocal cords), whereas the adult larynx is cylinder shaped, with the glottis being the narrowest portion. Therefore, uncuffed rather than cuffed endotracheal tubes (ETTs) are often used in children younger than 8 years of age or until a size 6.0-mm ETT is needed. The use of an inflated cuff on the ETT can put pressure on the cricoid ring, which may limit blood supply and lead to pressure necrosis of the cartilage. This complication of cuffed tube use is probably less important than once believed, and now there is expanded use of cuffed ETTs in children who require high pressures to ventilate (e.g., asthma, submersion injury). The shorter tracheal length predisposes the child to complications of endotracheal intubation such as intubation of the right maintain bronchus or ETT dislodgement. Therefore, it is important to know how to estimate depth of placement of the ETT (three times the interior diameter of the ETT or by use of the Broselow tape), to check placement by auscultation or capnography, and to reassess the patient’s clinical status frequently. The narrower trachea and shorter distance between tracheal rings, as well as the short neck and increased subcutaneous tissue in infants and young children, result in greater difficulty in locating anatomic landmarks to perform surgical cricothyrotomy and in increased likelihood of severe complications such creation of a false tract, pneumomediastinum, infection, or bleeding. Needle cricothyrotomy is recommended in these infants and children if an immediate surgical airway is needed. Differences between the adult and pediatric airway are also seen in the lower airways and in the lung. The large airways of the pediatric patient are narrower than those of an adult. This leads to greater susceptibility to obstruction by mucus, edema or foreign bodies, which then leads to greater airway resistance. This is explained by looking at Poiseuille’s law, which states that resistance to flow (R) is inversely proportional to the fourth power of the radius (r) of the lumen (R = 1/r4). Therefore, if the radius is halved, the resistance increases by 16-fold. This is especially true for children with a tracheostomy because insertion of the tracheostomy tube narrows the airway opening further. Therefore, the tracheostomy lumen can easily become blocked by secretions.7 It is important to suction all patients liberally, particularly if they are producing large amounts of secretions. In the lung, infants and children have less alveoli than adults. Several studies have shown that neonates have only one third to one half of the number of alveoli in the adult human lung. The number of alveoli reaches adult values by age 8.8,9 The fewer number of alveoli results in decreased area for gas exchange. Because they do not have extra alveoli for recruitment, young children increase their respiratory rate to increase minute ventilation and oxygenation, and to eliminate carbon dioxide, making tachypnea a hallmark sign of respiratory distress. This is more pronounced in children with lung disease (e.g., reactive airway disease, bronchopulmonary dysplasia). Early intervention with supplemental oxygen and bronchodilators and support of ventilation with a bag-mask device may prevent progression of the clinical status to respiratory failure. Physiologic Differences It has been demonstrated that neonates and infants (1 month to 1 year) may be preferential nose breathers,10 thus making

Chapter 2 — Respiratory Distress and Respiratory Failure

them susceptible to nasal obstruction (choanal atresia, mucus, blood). Miller and colleagues11 noted that 8% of infants at 30 to 32 weeks’ postconceptual age and 78% of term infants were capable of oral breathing in response to nasal occlusion. The ability to tolerate complete nasal occlusion occurs in most infants by 5 months of age. Therefore, if a neonate or infant is having any respiratory difficulty, it is important to suction out both nares to relieve any obstruction. Children have a basal oxygen consumption rate two to three times that of adults.12,13 Adults consume 2 to 3 mL of oxygen per kilogram per minute under normal basal conditions. Infants and young children metabolize 4 to 9 mL of oxygen per kilogram per minute.12,13 Infants and young children also have a diminished functional residual capacity as compared to adults. This is quite significant because it means that, during apnea, children will maintain “normal” oxygenation for less than half the time of an adult; in other words, children will experience desaturation with shorter times of apnea. Therefore, it is important to supply oxygen to all children showing any signs of respiratory distress. It is also probable that bag-mask ventilation may be required to maintain “normal” oxygenation during periods of apnea prior to intubation.14 Behavioral/Developmental Issues Infants and young children are not able to communicate like an older child or an adult. They cannot tell you how they feel or verbalize that they are short of breath or in pain. Therefore, attainment of knowledge of normal behavioral milestones is imperative so that an alteration of these behaviors may be recognized and signs of respiratory failure managed promptly.

Evaluation Evaluation of a child in respiratory distress must begin with understanding of physiologic states of respiratory compromise and characterization of the anatomic site of that compromise. Respiratory distress: A condition characterized by increased work of breathing. It is often associated with increase in respiratory rate, but in later stages rates may fall and be less than normal. Signs of airway obstruction such as change in body positioning, nasal flaring, grunting, retractions, stridor, or wheezing may be present. Nonspecific signs of anxiety, restlessness, and irritability with any of the previous signs may be seen and can indicate the need for immediate intervention to avoid the progression to respiratory failure. Respiratory failure: A condition in which the compensatory mechanisms are no longer able to maintain adequate oxygenation or ventilation. Respiratory failure is characterized by poor appearance, including decrease in muscle tone, poor interactiveness, “glassy-eyed” stare and inability to focus, and weak or absent speech or cry. Changes in skin color may occur and vary from pale to cyanotic. Respiratory arrest: A condition characterized by absence of respiratory effort (prolonged apnea). Upper airway obstruction: Obstruction of the flow of air/ oxygen from the oropharynx to the carina of the trachea.

Appearance

17

Work of breathing

Circulation to skin FIGURE 2–4. Pediatric Assessment Triangle. (From Gausche-Hill M, Henderson DP, Goodrich SM, et al [eds]: Pediatric Airway Management for the Prehospital Professional. Sudbury, MA: Jones & Bartlett, 2004, p 15.)

Lower airway obstruction: Obstruction of flow of air/oxygen within the bronchi and/or bronchioles from distal to the mainstem bronchi to the aveoli. Diseases of the lung: Inflammation, infection, or scarring of the aveoli or interstitium of the lung. Assessment Any child with respiratory complaints, or any child about whom the parent expresses concerns regarding respiratory status, however mild, requires a rapid and thorough evaluation. The initial overall evaluation should contain two parts: the Pediatric Assessment Triangle (PAT), which is used to obtain an immediate general impression of the seriousness of the illness or injury, and the initial physical assessment. Based on these assessment steps, the examiners, within seconds, will have a general impression of how ill the child is and whether they need to intervene with treatment immediately or if they can continue further evaluation with the focused history and physical examination.14,15 The PAT offers an orderly approach that can be used to assess children of all ages. It allows one to gather visual and auditory clues without touching the child. This “hands-off” assessment can allow the examiner to gather critical information from a distance without upsetting the child with an invasive physical examination.14 The PAT focuses on general appearance, work of breathing, and the circulatory status of the patient (Fig. 2–4). General Appearance How a child appears to an examiner demonstrates in part the adequacy of ventilation, oxygenation, brain perfusion, body homeostasis, and central nervous system function. The components of the assessment of the general appearance are summarized in the TICLS (pronounced “tickles”) mnemonic: tone, interactiveness, consolability, look/gaze, and speech/cry.14 These five characteristics (TICLS) offer a quick way to assess a patient’s general appearance. If the patient’s appearance seems normal, then it is likely that oxygenation, ventilation, and brain perfusion are at least adequate. However, if a child’s general appearance is grossly abnormal, immediate efforts must be made to assess and treat abnormalities in oxygenation, ventilation, and perfusion while completing the initial assessment. There is still the potential for serious illness, so frequent reassessment is mandatory (Table 2–2).

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SECTION I — Immediate Approach to the Critical Patient

Table 2–2

Findings of the PAT Used to Form a General Impression of the Physiologic State

PAT General Impression

Appearance

Work of Breathing

Circulation to the Skin

Stable Respiratory Distress

Normal Normal

Normal Normal

Respiratory Failure

Abnormal Poor tone Combative Listless Lethargic

Shock

Normal/abnormal* Poor tone Listless Lethargic Abnormal Poor tone, interactiveness Inconsolability Abnormal speech or cry Abnormal Unresponsive

Normal Abnormal Nasal flaring Grunting Stridor Wheezing Retractions Abnormal Grunting Stridor Retractions Tachypnea Bradypnea Apnea Normal

Normal

Normal

Abnormal Apneic

Abnormal Cyanotic

CNS/Metabolic Disorder

Cardiopulmonary Failure

Normal/abnormal* Pale Cyanotic

Abnormal Pale Mottled

*In early stages will be normal and later progresses to abnormal.

Work of Breathing Work of breathing reflects the child’s attempt to compensate for abnormalities in oxygenation and ventilation. Assessing work of breathing requires looking for signs of increased work of breathing and listening for abnormal airway sounds.

forward during exhalation. This visual sign suggests moderate to severe hypoxia. Nasal flaring is the exaggerated opening of the nostrils during labored breathing and indicates another form of accessory muscle use that reflects significant increase in the work of breathing.

VISUAL SIGNS

Abnormal positioning, respiratory rate, retractions, head bobbing and nasal flaring, are all visual signs that indicate increased work of breathing in an effort to improve oxygenation and ventilation. A few postures indicate compensatory efforts to increase airflow. A child who is in the “sniffi ng” position (child sits leaning forward) is trying to open up his or her airway and increase airflow. It is usually a result of severe upper airway obstruction (retropharyngeal abscess, foreign body, epiglottitis). A child who refuses to lie down or who leans forward on outstretched arms (tripod position) is attempting to use accessory muscles to improve breathing (severe bronchoconstriction; asthma, bronchiolitis). Respiratory rate changes with sleep and wake states, and normal rates vary with age. The goal of the PAT assessment of respiratory rate is to determine if the rate is slow, fast, or absent. Retractions are a common physical sign of increased work of breathing. They represent the use of accessory muscles to help breathing. Retractions can be easily missed unless they are looked for with the child undressed. They can occur in the supraclavicular area, intercostal area, and substernal area. When a child is approaching respiratory failure, retractions can decrease. This is an ominous sign and occurs when a child has exhausted compensatory mechanisms. Head bobbing is the use of accessory neck muscles in infants to increase inspiratory pressure and improve breathing. The child extends the neck while inhaling, then the head falls

AUDIBLE AIRWAY SOUNDS

Abnormal airway sounds provide information about breathing effort and anatomic location of airway obstruction. Normally, the movement of air in and out of the airway cannot be heard without a stethoscope. Airway sounds that can be heard without the use of a stethoscope are abnormal and indicate obstruction to the passage of air through the airway structures. The type of abnormal airway sound is related to the location of the disease process. Table 2–3 lists abnormal airway sounds and their location, causes, and possible interventions.15 Circulatory Status The third part of the PAT is a rapid evaluation of the circulatory system to determine the adequacy of cardiac output and perfusion of vital organs. The most important part of this assessment is to observe the skin. When there is inadequate blood volume or when the heart is unable to maintain output to the body, blood supply to vital organs is conserved by shunting blood away from less essential areas of the body such as the skin and mucous membranes, resulting in mottling, pallor, and/or cyanosis. Patients in respiratory failure may also show changes in skin color. Pallor is seen in early stages and cyanosis in late stages. Using the PAT gives the clinician a rapid overall impression of whether the child’s illness or injury is severe and life threatening before a more thorough hands-on evaluation is done.

Chapter 2 — Respiratory Distress and Respiratory Failure

Table 2–3

Abnormal Airway Sounds: Possible Causes and Immediate Management

Airway Sound

Description

Location

Causes

Immediate Management

Gurgling

Heard without a stethoscope; gurgling or bubbling Heard without a stethoscope; lowpitched nasal sound

Posterior pharynx Upper airway

Provide oxygen; suctioning

Heard without a stethoscope; “hot potato” voice Heard without a stethoscope; raspy voice with changes in volume and pitch High-pitched sound usually heard during inspiration; may also be heard on expiration

Upper airway

Inability to clear secretions or excessive fluid in upper airway Oropharynx partically obstructed by tongue or soft tissues (adenoids, tonsils) Peritonsilar abscess; epiglottitis

Rhonchi

Snoring

Muffled Speech Hoarse Speech

19

Upper airway

Head positioning; airway adjuncts Head positioning; support ventilation as needed

Upper airway

Glottic inflammation from URI; croup, nodules, GE reflux

No immediate treatment needed. Specific treatment dependent on cause

Upper airway

Air passing through narrowed laryngeal or subglottic areas; foreign body, obstruction, croup, epiglottitis, allergic reaction

Low-pitched musical, rough, rattling sounds

Upper airway; mainstem bronchus

Secretions, fluids, or narrowing in the large airways

Grunting

Brief, vocalization on expiration against a partially closed glottis. Low-pitched sound.

Upper or lower airway

Wheezing

Whistling, musical sound usually present on expiration but may also be present on inspiration

Lower airway; bronchioles; alveoli

Rales (Crackles)

Fine, high-pitched crackling sounds heard mid to late inspiration No sound on auscultation

Alveoli

Produces positive endexpiratory pressure (PEEP) to keep alveoli open; pneumonia, pulmonary contusion, pulmonary edema Partially obstructed lower airway; edema, secretions, spasm. Asthma most common cause, infection, reactive airway disease, pneumonia, allergic reaction Fluid or mucus in air sacs. Pneumonia most common cause; also pneumonitis. Obstructed airway due to foreign body or airway disease

Allow patient to stay in position of comfort; provide oxygen. Support ventilation if in respiratory failure or severe distress. Specific treatment dependent on cause. Provide oxygen; suctioning. Observe for adequate oxygenation and ventilation. Bronchodilator Usually indicative of moderate to severe hypoxia. Provide oxygen. Support ventilation as needed.

Stridor

Absence of Breath Sounds

Severe partial or complete airway obstruction; severe lung disease

Provide oxygen. Bronchodilator with MDI or by nebulization. Steroids. Support of ventilation as needed.

Provide oxygen. Observe for adequate oxygenation and ventilation Provide oxygen. Foreign body removal maneuvers. Trial of bronchodilator. Support of ventilation as needed.

Abbreviations: GE, gastroesophageal; MDI, metered-dose inhaler; URI, upper respiratory infection.

A child, who is alert and anxious, is breathing rapidly, and has retractions and normal skin color is a child in respiratory distress. If this child’s appearance becomes abnormal (i.e., listless, lethargic), then the child’s condition has deteriorated to respiratory failure. The PAT helps to determine how rapidly intervention is needed and what treatments may be needed immediately. For example, a child with respiratory failure or cardiopulmonary failure will need immediate support of ventilation and oxygenation, whereas a child who has respiratory distress initially may require only supplemental oxygen. The ABCDEs The second part of the initial assessment includes a physical evaluation of the ABCDEs: airway, breathing, circulation, disability, and exposure.14,15 After the PAT and the physical examination, it should be evident whether the patient is

stable or unstable. As one proceeds through the ABCDE evaluation, it is often necessary to start interventions prior to completing the evaluation. This can be done by delegating the task while the examination is being completed. A—Airway The PAT may identify the presence and possibly the location of airway obstruction but not necessarily the degree of obstruction. It is during this “hands-on” part of the initial evaluation that one assesses the severity of the illness. If the airway is not open, one must immediately perform maneuvers to attempt to open the airway. B—Breathing During the PAT, the child’s rate of breathing is assessed as either slow, fast, or absent. During the breathing examina-

20

SECTION I — Immediate Approach to the Critical Patient

tion, the number of breaths per minute is determined and the child’s chest is auscultated with a stethoscope. When determining an infant’s respiratory rate, it is important to actually count the number of respirations for at least 30 to 60 seconds because infants often have periodic breathing. Increased respiratory rate can indicate a number of conditions, including respiratory illness, and is a sign of respiratory distress. However, in and of itself respiratory rate can be misleading. Pain, cold, exercise, anxiety, and fever can lead to an increase in respiratory rate in the absence of hypoxia. For example, for every degree in temperature elevation, respiratory rate can increase up to 5 respirations per minute. Respiratory rate can also be increased in metabolic acidosis as a buffering mechanism and might not represent a primary respiratory abnormality at all. It is also important to realize that a child who has been showing evidence of increased work of breathing and who now has a normal respiratory rate may be becoming fatigued. Because respiratory rates may vary with external or internal stimuli, recording several rates may be more useful. The trend of the results is often more accurate than the initial documented rate. A normal respiratory rate must be placed in context with other clinical signs to determine if breathing is adequate. Finally, the normal respiratory rate slows as the patient ages (Table 2–4). Increases in vital capacity allow for increased tidal volume with growth and therefore slower rates to maintain minute ventilation. Unfortunately, most references have defined normal respiratory rates for well children without anxiety, pain, respiratory complaints (without pneumonia), or fever. Moreover, the cutoffs for defining tachypnea are much higher than most published standards.16 In fact, the cutoffs for defining an abnormal respiratory rate indicative of pneumonia are much higher. The World Health Organization defines tachypnea as ≥ 60 breaths per minute (bpm) for neonates (birth to 30 days), ≥ 50 bpm for infants 1 month to 1 year old, and ≥ 40 bpm for children 1 to 5 years old.17 Others have evaluated febrile children and found that a respiratory rate ≥ 59 at birth to 6 months old, ≥ 52 at 6 to 12 months old, and ≥ 49 at 1 to 2 years old was the optimum cutoff for predicting pneumonia in febrile infants and children.18 Minute ventilation is equal to tidal volume times respiratory rate (MV = TV × RR). Generally, young infants respond by increasing respiratory rate but have a limited ability to increase tidal volume. As respiratory rates increase in

response to hypoxia, there is not enough time during a respiratory cycle to achieve adequate tidal volume or to allow oxygen to move from the alveoli into capillaries, and respiratory failure ensues. During auscultation, it is important to note the absence of breath sounds or any abnormal lungs sounds during inhalation or exhalation. It is also important to evaluate air movement and effectiveness of the work of breathing (see Table 2–3). Absence of breath sounds may indicate severe airway obstruction (upper or lower), consolidation, effusion, or pneumo- or hemothorax. C—Circulation A general impression of the circulatory status of the patient is made from looking at the skin during the PAT. A more in-depth “hands-on” assessment is then made by measuring the rate and quality of the child’s pulse, skin temperature, capillary refi ll time, and blood pressure. The environmental temperature must be considered when evaluating skin temperature, capillary refi ll time, and skin color in children. Young children and infants are very susceptible to changes in temperature. It has been documented that capillary refi ll time is prolonged in cool temperatures, even in children with normal circulatory status.19 D—Disability Assessment of disability is the evaluation of the child’s neurologic status. This evaluation includes level of consciousness, motor movements, and typically pupillary status. Hypoxia, hypercarbia, and poor perfusion along with acute central nervous system injury can result in altered levels of consciousness. Assessments of level of consciousness in children are age dependent and may include the use of the AVPU (Alert, responsive to Voice, responsive to Pain, Unresponsive) scale or the modified Glasgow Coma Scale (GCS).14,15,20 Children who are only responsive to pain or who are unresponsive on the AVPU scale, and certainly children with a GCS score less than 9, if as a result of trauma, should undergo rapid sequence intubation (RSI) to control their airway, and provide neurologic resuscitation as needed to avert herniation. Children with a medical condition resulting in severe alteration of consciousness should be considered for RSI if their condition is not quickly reversible (see Chapter 3, Rapid Sequence Intubation). E—Exposure

Table 2–4 Age 0–6 month 6–12 months 1–3 years 4–6 years 7–9 years 10–14 years 14–18 years

Normal Respiratory Rates in Children* Respiratory Rate (per minute) 30–55 24–50 16–46 14–36 12–40 15–32 14–32

Adapted from Hooker EA, Danzl DF, Brueggmeyere M, Harper E: Respiratory rates in pediatric emergency patients. J Emerg Med 10:407–410, 1992. *Cutoffs for febrile infants and children may be slightly higher.

The PAT requires that the child’s clothing be removed enough to evaluate their face, chest, and skin. When completing the initial assessment, during the ABCDE evaluation, the clothing needs to be removed enough so the child can be fully evaluated for other physiologic and anatomic abnormalities. Ancillary Studies Assessment is ongoing and, depending on patient stability, includes a secondary assessment, focused history, and complete physical examination. For children who require stabilization or resuscitation, initial assessment and critical interventions take place simultaneously. Tools such as the Broselow-Luten tape have been developed to provide a rapid and accurate method of estimating weight, necessary drug dosages, and sizes of airway equipment.21,22

Chapter 2 — Respiratory Distress and Respiratory Failure

Pulse Oximetry Pulse oximetry can be used to determine the child’s oxygen saturation level (SaO2) and estimates the adequacy of the child’s oxygenation. It does not reflect ventilation. Its use is indicated in any patient with cardiopulmonary arrest; in unstable or critically ill patients; in patients with cardiopulmonary disease; and in patients with or with the potential for hypoxia, apnea, respiratory distress/failure, or shock. Continuous pulse oximetry is recommended in the care of critically ill or injured patients, as well as those patients for whom the potential for respiratory failure exists, as it has been shown that health care providers cannot detect hypoxemia by clinical examination alone.23 A pulse oximetry reading above 94% indicates oxygenation is probably adequate; however, a child in respiratory distress or early respiratory failure might be able to maintain oxygenation by increasing work of breathing and respiratory rate. Interpretation of pulse oximetry readings should be combined with the assessment of respiratory rate, work of breathing, and chest auscultation to obtain an accurate idea of respiratory status. Chapter 5 (Monitoring in Critically Ill Children) discusses the utility of and pitfalls associated with pulse oximetry in more detail. Carbon Dioxide (CO2) Detection/Monitoring End-tidal CO2 detectors are often used to confirm placement of an ETT in the trachea. If the ETT is placed correctly, as the patient is ventilated the CO2 detector should turn from its baseline purple color to yellow with expiration, and return to purple when 100% oxygen passes across the fi lter paper. These detectors have been shown to be reliable in non–cardiac arrest states and can be used in infants weighing as little as 2 kg.24 A pediatric-size detector should be used for infants and children who weigh 2 to 15 kg. For children who weigh more than 15 kg, an adult-size detector should be used. If an adult-size detector is used in an infant, it can be used to confirm tracheal placement of the ETT but must not be left in-line as the device has a large amount of dead space (38 mL), which could lead to hypoventilation in the small infant25 (see Chapter 5, Monitoring in Critically Ill Children). Capnography Capnography or continuous end-tidal CO2 monitoring is a noninvasive method for continuously assessing the level of CO2. Carbon dioxide is produced during cellular metabolism, transported to the heart, and exhaled via the lung. Continuous monitoring of end-tidal CO2 can provide information on adequacy of ventilation, metabolism, and circulation. Capnograpy has most commonly been used to verify ETT placement and monitor ventilation in the emergency department, operating room, and intensive care unit and during transport of critically ill patients.26-29 During cardiopulmonary resuscitation (CPR), continuous end-tidal CO2 concentrations vary directly with cardiac output produced by precordial compressions.30 During effective CPR, end-tidal CO2 correlates with the efficacy of cardiac compressions and identifies the return of spontaneous circulation and likelihood of survival.31,32 Continuous CO2 monitoring also may assist in detecting hypercapnic episodes and episodes of ETT dislodgement in mechanically ventilated patients.33 Finally, end-tidal CO2 measurement may provide an earlier indica-

21

tion of respiratory failure versus that provided by pulse oximetry or measure of respiratory rate alone during procedural sedation.34 Arterial Blood Gas Measurement As the use of pulse oximetry monitoring has become standard in most emergency departments, there is much less need for arterial blood gas measurement. Arterial blood gases are rarely needed in the evaluation of children for respiratory failure but may assist in assessment of shock states or presence of acidosis (metabolic or respiratory). Radiography In the emergency department, chest radiographs are often obtained on children with asthma, acute lower respiratory infections, foreign bodies, and hypoxia and to check ETT placement. Chest radiographs are of overall limited value and should be ordered and interpreted in the context of a complete medical history and physical examination. For example, experts have found that there is no evidence that chest radiography improves the outcome of ambulatory children with acute lower respiratory infection.35,36 In children with foreign bodies, the sensitivity and specificity of the chest radiograph in identifying the presence of an airway foreign body are 73% and 45%, respectively.37 Therefore, one should not rely on chest radiography for making a diagnosis if the clinical suspicion is high. Chest radiographs are often ordered in children with wheezing. Most children with wheezing have normal chest radiographs, and those with positive findings on chest radiograph have either increased respiratory rate, increased pulse, localized rales, or decreased breath sounds.38 Dalton found that only 14% of asthmatics have abnormal radiography findings that may change management and concluded that chest radiographs should be taken in children with asthma only if the child does not respond to initial therapy.39 Lastly, routine chest radiographs in infants with bronchiolitis are usually unnecessary; fever (≥38° C) and oxygen saturation less than 94% were findings most often associated with infi ltrates on radiographs in this population.40 Chest radiography has also been utilized to evaluate children with high fever. Bachur et al. demonstrated that pneumonia was diagnosed by chest radiography in 38 of 146 children (26%) with fever (>39° C) and an elevated peripheral white blood cell (WBC) count (>20,000/µL). Of note is that these children with occult pneumonia did not have hypoxia or tachypnea.41 Routine chest radiographs for asthma or acute respiratory infections without other signs (e.g., tachypnea, tachycardia, hypoxia, fever, elevated WBC) are unnecessary unless a patient is failing management, has chronic symptoms, has localized symptoms, or is at high risk (e.g., very young, immunocompromised). Etiologies of Respiratory Distress or Failure Many different diseases and conditions can lead to respiratory distress and/or failure. These processes often involve the respiratory system, but many systemic and neurologic processes can also lead to respiratory distress and/or failure. These etiologies are listed in Table 2–5. Many of these processes are discussed in detail in other chapters throughout this book.

22

SECTION I — Immediate Approach to the Critical Patient

Table 2–5

Etiologies of Respiratory Distress and Failure in Infants and Children

Upper Airway Laryngotracheobronchitis (croup) Epiglottitis Foreign body aspiration Adenotonsilar hypertrophy Peritonsilar, parapharyngeal, or retropharyngeal abscess Subglottic stenosis, web, hemangiomas Tracheomalacia Laryngoedema Congenital anomalies Anaphylaxis Disease of the Lung Bronchopulmonary dysplasia Cystic fibrosis Submersion injury Congestive heart failure Pneumonia Pneumonitis

Chest Wall Conditions Diaphragmatic hernia Pneumothorax/hemothorax/ chylothorax Severe kyphoscoliosis Severe pectus excavatum Other Diseases Cardiac disease Sepsis Obstructive sleep apnea (pickwickian syndrome)

Lower Airway Asthma Reactive airway disease Bronchiolitis Tracheobronchomalacia Foreign body aspiration α1-Antitrypsin deficiency Hydrocarbon aspiration

Systemic Central Nervous System Status epilepticus Encephalopathy Meningoencephalitis Brain abscess, hematoma, tumor Brain stem injury Drug intoxication Arnold-Chiari malformation Medication induced Spinal/Anterior Horn Cell Poliomyelitis Guillain-Barré disease Wernig-Hoffmann disease

Neuromuscular junction Myasthenia gravis Botulism Tetanus Myopathy/neuropathy General anesthesia Organophosphates

The initial diagnostic evaluation is used to determine if the patient is stable or unstable and to identify the category of respiratory disorder. If the patient is stable, then the physician can continue with the secondary assessment, complete history, and physical examination. Interventions may proceed based on physiologic dysfunction and category of respiratory dysfunction. It is important to reassess the patient frequently so that, if the patient becomes unstable, immediate management occurs. If the patient is unstable (respiratory distress, respiratory failure, respiratory arrest, cardiopulmonary failure or cardiopulmonary arrest), then the physician should begin immediate interventions to support oxygenation and perfusion.

Management Management proceeds based on assessment of need and in a logical fashion from the least to most invasive and complex interventions. These interventions may include all or some of the following: 1. Positioning of the head in the midline position with a towel under the shoulders or head.

FIGURE 2–5. Jaw-thrust maneuver to open the airway.

2. Opening the airway by performing a head tilt–chin lift in the medical patient or a jaw-thrust maneuver in the trauma patient (Fig. 2–5). 3. Suctioning the airway if the patient has oral or nasal secretions or blood. 4. Providing oxygen supplementation, either by low-flow systems such as a nasal cannula, or by simple face masks, which provide a low fraction of inspired oxygen (FiO2) (but greater than ambient FiO2), or systems that provide inspired oxygen levels of 95% or greater. These systems include partial non-rebreather masks for infants or full non-rebreather masks for older children. 5. Placing airway adjuncts such as a nasopharyngeal airway (can be used in the semiconscious patient) or an oropharyngeal airway (only used in the unconscious patient without a gag reflex). 6. Performing bag-mask ventilation to support ventilation and oxygenation for patients requiring assisted ventilation or neurologic resuscitation. 7. Considering advanced airway techniques when the management techniques listed previously do not improve the patient’s clinical status: RSI, and laryngoscopy and foreign body removal with Magill forceps. 8. Placing a laryngeal mask airway or performing cricothyrotomy (needle or surgical) for patients who cannot be ventilated with bag-mask ventilation or whose airway cannot be secured by endotracheal intubation (see Chapter 3, Rapid Sequence Intubation; and Chapter 4, Intubation, Rescue Devices, and Airway Adjuncts). Initial intervention will include positioning the head, opening the airway, and providing supplemental oxygen. Suctioning may be added for signs of increased secretions or blood in the airway. If positioning and suctioning do not open the airway, one should consider upper airway obstruction from a foreign body and perform age-specific obstructed airway techniques (back blows and chest thrusts for infants or abdominal thrusts for children > 1 year of age). Consider direct laryngoscopy with Magill forceps for possible foreign body removal. If airway obstruction continues, a surgical airway can be attempted with needle or surgical cricothyrotomy.

Chapter 2 — Respiratory Distress and Respiratory Failure

23

FIGURE 2–6. Placement of an oropharyngeal airway.

FIGURE 2–7. Bag-mask ventilation on a child; note hand position (EC clamp).

For patients without foreign body obstruction but who are unable to maintain a patent airway with positioning, the physician should place an airway adjunct such as a nasopharyngeal airway or an oropharyngeal airway. Nasopharyngeal airways are used in semiconscious patients and should be avoided in young infants, patients with bleeding disorders, or those with craniofacial injury. Oropharyngeal airways are used in unconscious patients without a gag reflex to keep the airway open, usually during bag-mask ventilation. Figure 2–6 demonstrates placement of the oropharyngeal airway in a pediatric patient. Bag-mask ventilation is indicated for the initial support of ventilation and oxygenation when compensatory mechanisms fail and the patient is in respiratory failure. If positioning, suctioning, adding airway adjuncts, or providing supplemental oxygen are not successful in improving a patient’s condition and assisted ventilation is needed, then bag-mask ventilation should begin without delay. The first step is to ensure the correct size of face mask is used. The correct size mask will measure from the bridge of the nose to the cleft of the chin. Once the mask is attached to the elbow adapter on the bag, a “C” is formed with the physician’s thumb and index finger. The mask is placed on the patient’s face, the physician’s thumb is wrapped around the mask at the end of the mask that lies on the bridge of the nose, and the index finger is placed around the lower part of the mask at the chin. The third, fourth, and fifth digits are placed along the angle of the patient’s jaw, forming an “E,” and the chin is pulled into the mask to ensure a seal. The entire hand position is called the “EC clamp” (Fig. 2–7).42 It is important not to place the “E” fingers in the soft tissue under the chin as pressure in this area can compress the airway or cause the tongue to fall back against the posterior pharynx, leading to airway obstruction. The Sellick maneuver (cricoid pressure) may be used if significant pressure is needed to ventilate, but it is possible to place too much pressure on the cricoid membrane and collapse the airway, leading to airway obstruction. To begin ventilation, the physician squeezes the bag for 1 to 2 seconds and with only enough force to cause chest rise, then releases the pressure on the bag. It is important to realize that the volume of air needed to provide adequate chest rise is

between 8 and 10 mL/kg. For a neonate only about 30 mL (2 tablespoons) of air is needed to cause adequate chest rise; a 1-year-old requires only about 105 mL (7 tablespoons). Excessive volume instilled with the bag-mask device can lead to gastric insufflation and vomiting.43 Gausche and colleagues showed that using the “squeeze, release, release” technique for bag-mask ventilation, versus using endotracheal intubation to ventilate infants and children in the prehospital setting, can lead to improved outcomes for children in respiratory failure.44 The person providing bag-mask ventilation should allow for slightly longer inspiratory times and then the patient is allowed time to passively exhale. The respiratory rate should be between 30 and 40 breaths/min in a neonate, 20 and 30 breaths/min in an infant, and no more than 20 breaths/min in a child. Modifications of this technique can be considered in patients when it is difficult to maintain a seal with one hand. In these cases, a two-person technique, with one person holding the mask with the EC clamp using both hands and the other squeezing the bag-mask device, may be used. In a case of upper airway obstruction, it has been shown that bag-mask ventilation with the patient in the prone position may be useful.45 Endotracheal intubation and RSI are utilized in patients requiring long-term support of oxygenation and ventilation; in patients requiring neurologic resuscitation (GCS score < 9); in patients requiring airway protection, such as those with burns, anaphylaxis, or overdose; and in patients in whom bag-mask ventilation fails to support oxygenation and ventilation. (Endotracheal intubation and RSI are discussed in more detail in Chapter 3 Rapid Sequence Intubation; and Chapter 4, Intubation, Rescue Devices, and Airway Adjuncts.) The Difficult Airway When dealing with children in an emergency department setting, it is imperative that one be able to anticipate a potentially difficult airway and have a backup plan if bag-mask ventilation and endotracheal intubation are unsuccessful. It is also necessary to have backup management plans when one comes across an unanticipated difficult airway.

24

SECTION I — Immediate Approach to the Critical Patient

Unlike the adult difficult airway, evaluation and management strategies for the difficult airway in children are not well described. This section discusses the evaluation, history, and physical examination of a patient prior to airway management to look for features that may indicate a difficult airway. History The American Society of Anesthesiologists Task Force on Management of the Difficult Airway stated that, although there is insufficient published evidence to evaluate the effect of a bedside medical history on predicting the presence of a difficult airway, there is suggestive evidence that some features of a patient’s medical history (congenital syndromes, acquired or traumatic disease states, or history of prior difficult intubation) may be related to the likelihood of encountering a difficult airway.46 Therefore, it is recommended that an airway history, whenever feasible, be conducted. Table 2–6 lists features that may be evident from the history that can indicate the possibility of encountering a difficult airway. Importantly, there are multiple congenital disorders and syndromes associated with anatomic and physiologic disorders that make airway management difficult (e.g., micrognathia, macroglossia, cervical spine disorders, hypotonia, midface disorders).47 Physical Examination According to the American Society of Anesthesiologists Task Force, an airway physical examination should be conducted, whenever feasible, prior to the initiation of airway manage-

Table 2–6

Historical Features That May Indicate a Difficult Airway

Feature

Anatomic Correlate

Prior history of difficult intubation Snoring/noisy breathing/obstructive sleep apnea Difficulty feeding secondary to cough or cyanosis Difficulty breathing with URI Recurrent croup

Narrow epiglottic angle; anterior vocal cords Enlarged adenoidal/tonsillar tissue

Juvenile rheumatoid arthritis TMJ syndrome Acquired conditions Croup Epiglottis Retropharyngeal abscess Ludwig’s angina Thermal injury Caustic ingestion Facial or neck trauma

Foreign body

ment in all patients. The intent of this examination is to detect physical characteristics that may indicate the presence of a difficult airway.46 Physical findings that may predict airway difficulty are listed in Table 2–7, and some are discussed below.47-52 The oropharyngeal examination is the first step to examining the airway. If possible, the patient’s oral cavity should be examined with his or her mouth open and tongue maximally protruded. If the patient is uncooperative or too young to cooperate, this can be done with a tongue blade with the patient lying down. The degree of mouth opening and the size of the tongue in relation to the oral cavity are assessed. Mallampati et al.53 classified airways on the basis of the degree of visualization of the faucial pillars, soft palate, and uvula. This classification has been used extensively in adults to predict the degree of difficulty with endotracheal intubation. Whether it can successfully predict difficulty in children is not known. Other findings in the oropharyngeal examination that may suggest difficult laryngoscopy and intubation are outlined in Table 2–7. After the oropharyngeal examination, the ability to extend the patient’s neck should be assessed. Neck extension is often necessary during laryngoscopy to be able to visualize the vocal cords. Obviously, neck extension should not be evaluated in a trauma patient when cervical spine trauma is suspected. However, the inability to extend the neck as a result of trauma or congenital syndromes, such as trisomy 21 or Goldenhar and Klippel-Feil syndromes, or acquired conditions, such as juvenile rheumatoid arthritis or prior cervical spine fi xation, is a predictor of the possibility of difficult laryngoscopy and intubation.49,51 A short mandible, micrognathia, or a small oral cavity make visualization of the airway challenging due to the anterior location of the airway

Possibly reduced oxygen reserve Enlarged adenoidal/tonsillar tissue Narrow glottic area, hemangioma Limited mouth opening Limited mouth opening Normal anatomy is altered, usually by swelling, leading to upper airway obstruction

Variety of reasons: obstruction, loss of landmarks, blood in airway, cervical spine stabilization Upper airway obstruction

Abbreviations: TMJ, temporomandibular; URI, upper respiratory infection.

Table 2–7

Findings on Physical Examination That May Predict a Difficult Airway

Trauma Facial and/or neck trauma Blood in airway Facial or oral burns Oropharyngeal Mallampati class III and class IV Macroglossia Small mouth Prominent central incisors Limited mouth opening (e.g., limited TMJ mobility, trismus from deep space infections, maxillofacial trauma) Laryngeal edema (e.g., infection, inhalation injury, caustic ingestion) Enlarged tonsils High-arched palate Foreign body Secretions in upper airway Swelling of intraoral structures (e.g., anaphylaxis, congenital syndromes) Other Short neck Limited neck extension or flexion Micrognathia (short mandible) Obesity Abbreviation: TMJ, temporomandibular.

Chapter 2 — Respiratory Distress and Respiratory Failure

25

Difficult Airway Algorithm 1. Assess the likelihood and clinical impact of basic management problems. A. Difficult ventilation C. Difficulty with patient cooperation or consent B. Difficult intubation D. Difficult tracheostomy 2. Actively pursue opportunities to deliver supplemental oxygen throughout the process of difficult airway management. 3. Consider the relative merits and feasibility of basic management choices: A.

Awake intubation

—vs—

Intubation attempts after induction of general anesthesia

B.

Non-invasive technique for initial approach to intubation

—vs—

Invasive technique for initial approach to intubation

C.

Preservation of spontaneous ventilation

—vs—

Ablation of spontaneous ventilation

4. Develop primary and alternative strategies.

A.

Airway approached by non-invasive intubation

Succeed*

Cancel case

B.

Awake intubation

Airway secured by invasive access*

Intubation attempts after induction of general anesthesia

Initial intubation attempts successful*

Fail

Consider feasibility of other optionsa

Invasive airway accessb*

Initial intubation attempts UNSUCCESSFUL FROM THIS POINT ONWARD CONSIDER 1. Calling for help 2. Returning to spontaneous ventilation 3. Awakening the patient

Face mask ventilation not adequate

Face mask ventilation adequate

Consider/attempt LMA LMA not adequate or not feasible

LMA adequate*

Non-emergency pathway Ventilation adequate, intubation unsuccessful

If both face mask and LMA ventilation become inadequate

Alternative approaches to intubationc

Successful intubation*

Emergency pathway Ventilation inadequate, intubation unsuccessful

Fail after multiple attempts

Call for help

Emergency non-invasive airway ventilatione

Successful ventilatione

Fail

Emergency invasive airway Invasive airway accessb*

Awaken Consider patientd feasibility of other optionsa

a Other options include (but are not limited to): surgery utilizing face mask or LMA anesthesia, local anesthesia infiltration or regional nerve blockade. Pursuit of these

options usually implies that mask ventilation will not be problematic. Therefore, these options may be of limited value if this step in the algorithm has been reached via the Emergency Pathway. b Invasive airway access includes surgical or percutaneous tracheostomy or cricothyrotomy. c Alternative non-invasive approaches to difficult intubation include (but are not limited to): use of different laryngoscope blades, LMA as an intubation conduit (with or without fiberoptic guidance), fiberoptic intubation, intubating stylet or tube changer, light wand, retrograde intubation, and blind oral or nasal intubation. d Consider re-preparation of the patient for awake intubation or canceling surgery. e Options for emergency non-invasive airway ventilation include (but are not limited to): rigid bronchoscope, esophageal-tracheal combitube ventilation, or transtracheal jet ventilation.

FIGURE 2–8. Guideline for management of the difficult airway. (Adapted from American Society of Anesthesiologists Task Force on Management of the Difficult Airway: Practice guidelines for management of the difficult airway. an updated report. Anesthesiology 95:1269–1277, 2003.)

26

SECTION I — Immediate Approach to the Critical Patient

Table 2–8

Suggested Equipment for the Difficult Airway Cart46,49,50

Exhaled CO2 detector (adult and pediatric) Face masks (neonate to adult) Laryngoscope blades of all sizes and styles Magill forceps Local anesthetics All sizes of naso- and oropharyngeal airways Suction equipment and catheters Self-inflating resuscitation bags Endotracheal tubes of all sizes, cuffed and uncuffed Endotracheal tube guides: Semirigid intubation stylets Light wand Forceps designed to manipulate the distal portion of the tracheal tube Gum elastic bougie Laryngeal mask airways, assorted sizes Flexible fiberoptic intubation equipment Emergency nonsurgical ventilation (at least one): Transtracheal jet ventilation Hollow jet ventilation stylet Tracheoesophageal Combitube Emergency surgical airway access: Cricothyrotomy equipment Commercially available cricothyrotomy kit for children The items listed represent only suggestions as some of these items will be available in standard intubation/airway trays. The contents of the difficult airway cart should be customized to meet the needs, preferences, and skills of the emergency department physicians.46 From Behringer EC: Approaches to managing the upper pathway. Anesthesiol Clin North America 20:813–832, 2002.

and the small area in which to manipulate the structures with laryngoscopy. Micrognathia is a prominent feature in Treacher-Collins and Pierre Robin syndromes.49,51 Micrognathia can also make it difficult to achieve an adequate seal during bag-mask ventilation. Although it is uncommon to encounter a difficult airway in a child, it is critical to be able to predict a difficult airway before using induction agents and neuromuscular blockade. Failure to predict a difficult airway and failure to have an alternative plan when encountering an unanticipated difficult airway can result in a life-threatening situation in which ventilation and oxygenation are impossible. It is imperative that emergency physicians have access to a difficult airway cart that contains additional equipment used to perform or facilitate intubation or to establish an airway. A list of suggested equipment is found in Table 2–8.46,48,49,51 It is also important to remember that calling early for assistance from anesthesia or otolaryngology when a difficult airway is anticipated is highly recommended. The American Society of Anesthesiologists Task Force has established a difficult airway algorithm to help with difficult airway management (Fig. 2–8).46

Summary Early recognition of respiratory distress and failure in an infant or child with appropriate interventions will optimize outcomes. Additional research is needed to identify factors leading to respiratory failure and devices that may accurately predict the need for early intervention. The role of the laryngeal mask airway in emergency settings is ill-defined at this

point in time, but this airway must be investigated as a possible tool to initially manage patients with respiratory failure. Evaluation of factors and examination techniques that can predict a difficult airway in children should be explored. Finally, optimal and cost-effective ways to maintain airway management skills for physicians who rarely perform these life-saving techniques on children need to be studied. REFERENCES 1. Dieckmann RD, Brownstein DR, Gausche-Hill M (eds): Pediatric Education for Prehospital Professionals. Sudbury, MA: Jones & Bartlett/ American Academy of Pediatrics, 2000. 2. Seidel JS, Henderson DP, Ward P, et al: Pediatric prehospital care in urban and rural areas. Pediatrics 88:681–690, 1991. 3. Isaacman DJ, Poirier MP, Gausche-Hill M, et al: Controversies in pediatric emergency medicine: prehospital emergencies. Pediatr Emerg Care 20:135–149, 2004. 4. Krauss BS, Harakal T, Fleisher GR: The spectrum and frequency of illness presenting to a pediatric emergency department. Pediatr Emerg Care 7:67–71, 1991. 5. Young KD, Gausche-Hill M, McClung CD, Lewis RJ: A large prospective population-based study of the epidemiology and outcome of outof-hospital pediatric cardiopulmonary arrest. Pediatrics 114:157–164, 2004. 6. Gausche M, Lewis RJ, Stratton SJ, et al: Effect of out-of-hospital pediatric endotracheal intubation on survival and neurological outcome: a controlled clinical trial. JAMA 283:783–790, 2000. 7. Gausche-Hill M: Introduction. In Gausche-Hill M, Henderson DP, Goodrich SM, et al (eds): Pediatric Airway Management for the Prehospital Professional. Sudbury, MA: Jones & Bartlett, 2004, pp 1–11. 8. Hislop AA, Wigglesworth JS, Desai R: Alveolar development in the human fetus and infant. Early Human Dev 13:1–11, 1986. 9. Zeltner TB, Caduff JH, Gehr P, et al: The postnatal development and growth of the human lung. Morphometry Respir Physiol 67:247–267, 1987. 10. Berry FA, Yemen TA: Pediatric airway in health and disease. Pediatr Clin North Am 41:153–180, 1994. 11. Miller MJ, Carlo WA, Strohl KP, et al: Effect of maturation on oral breathing in sleeping premature infants. J Pediatr 109:515–519, 1986. 12. Hill JR, Rahimtulla KA: Heat balance and the metabolic rate of newborn babies in relation to environmental temperatures and the effect of age and of weight on basal metabolic rate. J Physiol (Lond) 180:239–265, 1965. 13. Luten RC: The pediatric patient. In Walls RM (ed): Manual of Emergency Airway Management. Philadelphia: Lippincott, Williams & Wilkins, 2000, pp 143–152. 14. Pediatric assessment. In Dieckmann RD, Brownstein DR, Gausche-Hill M (eds): Pediatric Education for Prehospital Professionals. Sudbury, MA: Jones & Bartlett/American Academy of Pediatrics, 2000, pp 33–55. 15. Henderson DP: Assessment. In Gausche-Hill M, Henderson DP, Goodrich SM, et al (eds): Pediatric Airway Management for the Prehospital Professional. Sudbury, MA: Jones & Bartlett, 2004, pp 14–27. 16. Hooker EA, Danzl DF, Brueggmeyer M, Harper E: Respiratory rates in pediatric emergency patients. J Emerg Med 10:407–410, 1992. 17. Rothrock SG, Green SM, Fanelli JM, et al: Do published guidelines predict pneumonia in children presenting to an urban ED? Pediatr Emerg Care 17:240–243, 2001. 18. Taylor JA, Del Beccaro M, Done S, Winters W: Establishing clinically relevant standards for tachypnea in febrile children younger than 2 years. Arch Pediatr Adolesc Med 149:283–287, 1995. 19. Gorelick MH, Shaw KN, Baker MD: Effect of ambient temperature on capillary refi ll in healthy children. Pediatrics 92:699–702, 1993. 20. Trauma resuscitation and spinal immobilization. In Hazinski MF, Zaritsky AL, Nadkarni VM, et al (eds): PALS Provider Manual. Dallas, TX: American Heart Association, 2002, pp 253–286. 21. Lubitz DS, Seidel JS, Chameides L, et al: A rapid method for estimating weight and resuscitation drug dosages from length in the pediatric age group. Ann Emerg Med 17:576–581, 1988. 22. Luten R: Error and time delay in pediatric trauma resuscitation: addressing the problem with color-coded resuscitation aids. Surg Clin North Am 82:303–314, 2002.

Chapter 2 — Respiratory Distress and Respiratory Failure 23. Brown LH, Manring EA, Komegay HB, et al.: Can prehospital personnel detect hypoxemia without the aid of pulse oximeters? Am J Emerg Med 14:43–44, 1996. 24. Bhende MS, Thompson AE, Orr RA: Utility of an end-tidal CO2 detector in verifying endotracheal tube placement in infants and children. Ann Emerg Med 21:142–145, 1992. 25. Endotracheal intubation. In Gausche-Hill M, Henderson DP, Goodrich SM, et al (eds): Pediatric Airway Management for the Prehospital Professional. Sudbury, MA: Jones & Bartlett, 2004, pp 79–95. 26. Bhende MS: End-tidal carbon dioxide monitoring in pediatrics— clinical applications. J Postgrad Med 47:215–218, 2001. 27. Bhende MS, Thompson AE, Orr RA: Utility of an end-tidal CO2 detector during stabilization and transport of critically ill children. Pediatrics 89:1042–1044, 1992. 28. Palmon SC, Liu M, Moore LE, Kirsch JR: Capnography facilitates tight control of ventilation during transport. Crit Care Med 24:608–611, 1996. 29. Tobias JD, Lynch A, Garrett J: Alterations of end-tidal carbon dioxide during the intrahospital transport of children. Pediatr Emerg Care 12:249–251, 1996. 30. Falk JL, Rackow EC, Weil MH: End-tidal carbon dioxide concentration during cardiopulmonary resuscitation. N Engl J Med 318:607–611, 1988. 31. Sanders AB, Ewy GA, Bragg S, et al: Expired PCO2 as a prognostic indicator of successful resuscitation from cardiac arrest. Ann Emerg Med 14:948–952, 1985. 32. Garnett AR, Ornato JP, Gonzalez ER, Johnson EB: End-tidal carbon dioxide monitoring during cardiopulmonary resuscitation. JAMA 257:512–515, 1987. 33. Bhende MS: Capnography in the paediatric emergency department. Pediatr Emerg Care 15:64–69, 1999. 34. Hart LS, Berns SD, Houck CS, Boenning DAI: The value of end-tidal CO2 monitoring when comparing three methods of procedural sedation for children undergoing painful procedures in the emergency department. Pediatr Emerg Care 13:189–193, 1997 35. Swingler GH, Hussey GD, Zwarenstein M: Randomised controlled trial of clinical outcome after chest radiograph in ambulatory acute lowerrespiratory infection in children. Lancet 351:404–408, 1998. 36. Swingler GH, Zwarenstein M: Chest radiograph in acute respiratory infections in children. Cochrane Database Syst Rev 2:CD001268, 2000. 37. Silva AB, Muntz HR, Clary R: Utility of conventional radiography in the diagnosis and management of pediatric airway foreign bodies. Ann Otol Rhinol Laryngol 107:834–838, 1998. 38. Gershel JC, Goldman HS, Stein RE, et al: The usefulness of chest radiographs in fi rst asthma attacks. N Engl J Med 309:336–339, 1983.

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39. Dalton AM: A review of radiological abnormalities in 135 patients presenting with acute asthma. Arch Emerg Med 1:36–40, 1991. 40. Garcia Garcia ML, Calvo Rey C, Quevedo Teruel S, et al: Chest radiograph in bronchiolitis: is it always necessary? An Pediatr (Barc) 61:219– 225, 2004. 41. Bachur R, Perry H, Harper MB: Occult pneumonias: empiric chest radiographs in febrile children with leukocytosis. Ann Emerg Med 33:166–173, 1999. 42. Cooper A, Tunik M, Foltin G, et al: Teaching paramedics to ventilate infants: preliminary results of a new method. In Chameides L (ed): Proceedings of the International Conference on Pediatric Resuscitation. Washington, DC: Washington National Center for Education in Maternal and Child Health, June, 1994, p 8. 43. Melker RJ, Banner MJ: Ventilation during CPR: two-rescuer standards reappraised. Ann Emerg Med 14:397–402, 1985. 44. Gausche M, Lewis RJ, Stratton SJ, et al: Effect of out-of-hospital pediatric endotracheal intubation on survival and neurological outcome: A controlled clinical trial. JAMA 283:783–790, 2000. 45. Ghirga G, Ghirga P, Palazzi C, et al: Bag-mask ventilation as a temporizing measure in acute infectious upper-airway obstruction: does it really work? Pediatr Emerg Care 17:444–446, 2001. *46. American Society of Anesthesiologists Task Force on Management of the Difficult Airway: Practice guidelines for management of the difficult airway. an updated report. Anesthesiology 95:1269–1277, 2003. 47. Walker RW: Management of the difficult airway in children. J R Soc Med 94:341–344, 2001. 48. Jones KL (ed): Smith’s Recognizable Patterns of Human Malformation. Philadelphia: WB Saunders, 1997. *49. Sullivan KJ, Kissoon N: Securing the child’s airway in the emergency department. Pediatr Emerg Care 18:108–120, 2002. 50. Behringer EC: Approaches to managing the upper airway. Anesthesiol Clin North America 20:813–832, 2002. 51. Tobias JD: Airway management for pediatric emergencies. Pediatr Ann 25:323–328, 1996. 52. Kaide CG, Hollingsworth JC: Current strategies for airway management in the trauma patient, part II: managing difficult and failed airways. Trauma Reps 4:1–12, 2003. 53. Mallampati Sr, Gatt SP, Gugino LD, et al: A clinical sign to predict difficult tracheal intubation: a prospective study. Can Anaesth Soc J 32:429–434, 1985. *Selected readings.

Chapter 3 Rapid Sequence Intubation Steven G. Rothrock, MD

Key Points Immaturity of the autonomic nervous system in neonates and infants increases their propensity to develop bradycardia with airway manipulation, hypoxia, and succinylcholine use. Unique anatomic and physiologic properties require a different approach, medication dosing, and techniques for rapid sequence intubation in neonates, young infants, children, and adolescents. Preoxygenation for 2 minutes with 100% oxygen allows for only 2 minutes of apnea before desaturation occurs in healthy infants and even less time in ill infants. To ensure success, clinicians must use a consistent stepwise methodology for intubation that includes personnel and patient preparation, medication and equipment selection, procedural performance, confirmation of correct tube placement, and advancement to rescue techniques when appropriate.

Introduction and Background Airway manipulation during endotracheal intubation is associated with adverse cardiovascular effects (hypertension, bradycardia, tachycardia, arrhythmias) and increased intracranial, intraocular, and intragastric pressure in addition to airway trauma and hypoxia. Rapid sequence induction is the process of providing rapid sedation during general anesthesia in unprepared patients at risk for aspiration. Rapid sequence intubation (RSI) is used to describe rapid sequence induction using sedation and paralysis during endotracheal intubation while minimizing trauma, time to airway control, and complications of intubation and airway manipulation. Emergency medicine and pediatric emergency medicine physicians using RSI have ≥ 99% success rates for controlling an airway in children with traumatic and medical disorders without requiring surgical rescue techniques.1-3 28

Recognition and Approach Several features make the technique of rapid sequence induction more difficult in infants and children compared to adults. Infants and young children have less rigid support to their major airway structures.4 The soft palate and epiglottis obstruct the airway more commonly than the tongue in patients with an altered level of consciousness and in those undergoing anesthesia.5-7 In infants and children, these structures have less cartilaginous support than found in adults, increasing the propensity to collapse and obstruct during sedation. The tongue also encompasses a proportionately larger amount of the oropharynx, increasing the difficulty of mask ventilation and passage of airway devices. Immature diaphragmatic and intercostal muscle composition and positioning lead to more rapid fatigue and respiratory decompensation, accelerating the need to make airway decisions in the very young.4 The physiologic response to hypoxia and laryngeal manipulation is exaggerated in young infants. The neonatal cardiac conduction system has predominant intrinsic sympathetic activity within the sinus and atrioventricular nodes, resulting in a high resting heart rate.8 In contrast, little sympathetic innervation of the ventricles and bundle branches exists in neonates and young infants.9 The absence of nerves that directly supply the ventricles makes them less electrically stable and exaggerates the cardiac response to stress.8 This effect is offset by a predominant vagal nerve influence mediated by cholinergic fibers that directly supply the atrial and ventricular conduction systems.8,10 This autonomic imbalance predisposes the heart to profound accelerations and decelerations with stress. Bradycardia is induced by airway manipulation, hypoxia, and succinylcholine administration in infants ≤ 1 year old. By 1 year, autonomic imbalances diminish, limiting these adverse effects and limiting the theoretical basis for using atropine as a premedication.11,12 Neonates and young infants differ from older children and adults in their responses to many anesthetic agents. In the neonate, relatively larger extracellular fluid volume and blood volume, smaller muscle mass and fat stores, and greater blood flow to the central organs influence the effect and metabolism of drugs.8 Drug metabolism is less effective in neonates than in children due to incompletely developed hepatic enzyme systems and glomerular fi ltration. These factors contribute to increased toxicity and sensitivity to a variety of agents used during airway management (e.g.,

Chapter 3 — Rapid Sequence Intubation

benzodiazepines and narcotics) and a requirement for different drug doses. A smaller muscle mass and a larger volume of distribution require use of higher relative doses of succinylcholine at younger ages.13 Knowledge of these physiologic differences allows for selection of safer, rational choices during RSI. Prior to performing RSI, patients are preoxygenated with 100% O2 to create an oxygen reservoir. In healthy adults, the effect of this nitrogen washout is a maintenance of oxygen saturation greater than 90% for up to 8 minutes of apnea.14 Infants and young children consume more oxygen and have a smaller functional residual capacity compared to older children, adolescents, and adults.12,15 For this reason, infants and children will desaturate more quickly, resulting in a shortened window of opportunity for endotracheal intubation before hypoxia occurs.14 Selection of patients requiring RSI is one of the most important decisions made in the emergency department (ED). This technique should be considered in every patient requiring definitive airway control (e.g., respiratory failure, shock, altered mental status) in an emergency fashion in whom no contraindications exist.

Evaluation If time permits, obtain a brief history including allergies, prior problems with anesthesia, medications, time of last meal, and associated medical conditions. Disorders placing patients at risk for complications from RSI require immediate identification. Subacute or chronic burns and neurologic or muscle disease (e.g., muscular dystrophy) increase the risk of fatal hyperkalemia following succinylcholine administration and require use of nondepolarizing agents.16 Children with prior reactions to anesthetics or a family history of malignant hyperthermia or neuroleptic malignant syndrome should not receive succinylcholine.16 The presence of an upper respiratory infection or airway irritation (e.g., trauma, blood) increases the risk of laryngospasm and decreases the time to desaturation.17 Prior to paralysis, clinicians must make a determination of their ability to manually intubate and ventilate the patient based upon history, clinical features, and anatomic variables. Authors have analyzed the ability of intraoral (incisor-toincisor) distance, mandibular length, Mallampatti score, and thyromental distance to predict difficult intubations in adults undergoing general anesthesia. These parameters have poor utility in the ED. Only an intraoral distance less than 2.5 cm is statistically associated with difficult intubations in adult ED patients.18 No studies have analyzed the ability of any of these criteria to predict difficult intubations in infants or children. Children at risk for difficult intubations include those with a history of micrognathia, macroglossia, prominent dentition, cleft palate, limited temporomandibular joint mobility or congenital cervical spine disorders. Acquired abnormalities associated with difficult intubations include any disorder that distorts the neck, oral, or facial anatomy (e.g., burns, edema, blood, vomitus, infection), temporomandibular joint immobility (e.g., lateral airway abscess or trauma), or potential cervical spine trauma requiring immobility. Intrinsic or acquired airway and lung disease may make bag-mask ventilation difficult in patients who are sedated and paralyzed. Depending upon the urgency for airway control,

29

immediate surgical or alternate airway techniques (e.g., awake intubation, bronchoscopy) may be required in patients at risk for difficult intubations. A significant number of children with difficult intubations have no identifiable risk factors; therefore, rescue devices and alternative techniques must be prepared for every patient undergoing RSI (see Chapter 4, Intubation, Rescue Devices, and Airway Adjuncts).

Management Equipment Preparation Equipment preparation prior to patient arrival is essential to satisfactory completion of RSI. Every ED should be equipped with appropriate ventilation and bag-mask devices, oxygen masks, laryngoscope blades, oral airways, suctioning devices, endotracheal tubes (ETTs), laryngeal mask airways, and other rescue devices for all ages and sizes. A color-coded system (e.g., drawers in a cart or wall shelving) based on weight and age helps to rapidly select appropriately sized equipment. Monitoring devices, including cardiac monitors, pulse oximetry, and ETT placement confirmation devices (e.g., end-tidal CO2 monitors), should be available and checked systematically for proper functioning. Length-based estimates (e.g., Broselow-Luten tape) are a rapid and accurate means of equipment selection (Table 3–1). Age-based equipment selection may be employed, although this technique may be slightly less accurate than length-based estimates (Table 3–1). Straight laryngoscope blades are used until age 2 years, with either curved (e.g., McIntosh) or straight blades used above this age. For the youngest infants (120

Infants ≤1 yr old, all requiring >1 dose of succinylcholine

Extreme tachycardia or tachycardic arrhythmia

Lidocaine

1.5–2.0 mg/kg

3

Defasciculating or priming agent

1/10th paralytic dose below

3–4

Only useful 3 min before intubation N/A

Head injury suspected and weak sedative given Consider if >5 yr & possible increased intracranial pressure

High-degree atrioventricular block, amide anesthetic allergy See succinylcholine and nondepolarizing agents below

0.25–0.5

5–15

Trauma, head injury, hypovolemia

Adrenal suppression, underlying seizures

Induction Etomidate

0.3–0.4 mg/kg

Thiopental

3–5 mg/kg

0.5–1.0

10–30

Head injury, normal blood pressure

Hypotension, barbiturate allergy, porphyria

Ketamine (with atropine)

1–2 mg/kg

0.5–1.0

10

Asthma, noncardiac hypotension

Head injury, glaucoma, cardiogenic shock

Midazolam

0.1–0.3 mg/kg

1–5

20–30

Propofol

2.5 mg/kg

0.5–1.0

3–10

Absence of shock (do not use in preterm infants) Useful if paralytics contraindicated, age ≥3 years, and blood pressure is OK

Shock, hypersensitive to midazolam, narrowangle glaucoma Hypotension; hypersensitive to sulfites, soybean oil, egg yolk, or egg lectithin

0–1 year: 2–3 mg/kg 1–5 year: 1.5–2 mg/kg >5 years: 1–1.5 mg/kg 0.6 mg/kg (0.9 mg/kg)

0.5–1

3–8

Rapid paralysis

Cannot ventilate, neurologic or muscle disease, subacutechronic burn, hyperkalemia

Hyperkalemia; increased intracranial, gastric, and ocular pressure; fasciculations Hypotension, tachycardia or bradycardia, arrhythmias, bronchospasm See above See above

Paralytic Succinylcholine

Rocuronium

Mivacurium Vecuronium

0.15–0.25 mg/kg 0.1–0.2 mg/kg

1–1.5 (60)

Priming or defasciculating agent, cannot use succinylcholine

Unable to mask ventilate; use half dose if liver disease

2–2.5 2–5

10–20 30–45

See above See above

Unable to mask ventilate Unable to mask ventilate

*Dose for rapid sequence intubation. † See Table 3–1 for exact timing of medication administration.

Painful injection, myoclonus, vomiting, adrenal suppression Hypotension, bronchospasm (esp. if asthma), local necrosis Vomiting, hypersalivation, hypertension, tachycardia Hypotension, bradycardia Hypotension, bradycardia, flushing, acidosis, muscular twitching, pain on injection

32

SECTION I — Immediate Approach to the Critical Patient

increased heart rate or tachycardia in 88% to 95%, with a decreased heart rate in 12% and bradycardia in 0 to 2%39-41 In contrast, use of halothane with succinycholine in children leads to bradycardia in 14% to 30% of cases.32,40,42 Addition of atropine to succinylcholine may increase the overall number of dysrhythmias compared to use of succinycholine alone.17,43 Adding sedatives to the intubating regimen further diminishes the cardiovascular response and side effects from laryngoscopy and succinylcholine. Other important considerations include the ability of atropine to mask significant physiologic changes (e.g., assessing shock management, intracranial pressure changes, airway complications, pain, sedation level). Moreover, atropine increases temperature and the risk of malignant hyperthermia, increases ventricular arrhythmias, relaxes the lower esophageal sphincter with increased risk of aspiration, lowers the seizure threshold, induces confusion, and increases urinary retention. Atropine also has a narrow therapeutic index, increasing the potential for dosing errors.39,43,44 Despite prior recommendations, atropine use is no longer considered routine in infants and children undergoing intubation among many neonatologists and anesthesiologists in the United States, Canada, Europe, and Australia.43-47 As no controlled studies have proven when atropine is beneficial, evidence-based recommendations cannot be given. Atropine should always be readily available with appropriate dosing calculated prior to all intubations as its use may become necessary. If no contraindications exist prior to intubation, atropine should be administered to all infants ≤ 1 year old, to all patients receiving a second dose of succinylcholine regardless of age, and to all patients receiving ketamine, an agent that causes prominent airway secretions. Moreover, children who are already bradycardic require atropine prior to intubation, especially when succinylcholine is used. For all other cases, ED personnel should be prepared to administer atropine if bradycardia develops during or after intubation with the realization that bradycardia may be a clue to a coexisting physiologic derangement (e.g., airway blockage, hypoxia, increased intracranial pressure, profound shock) or prolonged airway manipulation. The correct dose of atropine is 0.02 mg/kg intravenously (IV), with a minimum of 0.1 mg and maximum of 0.6 mg per single dose. Lidocaine is a cardioactive agent that has been recommended by some experts to reduce intracranial pressure in patients with possible head trauma or space-occupying intracranial lesions who require endotracheal intubation.36,48,49 This recommendation has been based, in part, on adult studies that evaluated the intracranial pressure response to endotracheal suctioning in patients with tumors or a recent neurosurgical procedure.50-53 Lidocaine has been shown to suppress the cough reflex, and this mechanism may explain its benefit during endotracheal suctioning.50-52 Others have examined the effect of IV lidocaine administration on hemodynamic parameters during intubation, assuming that blunting the hemodynamic response to intubation would correlate with a diminished intracranial pressure response. Conflicting studies have found that IV lidocaine either has no effect on blood pressure54-63 or heart rate55-57,60-64 or attenuates a rise in blood pressure65-68 and heart rate58,59,65-68 during laryngoscopy and intubation. Upon further analysis of these studies, it appears that the addition of lidocaine to a strong sedating agent (e.g., thiopental, propofol) has minimal

to no additional hemodynamic blunting effect.57-59,61,63-65,69,70 A hemodynamic blunting effect is more likely when agents with less sedating or less cardiovascular effects are used (e.g., midazolam, etomidate).61,71,72 The optimum lidocaine dose is 1.5 to 2 mg/kg IV.66,68,73-75 To be effective, lidocaine must be given precisely 3 minutes prior to laryngoscopy.67,76 If given at 1, 2, or 5 minutes preintubation, its effects are diminished or absent.67,76 Lidocaine should be considered in patients who receive etomidate or midazolam as induction agents. Other cardioactive agents (especially β-blockers, calcium channel blockers, and short-acting narcotics) have been used to blunt the heart rate and blood pressure response to endotracheal intubation and lower the intracranial pressure response to intubation. Of these, esmolol has been shown most useful at blunting hemodynamic parameters.55,62 However, no pediatric studies have shown this to be a safe addition to RSI in the ED setting. Short-acting narcotics (e.g., fentanyl, alfentanil, sufentanil) also increase intracranial pressure and should be avoided during RSI if a head injury is possible.77,78 A “defasciculating” dose of a neuromuscular blocking agent is often administered prior to succinylcholine in adults to diminish side effects during RSI. Generally, this involves administration of a 1/10th intubating dose of a nondepolarizing agent or a 1/10th dose of succinylcholine IV 3 to 4 minutes prior to administration of a full dose of succinylcholine to decrease muscle fasciculations and intracranial, intragastric, and intraocular pressure. Children 5 years old and younger have less muscle mass and have minimal to no risk of fasciculations with succinylcholine administration. Thus, defasciculating agents are not recommended at this age. For children older than 5 years, use of a defasciculating agent is controversial. Importantly, experts have found that it is not the fasciculations that determine the cerebral response to succinylcholine. Instead, it is the effect of succinylcholine on muscle spindle afferent fibers that correlates with peak cerebral pressure and flow responses regardless of whether or not fasciculations occur.79 It is unclear if this muscle afferent signal is blocked by administration of a defasciculating agent.79,80 Moreover, administration of a defasciculating dose of a paralytic rarely can cause paralysis, adds to the multidrug cocktail given for RSI and thus increases the risk for dosing errors, and increases the time to intubation during RSI with succinycholine. This technique is best reserved for relatively stable patients older than 5 years when a 3- to 4-minute delay will not affect outcome. Alternately, a similar priming dose (1/10th of paralytic dose) of a nondepolarizing agent can be administered 3 to 4 minutes prior to the intubating dose of a nondepolarizing paralytic agent. This priming dose will decrease the time required to wait for complete paralysis by nearly one half depending upon which agent is administered. Medications (Sedatives and Paralytics) Multiple drugs can be used to induce anesthesia or unconsciousness during RSI. Clinicians need to be fully aware of indications, contraindications, side effects, and dosing for each of these medications (see Table 3–2). Sodium thiopental is a barbiturate that depresses the patient’s reticular activating system. This agent has a rapid uptake within the brain, producing a rapid onset, usually

Chapter 3 — Rapid Sequence Intubation

within 30 seconds. It also causes cerebral vasoconstriction, decreasing blood flow and intracranial pressure. It is ideal for patients with isolated increased intracranial pressure without hypotension. It should be avoided in patients with hypotension, hypovolemia, or cardiovascular instability.35 Etomidate is a carboxylated imidazole with sedativehypnotic properties that produces unconsciousness within 15 to 30 seconds of administration. It is not an analgesic, has little effect on blood pressure, and causes a slight decrease in systemic vascular resistance, cerebral blood flow, and intracranial pressure.37,81 Due to its cardiovascular and central nervous system protective effects, it is an ideal induction agent in trauma patients with and without head injury.82 Side effects include pain on injection, adrenocortical suppression (minimal with a single dose), hypertonicity, coughing, laryngospasm, hiccoughing, vomiting, occasional involuntary muscle movements, and muted ability to blunt blood pressure and heart rate responses to laryngeal manipulation.37,81 Due to these effects, many experts recommend adding other cardioprotective agents (e.g., benzodiazepines, lidocaine) when etomidate is used as an induction agent.37,81 The typical RSI dose is 0.3 to 0.4 mg/kg IV.81,82 Ketamine is a dissociative sedative that produces profound analgesia and amnesia. When used alone, it results in protective airway reflexes, spontaneous respirations, and cardiopulmonary stability. Its bronchodilating effects make it an ideal agent for intubation of asthmatics. Its hemodynamic protective effects allow for use in patients who are hypotensive due to volume depletion. Prominent salivation requires coadministration with atropine, although ketamine’s catecholamine stimulatory effects limit bradycardia when coadministered with succinylcholine. Ketamine raises intracranial pressure and intraocular pressure and should be avoided if either of these effects is a concern. Ketamine may have adverse effects if cardiogenic shock is present and should be avoided in most patients with cardiac-related hypotension. A typical IV dose is 1 to 2 mg/kg (administered with atropine), with an onset of less than 1 minute.83 Midazolam is a rapid-acting benzodiazepine that can be used as an induction agent in select cases. It has no analgesic properties and may worsen hypotension. It is most appropriately used in hemodynamically stable patients. Its dose should be reduced or an alternate agent selected in patients with severe cardiovascular instability. The typical induction dose is 0.1 to 0.3 mg/kg IV.35 Propofol is an IV anesthetic that can be used an induction agent. It has a rapid onset ( 1 Number of alternative techniques used Cormack glottic visualization score (0 = complete, 3 = nonvisualization) • Lifting force for laryngoscopy (0 or 1) • External laryngeal pressure to visualize cords (0 or 1) • Vocal cords abducted? (0 or 1) • • • •

*An ideal intubation would receive a score of zero.

Table 4–1

Indications for Intubation: NEAR I

Trauma Head injury General management Airway problem Face/neck trauma Burn/inhalational injury Traumatic arrest Total (trauma)

38 24 9 2 2 2 77

Medical Status epilepticus Toxin Cardiac arrest Asthma Pneumonia Sepsis Coma Congestive heart failure Other Total (medical) Unknown Total Overall

25 9 7 6 3 3 2 2 20 77 2 156

From Sagarin MJ, Chiang V, Sakles JC, et al: Rapid sequence intubation for pediatric emergency airway management. Pediatr Emerg Care 18:417–423, 2002.

It is often impossible to obtain detailed historical information before intubating a critically ill child. If time permits, however, a past medical history should focus on whether the patient has been intubated before and if any problems were experienced. The patient’s birth history may be contributory: former premature infants have a higher incidence of subglottic stenosis and of chronic respiratory insufficiency. Patients with certain genetic syndromes (e.g., Down syndrome, mucopolysaccharidoses) may be predisposed to distorted airway anatomy. It is essential to seek any history compatible with muscular dystrophy, the presence of which contraindicates the use of succinylcholine. If the current indication for endotracheal intubation (ETI) is trauma, maintaining cervical spine immobility is paramount, and an additional operator will be required for ETI. Likewise, certain preexisting diagnoses (e.g., Down syndrome) may predispose the patient to atlantoaxial instability, in which case cervical spine precautions should be employed. A list of preexisting medical diagnoses that should alert the emergency physician to the possibility of a difficult airway is provided in Table 4–2.2 All patients should be assumed to have a full stomach, and planning should account for this. In the absence of an identified difficult airway, RSI is the procedure of choice. Table 4–2

Preexisting Conditions That May Predispose to Difficult Airway Management in Children

Newborn Period Tracheal agenesis Laryngeal atresia Congenital fusion of jaws Congenital laryngeal stenosis Laryngeal web Congenital ankylosis of temporomandibular joint Cystic hygroma Craniofacial Dysmorphology Cleft lip/palate Micrognathic disorders (PierreRobin, Treacher-Collins, etc.) Goldenhar syndrome

Acute/Chronic Inflammatory Diseases Epiglottitis Tonsillitis Head/neck abcess (retropharyngeal, peritonsillar, submandibular) Gangrenous stomatitis Ludwig’s angina

Trauma Cervical spine injury Face/neck trauma Burn/inhalational injury Mass Lesions Head/neck tumors Hematoma/hemangiomas Lingual thyroid, epiglottic cyst Metabolic/Musculoskeletal Disorders Mucopolysaccharidoses Mucolipidoses Beckwith-Wiedemann syndrome Arthrogryposis Achondroplasia Other Trisomy 21 Cri-du-chat syndrome Russell-Silver syndrome Klippel-Feil syndrome Cockayne syndrome

From Frei FJ, Ummenhofer W: Difficult airway in pediatrics. Paediatr Anaesth 6:251–263, 1996.

39

Chapter 4 — Intubation, Rescue Devices, and Airway Adjuncts

Anatomy

Physiology

Pediatric intubation is, in general, easily accomplished, and the incidence of difficult intubation is less than in adults, who have many more acquired conditions that make intubation difficult. Important anatomic differences, however, distinguish the pediatric intubation from the adult, and, to a lesser degree, intubation of the infant from that of the older child. Age-related variations in size also mandate careful equipment selection and drug dosing. Specific considerations related to pediatric intubation are as follows: • Size—airway structures are smaller and the field of vision with laryngoscopy is more narrow • Adenoidal hypertrophy is common in young children, leading to: 䊊 Greater difficulty with nasotracheal intubation 䊊 Greater risk for injury to adenoidal tissue with resultant bleeding in the hypopharynx when laryngoscopy is performed • The tongue is large relative to the size of the oropharynx. • Superior larynx (Fig. 4–1)—often imprecisely referred to as “anterior,” the laryngeal opening in infants and young children is actually located in a superior position (in infants, the larynx is opposite C3-4 as opposed to C4-5 in adults). This makes the angle of the laryngeal opening with respect to the base of the tongue more acute and visualization by direct laryngoscopy more difficult. • The hyoepiglottic ligament (connects base of tongue to epiglottis) is more elastic in young children; thus, a laryngoscope blade in the vallecula may not elevate the epiglottis as efficiently as in an adult. • The epiglottis of children is narrow and angled acutely with respect to the tracheal axis; thus the epiglottis covers the tracheal opening to a greater extent and can be more difficult to mobilize. • The narrowest point of the young child’s airway occurs at the level of the cricoid cartilage instead of at the level of the glottic opening itself.

Respiratory Physiology LUNG

Infants have fewer and smaller alveoli than young children, and their overall gas exchange surface area is disproportionately small. Surface area reaches proportions similar to adulthood by 8 years of age. Channels for collateral ventilation (pores of Kuhn and Lambert’s channels) are absent in infancy. The overall effect of these phenomena is a greater tendency for alveolar hypoventilation and for the development of atelectasis during a respiratory illness.3 RESPIRATORY MECHANICS

The pediatric thoracic skeleton is largely cartilaginous and much more compliant than the adult skeleton. Elastic recoil of the chest wall in the young child is essentially absent. A given change in thoracic pressure will result in a larger change in lung volume, similar to the physiology seen in an adult with emphysema. A given change in volume is associated with little or no change in pressure, so that a greater amount of work is required to generate a tidal breath. The high compliance of the pediatric chest wall results in a closing volume (CV) (volume at which terminal bronchioles collapse because they are no longer supported by elastic recoil) that can be elevated with respect to functional residual capacity (FRC). If the already diminished elastic recoil is impaired (e.g., by supine positioning), CV can exceed FRC to an even greater extent, resulting in the absence of ventilation of some lung segments during normal tidal breathing. Young patients therefore have a greater tendency for intrapulmonary shunting and hypoxemia with the positioning required for airway management. Accessory respiratory muscles in young children are composed of a lower percentage of slow-twitch muscle fibers and are more susceptible to fatigue compared to the diaphragm. Also, the architecture of the pediatric thorax (horizontal rib orientation with extensive cartilage composition) is such that

Junction of chin and neck Epiglottis

FIGURE 4–1. Relative position of the pediatric larynx in the neck compared to that in the adult. (Adapted from Walls RA [ed]: Manual of Emergency Airway Management. Philadelphia: Lippincott Williams & Wilkins, 2000.)

Vocal cords Cricoid membrane Cricoid ring Infant

Adult

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SECTION I — Immediate Approach to the Critical Patient

intercostal and suprasternal muscles are poorly recruited to assist in respiratory effort. AIRWAY

Airway diameter and length increase with age. The distal airway (bronchioles) lags in growth behind the proximal airway during the first few years of life. Poiseuille’s law states that airway resistance is inversely proportional to the fourth power of the radius of the airway. Thus young children have higher resistance to airflow at baseline in their lower airways, and a change in airway diameter of a given dimension will have a much more profound effect on airway resistance in a small child than in an older child or adult. Such a change can occur as a result of edema, obstruction, or excess secretions. Illnesses that affect the caliber of small airways (such as asthma and viral bronchiolitis) produce a disproportionate increase in work of breathing in infants and children.3 CELLULAR OXYGENATION

Resting oxygen consumption in the newborn is twice that of an adult (6 mL/kg/min vs. 3 mL/kg/min), and increased adipose tissue provides a greater mass per volume of FRC than in the adult. Oxygen consumption in infants is extremely sensitive to physiologic derangements such as fever and hypothermia. The oxyhemoglobin dissociation curve for young infants is shifted to the left (greater affinity of hemoglobin for oxygen and poorer tissue oxygen delivery) by the presence of elevated amounts of fetal hemoglobin.3 Combined Effects of Respiratory Physiologic Factors The summary effects of the various respiratory physiologic phenomena described previously are a greater tendency for hypoxemia and arterial desaturation. Figure 4–2 shows a Time to Hemoglobin Desaturation with Initial FAO2=0.87 100

90

model of oxyhemoglobin desaturation4 to demonstrate the time to critical desaturation of several classes of patients, including children. According to this model, a healthy 10-kg child will desaturate to 90% after approximately 3 minutes of apnea, much more quickly than healthy or even moderately ill adults.5 This rapid desaturation is a product of two attributes: the greater oxygen consumption in children (described earlier) and the greater body mass index of young children, placing a greater relative demand on their pulmonary oxygen capacity. Desaturation rates vary with age. Infants preoxygenated with 100% oxygen for 2 minutes can maintain their oxyhemoglobin saturation above 90% for approximately 2 minutes, compared with almost 2.5 minutes for toddlers and over 4 minutes for children greater than 3 years of age. The time required for the saturation to fall from 95% to 90% is significantly shorter in infants than older children as well (8 seconds compared with 16 seconds).6 The rate of oxyhemoglobin desaturation has not been determined for children with varying degrees of systemic or pulmonary illness or injury, but it is logical to assume that it is even more rapid than described here, reinforcing the requirement for continuous monitoring of oxyhemoglobin saturation during intubation, as during all phases of the management of a seriously ill or injured child. When oxyhemoglobin saturation falls to 90%, intubation attempts are paused to permit bag-mask ventilation to restore adequate (>95%) oxygen saturation. Cardiovascular Physiology Children have higher vagal tone than older patients, so laryngoscopy has a much greater tendency to produce vagally mediated bradycardia in young children. Succinylcholine, which is formed by joining two acetylcholine molecules, can have significant cardiac muscarinic effect in children, aggravating the vagal effects of the laryngoscopy. Atropine, 0.02 mg/kg, should be administered to children under 10 years of age who are to receive succinylcholine for intubation. Children have a limited ability to vary stroke volume in order to maintain cardiac output, and, as a result, tachycardia is often the sole compensatory mechanism in low cardiac output states. Vagally mediated bradycardia can have a significantly deleterious effect on cardiac output.

SaO2, %

Neonatal Physiology 80 Mean time to recovery of twitch height from 1 mg/kg/ succinylcholine i.v.

70

60 0

10% 0

1

2

3

4

6.8

5 6 7 . Time of VE=0, minutes

Obese 127kg adult Normal 10kg child

50% 8

8.5

9

90% 10.2

10

Moderately ill 70kg adult Normal 70kg adult

FIGURE 4–2. Time to hemoglobin desaturation with initial FAO2 = 0.87. (From Benumof JL, Dagg R, Benumof R: Critical hemoglobin desaturation will occur before return to an unparalyzed state following 1 mg/kg intravenous succinylcholine [see comment]. Anesthesiology 87:979– 982, 1997.)

Neonates in particular have significantly fragile cardiopulmonary adaptive mechanisms. Hypoxia is very poorly tolerated and causes paradoxical bradycardia. Additionally, neonatal respiratory control is immature and uncoordinated, with newborns typically exhibiting periodic breathing (absence of respiratory effort for up to 15 seconds) for up to several weeks of life. Minute ventilation does not increase sufficiently in response to hypercarbia, so hypoxemia results in transient hyperventilation and actually progresses to respiratory depression as oxygen tension falls.

Equipment One of the challenges in airway management of children is the range of sizes of equipment necessary for safely and effectively caring for patients throughout the pediatric age range. Several rules of thumb have been designed and validated to minimize confusion pertaining to this issue; among the most

Chapter 4 — Intubation, Rescue Devices, and Airway Adjuncts

prevalently used is the length-based equipment selection, commonly accomplished through use of the Broselow-Luten tape and color-coding system. This and other sizing schema are discussed in more detail in this section as well as in Chapter 2 (Respiratory Distress and Respiratory Failure). Ventilation Equipment Bag-Valve-Mask Devices (Anesthesia vs. Self-inflating) Bag-valve-mask (BVM) devices fall into two broad classes. Self-inflating bags, or Ambu bags, are semirigid plastic elliptical bags that return to their original shape spontaneously after being compressed. A properly configured self-inflating bag has a one-way exhalation valve, requiring the bag to replenish itself from a high-flow oxygen supply, often combined with a reservoir system, to deliver high concentrations of oxygen (>90%). These bags can also deliver high concentrations of oxygen during active breathing by the patient. Anesthesia circuits consist of collapsible bags connected to an expiratory limb and a venting mechanism, most often a one-way valve allowing the egress of exhaled gases. Advantages to the use of anesthesia bags include the ability to provide 100% oxygen without a reservoir and a greater sensitivity to detect changes in airway pressure, with both spontaneous and assisted breaths. Most anesthesia circuits have an adjustable valve incorporated into the venting mechanism, allowing the operator to adjust the maximum amount of inspiratory pressure delivered to the patient; this may enable the operator to minimize barotrauma from elevated inflating pressures. Disadvantages of anesthesia circuits include the fact that they are more difficult to use by inexperienced personnel and the fact that they cannot be used in the absence of an air or oxygen source. Suctioning Ideally two separate suction devices should be available and opened to maximal suction. One should have a rigid tonsillar suction (Yankauer) tip attached for suctioning the mouth and oropharynx, and the second should have a smaller caliber flexible catheter for suctioning thin secretions in the hypopharynx or via the endotracheal tube, after intubation. If only one suction source is available, both suction tip devices should be at hand so that they can be interchanged if necessary. Endotracheal Intubation Laryngoscope The two predominant types of laryngoscope blades used in pediatric airway management are the straight (Miller, Wisconsin) and curved (MacIntosh). Both types can be used in children and adults successfully depending on operator experience. Most pediatric practitioners favor the use of straight blades when intubating young children because of the laxity of the supporting structures of the epiglottis discussed previously. For infants less than 1 year, straight laryngoscope blades with the widest flange (e.g., Wis-Hipple, Wisconsin, Flagg) are best for controlling the relatively large tongue.7,8 For older children, blades with a narrower flange (e.g., Miller) can control the tongue and decrease trauma to the gingiva and teeth. Further modification with a curve at the tip allows for the options of either direct elevation of the

Table 4–3

41

Laryngoscope Blades and Sizes

Laryngoscope Blade

Patient Age

Miller 0 Miller 1

Newborns up to 2.5 kg 0–3 mo

Wis-Hipple 1.5 Miller 2

3 mo–3 yr >3 yr

Miller 3

Large adolescents

Patient Length (Broselow-Luten Tape Color) NA 60.75–85 cm (pink, red, purple) 85–132.5 cm (yellow, white, blue, orange) 137.5–155 cm (green)

epiglottis via the blade or blade insertion into the vallecula (e.g., modified Miller, Phillips) in older infants.8 Appropriate sizes of blades for children of different ages, according to both age and Broselow-Luten sizing, are shown in Table 4–3. When properly inserted, the tip of a straight laryngoscope blade rests underneath the tip of the epiglottis, and, when upward force is applied, the blade physically lifts the epiglottis out of the way to expose the glottic opening, as depicted in Figure 4–3A. The curved blade can be used in exactly the same manner, but usually the blade is positioned such that the tip lies in the vallecula, anterior to the epiglottis, and upward traction pulls the epiglottis up and exposes the glottic opening, as shown in Figure 4–3B. Endotracheal Tubes The two most commonly applied rules of thumb for sizing of endotracheal tubes (ETTs) are the age-based rule and selection based on body length (the Broselow-Luten tape). The age-based rule is [Age in years/4] + 4 = ETT size The Broselow-Luten tape selects the size of ETT based on the length of the patient. Both age- and length-based rules have been shown to be accurate in the majority of patients, and both can be used depending on operator preference. Some data have shown that the age-based rule tends to overestimate ETT size, whereas the Broselow tape tends to underestimate it.9-12 Application of age-based sizing criteria to children younger than 2 years of age is less accurate; recommendations for ETT sizing in this age range are detailed in Chapter 2 (Respiratory Distress and Respiratory Failure). Another unvalidated “rule” that is often applied to children is that the diameter of a child’s airway is approximately the same diameter as the child’s fifth digit, and that an ETT with an outer diameter of that same size is an accurate choice of size. This simple guideline has unfortunately not stood up to validation testing, and cannot be recommended. It may be that the width of the nail of the fifth digit is a more accurate predictor of ETT size than the diameter of the finger itself.11,13 As mentioned earlier, the narrowest point in the airway of the young child occurs at the level of the cricoid cartilage, below the insertion of the vocal cords. In these patients, uncuffed endotracheal tubes are often the most appropriate

42

SECTION I — Immediate Approach to the Critical Patient

BVM ventilation, but provide no airway protection. In general, a patient who requires a device to maintain airway patency may also require intubation for airway protection. Both devices exist in a range of sizes suitable for all pediatric ages. The correct size of an OP airway for a patient can be estimated by the distance from the patient’s central incisors to the angle of the mandible; for NP airways, the correct size is estimated by the distance from the naris to the earlobe. OP airways, when properly positioned, tend to rest against the base of the tongue and, in conscious patients, can induce gagging and vomiting so they should be used only in the unconscious patient. An OP airway should always be used when an unconscious patient is undergoing bag-mask ventilation. Alternative Airway Techniques17

A

B FIGURE 4–3. A, Correct position and exposure of glottic opening with a straight laryngoscope blade. B, Correct position and exposure of glottic opening with a curved laryngoscope blade.

tubes to achieve easy passage through the upper airway and the ability to ventilate effectively without excessive air leak. The conformation of the airway approximates that of an adult by about age 8 years; children beyond that age most often require cuffed endotracheal tubes to achieve a good fit in the trachea. Multiple studies have shown that cuffed ETTs can be safely used in small children, and that the likelihood of postextubation stridor is not significantly increased by their use; additionally, anesthesia studies have shown decreased need for gas flow with cuffed ETT use, suggesting a better fit to the tracheal lumen with cuffed than uncuffed ETTs.14,15 Current recommendations state that “cuffed endotracheal tubes . . . may be appropriate under circumstances in which high inspiratory pressure is expected.”16 Airway Adjuncts (Oral Airways, Nasopharyngeal Airways) Oropharyngeal (OP) and nasopharyngeal (NP) airways can be used to maintain airway patency, particularly during

A number of devices and techniques have been used successfully in the operating room for ventilation during general anesthesia, and have also been used for both primary and rescue airway management in emergency patients. Some are specific devices that are placed into the airway, and these can be thought of as supraglottic (e.g., laryngeal mask airway [LMA]), infraglottic (e.g., Combitube), or surgical (e.g., percutaneous transtracheal jet ventilation, cricothyrotomy), to distinguish them from the glottic placement of an endotracheal tube. Other devices assist in the placement of an ETT by improving visualization of the glottic aperature, and include fiberoptic (both flexible and rigid) and video devices. LMAs (see discussion of use later) are available in multiple sizes and from multiple manufacturers to accommodate patients from newborn through adulthood. The Combitube (see discussion of use later) is available in sizes appropriate for patients of at least 48 inches in height. Newer supraglottic devices such as the cuffed oropharyngeal airway (COPA), the laryngeal tube (King LT), and the pharyngeal-tracheal lumen (PTL), exist in sizes appropriate for use in larger patients.

Monitoring A patient undergoing emergency ETI is potentially critically ill, and should have single-lead electrocardiography, oximetry, and blood pressure monitoring. Many operators find it helpful to have the tone of the oximeter made audible so that a change in heart rate (cadence) or saturation (pitch of tone) can be appreciated without viewing the readout. Bradycardia during laryngoscopy is usually caused by vagal influence, but hypoxemia must always be excluded by oximetry. Monitoring should continue from the preparatory phases through the intubation and throughout the period of postintubation care. Detection of exhaled carbon dioxide is the standard of care for confirmation of tracheal placement of an ETT, and should be performed in every case. This can be done using a colorimetric device, or by continuous capnography. Capnography can be useful in circumstances in which noninvasive continuous monitoring of alveolar ventilation is desirable (e.g., status asthmaticus, traumatic brain injury). In cases of prolonged cardiac arrest, when CO2 exchange has ceased, end-tidal CO2 (ETCO2) detection can be falsely negative, indicating esophageal placement when the tube is in the trachea. In cardiac arrest resuscitation, if ETCO2 is detected and the tube is inserted to the proper depth, tracheal

Chapter 4 — Intubation, Rescue Devices, and Airway Adjuncts

placement is assured. When ETCO2 detection is negative during circulatory arrest, alternate means of tube placement confirmation are required.

Techniques Orotracheal Intubation Airway Positioning ANATOMIC ASPECTS

Numerous anatomic features unique to children must be recognized with regard to airway positioning. Elevation of the occiput with respect to the shoulders, commonly employed in adults and adolescents, may worsen the view of the glottic opening in infants and toddlers. The infant or toddler should be supine on a flat surface with the head in a neutral position or with a small degree of extension at the neck. Excessive flexion or extension can result in airway obstruction in small children. CERVICAL SPINE PRECAUTIONS

When necessary, cervical spine immobilization requires the presence of an assistant maintaining the head in a neutral position. This can be performed by kneeling or standing at the intubator’s side and holding the child’s head from above the patient, or by standing at one side of the patient and reaching from below to hold the sides of the head. The purpose of the immobilization is to both prevent and detect any movement that might be occurring during that intubation that is changing the relationship between the head, neck, and torso. During intubation, the front of the cervical collar is opened to prevent restriction of jaw opening produced by the collar. JAW THRUST AND CHIN LIFT

Maintaining a patent airway in the supine patient involves displacing the mandibular block of tissue (jaw, floor of mouth, and tongue) anteriorly away from the posterior oropharynx. This can be accomplished by one or a combination of numerous techniques. Most commonly applied are the jaw thrust, in which the operator applies upward pressure behind the angle of the mandible on one or both sides of the patient, and the chin lift, in which the apex of the mandible is grasped and lifted upward. These techniques can be applied with one or two hands and with or without a mask in place. Difficulty maintaining airway patency with these techniques may be indicative of the need for an airway adjunct, or (worst case) a surgical approach to the airway. Preoxygenation As discussed previously, the time to desaturation of healthy, fully preoxygenated children is on the order of 2 to 3 minutes. Critically ill children have a shorter desaturation time. Preoxygenation is essential for children undergoing ETI, unless it is not possible. Despite adequate preoxygenation, a critically ill child can desaturate very quickly after apnea is induced, and continuous oximetry is essential. Critically ill children may require assisted ventilation during their apneic period to maintain arterial saturation, which makes good BVM technique as well as properly applied cricoid pressure (see next) of paramount importance.5,6,18,19

43

Cricoid Pressure/Laryngeal Manipulation The technique of cricoid pressure was initially described by Sellick in 1961 as a technique to prevent aspiration of regurgitated gastric contents during anesthesia induction and intubation.20 Sellick’s maneuver also prevents insufflation of air into the stomach with positive pressure ventilation. The technique is performed by applying firm pressure on the cricoid ring, displacing it backward to occlude the posterior esophagus. Sellick’s maneuver is applied as soon as the patient loses consciousness and is continued vigilantly until the endotracheal tube is placed, with the cuff inflated (if applicable) and position confirmed by ETCO2 detection. The generally accepted standard in adults is to apply 10 pounds (4.5 kg, 44 N) of pressure continuously. Published reports have shown that cricoid pressure is often applied incorrectly or ineffectively, and cases of vocal cord and glottis distortion and even airway obstruction due to improperly performed cricoid pressure maneuvers have been reported.21-23 Those performing the maneuver should be trained to do so. Current literature has not specifically examined the use of cricoid pressure for RSI in the ill child. While it is logical to extrapolate that decreased pressure is required for children, no data exist as to the optimal pressure required to occlude the pediatric esophagus. The pressure typically applied by anesthesiologists has been shown to be less than for adults (5 to 5.5 pounds), but whether this pressure is clinically appropriate is unknown.24 The theoretical rationale for the use of cricoid pressure in pediatric intubation is very strong. In addition to reducing the likelihood of gastric regurgitation with aspiration during intubation, Sellick’s maneuver also minimizes entry of air into the stomach during bag-mask ventilation. It is very often necessary to support ill children with positive pressure ventilation during RSI, and the prevention of gastric insufflation with cricoid pressure can be of great importance to minimize gastric distention and risk of regurgitation of gastric contents. Application of backward-upward-rightward pressure on the larynx—commonly referred to as “BURP”—optimizes the view of the glottic opening in cases of difficult laryngoscopy.20 An assistant applies direct pressure on the thyroid cartilage, displacing it dorsally, rostrally, and to the patient’s right. The BURP maneuver is superior to simple cricoid pressure in improving glottic visualization in difficult laryngoscopy cases.25 External laryngeal manipulation is a technique wherein the intubator uses his her right hand to maneuver the laryngeal structures while maintaining his her own line of sight with the airway opening.26 Once an optimal position is found, the intubator ensures that an assistant maintains that position of the larynx while the patient is intubated. This technique has been validated using videographic imaging in adults intubated by emergency medicine interns.27 Neither of these techniques has been studied in children, but both could be logically extrapolated to the pediatric patient as long as gentle external forces are used, as the amount of pressure needed to occlude or distort the pediatric airway is likely much less than that needed for an adult. Laryngoscopy (see Table 4-2, Fig. 4-1) The laryngoscope is held in the intubator’s left hand and the right hand is used to open the mouth. The blade is advanced into the oropharynx in such a way as to sweep the tongue to

44

SECTION I — Immediate Approach to the Critical Patient

the left side of the mouth and hold it there. Passing the blade to a midline position and gently down the esophagus will allow the intubator to visualize the glottis during gentle withdrawal of the blade. As the blade is withdrawn, the first structure that comes into view is the glottis, with the epiglottis held in an anterior position by the blade. Figure 4–3A and Figure 4-3B show the proper positioning of straight and curved laryngoscope blades. In the former case, the tip goes under the epiglottis, lifting it out of the way; in the latter, the tip rests in the vallecula and upward traction pulls the epiglottis up out of the line of sight. The curved blade can also be used to actively lift the epiglottis if necessary.16 Tube Insertion The ETT is held by the right hand and inserted while line of sight to the glottic opening is maintained with the laryngoscope. It is important not to allow the tube to obstruct the intubator’s view of the vocal cords. A common error that leads to obstruction of the line of sight during direct laryngoscopy is sliding the tube along the channel of the blade instead of at the right side of the mouth away from the blade. If a video laryngoscope is used (e.g., DCI Video MacIntosh, Karl Storz North America), the tube is placed by passing it along the channel of the blade and through the glottis under video visualization. In children with small mouths, an assistant can stretch the right corner of the mouth laterally to provide more space for the ETT. Midtracheal placement of the ETT tip is usually assured when the “double black line” (marked on the outside of an uncuffed ETT) is aligned with the vocal cords. Additionally, multiplying the inner diameter of the ETT by a factor of 3 gives the depth of insertion in centimeters (measured at the lip) that usually gives proper midtracheal positioning (this rule of thumb may incorrectly overestimate depth of placement in children younger than 2 years old). Confirmation of Placement ETCO2 detection is the standard of care to confirm proper ETT placement. Several types of ETCO2 detectors are commercially available. Most EDs use disposable colorimetric devices, which register exhaled CO2 by a change in color of an indicator, but some use capnometry, which digitally displays the exact partial pressure of exhaled CO2, or capnography, which provides a waveform. Several studies have supported the specificity and sensitivity of confirmation of placement of ETTs using ETCO2 in infants and children.28,29 In the patient in cardiopulmonary arrest, the absence of pulmonary blood flow may limit the amount of carbon dioxide in the alveoli, making ETCO2 prone to false-negative results (the tube is in the trachea, but the test indicates the tube is in the esophagus), but this occurs in only a subset of patients. Persistent detection of CO2, however, reliably indicates that the tube is in the airway.30 Concomitant physical examination will address the possibility that the tube, while in the airway, has been inadvertently placed in the supraglottic larynx, or in a mainstem bronchus. The imperfect specificity of ETCO2 in the arrested patient occasionally will require use of alternative devices to confirm ETT placement. Air aspirators, or esophageal detection devices (EDD), are one common class of such devices. The principle behind the use of the EDD relies on the collapsibility of the esophagus compared to the cartilage-reinforced

trachea. EDDs attempt to aspirate air from the endotracheal tube by negative pressure (examples include a syringe-like device and a semirigid plastic bulb that reinflates when squeezed). If negative pressure is applied to a tube in the trachea, the reinforced trachea will resist collapse and the EDD will fi ll with air, confirming that the tube is in the trachea. Negative pressure applied to a tube in the esophagus, on the other hand, will collapse the esophagus around the end of the tube and result in slow or incomplete filling of the EDD with air. EDDs have been shown to be accurate in older children.31 Some studies have shown their accuracy to be poor in children under 1 year of age and when used with uncuffed ETTs.32-34 At present, no recommendations exist for the routine use of EDDs in children, and these devices should be used only when there is uncertainty about tube position after use of ETCO2 detection. There is no method of confirming proper placement of an ETT that is 100% reliable. A combination of the techniques described here and clinical examination will provide the correct information in the vast majority of cases. Physical examination should not be used to overrule a “negative” ETCO2 detection (tube in esophagus) unless the patient is in cardiac arrest and clinical evidence strongly supports tracheal placement. Securing the ETT Securing an ETT is most often accomplished by one of two methods. Strips of adhesive tape can be torn longitudinally to allow half of each piece to attach to the patient’s face and the other to the shaft of the ETT. Alternatively, a number of prefabricated tube devices are commercially available. In the conscious or responsive patient, it may be necessary to place an adjunctive device between the incisors (a “bite block”) to prevent the patient from biting against the tube and occluding it. Oropharyngeal airways may be used for this purpose, along with rolls of gauze or other prefabricated devices. Alternative Intubation Techniques Blind Nasotracheal Intubation Blind nasotracheal intubation (BNTI) has little role in the modern ED, particularly in children, in whom it is more difficult than in adults because of the wider discrepancy between the pharyngeal and laryngeal axes, as well as the presence of large adenoidal tissue. BNTI is reserved for those cases in which oral intubation is deemed to be unlikely to succeed and alternative techniques, including fiberoptic intubation, are not available. The patient must be cooperative and spontaneously breathing to allow appreciation of breath sounds through the ETT as the tip is blindly inserted through one naris and advanced to just above the glottic opening. Pediatric experience with this technique is extremely limited. The anterosuperior location of the glottic opening with respect to the nasopharynx in infants and young children make the blind placement of a tube through a naris and into the trachea extremely difficult. Therefore, this technique is not recommended in children less than 10 years old. Lighted Stylet The lighted stylet relies on the characteristic appearance of light transilluminating the larynx through the anterior neck.

Chapter 4 — Intubation, Rescue Devices, and Airway Adjuncts

45

The ETT is threaded over the light wand, which is bent almost to a right angle to direct the lighted tip anteriorly toward the glottic opening. The wand-tube combination is then advanced blindly over the tongue and directed anteriorly toward the vocal cords. When the visible illumination goes from a diffuse circle of light to a more focused and clearly delineated outline of the glottic opening (sometimes called “coning”), the tube is advanced off the device into the trachea. Both reuseable and disposable light wand devices exist that can accommodate ETTs down to infant and pediatric sizes. Literature on the emergent use of this technique is limited. Fiberoptic Intubation Equipment for fiberoptic laryngoscopy exists in sizes small enough that fiberoptic techniques can be employed in any age of patient. Fiberoptic intubation requires training and experience, and can be acquired as a skill through training courses or in a simulation laboratory. It is uncommonly used in children, but offers the added advantage of a detailed airway examination that may avert intubation altogether (e.g., in smoke inhalation).

A

Distal cuff Proximal cuff

Digital Intubation This technique, which also has little role in modern airway management, is performed by advancing the index fi nger of one hand into the patient’s mouth and palpating the tip of the epiglottis. The intubator then pushes the epiglottis anteriorly with that fingertip while sliding an ETT along the side of the finger with the opposite hand. There is very little human, and even less pediatric, experience with this method.

Twin lumen

Retrograde Intubation This technique is rarely used in the ED in pediatric or adult patients, and involves percutaneously inserting a needle through the cricothyroid membrane and inserting a guidewire cephalad through the needle lumen until it can be pulled through the patient’s open mouth. An ETT is then threaded over the wire and advanced into the trachea. There is virtually no experience or study related to the use of this approach in the pediatric age group.

B FIGURE 4–4. Rescue devices. A, LMA classic (left) and the Fastrach intubating LMA. The former is available in sizes from neonate to large adult. The intubating LMA should only be used in patients over 30 kg. B, The Combitube is available in two sizes, SA (small adult) on left, and standard on right. Patients must be over 48 inches tall if a Combitube is to be used.

Rescue Devices Rescue devices are those that are used when intubation has failed or the operator judges that further attempts at orotracheal intubation are likely to be futile. Laryngeal Mask Airway The LMA consists of a teardrop-shaped inflatable cuff surrounding a fenestrated latex window that faces the glottic opening when properly positioned (Fig. 4–4A). The device is inserted into the open mouth of the patient and advanced until resistance is felt, at which point the cuff is inflated. Studies of the use of the LMA by various classes of personnel have shown that it is easy to place and rarely associated with significant complications.35,36 LMAs are made in a range of sizes that are appropriate for all ages from neonate to adult. A summary of appropriate sizes and cuff volumes for LMAs is given in Table 4–4. The LMA does not result in the placement of a cuffed ETT in the trachea, so it is generally believed that the device does not protect against aspiration. It appears that aspiration

Table 4–4

Laryngeal Mask Airway Sizes

Size

Patient Weight

1 11/2 2 21/2 3 4 5

30 kg; small adult Normal adult Large adult

Amount of Air in Cuff (mL) 4 7 10 14 20 30 40

risk may approximate that when bag-mask ventilation is employed.37 Data comparing LMA use to ETI and BVM ventilation are children is limited16 ; nonetheless, LMAs are widely used in operating room settings, EDs, and by some prehospital care communities.17 The patent for the original LMA has run out, and numerous products are now available, some claiming improvements over the original design.

46

SECTION I — Immediate Approach to the Critical Patient

Combitube

The Difficult Pediatric Airway

The Combitube consists of a dual-lumen tube with two inflatable cuffs. It is inserted blindly through the oropharynx and passes almost universally into the esophagus. Both cuffs are inflated, with a smaller cuff securing the distal end in either the esophagus or, rarely, the trachea (depending on where the device comes to lie) and a larger cuff fi lling the oropharynx so as to provide a seal. Ventilation is provided through sidestream ports in the tube, positioned just above the glottis. If the tube is placed in the trachea, sidestream ventilation will be unsuccessful, and the alternative lumen is used, ventilating the trachea directly through the distal end of the tube. The Combitube has a high rate of successful placement by hospital and prehospital personnel in patient simulators and adults.38,39 Combitubes are made in two sizes, and only the “SA” (small adult) size is suitable for pediatric use (Fig. 4–4B). The Combitube is restricted to patients greater than 48 inches in height, (typical size and weight of a 10 year old). No sizes of Combitube currently exist for pediatric patients of younger age.40 The PTL tube is a device similar to the Combitube, inserted via a blind technique and shown to be relatively easy to use.39 The PTL is also unavailable in pediatric sizes. Both the PTL and Combitube are safe to use in adolescent patients.

Difficulty in intubation in children can be due to chronic or acute conditions as discussed briefly earlier (see Table 4–2). A recent clinical review provides a detailed list of conditions that may predispose a child to a difficult intubation.2 Anticipating that a child will be difficult to intubate is hard to do with any degree of specificity or sensitivity. Predictors shown to be useful in adults, such as Mallampati and Cormack and Lehane scoring, have not been shown to be specific in children for predicting difficulty in ETI. Some empiric observations such as inability to move the neck (rheumatic disease, Klippel-Feil syndrome, arthrogryposis) or potential for morbidity from neck motion (trauma, Down syndrome), a small or distorted mandibular space (Pierre-Robin syndrome, Treacher-Collins syndrome), and tongue size are of predictive value for children in need of airway management. The difficult pediatric airway is a very rare clinical phenomenon. This very fact also means that not even experienced emergency medicine practitioners frequently manage the difficult pediatric airway. The need for fiberoptic or surgical management of a pediatric airway is most commonly encountered in the operating room, and therefore it is those subspecialists that frequently manage children via these techniques (anesthesiologists, otorhinolaryngologists) that are most likely to have enough experience to intervene in a facile manner. Two mnemonics often used for identifying difficult intubation in adults are presented here. The abnormalities identified by these rules of thumb are uncommon in children, but the general principles of signs of potential difficulty can be applied in a manner nonspecific to age. Thinking through these mnemonics may help the emergency medicine practitioner to identify children for whom paralysis (RSI) should be avoided or subspecialist assistance might be warranted.41,42 It must be noted that these mnemonics are derived from adult studies and have not been shown to be specific or sensitive in children. In general, when developing a system for identification of a potentially difficult intubation, sensitivity is much more important than specificity; that is, it is more valuable to identify every difficult airway at the expense of considering some to be difficult when they are not. The mnenomics are presented here as a representative framework for anticipating difficulty with a pediatric airway.

Surgical and Transtracheal Airway Procedures Emergency surgical airway management is rare, and particularly so in pediatrics. In the first phase of the multihospital NEAR study, only 1 of 156 emergency pediatric airways was managed by cricothyrotomy.1 The small size of the cricothyroid membrane, incomplete development of the normal external laryngeal landmarks, excessive mobility of the airway, and lack of rigidity of the structures make surgical airways particularly challenging in small children. Although tracheostomy is possible in even very small neonates under highly controlled conditions, emergency airway management accesses the airway through the cricothyroid membrane. Cricothyrotomy can be performed using an open surgical technique, percutaneously using a Seldinger technique, or by using a cricothyrotome (an instrument designed to access the membrane and provide an airway, usually in one or two steps.) There is no evidence in support of using any of the cricothyrotomes, including those represented as being specially designed for the pediatric airway. In general, such devices should be avoided. For children greater than 10 years old, surgical cricothyrotomy can be performed, particularly in older children, whose airway dimensions approach those of adults. Under age 10 years, needle cricothyrotomy is preferable; this can be accomplished using an angiocatheter of reasonable size. Jet ventilation requires the use of a special apparatus that incorporates a regulator to control pressure to limit barotrauma, and can be provided through this catheter. In infants less than 1 year old, bag ventilation is performed through the catheter by incorporating the ETT adaptor from a 3-mm ETT. Use of the bag in the small child minimizes the risks of barotrauma. There are no studies to clearly delineate the role of emergency transtracheal ventilation in pediatric patients, and the technique is rarely if ever used. It is relatively simple, however, and may be valuable in those small patients for whom a surgical airway is not feasible.

Lemon • Look externally for signs of procedural difficulty (facial/ oral characteristics, habitus, etc.) and potential difficulty with bag-mask ventilation (obesity, poor mask seal, airway obstruction, high ventilatory resistance [e.g., asthma]) • Evaluate the “3-3-2” rule (the interincisor gap of an open mouth should approximate three of the patient’s finger breadths; the distance from the mentum to the hyoid bone should also be three of the patient’s finger breadths; the distance from the thyroid notch to the floor of the mouth should be two of the patient’s finger breadths). While these measurements are not specifically validated in small children, they can serve as a guide to judge the accessibility of the upper airway for direct laryngoscopy. • Mallampati score (Fig. 4–5)

Chapter 4 — Intubation, Rescue Devices, and Airway Adjuncts

Class I: soft palate, uvula, fauces, pillars visible No difficulty

Class III: soft palate, base of uvula visible Moderate difficulty

Class II: soft palate, uvula, fauces visible No difficulty

Class IV: hard palate only visible Severe difficulty

FIGURE 4–5. Mallampati scoring system for visualization of pharyngeal structures. Easy intubation is anticipated by a score of 1 or 2, some difficulty is expected with a score of 3, and great difficulty or impossible intubation is associated with a score of 4. (From Whitten CE: Anyone can Intubate, 4th ed. San Diego: Mooncat Publications, 2004.)

• Obstruction (any evidence/suspicion for airway obstruction) • Neck mobility (i.e., reduction of neck mobility that limits the ability to put the neck in extended position for direct laryngoscopy) The Four Ds • Distortion of facial/neck/oral anatomy by disease process • Disproportion of neck, mandible, submandibular space • Dysmobility of jaw, neck • Dentition—edentulous adults are difficult to maintain a sealed bag-valve mask on; this seldom is true for edentulous infants

Success Rates and Complications Incidence of Complications Estimates of the incidence of complications of ETI vary.43-45 The definition of “complication” related to ETI is inconsistent across studies, encompassing such phenomena as predictable changes in physiology, imperfect fit of selected

47

equipment, and adverse events attributable directly to the process of laryngoscopy and ETT placement. The NEAR registry has employed a strict definitional scheme to differentiate between “true” complications (resulting from the procedure itself) and “technical problems” (cuff leak, detected ETI, equipment failure, etc.) or “physiologic alteration” (changes in physiology during or after ETI that may or may not be attributable to the intubation).1 This new nomenclature, while sensible, was not available at the time of publication of most other studies. Such phenomena as mainstem intubations, gastric distention, and failure to place a gastric tube for stomach decompression are cited as complications in other studies, resulting in misleading reports of complication rates that are higher than would have occurred had only true complications been included. Failure of Procedure Failure of laryngoscopy and ETI in children varies with the setting, patient age, and training and experience of the intubator. Prehospital studies of ETI in children have found success rates varying from 18% to 30% in infants and young children and 71% to 90% in older children and adolescents.46,47 ED-based studies of pediatric ETI show that success rates vary with age as well. Data from the NEAR study found that the first intubation attempt was successful in 60% of patients less than 5 years old, while success rates for older children ranged from 71% to 85%. In the same study, the first intubator was successful in 74% to 79% of children less than 5 years old and in 86% to 94% of children 6 to 18 years old.1 A landmark study comparing BVM ventilation to ETI in the prehospital management of children in need of respiratory support demonstrated no benefit of ETI over BVM, although the paramedics studied rarely undertook pediatric intubation in the large, urban center studied. In that study, unrecognized esophageal intubation occurred in 15 children, and 14 of these children died.48 Uniform use of ETCO2 detection is meant to reduce the occurrence of this event. Trauma (Oral, Pharyngeal, Laryngeal) Trauma to the oropharynx, teeth, lip, tongue, and larynx have been reported with ETI, but is uncommon and generally mild. The NEAR study identified direct trauma in only 1 of 156 intubation attempts; other studies of prehospital and ED pediatric intubations found a range of similarly infrequent incidences (0.5% to 4%).45,48,49 Young children have primary teeth, which are easily injured and avulsed and can pose an aspiration risk. Primary teeth overlie secondary tooth buds that can be damaged by forces exerted on primary teeth. Other pertinent anatomic features in children include the small mouth, large tongue, and prominent adenoidal tissue. Respiratory Complications (Aspiration, Air Leak Syndrome/Pneumothorax) The conversion from native negative pressure breathing to positive pressure ventilation via an ETT is associated with a significant increase in intrathoracic pressure, particularly in clinical situations in which lung or chest wall compliance is decreased. Complications from barotrauma, such as pneumothorax, interstitial emphysema, and subcutaneous air, can result from positive pressure ventilation. It is difficult to determine whether such phenomena, when observed, result

48

SECTION I — Immediate Approach to the Critical Patient

from the intubation or from the condition for which intubation was required. Emesis and aspiration of gastric contents are uncommon but significant events that can occur before, during, or after ETI. The common use of BVM ventilation for preoxygenation and for maintenance of arterial oxygen saturation during RSI may put small children at a greater risk of these complications. The use of cricoid pressure to prevent both gastric insufflation and regurgitation is designed for the prevention of these complications.

Table 4–5 Drug

Postintubation Sedation and Neuromuscular Blockade t1/2 (hr)

Sedatives and Analgesics Midazolam 1.7–2.6 Lorazepam 11–22 Diazepam 20–50 Fentanyl 1.7–2.6 Morphine 2–4 Meperidine 2–5

Clearance (mL/kg/min) 6.4–11 0.8–1.8 0.2–0.5 6.4–11 10–40 10–20

Physiologic Complications

Drug

Duration of Blockade (min)

Vagally mediated bradycardia related to laryngoscopy in children is discussed earlier in this chapter and in Chapter 2 (Respiratory Distress and Respiratory Failure). Cardiopulmonary interactions following the conversion from spontaneous negative pressure ventilation to positive pressure ventilation involve an increase in intrathoracic pressure resulting in a decrease in preload and possibly left ventricular afterload. The compliance of the chest wall in small children results in the need for greater changes in pressure to yield a given tidal volume, and so it can be extrapolated that the resultant preload changes may be more dramatic in young children. Left ventricular function in young children is affected more drastically by metabolic disturbances (hypoglycemia, acidosis, hypocalcemia), states that commonly accompany clinical situations in which ETI is necessary. Additionally, lower respiratory illnesses such as bronchiolitis and pneumonia, common indications for pediatric ETI, result in increased pulmonary vascular resistance, increased right ventricular diameter, and consequently (via ventricular interdependence) decreased left ventricular preload.50 Anyone performing ETI on a critically ill child should be wary of the concurrent presence of any disease state resulting in decreased preload (hypovolemia, capillary leak, blood loss), as well as whether the metabolic milieu can be optimized prior to ETI.

Neuromuscular Blocking Agents Rocuronium Vecuronium Pancuronium

20–30 (dose dependent) 30–60 40–75

Equipment-Related Complications Children who undergo intubation with ETTs of the wrong size or type can experience difficulty with maintaining appropriate oxygenation and ventilation. The rules of thumb commonly used for selection of types and sizes of equipment related to ETI are imperfect and yield estimates that are incorrect in certain circumstances. Additionally, and probably more commonly, availability of or practitioner familiarity with appropriate equipment is suboptimal. ETTs of incorrect size have been shown to be frequently used by both ED physicians and prehospital care providers, although such equipment variances have not been correlated with adverse patient outcomes.45,49

Postprocedural Care and Disposition A chest radiograph should be obtained following all intubations to confirm that endobronchial intubation is not present, and that the tube is well positioned below the glottis. Placement of the tip of an ETT either too deep (right mainstem bronchus) or too shallow (high in the trachea near the glottis) can predispose the patient to complications such as tube dislodgement, obstruction, and barotrauma.

Monitoring of pulse oximetry, heart rate, and blood pressure should be maintained until the patient is transferred from the ED or resuscitation efforts are terminated. When possible, continuous monitoring of ETCO2 is a useful adjunct, both for complications related to the ETT and ventilation system and for underlying disease processes. Issues Related to Transport Transport of the intubated child is a difficult task requiring expertise with airway management and the use of sedation and neuromuscular blockade in children. Sedatives, analgesics, and neuromuscular blocking agents are routinely employed in transport of the critically ill child. Some characteristics of commonly employed agents for these purposes are shown in Table 4–5; which agent is appropriate will depend on the individual child’s situation. Monitoring in transport can be more difficult due to the inability to auscultate heart and breath sounds, as well as the presence of movement artifacts in electrocardiography leads. Continuous monitoring of pulse oximetry, heart rate, blood pressure, and neurologic status are essential to safely transporting such patients. Bhende and colleagues examined the use of colorimetric ETCO2 detection for evaluating placement of ETTs in 58 intubated children while in transport; in all cases in which tube position was checked while en route, the location of the tube was correctly identified.28 Transport teams caring for intubated children must be able to at least intermittently (if not continuously) monitor the presence of ETCO2 as evidence of correct placement of the ETT. REFERENCES 1. Sagarin MJ, Chiang V, Sakles JC, et al: Rapid sequence intubation for pediatric emergency airway management. Pediatr Emerg Care 18:417– 423, 2002. 2. Frei FJ, Ummenhofer W: Difficult intubation in paediatrics. Paediatr Anaesth 6:251-63, 1996. 3. Helfaer MA, Nichols DG, Rogers MC: Developmental physiology of the respiratory system. In Rogers MC (ed): Textbook of Pediatric Intensive Care. Baltimore: Williams & Wilkins, 1996, pp 97–126. 4. Farmery AD, Roe PG: A model to describe the rate of oxyhaemoglobin desaturation during apnoea. Br J Anaesth 76:284–291, 1996. [Published erratum appears in Br J Anaesth 76:890, 1996.] 5. Benumof JL, Dagg R, Benumof R: Critical hemoglobin desaturation will occur before return to an unparalyzed state following 1 mg/kg intravenous succinylcholine [see comment]. Anesthesiology 87:979– 982, 1997.

Chapter 4 — Intubation, Rescue Devices, and Airway Adjuncts 6. Xue FS, Luo LK, Tong SY, et al: Study of the safe threshold of apneic period in children during anesthesia induction. J Clin Anesth 8:568– 574, 1996. 7. Levitan RM, Ochroch EA: Airway management and direct laryngoscopy: a review and update. Crit Care Clin 16:373–388, 2000. 8. Gronert BJ, Motoyama EK: Induction of anesthesia and endotracheal intubation. In Motoyama EK, Davis PJ (eds): Smith’s Anesthesia for Infants and Children. St. Louis: Mosby, 1996 pp 281–312. 9. Davis D, Barbee L, Ririe D: Pediatric endotracheal tube selection: a comparison of age-based and height-based criteria. AANA J 66:299– 303, 1998. 10. Hofer CK, Ganter M, Tucci M, et al: How reliable is length-based determination of body weight and tracheal tube size in the paediatric age group? The Broselow tape reconsidered. Br J Anaesth 88:283–285, 2002. 11. King BR, Baker MB, Braitman LE, et al: Endotracheal tube selection in children: a comparison of four methods. Ann Emerg Med 22:530– 534, 1993. 12. Luten RC, Wears RL, Broselow J, et al: Length-based endotracheal tube and emergency equipment in pediatrics. Ann Emerg Med 21:900– 904, 1992. [Published erratum appears in Ann Emerg Med 22:155, 1993.] 13. van den Berg AA, Mphanza T: Choice of tracheal tube size for children: fi nger size or age-related formula? Anaesthesia 52:701–703, 1997. 14. Khine HH, Corddry DH, Kettrick RG, et al: Comparison of cuffed and uncuffed endotracheal tubes in young children during general anesthesia. Anesthesiology 86:627–631; discussion 27A, 1997. 15. Deakers TW, Reynolds G, Stretton M, Newth CJ: Cuffed endotracheal tubes in pediatric intensive care. J Pediatr 125:57–62, 1994. *16. Part 10: Pediatric Advanced Life Support. Circulation 102:291I–342I, 2000. 17. Airway, ventilation, and mangement of respiratory distress and failure. In Hazinski MF, Zaritsky AL, Nadkarni VM, et al (eds): PALS Provider Manual. Dallas, TX: American Heart Association, 2002, pp 81–126. 18. Xue FS, Tong SY, Wang XL, et al: Study of the optimal duration of preoxygenation in children. J Clin Anesth 7:93–96, 1995. 19. Patel R, Lenczyk M, Hannallah RS, McGill WA: Age and the onset of desaturation in apnoeic children. Can J Anaesth 41:771–774, 1994. 20. Sellick B: Cricoid pressure to control regurgitation of stomach contents during induction of anesthesia. Lancet 2:404–406, 1961. 21. Brock-Utne JG: Is cricoid pressure necessary? [see comment]. Paediatr Anaesth 12:1–4, 2002. 22. Hartsilver EL, Vanner RG: Airway obstruction with cricoid pressure. Anaesthesia 55:208–211, 2000. 23. Palmer JHM, Ball DR: The effect of cricoid pressure on the cricoid cartilage and vocal cords: an endoscopic study in anesthetised patients. Anaesthesia 55:263–268, 2000. 24. Francis S, Enani S, Shah J, et al: Simulated cricoid force in paediatric anesthesia. Br J Anaesth 85:164P, 2000. 25. Takahata O, Kubota M, Mamiya K, et al: The efficacy of the “BURP” maneuver during a difficult laryngoscopy. Anesth Analg 84:419–421, 1997. 26. Benumof JL, Cooper SD: Quantitative improvement in laryngoscopic view by optimal external laryngeal manipulation. J Clin Anesth 8:136– 140, 1996. 27. Levitan RM, Mickler T, Hollander JE: Bimanual laryngoscopy: a videographic study of external laryngeal manipulation by novice intubators.[see comment]. Ann Emerg Med 40:30–37, 2002. 28. Bhende MS, Thompson AE, Orr RA: Utility of an end-tidal carbon dioxide detector during stabilization and transport of critically ill children. Pediatrics 89(6 Pt 1):1042–1044, 1992.

*Selected reading.

49

29. Bhende MS, Thompson AE, Cook DR, Saville AL: Validity of a disposable end-tidal CO2 detector in verifying endotracheal tube placement in infants and children [see comment]. Ann Emerg Med 21:142–145, 1992. 30. Bhende MS: End-tidal carbon dioxide monitoring in pediatrics—clinical applications. J Postgrad Med 47:215–218, 2001. 31. Morton NS, Stuart JC, Thomson MF, Wee MY: The oesophageal detector device: successful use in children. Anaesthesia 44:523–524, 1989. 32. Haynes SR, Morton NS: Use of the oesophageal detector device in children under one year of age. Anaesthesia 45:1067–1069, 1990. 33. Wee MY, Walker AK: The oesophageal detector device: an assessment with uncuffed tubes in children. Anaesthesia 46:869–871, 1991. 34. Sharieff GQ, Rodarte A, Wilton N, Bleyle D: The self-inflating bulb as an airway adjunct: is it reliable in children weighing less than 20 kilograms? Acad Emerg Med 10:303–308, 2003. 35. Lopez-Gil M, Brimacombe J, Alvarez M: Safety and efficacy of the laryngeal mask airway: a prospective survey of 1400 children. Anaesthesia 51:969–972, 1996. 36. Lopez-Gil M, Brimacombe J, Cebrian J, Arranz J: Laryngeal mask airway in pediatric practice: a prospective study of skill acquisition by anesthesia residents. Anesthesiology 84:807–811, 1996. 37. Brimacombe JR, Berry A: The incidence of aspiration associated with the laryngeal mask airway: a meta-analysis of published literature. J Clin Anesth 7:297–305, 1995. 38. Dorges V, Ocker H, Wenzel V, et al: Emergency airway management by non-anaesthesia house officers—a comparison of three strategies. Emerg Med J 18:90–94, 2001. 39. Rumball CJ, MacDonald D: The PTL, Combitube, laryngeal mask, and oral airway: a randomized prehospital comparative study of ventilatory device effectiveness and cost-effectiveness in 470 cases of cardiorespiratory arrest [see comment]. Prehospital Emerg Care 1:1–10, 1997. 40. Murphy MF: Special devices and techniques for managing the difficult or failed airway. In Walls RM (ed): Manual of Emergency Airway Management. Philadelphia: Lippincott, Williams & Wilkins, 2000, pp 68–81. 41. Murphy MF, Walls RM: The difficult and failed airway. In Walls RA (ed): Manual of Emergency Airway Management. Philadelphia: Lippincott Williams & Wilkins, 2000, pp 31–39. 42. Levitan RM: Practical Emergency Airway Management. Wayne, PA: Airway Cam Technologies, Inc., 2003. 43. Gnauck K, Lungo JB, Scalzo A, et al: Emergency intubation of the pediatric medical patient: use of anesthetic agents in the emergency department. Ann Emerg Med 23:1242–1247, 1994. 44. Nakayama DK, Gardner MJ, Rowe MI: Emergency endotracheal intubation in pediatric trauma. Ann Surg 211:218–223, 1990. 45. Easley RB, Segeleon JE, Haun SE, Tobias JD: Prospective study of airway management of children requiring endotracheal intubation before admission to a pediatric intensive care unit. Crit Care Med 28:2058–2063, 2000. 46. Aijian P, Tsai A, Knopp R, Kallsen GW: Endotracheal intubation of pediatric patients by paramedics [see comment]. Ann Emerg Med 18:489–494, 1989. 47. Kumar VR, Bachman DT, Kiskaddon RT: Children and adults in cardiopulmonary arrest: are advanced life support guidelines followed in the prehospital setting? [see comment]. Ann Emerg Med 29:743–747, 1997. 48. Gausche M, Lewis RJ, Stratton SJ, et al: Effect of out-of-hospital pediatric endotracheal intubation on survival and neurological outcome: a controlled clinical trial [see comment]. JAMA 283:783–790, 2000. [Published erratum appears in JAMA 283:3204, 2000.] 49. Brownstein D, Shugerman R, Cummings P, et al: Prehospital endotracheal intubation of children by paramedics [see comment]. Ann Emerg Med 28:34–39, 1996. 50. Robotham JL, Peters J, Takata M, Wetzel RC: Cardiorespiratory interactions. In Rogers MC (ed): Textbook of Pediatric Intensive Care. Baltimore: Williams & Wilkins, 1996, pp 369–396.

Chapter 5 Monitoring in Critically Ill Children Jonathan Marr, MD and Thomas J. Abramo, MD

Key Points Cyanosis is not an early or reliable indicator of hypoxemia in anemic children. Pulse oximetry is accurate when saturations are greater than 70%. Capnographic end-tidal CO2 is the most reliable method for confirming endotracheal tube placement. Oscillometric blood pressure measurements are accurate in pediatric patients.

the foundation of pediatric advanced life support. Goals are to assess for respiratory failure, shock, and the impact on end-organ function. An orderly approach that assesses the triad of respiratory effort, perfusion, and mental status will allow for early identification of critically ill children (see Chapter 2, Respiratory Distress and Respiratory Failure; Chapter 8, Circulatory Emergencies: Shock; and Chapter 9, Cerebral Resuscitation). Addition of noninvasive and invasive monitoring techniques will allow for early recognition of patient deterioration and rapid determination of response to therapy.

Evaluation and Management Noninvasive Monitoring Pulse Oximetry

Introduction Improved EMS systems and the development of transport medicine have increased the need for real-time information. Caring for the ill or injured child can be difficult since invasive blood draws (e.g., arterial blood gas) are not always easy to obtain and may not be tolerated if performed multiple times. Thus a noninvasive means of patient monitoring is a promising area of emergency pediatrics. Physicians must be aware of how new devices impact their clinical decision making and of the limitations of the information these devices provide. Noninvasive monitoring of critically ill children in the emergency department (ED) includes pulse oximetry, capnography, cardiac telemetry, and oscillometric blood pressure measurement. In the ED, invasive monitoring is usually limited to blood gases and occasionally continuous indwelling arterial pressure monitoring. Central venous pressure and mixed venous oxygen monitoring may become more common in the future.

Recognition and Approach Identification of the seriously ill and injured child in the ED requires rapid cardiopulmonary assessment and has become 50

Pulse oximetry has become an essential tool in the ED and is often referred to as the fifth vital sign. Furthermore, continuous evaluation of arterial oxygen saturation remains an important monitoring technique during stabilization and transport since providers cannot reliably detect hypoxemia by clinical examination alone.1 Historically, the pulse oximeter has been utilized in research since 1935. The principle of pulse oximetry is based on the Beer-Lambert law, which states that the concentration of an absorbing substance in solution can be determined from the intensity of light transmitted through that solution.2 Simply stated, arterial oxygen saturation is based on the differential absorption of red and infrared photons by oxyhemoglobin and deoxyhemoglobin measured by the pulse oximeter. Two light-emitting diodes (LEDs) in the pulse oximeter probe each emit light of specific wavelength from one side of the oximeter that passes through locations such as the digits or earlobe, with cutaneous pulsatile blood flow. Other possible monitoring sites include the nares, the cheek at the corner of the mouth, and the tongue.3 A photodiode detector at the far side of the oximeter measures the intensity of transmitted light at each wavelength. Oxygen saturation is derived from calibration curves that associate the absorbance ratios to arterial oxygen saturation. Initial calibration curves were derived from Beer-Lambert calculations, but more accurate calibration curves have come

Chapter 5 — Monitoring in Critically Ill Children

Table 5–1

Sources of Errors in Pulse Oximetry

Light interference • Ambient light • Penumbra effect Optical shunting • Probe malposition • Oversized probe Motion artifact Low signal-to-noise ratio • Shock • Cardiac arrest Dyshemoglobinemias • Carboxyhemoglobin • Methemoglobin • Sickle cell anemia (crisis) Dyes Other • Anemia • Blue or black nail polish

Venous pulsations • Obstructed venous return • Severe right heart failure • Tricuspid regurgitation • Dependent limb • Tourniquet constriction • High positive pressure ventilation

from experimentally derived data. These curves are based on measurements in healthy young volunteers after induction of hypoxemia with coincident determination of oxygen saturation by both pulse oximeter and in vitro laboratory cooximeter.2 Due to limitations in the degree of hypoxemia induced in volunteers, levels below 75% to 80% are extrapolated and thus subject to significant bias as oxygen saturation decreases. In general, pulse oximeters are accurate to within ± 3% at arterial saturations greater than 70%.4,5 Pulse oximetry error can come from a variety of sources (Table 5–1). The most common cause of an erroneous reading is related to false signals caused by the detection of nontransmitted light. Ambient light is a major source of interference, and sources include fluorescent lighting, surgical lamps, infrared heating lamps, fiberoptic instruments, and sunlight.6,7 Optical shunting occurs when light reaches the photodetector without passing through an arterial bed, and takes place when probes are malpositioned or oversized. This is also called the penumbra effect,8 and yields a calculated saturation in the low 80s despite normal saturations. In hypoxic patients, however, the penumbra effect from ambient light and optical shunt will lead to overestimation of their oxygen saturation.9 Movement creates high-amplitude signals that are mistaken for arterial pulsations and cause erroneous calculations in saturation values. The net effect of motion artifact is to factitiously lower pulse the oximeter saturation. Internal algorithms in newer generation oximeters have attempted to attenuate errors due to motion artifact. Similarly, states of venous pulsation causing congestion also cause false signals that artificially lower oxygen saturation readings.10 These states include obstructed venous return, severe right heart failure, tricuspid regurgitation, measurements in a dependent limb, constrictive tourniquets, and high positive pressure ventilation. States of absent or low-amplitude pulses create a low signal-to-noise ratio, causing the pulse oximeter to “search” for a saturation reading. This will occur in the seriously ill patient, in whom such information is essential. Fortunately, in most instances the failure to detect signal is more often due to local vasoconstriction rather than systemic hypotension. Earlobe probes have been suggested to produce better

51

signals compared to digit probes.11 Their use is supported by evidence that the earlobe is less vasoactive than the nail bed and thus less susceptible to vasoconstrictive effects.12 Carboxyhemoglobin and methemoglobin are dyshemoglobinemias not capable of carrying oxygen and thus affect oxygen-carrying capacity. Hemoglobin exists in varying states: bound to oxygen (oxyhemoglobin or O2Hb), unbound to oxygen (reduced hemoglobin or Hb), bound to carbon monoxide (carboxyhemoglobin or COHb), and altered to a ferric state (methemoglobin or MetHb). Dyshemoglobinemias absorb light used by the pulse oximeter and will produce false absorptions attributed to O2Hb and Hb. High levels of COHb will cause pulse oximeter saturations to be overestimated.13-15 Methemoglobin, formed as iron is oxidized to the ferric state, occurs congenitally or from exposure to anesthetics, sulfa drugs, or nitrites.2 Increasing levels of MetHb lead to concomitant decreases in pulse oximetry saturations to a plateau of 82% to 85%.16,17 Intravenous dyes are known to cause falsely low measured oxygen saturations by pulse oximeter. Methylene blue has been documented to cause profound decrease in measured oxygen saturations with pulse oximetry.18 Indocyanine green is used in angiography of the retina, and indigo carmine to evaluate for dysplasia in ulcerative colitis. These dyes can cause falsely low pulse oximeter readings that occur 35 to 40 seconds after dye administration.18 Pulse oximetry readings have reportedly underestimated the degree of hypoxemia in severe anemia,19 but one study found pulse oximetry to be accurate down to a Hb level of 2.3 g/dl in nonhypoxic adult patients.20 Skin pigmentation has had variable effects on pulse oximetry and likely has negligible effects on accuracy. Nail polish, specifically black or blue colors, demonstrated the most interference with pulse oximeter readings, lowering oximetry values by 6% in one study.2,16 Solutions to this problem include removing the nail polish or placing the probe sideways to remove the nail from the transmission path. In the ED, pulse oximetry serves to detect arterial hypoxemia from respiratory, cardiac, infectious, and metabolic etiologies while facilitating timely intervention before a patient deteriorates. Furthermore, pulse oximetry is used to monitor patients who are sedated for imaging or who undergo procedural sedation and analgesia for painful procedures. The Joint Commission on Accreditation of Healthcare Organizations has recognized the need for noninvasive monitors to improve patient safety. Current-generation pulse oximeters have improved algorithms that improve accuracy with patient movement while continuing to use transmitted light to determine saturations. Other advances include recent Food and Drug Administration approval of a new method for continuous, noninvasive measurement of carbon monoxide in blood (http://masimo. com/Rainbow/rb-overview.htm). Reflectance oximeters provide innovative technology that detects “backscatter” of light from LEDs and estimates arterial oxygen saturations. Testing of reflection oximetry of retinal blood to measure cerebral oxygenation and perfusion has been in development for the last decade.21 Unfortunately, reflectance oximeters lack accuracy and have increased susceptibility to noise, and have remained inappropriate for current clinical practice. Nearinfrared technology is a noninvasive and relatively low-cost optical technique that is used to measure tissue O2 saturation,

52

SECTION I — Immediate Approach to the Critical Patient

Colorimetric Device Color

Color

Percent CO2

Purple Tan Yellow

2%

Memory Aid Purple = Problem Tan = Think Yellow = YES!

D

C

paCO2

Table 5–2

A

B

E

*Normal expired end-tidal CO2 is 5%.

changes in hemoglobin volume, and, indirectly, brain/muscle blood flow and muscle O2 consumption.22 Currently, this technology remains in development with ongoing research.23,24 Capnography/End-Tidal CO2 While pulse oximeters measure oxygenation, the other functional component of the respiratory system that can be noninvasively measured is ventilation, or elimination of CO2. Diseases that cause respiratory distress or failure interfere with exchange of oxygen and carbon dioxide via ventilation/ perfusion mismatch, loss of lung compliance, increased airway resistance, or impairment of respiratory drive. End-tidal CO2 (ETCO2) monitoring is a noninvasive means for following levels of CO2 in the exhaled breath.25 Carbon dioxide can be measured qualitatively by colorimetric CO2 detectors or quantitatively by infrared capnometers.26,27 Since CO2 is the by-product of cellular metabolism and is transported by the circulatory system to be eliminated via exhalation, measurement by capnometry provides an indirect measure of systemic metabolism, cardiac output, and ventilation.28,29 Either colorimetric detector or infrared spectroscopy achieves confirmation of CO2 in the ED. Colorimetric devices have a pH-sensitive paper that produces a reversible color scale based on the concentration of CO2 (Table 5–2).30 Accuracy is affected by humidity, secretions, or contamination with gastric contents or acidic drugs, but is safe in brief use in infants and children greater than 1 kg.26 Colorimetric detectors are semiquantitative and cannot detect hypo- or hypercarbia, right mainstem bronchus intubation, or oropharyngeal intubation in a spontaneously breathing patient.26 False-negative results occur during cardiac arrest, severe airway obstruction, pulmonary edema, and severely hypocarbic infants. Despite these limitations, colorimetric detectors have shown prognostic value in pediatric cardiopulmonary resuscitation (CPR), while a capnometric or capnographic rise in ETCO2 to greater than 15 mm Hg precedes return of spontaneous circulation in adults.31 Carbon dioxide molecules absorb infrared radiation at a specific wavelength; thus, when fi ltered infrared light passes through a CO2-containing sample and is compared with a known standard, the concentration of ETCO2 is obtained.26,27 A capnogram is a graphic display of the CO2 waveform over time (Fig. 5–1). ETCO2 measurement has been found to be the most reliable method of confirming endotracheal tube position and can distinguish between endotracheal and esophageal intubation.26,29,32,33 Furthermore, continuous ETCO2 monitoring can detect airway obstruction and inadvertent extubation more rapidly than pulse oximetry.34 Thus, the American Heart Association guidelines require secondary confirma-

t Time FIGURE 5–1. Capnogram showing the typical curves and loops seen in mechanical ventilation.87 Point A, end of inhalation; point B, beginning of expiration; segment B–C, appearance of CO2; segment C–D, flow in uniformly ventilated alveoli with near-constant CO2; point D, end-tidal CO2; segment D–E, inspiratory phase. Abnormal shapes can provide clues to clinical findings. A rising segment C–D with no plateau is suggestive of prolonged expiration and differential emptying of alveoli, as noted with asthma or partially obstructed endotracheal tubes (ETTs). Sudden decrease in CO2 with no waveform suggests dislodged ETT, esophageal intubation, obstructed ETT, or ventilator disconnection.

tion of proper tube placement in all patients with a perfusing rhythm by capnography or exhaled CO2 detection immediately following intubation and during transport.35 Although an exponential decrease in ETCO2 occurs in cardiac arrest or severe sudden hypotension, it remains a valuable clinical tool during CPR. During effective CPR, ETCO2 has been shown to correlate with cardiac output,36 efficacy of cardiac compression, return of spontaneous circulation (ROSC), and survival.37 ETCO2 greater than 10 mm Hg during the first 20 minutes was shown to be associated with ROSC,38 whereas a value less than 10 mm Hg at 20 minutes predicted death.39 Following ROSC, ETCO2 values return to normal.40,41 Recently, continuous ETCO2 monitoring in nonintubated pediatric patients has been shown to be useful for monitoring respirations during seizures42,43 and sedation and monitoring acid-base status in diabetic ketoacidosis.44 Other studies have shown that ETCO2 correlates with arterial partial pressure of CO2 (Pco2) measurements.45-47 Blood Pressure Oscillometry Oscillometry is based on the principle that the artery wall oscillates when blood flows through an artery during cuff deflation.48 The rapid increase in oscillation amplitude estimates systolic pressure, while the sudden decrease in oscillation approximates diastolic pressure; the period of maximal oscillation is used to estimate mean intra-arterial blood pressure.49 The estimation of systolic and diastolic values is determined indirectly from an empirically derived manufacturer-specific algorithm.50 Noninvasive oscillometric (automated) blood pressure measurements are as accurate as auscultatory measurements, with less interobserver variability in children.51 Oscillometry-derived blood pressures have limitations. Large differences in estimated pressure readings between various manufacturers’ devices are thought to be secondary to proprietary algorithms that provide blood pressure estimates. However, systolic blood pressure can average as much as 10 mm Hg above that obtained by auscultation, while diastolic blood pressure measurements are 5 mm Hg higher in children.12 For this reason, standard blood pressure tables that define normal values for children may not apply to blood

Chapter 5 — Monitoring in Critically Ill Children

pressure measurements obtained by oscillometric methods.52 Others note poor correlation with diastolic blood pressures. In addition, the devices do not perform well in the presence of limb movement or dysrhythmias.53 Finally, mean arterial pressures may be significantly underestimated in patients with widened pulse pressures.54 Ultrasonic Doppler devices for blood pressure measurement have recently been developed, but have not become established in clinical practice. The probe is placed over an extremity artery while a proximal cuff is slowly deflated; systolic pressure is estimated with appearance of the first Doppler signal, and diastolic pressure is read when the strength and quality of the signal decrease.55 This technique may be helpful for intermittent blood pressure measurements when the oscillometric device is not able to provide pressure readings and an arterial line is not available. Another method to estimate systolic blood pressure includes the needle-bounce technique, which is used by anesthesiologists and flight nurses/physicians and obviates the need to auscultate Korotkoff sounds.55 Using a sphygmomanometer, the inflated cuff is slowly deflated and the first visible bounce of the needle correlates with systolic blood pressure. Pulse oximetry can estimate systolic blood pressure by the reappearance of waveforms during deflation56 or by the disappearance of waveform during inflation.57 Inflation and deflation, however, must be performed slowly (2 to 3 mm Hg/sec) in order for this technique to be accurate.2 A continuous partial radial artery compression device has been developed utilizing an oscillometric technique to indirectly measure blood pressure. Continual variable pressure is placed over the radial artery, and pulse pressure waveforms are measured and recorded in real time. This information is processed through a proprietary algorithm generating systolic, diastolic, and mean pressures. A recent study demonstrated that this device performed as well as oscillometric assessment and arterial line pressures.58 Pediatric studies are currently ongoing. Continuous ECG Monitoring Continuous electrocardiographic (ECG) monitoring is required in all patients at risk for cardiac, pulmonary, or neurologic deterioration in the ED. All systems use electrodes that transmit potentials from the heart through the tissues. The ECG signal is then amplified, fi ltered, and displayed on an oscilloscope. Three- and five-lead systems are available. Lead II can be used to detect most arrhythmias, while the CM5 configuration (right arm electrode at the manubrium, left arm at the V5 position, and final lead at the left shoulder) detects most left ventricular ischemic events. Electrical interference and artifacts can occur from several sources (any electrical device powered by alternating current, shivering, movement). Placement of electrodes over bony prominences reduces some of the artifacts. High skin impedance is another common cause of poor signals. Removing skin oils with alcohol diminishes this interference. Tissue Perfusion Monitoring The assessment of perfusion status in critically ill patients traditionally has been obtained by global indices such as blood pressure, heart rate, urine output, and mental status. These indices, however, are delayed in exhibiting early signs of severe perfusion defects.59 Early detection of tissue hypo-

53

perfusion by regional monitoring is based on the concept that blood flow is the primary determinant of tissue carbon dioxide.60 Gastric tonometry indirectly assesses the splanchnic circulation, which receives up to 25% of cardiac output and contains 20% to 25% of the systemic blood volume.61 During low-flow states (i.e., shock), large areas become hypoperfused, increasing anaerobic metabolism, lactate, and CO2 production.62 Tonometry measures the partial pressure of CO2 that freely diffuses across gastric mucosa, providing early and accurate information about tissue perfusion.63 Pediatric studies, however, are limited and gastric tonometry has not been widely implemented in younger age groups due to technical and artifact problems. Sublingual capnometry has emerged as an alternative to monitoring tissue perfusion. The carbon dioxide–sensing optode (optical sensor) forms carbonic acid upon exposure to carbon dioxide. The pH change causes a shift in the fluorescence of the indicator and is converted to a carbon dioxide concentration. Multiple studies have suggested that sublingual capnometry is predictive of severity of shock64 and outcome.65 These studies are small and primarily reflect adult findings. Nonetheless, sublingual capnometry has emerged as a promising technique of noninvasive monitoring of perfusion and hemodynamic disturbances. Invasive Testing/Monitoring Critical Lab Monitoring Arterial blood gas (ABG) analysis is the most commonly used tool for monitoring the effectiveness of oxygenation, ventilation, quantification of acid-base status, and response to therapy. Measured variables are partial pressures of oxygen (Po2) and carbon dioxide (Pco2) and hydrogen ion concentration (pH), while other values, such as concentration of total hemoglobin (tHb), O2Hb saturation, saturations of the dyshemoglobins (COHb and MetHb), plasma bicarbonate, and base excess/deficit, are calculated.66 In clinical practice, Pco2 is the best measure of ventilation and adequacy of breathing. The Po2 represents oxygen dissolved in the blood and can be low secondary to low atmospheric pressure (e.g., high altitude), hypoventilation, lung disease causing ventilation/perfusion (V/Q) mismatch (e.g., asthma, pneumonia), loss of pulmonary architecture (e.g., emphysema), and shunt (e.g., cyanotic heart disease). Distinguishing between hypoventilation and V/Q mismatch can be accomplished by calculating the alveolar-arterial (A-a) gradient using the fraction of inspired oxygen (FiO2), Po2, and Pco2 : FiO2 × air pressure (713 × 0.21 or 150 at sea level, room air) − (Po 2 + Pc o 2/0.8) Contemporary research has shown comparable accuracy of venous blood gases with ABGs for measuring pH and bicarbonate (HCO3) in adult diabetic ketoacidosis.67 Studies also have shown a correlation between arterial and capillary pH and Pco2 in acutely ill children.68,69 Others have shown a correlation between pH, Pco2, base excess (BE), and HCO3 in ABG, capillary blood gas, and venous blood gas values.70 The accuracy of arterial blood gases is influenced by air bubbles within the sample; the resultant gas equilibrium between air and arterial blood lowers arterial carbon dioxide pressure and increases arterial oxygen pressure.71 Time and

54

SECTION I — Immediate Approach to the Critical Patient

Table 5–3

Unmeasured Anions

Organic acids • Lactate • Ketoacids • Albumin Inorganic acids • Phosphates • Sulfates Exogenous • Salicylate • Formate • Nitrate • Penicillin Miscellaneous • Acetate • Paraldehyde • Ethylene glycol • Methanol • Ethanol • Urea • Glucose Data from Rhodes and Cusack76 and Balasubramanyan et al.72

temperature are other variables that affect accuracy. If the sample cannot be analyzed quickly, it should be placed on ice and cooled to 5°C, at which it can be stored for up to an hour. Complications associated with arterial punctures include pain, arterial injury, thrombosis, hemorrhage, and aneurysm formation. The BE has traditionally been used to assess acid-base status and estimate unmeasured anion concentrations (Table 5–3). First, standard bicarbonate is calculated from measured blood gas pH using the Henderson-Hasselbalch equation; the Pco2 is kept constant at 40 torr to isolate the metabolic contribution and remove the respiratory component.72 Next the difference between standard bicarbonate and 22.9, multiplied by a factor of 1.2, calculates the BE.73 A BE values ≤−5 is considered a clinically significant metabolic acidosis. Moreover, BE values ≤−8 predict a higher mortality (23% vs. 6% if BE >−8) in pediatric trauma victims.74 One limitation is that the calculations of BE assume normal water content, electrolytes, and albumin; these values are more than likely altered in critically ill children and are more apt to introduce error. The presence in critically ill patients of metabolic acidosis based on BE values was thought to reflect elevated lactic acid levels, poor perfusion, and concomitant organ dysfunction. This principle has since been challenged75-77 because hyperchloremia skews the BE to suggest false acidosis,78 and BE poorly correlates with lactic acidosis.72,77 In adults, a strong ion gap (SIG) greater than 2 mEq/L is more accurate than BE in detecting true tissue acidosis,77 identifying patients with lactic acidosis and splanchnic hypoperfusion with multiorgan dysfunction, and predicting mortality.72 The SIG represents a complex calculation that measures the difference between strong anions and strong cations and is the mathematical difference between the apparent strong ion difference (SIDa) and the effective strong ion difference (SIDe).79 An elevated SIG greater than 2 mEq/ L signifies that unmeasured strong anions are present in the bloodstream:

SIDa = [Na+ + K+ + Ca2+ + Mg2+ − Cl− − lactate − urate] SIDe = [albumin × (0.123 × pH − 0.631)] + [PO4 × (0.309 × pH − 0.469)] + HCO3 SIG = SIDa − SIDe (abnormal SIG is > 2 mEq/L) In the absence of oxygen, lactate is a by-product of glycolysis to maintain energy production (ATP) when pyruvate cannot enter the Krebs cycle.80 Lactate abruptly increases when oxygen delivery falls to a critical level and concomitant decrease in oxygen extraction occurs.81 Clearance occurs via the liver and kidneys, and normal arterial lactate levels are between 0.5 and 1 mEq/L. Traditionally, elevated blood lactate levels in hemodynamically unstable patients are thought to reflect circulatory shock, arterial hypoxemia, or both. Elevated lactate levels are described in circulatory shock, acute lung injury, sepsis, and multiorgan failure, and are an indicator of severe inflammatory cascade. Increasing lactate levels are associated with organ dysfunction, adverse events, and mortality in adult patients with shock, trauma, and sepsis.76 Nonetheless, lactate levels remain useful indicators for indirectly monitoring perfusion and oxygen delivery/consumption. Continuous Indwelling Arterial Monitoring Patients requiring close arterial blood pressure monitoring or frequent arterial blood gas analysis may require arterial cannulation for continuous monitoring. The transducer that translates the blood pressure into a waveform can be set to alarm if specific high or low values for mean arterial pressure, systolic blood pressure, or diastolic blood pressure are reached. The dicrotic notch signifying aortic valve closure should be greater than one third of the height of the systolic pressure unless cardiac output is depressed (Fig. 5–2A). The slope of the upstroke reflects myocardial contractility, with a diminished slope indicating shock (Fig. 5–2B). Formulas can be used to estimate stroke volume by measuring the area from the beginning of the upstroke to the dicrotic notch. Multiplying this value by the heart rate will estimate the cardiac output. Finally, the downward slope during diastole indirectly assesses resistance to cardiac outflow. Vasoconstriction causes a slow fall in this slope. Importantly, mean arterial pressure will be higher when measured at the periphery (e.g., distal lower extremity) compared to more centrally obtained pressures. Auscultatory measurements may give a slightly lower value than continuous indwelling catheter measurements. Falsely lowered values may be present if vasoconstriction occurs (e.g., severe shock, hypothermia, or vasopressor administration). Importantly, loss of a normal waveform or any distal extremity problems (pain, blanching, loss of pulse) may indicate thrombotic obstruction and the need to remove the cannula. A dampened waveform (increased diastolic and decreased systolic blood pressure) can be due to air bubbles, blood clots, soft tubing, or a soft diaphragm within the pressure transducer. Central Venous Pressure Monitoring Central venous pressure monitoring is used in critically ill patients who are in circulatory failure, require massive fluid or blood replacement, or have a compromised cardiovascular system. New interest in goal-directed therapy for septic shock

Chapter 5 — Monitoring in Critically Ill Children Systolic BP Dicrotic notch

A Diastolic BP

First shoulder T1

Second shoulder T2

Pressure Flow

55

Inaccurate CVP monitoring can result from a malpositioned catheter tip within the internal jugular vein, subclavian vein, or right ventricle or migration between discordant locations. Radiographic confirmation can limit this complication. Readings must be obtained using the same reference level at the midaxillary line with the patient supine. Measurements are taken at rest and during exhalation. Coughing, straining, positive pressure ventilation, air bubble within the catheter, and possibly vasopressors can falsely raise CVP values. Falsely low readings occur with catheter obstruction or contact with the vessel wall. Mixed Venous Oxygen Saturation

Aortic valve closure (incisura) Tj

Foot of the pulse Tf

Pulse duration TT

B Figure 5–2. A, Blood pressure (BP) translated to waveform during continuous BP monitoring. B, Correlation of blood pressure and arterial blood flow.

has increased the potential use of this tool in critically ill infants and children presenting to the ED.82 Following placement of a central venous catheter (see Chapter 161, Vascular Access), measurement of central venous pressure (CVP) can be used to diagnose disorders and guide treatment. A normal CVP is 5 to 12 cm H2O, with low values indicating a low right atrial pressure and hypovolemic or distributive shock. High values indicate cardiogenic shock, overhydration, pulmonary embolism, tension pneumothorax, valvular heart disease (e.g., pulmonary stenosis), pericardial tamponade, or restrictive pericarditis. Importantly, changes in CVP readings following infusion of a fluid bolus reflect intravascular volume and are more important predictors of volume abnormalities. Following a 10-ml/kg fluid bolus, the CVP is expected to rise 3 to 4 cm H2O. If this number drops rapidly (in 25% Opioid, imidazoline (clonidine) poisoning Hypoglycemia due to oral hypoglycemic agent (sulfonylurea) toxicity Carbon monoxide toxicity Pure anticholinergic poisoning Organophosphate, nerve agent toxicity; use in conjunction with atropine Isoniazid-induced seizures, Gyromitra mushroom, monomethylhydrazine Clinical bleeding due to coumadin, brodifacoum toxicity

Common Toxicants and Drugs Removed by Hemodialysis or Charcoal Hemoperfusion

Bromide Carbamazepine Chloral hydrate Ethylene glycol Isopropanol Lithium Metformin Methanol Phenobarbital Salicylates Theophylline Valproic acid

are hemodynamically unstable and avoid the problem of rebound toxicity (i.e., lithium). Consultation with a medical toxicologist and nephrologist can help decide which modality is best for the clinical situation. There are other mechanisms that can enhance the elimination of poisons. These include urinary alkalinization for salicylates and multiple doses of activated charcoal for theophylline, salicylates, and phenobarbital (see Chapter 133, Classic Pediatric Ingestions; and Chapter 136, Adverse Effects of Anticonvulsants and Psychotropic Agents). Consider consulting a medical toxicologist for patients who are critically ill, who require specific antidotes, or who have ingested unusual or lethal toxins (Table 10–13).

Table 10–13

Suggested Guidelines on When to Consider Consulting a Medical Toxicologist

Calcium channel antagonist/β-blocker ingestion with hypotension and/or bradycardia Cyclic antidepressant ingestion with coma, seizures, hypotension, and/or dysrhythmias Toxic alcohol ingestion (ethylene glycol, methanol) Organophosphates/carbamate exposure with symptoms Acute heavy metal exposure (arsenic, mercury) with symptoms Snake envenomation Intractable seizures secondary to toxic substance Critically ill patient requiring: Special antidote—digoxin Fab, methylene blue, glucagon, antivenom Hemodialysis Hyperbaric oxygen

Summary Decision making regarding the disposition of a poisoned patient depends on numerous factors, including the type of exposure, the toxicant itself, the circumstances surrounding the exposure, and the child’s social situation. Because most unintentional ingestions in young children result in either no or mild sequelae, these children can usually be discharged after an observation period of 4 to 6 hours. Utilization of the regional poison control center can help clinicians make these disposition decisions based on the particular exposure/ingestant. A common toll-free number

Chapter 10 — General Approach to Poisoning

is available nationally (1-800-222-1222) so that all health care providers as well as the public have 24-hour access to their regional poison control center for poison and drug information. “Medical clearance” of a patient who has had a potentially toxic exposure sometimes can be more problematic in the pediatric population. Any child or adolescent who presents with an intentional ingestion/overdose and does not need to be admitted for a medical reason must have a psychiatric assessment to determine whether further inpatient hospitalization is warranted. Most intentional ingestions warrant inpatient psychiatric hospitalization. If the circumstances are carefully evaluated and it is believed that the patient can be safely discharged, urgent follow-up with mental health services must be assured. Pediatric poisonings are a common cause of presentations to emergency departments. Very few unintentional ingestions in young children require hospitalization. Yet there is a selected list of drugs and substances that can cause serious toxicity even when ingested in small amounts. Fatalities in young children due to poisonings have decreased dramatically since the 1950s due to numerous factors—product reformulations, child-resistant packaging, heightened parental awareness of product toxic effects, intervention by poison information centers, and treatment by specially trained health care professionals. The profi le of intentional overdoses in adolescents is similar to that of young adults in terms of intent, nature of polysubstance ingestion, and type of substances ingested. However, the prognosis of adolescents who seek health care because of available parental oversight is excellent. Evaluation of the potentially poisoned patient relies primarily on the history and physical examination. Recognizing specific clinical toxidromes may help the clinician to recognize particular classes of drugs, which can then help guide further evaluation and therapy. The mainstay of therapy for most poisoned patients is supportive care. There are a limited number of antidotes that can limit the toxicity of specific drugs and toxicants. In addition, there are different modalities to enhance the elimination of a limited number of drugs and toxicants that may be initiated in the emergency department. Ocular, dermal, and/or gastrointestinal decontamination may be necessary depending on the route of exposure and time since the exposure took place. Research in the last 10 years has provided evidence to support the avoidance of routine gastric emptying for all ingestions in the emergency department. Whole-bowel irrigation is a new decontamination modality for selected ingestions that are not amenable to charcoal therapy. It is important for the emergency physician to remember other resources available—particularly the regional poison control center and the medical toxicologist, who may be at the health care facility or available through the poison control center. REFERENCES 1. Watson WA, Litovitz TL, Rodgers GC, et al: 2004 Annual Report of the American Association of Poison Control Centers Toxic Exposures Surveillance System. Am J Emerg Med 23:589–666, 2004. 2. Jonville AE, Autret E, Bavoux F, et al: Characteristics of medication errors in pediatrics. DICP Ann Pharmacother 25:1113–1118, 1991.

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3. Santell JP, Cousins D: Medication errors—documenting and reducing medication errors. US Pharmacist 28(7), 2003. Available at http/ uspharmacist.com/index.asp?show=article&page=8-1120.htm 4. Li SF, Lacher B, Crain EF: Acetaminophen and ibuprofen dosing by parents. Pediatr Emerg Care 16:394–397, 2002. 5. Rodgers GB: The safety effects of child-resistant packaging for oral prescription drugs: two decades of experience. JAMA 275:1661–1665, 1996. 6. Litovitz T, Manoguerra A: Comparison of pediatric poisoning hazards: an analysis of 3.8 million exposure incidents. A report from the American Association of Poison Control Centers. Pediatrics 89(6 Pt 1):999–1006, 1993. 7. Emery D, Singer JI: Highly toxic ingestions for toddlers: when a pill can kill. Pediatr Emerg Med Rep 3(12):111–119, 1998. 8. Shannon M: Ingestion of toxic substances by children. N Engl J Med 342:186–191, 2000. *9. Bar-Oz B, Levichek Z, Koren G: Medications that can be fatal for a toddler with one tablet or teaspoonful: a 2004 update. Pediatr Drugs 6(2):123–126, 2004. 10. Gupta S, Taneja V: Poisoned child: emergency room management. Indian J Pediatr 70(Suppl 1):S2–S8, 2003. 11. Henretig FM: Special considerations in the poisoned pediatric patient. Emerg Med Clin North Am 12:549–567, 1994. 12. Anderson BJ, Holford NG, Armishaw JC, et al: Predicting concentrations in children presenting with acetaminophen overdose. J Pediatr 135:290–295, 1999. 13. Hoffman RS, Smilkstin MJ, Howland MA, et al: Osmol gaps revisited: normal values and limitations. Clin Toxicol 31:81–93, 1993. 14. Ashbourne JF, Olson KR, Khayam-Bashi H: Value of rapid screening for acetaminophen in all patients with intentional drug overdose. Ann Emerg Med 18:1035–1038, 1989. *15. Belson MG, Simon HK, Sullivan K, Geller RJ: The utility of toxicologic analysis in children with suspected ingestions. Pediatr Emerg Care 15:383–387, 1999. 16. Liebelt EL, Francis PD, Woolf AD: ECG lead aVR versus QRS interval in predicting seizures and arrhythmias in acute tricyclic antidepressant overdose. Ann Emerg Med 18:348–351, 1989. 17. Traub SJ, Hoffman RS, Nelson LS: Body packing—the internal concealment of illicit drugs. N Engl J Med 349:2519–2526, 2003. 18. Liebelt EL, DeAngelis CD: Evolving trends and treatment advances in pediatric poisoning. JAMA 282:1113–1115, 1999. 19. Riordan M, Rylance G, Berry K: Poisoning in children: general management. Arch Dis Child 87:392–396, 2002. 20. American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical Toxicologist: Position statement: ipecac syrup. Clin Toxicol 35:699–709, 1997. *21. Pond SM, Lewis-Driver DJ, William GM, et al: Gastric emptying in acute overdose: a prospective randomized controlled trial. Med J Aust 163:345–349, 1995. 22. American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical Toxicologist: Position statement: gastric lavage. Clin Toxicol 35:711–719, 1997. 23. Tenenbein M, Cohen S, Sitar DS: Whole bowel irrigation as a decontamination procedure after acute drug overdose. Arch Intern Med 147:905–907, 1987. *24. Liebelt EL: Newer antidotal therapies for pediatric poisonings. Clin Pediatr Emerg Med 1:234–243, 2000. 25. Pond SM: Extracorporeal techniques in the treatment of poisoned patients. Med J Aust 154:617–622, 1991. 26. Blackman K, Brown SF, Wilkes GJ: Plasma alkalinization for tricyclic antidepressant toxicity: a systematic review. Emerg Med 13:204–210, 2001. 27. McKinney PE, Rasmussen R: Reversal of severe tricyclic antidepressant-induced cardiotoxicity with intravenous hypertonic saline solution. Ann Emerg Med 42:20–24, 2003. 28. Clark RF, Wethern-Kestner S, Vance MV, et al: Clinical presentation and treatment of black widow spider envenomation: a review of 163 cases. Ann Emerg Med 21:782–787, 1992. 29. Dart RC, Seifert SA, Boyer LV, et al: A randomized multicenter trial of Crotalidae Polyvalent Immune Fab (ovine) antivenom for the treatment for crotaline snakebite in the United States. Arch Intern Med 161:2030–2036, 2001.

*Selected readings.

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30. Lavonas EJ, Gerardo CJ, O’Malley J, et al: Initial experience with Crotalidae Polyvalent Immune Fab (ovine) antivenom in the treatment of copperhead snakebite. Ann Emerg Med 43:200–206, 2004. 31. Graudins A, Stearman A, Chan B: Treatment of the serotonin syndrome with cyproheptadine. J Emerg Med 16:615–619, 1998. 32. Meythaler JM, Roper JF, Brunner RC: Cyproheptadine for intrathecal baclofen withdrawal. Arch Phys Med Rehabil 84:638–642, 2003. 33. Woolf AD, Wenger T, Smith TW, et al: The use of digoxin-specific Fab fragments for severe digitalis intoxication in children. N Engl J Med 326:1739–1744, 1992. 34. Brent J, McMartin K, Phillips S, et al: Fomepizole for the treatment of ethylene glycol poisoning. N Engl J Med 340:832–838, 1999. 35. White CM: A review of potential cardiovascular uses of intravenous glucagon administration. J Clin Pharmacol 39:442–447, 1999.

36. Yuan TH, Kerns WP, Tomaszewski CA, et al: Insulin-glucose as adjunctive therapy for severe calcium channel antagonist poisoning. J Toxicol Clin Toxicol 37:463–474, 1999. *37. Boyer EW, Duic PA, Evans A: Hyperinsulinemia/euglycemia therapy for calcium channel blocker poisoning. Pediatr Emerg Care 18:36–37, 2002. 38. Boyle PJ, Justice K, Krentz AJ: Octreotide reverses hyperinsulinemia and prevents hypoglycemia induced by sulfonylurea overdoses. J Clin Endocrinol Metab 76:752–756, 1993. 39. Krentz AJ, Boyle PJ, Justice KM: Successful treatment of severe refractory sulfonylurea-induced hypoglycemia with octreotide. Diabetes Care 16:184–186, 1993. *40. Burns MJ, Linden CH, Graudins A, et al: A comparison of physostigmine and benzodiazepines for the treatment of anticholinergic poisoning. Ann Emerg Med 35:374–381, 2000.

Chapter 11 Altered Mental Status/Coma Joseph J. Zorc, MD

Key Points The approach to a child with altered mental status requires an organized and prioritized process of stabilization, assessment, differential diagnosis, and definitive management. In a patient with altered mental status, inability to provide a history or cooperate with assessment mandates a detailed physical examination with a particular focus on vital signs and neurologic examination. Reversible causes of altered mental status such as hypoglycemia and opiate ingestion should be immediately identified and treated prior to further tests or interventions. Multiple diagnostic tests may be indicated in the evaluation of a child with altered mental status. Consideration should be given to the appropriate sequence of tests based on suspicion of a focal central nervous system process versus a systemic process.

Introduction and Background Altered mental status in a child is a particularly challenging clinical problem for an emergency physician. At initial presentation, the etiology is frequently unclear, and potential impairment of airway, breathing, and circulation requires a rapid and focused assessment. Reversible causes such as hypoglycemia and opioid ingestion need to be identified and treated prior to other procedures. History and physical examination are important and may provide key clues, but may be limited by the inability of the patient to cooperate with the evaluation. The differential diagnosis of a child with altered mental status is extensive and ranges in severity from self-limited processes requiring brief supportive care to lifethreatening causes requiring aggressive intervention. Medications such as sedatives for radiographic tests or paralytics for intubation may interfere with later assessment and need to be considered carefully. For these reasons, an altered

mental status requires a structured, ordered approach to evaluation and management.

Recognition and Approach Altered mental status occurs when the ability of a child to arouse and interact with the external environment differs from normal. Abnormality in mental status must be interpreted in the context of normal stages of childhood development as well as the baseline functioning of the specific patient being evaluated. Careful assessment and documentation of the degree of alteration is important to identify changes in mental status over time. Terms for depressed mental status are often used loosely, although specific definitions over the spectrum of abnormality have been classically described.1 Confusion is a state in which cognitive abilities are slowed and impaired. Delirium represents an increased level of disability with disordered thinking, delusion, and often agitated behavior. Obtundation is a state in which the patient is less alert and disinterested in the environment. Stupor is a further progression in which stimulation is required to obtain arousal. Coma is the end point on the spectrum in which the patient does not respond to stimulation. While these terms are often used to describe infants and children with an altered mental status, it is helpful for clinicians to describe the exact nature of the abnormal behavior and to attempt to apply objective descriptors or rating scales to their behavior. Descriptive scales that numerically rate components of consciousness, such as eye opening, verbal, and motor activity, have been developed. One such example is the Glasgow Coma Scale (GCS).2 Although originally developed for use after head injury, the GCS has been applied widely as a quantitative measure of altered mental status, and adaptations are available for preverbal children (Table 11–1).3,4 Although useful in research and in the clinical setting to document trends in progression of symptoms over time, the reliability and validity of the GCS for use in the acute setting has been questioned.5 Little information exists about the use of the GCS in young children. The GCS should be used as a supplement to a more detailed assessment and descriptive documentation of alteration in mental status. The approach to a patient with altered mental status is typically dichotomized into two broad categories of etiology: disturbances localized within the central nervous system and systemic disorders (Table 11–2). Mass lesions within the central nervous system, such as tumor or hematoma, may be 115

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Table 11–1

Glascow Coma Scale (GCS) with Adaptations for Preverbal Children*

Eye Opening

Best Motor Response

Best Verbal Response

0–1 yr Spontaneous (4)

0–1 yr Spontaneous movement (6) Localizes pain (5) Flexion withdrawal (4)

0–2 yr Normal cry, coos, smiles (5) Cries (4) Inappropriate cry, screams (3) Grunts (2) No response (1)

To shout (3) To pain (2) No response (1) >1 yr Spontaneous (4) To verbal (3) To pain (2) No response (1)

Flexor posturing (3) Extensor posturing (2) No response (1) >1 yr Spontaneous movement (6) Localizes pain (5) Flexion withdrawal (4) Flexor posturing (3) Extensor posturing (2) No response (1)

2–5 yr Appropriate words (5) Inappropriate words (4) Cries or screams (3) Grunts (2) No response (1) >5 yr Oriented (5) Disoriented conversation (4) Inappropriate words (3) Incomprehensible, moans (2) No response (1)

*GCS scores ranges from 3 (worst) to 15 (best).

further subdivided into supra- and subtentorial based on the location of the lesion relative to the tentorium cerebelli, the dural fold that divides the anterior from the posterior fossa. This anatomy has clinical relevance because the midbrain at the level of the tentorium contains the reticular activating system, the network of neurons passing from spinal cord and brainstem to the cerebral cortex that plays a key role in maintaining consciousness. Mass lesions can compress this area and cause altered mental status, often accompanied by focal neurologic findings in nearby cranial nerves. In contrast, abnormalities causing altered mental status at the level of the cerebral cortex affect the brain diffusely through reduced delivery of a necessary substrate, effects of a toxin, or other widespread neuronal injury. The presence of focal findings may suggest a structural central nervous system lesion, although this is not entirely reliable as some systemic processes (e.g., hypoglycemia) may present with asymmetric findings.

Clinical Presentation Evaluation of a child with altered mental status begins with a rapid assessment of airway, breathing, and circulation. Since unrecognized trauma is a concern, airway stabilization should be accomplished with manual stabilization of the cervical spine in the midline; a jaw thrust and other airway adjuncts such as a nasopharyngeal or oral airway may be useful depending upon the level of consciousness of the patient (see Chapter 2, Respiratory Distress and Respiratory Failure). Assessment of breathing, provision of 100% oxygen, and circulatory assessment of pulses, perfusion, and cardiac rhythm with continuous monitoring should follow. A rapid determination of the level of consciousness should proceed while intravenous access is being obtained. A useful

Table 11–2

Differential Diagnosis of Altered Mental Status

Central Nervous System Disturbances Trauma Mass lesion (epidural, subdural, intracerebral hematoma) Diffuse or localized cerebral edema Cerebral contusion Tumors (often with hemorrhage) Hydrocephalus Circulation disorders Cerebrovascular accident Cerebral venous thrombosis Infection/inflammation Meningitis Encephalitis Cerebral abscess Subdural empyema Cerebritis Seizure Subclinical status epilepticus Postictal state Systemic Disorders Hypoxemia Hypo/hyperthermia Hypoglycemia Endocrine disorders Diabetic ketoacidosis Addisonian crisis Thyrotoxicosis, hypothyroidism Electrolyte disorders: sodium, potassium, calcium, magnesium Hepatic encephalopathy/Reye’s syndrome Uremic encephalopathy/hemolytic-uremic syndrome Inborn errors of metabolism Exogenous toxins Opiates Barbiturates/benzodiazepines Anticonvulsants: carbamazepine, phenytoin, valproic acid Organophosphate poisoning Anticholinergics: atropine, tricyclic antidepressants, phenothiazines Lead Metabolic acidosis (“MUDPILES”) Methanol Uremia Paraldehyde Isoniazid, iron Lactic acidosis: carbon monoxide, cyanide Ethanol, ethylene glycol Salicylates Systemic infection Sepsis Toxin-producing (e.g., Shigella) Strangulated or herniated bowel Intussusception Volvulus Adapted from Green M: Coma. In Pediatric Diagnosis, 6th ed. Philadelphia: WB Saunders, 1998, pp 338–345.

first assessment is guided by the acronym AVPU: alert at baseline, requires verbal stimuli to arouse, requires painful stimuli, or unresponsive to painful stimuli. More formal assessment and documentation of the level of unconsciousness by description and numerical GCS can follow. Diagnostic evaluation begins with measurement of serum glucose using a bedside glucometer. Conservative guidelines suggest that blood glucose concentrations below 40 mg/dl should be considered abnormal at any age; blood glucose concentration between 40 and 50 mg/dl require further eval-

Chapter 11 — Altered Mental Status/Coma

uation at any age, but may possibly be normal in neonates; and blood glucose concentrations below 60 mg/dl beyond early infancy should be considered borderline, with further evaluation required. Inaccuracies of bedside glucose meters should be taken into account when determining whether to undertake further evaluation and treatment for hypoglycemia. Some texts actually recommend a trial of empirical treatment with glucose in patients with unknown coma for levels as high as 80 to 100 mg/dl, but individual circumstances must be accounted for.6 Glucose can be given according to the “rule of 50,” whereby the product of the volume (ml/kg) and the concentration of the glucose solution should be 50 (e.g., 2 ml/kg of 25% dextrose or 5 ml/kg of 10% dextrose). Common causes of hypoglycemia that may lead to altered mental status in a child are discussed more fully elsewhere (see Chapter 106, Hypoglycemia). Ketotic (starvation) hypoglycemia, sepsis, inborn errors of metabolism, and ingestions of ethanol or oral hypoglycemic agents are among the more common causes in children.7 Nalaxone should be administered to all patients with an altered mental status of unknown etiology or suspected opioid overdose. The clinician should not rely on the presence of pupillary constriction (miosis) to diagnose opioid overdose since meperidine, pentazocine, diphenoxylate/ atropine (Lomotil), propoxyphene,and drug-induced hypoxia and co-ingestants may cause pupillary dilation (mydriasis). The empirical dose of naloxone is now recommended at 0.01 mg/kg intravenously. Give a subsequent dose of 0.1 mg/ kg if there is an inadequate response. Use intramuscularly, subcutaneously or via endotracheal tube if the intravenous route is not available. Larger doses may be required for certain ingestions (e.g., diphenoxylate atropine [Lomotil], methadone, propoxyphene, pentazocine, fentanyl derivatives, and certain forms of heroin [black tar]). If a response is observed, the patient should be monitored closely with consideration for a naloxone infusion as the half-life of many ingested agents is longer than the 60- to 90-minute effect of naloxone.8 Unlike adults, in whom withdrawal may be a concern, trial of an empirical dose of naloxone has little potential for adverse effects in children and may also produce a partial response in other situations such as clonidine overdose or intussusception (see discussion later). Other reversal agents, such as the benzodiazepine antagonist flumazenil, should not be given empirically in unknown cases due to the risk of seizure or interaction with other potential ingestions.9 This agent should be reserved for situations in which an overdose of benzodiazepine alone is established, as in an iatrogenic overdose. Other agents typically administered empirically to adults, such as thiamine, are also generally not required in children. The history should begin with a focused review of allergies, medications for the child or others in the household, and prior medical history. A thorough review of events leading up to the onset of symptoms should follow and may be best obtained by another clinician not involved in the acute stabilization. Frequently the caregiver most familiar with these events may not have accompanied the child, and reaching this person by telephone may provide key information. In particular, recent history of trauma and symptoms of infection or increased intracranial pressure should always be suspected. Many pediatric ingestions occur in new environments where the normal exploratory behavior of

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young children places them in contact with unsecured toxins; this may point toward a toxicologic cause. Physical examination should begin with obtaining vital signs. Patterns of abnormalities in vital signs accompanying other clinical findings may indicate a “toxidrome” associated with classes of toxic ingestions (see Chapter 10, General Approach to Poisoning) that may be helpful in establishing a diagnosis. Cushing’s triad is a classic pattern of bradycardia, bradypnea, and hypertension that has been described in association with elevated intracranial pressure. Patterns of abnormal respiration have also been described with various states of altered mental status. The Cheyne-Stokes variation is an alternation of deep and shallow breathing usually associated with metabolic encephalopathy. Central hyperventilation and “apneustic” inspiratory pauses have been described with various brainstem lesions.1 The presence of fever may indicate an infection, exogenous heat exposure, and other potential diagnoses (e.g., thryotoxicosis; ingestion of salicylate or sympathomimetic or anticholinergic agents). Hypothermia may be associated with cold exposure or metabolic abnormalities such as hyponatremia. Hypertension may also cause altered mental status in the setting of hypertensive crisis (see Chapter 65, Hypertensive Emergencies). However, hypertension may also be a compensatory response to elevated intracranial pressure, in which case treatment of the primary process is indicated as a priority to maintain cerebral perfusion pressure.10 In summary, physical findings may provide important clues to a definitive diagnosis of altered mental status in children (Table 11–3). Neurologic Examination A thorough neurologic examination can aid in narrowing the differential diagnosis. In particular, the cranial nerves are of importance, as the nuclei of these nerves are located close to the reticular activating system in the brainstem and may indicate dysfunction due to a focal mass lesion compressing this area. Pupillary findings also aid in identifying the cause of altered mental status. Pupils can be small or mid-sized and symmetrically reactive in metabolic coma (e.g., hypoglycemia, encephalitis, ethanol poisoning). Constricted pupils may be seen with opioid ingestion, although some reactivity usually remains on close examination. Central lesions in the pons can also cause bilaterally constricted pupils. Asymmetrically reactive pupils should raise concern for a focal mass lesion unless there is a history of eye trauma or direct exposure to a mydriatic agent (e.g., ipratropium). Horner’s syndrome occurs when there is injury to the hypothalamus or sympathetic chain nerves, resulting in a small but usually reactive pupil (miosis) associated with ptosis and anhidrosis. Herniation syndromes are a constellation of findings that are the end result of significant elevation in intracranial pressure (see Chapter 42, Conditions Causing Increased Intracranial Pressure). The “uncal syndrome” occurs when the uncus, the medial part of the temporal lobe, herniates through the tentorium due to elevated pressure superiorly, causing compression of the oculomotor nerve and a unilateral dilated and fi xed pupil, usually on the side of the mass lesion. Progression of elevated pressure on one side or symmetric elevation of intracranial pressure due to diffuse swelling or hydrocephalus can cause central herniation with bilateral pupillary and occulomotor impairment as well as decerebrate extensor

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Table 11–3

Physical Clues to the Diagnosis of Infants and Children with Altered Mental Status*

Physical Finding

Diagnosis

Hypotension

• Any disease causing hypotension can directly cause an altered mental status (e.g., bleeding, sepsis, trauma) • Toxins: antihypertensive agents (e.g., β-blockers, calcium channel blockers), barbiturates, benzodiazepines, clonidine overdose (late), cyanide poisoning (late), narcotics • Intracranial bleed • Intracranial mass • Hypertensive encephalopathy • Eclampsia • Postictal state • Hypoglycemia • Toxins: agents causing neuroleptic malignant syndrome and serotonin syndrome, clonidine overdose (early), cyanide poisoning (early), monoamine oxidase inhibitors, phencyclidine, sympathomimetics • Meningitis • Encephalitis • Early sepsis • Malignant hyperthermia or neuroleptic malignant syndrome • Toxins: anticholinergics, nerve agents/gases (Sarin, Soman, Tabun, VX gas, Substance 33), organophosphates, sympathomimetics • Adrenal insufficiency, crisis • Prolonged hypoglycemia • Hypothyroidism • Sepsis (late) • Environmental exposure to cold • Toxins: barbiturates, benzodiazepines, hypoglycemic agents, or any toxin that causes patients to be immobilized and hypometabolic for prolonged periods Nonspecific and can occur with most diseases • Impending brainstem herniation • Respiratory failure of any etiology • Cardiac disorders • Toxins: β-blockers, calcium channel blockers, clonidine, cyanide, digoxin, γ-hydroxybutyrate (GHB), opioids, organophosphates • Metabolic acidosis from any cause • Toxins: isoniazid, nicotine, salicylates, theophylline, toxic alcohols • Respiratory failure of any etiology • Toxins: benzodiazepines, botulinum, GHB, narcotics, sedative-hypnotics • Meningitis • Encephalitis • Sepsis • Toxins: nerve agents/gases (Sarin, Soman, Tabun, VX gas, Substance 33), organophophates, sympathomimetics • Toxins: anticholinergics, antihistamines, drug withdrawal, GHB, nerve agents/gases, organophosphates, and sympathomimetics rarely cause mydriasis when nicotinic effects exceed muscarinic effects • Pontine bleed or stroke • Coma from benzodiazepine, barbiturate or ethanol • Toxins: anticholinesterase, clonidone, narcotics, nicotine • Intussuception • Volvulus • Strangulated or herniated bowel • Toxins: iron • Hypoxia • Hypoglycemia from any cause • Intracranial mass, bleed, or infection • Toxins: all drugs causing hypoxia, anticholinergics, antidepressants, amphetamines, baclofen, β-blockers, camphor, carbamazepine, carbon monoxide, cocaine, cyanide, ethanol withdrawal, GHB, hypoglycemic agents, isoniazid, lidocaine, lindane, lithium, meperidine, propoxyphene, phencyclidine, salicylates, sympathomimetics, theophylline, water hemlock plant

Hypertension

Hyperthermia

Hypothermia

Tachycardia Bradycardia

Tachypnea Bradypnea Diaphoresis

Mydriasis (bilateral) Miosis Abdominal pain or rectal bleeding Seizure

*List is not all inclusive.

posturing. Compression of the brainstem leads to altered respiratory and cardiovascular status and death. Other patterns of herniation occur elsewhere in the cranium, including across the midline falx cerebri or at the level of the brainstem into the foramen magnum. The presence of an open fontanelle in a young child may provide evidence of increased intracranial pressure but does not eliminate the risk of brain herniation from one compartment to another. Evidence of herniation calls for aggressive management of intracranial pressure with mannitol and emergent neurosurgical evalua-

tion (see Chapter 9, Cerebral Resuscitation). Recent evidence suggests that 3% saline may be useful in management of intracranial hypertension.11 Since intracranial pressure rises dramatically once compensatory responses in the brain have been overcome, even small interventions to reduce intracranial volume may be effective. Controlled hyperventilation can reduce intracranial pressure in emergent situations by reducing cerebral blood flow, although this may have detrimental results if used for prolonged periods beyond the goal of a partial pressure of CO2 of 35 mm Hg.12

Chapter 11 — Altered Mental Status/Coma

Other important findings on neurologic examination include an assessment of tone, reflexes, and motor activity to detect seizure activity. Subclinical status epilepticus can be a cause of altered mental status. Decorticate posturing with flexion of the arms and extension of the legs may accompany lesions in the cerebral hemispheres.1 Decerebrate extensor posturing of the arms and legs usually indicates dysfunction at the level of the midbrain or cerebellum or, alternatively, severe metabolic dysfunction. Funduscopic examination should be performed to detect retinal hemorrhages associated with shaken infant syndrome; papilledema may indicate long-standing increased intracranial pressure, although it is not a reliable early finding after an acute insult. Brainstem control of eye movements can be assessed with a “doll’s-eye” maneuver of the head or cold caloric testing, although these interventions are not usually indicated during the initial assessment in the emergency department. The remainder of the physical examination involves a thorough head-to-toe secondary survey looking for subtle skin fi ndings such as bruising or rash, abdominal mass associated with intussusception, or other abnormalities. Odors on the breath or in the urine may be indicative of diabetic ketoacidosis, ethanol ingestion, or various metabolic derangements. Psychogenic causes of coma due to conversion reaction or other causes are uncommon in children and typically can be identified on examination by the presence of voluntary responses such as resistance to movement or withdrawal from noxious stimuli. Differential Diagnosis The differential diagnosis of altered mental status is broad and may be organized in several ways. Categorization of physical findings into central nervous system versus systemic (see Table 11–2) is helpful from a pathophysiologic standpoint, although a mnemonic device may be most useful in the acute setting to ensure that all important diagnoses have been considered (Table 11–4). Vascular abnormalities causing altered mental status are uncommon in children and usually are associated with underlying chronic conditions such as sickle cell disease or prothrombotic states (see Chapter 44, Central Nervous System Vascular Disorders). Infection can alter mental status through direct involvement of the central nervous system from a variety of viral, bacterial, fungal, or parasitic causes (see Chapter 43, Central Nervous System Infections). Infections outside of the central nervous system can alter mental status via systemic effects or toxins produced by organisms such as the Shiga toxin from Shigella. Toxicologic causes of altered mental status are diverse and

Table 11–4

VITAMINS Mnemonic for Altered Mental Status

Vascular: stroke, inflammatory cerebritis, migraine Infection: meningitis, encephalitis, brain abscess, toxin-producing organism (e.g., Shigella) Toxins Accident/Abuse: traumatic epidural, subdural, or diffuse axonal injury Metabolic: renal, hepatic, endocrine, electrolytes, inborn error Intussusception Neoplasm: tumor, hydrocephalus Seizure: subclinical status epilepticus, postictal state

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are more fully discussed elsewhere (see Chapter 10, General Approach to Poisoning). Clues to presence of a toxic ingestion include the presence of clinical toxidromes such as bradycardia/bradypnea (opioid, sedative-hypnotic) or tachycardia/tachypnea (sympathomimetic, anticholinergic). Other findings such as the size of the pupils (usually small in opioid ingestions), the condition of the skin (dry in anticholinergic toxicity), or the presence of acidosis on laboratory evaluation can help to further specify the toxin involved. Trauma can affect mental status by direct compression of the reticular activating system from an epidural or subdural hematoma with focal findings, or by intracerebral contusion, focal hemorrhage, or diffuse axonal injury (see Chapter 15, Trauma in Infants; and Chapter 17, Head Trauma). Epidural hematomas usually arise from injury to arterial vessels underlying a skull fracture; symptoms may progress rapidly to unconsciousness after an initial lucid period. Subdural hematomas are usually more indolent and may be a marker of diffuse axonal injury such as that seen in the shaken infant syndrome. These infants often appear to have a metabolic cause of altered mental status due to the nonfocal nature of the injury. If child abuse is suspected, a skeletal survey may identify occult injuries and assist with the diagnosis. Metabolic causes of altered mental status are multiple and covered fully in Chapters 110 through 115. Young children are predisposed to hypoglycemia due to reduced glycogen stores that result in a risk for ketotic hypoglycemia with a prolonged fast. Absence of ketones in the urine in the setting of hypoglycemia should raise the concern of an inborn error of metabolism such as a fatty acid oxidation defect.13 Inborn errors of metabolism typically present in newborns or in young infants at the time of an illness or when new foods are introduced, when catabolic processes fail and the body is unable to appropriately break down protein, fat, or carbohydrate. Inborn errors may require consultation with an endocrinology or metabolism specialist as well as detailed laboratory testing to make a complete diagnosis. Hepatomegaly or laboratory abnormalities such as hypoglycemia, hyperammonemia, and acidosis are clues to the presence of these disorders. Metabolic causes such as electrolyte abnormalities or hepatic, renal, or endocrine disorders will usually be detected on routine chemistry screening. Infants with strangulated or incarcerated bowel (e.g., intussusception or volvulus) can present with lethargy. This unique presentation in infants and toddlers has been described in up to half of intussusception cases in one series.14 These children are often initially considered to have systemic infections or toxic ingestions and often have significant delays in diagnosis and treatment.15 The cause of altered mental status associated with intussusception is unclear. Case reports of reversal with naloxone indicate that this process may be mediated by the release of endogenous opioid substances in the gut16 (see Chapter 74, Intussuception). Ruling out serious bowel disorders in a lethargic infant based on physical examination or plain radiographs may be difficult, and contrast or air enema, ultrasound, an upper gastrointestinal series, and/or surgical consultation may be required.17 Finally, other abnormalities in the central nervous system, such as intracranial mass lesions and hydrocephalus, should always be considered. Young infants with obstructive hydrocephalus may present with increased head circumference and

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“sunsetting” of the eyes (paralysis of upward gaze) due to compression of the ocular nuclei. Various seizures may alter mental status during and following an ictal event. Generalized seizures often are accompanied by tonic-clonic activity, but subtle subclinical status epilepticus may require electroencephalography to make a definitive diagnosis. A seizure accompanied by a postictal state can be identified by the presence of an acidosis that clears rapidly. Empirical therapy with a benzodiazepine or other antiepileptic may be indicated if ongoing subclinical seizure is suspected. Absence seizures usually alter mental status for brief periods with return to baseline, as opposed to partial complex seizures, which usually are longer and may be followed by a postictal period. If a prolonged generalized tonic-clonic seizure has occurred, a postictal state may alter mental status for a period of several hours.

Management Many potential etiologies can cause altered mental status, so an ordered process is required to organize diagnostic testing and management. If hypoglycemia and opioid ingestion have been ruled out, the next steps will be dictated by the depth of impairment and clues to the diagnosis on history and physical examination.18 Multiple etiologies may occur simultaneously; for example, a postictal state may follow a seizure due to a toxic ingestion. For this reason, it is difficult to organize management into a simple algorithm. Investigation should be individualized, with multiple potential etiologies ruled out in parallel based on clinical judgment. Initial laboratory tests are obtained after the secondary survey so that they can be processed while other examinations are being completed. Screening tests typically include serum electrolytes, renal and liver function tests, and a complete blood count. A venous blood gas determination of acid-base status/carboxyhemoglobin level may also be appropriate. Serum ammonia level may be considered if liver disease or an inborn error of metabolism is suspected. The laboratory evaluation should also include levels of any anticonvulsant medications prescribed or potentially ingested by the patient. Toxicology screens vary by institution, so it is important to be aware of what is being ordered. Utility in the acute setting varies greatly depending upon which test is ordered. Urine drugs of abuse screens are helpful in the initial evaluation to screen for opioids, barbiturates, cannabis, cocaine, amphetamines, phencyclidine, and benzodiazepines, although other important substances may be missed (e.g., some synthetic opiates, γ-hydroxybutyrate, lysergic acid diethylamide).19 Serum toxicology screens include ethanol levels and may also include acetaminophen, salicylate, and other drugs that are appropriate for empirical testing. An electrocardiogram should be obtained if primary cardiac disease or a toxic ingestion is suspected. Imaging of the brain is clearly indicated in altered mental status when there is a concern for an intracranial process (history of trauma, focal neurologic findings, signs of elevated intracranial pressure) or when the etiology is unknown. The usual initial study is computed tomography (CT) of the brain without contrast. Intravenous contrast can be added if tumor or an inflammatory process is suspected. CT may not identify posterior fossa masses, and further imaging may be required after the initial study.

Since imaging and other tests may require transport to another location, consideration should be given to the stability of the patient and the ability to protect the airway. The decision to control the airway should be individualized based on the patient’s level of alertness, presence of airway reflexes, and expected course. If trauma is suspected, aggressive management should be considered, whereas self-limited processes such as seizure may require only monitoring and supportive care. Airway management should be performed under controlled circumstances with measures taken to avoid increases in intracranial pressure (see Chapter 3, Rapid Sequence Intubation). Short-acting sedatives and paralytics are preferred to allow for serial reassessment of mental status and neurologic examination. For altered mental status due to suspected infection, the issue of when to obtain cerebrospinal fluid versus CT scan is controversial. Increased intracranial pressure from a mass lesion or obstruction of the ventricular system is a contraindication to lumbar puncture. Imaging is recommended prior to lumbar puncture for a patient with an undifferentiated cause of altered mental status, as clinical examination may not easily identify these contraindications.20 In addition, some studies have described a temporal association between lumbar puncture and herniation in cases of severe meningitis, although the causal nature of this relationship is debated.21 Imaging does not reliably predict marked elevation in intracranial pressure.22 In general, when cerebrospinal fluid is obtained in a patient with altered mental status, caution is advised; close monitoring, measurement of cerebrospinal fluid pressure, and careful withdrawal of the minimal amount of fluid required with a small-bore needle are recommended. Empirical treatment with antibiotics should not be delayed for imaging or other procedures if intracranial infection is suspected. If an etiology for altered mental status is still unclear after initial tests are completed, further tests for occult etiologies are appropriate. Since intussusception is difficult to rule out based on clinical findings, an ultrasound or barium enema may be indicated. Subclinical status epilepticus may require electroencephalographic monitoring for detection.23 If this is not available, empirical treatment with anticonvulsant medications may be appropriate. It may not be possible to confirm encephalitis in the acute setting, and empirical treatment with intravenous acyclovir to treat herpes should be considered. In some cases no diagnosis can be made acutely, and supportive care can be provided with appropriate consultation with neurologists, toxicologists, or other consultants to further investigate other causes. All of the above-mentioned measures can be incorporated into a general altered mental status management algorithm, although alternative management options should be tailored to the patient’s presentation and the clinician’s suspicion for specific disorders (Fig. 11–1).

Summary Definitive management of a child with altered mental status will depend upon the etiology and the response to initial management. Patients with persistent symptoms or unclear etiology require hospitalization for close observation and specialty consultation. In many cases this will require admission to an intensive care unit. Prognosis of altered mental

Chapter 11 — Altered Mental Status/Coma

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Apply cardiac monitor and pulse oximeter Support respirations Protect cervical spine if trauma suspected Support blood pressure with fluids Obtain bedside glucose If glucose normal—administer naloxone 0.01 mg/kg; subsequent dose 0.1 mg/kg if inadequate response

If good response to glucose or nalaxone, identify cause and treat underlying disease

Non-focal neurologic exam Pupils equal and reactive No signs, symptoms or history of trauma

Consider the following: CBC, electrolytes, BUN, creatinine Calcium, LFTs, ammonia ABG ECG UA Rapid drug screen Empiric antibiotic therapy (administer if meningitis or encephalitis suspected and consider CT prior to LP)

Focal neurologic exam Unreactive or unequal pupils Signs of trauma

Cranial CT scan

If CT positive, treat underlying disorder

If CT negative

Cause determined? NO YES

Cranial CT Lumbar puncture + -

FIGURE 11–1. Approach to the infant or child with altered mental status of unknown cause. Abbreviations: ABG, arterial blood gases; BUN, blood urea nitrogen; CBC, complete blood count; CT, computed tomography; ECG, electrocardiogram; EEG, electroencephalogram; GI, gastrointestinal; LFT, liver function test; LP, lumbar puncture; MRI, magnetic resonance imaging; UA, urinalysis; US, ultrasound; UGI, upper gastrointestinal.

Consider: MRI EEG Comprehensive tox screen Evaluation of GI tract (US, air or contrast enema, UGI) Detailed metabolic work-up for inborn errors or endocrine disease

status varies widely based on the etiology; mortality ranges from 3% to 84% by diagnosis in children with nontraumatic coma.24 The impression that young children recover more fully from coma than adults has been questioned as more detailed studies have explored cognitive outcomes in depth.25 Altered mental status in a child is a challenging clinical scenario for an emergency physician. With an organized

Treat and admit to hospital

Supportive case Admit to hospital Consult subspecialist

process for evaluation and management, the physician should be able to detected and managed most causes effectively in the emergency department. Future research in this area will likely focus on improving descriptive scales for altered mental status in children and developing more accurate diagnostic testing and treatments for the multiple potential causes of altered mental status.

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REFERENCES *1. Plum F, Posner J: The Diagnosis of Stupor and Coma, 3rd ed. Philadelphia: FA Davis, 1982. 2. Teasdale G, Jennett B: Assessment of coma and impaired consciousness: a practical scale. Lancet 2:81–84, 1974. 3. James HE: Neurologic evaluation and support in the child with an acute brain insult. Pediatr Ann 15:16–22, 1986. 4. Gemke RJ, Tasker RC: Clinical assessment of acute coma in children. Lancet 35:926–927, 1998. *5. Gill MR, Reiley DG, Green SM: Interrater reliability of Glasgow Coma Scale scores in the emergency department. Ann Emerg Med 43:215– 223, 2004. 6. Delaney KA: Dextrose. In Goldfrank LR, Flomenbaum NE, Lewin NA, et al (eds): Goldfrank’s Toxicologic Emergencies. New York: McGrawHill, pp 606–610. 7. Pershad J, Monroe K, Atchison J: Childhood hypoglycemia in an urban emergency department: epidemiology and a diagnostic approach to the problem. Pediatr Emerg Care 14:268–271, 1998. 8. Lewis JM, Klein-Schwartz W, Benson BE, et al: Continuous naloxone infusion in pediatric narcotic overdose. Am J Dis Child 138:944–946, 1984. 9. Gueye PN, Hoffman JR, Taboulet P, et al: Empiric use of flumazenil in comatose patients: limited applicability of criteria to defi ne low risk. Ann Emerg Med 27:730–735, 1996. *10. Poss WB, Brockmeyer DL, Clay B, Dean JM: Pathophysiology and management of the intracranial vault. In Rogers MC, Nichols DG, Ackerman AD, et al (eds): Textbook of Pediatric Intensive Care, 3rd ed. Baltimore: Williams & Wilkins, 1996, pp 645–665. 11. Simma B, Burger R, Falk M, et al: A prospective, randomized, and controlled study of fluid management in children with severe head injury: lactated Ringer’s solution versus hypertonic saline. Crit Care Med 26:1265–1270, 1998. *Selected readings.

12. Muizelaar JP, Marmarou A, Ward JD, et al: Adverse effects of prolonged hyperventilation in patients with severe head injury: a randomized clinical trial. J Neurosurg 75:731–739, 1991. 13. Hostetler MA, Arnold GL, Mooney R, et al: Hypoketotic hypoglycemic coma in a 21-month-old child. Ann Emerg Med 34:394–398, 1999. 14. Heldrich FJ: Lethargy as a presenting symptom in patients with intussusception. Clin Pediatr 25:363–365, 1986. *15. Conway EE: Central nervous system fi ndings and intussusception: how are they related? Pediatr Emerg Care 9:15–18, 1993. 16. Tenenbein M, Wiseman NE: Early coma in intussusception: endogenous opioid induced? Pediatr Emerg Care 3:22–23, 1987. 17. Bhisitkul DM, Listernick R, Shkolnik A, et al: Clinical application of ultrasonography in the diagnosis of intussusception. J Pediatr 121:182– 186, 1992. *18. Kirkham FJ: Non-traumatic coma in children. Arch Dis Child 85:303– 312, 2001. 19. Rainey PM: Toxicology screening. In Goldfrank LR, Flomenbaum NE, Lewin NA, et al (eds): Goldfrank’s Toxicologic Emergencies. New York: McGraw-Hill, pp 82–89. 20. Quality Standards Committee of the American Academy of Neurology: Practice parameters: lumbar puncture. Neurology 43:625–627, 1993. 21. Rennick G, Shann F, de Campo J: Cerebral herniation during bacterial meningitis in children. BMJ 306:953–955, 1993. 22. Shetty AK, Desselle BC, Craver RW, et al: Fatal cerebral herniation after lumbar puncture in a patient with a normal computed tomography scan. Pediatrics 103:1284–1287, 1999. 23. Towne AR, Waterhouse EJ, Boggs JG, et al: Prevalence of nonconvulsive status epilepticus in comatose patients. Neurology 54:340–345, 2000. *24. Wong CP, Forsyth RJ, Kelly TP: Incidence, aetiology, and outcome of non-traumatic coma: a population based study. Arch Dis Child 84:193– 199, 2001. 25. Forsyth RJ, Wong CP, Kelly TP, et al: Cognitive and adaptive outcomes and age at insult effects after non-traumatic coma. Arch Dis Child 84:200–204.

Chapter 12 Approach to Multisystem Trauma Lance Brown, MD, MPH

Key Points Mechanism of injury is a relatively poor predictor of injury severity. An age-appropriate primary survey facilitates the physical examination and limits unnecessary testing. Laboratory studies have minimal utility in the management of most traumatized children. Computed tomograpic scanning is indispensable in evaluating children at risk for multisystem trauma. Nonoperative management of selected intra-abdominal and intracranial injuries is now common.

Introduction and Background Using an evidence-based approach to pediatric multisystem trauma care is problematic. Due to the absence of agreedupon definitions for “pediatric” and “multisystem,” various age thresholds for considering a subject “pediatric” exist. Development progresses at a somewhat different rate for each child. Authors of “pediatric” studies have included individuals who present to a children’s hospital without a specific age threshold identified1-3 and individuals younger than 21 years of age,4 19 years of age,5 18 years of age,6-9 16 years of age,10-12 15 years of age,13,14 or 11 years of age.15 The inclusion of both preverbal infants and physiologic adults in many of these studies weakens the validity of proposed conclusions regarding “pediatric” trauma.16 The term multisystem and synonyms such as “polytrauma” lack agreed-upon definitions. “Multisystem” most appropriately refers to multiple, serious injuries sustained by a single child following blunt trauma, or to whole-body blunt forces that place a child at risk for multiple internal injuries.17 This may partially explain why many studies from the pediatric trauma literature focus on injuries to a single body region.2,3,5-9,18-39 Unfortunately, many injuries are unlikely to be found in isolation, making uniform management recommendations difficult.

The management of children who have sustained multisystem trauma involves coordinated care among multiple specialists. These children not only require the unique skills of the emergency physician, but may also require care by an orthopedic surgeon, neurosurgeon, pediatric or general surgeon, otolaryngologist, plastic surgeon, maxillofacial surgeon, or urologist. Given the difficulties in developing an evidence-based understanding of pediatric multisystem trauma, conflicts regarding management may arise among these specialties. Although still evolving, the science of pediatric trauma care offers reasonable evidence on which physicians can base their diagnostic and management plans.

Recognition and Approach To some extent, the unique anatomic and physiologic features of children and the mechanism of injury predispose children to specific injuries. Pedestrian motor vehicle trauma victims often have multiple injuries, including injuries to the head, thorax, and pelvis. Unrestrained motor vehicle occupants are at significant risk for head, face, and cervical injuries, while restrained passengers are at risk for cervical spine, lumbar spine, and solid and hollow organ injury. Additionally, seat belts, when used without a booster seat for children 4 to 9 years of age, increase the risk of bowel/bladder rupture or hematoma.40 Bicyclists who are injured are at risk for head injury (especially if unhelmeted), upper extremity trauma, and handlebar injuries to the pancreas and bowel.40 Falls from the second story of a building or higher increase the risk of head injury, with long-bone fractures increasing with falls from the third story, and thoracoabdominal injuries dramatically rising at the fifth story.41 Anatomic and physiologic developmental differences help to identify distinct injuries and responses to injury within different age groups. Head injuries are common in younger infants and children. The relatively larger size of an infant’s head dramatically increases the risk that the skull will be involved in most blunt force mechanisms. The skull is relatively soft in infants and toddlers. Forces are more easily transmitted through a weaker, immature skull to soft developing neural tissue. Unlike older children, infants with open fontanelles and sutures may actually develop hypotensive shock due to intracranial bleeding. Unlike adults, children frequently develop intracranial hyperemia following head injury, which increases cerebral blood flow, intracranial blood volume, and intracranial pressure.42 123

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Thoracoabdominal injuries are an important cause of mortality in infants and children, accounting for 10% to 20% of all trauma-related deaths.43 The greater pliability of the thoracic cage in young children permits the ribs to be easily compressed without fracturing and without obvious external evidence of trauma. As a result, pulmonary contusions occur without rib fractures.44 As the bony rib cage ossifies, fractures and obvious chest wall trauma become more common. Since the chest is relatively small compared to the head and abdomen of infants and young children, isolated thoracic trauma is uncommon. Solid abdominal organs are larger in children compared to adolescents and adults, increasing their propensity to be traumatized during blunt force injuries. Infants and young children have poorly developed abdominal muscles, a more protuberant abdomen, and less fatty insulation compared to adults, thus increasing their risk for injury during blunt trauma. The pediatric kidney retains fetal lobulations, leading to a higher risk for fracture. The spleen’s capsule is relatively thicker at younger ages, allowing for an increased ability to contain traumatic splenic bleeding and improving the possibility that injuries can be managed nonoperatively. Importantly, the bladder is an abdominal organ in young children, increasing the possibility for injury following abdominal trauma.40 A child’s smaller body leads to traumatic forces that are often distributed over a smaller body mass, increasing the number of systems injured during trauma. A larger relative surface area and increased metabolic rate promote hypothermia, complicating the management of shock. Physiologic characteristics account for important cardiopulmonary responses to injury. A smaller functional residual capacity and increased oxygen consumption account for an increased risk of respiratory failure with blunt thoracic trauma and hypovolemic shock. Infants and children more readily maintain a normal blood pressure with significant bleeding, compared to adults and adolescents. As much as 25% to 30% of circulating blood volume might be lost before hypotension develops. As blood loss occurs, increases in systemic vascular resistance and peripheral vasoconstriction makes vascular access difficult. Tachycardia is a poor marker for blood loss due to the significant variability with age, pain, temperature, and stress. Capillary refi ll time is often cited as a useful marker for blood loss and shock in children. However, this test is an unreliable marker for hypovolemia due to high interobserver variation, large fluctuations with environmental temperatures, and variability in measurement techniques and individual responses to hypovolemia.40

Evaluation Injury severity occurs along a continuum from minimal injury to full traumatic arrest. At either end of the spectrum, the evaluation is typically straightforward. When a child has obviously sustained minimal injury or is uninjured, a focused history and physical examination followed by reassurance or some basic first aid (e.g., abrasion care) is all that is typically required. When confronted with a critically injured child, a protocol-driven assessment with attention to definitive airway management, prompt vascular access, and the performance of any invasive, potentially life-saving procedures is warranted. Few would question the ordering of any radiographic or laboratory test deemed potentially useful in this

extreme situation. Although emotionally and technically challenging, the decision-making processes in these cases can be formulaic. In contrast, cases with intermediate acuity or concern for subtle injuries offer a much greater challenge for the experienced emergency physician. In these cases, selective diagnostic testing is indicated and decision making is fairly complex. For emergency physicians more familiar with the resuscitation of traumatized adults, there are some important differences between children and adults that may have a substantial impact on the trauma evaluation (Table 12–1). Decision making in pediatric trauma requires knowledge of child development and proper resource utilization with regard to prehospital triage, trauma team activation, laboratory tests, and radiographic tests. The primary survey has been considered a critical element to proper trauma care.45,46 Although this sequential approach of progressing through airway, breathing, circulation, disability, and exposure (the ABCDEs) is simple and has been advocated for decades, it has not been evaluated in children. Nonetheless, it has been explicitly stated that children should simply be treated the same as adults with regard to the primary survey.45 Clinical experience suggests that applying this approach to the awake, alert, traumatized child may complicate, rather than facilitate, the evaluation and management. The typical approach involves donning masks and gowns, using loud voices, promptly applying monitoring devices, cutting clothing off, and promptly attempting intravenous line placement while keeping a child tied to a board and telling them to hold still. This can be unkind and decreases the likelihood of a meaningful physical examination. Without a meaningful physical examination, assessment of the child’s mental status, abdomen, and spine are less reliable. Prolonged immobilization in a cervical collar on a hard board may lead to iatrogenic neck pain, back pain, and impaired respiratory capacity.47,48 This, in turn, may lead to unnecessary sedation and radiologic testing. The classically implemented primary survey is likely to be effective and appropriate for evaluating the traumatized child with grossly altered mental status, or who is critically ill or comatose. An alternative approach may be more successful in evaluating awake, alert, traumatized children (Table 12–2). Although this has not been prospectively evaluated for safety and efficacy, this approach can be considered in patients who appear to be stable and have normal mental status. Predictors of Serious Injury Identifying predictors of serious injury is needed for the development of decision rules for prehospital triage and trauma team activation. These two events have the greatest impact on overall trauma resource utilization. For example, a simple decision rule to determine which children are likely to require services available only at a specialty pediatric trauma center would likely reduce unnecessary transport to those centers. Similarly, for children brought to specialty trauma centers, identification of those at high risk for needing prompt surgical intervention would result in better use of surgical consultation and avoid disruption of other important patient care activities outside the emergency department. Although there are no completely reliable predictors of the need for care at a trauma center, knowledge of trauma scores and their limitations may be useful. The Pediatric Trauma Score (PTS) was initially developed as a tool to quickly deter-

Chapter 12 — Approach to Multisystem Trauma

Table 12–1

Common Pediatric Characteristics That Impact Trauma Presentation, Management, and Outcome

Characteristics

Potential Impact on Trauma Care

Heart rate

• Tachycardia is common and is not specific for bleeding or hypotension. • Bradycardia is a prearrest event often signifying shock or respiratory failure. • Up to 25–30% of blood volume may be lost before significant hypotension develops.

Blood pressure

• Open fontanelle and sutures can lead to significant uncontrolled bleeding and cause hypotension in young infants. • Hyperermia/vasodilation is common in children with head injury, compared to vasoconstriction/ischemia in adults. • Immature and flexible ligaments lead to false appearance of subluxation C2-3, and disparity in growth rates at C1-2 leads to false appearance of C1 burst fracture (pseudo-Jefferson’s fracture). • The relatively large head means that centrifugal and rotational forces more commonly lead to trauma at C1 and C2 in children under 8 years, while C5-7 injuries are more common at or above this age. • Myocardium and coronary arteries are normal, with less risk for myocardial contusion.

Head

Cervical spine

Myocardium and coronary arteries Lungs and ribs

• Less functional residual capacity and higher oxygen consumption (1) increase the risk for respiratory failure with chest trauma and with shock and (2) lead to quicker desaturation during rapid sequence intubation and sedation. • Pliant ribs are less able to protect the liver and spleen during blunt trauma. • Pliability means fewer aortic and major vascular injuries resulting from blunt trauma.

Blood vessels Bones Sold abdominal organs Kidneys Spleen Stomach Bowel Bladder

Table 12–2

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• Immaturity results in fewer rib fractures, less obvious chest wall trauma with significant pulmonary injury, and unique growth plate injuries. • Relatively larger size, less fat insulation, and less well-developed abdominal muscles increase risk of blunt traumatic injury. • Kidneys retain fetal lobulations and are less protected by location and musculature, increasing risk of fracture. • Relatively thicker capsule at younger ages may decrease risk for rupture and increase probability of successful nonoperative management. • More distended and less protected within the abdomen, increasing the propensity to perforation or respiratory compromise. • Small bowel is prone to injury, typically in 4- to 9-year-olds, with seat belt that encircles abdomen instead of pelvis. • Abdominal structure in the very young is more likely to rupture with blunt force.

Suggested Principles for a Modified Evaluation of the Awake, Alert, Traumatized Child

• Number of individuals at the bedside can be minimized (one emergency physician and one nurse is ideal). • Quiet voices should be used at all times. • No commands should be directed at the child. • Attachment of monitors to the child may be delayed if deemed appropriate by the emergency physician. • Cutting off clothes may be deferred at the discretion of the emergency physician. • All explanations provided to the child should be age appropriate. • Analgesia should be provided as soon as possible. • Techniques such as distraction should be used to calm the child as needed. • Mental status should be continually assessed by having a conversation with the child. • Removal of the cervical collar should take place safely but expeditiously. • Removal from the spinal board should take place as soon as possible. • Parents and guardians should be allowed to come to the bedside as soon as possible.

mine the need to transport children to a trauma center49 (Table 12–3). Initial studies found that children with a PTS less than 0 had 100% mortality, those with a PTS of 1 to 4 had 40% mortality, those with a PTS of 5 to 8 had 7% mortality, and those with a PTS greater than 8 had virtually no mortality following trauma.50,51 Based on these data, a PTS

Table 12–3

Pediatric Trauma Score Score

Patient Feature

+2

+1

−1

Weight (kg) Airway Systolic blood pressure (mm Hg) Mental status Open wound Extremity fracture

>20 Patent >90

10–20 Maintainable 50–90

29 10–29 6–9 1–5 0

*Add total points (0 to 4) for each category to obtain score.

scoring in identifying children who potentially require trauma center care. There is a growing body of evidence that some of the traditionally accepted predictors of injury severity do not effectively risk-stratify traumatized children. Although frequently cited and historically relied upon, mechanism of injury tends to be a relatively poor predictor of injury severity. Still, published trauma team activation criteria include various mechanisms of injury.13,56-59 These mechanisms typically include falls from a height greater than 3 to 6 m (10 to 20 feet), rollover motor vehicle accidents, pedestrian struck at greater than 16 to 32 km/hr (10 to 20 miles/hr), passenger ejection from the vehicle, death of a co-occupant of the same vehicle, and the need for a extrication from the vehicle lasting longer than 20 minutes.13,54,55,60-62 These mechanisms have a certain degree of intuitive appeal; however, there is building evidence that they do not accurately predict serious injuries.13,15,56,58,61-64 In addition, there is also a risk of false histories. It has been suggested that, if a short vertical fall is offered as the mechanism of injury and the child has sustained a serious injury, the history is most likely false15,61 (see Chapter 119, Physical Abuse and Child Neglect). This concept that the mechanism of injury alone fails to predict serious injury is also supported by studies of adults.58,65-69 However, there is one mechanism of injury that is predictive of specific intra-abdominal injuries. A “handlebar injury” has been associated with pancreatic and bowel injuries in children in addition to liver and spleen injuries.70-73 In these cases, a bicycle-riding child loses control and the end of the bicycle handlebar strikes the child directly in the epigastrium during the fall. Similar injuries occur when a child is struck in the abdomen with the end of a baseball bat or kicked in the epigastrium, for example. These types of injuries result in a substantial force being applied to a relatively small area of the abdomen. In addition to the more common solid organ injuries, particular attention should be given to diagnosing pancreatic and small bowel injuries in these children. Another frequently cited predictor of serious injury is loss of consciousness. Brief loss of consciousness, as an isolated symptom, does not predict intracranial injury.74-78 In one study, loss of consciousness had a positive predictive value of only 9%.76 Although there is now compelling evidence to suggest that a history of brief loss of consciousness does not accurately predict intracranial injuries identifiable on computed tomography (CT) scan of the head, consensus groups persist in recommending CT scans of the head based solely on a history of loss of consciousness79 (see Chapter 17, Head Trauma). The use of seat belts and child safety seats, and placing children in the back seat of a vehicle, decrease the likelihood

of morbidity and mortality for children who are passengers in motor vehicle crashes.80,81 Properly restrained younger children are also less likely to require transport to the hospital.82,83 Laboratory Testing A small body of literature has evaluated the utility of laboratory tests in evaluating cases of pediatric multisystem trauma. In general, the diagnostic utility of laboratory tests is minimal.84-86 A substantial problem with evaluating laboratory tests is that the outcome of interest in cases of multisystem trauma is heterogeneous. The clinician desires to find all “serious injuries.” In addition, because of differences in study design, authors of different studies may arrive at incompatible conclusions. While one author examines the utility of a test as a screening tool (thereby looking for high sensitivity), another author may examine that same test, but assess its utility as a diagnostic tool (thereby looking for high specificity). Their stated conclusions may be contradictory. Ancillary laboratory tests rarely identify unsuspected injuries in awake, alert, cooperative children without severe trauma. One author evaluated 3939 laboratory screening tests obtained in 285 consecutive children with minimal to moderate injury admitted to a pediatric trauma center, and 91 patients with proven intra-abdominal injury.86 The abdominal examination combined with a urinalysis detected 98% of all injuries and 100% of injuries requiring surgical intervention.86 Laboratory values often provide only confirmatory evidence that an injury is present and are not diagnostic.87 Coagulation studies, including platelet count, prothrombin time, and partial thromboplastin time, are seldom useful in previously healthy children.88 Children who receive multiple units of transfused blood are at risk for developing coagulopathies. Electrolyte abnormalities are uncommon in acute trauma. In children with shock due to acute blood loss, a metabolic acidosis can be expected.89,90 Important electrolyte abnormalities that occur primarily following massive transfusions include hyperkalemia, metabolic alkalosis, hyperphosphatemia, and hypocalcemia. Liver function tests are elevated in most cases of blunt hepatic trauma.91 One study found that the presence of either a serum aspartate aminotransferase (AST) greater than 450 IU/L or a serum alanine aminotransferase (ALT) greater than 250 IU/L was 100% sensitive and 92% specific in detecting hepatic trauma in children with blunt abdominal trauma.92 AST and ALT were highest in the first 12 hours, declining to normal within 5 days of injury.92 A large review of adult and pediatric blunt abdominal trauma victims found that the presence of either an AST or ALT greater than 130 IU/L was 100% sensitive in detecting liver injuries.93

Chapter 12 — Approach to Multisystem Trauma

Since CT is recommended to identify and grade suspected liver injuries, liver function tests are generally not required in managing liver injuries. Their main use might be to identify unsuspected injuries in children who do not undergo CT or who are being evaluated for other disorders. Amylase and lipase elevations are common in patients with blunt abdominal trauma. However, these tests have poor sensitivity, with elevations reported in only 13% to 77% of CT or laparoscopically proven cases of pancreatic trauma.94-100 Repeat values over time may increase the sensitivity of these tests in detecting significant pancreatic injury.98 Amylase and lipase levels cannot discriminate between pancreatic and nonpancreatic trauma. Pancreatic enzyme abnormalities are elevated in nearly half of all blunt trauma victims.97 One study found than only 2% of patients with an elevated amylase or lipase level actually had a pancreatic injury.97 Moreover, as few as 13% with pancreatic trauma have elevated pancreatic enzymes.100 Because of the poor discriminatory ability of these tests, they should not be relied upon to diagnose or exclude pancreatic injury. Hematuria is commonly seen in seriously injured children.101 Hematuria can indicate trauma anywhere within the genitourinary system. Of note, hematuria is absent in up to 50% of patients with renal pedicle injuries (associated with massive trauma) and isolated ureteral injuries (e.g., gunshot and stab wounds).102-104 In general, evaluation of these patients is straightforward, and all require radiologic evaluation. Importantly, most serious renal injuries occur in patients with other indications for CT of the abdomen/pelvis or gross hematuria. Debate has existed concerning the appropriate workup of patients with only minor blunt trauma, no lower genitourinary injury, minimal or no symptoms, and microscopic hematuria. In the past, radiologic evaluation was performed on all children with any degree of hematuria in the belief that minor degrees of hematuria might be the only indicator of serious renal injury or of hidden congenital renal disorders.105 This approach is no longer universally accepted106,107 (see Chapter 21, Pelvic and Genitourinary Trauma). Most diagnostic laboratory studies provide no useful information in previously healthy children with blunt abdominal trauma. Laboratory studies might be helpful in children with an underlying disease, hypotension, or the need for multiple units of blood, or who are at risk for developing specific complications following admission (e.g., coagulopathy, electrolyte disorders). Imaging Studies The utility of the traditional “C-spine, chest, pelvis” set of plain radiographs has not been adequately studied in children. Understanding the role of these radiographs in the setting of alternative imaging modalities such as CT and magnetic resonance imaging (MRI) is becoming increasingly important. Although large, well-designed studies have provided important information on when adults do not require cervical spine imaging, studies in children are limited.108-110 A large prospective series of trauma patients found that adult trauma victims did not require imaging if they met the following NEXUS criteria: a normal mental status, no midline neck tenderness, no distracting injury, no intoxication with drugs or alcohol, and no motor or sensory deficits.109 This study also included 2160 patients 8 to 17 years old and 817

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patients 2 to 8 years old with a total of 30 cervical spine injuries.111 Although the criteria were 100% sensitive in detecting all cervical spine injuries at these ages, there were too few injuries to adequately assess the NEXUS criteria for use with children. Importantly, this study only included 88 patients less than 2 years old, limiting the applicability of these criteria to this age group. The total number of cervical spine injuries was small, with only 30 document injuries (1% of cases). To verify that these criteria will be highly sensitive, they need to be done in larger studies that include more pediatric injuries. Flexion-extension, oblique, and odontoid radiographs rarely reveal abnormalities in children.112-114 However, the number of patients in each of these studies was small. Clinical experience supports the minimal utility of these studies for evaluating traumatized children. In cases where the cervical spine cannot be cleared clinically or with plain radiographs, maintaining spinal precautions until an MRI can be obtained is prudent.116 In essence, MRI is the criterion standard for evaluating the spine of the unconscious child. Indications for obtaining a chest radiograph in pediatric trauma are not clear. In one case-control study, the presence of an abnormal respiratory rate for age, chest tenderness, or back abrasions was 100% sensitive for identifying children with abnormal chest radiographs.117 Clinical experience suggests that grunting respirations, hypoxia, asymmetric breath sounds, and dyspnea are indications for chest radiography. Endotracheal intubation, thoracostomy tube insertion, and central vascular access in the internal jugular or subclavian veins are also indications for chest radiography. A single study examined whether CT of the chest should replace plain radiographs.118 The authors concluded that plain radiographs should remain the primary imaging modality in the setting of blunt pediatric trauma. Children are less likely to sustain pelvic fractures than adults.36 This appears to be true regardless of the mechanism of injury. There is seldom the need for a rapid, bedside assessment of the pelvis using plain radiography.36,119 It has been shown that pelvic fractures can be readily identified on CT scanning of the abdomen and pelvis.120 The routine ordering of pelvic radiographs may be unnecessary, particularly in situations in which a child will be undergoing CT scanning of the abdomen and pelvis based on other indications. CT scanning has been the greatest advance in pediatric trauma management in the last few decades. CT scanning offers a painless, noninvasive, detailed set of images of the interior of the head and torso. There is ongoing work to determine the exact indications for CT scanning of the head, abdomen, and pelvis in the setting of pediatric multisystem trauma. Although there are proposed indications for head CT scanning and for abdominal and pelvic CT scanning (see Chapter 17, Head Trauma; Chapter 24, Thoracic Trauma; and Chapter 25, Abdominal Trauma), abnormal mental status is an indication for all three scans since it is impossible to confidently rule out intracranial or intra-abdominal injuries based on the clinical examination. Other indications for CT scanning of the abdomen and pelvis include gross hematuria, lap belt injury, nonaccidental trauma, handlebar injury, and abdominal tenderness.70-73,121 Although CT scanning of the abdomen and pelvis is very effective for evaluating injuries to solid organs such as the liver, spleen, and kidney, it is

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Table 12–5

Selected General Concepts for the Emergency Department Management of Children at Risk for Multisystem Trauma

• Whenever possible, prolonged chemical paralysis should be avoided. Children who have sustained head injuries may develop seizures. If the child’s muscle activity has been masked by medications, seizures may go unnoticed. This leaves a child as risk for unrecognized status epilepticus and severe brain injury. For the intubated child, adequate sedation should be provided rather than prolonged chemical paralysis whenever possible. (See Chapter 3, Rapid Sequence Intubation; and Chapter 40, Seizures.) • A negative CT scan does not rule out all intra-abdominal injuries. Although CT scanning is excellent at identifying or ruling out most solid organ injuries, pancreatic and bowel injuries may not be apparent on initial scans.9,34,35,37,122-124 If a child has persistent abdominal pain or tenderness, but a negative CT scan of the abdomen and pelvis, admission for observation and repeat evaluations is typically warranted. In this way, more subtle injuries such as those to the pancreas and bowel can be identified. (See Chapter 25, Abdominal Trauma.) • Hemodynamic instability warrants the prompt administration of packed red blood cells. A child who has persistent tachycardia or hypotension after the administration of two or three 20-ml/kg boluses of crystalloid (usually normal saline, although lactated Ringer’s solution is acceptable) should receive at least 10 ml/kg of packed red blood cells.128,129 Since hemodynamic instability is often due to bleeding, the administration of packed red blood cells is also an appropriate initial treatment. (See Chapter 25, Abdominal Trauma; and Chapter 132, Utilizing Blood Bank Resources/Transfusion Reactions and Complications.) • Nonoperative management is becoming increasingly common. The detailed and timely anatomic information available from CT scanning has allowed for nonoperative management of some intra-abdominal and intracranial injuries.5,130-139 This trend has led to infrequent laparotomies at major pediatric trauma centers.140 This trend will likely continue and will increase the role of emergency physicians in the management and study of pediatric multisystem trauma. (See Chapter 25, Abdominal Trauma; and Chapter 17, Head Trauma.) Abbreviation: CT, computed tomography.

not sensitive in ruling out pancreatic, mesenteric, or bowel injuries.9,34,35,37,122-124 Despite the valuable information gained, there are potential deleterious effects of radiation incurred to a child undergoing multiple CT scans in the setting of trauma. A risk:benefit analysis is indicated to minimize unnecessary CT scanning. The utility of Focused Abdominal Sonography for Trauma (FAST), now widely used in the emergency department evaluation of adult trauma patients, is controversial in children who have sustained multisystem trauma. Ultrasound is an excellent test for identifying free fluid (i.e., blood) within the abdomen.125 However, the presence or absence of free fluid does not necessarily impact management.126,127 Since the presence of free fluid in a child’s abdomen does not indicate the need for immediate laparotomy except in very rare instances, ultrasound rarely impacts the clinical management of children who are at risk for multisystem trauma. In addition, there are solid organ injuries identifiable on CT scanning that are clinically important to identify, but do not lead to free fluid in the abdomen. These injuries, therefore, will be missed on ultrasound. Those individuals for whom ultrasound might be useful are almost always the same children who meet the indications for CT scanning of the abdomen and pelvis (see Chapter 179, Ultrasonography).

Management Management is guided by the results of the initial evaluation. The combination of individual injuries that can be identified during the evaluation of a child who is at risk for multisystem trauma is nearly infinite (see Section II, Approach to the Trauma Patient). However, a few general concepts are useful for managing a child who is at risk for multisystem trauma (Table 12–5).

Summary Our understanding of pediatric multisystem trauma is evolving. This is reflected in the currently available literature. Traditionally accepted predictors of injury severity such as mechanism of injury and brief loss of consciousness have

been shown to have limited utility in risk-stratifying traumatized children. An age-appropriate evaluation offers the clinician the greatest opportunity for obtaining a meaningful physical examination and for minimizing unnecessary testing. The traditional “C-spine, chest, pelvis” set of radiographs is no longer universally accepted due to limited utility. MRI is the criterion standard for evaluating the spine of the unconscious child. When indicated, CT scanning is the most effective means of evaluating the head, abdomen, and pelvis. Nonoperative management of some intra-abdominal and intracranial injuries has become increasingly common. This necessitates that emergency physicians have a detailed, evidence-based knowledge of the evaluation and management of children who are at risk for multisystem trauma. REFERENCES 1. Connors JM, Ruddy RM, McCall J, et al: Delayed diagnosis in pediatric blunt trauma. Pediatr Emerg Care 17:1–4, 2001. 2. Laham JL, Cotcamp DH, Gibbons PA, et al: Isolated head injuries versus multiple trauma in pediatric patients: do the same indications for cervical spine evaluation apply? Pediatr Neurosurg 21:21–226, 1994. 3. Brown RL, Brunn MA, Garcia VF: Cervical spine injuries in children: a review of 103 patients treated consecutively at a level 1 pediatric trauma center. J Pediatr Surg 36:1107–1114, 2001. 4. Danseco ER, Miller TR, Spicer RS: Incidence and costs of 1987–1994 childhood injuries: demographic breakdowns. Pediatrics 105:e27, 2000. 5. Davis DH, Localio AR, Stafford PW, et al: Trends in operative management of pediatric splenic injury in a regional trauma system. Pediatrics 115:89–94, 2005. 6. Baker C, Kadish H, Schunk JE: Evaluation of pediatric cervical spine injuries. Am J Emerg Med 17:230–234, 1999. *7. Viccellio P, Simon H, Pressman BD, et al: A prospective multicenter study of cervical spine injury in children. Pediatrics 108:e20, 2001. 8. Palchak MJ, Holmes JF, Vance CW, et al: A decision rule for identifying children at low risk for brain injuries after blunt head trauma. Ann Emerg Med 42:492–506, 2003. 9. Jerby BL, Attorri RJ, Morton D Jr: Blunt intestinal injury in children: the role of the physical examination. J Pediatr Surg 32:580–584, 1997 10. Holmes JF, Sokolove PE, Brant WE, et al: A clinical decision rule for identifying children with thoracic injuries after blunt torso trauma. Ann Emerg Med 39:492–499, 2002. *Selected readings.

Chapter 12 — Approach to Multisystem Trauma 11. Holmes JF, Sokolove PE, Brant WE, et al: Identification of children with intra-abdominal injuries after blunt trauma. Ann Emerg Med 39:500–509, 2002. 12. Thompson EC, Perkowski P, Villarreal D, et al: Morbidity and mortality of children following motor vehicle crashes. Arch Surg 138:142– 145, 2003. *13. Qazi K, Wright MS, Kippes C: Stable pediatric blunt trauma patients: is trauma team activation always necessary? J Trauma 45:562–564, 1998. 14. Orzechowski KM, Edgerton EA, Bulas DI, et al: Patterns of injury to restrained children in side impact motor vehicle crashes: the side impact syndrome. J Trauma 54:1094–1101, 2003. *15. Brown L, Moynihan JA, Denmark TK: Blunt pediatric head trauma requiring neurosurgical intervention: how subtle can it be? Am J Emerg Med 21:467–472, 2003. 16. Brown L: Heterogeneity, evidence, and salt. Can J Emerg Med 6:165– 166, 2004. 17. Spady DW, Saunders DL, Schopflocher DP, et al: Patterns of injury in children: a population-based approach. Pediatrics 113:522–529, 2004. 18. Pang G, Wilberger JE: Spinal cord injury without radiographic abnormalities in children. J Neurosurg 57:114–129, 1982. *19. Bosch PP, Vogt MT, Ward WT: Pediatric spinal cord injury without radiographic abnormality (SCIWORA): the absence of occult instability and lack of indication for bracing. Spine 27:2788–2800, 2002. 20. Bass DH, Semple PL, Cywes S: Investigation and management of blunt renal injuries in children: a review of 11 years’ experience. J Pediatr Surg 26:196–200, 1991. 21. Fleisher G: Prospective evaluation of selective criteria for imaging among children with suspected blunt renal trauma. Pediatr Emerg Care 5:8–11, 1989. 22. Lieu TA, Fleisher GR, Mahboubi S, et al: Hematuria and clinical fi ndings as indications for intravenous pyelography in pediatric blunt renal trauma. Pediatrics 82:216–222, 1988. 23. Morey AF, Bruce JE, McAninch JW: Efficacy of radiographic imaging in pediatric blunt renal trauma. J Urol 156:2014–2018, 1996. 24. Hashmi A, Klassen T: Correlation between urinalysis and intravenous pyelography in pediatric abdominal trauma. J Emerg Med 13:255– 258, 1995. 25. Cass AS: Blunt renal trauma in children. J Trauma 23:123–127, 1983. 26. Stein JP, Kaji DM, Eastham J, et al: Blunt renal trauma in the pediatric population: indications for radiographic evaluation. Urology 44:406– 410, 1994. 27. Taylor GA, Eichelberger MR, Potter BM: Hematuria: a marker of abdominal injury in children after blunt trauma. Ann Surg 208:688– 693, 1988. 28. Stalker HP, Kaufman RA, Stedje K: The significance of hematuria in children after blunt abdominal trauma. AJR Am J Roentgenol 154:569–571, 1990. 29. Brown SL, Haas C, Dinchman KH, et al: Radiologic evaluation of pediatric blunt renal trauma in patients with microscopic hematuria. World J Surg 25:1557–1560, 2001. 30. Abou-Jaoude WA, Sugarman JM, Fallat ME, et al: Indicators of genitourinary tract injury or anomaly in cases of pediatric blunt trauma. J Pediatr Surg 31:86–90, 1996. 31. Smith EM, Elder JS, Spirnak JP: Major blunt renal trauma in the pediatric population: is a nonoperative approach indicated? J Urol 149:546–548, 1993. 32. Nance ML, Lutz N, Carr MC, et al: Blunt renal injuries in children can be managed nonoperatively: outcome in a consecutive series of patients. J Trauma 57:474–478, 2004. 33. Quinlan DM, Gearhart JP: Blunt renal trauma in childhood: features indicating severe injury. Br J Urol 66:526–531, 1990. 34. Nadler EP, Gardner M, Schall LC, et al: Management of blunt pancreatic injury in children. J Trauma 47:1098–1103, 1999. 35. Desai KM, Dorward IG, Minkes RK, et al: Blunt duodenal injuries in children. J Trauma 54:640–646, 2003. 36. Demetriades D, Karaiskakis M, Velmahos GC, et al: Pelvic fractures in pediatric and adult trauma patients: are they different injuries? J Trauma 54:1146–1151, 2003. 37. Jobst MA, Canty TG Sr, Lynch FP: Management of pancreatic injury in pediatric blunt abdominal trauma. J Pediatr Surg 34:818–824, 1999.

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38. Lin PH, Barr V, Bush RL, et al: Isolated abdominal aortic rupture in a child due to all-terrain vehicle accident—a case report. Vasc Endovascular Surg 37:289–292, 2003. 39. Prasad VS, Schwartz A, Bhutani R, et al: Characteristics of injuries to the cervical spine and spinal cord in polytrauma patient population: experience from a regional trauma unit. Spinal Cord 37:560–568, 1999. 40. Rothrock SG, Green SM, Morgan R: Abdominal trauma in infants and children: prompt identification and early management of serious and life threatening injuries. Part I: Injury patterns and initial assessment. Pediatr Emerg Care 16:106–115, 2000. 41. Barlow B, Niemirska M, Gandhi R: Ten years of experience with falls from a height in children. J Pediatr Surg 18:509–511, 1983. 42. Vavilala MS, Lee LA, Boddu K, et al: Cerebral autoregulation in pediatric traumatic brain injury. Pediatr Crit Care Med 5:257–263, 2004. 43. Cooper A, Barlow B, DiScala C, String D: Mortality and truncal injury: the pediatric perspective. J Pediatr Surg 29:33–38, 1994. 44. Peclet MH, Newman KD, Eichelberger MR, et al: Thoracic trauma in children: an indicator of increased mortality. J Pediatr Surg 25:961– 965, 1990. 45. American College of Surgeons, Committee on Trauma: Initial assessment and management. In Advanced Trauma Life Support Student Manual. Chicago: American College of Surgeons, 1997, p 26. 46. Tepas JJ III, Fallat ME, Moriarty TM: Trauma. In Gausche-Hill M, Fuchs S, Yamamoto L (eds): APLS: The Pediatric Emergency Medicine Resource. Sudbury, MA: Jones and Bartlett, 2004, pp 274–283. *47. Schafermeyer RW, Ribbeck BM, Gaskins J, et al: Respiratory effects of spinal immobilization in children. Ann Emerg Med 20:115–117, 1991. *48. Chan D, Goldberg R, Tascone A, et al: The effect of spinal immobilization on healthy volunteers. Ann Emerg Med 23:48–51, 1994. 49. Tepas JJ, Mollitt DL, Talbert JL, et al: The Pediatric Trauma Score as a predictor of injury severity in the injured child. J Pediatr Surg 22:14–18, 1987. 50. Tepas JJ, Ramenofsky ML, Mollitt DL, et al: The Pediatric Trauma Score as a predictor of injury severity: an objective assessment. J Trauma 28:425–427, 1988. 51. Ramnofsky M, Luterman A, Quindlen E, et al: Maximum survival in pediatric trauma: the ideal system. J Trauma 24:818–823, 1984. 52. Eichelberger MR, Gotschall CS, Sacco WJ, et al: A comparison of the Trauma Score, the Revised Trauma Score, and the Pediatric Trauma Score. Ann Emerg Med 18:1053–1058, 1989. 53. Kauffman CR, Maier RV, Rivara FP, et al: Evaluation of the Pediatric Trauma Score. JAMA 263:69–72, 1990. 54. Nayduch DA, Moilin J, Rugledge R, et al: Comparison of the ability of adult and pediatric trauma scores to predict pediatric outcome following major trauma. J Trauma 31:452–457, 1991. 55. Saladino R, Lund D, Fleisher G: The spectrum of liver and spleen injuries in children: failure of the Pediatric Trauma Score and clinical signs to predict isolated injuries. Arm Emerg Med 20:636–640, 1991. 56. Dowd MD, McAneney C, Lacher M, et al: Maximizing the sensitivity and specificity of pediatric trauma team activation criteria. Acad Emerg Med 7:1119–1125, 2000. 57. Sola JE, Scherer LR, Haller JA, et al: Criteria for safe cost-effective pediatric trauma triage: prehospital evaluation and distribution of injured children. J Pediatr Surg 29:738–741, 1994. *58. Terregino CA, Reid JC, Marburger RK, et al: Secondary emergency department triage (supertriage) and trauma team activation: effects on resource utilization and patient care. J Trauma 43:61–64, 1997. 59. Chen LE, Snyder AK, Minkes RK, et al: Trauma stat and trauma minor: are we making the call appropriately? Pediatr Emerg Care 20:421–425, 2004. 60. Nuss KE, Dietrich AM, Smith GA: Effectiveness of a pediatric trauma team protocol. Pediatr Emerg Care 17:96–100, 2001. 61. Chadwick DL, Chin S, Salerno C, et al: Deaths from falls in children: how far is fatal? J Trauma 31:1353–1355, 1991. 62. Tarantino CA, Dowd D, Murdock TC: Short vertical falls in infants. Pediatr Emerg Care 15:5–8, 1999. 63. Newgard CD, Lewis RJ, Jolly BT: Use of out-of-hospital variables to predict severity of injury in pediatric patients involved in motor vehicle crashes. Ann Emerg Med 39:481–491, 2002. 64. Williams RA: Injuries in infants and small children resulting from witnessed and corroborated free falls. J Trauma 31:1350–1352, 1991.

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65. Simon BJ, Legere P, Emhoff T, et al: Vehicular trauma triage by mechanism: avoidance of the unproductive evaluation. J Trauma 37:645– 649, 1994. 66. Kohn MA, Hammel JM, Bretz SW, et al: Trauma team activation criteria as predictors of patient disposition from the emergency department. Acad Emerg Med 11:1–9, 2004. 67. Palanca S, Taylor DM, Bailey M, et al: Mechanisms of motor vehicle accidents that predict major injury. Emerg Med 15:423–428, 2003. 68. Shatney CH, Sensaki K: Trauma team activation for “mechanism of injury” blunt trauma victims: time for a change? J Trauma 37:275– 281, 1994. 69. Goodacre S, Than M, Goyder EC, et al: Can the distance fallen predict serious injury after a fall from a height? J Trauma 46:1055–1058, 1999. 70. Erez I, Lazar L, Gutermacher M, et al: Abdominal injuries caused by bicycle handlebars. Eur J Surg 167:331–333, 2001. 71. Clarnette TD, Beasley SW: Handlebar injuries in children: patterns and prevention. Aust N Z J Surg 67:338–339, 1997. 72. Acton CH, Thomas S, Clark R, et al: Bicycle incidents in children— abdominal trauma and handlebars. Med J Aust 160:344–346, 1994. 73. Winston FK, Shaw KN, Kreshak AA, et al: Hidden spears: handlebars as injury hazards to children. Pediatrics 102:596–601, 1998. 74. Gruskin KD, Schutzman SA: Head trauma in children younger than 2 years: are there predictors for complications? Arch Pediatr Adolesc Med 153:15–20, 1999. 75. Dietrich AM, Bowman MJ, Ginn-Pease ME, et al: Pediatric head injuries: can clinical factors reliably predict an abnormality on computed tomography? Ann Emerg Med 22:1535–1540, 1993. 76. Quayle KS, Jaffe DM, Kuppermann N, et al: Diagnostic testing for acute head injury in children: when are head computed tomography and skull radiographs indicated? Pediatrics 99:e11, 1997. 77. Simon B, Letourneau P, Vitorino E, et al: Pediatric minor head trauma: indications for computed tomographic scanning revisited. J Trauma 51:231–238, 2001. 78. Palchak MJ, Holmes JF, Vance CW, et al: Does an isolated history of loss of consciousness or amnesia predict brain injuries in children after blunt head trauma? Pediatrics 113:e507–e513, 2004. 79. Schutzman SA, Barnes P, Duhaime AC, et al: Evaluation and management of children younger than two years old with apparently minor head trauma: proposed guidelines. Pediatrics 107:983–993, 2001. 80. Osberg JS, Di Scala C: Morbidity among pediatric motor vehicle crash victims: the effectiveness of seat belts. Am J Public Health 82:422– 425, 1992. 81. Valent F, McGwin G, Hardin W, et al: Restraint use and injury patterns among children involved in motor vehicle collisions. J Trauma 52:745–751, 2002. 82. Caviness AC, Jones JL, Deguzman MA, et al: Pediatric restraint use is associated with reduced transports by emergency medical services providers after motor vehicle crashes. Prehosp Emerg Care 7:448– 452, 2003. 83. Phelan KJ, Khoury J, Grossman DC, et al: Pediatric motor vehicle related injuries in the Navajo Nation: the impact of the 1988 child occupant restraint laws. Inj Prev 8:216–220, 2002. 84. Cotton BA, Beckert BW, Smith MK, et al: The utility of clinical and laboratory data for predicting intraabdominal injury among children. J Trauma 56:1068–1075, 2004. 85. Ford EG, Karamanoukian HL, McGrath N, et al: Emergency center laboratory evaluation of pediatric trauma victims. Am Surg 56:752– 757, 1990. 86. Isaacman DJ, Scarfone RJ, Kost SI, et al: Utility of routine laboratory testing for detecting intra-abdominal injury in the pediatric trauma patient. Pediatrics 92:691–694, 1993. 87. Foltin GL, Cooper A: Abdominal trauma. In Barkin RM, Caputo GL, Jaffe DM, et al (eds): Pediatric Emergency Medicine: Concepts and Clinical Practice, 2nd ed. St. Louis: CV Mosby, 1997, pp 335–354. 88. Holmes JF, Goodwin H, Land C, et al: Coagulation studies in pediatric blunt trauma patients [Abstract]. Ann Emerg Med 32:S39, 1998. 89. Davis JW, Mackersie RC, Holbrook TL, et al: Base deficit as an indicator of significant abdominal injury. Ann Emerg Med 20:842–844, 1991. 90. Bannon MP, O’Neill CM, Martin M, et al: Central venous oxygen saturation, arterial base deficit, and lactate concentration in trauma patients. Am Surg 61:738–745, 1995.

91. Oldham KT, Guice KS, Kaufmann RA, et al: Blunt hepatic injury and elevated hepatic enzymes: a clinical correlation in children. J Pediatr Surg 19:457–461, 1984. 92. Hennes HM, Smith DS, Schneider K, et al: Elevated liver transaminase levels in children with blunt abdominal trauma: a predictor of liver injury. Pediatrics 86:87–90, 1990. 93. Sahdev P, Garramone RR, Schwartz RJ, et al: Evaluation of liver function tests in screening for intra-abdominal injuries. Ann Emerg Med 20:838–841, 1991. 94. Akhrass R, Kim K, Brandt C: Computed tomography: an unreliable indicator of pancreatic trauma. Am Surg 62:647–651, 1996. 95. Gorenstein A, O’Halpin D, Wesson DE, et al: Blunt injury to the pancreas in children: selective management based on ultrasound. J Pediatr Surg 22:1110–1118, 1987. 96. Smith SD, Nakayama DK, Gantt N, et al: Pancreatic injuries in children due to blunt trauma. J Pediatr Surg 23:610–614, 1988. 97. Buechter KJ, Arnold M, Steele B, et al: The use of serum amylase and lipase in evaluating and managing blunt abdominal trauma. Am Surg 56:204–208, 1990. 98. Shilyansky J, Sena LM, Kreller M, et al: Nonoperative management of pancreatic injuries in children. J Pediatr Surg 33:343–349, 1998. 99. Sivit CJ, Eichelberger MR, Taylor GA, et al: Blunt pancreatic trauma in children: CT diagnosis. AJR Am J Roentgenol 158:1097–1100, 1992. 100. Simon HK, Muehlberg A, Linakis JG: Serum amylase determinations in pediatric patients presenting to the ED with acute abdominal pain or trauma. Am J Emerg Med 12:292–295, 1994. 101. Taylor GA, Eichelberger MR, O’Donnell R, et al: Indications for computed tomography in children with blunt abdominal trauma. Ann Surg 213:212–218, 1991. 102. Boone TB, Gilling PJ, Husmann DA: Ureteropelvic junction disruption following blunt abdominal trauma. J Urol 150:33–36, 1993. 103. Cass AS: Blunt renal trauma in children. J Trauma 23:123–127, 1983. 104. Morey AF, Bruce JE, McAninch JW: Efficacy of radiologic imaging in pediatric blunt renal trauma. J Urol 156:2014–2018, 1996. 105. Emmanuel B, Weiss H, Gollm P: Renal trauma in children. J Trauma 17:275–278, 1977. 106. Holmes JF, Sokolove PE, Land C, et al: Identification of intraabdominal injuries in children hospitalized following blunt torso trauma. Acad Emerg Med 6:799–806, 1999. 107. Perez-Brayfield MR, Gatti JM, Smith EA, et al: Blunt traumatic hematuria in children: is a simplified algorithm justified? J Urol 167:2543– 2547, 2002. 108. Stiell IG, Wells GA, Vandemheen KL, et al: The Canadian c-spine rule for radiography in alert and stable trauma patients. JAMA 286:1841– 1848, 2001. 109. Hoffman JR, Mower WR, Wolfson AB, et al: Validity of a set of clinical criteria to rule out injury to the cervical spine in patients with blunt trauma: National Emergency X-Radiography Utilization Study Group. N Engl J Med 343:94–99, 2000. 110. Slack SE, Clancy MJ: Clearing the cervical spine of paediatric trauma patients. Emerg Med J 21:189–193, 2004. 111. Viccellio P, Simon H, Pressman BD, et al: A prospective multicenter study of cervical spine injury in children. Pediatrics 108:e20, 2001. 112. Ralston ME, Chung K, Barnes PD, et al: Role of flexion-extension radiographs in blunt pediatric cervical spine injury. Acad Emerg Med 8:237–245, 2001. 113. Ralston ME, Ecklund K, Emans JB, et al: Role of oblique radiographs in blunt pediatric cervical injury. Pediatr Emerg Care 19:68–72, 2003. 114. Buhs C, Cullen M, Klein M, et al: The pediatric trauma c-spine: is the “odontoid” view necessary? J Pediatr Surg 35:994–997, 2000. *115. Lee SL, Sena M, Greenholz SK, et al: A multidisciplinary approach to the development of a cervical spine clearance protocol: process, rationale, and initial results. J Pediatr Surg 38:358–362, 2003. 116. Launay F, Leet AL, Sponseller PD: Pediatric spinal cord injury without radiographic abnormality: a meta-analysis. Clin Orthop Relat Res 433:166–179, 2005. 117. Gittleman MA, Gonzalez-del-Rey J, Brody A, et al: Clinical predictors for the selective use of chest radiographs in pediatric blunt trauma evaluations. J Trauma 55:670–676, 2003. 118. Renton J, Kincaid S, Ehrlich PF: Should helical CT scanning of the thoracic cavity replace the conventional chest x-ray as a primary assessment tool in pediatric trauma? An efficacy and cost analysis. J Pediatr Surg 38:793–797, 2003.

Chapter 12 — Approach to Multisystem Trauma *119. Guillamondegui OD, Mahboubi S, Stafford PW, et al: The utility of the pelvic radiograph in the assessment of pediatric pelvic fractures. J Trauma 55:236–239, 2003. *120. Vo NJ, Gash J, Browning J, Hutson RK: Pelvic imaging in the stable trauma patient: is the AP pelvic radiograph necessary when abdominopelvic CT shows no acute injury? Emerg Radiol 10:246–249, 2004. 121. Taylor GA, Eichelberger MR, Potter BM: Hematuria: A marker of abdominal injury in children after blunt trauma. Ann Surg 208:688– 693, 1988. 122. Kurkchubasche AG, Fendya DG, Tracy TF, et al: Blunt intestinal injury in children: diagnostic and therapeutic considerations. Arch Surg 132:652–658, 1997. 123. Frick EJ, Pasquale MD, Cipolle MD: Small-bowel and mesentery injuries in blunt trauma. J Trauma 46:920–926, 1999. 124. Graham JS, Wong AL: A review of computed tomography in the diagnosis of intestinal and mesenteric injury in pediatric blunt abdominal trauma. J Pediatr Surg 31:754–756, 1996. 125. Rathaus V, Zissin R, Werner M, et al: Minimal pelvic fluid in blunt abdominal trauma in children: the significance of this sonographic fi nding. J Pediatr Surg 36:1387–1389, 2001. 126. Coley BD, Mutabagani KH, Martin LC, et al: Focused abdominal sonography for trauma (FAST) in children with blunt abdominal trauma. J Trauma 48:902–906, 2000. 127. Benya EC, Lim-Dunham JE, Landrum O, et al: Abdominal sonography in examination of children with blunt abdominal trauma. AJR Am J Roentgenol 174:1613–1616, 2000. 128. Robinson WP 3rd, Ahn J, Stiffler A, et al: Blood transfusion is an independent predictor of increased mortality in nonoperatively managed blunt hepatic and splenic injuries. J Trauma 58:437–444, 2005. 129. Patrick DA, Bensard DD, Janik JS, et al: Is hypotension a reliable indicator of blood loss from traumatic injury in children? Am J Surg 184:555–560, 2002.

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130. Rutledge R, Hunt JP, Lentz CW, et al: A statewide, population-based time-series analysis of the increasing frequency of nonoperative management of abdominal solid organ injury. Ann Surg 222:311–322, 1995. 131. Ceylan S, Kuzeyli K, Ilbay K, et al: Nonoperative management of acute extradural hematomas in children. J Neurosurg Sci 36:85–88, 1992. 132. Tuncer R, Kazan T, Uçar C, et al: Conservative management of epidural haematomas: prospective study of 15 cases. Acta Neurochir 121:48–52, 1993. 133. Paddock HN, Tepas JJ, Ramenofsky ML, et al: Management of blunt pediatric hepatic and splenic injury: similar process, different outcome. Am Surg 70:1068–1072, 2004. 134. Partrick DA, Moore EE, Bensard DD, et al: Operative management of injured children at an adult level I trauma center. J Trauma 48:894– 901, 2000. 135. Rossi D, de Ville de Goyet J, de Cléty SC, et al: Management of intraabdominal organ injury following blunt abdominal trauma in children. Intensive Care Med 19:415–419, 1993. 136. Fallat ME, Casale AJ: Practice patterns of pediatric surgeons caring for stable patients with traumatic solid organ injury. J Trauma 43:820–824, 1997. 137. Ozturk H, Dokucu AI, Onen A, et al: Non-operative management of isolated solid organ injuries due to blunt abdominal trauma in children: a fi fteen-year experience. Eur J Pediatr Surg 14:29–34, 2004. 138. Leone RJ Jr, Hammond JS: Nonoperative management of pediatric blunt hepatic trauma. Am Surg 67:138–142, 2001. 139. Lahat E, Livne M, Barr J, et al: The management of epidural haematomas—surgical versus conservative treatment. Eur J Pediatr 153:198– 201, 1994. *140. Green SM, Rothrock SG: Is pediatric trauma really a surgical disease? Ann Emerg Med 39:537–540, 2002.

Chapter 13 Sepsis Jesus M. Arroyo, MD, James J. McCarthy, MD, and Brent R. King, MD

Key Points The sepsis syndrome is the combination of the systemic inflammatory response syndrome (SIRS) and presence of an infection. Key early physical findings in pediatric sepsis include age-specific hypotension, oliguria, prolonged capillary refi ll time (>5 seconds), core-to-peripheral temperature gap greater than 3° C, age-specific tachypnea, hypoxia, lethargy, petechiae, fever greater than 38.5° C, or hypothermia (temperature 180 >180 >180 >140 >130 >110

34 >22 >18 >14

200 beats/min • Two of the following:
Metabolic acidosis: base deficit > 5.0 mEq/L
Elevated lactate > 2 × upper limit of normal
Oliguria
Capillary refill >5 sec
Core-to-peripheral temperature gap > 3° C PaO2/FIO2 < 300 PaCO2 > 65 mm Hg PaO2 < 40 mm Hg Requirement for mechanical ventilatory support Intercranial hypertension requiring intervention Glasgow Coma Scale score 3 points INR > 2 Platelets < 80,000/mm3 Hemoglobin < 5 g/dl White blood cell count < 3000 Creatine > 20 mg/dl Total bilirubin ≥ 5 mg/dl ALS > 2 × normal

Respiratory

Neurologic Hematologic

Renal Hepatic

*Adapted from Goldstein B, Grior B, Randolph A, et al: International Pediatric Sepsis Consensus Conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 6:2–8, 2005; and from Tantaléan JA, Léon RJ, Santos AA, Sánchez E: Multiple organ dysfunction syndrome in children. Pediatr Crit Care Med 4:181–185, 2003. Abbreviations: ALS, alanine aminotransferase; FIO2, fraction of inspired oxygen; INR, international normalized ratio; PaCO2, arterial partial pressure of carbon dioxide; PaO2, arterial partial pressure of oxygen.

being seriously considered should undergo measurement of serum acid-base status and serum lactate determination. Some authors have suggested that mixed venous oxygen saturation be measured initially and later to gauge response to therapy. Since some children have risk factors for reduced cortisol levels and an impaired response to physiologic stress, many investigators have recommended that cortisol levels be drawn, and supplemental steroids be administered empirically to such children. Others have suggested that an adrenocorticotrophic hormone (ACTH) stimulation test be conducted before administration of steroids.20 C-reactive protein plays a role in the sepsis cascade and is easily measured, but its utility as a marker of severity of illness or a guide to further therapy is unclear. Other more esoteric laboratory studies of mediators involved in the evolution of SIRS, sepsis, septic shock, and/or MODS (e.g., procalcitonin, IL-1, IL-6, nitric oxide metabolites) have been described in the literature, but currently these are utilized most often in research settings. Imaging studies should be ordered as indicated by the clinical scenario, for example, obtaining a chest radiograph when pneumonia is suspected. Computed tomography may help to identify clinically occult abscesses and to delineate the extent to which a particular organ is involved. As described later, bedside ultrasonography can be used to

evaluate cardiac function as myocardial depression is a well-recognized complication of sepsis.21 More formal echocardiography might also be used to identify possible endocarditis. Differential Diagnosis Because the symptoms of sepsis are nonspecific, the differential diagnosis is necessarily broad. Many conditions that cause severe illness and shock can mimic sepsis, and some of these are, in fact, closely related conditions. Toxic shock syndrome must be considered in the infant or child presenting with a clinical picture consistent with septic shock. In certain infants, necrotizing enterocolitis might be confused with sepsis; meningitis or encephalitis might also resemble sepsis. Because sepsis may ultimately cause shock, septic shock can be confused with other types of shock. While hemorrhagic and neurogenic shock are in the differential diagnosis, cardiogenic shock from congenital heart disease or viral myocarditis is most likely to be confused with sepsis. The child with cardiogenic shock is more likely to present with congestive heart failure. It has recently been demonstrated that emergency physicians using bedside ultrasonography can identify impaired cardiac wall motion and decreased ejection fraction with reasonable accuracy.22 As this technology becomes more widely used, it may be possible to identify those patients whose symptoms are at least partially caused by cardiac dysfunction. Hemorrhagic and neurogenic shock generally follow significant trauma. Without such a history, with the exception of the adolescent female with a ruptured ectopic pregnancy, the clinician must consider inflicted injury. Children who have impaired production of cortisol, and are less able to tolerate physiologic stress, may present with shock or a sepsis-like picture. Included are children with congenital adrenal hyperplasia and those with severe pituitary or adrenal dysfunction. It is important to note that a similar picture can be created by the chronic administration of steroid hormones. Any severe illness can mimic sepsis, but most such illnesses are rare in the pediatric age group and most present with clues that direct the clinician toward the specific etiology. Consider the possibility of rare conditions such as pulmonary embolus, acute renal failure, myocardial infarction, or aortic dissection when the clinical picture indicates such consideration or is confusing.

Management The foundations of sepsis management are establishment and maintenance of a patent airway, effective ventilation and oxygenation, circulatory support, treatment of infection, and exclusion of alternative diagnoses. Adherence to rigorous treatment protocols, and awareness of the concept of early goal-directed therapy (EGDT) have resulted in a 92% decrease in sepsis-related mortality over the last 4 decades.22a It is critical to recognize that most of the recommendations noted in this section are derived from studies of adult patients. Few, if any, similar studies involving infants and children are available; therefore, these recommendations must be approached with caution. However, many have proven themselves in the clinical arena, and they represent the best therapy available for a potentially devastating disease process.

Chapter 13 — Sepsis

A 9-year retrospective review of infants transported a tertiary care center with sepsis and septic shock demonstrated that better survival was associated with aggressive resuscitation by the referring physicians.23 Early aggressive treatment in the community was clearly beneficial, but many septic patients were frequently underresuscitated in community emergency departments.23 When the diagnosis of sepsis is being considered, treatment must be instituted immediately. Circulatory and respiratory support are vitally important. Antimicrobial therapy plays an important role but is in and of itself insufficient. The progression of sepsis in children is different from that seen in adults. Whereas an adult patient might experience a gradual deterioration, children often appear stable for an extended period only to experience a precipitous decline in vital function. Antimicrobial therapy is a key component of treatment and should be started as soon as possible. Treatment should include one or more antimicrobial agents with activity against the most likely pathogens, taking into account communityand facility-specific patterns of bacterial resistance, and mitigating host factors. Unless rapid testing has identified a specific agent, prudence dictates the selection of broadspectrum agents until specific pathogens have been identified (Table 13–4). Patients who are immune deficient or who are at risk for particularly virulent bacteria (e.g., Pseudomonas) should be treated with several antibiotics appropriately, but broadly directed at the suspected pathogens. Additionally, in some cases, a potential source of infection can be eliminated. Abscesses can be drained, necrotic tissue can be incised, and indwelling catheters can be removed. Circulatory support is critical and should be initiated before hypotension and other signs of shock have developed. Effectiveness of therapy should be monitored by evaluation of several parameters, including heart rate, urine output, mental status, respiratory rate, serum acid-base status, and serum lactate, in addition to blood pressure and pulse pressure. Some authors have advocated continuous measurement Table 13–4

Age-Specific Recommendations for Initial Empiric Antibiotic Selection in Sepsis

Age

Antibiotics

Neonates < 1 wk old

Ampicillin 25 mg/kg q8h and Cefotaxime 50 mg/kg q8h Ampicillin 25 mg/kg q8h and Cefotaxime 50 mg/kg q8h or ceftriaxone 75 mg/kg q24h Cefotaxime 50 mg/kg q8h or Ceftriaxone 100 mg/kg q24h Cefepime 50 mg/kg q8h or Imipenem 25 mg/kg q6h or Meropenem 60 mg/kg q8h Suspected MRSA—add vancomycin Suspected VRE—add linezolid Abdominal processes—add anaerobic coverage Urinary pathogen—add aminoglycoside Suspected pulmonary infection—add macrolide

Neonates 1–4 wk Children Adolescents/young adults Special considerations

*Selections should be tailored to suspected sources, local resistance patterns, and patient allergies. Abbreviations: MRSA, methicillin-resistant Staphylococcus aureus; VRE, vancomycin-resistant enterococcus.

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of central venous pressure and arterial pressure rather than blood pressure. Aggressive early volume resuscitation is the cornerstone of initial therapy. While physicians often do an excellent job in the management of sepsis, they frequently do not administer enough volume when resuscitating septic patients and fail to follow the current advanced life support guidelines.23 They should first administer 20 ml/kg of crystalloid and give subsequent boluses based upon patient response. Some authors advocate the administration of colloid after several boluses of crystalloid because it can provide similar clinical effects with a smaller volume of administration. However, no studies have demonstrated a definite benefit of one fluid type over another. The risk of overhydration is overstated. Aggressive fluid resuscitation in excess of 40 ml/kg in the first hour of treatment is associated with increased survival with no increased risk of acute respiratory distress syndrome (ARDS) or cardiogenic pulmonary edema.24 Evaluation of EGDT for severe sepsis and septic shock in a major adult sepsis clinical trial16 suggested that initial therapy should be dictated by mixed venous oxygen saturation, hematocrit, and central venous pressure. The goal of volume expansion should be a central venous pressure of 8 to 12 mm Hg except in the case of mechanically ventilated patients, who require higher central venous pressure of 12 to 15 mm Hg due to elevated intrathoracic pressures. Volume expansion might help to restore systemic circulation and reverse the sepsis cascade, but alone may not be sufficient. Mixed venous oxygen saturation, measured by a Swan-Ganz catheter or other special measurement device, should be maintained above 70%. During the first 6 hours of treatment, if fluid therapy has achieved a central venous pressure of 8 to 12 mm Hg (12 to 15 mm Hg in mechanically ventilated patients) and the patient’s mixed venous oxygen saturation remains below 70%, further therapy is guided by the hematocrit. For a hematocrit below 30%, blood is transfused. If the hematocrit is normal or if transfusion fails to achieve a mixed venous oxygen saturation of 70%, dobutamine is administered until this goal has been achieved or to a maximum dose of 20 mcg/kg/min (see Chapter 8, Circulatory Emergencies: Shock). In the absence of mixed venous oxygen saturation, the treating physician should aim for a central venous pressure of 8 to 12 mm Hg (12 to 15 mm Hg if mechanically ventilated) and a hematocrit no less than 30%. Once these goals have been met, signs of poor perfusion should be treated with dobutamine as described. Dobutamine is recommended because it is assumed that, given adequate left ventricular fi lling pressures and red blood cell volume, the most likely source of impaired perfusion is depressed cardiac output. As described earlier, bedside ultrasound may allow the clinician to determine the effectiveness of cardiac activity and help guide therapy. EGDT has been demonstrated to improve the mortality from sepsis in adults. These guidelines have not been tested in children, but several investigators have found that, in conjunction with goal-directed therapy, implementation of the American College of Critical Care Medicine Pediatric Advanced Life Support guidelines results in improved clinical outcomes.25 Published guidelines for the treatment of pediatric and neonatal sepsis have incorporated these elements (Fig. 13–1).

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SECTION I — Immediate Approach to the Critical Patient Recognize SIRS/Sepsis IV access Airway management/supplemental oxygen Neonatal

Pediatric

Fluid bolus 10 cc/kg up to 60 cc/kg Correct hypoglycemia, hypocalcemia Start prostaglandin infusion until echo shows no ductal dependent lesion

Fluid bolus 20 cc/kg up to 60 cc/kg Correct hypoglycemia, hypocalcemia

Observe Fluid responsive?

Yes

Yes

Fluid responsive? No

Observe

No

Establish central access Titrate dopamine

Establish central access Titrate dopamine and dobutamine Fluid/dopamine refractory Titrate epinephrine for cold shock Titrate norepinephrine for warm shock

Fluid/dopamine refractory Titrate epinephrine Alkalinization for pulmonary hypertension and acidosis

Catecholamine resistant shock Consider hydrocortisone if at risk for adrenal insufficiency

Catecholamine resistant shock Cold shock Normal blood pressure SVC O2 < 70% Cold shock Normal blood pressure Poor LV function Central venous O2 < 70%

Titrate vasodilator or Type III PDE inhibitor with volume loading

Cold or warm shock Poor RV function Pulmonary hypertension Central venous O2 < 70%

Nitric oxide

Cold shock Low blood pressure Central venous O2 < 70%

Warm shock Low blood pressure

Titrate vasodilator or Type III PDE inhibitor with volume loading

Warm shock Low blood pressure

Titrate volume and epinephrine (consider low dose vasopressin)

Titrate volume and epinephrine Refractory shock consider

Refractory shock

ECMO

FIGURE 13–1. Algorithm for treatment of pediatric and neonatal sepsis. (Adapted from Carcillo JA, Fields AI; American College of Critical Care Medicine Task Force Committee Members: Clinical practice parameters for hemodynamic support of pediatric and neonatal patients in septic shock. Crit Care Med 30:1365–1378, 2002.)

Other vasopressors can be added to achieve specific desired effects. If cardiac output cannot be determined or is adequate after volume resuscitation, the physician should consider dopamine or norepinephrine. One of these drugs can be added to dobutamine for persistent hypotension despite correction of cardiac output. These agents are preferred over epinephrine because they cause less profound tachycardia and less vasoconstriction of the splanchnic bed. However, there is evidence of an age-dependent resistance to dopamine,26 and failure to respond should prompt the clinician to employ another agent. Phenylephrine causes vasoconstric-

tion without tachycardia and could be chosen when vasodilatory shock is strongly suspected. Ideally, the administration of vasopressors should be guided by continuous arterial pressure monitoring. Such monitoring is not universally available in the emergency department. In its absence, the clinician should rely upon measurement of peripheral blood pressure, urine output, mental status, and systemic acid-base status until the patient can be transferred to an intensive care unit. One should consider adding a short-acting, titratable vasodilator such as nitroprusside or nitroglycerine for patients

Chapter 13 — Sepsis

with strong evidence of elevated peripheral vascular resistance and depressed cardiac output unresponsive to the previously discussed therapies. If these agents fail to improve cardiac output and peripheral perfusion, then milrinone or amrinone should be considered. Abnormally low cardiac output in pediatric patients is associated with increased mortality, so every effort should be made to ensure that it is normal. Children with cortisol deficiency may be resistant to vasopressor therapy. At least one trial has demonstrated improved outcome when such children are identified and treated promptly.25 Adrenal insufficiency can be the result of sepsis itself (e.g., Waterhouse-Friederichsen syndrome), but is more likely to be the result of a congenital or acquired endocrinopathy or chronic steroid use. Experts recommend administration of stress doses of corticosteroids (e.g., hydrocortisone 1 to 2 mg/m2/hr) for children with potential adrenal insufficiency and higher doses (25 to 50 mg/m2 loading dose followed by 1 to 2 mg/m2/hr) for shock states associated with Waterhouse-Friderichsen syndrome. However, two adult studies have demonstrated worse outcomes in patients receiving high-dose corticosteroids (e.g., more than 300 mg/ day), so excessively high doses are not recommended.27-29 When uncertainty exists regarding the state of the patient’s pituitary-adrenal axis, a cortisol stimulation test can be obtained. Patients who have an adequate response to ACTH do not need exogenous steroids. This test is impractical in many emergency departments; dexamethasone (0.6 to 1 mg/ kg) will not interfere with the stimulation test and can be safely given if this test is deemed necessary at a later point. Corticosteroids have not been demonstrated to be beneficial to patients who have normal cortisol production and should not be administered in this situation. Priority should be given to the patient’s electrolyte balance and glucose levels. Maintenance of serum glucose at levels between 80 and 150 mg/dl has been associated with improved survival.29a Hypoglycemia should be avoided and hyperglycemia should be treated with regular insulin, administered intravenously. Glucose levels should be monitored frequently. Calcium can be depleted during septic shock but should only be replaced if indicated by a low serum ionized calcium level. Several immune-modulating agents that theoretically decrease the exogenous immune response and improve tissue ischemia have been investigated as potential therapies in pediatric sepsis. Thus far, only recombinant human activated protein C has shown minimal benefit, and only in adult patients.30 Activated protein C decreases serum levels of activated factors V and VIII, thus decreasing thrombin formation and increasing fibrinolysis. Both tissue pathway factor inhibitor and interferon gamma have produced some promising early results in clinical trials. Studies of plasma fi ltration have demonstrated that this therapy can reduce amounts of circulating acute-phase reactants, but has thus far not been shown to improve outcomes.30a Many children with sepsis will require mechanical ventilation. Recent literature suggests that ventilator-associated lung injury contributes to ARDS both by direct barotruma and by increased pulmonary cytokine production. Experts now recommend ventilation with low tidal volumes (e.g., 6 ml/kg), low end-expiratory pressures, and, if necessary, permissive hypercapnia.31-33 Because many of these patients

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will be intubated in the emergency department, emergency physicians must understand these issues and adhere to these principles during both manual and mechanical ventilation. Neonates with advanced sepsis present some unique challenges. The acidosis associated with sepsis can lead to persistent patency of the ductus arteriosus and, in some cases, to persistent pulmonary hypertension. This disease state can create a vicious cycle of hypoxemia and worsening acidosis and can ultimately cause right ventricular failure. Inhaled nitric oxide is currently used in neonatal units and by many neonatal transport teams to avert this complication. In most emergency departments, treatment would primarily include supplemental oxygen and correction of acidosis.

Summary Recognition and management of sepsis in the pediatric population requires early diagnosis and aggressive, goal-directed therapy. Emergency physicians must be very familiar with the specific criteria for SIRS, stay attuned to possible subtle presentations of infection in infancy and childhood, and be highly suspicious for the diagnosis of sepsis in infants and immunocompromised children. Effective initial stabilization can be performed in a variety of settings. However, with rare exceptions, all septic pediatric patients require prompt transfer to tertiary care centers, preferably those with pediatric-specific critical care units. Isotonic intravenous fluids, blood product transfusions, ventilatory support, early appropriate antibiotics, and early surgical intervention for abscesses and acute abdominal processes are the mainstays of therapy. Initial therapeutic efforts should be focused on aggressive restoration of volume and, if necessary, ion-tropic support. Treatment decisions should be based on a balance between potential benefits and potential harms. Because septic children and adults have differing mortality rates, treatment-related morbidity may not always favor intervention. Research in sepsis is particularly challenging, and is more so in children. The new consensus defi nition of sepsis helps to provide a framework to generate multicenter trials. As our knowledge and understanding of the pathophysiology of sepsis continue to grow, our ability to intervene will move beyond antibiotics and supportive therapy. Areas of promise and current trials include serum markers for sepsis, “designer antibiotics,” and coagulation- and inflammatory–pathway specific therapies. REFERENCES 1. Levy MM, Fink MP, Marshal JC, et al: 2001 SCCM/ESICM/ACCP/ ATS/SIS International Sepsis Defi nitions Conference. Intensive Care Med 29:530–538, 2003. 2. Goldstein B, Grior B, Randolph A, et al: International Pediatric Sepsis Consensus Conference: defi nitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 6:2–8, 2005. 3. Bone RC, Sprung CL, Sibbald WJ: Defi nitions for sepsis and organ failure. Crit Care Med 20:724–726, 1992. 4. Burns JP: Septic shock in the pediatric patient: pathogenesis and novel treatments. Pediatr Emerg Care 19:112–115, 2003. 5. Thomas L: Germs. N Engl J Med 287:553–555, 1972. 6. Meakins JL, Pietsch JB, Bubenick O, et al: Delayed hypersensivity: indicator of acquired failure of host defenses in sepsis and trauma. Ann Surg 186:241–250, 1977.

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7. Oberholzer A, Olberholtzer C, Moldawer LL: Sepsis syndromes: understanding the role of innate immunity. Shock 16:83–96, 2001. 8. Watson RS, Carcillo JA, Linde-Zwirble WT, et al: The epidemiology of severe sepsis in children in the United States. Am J Respir Crit Care Med 167:695–701, 2003. 9. Angus DC, Linde Zwirble WT, Liddicker J, et al: Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 29:1303–1310, 2001. 10. Parrillo JE: Pathogenetic mechanisms of septic shock. N Engl J Med 328:1471–1477, 1993. 11. Kurahashi K, Kajikawa O, Sawa T, et al: Pathogenesis of septic shock in Pseudomonas aeruginosa pneumonia. J Clin Invest 104:743–750, 1999. 12. Abbas AK, Murphy KM, Sher A: Functional diversity of helper T lymphocytes. Nature 383:787–793, 1996. 13. Hotchkiss RS, Karl IE: The pathophysiology and treatment of sepsis. N Engl J Med 384:138–150, 2003. 14. Levi M, Ten Cate H: Disseminated intravascular coagulation. N Engl J Med 341:586–592, 1999. 15. Despond O, Proulx F, Carcillo JA, Lacroix J: Pediatric sepsis and multiple organ dysfunction syndrome. Curr Opin Pediatr 13:247–253, 2001. 16. Rivers E, Nguyen B, Havstad S, et al: Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 345:1368– 1377, 2001. 17. Martinot A, Leclerc F, Cremer R, et al: Sepsis in neonates and children: defi nitions, epidemiology, and outcome. Pediatr Emerg Care 13:277– 281, 1997. 18. Kreger BE, Craven DE, Carling P, et al: Gram-negative bacteremia. III. Reassessment of etiology, epidemiology and ecology in 612 patients. Am J Med 60:332–343, 1980. 19. Weinstein MP, Murphy JR, Reller LB, et al: The clinical significance of positive blood cultures: a comprehensive analysis of 500 episodes of bacteremia and fungemia in adults. II. Clinical observations, with special reference to factors influencing prognosis. Rev Infect Dis 5:54– 70, 1983. 20. Dellinger RP, Carlet JM, Masur H, et al; Surviving Sepsis Campaign Management Guidelines Committee: Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 32:858–873, 2004 21. Monsalve F, Rucabado L, Salvador A, et al: Myocardial depression in septic shock caused by meningococcal infection. Crit Care Med 12:1021–1023, 1984. 22. Moore CL, Rose GA, Tayal VS, et al: Determination of left ventricular function by emergency physician echocardiography of hypotensive patients. Acad Emerg Med 9:186–193, 2002.

22a. Arnal AE, Stein F: Pediatric septic shock: Why has mortality decreased?—The utility of goal directed therapy. Sem Pediatr Infect Dis 14:165–172, 2003. 23. Han YY, Carcillo JA, Dragotta MA, et al: Early reversal of pediatricneonatal septic shock by community physicians is associated with improved outcome. Pediatrics 112:793–799, 2003. 24. Carcillo JA, Davis AL, Zaritsky A: Role of early fluid resuscitation in pediatric septic shock. JAMA 266:1242–1245, 1991. 25. Carcillo JA, Fields AI; American College of Critical Care Medicine Task Force Committee Members: Clinical practice parameters for hemodynamic support of pediatric and neonatal patients in septic shock. Crit Care Med 30:1365–1378, 2002. 26. Bhatt-Mehta V, Nahata MC, McClead RE, et al: Dopamine pharmacokinetics in critically ill newborn infants. Eur J Clin Pharmacol 40:593– 597, 1991. 27. Cronin L, Cook DJ, Carlet J, et al: Corticosteroid treatment for sepsis: a critical appraisal and meta-analysis of the literature. Crit Care Med 23:1430–1439, 1995. 28. Veterans Administration Systemic Sepsis Cooperative Study Group: Effect on high-dose glucocorticoid therapy on mortality in patients with clinical signs of sepsis. N Engl J Med 317:659–665, 1987. 29. Bone RC, Fisher CJ, Clemmer TP: A controlled clinical trial of highdose methyprednisolone in the treatment of severe sepsis and septic shock. N Engl J Med 317:653–658, 1987. 29a. Dellinger RP, Carlet JM, Masur H, et al: Surviving sepsis campaign management guidelines committee: Surviving sepsis campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 32:858–873, 2004. 30. Bernard GR, Vincent JL, Laterre PF, et al: Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 344:699–709, 2001. 30a. Despond O, Proulx F, Carcillo JA, Lacroix J: Pediatric sepsis and multiple organ dysfunction syndrome. Curr Opin Pediatr 13:247–255, 2001. 31. Bidani A, Tzouanakis AE, Cardenas VJ, et al: Permissive hypercapnia in acute respiratory failure. JAMA 272:957–962, 1994. 32. Ventilation with lower tidal volumes as compared with the traditional tidal volume for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med 342:1301–1308, 2000. 33. Hickling KG, Walsh J, Henderson S, et al: Low mortality rate in adult respiratory distress syndrome using low-volume, pressure-limited ventilation with permissive hypercapnia: a prospective study. Crit Care Med 22:1568–1578, 1994.

Chapter 14 Anaphylaxis Suzanne M. Beno, MD

Key Points Survival is dependent upon immediate recognition and intervention. Rapid administration of intramuscular epinephrine is first-line therapy for anaphylaxis. Children with asthma are at increased risk for delayed and more severe reactions.

Introduction and Background Anaphylaxis has long been recognized as a severe, lifethreatening reaction that involves multiple target organs, including skin, respiratory, gastrointestinal, cardiovascular, and neurologic systems.1 Consensus regarding its exact definition currently does not exist and there is considerable disagreement about its prevalence, diagnosis, and management. A recent practice parameter addresses these issues and attempts to provide an evidence-based approach to the definition of this condition.2 Anaphylaxis is considered to be highly likely when any one of the following three criteria is present: 1. Acute onset of an illness (minutes to hours) involving skin/mucosa and either respiratory compromise or hypotension (associated symptoms) 2. Two or more of the following that occur rapidly after exposure (minutes to hours) to a likely allergen for that patient: skin/mucosal involvement, respiratory compromise, hypotension and associated symptoms, and persistent gastrointestinal symptoms 3. Hypotension after exposure to known allergen for that patient (minutes to hours) The term anaphylaxis encompasses both immunoglobulin E (IgE)–mediated reactions and non–IgE-mediated mechanisms (anaphylactoid reactions); the difference impacts allergen counseling but is of little consequence in the immediate management of the patient.2

Recognition and Approach Epidemiology data in the general population are sparse and affected by variable definitions, coding, and misclassification

errors. Population data from the 1980s estimated an annual occurrence rate of 30 per 100,000 person-years, while more recent literature suggests occurrence rates as high as 590 per 100,000 person-years.3 The actual incidence, especially in children, remains uncertain as very few population-based studies exist. A prevalence study using rates of injectable epinephrine dispensing data in Manitoba supports various retrospective reviews suggesting a 1% prevalence in the community. This study specifically noted a peak in anaphylaxis from all triggers in early childhood with a gradual decline toward adolescence.4 Anaphylaxis is generally considered to be at the severe end of the generalized hypersensitivity spectrum, with respiratory and/or cardiovascular involvement denoting severity. Different grading systems have been explored, and are based upon the current proposed definition for anaphylaxis.2 A systematic compilation of the frequency of signs and symptoms in anaphylaxis is shown in Table 14–1.

Evaluation Anaphylaxis is an immediate uniphasic reaction invoking various end-organ responses in the skin, respiratory tract, and cardiovascular and gastrointestinal systems. Other patterns of anaphylaxis exist, and include delayed onset (>30 minutes postexposure), protracted or persistent reactions (can last up to 32 hours), and biphasic reactions in which recurrence of symptoms follows a symptom-free period (8 to 12 hours). The resultant reaction in a biphasic response is usually more severe and less amenable to treatment.6,7 The majority of anaphylaxis will present with some degree of cutaneous involvement, such as flushing, pruritus, urticaria, and angioedema, but these symptoms may be either overlooked or missed after epinephrine administration.8 Other classic features include signs of upper and lower airway obstruction, gastrointestinal symptoms, syncope, hypotension, and dizziness. In its severe form, anaphylaxis can result in cardiovascular collapse and death. The most common etiologies of anaphylactic reactions include reactions to food, medications, Hymenoptera stings, and latex.2 Certain groups of children are more prone to anaphylaxis. Children with neural tube defects and/or genitourinary abnormalities requiring self-catheterization are at increased risk for latex allergy. Children with asthma, particularly if poorly controlled, have an increased incidence of fatal anaphylaxis.6,9,10 141

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SECTION I — Immediate Approach to the Critical Patient

Table 14–1

Signs and Symptoms: Frequency of Occurrence in Anaphylaxis (%)

Cutaneous Urticaria/angioedema Flushing Pruritis w/o rash Respiratory Upper airway Dyspnea, wheeze Rhinitis Gastrointestinal Nausea, vomiting, diarrhea Dizziness, Syncope, Decreased Blood Pressure Neurologic Seizure/HA Seizure alone Miscellaneous Substernal chest pain

Lieberman et al. 5 (mostly adults)

Lee and Greenes35 (children): N = 106

Dibs and Baker36 (children): N = 55

>90 85–90 45–55 1 min *Children with clinical indicators of possible brain injury. Children with concerning or unknown mechanism. Abbreviation: LOC, loss of consciousness. Table adapted from Schutzman et al.30 †

Unwitnessed trauma Vague or absent history of trauma

Low Risk: Observation Low-energy mechanism No signs or symptoms ≥2 hr after injury >3–6 mo of age

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SECTION II — Approach to the Trauma Patient

Presence of a scalp hematoma is a predictor of a skull fracture and, if relatively large, predictive of intracranial hemorrhage.30 Cervical spine injuries in children are uncommon, occurring in about 1% of all pediatric trauma victims.27,31 The incidence is undoubtedly lower in infants. Two proposed explanations for the low incidence are that (1) infants may not be exposed to the dangerous mechanisms that cause these injuries, or (2) infants with injuries to the upper cervical spine have lethal injuries that are never specifically identified, at least not in the ED.27 There are few studies addressing infants with cervical spine injuries. Infants involved in a high-risk mechanism of injury should undergo a careful physical examination. Diagnostic imaging of the cervical spine should be obtained in the presence of cervical spine tenderness, crepitus or bony step-off, or altered mental status, or in patients with focal motor deficit or paralysis of an extremity. The assessment of tenderness is often impossible in infants. The choice of imaging study is controversial. Initially, a radiograph with anterior-posterior and lateral views is generally recommended. These radiographs will generally allow adequate visualization of the entire cervical spine.18 The utility of the odontoid view radiograph in the presence of a normal lateral view is questionable and can be technically challenging in infants. A study of pediatric radiologists’ practice in using the open-mouth odontoid view in young children found significant variability in its perceived utility.32 If the plain radiographs are negative, an infant suspected of having a cervical spine injury should undergo MRI of the spine. MRI is sensitive for detecting ligament disruptions, and can define the extent of the any clinically significant spinal cord injury. MRI is also useful in the obtunded, intubated infant.33 A CT scan of the cervical spine can be used to delineate and clarify anomalies detected on the plain fi lm; however, CT scanning does not allow for imaging of the spinal cord. Clinical experience suggests that the traumatized infant who is awake, moving all extremities, easily consoled, and without neck pain or other major injury may be clinically cleared from cervical spine immobilization. Indications for imaging the chest and extremities of the traumatized infant are similar to those for older children (see Chapter 12, Approach to Multisystem Trauma; Chapter 19, Upper Extremity Trauma; Chapter 20, Lower Extremity Trauma; and Chapter 24, Thoracic Trauma). Infants who present to the emergency department with suspected abdominal trauma might have external bruising, abdominal distention, or tenderness on palpation. In the past, the hemodynamically unstable infant with abdominal trauma was taken directly to surgery, whereas the hemodynamically stable patient underwent laboratory evaluation and CT scan. The introduction of the “focused abdominal sonography for trauma” (FAST) scan to emergency medicine has altered how adults with blunt abdominal trauma are approached and managed. Using a portable ultrasound machine, the FAST scan quickly detects fluid in the abdomen, pelvis, or pericardium. It is gaining worldwide acceptance as an efficient screening tool. A positive scan in a hemodynamically unstable adult indicates the need for a laparotomy. The role of the FAST scan in pediatrics is currently being investigated.34 The advantages to FAST scanning are the availability at the bedside, speed, low cost, and avoidance of exposure to ionizing radiation. CT scanning, in contrast, can be time consuming and expensive, may require sedation, and exposes

the infant to ionizing radiation.33 An advantage of the CT scan, however, is that it provides an accurate diagnosis of parenchymal and retroperitoneal injuries, whereas sonography is poor at identifying organ-specific injuries or injuries that do not produce free fluid (i.e., blood) in the abdominal cavity. Since most cases of pediatric abdominal organ injury are now managed nonoperatively, this may be a serious limitation to the use of FAST scanning in the evaluation of traumatized infants.26

Management The management of traumatized infants should proceed efficiently. The bimodal distribution of injury severity should be kept in mind, necessitating early and aggressive treatment for clearly injured patients and a conservative approach to those who appear well. Because infants have a small blood volume and limited pulmonary reserve, they can progress rapidly to uncompensated shock and death (see Chapter 8, Circulatory Emergencies: Shock). Securing the airway is the principal goal in the management of traumatized infants. Indications for intubation include unstable vital signs, respiratory distress, shock, and signs of significant head injury. In the obtunded infant with significant injury, head trauma should be presumed and rapid sequence intubation performed (see Chapter 3, Rapid Sequence Intubation). The use of lidocaine to decrease the risk of elevating the intracranial pressure during intubation35,36 and atropine to avoid bradycardia37 are both controversial. Due to the shortened length of the infant trachea, it is easy for the endotracheal tube to enter the right mainstem bronchus. If a postintubation chest radiograph shows a whiteout of the left hemithorax in the setting of a right mainstem intubation, the first consideration should be a right mainstem intubation and not massive hemothorax. A trial of pulling the endotracheal tube back into an appropriate position may resolve the radiographic whiteout and minimize iatrogenic trauma. Fluid resuscitation requirements are based on the physical examination findings. The presence of poor perfusion and tachycardia indicates the need for fluid resuscitation. An intravenous or intraosseous bolus of 20 ml/kg crystalloid (e.g., normal saline) is the most readily available and appropriate initial management option. Re-evaluation after the initial fluid bolus can guide further management decisions. In the hemodynamically unstable patient, the need for colloid or blood products should be anticipated early to allow the blood bank adequate preparation time. Vascular access in the volume-depleted infant can be very challenging. Oftentimes an intraosseous needle is the most practical and efficient early option (see Chapter 161, Vascular Access). Infants are prone to becoming hypothermic due to their relatively large body surface area. Replacing wet linens with warm blankets will assist in stabilization and assessment. Use of warming lights and warmed intravenous fluids may also be beneficial. Oftentimes a cold, crying, tachycardic infant with poor capillary refi ll will improve with these basic interventions. Infants also have relatively small glycogen stores and are prone to develop hypoglycemia when stressed and kept nil per os (NPO) (see Chapter 106, Hypoglycemia). Blood sugars should be frequently monitored and hypoglycemia should be treated promptly.

Chapter 15 — Trauma in Infants

The pliable chest wall in infants makes rib fractures less common than pulmonary contusion, and also makes signs of external trauma unreliable in predicting deeper injury. On chest radiograph, pulmonary contusions can appear as scattered patchy infi ltrates or a complete whiteout of the involved lung. Management requires early endotracheal intubation and application of sufficient positive end-expiratory pressure to open the alveoli. A pulmonary contusion that appears as a whiteout of one side of the chest must be differentiated from a hemothorax. However, pulmonary contusions are much more common than hemothoraces. Yet, when complete unilateral whiteout is seen, tube thoracostomy may be indicated (see Chapter 168, Thoracostomy Tube). A gentle approach, to avoid placing the thoracostomy tube directly into the injured lung parenchyma, is prudent.

Summary Accidental injuries in infants most often result from falls, scald burns, falling objects, or motor vehicle accidents. Fortunately, these injuries are seldom severe. Primary preventative interventions have had a positive influence on the epidemiology of accidental infant trauma as evidenced by a decrease in the frequency and severity of injuries. Research into preventative measures has been successful in the past (e.g., car seats) and offers an excellent opportunity for the improvement in the health of infants. The pronounced physiologic differences between adults and infants alter how injuries are managed in the ED. Trauma guidelines and protocols developed for management of adult trauma (i.e., the Advanced Trauma Life Support course) may not be applicable to the care of the injured infant. Research directed toward development of a tailored approach to the injured infant should include recognition of injuries, stabilization, appropriate diagnostic testing and treatment, and techniques for proper sedation and analgesia. Infants with major injuries will benefit from admission or transfer to a pediatric intensive care unit. REFERENCES 1. Powell EC, Tanz RR: Adjusting our view of injury risk: the burden of nonfatal injuries in infants. Pediatrics 110:792–796, 2002. 2. Agran PF, Anderson C, Winn D, et al: Rates of pediatric injuries by 3month intervals for children 0 to 3 years of age. Pediatrics 111:e683– e692, 2003. *3. Stewart GM, Meert K, Rosenberg NM. Trauma in infants less than three months of age. Pediatr Emerg Care 9:199–201, 1993. 4. Pickett W, Streight S, Simpson K, et al: Injuries experienced by infant children: a population-based epidemiological analysis. Pediatrics 111: e365–e370, 2003. 5. Warrington SA, Wright CM, ALSPAC Study Team: Accidents and resulting injuries in premobile infants: data from the ALSPAC study. Arch Dis Child 85:104–107, 2001. *6. Berg MD, Corneli HM, Vernon DD, et al: Effect of seating position and restraint use on injuries to children in motor vehicle crashes. Pediatrics 105:831–835, 2000 7. Howard AW: Automobile restraints for children: a review for clinicians. CMAJ 167:769–773, 2002. 8. Arbogast KB, Cornejo RA, Morris SD, et al: Showing (motor vehicle) restraint: a primer for emergency physicians. Clin Pediatr Emerg Med 4:90–120, 2003. 9. Enrione MA: Current concepts in the acute management of severe pediatric head trauma. Clin Pediatr Emerg Med 2:28–40, 2001. *Selected readings.

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*10. Greenes DS, Schutzman SA: Infants with isolated skull fracture: what are their clinical characteristics, and do they require hospitalization? Ann Emerg Med 30:253–258, 1997. 11. Duhaime AC, Alario AJ, Lewander WF, et al: Head injury in very young children: mechanisms, injury types and ophthalmologic fi ndings in 100 hospitalized patients younger than 2 years of age. Pediatrics 90:279–285, 1992. 12. Cantor RM, Leaming JM: Pediatric trauma. In Marx JA, Hockberger RS, Walls RM (eds): Rosen’s Emergency Medicine: Concepts and Clinical Practice, 5th ed. St. Louis: Mosby, 2002, pp 267–281. 13. Gruskin KD, Schutzman SA: Head trauma in children younger than 2 years—are there predictors for complications? Arch Pediatr Adolesec Med 153:15–20, 1999. 14. Biros MH, Heegaard WG: Head trauma. In Marx JA, Hockberger RS, Walls RM (eds): Rosen’s Emergency Medicine: Concepts and Clinical Practice, 5th ed. St. Louis: Mosby, 2002, pp 286–314. 15. Dias MS: Traumatic brain and spinal cord injury. Pediatr Clin North Am 51:271–303, 2004. 16. Hardwood-Nash DC, Hendrick EB, et al: The significance of skull fractures in children. Radiology 101:151–155, 1971. *17. Hoffman JR, Mower WR, Wolfson AB, et al: Validity of a set of clinical criteria to rule out injury to the cervical spine in patients with blunt trauma. National Emergency X-Radiography Utilization Study Group. N Engl J Med 343:94–99, 2000. 18. Proctor MR: Spinal cord injury. Crit Care Med 30:S489–S499, 2002. 19. Kriss VM, Kriss TC: SCIWORA (spinal cord injury without radiographic abnormality) in infants and children. Clin Pediatr 35:119–124, 1996. 20. Pang D, Wilberger JE: Spinal cord injury without radiographic abnormalities in children. J Neurosurg 57:114–129, 1982. 21. Furnival RA: Controversies in pediatric thoracic and abdominal trauma. Clin Pediatr Emerg Med 2:48–62, 2001. 22. Bliss K, Silen M: Pediatric thoracic trauma. Crit Care Med 30:S409– S415, 2002. 23. Holmes JF, Sokolove PE, Brant WE, et al: A clinical decision rule for identifying children with thoracic injuries after blunt torso trauma. Ann Emerg Med 39:492–499, 2002. 24. Holmes JF, Sokolove PE, Brant WE, et al: Identification of children with intra-abdominal injuries after blunt trauma. Ann Emerg Med 39:500–509, 2002. *25. Bulloch B, Schubert CJ, Brophy PD, et al: Cause and clinical characteristics of rib fractures in infants. Pediatrics 105:e48, 2001. 26. Gaines BA, Ford HR: Abdominal and pelvic trauma in children. Crit Care Med 30:S416–S423, 2002. *27. Viccellio P, Simon H, Pressman BD, et al: A prospective multicenter study of cervical spine injury in children. Pediatrics 108:e20, 2001. 28. Lloyd DA, Carty H, Patterson M, et al: Predictive value of skull radiography for intracranial injury in children with blunt head injury. Lancet 349:821–824, 1997. 29. Committee on Quality Improvement, American Academy of Pediatrics, & Commission on Clinical Policies and Research, American Academy of Family Physicians: The management of minor closed head injury in children. Pediatrics 104:1407–1415, 1999. *30. Schutzman SA, Barnes P, Duhaime AC, et al: Evaluation and management of children younger than two years old with apparently minor head trauma: proposed guidelines. Pediatrics 107:983–993, 2001. 31. Patel JC: Pediatric cervical spine injuries: defi ning the disease. J Pediatr Surg 36:373–376, 2001. *32. Swischuk LE, John SD, Hendrick EP. Is the open mouth odontoid view necessary in children under 5 years? Pediatr Radiol 30:186–189, 2000. 33. Frank JB, Lim CK, Flynn JM, et al: The efficacy of magnetic resonance imaging in pediatric cervical spine clearance. Spine 27:1176–1179, 2002. 34. Soudack M, Epelman M, Maor R, et al: Experience with focused abdominal sonography for trauma (FAST) in 313 pediatric patients. J Clin Ultrasound 32:53–61, 2004. 35. Bozeman WP, Idris AM: Intracranial pressure changes during rapid sequence intubation: a swine model. J Trauma 58:278–283, 2005. 36. Robinson N, Clancy M: In patients with head injury undergoing rapid sequence intubation, does pretreatment with intravenous lignocaine/ lidocaine lead to an improved neurologic outcome? A review of the literature. Emerg Med J 18:419, 2001. 37. Fastle RK, Roback MG: Pediatric rapid sequence intubation: incidence of reflex bradycardia and effects of pretreatment with atropine. Pediatr Emerg Care 20:651–655, 2004.

Chapter 16 Oral, Ocular, and Maxillofacial Trauma Ran D. Goldman, MD and Steven G. Rothrock, MD

Key Points Nasal bone and mandibular fractures are the most common facial fractures in children, while midface and Le Fort fractures are uncommon. Head and face injuries occur in most infants and children who are abused. Computed tomography scanning is the radiologic test of choice for most facial injuries in children. Facial fractures that do not result in functional (e.g., limited eye movements, visual changes, malocclusion) or cosmetic problems are seldom serious.

Introduction and Background The etiology of facial injury depends mostly on a child’s age. In a large series from Austria, the main causes of facial trauma in children less than 15 years old were play (58%) and sports (32%). Half of all children had soft tissue injuries, and three quarters had dentoalveolar injuries.1 Facial fractures only occur in a minority of children with facial injury and are most commonly due to motor vehicle accidents.2-4 Other important fracture causes include falls, sports injuries, bicycle/motorcycle accidents, and assaults.2-4 One easily overlooked mechanism is abuse, with facial bruising or abrasions occurring in the majority of abused infants and children.5 Boys have a 1.5- to 3-fold greater risk of facial injury compared to girls.1,3,4,6,7 In addition, the risk of facial fracture occurring with facial trauma rises with increasing age. While 5% to 15% of all facial fractures occur in children less than 16 years old, fewer than 1% occur in those less than 5 years old.8-12 While nasal bone fractures are the most common pediatric facial fracture, the most frequent fracture site in admitted patients is the mandible (Fig. 16–1), followed by the zygomatic arch and alveolar ridge.3,4 Less common fracture sites 154

include the orbital floor, the hard palate, and rarely the midface (Le Fort fractures). Importantly, Le Fort fractures almost never occur in children under 10 years old. Associated injuries occur in most children with facial trauma, including intracranial, spine, eye, dental, and nerve injuries. For those children with serious injury mechanisms, thoracoabdominal and orthopedic injuries must be excluded.

Recognition and Approach While children under 7 years old are at risk for soft tissue injury, fractures are uncommon at this age.13 Eighty percent of cranial growth occurs during the first years of life. After age 2, the face begins to grow faster than the skull. In a newborn infant, the ratio of cranial volume to facial volume is 8 : 1, while in adults this ratio is 2 : 1.13 Therefore, trauma is more likely to impact the skull and forehead and less likely to injure midfacial structures in young children. This disproportionate growth results in more frequent orbital roof (cranial floor) fractures in infants and more frequent associated neurologic trauma. In contrast, lower orbital fractures generally occur after age 7, have less associated intracranial injury, and more often require surgical reconstruction.13 Other protective features of a young child’s face include underdeveloped paranasal sinuses, increased number of facial fat pads, unerupted dentition that strengthens the maxilla and mandible, and relatively flexible bone. In contrast to young children, adolescents have higher rates of facial trauma due to a mature facial skeleton and more adult activity profi le. Clinicians must be able to recognize the location of important structures when confronted with children with facial trauma (Fig. 16–2). The major portions of the facial nerve are posterior to a vertical line perpendicular to the lateral canthus.14 Facial nerve injuries anterior to this line only require repair if they involve solitary terminal branches (i.e., marginal mandibular branch, frontal branch).14 The parotid gland lies anterior to the sternomastoid and external auditory meatus and inferior to the posterior two thirds of the zygomatic arch. Stensen’s duct exits the parotid and traverses along the middle third of a line drawn from the tragus to the midportion of the upper lip. This duct opens into the mouth opposite the secondary maxillary molar. The buccal branch

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Coronoid < 1%

Mandibular foraman Condyle 35%

Alveolar ridge

Ramus 8%

Angle 18%

Mental foramen FIGURE 16–1. Most common location of mandibular fractures in children.

Symphysis 24% Body 15%

D H E

A

A

F

G B C

A

C

B

FIGURE 16–2. The parotid duct (A) traverses the middle third of a line connecting the tragus to the middle of the upper lip. Repair of facial nerve branches beyond a vertical line (B) originating at the lateral canthus is usually not required. Trigeminal nerve branches exit the face at foramina located along this line (C) (vertical line through pupil), including the supraorbital branch of the ophthalmic nerve (V1), the infraorbital branch of the maxillary nerve (V2), and the mental nerve (branches of the trigeminal nerve) (V3). The distance between the medial canthi of each eye (D) should be no greater than the size of the palpebral fissure (red line) (E). The parotid gland (F) lies below the zygomatic arch and anterior to the sternomastoid muscle (G). Major branches of the facial nerve (H) run through the parotid gland.

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of the facial nerve traverses the midportion of Stensen’s duct, and injuries of the duct and nerve often coexist.

Evaluation History Initially, the clinician should exclude life-threatening injury (e.g., inadequate airway, blood loss), immobilize the cervical spine, provide suctioning, and administer oxygen if needed. Patients should be asked if they are having difficulty breathing, or if they have bleeding into the mouth or pharynx. When time permits, the mechanism and forces that caused the injury should be determined. Patients should be asked if they have vision loss, monocular diplopia, or eye pain, which may suggest ocular or orbital trauma. Binocular diplopia suggests orbital trauma or extraocular muscle or nerve injury. Facial numbness may occur with trauma to the branches of the trigeminal nerve, fractures, or swelling and trauma near their respective foramina. Hearing loss may be due to temporal bone fracture or direct ear trauma. Malocclusion and difficulty opening or closing the mouth can occur with mandibular or zygomatic trauma.

A

Physical Examination Prior to examination, the clinician should ensure that appropriate lighting and tools are present, including a headlamp or mirror, tongue blades, a suction device, a nasal speculum, an otoscope, and an ophthalmoscope. The examination should begin with a visual inspection of the face and skull from all angles, paying attention to sites of asymmetry, bruising, and swelling. Lacerations or blunt trauma that involves specific landmarks may indicate damage to the lacrimal duct, parotid duct, or cranial nerves (see Fig. 16–2). A bird’s-eye view (looking down from above) may reveal asymmetric malar eminences with zygomatic fractures, or enophthalmos or exophthalmos with orbital trauma (Fig. 16–3). The inside of the nose is examined for septal hematomas, and the inside of the mouth for bleeding, deformity, or hematoma suggesting fracture. If there is bleeding around a tooth near a mandible fracture, it must be assumed that the fracture is open. A sublingual hematoma is common with mandibular fractures. The insides of the ears are examined for bleeding, fluid leak, lacerations, or a purplish tympanic membrane consistent with temporal bone or basilar skull fracture. The face and cranium are palpated to detect areas of tenderness, bony irregularities, or crepitus. Mobility of the midface may be tested by grasping the anterior alveolar arch and pulling forward. Malocclusion or trismus can be assessed by having the patient open and close the mouth while palpating the mandibular condyles by placing a finger within or just below the external auditory canal. Cooperative patients can be asked to bite down on a tongue blade. In adolescents and adults, the inability to break the blade when it is twisted is 95% sensitive for mandibular fractures.15 The patient should be asked to smile, frown, raise the eyebrows, and open and close the eyes tightly to assess facial nerve integrity. Sensation to terminal trigeminal nerve branches should be tested (see Fig. 16–2). A thorough eye examination is required in all infants and children with facial trauma. The eyelids should be inspected

B FIGURE 16–3. A, Normal appearance to facial contour looking anteriorly at face. B, Bird’s-eye view of the face demonstrating swelling of the right malar eminence.

for lacerations that involve the tarsal plate, either the canthus or potentially the lacrimal duct. If the distance between the medial canthi is greater than the horizontal width of an orbit (or 35 to 40 mm in a child > 5 years old), telecanthus is present and a midfacial fracture is likely. Extraocular muscles are tested for entrapment (e.g., limited upward gaze with orbital blowout fracture). Visual acuities should be obtained in older, cooperative children. The clinician should assess pupil size, test direct and indirect pupillary reaction to light,

Chapter 16 — Oral, Ocular, and Maxillofacial Trauma

and directly examine the cornea. Fluorescein administration and slit-lamp examination may be required. Lack of cooperation, anxiety, pain, and limited communication skills can interfere with proper evaluation of infants and children with facial injuries. Appropriate analgesia and sedation should be administered depending upon the patient’s airway, associated injuries, and medical condition (see Chapter 159, Procedural Sedation and Analgesia). An integral part of evaluating infants and children with facial trauma includes a head-to-toe examination for nonfacial injuries.16 Associated injuries are present in up to 87% of children facial fractures.3 In addition, early photographs may be helpful in preoperative planning and patient counseling, as well as for prospective medicolegal matters. Radiology With the exception of a Panorex view, plain radiography usually provides limited diagnostic information to the clinical examination and limited information regarding facial fractures in children.3 Nearly half of all significant facial fractures in children are missed by plain radiography.3 For this reason, children with suspected facial bone injury usually require a computed tomography (CT) scan of the face. Typically, facial CT consists of 3-mm slices taken in the axial plane with both axial and coronal reconstruction.10,17 Threedimensional reconstruction can provide even more detail regarding fractures. One quick clue to the presence of a midface fracture is the presence of fluid within the paranasal sinuses. In adults, nearly 100% of all midface fractures (excluding nasal, and zyomatic fractures) have associated paranasal sinus fluid.18 A panoramic view (Panorex) of the mandible can display upper and lower teeth and the mandibular condyles; however, full cooperation of the injured child is needed and an upright posture must be maintained. Supplemental oblique mandible views (mandible series) can be used to evaluate the mandibular condyles and rami. A Towne’s view (anterior-posterior view 35 degrees caudad) can be helpful for zygoma and mandibular rami fractures. Other views, including the Waters’ (occipitomental), submentovertex (jug-handle), and Caldwell’s (posterior-anterior) views, have largely been supplanted by facial CT due to its superior accuracy at identifying facial fractures. Clinical features suggestive of the need for facial CT have been identified in adults and can be recognized by the mnemonic LIPS-N, which stand for lip laceration, intraoral laceration, periorbital contusion, subconjunctival bleeding, and nasal laceration.19 Others have identified the following features in 96% of all orbital fractures and 98% of all orbital fractures requiring surgery: blepharohematoma, subcutaneous emphysema, a palpable deformity or gap, infraorbital anesthesia, enophthalmos, exophthalmos, abnormal ocular motility, diplopia, abnormal papillary reaction, or vision problems.20 It is uncertain if the mnemonic LIPS-N or other identified features in adults are equally sensitive in identifying fractures in children. Children who require head CT are another population who are at high risk for facial fractures. Ten percent to 12% of patients requiring a head CT will have a facial fracture.4,19,21 In the subset of patients with severe head injury (i.e., those who are intubated), up to 29% will have facial fractures; many of which are unsuspected.22

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Management Initial Management Management of any child with facial injury initially begins with assessment of airway patency. Accompanying head injury may lead to apnea and decreased airway tone with obstruction. Contrary to popular belief, airway obstruction in patients with an altered mental status is more likely due to hypotonia with collapse of the hypopharynx, soft palate, and epiglottis and not obstruction by the tongue.23-25 For this reason, airway maneuvers that move the tongue anteriorly (e.g., chin lift, jaw thrust) are not always successful at opening an obstructed airway. For the same reason, use of an oral airway in obstructed patients may be unsuccessful and oral intubation may be required at an early stage. Clinicians must realize that sedation and paralysis may be extremely difficult in patients with significant mandible or maxillary fractures. Blood and secretions should be gently suctioned from the mouth, and foreign bodies such as as teeth or bone fragments identified and removed. Intubation in cases of distorted anatomy might be necessary as a preventive measure and should not be delayed. Before intubation, a team experienced in difficult airway management and all the necessary equipment must be at the bedside (see Chapter 3, Rapid Sequence Intubation; and Chapter 4, Intubation, Rescue Devices, and Airway Adjuncts). Warning signs such as stridor, drooling, active bleeding, or hematoma on the face or neck indicate immediate or impending airway compromise and mandate intubation. Cervical spine stabilization is crucial for children with facial injury, in order to prevent further damage to cervical structures affected by the trauma. A head-to-toe evaluation is required to exclude other life-threatening injuries (see Chapter 12, Approach to Multisystem Trauma). Maxillofacial Fractures Mandibular Fractures Mandibular fractures are the most common facial fractures found in hospitalized children.26 The mandible includes the condyle, ramus, body, angle, and arch (symphysis and parasymphysis) (see Fig. 16–1). Fractures of the mandible are relatively common compared to other bones in the face, mostly due to transferred force through the overlying fat tissue. Condylar fractures, in particular, are common since the condyles are heavily vascularized and thin in children.26 Most mandibular fractures with normal occlusion and movement are usually treated with a soft diet and movement exercise. Most condylar, body, and angle fractures fall within this category and are treated conservatively. If malocclusion or movement limitations are present or an open fracture is present, immobilization is required via surgery, or splinting. Midface and Maxillary Fractures Maxillary fractures are infrequent in young children and occur primarily in children ≥ 10 years old.1,4 The Le Fort classification used to classify maxillary fractures in adolescents and adults is based on the horizontal level of the fracture. Le Fort I fractures result in separation of the maxilla from the palate. These fractures may result from a force on the maxillary alveolar rim in a descending direction. Le Fort

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II fractures result in separation of the cranium from the midface. Le Fort III is the most severe fracture and results in complete separation of the facial bones from the cranium. Displaced midface fractures require open reduction and rigid internal fi xation.26 Nasoethmoid Fractures Nasoethmoid fractures occur when there is disruption at the nasofrontal suture, nasal bones, medial orbital rim, and infraorbital rim. If all four sides are involved, a central fragment may exist. Surgery will be required if telecanthus is present, or there is disruption of bony or soft tissue support for the eye.13,26 Nasal fractures are the most common facial bone injury in children. The younger the child, the lower the risk of nasal fracture since the cartilaginous part of the nose is larger and more elastic. Clinical interpretation of a nasal fracture is usually difficult in the emergency department (ED) due to swelling and hematoma in the area as a result of the injury. It may be necessary to wait a few days to determine if a fracture actually occurred. Nasal radiographs are usually not necessary in the ED unless ordered for parental reassurance.27 Radiographs are nonspecific, and even if a fracture is suspected, they do not alter subsequent management. High vascularity of the nose cause significant bleeding even after minor soft tissue injury. Septal hematoma is one of the known complications after such bleeding, and is an indication for immediate evacuation. Unilateral nasal obstruction is common in septal hematoma, and rhinoscopy will show a bulging mass (usually purple) in one nostril. Evacuation of septal hematoma will relieve pain due to pressure in the area, and will also prevent septal deformity. Infection in the area is also possible. Once the hematoma is drained, oral antibiotics should be administered. Zygomaticomaxillary Complex Fractures Zygomaticomaxillary complex fractures are uncommon under the age of 5 years, before the maxillary sinus becomes aerated. Low-impact injuries often result in greenstick fractures, which are usually nondisplaced and often require no treatment. Open reduction and internal fi xation is required for displaced, comminuted, or unstable fractures. Functional deficits (e.g., diplopia, or infraorbital sensory loss) also often require surgery.26

ring in boys. Ocular trauma is the leading cause of noncongenital unilateral blindness in children under 20 years old and the foremost cause for enucleation of the eye in children, especially in boys.30 Most major eye trauma in children occurs during sports activities because proportionally more children and adolescents participate in high-risk activities. Basketball, baseball, racquet sports, martial arts, wrestling, and archery are the most frequent cause of injury. BB and pellet guns also present an extreme hazard to children. Understanding the mechanism of injury is important for planning management better. Clinicians must determine if there is blunt or sharp object injury, if a foreign body is present in the eye, and if protected devices were used. As assessment of pain, photophobia, eye movements (diplopia), and visual acuity will aid in determining the nature of the injury. Visual acuity examination is the most important part of the physical examination and should be separately performed for each eye. Finger counting, the “E” chart, and a numeric chart can be used for examination of the injured child. If needed, a topical anesthetic (such as tetracaine or proparacaine) should be administered to ensure adequate examination. During examination of the eyes and orbit, the emergency physician should examine the integrity of the orbital rims, orbital floor, vision, extraocular motion, position of the globe, and intercanthal distance. A complaint of diplopia or limited extraocular movements on examination is usually the result of entrapment and dysfunction of extraocular muscles with associated orbital floor blowout fractures. Cranial nerve palsy from associated head injury can also result in headache and diplopia. With globe or scleral rupture, severe external disruption of the eye is not always evident. With rupture, the iris or choroids will extent toward the wound, resulting in a dark (blue or black) spot on the sclera (Fig. 16–4). The pupil may take a dysmorphic or teardrop shape. Pupils are usually examined as part of the neurologic evaluation in the primary survey. However, they should be examined carefully in any suspected injury. The clinician should assess size, shape, and direct plus indirect reaction to light. While anisocoria could be a normal phenomenon in a small percentage of the population, this finding may indicate

Frontal Bone/Sinus Fractures The frontal sinus becomes developed by age 6 to 8 years. Before this age, frontal sinus fractures are uncommon. Anterior sinus table fractures that are not displaced can be observed, with most experts administering antibiotics since the fracture connects to a sinus. Because displaced anterior fractures are associated with mucocele formation, nasofrontal duct obstruction, and cosmetic deformity, surgical repair is generally required. Posterior wall fractures should be treated as an open skull fracture with the potential for associated cerebrospinal fluid leak. Neurosurgical consultation is required. Orbital Trauma Childhood is the most common period for serious eye injuries throughout life,28,29 with the majority of injuries occur-

FIGURE 16–4. Scleral rupture with extruded uvea, which appears brown-black.

Chapter 16 — Oral, Ocular, and Maxillofacial Trauma

a possible injury to the third cranial nerve or increased intraocular pressure (IOP). A combination of ptosis, miosis, and anhydrosis, known as Horner’s syndrome, suggests a lesion of the sympathetic pathway. In the ED, direct ophthalmoscopy and slit-lamp examination may be required to evaluate the cornea, anterior and posterior chambers, and retina. Measurement of IOP is contraindicated in suspected globe rupture, but may help to identify retrobulbar hemorrhage causing increased IOP. Except for cases of large radiopaque foreign bodies, plain radiography of the ocular system is usually unhelpful. For sites with expertise, ultrasonography can be used to identifying ocular foreign bodies, retinal detachment, vitreous hemorrhage, and globe rupture.31 For most other sites, CT with thin slices (1 to 1.5 mm) in the canthal-meatal plane, with sagittal and coronal reconstruction, is used for identification of potential intraocular injuries.32 Orbital CT is 75% sensitive and 93% specific for identifying globe rupture.33 CT is also accurate at identifying ocular foreign bodies.32 Helical CT can detect all steel and copper foreign bodies larger than 1 mm3 and most glass foreign bodies larger than 2 mm3.34 Wood and plastic can be difficult to visualize using typical bone and soft tissue CT windows since wood may be isodense with air and fat. To identify wooden foreign bodies, the CT window should be adjusted to allow visualization of soft tissue contrast and show an attenuation difference between the wood and surrounding tissue, or the alternating density pattern of the grain of the wood. Alternately, magnetic resonance imaging can be used to identify wood or plastic foreign bodies once metallic foreign bodies have been excluded. Orbital Fractures Following blunt compressive eye trauma, the eyeball may be pushed posteriorly and induce pressure that causes “blowout” of one or more bones of the orbital wall. Unlike adults, children are particularly susceptible to pure orbital fractures, usually of the “trapdoor” type.35 Most of the orbital floor is immature in childhood, and this elasticity makes the orbital bones more susceptible to fractures when pushed against external force. The fracture is usually linear along the obliquely situated infraorbital canal, resulting in trapping of muscles. These fractures occur when a circular segment of the bony orbit fractures and becomes displaced, but remains attached on one side. Afterward, orbital contents can herniate through the fractured site, with entrapment of the herniated contents.36 Blowout fractures of the orbital wall are usually diagnosed clinically after observation of asymmetric and restricted eyeball movement. Trapping of the intraocular muscle prevents movement of the eye away from the fracture site. While orbital hemorrhage is a differential diagnosis in this clinical scenario, lack of normal range of motion should raise a high suspicion of orbital fracture in an injured child. Due to the disrupted wall, the eyeball might fall back into the fracture, and the eye will also look sunken. Orbital roof fracture occurs mostly in children under 5 years, because of a proportionally larger cranium and the lack of frontal sinus pneumatization, while orbital floor fractures occur later in childhood, after facial growth and the pneumatization of the paranasal sinuses. Orbital roof fractures are particularly hazardous because of the possible communication between the orbit and the intracranial cavity.

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Pulsating proptosis could serve as a clue to the presence of such a fracture. A history of a blow to the brow in conjunction with late periorbital ecchymosis may be an important clue to the injury. Orbital floor fractures are less common but could cause partial or complete injury to the infraorbital nerve, causing ipsilateral numbness of the malar region. This is usually a transient phenomenon. Periorbital ecchymosis, lid edema, subconjuctival hemorrhage, and diplopia are the most common presenting signs. Most patients have a severe limitation of ocular movement caused by direct entrapment of the inferior rectus muscle into the fracture site, and many patients, especially those with muscle entrapment, will suffer extreme pain with eye movements and will present with nausea and vomiting.37 Ophthalmologic consultation is important in cases of suspected orbital wall fracture since in some cases an intraorbital injury is accompanied by other skeletal fractures. CT scan is the radiologic test of choice for children with suspected orbital bony injury, and both axial and coronal views are necessary.38 The emergency physician should always consider the possibility of child abuse30 in cases of orbital fracture in young children. The ED staff also has a role in teaching the young patient and the family how to effectively protect the eye from trauma, especially due to foreign bodies. The use of protective eyewear during activities associated with ocular trauma, such as sports, is of great importance. Ruptured Globe A rupture of the globe is rare and can occur after significant laceration of the cornea or sclera due to sharp objects or blunt trauma. The limbus (beneath the insertions of the rectus muscle) and the equator of the globe are the weakest areas of the sclera and most prone to rupture following blunt trauma. Visual loss, bloody chemosis (especially localized), a soft globe, and an abnormally deep anterior chamber are seen with rupture. The uvea may appear as a dark mass prolapsing through the ruptured site (see Fig. 16–4). Associated hyphema, lens dislocation, and vitreous hemorrhage also may occur. When a rupture is suspected, a protective shield should be placed over the eye. Broad-spectrum intravenous antibiotics effective against skin flora (Streptococcus and Staphylococcus aureus/epidermidis) and tetanus prophylaxis should be administered, as well as analgesics and sedatives if needed. Antiemetics may be required to diminish increased IOP from vomiting. For children requiring intubation, debate exists as to the appropriate use of muscle relaxants. Succinylcholine can increase IOP by an average of 9 mm Hg following administration. However, these effects can be blunted by multiple medications (see Chapter 3, Rapid Sequence Intubation). Moreover, rare ocular injury following use of succinylcholine has primarily been reported in patients receiving light or inadequate sedation.39 For this reason, some experts still recommend use of succinylcholine for patients at risk for a difficult airway due to its fast onset and short duration, as long as efforts are made to attenuate its IOP effects.39 For all other patients, non-depolarizing muscle relaxants are recommended.39 Following patient stabilization, immediate pediatric ophthalmologist consultation is required if scleral rupture is suspected since damage to the posterior segment of the eye can cause permanent visual loss.

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Retrobulbar Hemorrhage Retrobulbar hemorrhage can lead to rapid compression of the optic nerve and irreversible vision loss. Patients usually have severe blunt trauma, proptosis, vision loss with afferent pupillary defect, chemosis, and increased IOP. CT is often diagnostic. Treatment consists of a lateral canthotomy with lysis of the inferior lateral canthal tendon. Depending upon the availability of backup, severity of vision loss, and IOP, this procedure may need to be performed in the ED. This allows the orbital contents to move forward, releasing pressure on the optic nerve. Optic Nerve Injury The optic nerve is divided into a small intraocular portion and a long mobile intraorbital portion, and intracanalicular (within the bony canal) and intracranial segments. Fractures within the bony canal may occur with severe head or midface injury, with transection of the optic nerve. Alternately, shearing, compression, or tearing or arterioles along the course of the nerve from blunt trauma may disrupt the arterial supply. Depending upon the cause of trauma, the eye may have a normal appearance. Visual loss may be severe or complete, and an afferent pupillary defect may be present. Funduscopic examination may be normal, with eventual development of pallor. Orbital CT can identify the site of trauma. Surgical decompression may be necessary with disruption of the intracanalicular optic nerve, while the use of high-dose steroids is controversial for these injuries. Posterior Eye Injuries (Vitreous and Retinal Trauma) While the posterior segments of the eye are not involved in eye trauma as often as anterior structures, these injuries are more likely to result in permanent visual loss. The retina or vitreous is involved in half of all severe open and closed globe injuries.40 Retinal detachment can occur from blunt trauma deforming the eye with peripheral tears, while penetrating trauma can result in direct localized tears or rupture. While retinal detachments do not cause pain, associated ocular trauma may be painful. Symptoms of detachment include floaters due to bleeding, flashing lights, and variably decreased visual acuity depending upon the location of the detachment and amount of bleeding. Patients may complain of a curtain coming down, up, or across their visual field. The anterior segment is usually normal, while the red reflex may be absent with a hazy or gray appearance to the retina, on funduscopic examination. Importantly, direct ophthalmoscopy may not reveal the site of detachment. If an optic nerve injury or significant retinal detachment is present, an afferent pupillary defect may be present.40 Isolated vitreous hemorrhage or detachment can produce symptoms similar to retinal detachment. However, an afferent pupillary defect will not be present. Ophthalmologic consultation is required to exclude or treat associated retinal and optic nerve trauma.40 Iris and Ciliary Trauma Traumatic iridocyclitis can occur from blunt trauma with contusion, causing inflammation of the iris and ciliary body with resulting ciliary spasm. Children complain of photo-

phobia, redness, and pain with onset often delayed until 1 to 3 days after the injury. The pupil is usually constricted (traumatic miosis). However, if the sphincter is torn or injured, traumatic mydriasis or an irregular or scalloped pupil margin may be present. In iritis, slit-lamp examination will reveal flare and cells. Initially, the IOP may be low or normal. Treatment consists of a cycloplegic to relax the iris and ciliary body (e.g., homatropine) and pain medications. If the iris root is separated from the ciliary body, iridodialysis is present. This results in the iris bowing toward the pupil. A coexisting hyphema is often present. Patients may complain of glare, photophobia, and monocular diplopia. A double-pupil appearance to the pupil may be present on examination. Initially, treatment is directed at managing the hyphema. Late surgical repair may be required for double vision, persistent glare, or cosmesis. While initial IOPs are often depressed, glaucoma often occurs in the ensuing 3 months. Damage to the structures of the anterior chamber may impede drainage of aqueous humor from the eye and lead to acute glaucoma. Patients who present with eye pain following blunt trauma require measurement of IOP once rupture and cornea trauma have been excluded. Lens Injury Blunt lens trauma can lead to cataract formation. If the lens capsule is torn, swelling and opacification of the lens can occur. Blunt injury to the lens also can disrupt the lens zonules that encircle the lens and anchor it to the ciliary body. The lens can fall partially (subluxation) or completely (dislocation) away. The edge of the lens may be at the pupillary border, or the entire lens may be dislocated into the anterior or posterior chamber. Patients may complain of visual blurring or monocular diplopia. Iridodonesis or trembling of the iris may be seen following rapid eye movements if the lens is dislocated. If the lens is trapped within the pupil or touching the cornea (anterior dislocation), acute glaucoma may occur and emergency surgery is required. Isolated posterior dislocations do not require emergency surgery. Hyphema A hyphema refers to accumulation of blood in the anterior chamber of the eye. The blood may be layered inferiorly or may be spread diffusely throughout the anterior chamber. Blood is normally caused by a tear in the iris root and bleeding from arterioles supplying the iris. Complications occur from obstruction of the outflow of the anterior chamber, with resulting inflammation and increased IOP. Patients with sickle cell disease or trait, those with thalassemia, or those taking anticoagulants are at risk for central retinal artery and optic nerve damage from less than severe elevations in IOP. Patients are at risk for rebleeding 3 to 5 days after the initial injury due to clot lysis and retraction. Management should be coordinated with an ophthalmologist. Initial treatment consists of supportive care, with initial bed rest and elevation of the head of the bed 30 degrees and application of a protective barrier. Patients with large hyphemas (i.e., > 50% of the anterior chamber) may benefit from admission. Patients should avoid aspirin and nonsteroidal anti-inflammatory medications. Topical anticholinergics are

Chapter 16 — Oral, Ocular, and Maxillofacial Trauma

administered to stabilize the blood-aqueous barrier and improve symptoms from associated iritis. Topical steroids are also administered. Patients at high risk for rebleeding are treated with oral steroids. Oral aminocaproic acid is administered to enhance clot lysis. Initially, IOP elevations may be treated with topical β-blockers, α-agonists, or carbonic anhydrase inhibitors. Surgery is indicated for persistent elevation of IOP, corneal blood staining, or select patients with sickle cell disease or trait.41 Corneal Injuries Corneal injuries are one of the most common reasons for pediatric visits to the emergency department with ophthalmologic complaints. Self-inflicted injuries from fingers, chemicals, or contact lenses are common, as are injuries inflicted by foreign bodies in the eye. Pain is a prominent complaint in patients with corneal injury. Corneal injury should be part of the assessment of the crying infant since irritability is a common presenting symptom in this age group. Excessive tearing, photophobia, and complaints of a foreign body sensation are common. While changes in visual acuity are hard to assess due to pain, tearing and frequent blinking are easily noticed on examination. Visual acuity is part of the eye physical examination in children with suspected injury. However, normal visual acuity does not rule out corneal trauma. Examination with fluorescein should follow. The first step should be administration of a topical anesthetic such as tetracaine or proparacaine, followed by a drop of fluorescein from a wet sterile paper strip in the inferior fornix. Foreign body or abrasion can easily be seen under cobalt blue light as corneal lesions will fluoresce brightly. Corneal Abrasion Corneal abrasions are the most common eye injury in all ages and are especially common among older children who wear contact lenses. Although found in about 10% of visits with a chief complaint related to eye problem in EDs, the actual estimated incidence of corneal abrasions in children is not known. Current management of corneal abrasion in children is based on treatment established in adults. Recommended therapy consists of eye patching, cycloplegic drops, and antibiotics. Cycloplegic drops prevent discomfort from ciliary spasm, and antibiotics are administered to prevent infection.42 In the past, patching was thought to facilitate healing and to relieve pain due to decreased shearing forces over the defect.43 However, routine use of a patch has been questioned because it impairs binocular vision; obscures half of the visual field; may carry a risk for anaerobic infections, particularly in children using contact lenses; and does not improve the rate of healing.44,45 Although no clear evidence exists, many ophthalmologists prescribe a topical antibiotic (e.g., fluroquinolone) for infection prophylaxis after corneal abrasion in children. All children except those with a very mild corneal abrasion should have a slit-lamp examination. In all significant corneal injuries, examination by an ophthalmologist is desirable for management and further follow-up after discharge from the ED. Close follow-up care of children with corneal abrasions is necessary because of a possible progression of the abrasion to an ulcer.

161

Soft Tissue Injuries Eyelid Lacerations Eyelid lacerations are common in children with blunt and penetrating facial trauma. While relatively easy to detect externally, an underlying eye injury should always be suspected and skilled evaluation of the eye should take place before correction of the laceration. Ocular injury is assumed to be present in any full-thickness penetration of the eyelid. Importantly, visualization of fat from an eyelid injury indicates full-thickness injury with septal trauma and possible levator injury. The lids should be everted and the conjunctival surface examined in all eyelid injuries. If there is any suspicion that ocular penetration has occurred from penetrating trauma (e.g., pellets or BBs), an orbital CT should be obtained. Hyphema, orbital fractures, orbital penetration, and other ocular adnexal trauma often occurs with lid trauma. To test levator function, the position of the brow is fi xed and the patient is asked to look up and down. If the canthal angles are rounded, medial or lateral canthus trauma is likely. With eyelid margin lacerations, there is often retraction of tissue due to orbicularis contraction, and the eyelid appears avulsed.46 However, this tissue often stretches out to its normal size. Lacerations of the nasolacrimal duct puncta or medial to this site require probing of the canaliculus for possible injury. Sensation above the orbital rim should be tested to exclude supraorbital nerve injury. Depending upon the child’s age, anxiety level, and complexity of repair, eyelid lacerations may require moderate to deep sedation (see Chapter 159, Procedural Sedation and Analgesia). Simple partial-thickness lacerations may be repaired using 6-0 or 7-0 nylon sutures. However, plastic surgery or ophthalmology repair is required for fullthickness lacerations or those with a high potential for cosmetic deformity, canthal ligament involvement, lid margin involvement, lacrimal damage (e.g., medial lower eyelid), tissue avulsion, or levator involvement. Ear Trauma Blunt trauma to the external ear canal may result in hematoma, laceration to the auricle, cartilage trauma, and fractures of adjacent skull or facial bones. A subperichondrial hematoma may result from blunt trauma to the pinna. Failure to recognize and treat this condition early usually leads to a visual deformity. The pinna becomes a shapeless, reddish purple mass when blood collects between the perichondrium and the cartilage. Because the perichondrium carries the blood supply to the cartilage, avascular necrosis of the cartilage may occur. Organized, calcified hematoma may result in “cauliflower ear.” Collection of blood or serous fluid between the perichondrium and cartilage may be successfully treated by needle aspiration under sterile conditions, followed by the application of a pressure dressing. If a hematoma recurs within 48 hours, formal incision and drainage are then required. For lacerations of the pinna that penetrate the cartilage and skin on both sides, treatment is aimed at covering the exposed cartilage and minimizing deformity. Cartilage is avascular with a high risk of infection and minimal healing ability. Prior to any repair, devitalized tissue is removed. The cartilage is approximated with overlying perichondrium using 4-0 or 5-0 absorbable sutures. Next, the posterior skin

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surface is closed with 5-0 nonabsorbable sutures. Then the anterior surface is closed with 5-0 or 6-0 nonabsorbable sutures with attention to joining landmarks and everting wound edges along the rim of the ear so that notching does not occur. Following repair, a compression dressing is applied to ensure a hematoma does not develop. Antibiotics should be administered to patients with devitalized or contaminated wounds. If there is not enough skin to cover cartilage (i.e., indicating a need for a skin flap) or if there is a high potential for deformity, plastic surgical consultation should be obtained.47 Forceful blows to the mandible may be transmitted to the anterior wall of the ear canal (posterior wall of the glenoid fossa). Displaced fragments from a fractured anterior wall may cause stenosis of the canal and must be reduced or removed using a general anesthetic. Abrasions and lacerations of the external auditory canal are common and may be caused either by the patient or iatrogenically while trying to remove wax. Eardrops containing antibiotics are usually effective in preventing an external otitis resulting from secondary infection. Aminoglycoside drops should be avoided in the presence of a tympanic membrane perforation.

possible. In either instance, ophthalmology consultation is required.

Oral and Tongue Lacerations

The parotid gland occupies a key location within the face, with important facial nerve branches and the parotid duct contained within its structure (see Fig. 16–2). It lies anterior to the sternomastoid muscle and inferior to the zygoma. Importantly, the buccal branch of the facial nerve, which supplies the buccinator, closely approximates the position of the parotid duct. Injury to the parotid duct or buccal branch of the facial nerve requires exploration for corresponding injury to the adjacent structure. In general, parotid duct injuries require exploration and repair by a plastic surgeon.

Most inner lip and tongue lacerations do not require suturing. Importantly, lacerations that penetrate the oral mucosa require close inspection to exclude a tooth fragment or other foreign body. Patients with lacerations involving the gingiva also require evaluation to ensure that no associated fracture is present. Lacerations with large flaps and those with uncontrolled bleeding, that gape and are likely to collect food, or that involve an extensive amount of the tongue edge and may cause functional impairment require repair in the ED. The maxillary frenulum has no function and does not require repair unless trauma is extensive and extends into the surrounding mucosa. In contrast, the lingual frenulum is highly vascular and more likely to require repair to prevent continued bleeding. Lacerations that cause a degloving injury to the gum margin also require repair, usually by an oral surgeon. For intraoral repair, absorbable sutures are used in all cases. For through-and-through tongue lacerations, the muscle layer is closed separately. Moderate sedation is often required for children who need tongue laceration repair (see Chapter 159, Procedural Sedation and Analgesia). Other Structures NASOLACRIMAL SYSTEM

Tears drain from the eye via puncta into the upper and lower canaliculi at the medial aspect of the eye. These puncta are directed posteriorly toward the globe and usually cannot be visualized unless the lids are everted. The upper and lower canaliculi merge to form a common canaliculus that drains into the lacrimal sac, which then drains into the nasolacrimal duct, which courses inferiorly and posteriorly through the maxilla, draining inferiorly to the inferior turbinate. Children with upper or lower eyelid trauma that is medial to the pupil require examination to exclude trauma to these structures. Moreover, if medial canthal disruption is present (e.g., rounded medial canthus), nasolacrimal trauma is also

NERVES

Five branches of the facial nerve supply motor innervation to facial muscles: the temporal, zygomatic, buccal, mandibular, and cervical branches. Paralysis of the facial nerve can affect the forehead, eyebrow, eye, nose, mouth, lips, or platysma, depending on the branches of the facial nerve affected. If hearing or taste is affected or decreased tear production is present in the ipsilateral eye, then facial nerve injury is localized to its intratemporal course (e.g., temporal bone fracture) where it give off branches involved in hearing and taste. The trigeminal nerve innervates the muscles of mastication (temporalis and masseter) and sensation to the face (see Fig. 16–2) In general, nerve injury due to penetrating trauma requires acute repair. Blunt traumatic injuries with associated fractures (e.g., temporal bone) may require decompression or may be managed conservatively depending upon the presence of associated facial injuries. In some instances, surgeons may base their decision to operate on the extent of injury noted during electrodiagnostic testing. PAROTID DUCT

Summary Oral, facial, and ocular injuries are common injuries that are easily overlooked. Clinical evaluation requires knowledge of important anatomic landmarks. While the clinical evaluation of infants and children with facial fractures can be difficult, CT is the ideal imaging study for evaluating children with potential fractures. Play, sports, and motor vehicle accidents are common causes of facial trauma in children. However, clinicians must consider and exclude the diagnosis of abuse in all cases. Importantly, patients with closed injuries and no functional deficit (e.g., visual loss, sensory/motor loss, malocclusion) usually require no acute intervention. Unless they are open, most facial fractures that are displaced or comminuted or that result in a functional deformity may wait until swelling subsides (2 to 4 days) before undergoing surgery. REFERENCES 1. Gassner R, Tuli T, Hachl O, et al: Craniomaxillofacial trauma in children: a review of 3,385 cases with 6,060 injuries in 10 years. J Oral Maxillofac Surg 62:399–407, 2004. 2. Tanaka N, Uchide N, Suzuki K, et al: Maxillofacial fractures in children. J Craniomaxillofac Surg 21:289–293, 1993. 3. Holland AJ, Broome C, Steinberg A, Cass DT: Facial fractures in children. Pediatr Emerg Care 17:157–160, 2001. 4. Ferreira PC, Amarante JM, Silva PN, et al: Retrospective study of 1251 maxillofacial fractures in children and adolescents. Plast Reconstr Surg 115:1500–1508, 2005.

Chapter 16 — Oral, Ocular, and Maxillofacial Trauma 5. Cairns AM, Mok JY, Welbury RR: Injuries to the head, face, mouth, and neck in physically abused children in a community setting. Int J Paediatr Dent 15:310–318, 2005. 6. Zerfowski M, Bremerich A: Facial trauma in children and adolescents. Clin Oral Invest 2:120–124, 1998. 7. Lim LH, Kumar M, Myer CM 3rd: Head and neck trauma in hospitalized pediatric patients. Otolaryngol Head Neck Surg 130:255–261, 2004. 8. Gussack GS, Luterman A, Powell RW, et al: Pediatric maxillofacial trauma: unique features in diagnosis and treatment. Laryngoscope 97(8 Pt 1):925–930, 1987. 9. Kaban LB: Diagnosis and treatment of fractures of the facial bones in children 1943–1993. J Oral Maxillofac Surg 51:722–729, 1993. 10. Koltai PJ, Rabkin D, Hoehn J: Rigid fi xation of facial fractures in children. J Craniomaxillofac Trauma 1:32–42, 1995. 11. McGraw BL, Cole RR: Pediatric maxillofacial trauma. Arch Otolaryngol Head Neck Surg 116:41–45, 1990. 12. Rowe NL: Fractures of the facial skeleton in children. J Oral Surg 26:505–515, 1967. 13. Koltai PJ, Amjad I, Meyer D, et al: Orbital fractures in children. Arch Otolaryngol Head Neck Surg 121:1375–1379, 1995. 14. Hogg NJV, Horswell BW: Soft tissue pediatric facial trauma: a review. J Can Dent Assoc 72:549–552, 2006. 15. Alonso LL, Purcell TB: Accuracy of the tongue blade test in patients with suspected mandibular fracture. J Emerg Med 13:297–304, 1995. 16. Sinclaire D, Schwartz M, Gruss J, McLellan B: A retrospective review of the relationships between facial fractures, head injuries and cervical spine injuries. J Emerg Med 6:109–112, 1988. 17. Koltai PJ, Wood GW: Three-dimensional CT reconstruction for the evaluation and surgical planning of facial fractures. Otolaryngol Head Neck Surg 95:10–15, 1986. 18. Lambert DM, Mirvis SE, Shanmuganathan K, Tilghman DL: Computed tomography exclusion of osseous paranasal sinus injury in blunt trauma patients: the clear sinus sign. J Oral Maxillofac Surg 55:1207– 1211, 1997. 19. Holmgren EP, Dierks EJ, Assael LA, et al: Facial soft tissue injuries as an aid to ordering a combination head and facial computed tomography in trauma patients. J Oral Maxillofac Surg 63:651–654, 2005. 20. Exadatylos AK, Sclabas GM, Smolka K, et al: The value of computed tomographic scanning in the diagnosis and management of orbital fractures associated with head trauma: a prospective, consecutive study at a level I trauma center. J Trauma 58:336–341, 2005. 21. Holmgren EP, Dierks EJ, Homer LD, Potter BE: Facial computed tomography use in trauma patients who require a head computed tomogram. J Oral Maxillofac Surg 62:913–918, 2004. 22. Rehm CG, Ross SE: Diagnosis of unsuspected facial fractures on routine head computerized tomographic scans in the unconscious multiply injured patient. J Oral Maxillofac Surg 53:522–524, 1995. 23. Boidin MP: Airway patency in the unconscious patient. Br J Anaesth 57:306–310, 1985. 24. Nandi PR, Charlesworth CH, Taylor SJ, et al: Effect of general anaesthesia on the pharynx. Br J Anaesth 66:157–162, 1991. 25. Abernethy LJ, Allan PL, Drummond GB: Ultrasound assessment of the position of the tongue during induction of anaesthesia. Br J Anesth 65:744–748, 1990.

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26. Zimmerman CE, Troulis MJ, Kaban LB: Pediatric facial fractures: recent advances in prevention, diagnosis and management. Int J Oral Maxillofac Surg 35:2–13, 2006. 27. Stucker FJ, Bryarly RC, Shockley WW: Management of nasal trauma in children. Arch Otolaryngol 110:190, 1984. 28. Apt L, Sarin LK: Causes for enucleation of the eye in infants and children. JAMA 181:948, 1962. 29. Macewen CJ: Eye injuries: a prospective survey of 5671 cases. Br J Ophthalmol 73:888, 1989. 30. Strahlman E, Elman M, Daub E, Baker S: Causes of pediatric eye injuries: a population-based study. Arch Ophthamol 108:603–606, 1990. 31. Blaivas M, Theodoro D, Sierzenski PR: A study of bedside ocular ultrasonography in the emergency department. Acad Emerg Med 9:791–799, 2002. 32. Mafee MF, Mafee RF, Malik M, Pierce J: Medical imaging in pediatric ophthalmology. Pediatr Clin North Am 50:259–286, 2003. 33. Joseph DP, Pieramici DJ, Beauchamp NJ: Computed tomography in the diagnosis and prognosis of pen globe injuries. Ophthalmology 107:1899–1906, 2000. 34. Rhea JT: Helical CT and 3-dimensional CT of facial and orbital injury. Radiol Clin North Am 37:489–513, 1999. 35. Grant JH III, Patrinely JR, Weiss AH, et al: Trapdoor fracture of the orbit in a pediatric population. Plast Reconstr Surg 109:482–489, 2002. 36. Bansagi ZC, Meyer DR: Internal orbital fractures in the pediatric age group: characterization and management. Ophthalmology 107:829– 836, 2000. 37. Egbert JE, May K, Kersten RC, Kulwin DR: Pediatric orbital floor fracture: direct extraocular muscle involvement. Ophthalmology 107:1875–1879, 2000. 38. Lee HJ, Jilani M, Frohman L, Baker S: CT of orbital trauma. Emerg Radiol 10:168–172, 2004. 39. Chidiac EJ, Raiskin AO: Succinylcholine and the open eye. Ophthalmol Clin North Am 19:279–285, 2006. 40. Pieramici DJ: Vitreoretinal trauma. Ophthalmol Clin North Am 15:225–234, 2002. 41. Kuhn F, Mester V: Anterior chamber abnormalities and cataract. Ophthalmol Clin North Am 15:195–203, 2002. 42. Dhillon B, Fleck B: Disease of the eye and orbit. In Barnard S, Edgar D (eds): Pediatric Eye Care. Cambridge: Blackwell Sciences, 1996, pp 243–267. 43. Levin AV: Eye emergencies: acute management in the pediatric ambulatory care setting. Pediatr Emerg Care 7:367–377, 1991. 44. Clemons CS, Cohen EJ, Arentsen JJ, et al: Pseudomonas ulcers following patching of corneal abrasions associated with contact lens wear. CLAO J 13:161–164, 1987. 45. Michael JG, Hug D, Dowd MD: Management of corneal abrasion in children: a randomized clinical trial. Ann Emerg Med 40:67–72, 2002. 46. Long J, Tann T: Adnexal trauma. Ophthalmol Clin North Am 15:179– 184, 2002. 47. Park SS, Hood RJ: Management of facial cutaneous defects. Part II: auricular reconstruction. Otolaryngol Clin North Am 34:713–738, 2001.

Chapter 17 Head Trauma Vincent J. Grant, MD

Key Points Head trauma is common and a significant source of pediatric morbidity and mortality. Injury prevention is the only intervention that can minimize primary traumatic brain injury. The main goals of the emergency department management of head-injured children are to identify serious intracranial injuries and minimize secondary traumatic brain injury. Signs and symptoms of head injury do not correlate well with the risk of intracranial injuries. In the evaluation of most head-injured children, the greatest challenge is deciding when it is safe to evaluate these children without performing computed tomographic scanning of the head.

Introduction and Background Emergency physicians treat children with head injuries every day.1,2 These injuries range from trivial to fatal. Along this severity spectrum, many management issues and controversies arise. Familiarity with these issues and controversies allows emergency physicians to make rational and reasoned decisions in the face of conflicting or absent evidence. One approach to categorizing head injuries is to group them according to the patient’s Glasgow Coma Scale score3 (Table 17–1). According to this scheme, children with mild injuries have Glasgow Coma Scale scores of 13, 14, and 15; those with moderate injuries have scores from 9 to 12; and those with severe injuries have a score of 8 or less.4 Although relatively simple in concept, there are several problems with this approach. The Glasgow Coma Scale score seems to have only modest interrater reliability.5 This calls into question the reproducibility of studies based on this categorization scheme. In addition, Glasgow Coma Scale scores do not adequately correlate with intracranial injuries identified on computed tomographic (CT) scanning of the head.6 This suggests that this categorization scheme is not a valid surrogate for brain injuries. The Glasgow Coma Scale was intended for use 164

in the era before the widespread availability of CT scanning. To consider a patient with a completely normal evaluation (Glasgow Coma Scale score 15) and a patient who is confused and localizes pain (Glasgow Coma Scale score 13) to both have the same category of head injury is counterintuitive. Nonetheless, this categorization scheme is commonly used. There have been modifications to the Glasgow Coma Scale to make it more applicable to children.7,8 These modified scoring systems have the same problems as the original.

Recognition and Approach Traumatic brain injury is the leading cause of death and disability in pediatric trauma.9-11 In the United States, traumatic brain injury accounts for approximately 3000 deaths, 50,000 hospitalizations and 650,000 emergency department visits annually.12,13 Most children have a greater propensity for head injuries than most adults. Children tend to have proportionately larger heads, relatively weaker neck musculature, and less refined coordination than adults. In addition, they participate in different daily activities, are less inclined to understand and use safety equipment, have underdeveloped judgment, and may lack the required supervision to keep them safe. Infants, in particular, are at risk for nonaccidental trauma and have relatively thin skulls (see Chapter 119, Physical Abuse and Child Neglect). The mechanisms of injury for pediatric head injuries are age dependent. The majority of accidental head injuries in younger children are due to falls and motor vehicle accidents. Adolescents are more likely to have injuries related to sporting or recreational activities, although motor vehicle accidents are also a frequent cause of head injuries in this age group. Penetrating head injuries are relatively rare in children and uncommon in most populations of adolescents. Gang activities in some adolescents increases the risk of penetrating head injuries (see Chapter 157, Interpersonal and Intimate Partner Violence). One conceptually simple approach to traumatic brain injuries categorizes them as either primary or secondary. Primary brain injury occurs at the time of the injury. At the time of impact, cellular and structural damage occurs. We currently have no effective treatments for primary brain injuries. The only effective intervention yet to be identified is injury prevention.14 Effective interventions include laws mandating the use of seat belts, car seats, and bicycle helmets.15,16 Although emergency physicians can play an important role in promoting injury prevention, this does not

Chapter 17 — Head Trauma

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help the child who presents having already sustained a head injury. Secondary brain injury occurs after the time of the initial impact. The major causes of secondary brain injury include hypoxia, hypotension, and intracranial hypertension.17 Examples of secondary brain injury include anoxic brain injury from hypoxia that occurs after an injury or brain herniation due to an expanding intracranial hemorrhage or brain swelling. Left untreated, secondary brain injury can lead to progressive neurologic deterioration and death. Prehospital and emergency department care is directed at minimizing secondary brain injury.

a practice guideline for infants and young children determined that loss of consciousness and vomiting did not correlate with clinically significant findings on CT scanning.26 Strangely, this group acknowledged this and yet still recommended CT scanning for children who lost consciousness for greater than 1 minute or who vomited five or more times.26 One group suggested that infants could present in an “occult” manner without appreciable signs or symptoms of head injury.27 Another group disputed the existence of “occult” head injuries.21 The reasons for the variability in the findings of these studies are not entirely clear. It is conceivable that the heterogeneity of the injury types, the ages and development of the children in the study populations, and the outcomes of interest led to conflicting and confusing results. The greatest advances in evaluating children with head injuries are in imaging. CT scanning has had the greatest impact. The decision about when to obtain a CT scan, however, is not always clear. The greatest controversy exists for those children at the less severe end of the injury spectrum. It is clear that a traumatized, comatose child requires CT scanning of the head. At the other end of the severity spectrum, the decision on when to perform CT scanning is controversial. It is probably reasonable to perform CT scanning on children who have abnormal mental status and infants with relatively large scalp hematomas.23,24,28-31 Isolated, brief loss of consciousness is probably not an indication for CT scanning.20 Beyond that, it is difficult to universally define when CT scanning is indicated. There is no role for skull radiographs in the identification of intracranial injuries as the intracranial contents are not seen on plain radiographs. Since intracranial injuries occur in the absence of skull fractures, skull radiographs poorly risk-stratify children for the presence of intracranial injuries. Magnetic resonance imaging is currently too time consuming for the evaluation of acutely injured children in the emergency department.32

Evaluation

Management

Several intuitively appealing signs and symptoms that potentially predict the presence of a clinically significant head injury have been studied. These include abnormal mental status, loss of consciousness, amnesia to the event, a Glasgow Coma Scale score less than 15, skull fracture, scalp hematoma, a focal neurologic examination, irritability, a bulging fontanelle, vomiting, seizure, and headache.18-22 One meta-analysis found that loss of consciousness, skull fracture, focal neurologic signs, and a Glasgow Coma Scale score less than 15 are strong risk factors for intracranial injuries.23 Another group found that loss of consciousness, amnesia to the event, or both did not correlate with traumatic brain injuries on CT scanning.24 The NEXUS II investigators took another approach.22,25 This group suggested that, if the following seven criteria were not present, the risk of clinically significant intracranial injury was very low: (1) evidence of significant skull fracture, (2) altered level of alertness, (3) neurologic deficit, (4) persistent vomiting, (5) presence of scalp hematoma, (6) abnormal behavior, and (7) coagulopathy.22 The implication, of course, is that if these seven criteria are not present, CT scanning is not needed. Although the authors note that their decision criteria worked well in children younger than 3 years of age, the number of these young children in this study was small. After reviewing the available literature, one group proposing

Management of head-injured children is directed at specific findings on physical examination and CT scanning results. The management of head-injured children needs to take into account the possibility of multisystem trauma and follow general principles of resuscitating children (see Chapter 1, Approach to Resuscitation and Advanced Life Support for Infants and Children; Chapter 3, Rapid Sequence Intubation; and Chapter 12, Approach to Multisystem Trauma). There has been some interest in using controlled hypothermia to treat severe brain injuries. Laboratory studies have shown that moderate hypothermia decreases neuronal loss, decreases excessive neurotransmitter release, and prevents disruption of the blood-brain barrier.33 Hypothermia has not been adequately studied to recommend it at this time. More detailed basic and advanced cerebral resuscitation techniques are described in detail elsewhere (see Chapter 9, Cerebral Resuscitation).

Table 17–1

Glasgow Coma Score Scale Score

Eye Opening Spontaneous To verbal stimulation To painful stimulation No eye opening Motor Obeys commands Localizes pain Withdraws to pain Flexion posturing Extension posturing No motor response Verbal Alert and oriented Confused Inappropriate language Incoherent language No verbal response

4 3 2 1 6 5 4 3 2 1 5 4 3 2 1

From Teasdale G, Jennett B: Assessment of coma and impaired consciousness: a practical scale. Lancet 2:81–84, 1974.

Impending Herniation In severely head injured children there is the possibility of impending brain herniation. This is usually evident on physical examination by the presence of a bulging fontanelle, unequal or fi xed and dilated pupils, and posturing or coma. If the child is hemodynamically stable enough to undergo CT

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scanning, the scan may reveal intracranial bleeding or diffuse axonal injury. Diffuse axonal injury is the proposed mechanism for patients who suffer severe closed head injury without the presence of obvious macroscopic intracranial injuries, such as contusion, hematoma, or cerebral edema on CT scanning.34 A few interventions have been recommended for decreasing intracranial hypertension. One is elevation of the head of the bed 30 degrees.35 This has been recommended for children, but has not been studied in children. Although generally recommended several years ago, hyperventilation is to be avoided as it is now thought to lead to intracranial blood vessel constriction and brain ischemia.36,37 Instead of the traditional mannitol used to treat adults, the use of 3% hypertonic saline (which can be given as a bolus of 3 ml/kg intravenously) is gaining acceptance as a means of treating and preventing intracranial hypertension38,39 (see Chapter 9, Cerebral Resuscitation). Scalp Injuries Although it is a highly vascular structure that bleeds profusely when injured, the scalp is underestimated in its contribution to head injury morbidity. In young infants, scalp injuries, with or without an opening in the skin, can cause deterioration from hemorrhagic shock.19,40 In particular, a subgaleal hematoma in an infant may be a significant source of hypovolemia from scalp hemorrhage without any signs of external bleeding. Skull Fractures There are four main types of skull fractures: linear, depressed, diastatic, and basilar. Linear skull fractures are the most common type of fracture seen in pediatrics, comprising approximately 75% to 90% of all fractures.19 A depressed skull fracture includes any skull fracture in which the bone fragment is depressed below the inner table of the skull. A depressed skull fracture typically requires operative elevation if it is depressed to a depth greater than the thickness of the skull.19 Diastatic fractures involve sutures. One common complication of both depressed and diastatic fractures is the leptomeningeal cyst or “growing” fracture. This complication arises when a tear in the dura allows the arachnoid membrane to penetrate the fracture, leading to demineralization of the bone fragments at the fracture site and penetration of cerebrospinal fluid into the subarachnoid space.41 Healing is impaired, and therefore necessitates careful followup, with surgical repair being occasionally required if the fracture continues to “grow” 2 to 3 months following the injury. Basilar skull fractures account for up to 20% of all skull fractures, and classically have distinctive clinical features, including periorbital ecchymosis (“raccoon eyes”), postauricular mastoid ecchymosis (Battle’s sign), hemotympanum, and cerebrospinal fluid rhinorrhea or otorrhea. In these cases, ecchymosis is not typically present on presentation to the emergency department. Complications of basal skull fractures include facial nerve palsy, cerebrospinal fluid fistulas, and meningitis. Antibiotic prophylaxis for basilar skull fractures is not recommended as this may lead to subsequent meningitis with resistant bacteria.19 Intracranial Hemorrhages Intracranial hemorrhages represent the most common lifethreatening complications of head injuries. As a group, these

injuries occur in up to 12% of patients with mild head injuries alone.41 Early diagnosis of intracranial hemorrhage is essential to allow identification of the subgroup that requires prompt neurosurgical management. Intracranial hemorrhages can be divided into four main types: parenchymal contusions, epidural hematomas, subdural hematomas, and subarachnoid hemorrhages. Parenchymal contusions develop as a result of direct impact between the brain and the overlying skull, causing a focal area of bruising, hemorrhage, and edema. Contusions are either caused by abrupt acceleration of the head, causing a “coup” injury on the same side as impact, or by abrupt deceleration of the head, causing a “contrecoup” injury on the opposite side from impact. Immediate surgical intervention is not usually indicated for parenchymal contusions. Epidural hematomas are collections of blood between the skull and the dura of the brain. Because the dura is tightly adhered to the skull in certain areas, the collection of hemorrhage grows in a characteristic lens-shaped pattern. The vessel injury in question can be either arterial or venous, but the most significant injuries are from arterial injury, typically the middle meningeal artery. There may be an associated skull fracture. The clinical presentation may lead to false reassurance, because the typical presentation usually includes a lucid interval of time between the initial injury and rapid neurologic deterioration associated with rapid expansion of the hematoma. Small epidural hematomas have been shown to occur after minor head trauma in alert children with no focal neurologic signs.42 Larger epidural hematomas usually require urgent neurosurgical intervention.31 Prognosis is excellent with early treatment.31 Subdural hematomas are collections of blood between the dura and the arachnoid membrane. This hemorrhage is most commonly a result of torn bridging veins in the subdural space, that present as crescent-shaped lesions on CT. Typically, these lesions are not associated with skull fractures, and occur most often as a result of rapid acceleration/deceleration.43 Compared to epidural hematomas, subdural hematomas are less amenable to neurosurgical intervention, and outcomes may be poor, with up to 50% of patients developing profound disabilities regardless of the treatment provided.43 Subarachnoid hemorrhage occurs as a result of damage to superficial vessels running along the surface of the brain, underneath the arachnoid membranes. The blood is irritating to the meninges, sometimes causing nuchal rigidity and severe headache. These lesions can result in vasospasm and further ischemic injury, but rarely require acute intervention. Posttraumatic Seizures Posttraumatic seizures occur in as many as 5% to 10% of all head-injured children. The timing of the seizures is classified as immediate, early, and late. Immediate posttraumatic seizures occur at the time of injury, and are thought to be due to instant depolarization of the cortex in response to the injury. This type of seizure generally does not recur. These “impact seizures” are not predictive of clinically significant intracranial injuries, nor do they require any specific treatment or imaging. In contrast, early seizures occur after the impact, but within 24 hours of the injury. Early seizures are more likely to be a manifestation of an intracranial injury and therefore warrant imaging. Late seizures occur greater than 1 week after injury and are a result of scarring and

Chapter 17 — Head Trauma

mechanical irritation of the brain.41 The routine use of prophylactic antiepileptic medications after minor head injuries is not necessary.41,44 Children with repeated seizures or those in status epilepticus require prompt management of their seizures (see Chapter 40, Seizures). Transient Cortical Blindness and TraumaTriggered Migraine Since the mid-1960s, with Bodian’s original description of six children who had transient loss of vision for a few hours following trauma, transient cortical blindness has been recognized as a complication of head trauma.45-49 Traumatic cortical blindness is typically seen in children and young adults who have sustained minor head injury, brief or no loss of consciousness, blindness occurring within hours of the head injury, normal pupils and fundi, and a normal CT scan of the head.50 Particularly in the young child with limited language skills, assessing blindness may be exceedingly difficult and the patient may simply exhibit anxiety and agitation.51 There appears to be some overlap with transient cortical blindness and what has been called “traumatriggered migraine.”52,53 In these cases, a child sustains a blow to the head and then has a clinical presentation like that of a classic or complicated migraine (see Chapter 41, Headaches). Visual disturbances include scintillating scotoma, homonymous hemianopia, blurred vision, tunnel vision, or transient blindness. These symptoms usually resolve and are then replaced by headache, nausea, and vomiting. The patient may exhibit confusion or incoherence, paresthesias, dysphasia, and hemiparesis. Children may become agitated and combative.52 The etiology of transient cortical blindness and trauma-triggered migraine is unknown. Theories to explain these events have centered on vasospasm and localized cerebral edema.54 Although β-blocker therapy has been considered a treatment for posttraumatic migraines, there is currently no standard treatment.53

Summary The disposition and prognosis for head-injured children is dependent on the type and degree of injury. Most children who have negative CT scans and have resolution of their symptoms in the emergency department can be safely discharged home. There is no need for awakening the child throughout the night as the likelihood of a missed clinically significant intracranial injury is very low. Exceptions to this include hemophiliacs and children on warfarin, in whom the risk of a delayed bleed is much greater. Children who are awake and have small intracranial bleeds may be admitted or transferred to a facility with a pediatric neurosurgeon and a monitored intensive care area. Severely injured children will require admission or transfer to a pediatric intensive care unit for pediatric neurosurgical evaluation. An area of some controversy is the management of child diagnosed with a concussion who has a normal CT scan of the head. A concussion is a transient alteration in mental status following a blow to the head. The main controversy surrounds the decision as to when a child may return to sporting activities. There are no evidence-based guidelines; however, there are some consensus-based recommendations.55 For children who experience transient confusion with resolution of symptoms within 15 minutes and without

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loss of consciousness, the recommendation is to have the child be immediately removed from play and return to play if his or her mental status is normal after 15 minutes on the sidelines. For children who experience transient confusion for longer than 15 minutes without loss of consciousness, the recommendation is to have the child sit out for the rest of the day and return to play in 1 week if the neurologic examination is normal at that point. For children who experience any loss of consciousness, the recommendation is for removal from play for 1 week if the loss of consciousness lasts for a few seconds or 2 weeks if the loss of consciousness lasts longer than that. For these children, the child needs to be asymptomatic at rest and with exertion to return to play after sitting out for a week or two. Survivors of traumatic brain injury are at increased risk for long-term neuropsychological deficits in the areas of verbal reasoning, learning and recall, attention, executive functions, and constructional skills. If these functions recover, the recovery period may last years.56 Children with traumatic brain injuries are also at risk of psychiatric disturbances, such as major depression and anxiety disorders, attention-deficit/hyperactivity disorder, and organic personality disorder.57,58 REFERENCES 1. Jager TE, Weiss HB, Coben JH, et al: Traumatic brain injuries evaluated in U.S. emergency departments, 1992–1994. Acad Emerg Med 7:134– 140, 2000. 2. Thurman DJ, Alverson C, Dunn KA, et al: Traumatic brain injury in the United States: a public health perspective. J Head Trauma Rehabil 14:602–615, 1999. 3. Teasdale G, Jennett B: Assessment of coma and impaired consciousness: a practical scale. Lancet 2:81–84, 1974. 4. Kraus JF, Fife D, Conroy C: Pediatric brain injuries: the nature, clinical course, and early outcomes in a defi ned United States population. Pediatrics 79:501–507, 1987. 5. Gill MR, Reiley DG, Green SM: Interrater reliability of Glasgow Coma Scale scores in the emergency department. Ann Emerg Med 43:215– 223, 2004. 6. Ratan SK, Pandey RM, Ratan J: Association among duration of unconsciousness, Glasgow Coma Scale, and cranial computed tomography abnormalities in head-injured children. Clin Pediatr 40:375–378, 2001. 7. Durham SR, Clancy RR, Leuthardt E, et al: CHOP infant coma scale (Infant Face Scale): a novel coma scale for children less than two years of age. J Neurotrauma 17:729–737, 2000. 8. Hahn YS, Chyung C, Barthel MJ, et al: Head injuries in children under 36 months of age. Childs Nerv Syst 4:34–49, 1988. 9. National Vital Statistics System: Ten Leading Causes of Death, United States 1999. Atlanta, GA: National Center for Injury Prevention and Control, 1999. 10. Hoyert DL, Arias E, Smith B, et al: Final Data for 1999: National Vital Statistics Reports, Vol 49. Hyattsville, MD: National Center for Health Statistics, 2001. 11. National Center for Injury Prevention and Control: Traumatic Brain Injury in the United States: A Report to Congress. Atlanta: Centers for Disease Control and Prevention, 1999. 12. Centers for Disease Control and Prevention: 2000 National Hospital Ambulatory Medical Care Survey, Emergency Department File 2002 [on CD-ROM]. Vital Health Stat 13(33):1. 13. National Center for Injury Prevention and Control: Traumatic Brain Injury in the United States: Assessing Outcomes in Children. Atlanta, GA: Centers for Disease Control and Prevention, 2002. 14. McCaig LF, Burt CW: National Hospital Ambulatory Medical Care Survey: 2002 Emergency Department Summary. Adv Data 340:1. 15. National Center for Health Statistics: Healthy People 2010: Focus Area 15: Injury and Violence Prevention. Hyattsville, MD: Public Health Service, 2004.

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16. National Center for Health Statistics: Healthy People 2000 Final Review. Hyattsville, MD: Public Health Service, 2001. 17. Kokoska ER, Smith GS, Pittman T, et al: Early hypotension worsens neurological outcome in pediatric patients with moderately severe head trauma. J Pediatr Surg 33:333–338, 1998. 18. Quayle KS, Jaffe DM, Kuppermann N, et al: Diagnostic testing for acute head injury in children: when are computed tomography and skull radiographs indicated? Pediatrics 99:e11, 1997. 19. Woestman R, Perkin R, Serna T, et al: Mild head injury in children: identification, clinical evaluation, neuroimaging, and disposition. J Pediatr Health Care 12:288–298, 1998. *20. American Academy of Pediatrics; Commission on Clinical Policies and Research, American Academy of Family Physicians: The management of minor closed head injury in children. Pediatrics 104:1407– 1415, 1999. 21. Brown L, Moynihan JA, Denmark TK: Blunt pediatric head trauma requiring neurosurgical intervention: how subtle can it be? Am J Emerg Med 21:467–472, 2003. 22. Oman JA, Cooper RJ, Holmes JF, et al: Performance of a decision rule to predict need for computed tomography among children with blunt head trauma. Pediatrics 117:238–246, 2006. *23. Dunning J, Batchelor J, Stratford-Smith P, et al: A meta-analysis of variables that predict significant intracranial injury in minor head trauma. Arch Dis Child 89:653–659, 2004. *24. Palchak MJ, Holmes JF, Vance CW, et al: A decision rule for identifying children at low risk for brain injuries after blunt head trauma. Ann Emerg Med 42:492–506, 2003. 25. Mower WR, Hoffman JR, Herbert M, et al, for the NEXUS II Investigators: Developing a decision instrument to guide computed tomographic imaging of blunt head injury patients. J Trauma 59:954–959, 2005. *26. Schutzman SA, Barnes P, Duhaime AC, et al: Evaluation and management of children younger than two years old with apparently minor head trauma: proposed guidelines. Pediatrics 107:983–993, 2001. 27. Greenes DS, Schulzman SA: Occult intracranial injury in infants. Ann Emerg Med 32:680–686, 1998. 28. Greenes DS, Schutzman SA: Clinical indicators of intracranial injury in head-injured infants. Pediatrics 104:861–867, 1999. 29. Gruskin KD, Schulzman SA: Head trauma in children younger than 2 years: are there predictors for complications? Arch Pediatr Adolesc Med 153:15–20, 1999. *30. Haydel MJ, Shembekar AD: Prediction of intracranial injury in children aged five years and older with loss of consciousness after minor head injury due to nontrivial mechanisms. Ann Emerg Med 42:507– 514, 2003. 31. Beni-Adani L, Flores I, Spektor S, et al: Epidural hematoma in infants: a different entity? J Trauma 46:306–311, 1999. 32. American Academy of Pediatrics, Section on Radiology: Diagnostic imaging of child abuse. Pediatrics 105:1345–1348, 2000. *33. Enrione MA: Current concepts in the acute management of severe pediatric head trauma. Clin Pediatr Emerg Med 2:28–40, 2001. 34. Mittl RL, Grossman RI, Hichle JF, et al: Prevalence of MR evidence of diffuse axonal injury in patients with mild traumatic brain injury and normal head CT fi ndings. Am J Neuroradiol 15:1583–1589, 1994. 35. Feldman Z, Kanter MJ, Robertson CS, et al: Effect of head elevation on intracranial pressure, cerebral perfusion pressure, and cerebral blood flow in head-injured patients. J Neurosurg 76:207–211, 1992. *Selected readings.

36. Skippen P, Seear M, Poskitt K, et al: Effect of hyperventilation on regional cerebral blood flow in head-injured children. Crit Care Med 25:1402–1409, 1997. 37. Sharples PM, Stuart AG, Matthews DS, et al: Cerebral blood flow and metabolism in children with severe head injury. Part 1: Relation to age, Glasgow coma score, outcome, intracranial pressure, and time after injury. J Neurol Neurosurg Psychiatry 58:145–158, 1995. 38. Khanna S, Davis D, Peterson B, et al: Use of hypertonic saline in the treatment of severe refractory posttraumatic intracranial hypertension in pediatric traumatic brain injury. Crit Care Med 28:1144–1151, 2000. 39. Peterson B, Khanna S, Fisher B, et al: Prolonged hypernatremia controls elevated intracranial pressure in head-injured pediatric patients. Crit Care Med 28:1136–1143, 2000. 40. Meyer P, Legros C, Orliaguet G: Critical care management of neurotrauma in children: new trends and perspectives. Childs Nerv Syst 15:732–739, 1999. 41. Savitsky EA, Votey SR: Current controversies in the management of minor pediatric head injuries. Am J Emerg Med 18:96–101, 2000. 42. Schutzman SA, Barnes PD, Mantello M, et al: Epidural hematoma in children. Ann Emerg Med 22:535–541, 1993. 43. Jayawant S, Rawlinson A, Gibbon F, et al: Subdural hemorrhage in infants: population based study. BMJ 317:1558–1561, 1998. 44. Dias MS, Carnevale F, Li V: Immediate posttruamtic seizures: is routine hospitalization necessary? Pediatr Neurosurg 30:232–238, 1999. 45. Bodian M: Transient loss of vision following head trauma. N Y State J Med 64:916–920, 1964. 46. Harrison DW, Walls RM: Blindness following minor head trauma in children: a report of two cases with a review of the literature. J Emerg Med 8:21–24, 1990. 47. Rodriguez A, Lozano JA, del Pozo D, et al: Post-traumatic transient cortical blindness. Int Ophthalmol 17:277–283, 1993. 48. Eldridge PR, Punt JA: Transient traumatic cortical blindness in children. Lancet 1:815–816, 1988. 49. Gleeson AP, Beatrie TF: Post-traumatic transient cortical blindness in children: a report of four cases and a review of the literature. J Accid Emerg Med 11:250–252, 1994. 50. Yamamoto LG, Bart RD: Transient blindness following mild head trauma: criteria for benign outcome. Clin Pediatr 27:479–483, 1988. 51. Woodward GA: Posttraumatic cortical blindness: are we missing the diagnosis in children? Pediatr Emerg Care 6:289–292, 1990. 52. Haas DC, Lourie H: Trauma-triggered migraine: an explanation for common neurological attacks after mild head injury. J Neurosurg 68:181–188, 1988. 53. Hochstetler K, Beals RD: Transient cortical blindness in a child. Ann Emerg Med 16:218–219, 1987. 54. Ferrera PC, Reicho PR: Acute confusional migraine and trauma-triggered migraine. Am J Emerg Med 14:276–278, 1996. 55. Practice parameter: The management of concussion in sports (summary statement)—report of the Quality Standards Subcommittee. Neurology 48:581–585, 1997. 56. Yeates KO, Taylor HG, Wade SI, et al: A prospective study of short and long-term neuropsychological outcomes after traumatic brain injury in children. Neuropsychology 16:514–523, 2002. 57. Swift EE, Taylor HG, Kaugars AS, et al: Sibling relationships and behavior after pediatric traumatic brain injury. J Dev Behav Pediatr 24:24– 31, 2003. 58. Wase SL, Taylor HG, Drotar D, et al: Family burden and adaptation during the initial year after traumatic brain injury in children. Pediatrics 102:110–116, 1998.

Chapter 18 Neck Trauma Jan M. Shoenberger, MD and William K. Mallon, MD

Key Points Early definitive airway management with rapid sequence intubation can be lifesaving in blunt and penetrating neck trauma. Identifying the zone of injury (I, II, and III) is important for determining the appropriate management plan. Penetrating facial trauma below the horizon of the pupils may result in zone III neck injuries. Neurologic deficits, even if transient, suggest a vascular or spinal cord injury.

Introduction and Background The mechanisms of injury for cases of pediatric neck trauma are numerous and heterogeneous. The most common cause of both penetrating and blunt neck injuries is motor vehicle accidents. Penetrating injuries occur most frequently in adolescents, including accidental injuries and injuries received when they are victims of violent crime.1,2 Penetrating neck wounds from impalement, dog and human bites, and fireworks are also reported.3-5 Mechanisms of injury causing blunt neck trauma include bicycle injuries, sports injuries, falls, near-hangings, and scooter and in-line skating injuries.6-14 Trampoline use is associated with both neck injuries and cervical spine injuries15,16 (see Chapter 23, Spinal Trauma).

Recognition and Approach Neck anatomy is complex, with many vital structures contained within a relatively small, flexible space. To describe neck injuries, a commonly accepted approach is to divide the neck into three anatomic zones designated I, II, and III (Fig. 18–1). The numbering is somewhat counterintuitive, with zone III being the most cephalad. Zone I extends inferiorly from the cricoid cartilage to the clavicles. Injuries in this region carry a higher mortality because they can involve major vessels, lung apices, and the esophagus, trachea, thyroid structures, and thoracic duct. Zone I is difficult to access

surgically. Zone II consists of the area between the cricoid cartilage and the angle of the mandible. Zone II is where the majority of neck wounds occur. The major structures in zone II include the trachea, esophagus, larynx, spinal cord, jugular veins, and carotid arteries. Injuries in zone II carry a lower mortality. The assessment and surgical management of zone II neck injuries is easier than that in the other two zones due to the absence of bony obstruction. Zone III comprises the area between the angle of the mandible and the base of the skull. The major structures in zone III include the pharynx, jugular veins, and vertebral and carotid arteries. Penetrating facial trauma as high as the horizon of the pupils may result in zone III neck injuries. Injuries to the spinal cord may occur in conjunction with injuries to any zone. Zone II injuries account for about 50% of neck injuries, with zones I and III accounting for about 25% each.17,18 The neck can also be divided into anterior and posterior triangles. Wounds in the anterior and lateral aspects of the neck pose the greatest threat to a patient’s airway because of their proximity to the trachea, larynx, laryngeal nerves, and vessels of the neck.19 Trauma involving the area posterior to the trapezius ridge is the least likely to involve vital structures. The neck is a three-dimensional structure, and the apparent depth of wounds contributes to the overall assessment and management plan. For example, for anterior penetrating wounds, if the platysma muscle has been violated, the management approach is much more aggressive than if it has not been violated. The anatomic relationships in the pediatric neck differ from those seen in adults (Table 18–1). Because the pediatric neck is much shorter, the zones of the neck are less distinct; thus the surgeon will have less operative exposure. The vascular structures are proportionately larger and have less muscle and soft tissue protection than seen in most adults. Compared with adults, hematomas may expand and extend more rapidly in children due to greater tissue pliability. The larynx is in a more anterior position and the trachea is shorter.20 A smaller mandible and chin result in children being less likely to “take it on the chin.” The pediatric airway is more flexible and has bulkier adjacent soft tissues, increasing the potential for early obstruction.21

Evaluation The prehospital care phase should include consideration of cervical immobilization. Clinical experience suggests that 169

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Table 18–1

Characteristics of the Pediatric Neck

Anterior airway Indistinct transitions between the zones of the neck Obscured laryngeal landmarks Relatively small chin Short neck Small cricothyroid membrane Small muscle mass

Zone III

Zone II

Zone I

A

derangement of the airway structures developing in a dynamic fashion. False reassurance may develop because the skin overlying the neck may be relatively normal in appearance even in cases of substantial internal injury. An airway injury is suspected if the child exhibits stridor, hoarseness, subcutaneous emphysema, or air bubbling from any wound. Other signs of serious neck injuries include a vascular bruit, a pulse deficit, a neurologic deficit, hemoptysis, hematemesis, and crepitance.23 In general, it is unwise to probe neck wounds. Probing blindly can disrupt hematomas, can cause new injuries, and is uncomfortable. Probing also can be misleading due to mobile tissue planes. The major decision node for neck injuries relates to the airway and hemodynamic stability of the patient. Unstable patients generally require prompt surgical exploration. Previously, “all” zone II penetrating neck injuries underwent surgical exploration. This historical approach is increasingly uncommon.24 For stable children, computed tomographic (CT) angiography is currently the imaging modality of choice for assessing vascular injuries.25 Ultrasound with color flow Doppler technique is another valuable imaging tool, but has not been studied as extensively as CT angiography.26,27 For serious, stable, penetrating injuries, CT angiography is often combined with esophagoscopy, laryngoscopy, and bronchoscopy to fully evaluate vital structures.17

Management

Zone III Zone II Zone I

B FIGURE 18–1. Zones of the neck. A, Anterior view. B, Lateral view.

some prehospital care providers place all traumatized individuals in cervical spine precautions. This global approach has been challenged, particularly with regard to penetrating injuries.22 The utility of cervical spine immobilization in most cases of neck injuries is probably very low. In addition, cervical collars make it difficult to visualize important lifethreatening signs and hinder access to sites of bleeding. In the emergency department, the assessment and management of the airway is the highest initial priority21 (see Chapter 2, Respiratory Distress and Respiratory Failure). Patients with penetrating neck injuries may have an internal

The primary tasks for emergency physicians in the setting of serious neck injuries are airway and hemorrhage control. Orotracheal intubation is the preferred route for definitive airway control. This can best be achieved with rapid sequence intubation28 (see Chapter 3, Rapid Sequence Intubation). The decision on when to intubate is not always clear. In general, anticipating deterioration and airway occlusion is prudent. However, this must be balanced with the risk of performing an unnecessary intubation and causing airway trauma. If airway compromise is imminent and intubation is not successful, needle jet ventilation may be a reasonable temporizing measure pending definitive airway control. Similar to other body regions, active bleeding can usually be controlled with direct pressure. Obviously, applying excessive pressure to the structures of the neck can have deleterious effects. The balance between applying sufficient pressure to control hemorrhage and avoiding excessive pressure can be difficult. Acute anemia from hemorrhage may require the transfusion of packed red blood cells. Consultation with trauma surgeons and ear, nose, and throat surgeons is indicated in many cases of serious neck injuries. Consultation with a neurosurgeon for suspected spinal cord injuries is also indicated.

Chapter 18 — Neck Trauma

Summary Specific risk criteria that differentiate “minor” from “major” neck injuries have not been identified. Nonetheless, most blunt neck injuries in children require no imaging, require no testing, and have few complications. After a “brief” period of observation, these children can be discharged home with close follow-up. For moderate blunt injuries, there are no definitive pediatric studies. The utility of relatively prolonged observation or imaging is unclear. More severe blunt neck injuries and all but the obviously superficial penetrating injuries require multidisciplinary evaluation and management. Disposition depends on the results of imaging studies and visualization of structures with endoscopy. Given the heterogeneity of neck injuries, the prognosis of these children varies greatly. REFERENCES 1. Freed HA, Milzman DP, Holt RW, et al: Age 14 starts a child’s increased risk of major knife or gun injury in Washington, DC. J Natl Med Assoc 96:169–174, 2004. 2. Holland P, O’Brien DF, May PL: Should airguns be banned? Br J Neurosurg 18:124–129, 2004. 3. Feldman KA, Trent R, Jay MT: Epidemiology of hospitalizations resulting from dog bites in California. Am J Public Health 94:1940–1941, 2004. 4. Martinez-Lage JF, Mesones J, Gilabert A: Air-gun pellet injuries to the head and neck in children. Pediatr Surg Int 17:657–660, 2001. 5. Khan MS, Kirkland PM, Kumar R: Migrating foreign body in the tracheobronchial tree: an unusual case of fi rework penetrating neck injury. J Laryngol Otol 116:148–149, 2002. 6. Joffe M, Ludwig S: Stairway injuries in children. Pediatrics 82:457–461, 1988. 7. Digeronimo RJ, Mayes TC: Near-hanging injury in childhood: a literature review and report of three cases. Pediatr Emerg Care 10:150–156, 1994. 8. Nguyen D, Letts M: In-line skating injuries in children: a 10-year review. J Pediatr Orthop 21:613–618, 2001. 9. Parker JF, O’Shea JS, Simon HK: Unpowered scooter injuries reported to the Consumer Product Safety Commission: 1995–2001. Am J Emerg Med 22:273–275, 2004. 10. Claes I, Van Schil P, Corthouts B, et al: Posterior tracheal wall laceration after blunt neck trauma in children: a case report and review of the literature. Resuscitation 63:97–102, 2004.

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11. Corsten G, Berkowitz RG: Membranous tracheal rupture in children following minor blunt cervical trauma. Ann Otol Rhinol Laryngol 111:197–199, 2002. 12. Starr BE, Shubert A, Baumann B: A child with isolated Horner’s syndrome after blunt neck trauma. J Emerg Med 26:425–427, 2004. 13. Kadish H, Schunk J, Woodward GA: Blunt pediatric laryngotracheal trauma: case reports and review of the literature. Am J Emerg Med 12:207–211, 1994. 14. Ford HR, Gardner MJ, Lynch JM: Laryngotracheal disruption from blunt pediatric neck injuries: impact of early recognition and intervention on outcome. J Pediatr Surg 30:331–334, 1995. 15. Brown PG, Lee M: Trampoline injuries of the cervical spine. Pediatr Neurosurg 32:170–175, 2000. 16. Woodward GA, Furnival R, Schunk JE: Trampolines revisited: a review of 114 pediatric recreational trampoline injuries. Pediatrics 89:849– 854, 1992. 17. Kim MK, Buckman R, Szermeta W: Penetrating neck trauma in children: an urban hospital’s experience. Otolaryngol Head Neck Surg 123:439–443, 2000. 18. Mutabagani KH, Beaver BL, Cooney DR, et al: Penetrating neck trauma in children: a reappraisal. J Pediatr Surg 30:341–344, 1995. 19. Desjardins G, Varon AJ: Airway management for penetrating neck injuries: the Miami experience. Resuscitation 48:71–75, 2001. 20. Gerardi MJ, Sacchetti AD, Cantor RM, et al: Rapid-sequence intubation of the pediatric patient. Ann Emerg Med 28:55–74, 1996. 21. Lim LH, Kumar M, Myer CM 3rd: Head and neck trauma in hospitalized pediatric patients. Otolaryngol Head Neck Surg 130:255–261, 2004. 22. Barkana Y, Stein M, Scope A: Prehospital stabilization of the cervical spine for penetrating injuries of the neck—is it necessary? Int J Care Injured 31:305–309, 2000. 23. Goudy SL, Miller FB, Bumpous JM: Neck crepitance: evaluation and management of suspected aerodigestive tract injury. Laryngoscope 112:791–795, 2002. 24. Sriussadaporn S, Pak-Art R, Tharavej C, et al: Selective management of penetrating neck injuries based on clinical presentations is safe and practical. Int Surg 86:90–93, 2001. 25. Munera F, Soto JA, Palacio DM, et al: Penetrating neck injuries: helical CT angiography for initial evaluation. Radiology 224:366–372, 2002. 26. Corr P, Abdool Carrim AT, Robbs J: Colour-flow ultrasound in the detection of penetrating vascular injuries of the neck. S Afr Med J 89:644–646, 1999. 27. Demetriades D, Theodorou D, Cornwell E 3rd, et al: Penetrating injuries of the neck in patients in stable condition: physical examination, angiography, or color flow Doppler imaging. Arch Surg 130:971–975, 1995. 28. Mandavia DP, Qualls S, Rokos I: Emergency airway management in penetrating neck injury. Ann Emerg Med 35:221–225, 2000.

Chapter 19 Upper Extremity Trauma Michael D. Burg, MD and Sieuwert-Jan C. ten Napel, MD

Key Points Pediatric upper extremity trauma is extremely common and therefore a major source of morbidity. Determining the need for radiographs in an acutely injured child is often difficult. Radiographs comparing the injured arm to the uninjured arm are not routinely indicated. Injuries may be produced by a single major trauma or accident, repeated minor trauma, nonaccidental trauma, or physiologic stress on a pathologic site. Recognizing activity-injury patterns and the ages at which these injuries tend to occur may allow for the identification of subtle fractures and fracture-dislocations.

Selected Diagnoses Shoulder Injuries Clavicular Fractures Acromioclavicular Separation Shoulder Dislocation Shoulder Injuries in the Child Athlete Upper Arm and Elbow Injuries Humeral Fractures Radial Head Subluxation Elbow Fractures Elbow Dislocation Elbow Injuries in the Child Athlete Forearm Injuries Forearm Fractures Monteggia Fracture-Dislocation Galeazzi Fracture-Dislocation Greenstick Fractures Wrist and Hand Injuries Wrist Fractures Hand Fractures Nail Bed Injuries 172

Discussion of Individual Diagnoses Shoulder Injuries Clavicular Fractures In children, the clavicle is the most commonly broken bone in the shoulder region, accounting for 8% to 15% of all fractures in this population.1,2 The clavicle may be injured during delivery (0.4% to 1.5% of all newborns), and accounts for nearly 90% of all obstetric fractures. Clavicle fractures in newborns are associated with shoulder dystocia, increased birth weight, and increased gestational age.3,4 Clavicular fractures are classified by anatomic location: medial third, middle third, and distal third.5 The middle third is the most frequently fractured, accounting for 80% of all clavicular fractures; most of them are nondisplaced.2 Distal third fractures range from 15% in incidence.2,6 Medial third fractures are relatively uncommon, accounting for 5% of all clavicle fractures in children and adolescents.2 A fall on the shoulder is the most common injury mechanism. Others include a direct blow to the clavicle and a fall on an outstretched hand, the latter being a relatively uncommon cause.7 Clavicle fractures also occur in multitrauma patients, in whom the injury is often a minor problem.8 A child with a broken clavicle will characteristically present supporting the elbow on the affected side with the contralateral hand. Often the head will be turned toward the fracture in order to relax the sternocleidomastoid muscle. Spasm of the sternocleidomastoid or trapezius muscle may lift the proximal fragment superiorly.9,10 A visible and palpable deformity can be found along with variable degrees of tenderness. The skin overlying the fracture may be tented, and limited shoulder motion may be seen.10 Assessment of distal neurovascular status is an important part of the evaluation. Plain radiographs are usually sufficient for diagnosis and management.10 Ultrasound can be used to detect clavicle fractures in newborns.11 Most clavicular fractures are treated conservatively. A sling to support the elbow and forearm and pain medication are generally all that is required. A randomized controlled trial found that slings caused less discomfort and possibly fewer complications than treatment with a figure-of-eight bandage. The functional and cosmetic results were identical.12 No statistically significant difference was found in the speed of recovery between these two conservative therapies.13 The sling should be used during waking hours for at least 2

Chapter 19 — Upper Extremity Trauma

weeks, and longer in children older than 12 years. Parents should be advised about callus formation and resultant deformity, which can be visible for up to a year.10 Clavicle fractures in children seldom require operative management. A study of 939 clavicular fractures reported a 1.6% operative rate. Operative indications included open fractures, soft tissue impingement, skin perforation potential, severe shortening of the shoulder girdle with or without displaced intermediate fragments, and displaced fractures with potential risk to the neurovascular bundle or mediastinal structures.14 In another study, 2 of 26 children with distal clavicle fractures underwent operation; all others were treated conservatively with good results.6 Excellent results were found in all of 25 children with conservative treatment of lateral clavicle fractures.15 Acromioclavicular Separation True acromioclavicular separations in young children are rare. A fall on the point of the shoulder usually results in an acromioclavicular separation in the adult or older adolescent, but in children results in fractures through the physis or metaphysis.10 Because distal clavicular epiphyseal ossification does not occur until the age of 18 or 19 years, fractures in this area appear as acromioclavicular dislocations or pseudodislocations.16,17 Superior displacement of the lateral clavicle occurs due to a tear in the thick periosteal tube surrounding the distal clavicle. The lateral clavicular epiphysis, along with the acromioclavicular and coracoclavicular ligaments, usually remains intact.10,17 Injury mechanisms include birth trauma, child abuse, falls, and motor vehicle crashes. Children will present with pain or tender-ness over the acromioclavicular region.17 Nondisplaced to moderately displaced fractures require symptomatic treatment with a sling. Operative stabilization is required in injuries with marked displacement of the fracture fragments.10,16-18 Shoulder Dislocation

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attention.24 Acute shoulder injuries are commonly seen in football, bicycling, snowboarding, skiing, wrestling, and baseball.10 Injuries can also occur due to repetitive stress and are common in swimmers, gymnasts, cheerleaders, and baseball players (see Chapter 98, Overuse Syndromes and Inflammatory Conditions).25 One overuse injury in children is “little leaguer’s shoulder.” It represents a stress fracture of the proximal humerus growth plate.25 The patient with this injury will complain of pain during throwing localized to the proximal humerus. On physical examination, tenderness to palpation over the proximal or lateral aspect of the humerus is found.26 This condition is mostly seen between 11 and 13 years of age and can be treated with rest.10 Ninety-one percent of those with little leaguer’s shoulder were asymptomatic while playing baseball after a 3-month rest period.26 Upper Arm and Elbow Injuries Humeral Fractures PROXIMAL HUMERAL FRACTURES

Proximal humeral epiphyseal fractures are rare and occur more in adolescents than younger children.27 If they occur, therapy is primarily conservative.28,29 Patients present with shoulder swelling and pain, especially when moving the shoulder joint. A neurovascular examination is an important part of the evaluation, as are anteroposterior and lateral radiographs.20,30,31 Nonoperative treatment is appropriate in almost all cases, even with severely displaced fractures, and consists of a hanging cast or simple sling.27 The magnitude of displacement alone does not justify operative management.32 Proximal humeral fractures have excellent remodeling capacity.32,33 Open fractures, those causing neurovascular compromise, pathologic fractures in juvenile bone cysts, and displaced fractures of the articular surface are operative indications.28,31,33 HUMERAL SHAFT FRACTURES

Limited recent literature exists concerning the incidence and presentation of shoulder dislocations in children. Optimal reduction techniques are also not well studied, so standard adult techniques are generally used. A 5-year survey study found a 4.2% incidence of primary anterior dislocation in children ages 12 to 17 years.19 Anterior dislocations in children less than 10 years of age are uncommon.20 Recent literature does address the incidence of re-dislocation after a primary dislocation in adolescents. The recurrence rates after primary dislocation range from 72% to 86% for teens.19,21 Fewer re-dislocations were found in younger patients in two studies,19,21 and it was hypothesized that this may be due to greater shoulder capsule elasticity in younger patients.19 This finding contradicts that of a study reporting a 100% recurrence rate in 21 children with open physes.22 Another study found that the type and duration of immobilization technique had no effect on re-dislocation rate.23 The high incidence of re-dislocation or shoulder instability makes orthopedic follow-up after treatment in the emergency department prudent.

Humeral shaft fractures comprise a small percentage of all fractures in children, with an increased incidence in adolescence.34 Therapy is mainly conservative, and generally only angulations greater than 10 degrees need surgical stabilization, the preferred method being elastic-stable intramedullary nailing.28 Humeral fractures can cause radial nerve palsy. Most have a good prognosis, and expectant management is advocated.35,36 Impaired brachioradialis muscle functioning, wrist extension, and finger and thumb extension are seen with radial nerve injury.35 Of 222 diaphyseal fractures in children, 8 patients had radial nerve palsy and 1 patient had ulnar nerve palsy; all were transitory.36 The clinician must be alert to the possibility of child abuse in toddlers with humeral shaft fractures. Midshaft or metaphyseal humeral fractures were found to be a marker for abuse in those under 3 years of age.37 A study in a similar population classified 18% of humeral shaft fractures as probably due to abuse but cautioned that neither fracture pattern nor age is diagnostic of abuse.38

Shoulder Injuries in the Child Athlete

SUPRACONDYLAR FRACTURES

An ever-increasing number of children participate in organized sports and recreational programs. Over one third of young athletes will sustain injuries requiring medical

The supracondylar humerus fracture is the most common elbow fracture in children, accounting for more than half of all pediatric elbow fractures39,40 and 3% to 18% of all

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fractures seen in children.1,34 Diagnosis of these fractures can be challenging, and, if missed or improperly treated, vascular, neurologic, and structural complications can occur. A fall on an outstretched hand with elbow extension is the main cause (70% to 90%) of these fractures.41,42 The majority of supracondylar fractures occur in the first decade of life, with a peak incidence between ages 4 and 7 years.34,39,42 The nondominant arm is more often injured than the dominant arm.34,39,40,42 In children, ligamentous strength exceeds bone strength. When falling with the hand outstretched and the elbow extended, the collateral ligaments of the elbow prevent hyperextension at the joint space and the olecranon transmits the longitudinal force to the supracondylar region, which fractures.41 These extension-type injuries account for almost all supracondylar fractures.43 Extension-type supracondylar fractures are divided into three types based on displacement: type I, minimal or none; type II, partially intact posterior cortex with angulation but without complete displacement; and type III, completely displaced.44 Flexion-type fractures are caused by a direct fall on the elbow with impact on the olecranon, resulting in a posterior cortical disruption and anterior displacement or angulation.41,43 Children with supracondylar fractures will complain of arm or elbow pain. They often hold the injured arm in an extended, pronated position. The elbow will be swollen and resistant to movement. The distal humerus will be focally tender.41 Assessment and documentation of distal neurovascular status is critically important. The reported incidence of specific nerve injury varies widely.41,45 The median nerve is most commonly injured (28% to 60%), with the anterior interosseous branch most commonly involved (80%). The radial nerve is involved in 26% to 61% of cases and the ulnar nerve in 11% to 15%.45-47 Anterior interosseous nerve impairment results in mild weakness of forearm supination, of the flexor digitorum profundus to the index finger, and of the flexor pollicis longus. Nerve function is assessed by asking the patient to make an “OK” sign and testing this for strength.41 Complete radial, median, and ulnar nerve functional testing are important, although this may be difficult in a child in pain. Type III fractures are those most often associated with neurovascular damage.40,45-48 Vascular status is assessed by checking capillary refi ll, color, distal pulses, and skin temperature. The uninjured arm may serve as a control. A Doppler ultrasound device is used if the pulses are faint or nonpalpable. Vascular compromise is most often due to a brachial artery injury,49 and immediate orthopedic consultation is warranted. If neurovascular compromise exists, the initial treatment is immediate reduction. If an orthopedist is not readily available, the emergency physician should perform the reduction.41 If the radial pulse is not palpable while the hand stays well perfused, no consensus exists on optimal treatment. A strategy of closed reduction and internal fi xation followed by close observation and neurovascular checks is advocated by some.49,50 Others recommend a more aggressive approach: immediate surgical exploration.51-53 Radiographs of the elbow are obtained to confirm the diagnosis and estimate the degree of distraction and angulation. On a properly obtained, normal lateral radiograph, a line drawn down the anterior cortical margin of the humerus should intersect the middle third of the capitellum (Fig. 19– 1). With extension-type fractures, the anterior humeral line will pass anterior to this area, and with flexion-type injuries

FIGURE 19–1. Radiographic line that is demonstrated on a lateral radiograph of the elbow. The anterior humeral line is drawn down the outer edge of the anterior cortex of the distal end of the humerus. As the line is drawn distally through the capitellum, it should pass through the middle of the capitellum. (From Green NE, Swiontkowski MF [eds]: Skeletal Trauma in Children, 3rd ed. Philadelphia: WB Saunders, 2003.)

the line will pass posteriorly. A line drawn along the midshaft of the proximal radius should intersect the capitellum in all radiographic views.41 The significance of a positive posterior “fat pad sign” is uncertain. Only 9 of 54 children with joint effusions and no identifiable fracture immediately after elbow trauma ultimately had evidence of a healing fracture.54 In a prospective study limited to children, the presence of a posterior fat pad was predictive of fracture in 76% of patients.55 It seems prudent to continue to treat children with elbow trauma and posterior fat pad signs as though they have occult supracondylar fractures (Fig. 19–2). A comparison of radiography of traumatized elbows with magnetic resonance imaging (MRI) concluded that a less severe spectrum of injury occurred in children with normal findings on radiographs versus those with an effusion.56 Studies show that comparison views of the uninjured elbow in children with a spectrum of injuries do not improve diagnostic accuracy and are unnecessary.57,58 Type I fractures are typically treated with a long arm posterior splint for 3 weeks with the elbow flexed to 90 degrees and the forearm in a neutral position. The most likely pitfall associated with type I fractures is missing the diagnosis.41 Treatment of type II and III fractures depends on the degree of displacement and fracture stability. Definitive therapy includes closed reduction and internal fi xation.48 The distal neurovascular status of patients with supracondylar fractures must be reassessed in a timely fashion. For type I fractures this can be done on an outpatient basis, but for type II and III fractures, hospitalization is recommended.41 Most nerve injuries due to supracondylar fractures are neurapraxias. Motor deficits typically resolve over 7 to 12 weeks; sensory recovery can take as long as 6 months.46,59 A feared complication described after vascular injury is compartment syndrome (see Chapter 22, Compartment Syndrome). Untreated compartment syndrome may lead to Volkmann’s ischemic contracture which is characterized by fi xed elbow flexion, forearm pronation, wrist flexion, metacarpophalangeal joint extension, and interphalangeal joint flexion.48 Immobilizing the elbow in a position more flexed than 90 degrees can lead to increased pressure in the antecubital region and increase the risk of compartment syndrome.60 Inadequately reduced or stabilized fractures may heal with a varus deformity.48,61

Chapter 19 — Upper Extremity Trauma

A

Fat pad in olecranon fossa

Anterior fat pad

B

C FIGURE 19–2. A, Anterior “fat pad sign” on lateral study (white arrow). B, The anterior fat pad is normally a thin radiolucent stripe, and the posterior fat pad is not seen. C, An effusion displaces both fat pads. This posterior fat pad is now visible. (From Marx JA, Hockberger RS, Walls RM, et al [eds]: Rosen’s Emergency Medicine: Concepts and Clinical Practice, 5th ed. St. Louis: Mosby, 2002.)

Radial Head Subluxation Radial head subluxation is also known as pulled elbow or nursemaid’s elbow. Most radial head subluxations occur in children 1 to 3 years of age. The presumed pathophysiology of this injury is entrapment of the immature radial head

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distal to the annular ligament that occurs during longitudinal traction on the arm.62,63 This often happens when a child sinks toward the ground while being held at the wrist. However, in approximately 50% of cases, a “pull” mechanism of injury is not elucidated.64 Parents or other caregivers are occasionally unable or unwilling to provide an accurate history either because they did not witness the injury or because they are afraid of being considered abusive. Simple observation will generally reveal a nondistressed child with the affected arm held immobile at the side, in minimal flexion at the elbow and pronation at the wrist. No deformity will be seen. The child will generally cry out if the elbow is moved or if pressure is placed on the radial head. Local swelling is uncommon. The remainder of the physical examination will be unremarkable. When the history and physical examination findings are consistent with radial head subluxation, radiographs are not required to confirm the diagnosis.65 However, many physicians do order radiographs in children with arm injuries when the history is unclear or when the physical examination suggests an alternative diagnosis.66 Classically, reduction of a radial head subluxation is performed by supinating the patient’s wrist and flexing the elbow while palpating the radial head.67 A click over the radial head generally signifies successful reduction. Children less than 2 years of age may have a slower return to normal functioning.68 Two relatively recent papers describe a hyperpronation method of reduction for radial head subluxations.63,69 In this method, hyperpronation of the forearm is followed by elbow flexion. Both studies found hyperpronation to be superior to supination, with success rates of 80% versus 69% in one study69 and 95% versus 77% 63 on first attempts. A trend toward less pain with the hyperpronation technique was reported in one study.69 After a reduction attempt, the child is expected to begin using the injured arm, generally within 15 minutes. If this does not occur, there are three main possibilities: unsuccessful reduction, alternative diagnosis (fracture), or slow resolution. Second and even third attempts at reduction are completely acceptable. Fractures about the elbow and at more distant sites (especially the clavicle) should be considered as well. Children under the age of 2 years may take longer to begin using their injured arm even after successful reduction.68 Immobilization with a collar and cuff or sling is a classic, non–evidence-based recommendation, but is impractical given the ages of children affected by this process and its benign course. No immobilization is needed. Parents should be cautioned not to pull on the child’s arms. Analgesics are infrequently needed after reduction. Elbow Fractures The elbow consists of a complex series of three unions, the radiocapitellar and radioulnar articulations and the articulation of the distal humerus with the olecranon fossa of the ulna.70,71 A large variety of elbow fractures have been described. Three of the more common periarticular elbow fractures are described in this section. Complicating the evaluation of the child with an elbow fracture is the fact that six ossification centers exist around the joint (Fig. 19–3). Knowing the location of the ossification centers and the age at which each appears is important when evaluating children with elbow trauma. The mnemonic CRMTOL (Come Read My Tale Of Love), standing for capitellum, radial head, medial

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6. Lateral epicondyle

3. Medial epicondyle

1. Capitellum 4. Trochlea

these injuries. Even the terms radial head and radial neck are often used interchangeably in the literature. Additionally, identifying which injuries should be treated with closed reduction versus percutaneous versus open reduction is murky. Finally, defi nitive studies assessing functional outcomes, range of motion, and complications among the treatment options are lacking. Minimally displaced fractures can be treated with long arm immobilization with the elbow flexed to 90 degrees.75 Orthopedic consultation is required for all other fractures involving the radial head and neck. Up to half of these patients will have other associated elbow fractures; elbow or radial head dislocation may accompany these injuries as well.75 FRACTURES OF THE LATERAL EPICONDYLE

2. Radial head 5. Olecranon (not shown)

FIGURE 19–3. The six ossification centers of the elbow: 1, capitellum; 2, radial head; 3, medial epicondyle; 4, trochlea; 5, olecranon (not shown); and 6, lateral epicondyle. (From Connolly JF [ed]: DePalma’s The Management of Fractures and Dislocations: An Atlas. Philadelphia: WB Saunders, 1981.)

epicondyle, trochlea, olecranon, and lateral epicondyle, can be used to recall the names of the ossification centers. The age in years at which each appears is variably quoted as: capitellum, 1 to 2; radial head, 4 to 5; medial epicondyle, 4 to 7; trochlea, 8 to 10; olecranon, 8 to 10; and lateral epicondyle, 10 to 11.70-73 Ossification of these centers in boys tends to lag that in girls by about 1 year.70 The literature does not support the routine use of comparison radiographs of the contralateral, uninjured elbow to improve diagnostic accuracy.57,58 However, in selected cases, comparison views may be helpful. In the case of a diagnostic dilemma, additional radiographs or alternate imaging techniques (computed tomography, MRI, bone scan, others) may be helpful. At least one study of children with elbow trauma demonstrated that MRI detected a wide spectrum of injuries not apparent on plain radiographs. However, this same study found that the additional sensitivity of MRI did little to alter treatment.56 For the child with a worrisome mechanism of injury and physical examination, but with normal radiographs, a reasonable plan is to immobilize the elbow in a splint, prescribe analgesia, and arrange follow-up with an orthopedist.74 RADIAL HEAD AND NECK FRACTURES

These injuries constitute approximately 5% to 15% of all pediatric elbow fractures, and their optimal treatment is an area of active controversy.75,76 Generally these fractures occur due to a fall on an outstretched hand.75 Nine and one-half years is the mean age for radial neck fractures; 13 years is the mean age for radial head fractures.75,76 Boys and girls are at equal risk.75 The child with this injury usually holds the elbow slightly flexed. Flexion-extension, pronationsupination, and radial head palpation cause pain. There is no consensus among orthopedists regarding classification of

This injury is difficult to diagnose and is fraught with a variety of complications including nonunion, malunion, late stiffness, late ulnar nerve palsy, avascular necrosis of the lateral condyle, and deformity.71,72,77,78 The usual mechanism for a lateral condyle fracture is a fall on an outstretched hand with the elbow extended and the forearm supinated. Varus stress acts to avulse the lateral condyle.71,72,77 This is the second most common pediatric elbow fracture.72 Swelling and tenderness are usually found only over the lateral portion of the elbow, and acute neurovascular compromise is unusual.72 Radiographs should include anteroposterior, lateral, and oblique views. The oblique view is most likely to show the injury and true degree of fracture displacement.71,72 Nondisplaced or minimally displaced fractures (0 to 2 mm) are treated with a long arm cast.71,72 Close follow-up is important since up to 10% of these fractures may displace while immobilized.77,78 Fractures displaced more than 2 mm require orthopedic consultation. Some advocate open reduction and internal fi xation for all these injuries, while some perform closed reduction and pinning for fractures displaced 2 to 4 mm and open procedures for more widely displaced fractures.71,72,79 FRACTURES OF THE MEDIAL EPICONDYLE

Medial epicondyle avulsion fractures, which occur at the growth plate, can occur due to acute or chronic valgus stress on the elbow. Throwers (e.g., baseball pitchers) are prone to this type of injury.80 Medial epicondyle fractures are also commonly seen along with pediatric elbow dislocations.81 Children with fractures of the medial epicondyle typically present with localized pain, swelling, and tenderness directly over the medial epicondyle.70,80 If the injury is due to chronic overuse in a thrower, there may be a history of decreased throwing effectiveness or distance. Nondisplaced fractures are treated with a short period of immobilization and pain relief.80 Those children with displaced fractures should be referred to an orthopedist for consideration of operative repair.70,80,82 Controversy exists over operative indications in isolated, displaced medial humeral epicondyle fractures. One retrospective study found similar functional outcomes in nonsurgical versus surgical management of this injury.83 Fracture fragments within the joint space require emergent extrication and fi xation.80,84 Elbow Dislocation This is an uncommon injury in children, with the peak incidence during the early teen years.10,86 Contact sports and falls

Chapter 19 — Upper Extremity Trauma

account for most of these injuries. Most dislocations are posterior and closed, but a wide spectrum of dislocation patterns has been described10,81 (Fig. 19–4). A variety of associated fractures are seen with elbow dislocations.81,85 Injuries to the median, ulnar, and radial nerves have been described, as well as vascular injuries. Nerve entrapment or a fracture fragment within the ulnohumeral joint mandates immediate surgery.86 If elbow reduction attempts are unsuccessful, an entrapped fracture fragment or interposed soft tissue should be suspected.10 Elbow Injuries in the Child Athlete Over 30 million children in the United States participate in organized sports. The incidence of upper extremity injury is second only to ankle and knee injuries in the child athlete.87 Although a wide variety of acute elbow injuries can be sustained by the child athlete, one chronic overuse injury seen by emergency physicians is “little leaguer’s elbow.” The repetitive valgus stress induced by throwing or similar motions produces osseous damage of the elbow. While little leaguer’s elbow was originally described in baseball pitchers, it is also seen in nonpitching baseball players, racquet sport players, football players, and others.10 Most with this condition will complain of medial elbow pain. When questioned, the athlete with little leaguer’s elbow will also report decreased throwing effectiveness or distance.10,88 Radiographs may reveal hypertrophy or separation of the medial humeral condyle.89 The optimal “treatment” is prevention, through a combination of rest, proper throwing mechanics, and avoidance of overexertion. Once little leaguer’s elbow develops, rest—until there is complete resolution of pain—is important. When activity resumes, proper throwing mechanics are key to preventing recurrence.90 Forearm Injuries Forearm Fractures Distal forearm fractures occur most commonly at the time of the pubertal growth spurt in early adolescence. This is

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likely due to increased physical activity that occurs at this time of life and decreased bone strength due to enhanced bone turnover.91 Most of these fractures occur due to a fall on an outstretched hand, although direct local trauma can produce them as well.92 Acceptable pronation, supination, and cosmesis are the main treatment outcomes of interest.92 Outcomes are largely dependent on fracture angulation at the time of fracture healing. Fracture angulation, in turn, depends on the quality and maintenance of the initial reduction.93 Most pediatric forearm fractures can be successfully treated with a combination of reduction and immobilization. There is controversy regarding the treatment of completely displaced metaphyseal fractures of the distal radius. Since up to 21% of distal radius fractures displace after successful reduction,94 some have suggested the use of percutaneous Kirschner wires to maintain reduction.95 For diaphyseal forearm fractures, failure of closed reduction is the most common surgical indication. Adolescents with these injuries are generally treated with internal fi xation and early mobilization like adults with these injuries.96 During the physical examination of these children, particular attention paid to the wrist and elbow will make missing a Monteggia or Galeazzi fracture-dislocation less likely.92 Most nerve injuries resulting from forearm fractures are neuropraxias that typically resolve within several weeks without specific intervention. Monteggia Fracture-Dislocation Isolated ulna fractures in children are uncommon.97 A Monteggia fracture-dislocation is an ulnar fracture in association with a radial head dislocation.98 Four primary Monteggia-type injuries have been described, with the type dependent upon the fracture location and the direction of ulnar dislocation.99 It is well established that Monteggia fracture-dislocations are misdiagnosed by both emergency physicians and radiologists.99 The injury generally results from a fall on an outstretched hand. Boys more commonly sustain this injury, and the average age is approximately 7 years with a wide range.100 The wrist and elbow must be carefully examined for fractures and dislocations. Patients with an isolated ulna fracture and radial head tenderness may have spontaneously reduced their dislocation. Neurologic deficits may be found in up to 17% of patients. They are generally neurapraxias and resolve over weeks to months.100 If a Monteggia fracture-dislocation is suspected, radiographs of the wrist and elbow (in addition to the forearm) are indicated. To avoid missing this injury, it is essential to recognize that in normal radiographs, the midshaft of the proximal radius points at the capitellum in all views.100 Closed reduction of both components of the fracture-dislocation and immobilization are used to treat most of these injuries. Open reduction may be required in the case of an otherwise irreducible radial head or an unstable ulna fracture.99 Galeazzi Fracture-Dislocation

FIGURE 19–4. Posterior dislocation of the elbow. A, Lateral radiograph of the elbow. The ulna and radius are displaced posteriorly. B, Anteroposterior radiograph of the posterior dislocation of the elbow. (From Green NE, Swiontkowski MF [eds]: Skeletal Trauma in Children, 3rd ed. Philadelphia: WB Saunders, 2003.)

The Galeazzi fracture-dislocation is an uncommon but important injury in children.101 The Galeazzi fracturedislocation is a radial shaft fracture in association with a distal radioulnar joint dislocation.101 The injury is usually caused by a fall on an outstretched hand with the forearm in pronation. Careful examination of the wrist is helpful in avoiding missing this injury.101 Children with a Galeazzi

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fracture dislocation will not be able to fully promote and supinate their forearms. Treatment involves closed reduction and immobilization.101-103 Greenstick Fractures

been reported in association with distal radius fractures.116 Tenderness in the anatomic snuffbox or scaphoid compression pain should cause the treating physician to consider a scaphoid fracture and treat for same. A wide variety of carpal fractures and dislocations have been described in children, all in small case series. Care is therefore individualized.

This fracture type involves a break in one bony cortex and compression of the bony cortex opposite the fracture site. In one large series of over 3300 pediatric patients with upper extremity fractures, greenstick fractures occurred in just over 5% of patients.104 However, another large study found a nearly 52% incidence of greenstick fractures.105 Subject selection for these studies likely explains this discrepancy. The decision to reduce these fractures generally depends on the amount of angulation present. If reduction is required, the angulation is overcorrected toward the cortical break, in essence completing the fracture so as to prevent persistent angulation and resultant deformity. A splint is then applied.

Hand injuries are common in children of all ages, and fractures make up 15% to 19% of all hand injuries.117-119 Fracture incidence has a bimodal distribution, with distal phalanx injuries predominating at age 1 year and other phalangeal and metacarpal injuries peaking at age 12 years.120,121 Most pediatric hand fractures heal uneventfully.122 Open fractures, those involving articular surfaces, comminuted fractures, and markedly displaced and angulated fractures mandate the timely involvement of a hand surgeon or orthopedist experienced in caring for head injuries.

Wrist and Hand Injuries

METACARPAL FRACTURES

Wrist Fractures

The shaft is the most commonly fractured metacarpal region in children; however, articular and periarticular fractures do occur.120,122 A volar angulated fracture involving the neck of the fourth or fifth metacarpal (i.e., a boxer’s fracture) often occurs when a hard surface is punched. Evidence to guide the optimal treatment of these injuries is scant. Depending on community standards and degree of angulation, these fractures can be reduced120 or left in place and the digit either buddy taped or placed in an ulnar gutter splint. Rotational deformity of the affected digit needs to be identified since healing and regrowth will not correct this abnormality. To check for rotational deformity, the patient should be asked to fully flex all the digits. In full flexion, all digit tips should point evenly at the thenar eminence. Overlap, indicating rotation, should prompt consultation with a hand surgeon. Similarly, fractures at the base of the thumb metacarpal require hand surgeon consultation.120,123

DISTAL RADIUS FRACTURES

These injuries are common in children and generally result from a fall onto an outstretched hand.105 The most common type of distal radius fracture is the buckle fracture (also known as a torous fracture).106-109 These minor fractures tend to do very well with a removable splint that can be worn for three to four weeks.106-108 These fractures seldom have complications and can be managed by either primary care physicians or orthopedists. In more severe injuries, there may be a distal “both bones” fracture involving both the radius and ulna. Local tenderness and swelling are invariably present, but may be somewhat subtle. If angulated or displaced, these fractures typically require closed reduction that can be performed by the emergency physician or an orthopedist. There is no universally accepted degree of residual angulation after reduction and local standards tend to guide the acceptance of a reduction attempt. Younger children have greater degrees of acceptable residual angulation.110 This is due to a greater capacity for remodeling in younger children. For very distal injuries that may involve the growth plate, orthopedic follow-up is prudent.111 In general, children with distal radius fractures do well. Resultant traumatic arthritis is rare.112 CARPAL INJURIES

Pediatric carpal fractures are uncommon. This may be because the carpus is largely unossified throughout much of early childhood. Adolescents, whose carpal bones are nearly completely ossified, have adult-type injury patterns.113 The scaphoid is the most commonly fractured carpal bone in children, as it is in adults, although the patterns of injury are different.113 More are located distally, they more often involve a single cortex, and they are more often nondisplaced.114 The peak incidence of scaphoid fractures occurs at age 12 years.113 Radiographs done in the emergency department may easily miss scaphoid fractures. MRI is far more sensitive for fracture detection in this region.115 However, no study has examined the benefit of early detection of scaphoid injuries, so long as they are suspected, immobilized in a thumb spica splint, and referred for follow-up. Scaphoid fractures have

Hand Fractures

PROXIMAL PHALANX FRACTURES

Many of these fractures in children are articular or periarticular.120,123 Radiographs including posteroanterior, lateral, and oblique views are helpful to avoid missing subtle injuries.120 A common injury pattern is the Salter type II fracture at the phalangeal base123 (see Fig. 20–2). If it involves the little finger, the digit is usually abducted and extended. Reduction is performed by using a pencil in the fourth web space to lever the fracture back into place. Reduction is maintained by buddy taping.120,123 Fractures at the base of the thumb’s proximal phalanx are often Salter type III fractures and can be considered the childhood equivalent of ulnar collateral ligament rupture (i.e., gamekeeper’s or skier’s thumb). Although experts are not in perfect agreement on treatment, in general, minimally displaced fractures can be immobilized without reduction. Displaced fractures require reduction and internal fi xation.120,123 Distal periarticular or articular fractures can be easily overlooked. The mechanism of injury may be a tip-off. One paper suggests this fracture type occurs when a child’s digit is closed in a car door and forcibly extracted. It further states that the fracture fragment may be purely cartilaginous, making radiographic visualization of it difficult.120 Another suggests that oblique radiographs may be particularly helpful

Chapter 19 — Upper Extremity Trauma

in diagnosing these injuries.123 In any event, displaced distal fractures involving the articular surface must be reduced and internally fi xed.120,123 MIDDLE PHALANX FRACTURES

Many of these fractures are similar to those seen in the proximal phalanges 2 through 5.120 Nondisplaced articular fractures are treated with buddy taping. Fractures displaced more than 2 mm require reduction and internal fi xation.120,123 DISTAL PHALANX FRACTURES

Many of these involve crush injury to the fingertip, nail, and nail bed and vary widely in severity.120,123-125 As one would expect, outcome and degree of initial injury are correlated.124 Traditionally, open crush injuries are treated with antibiotics to reduce the risk of osteomyelitis,120 although this is not an evidence-based recommendation. A prescription for oral antibiotics is probably adequate. Mallet fi nger–type fractures are generally treated with closed reduction and immobilization in slight hyperextension.123 Nail Bed Injuries For subungual hematomas larger than 25%, nail removal and nail bed repair is often advocated. However, a 1999 study has called this recommendation into question.125 It found that, in children with an intact nail and nail margin and a subungual hematoma, trephination versus nail bed repair produced similarly excellent results (see Chapter 173, Management of Digit Injuries and Infections). REFERENCES *1. Landin LA: Epidemiology of children’s fractures. J Pediatr Orthop B 6:79–83, 1997. 2. Nordqvst A, Petersson C: The incidence of fractures of the clavicle. Clin Orthop 300:127–132, 1994. 3. Many A, Brenner SH, Yaron Y, et al: Prospective study of incidence and predisposing factors for clavicular fracture in newborn. Acta Obstet Gynecol Scand 75:378–381, 1996. 4. Roberts SW, Hernandez C, Maberry MC, et al: Obstetric clavicular fracture: the enigma of normal birth. Obstet Gynecol 86:978–981, 1995. 5. Post M: Current concepts in the treatment of fractures of the clavicle. Clin Orthop 245:89–101, 1989 6. Wilfi nger C, Hollwarth M: Lateral clavicular fractures in children and adolescents. Unfallchirurgie 105:602–605, 2002. 7. Stanley D, Trowbridge EA, Norris SH: The mechanism of clavicular fractures: a clinical and biomechanical analysis. J Bone Joint Surg Br 70:461–464, 1988. 8. Rozycki GS, Tremblay L, Feliciano DV, et al: A prospective study for the detection of vascular injury in adult and pediatric patients with cervicothoracic seat belt signs. J Trauma 52:618–623, 2002. 9. Goddard NJ, Stabler J, Albert JS: Atlanto-axial rotatory fi xation and fracture of the clavicle: an association and classification. J Bone Joint Surg Br 72:72–75, 1990. *10. Kocher MS, Waters PM, Micheli LJ: Upper extremity injuries in the paediatric athlete. Sports Med 30:117–135, 2000. 11. Blab E, Geissler W, Rokitansky A: Sonographic management of infantile clavicular fractures. Pediatr Surg Int 15:251–254, 1999. 12. Andersen K, Jensen PO, Lauritzen J: Treatment of clavicular fractures: figure-of-eight bandage versus a simple sling. Acta Orthop Scand 58:71–74, 1987. 13. Stanley D, Norris SH: Recovery following fractures of the clavicle treated conservatively. Injury 19:162–164, 1988. 14. Kubiak R, Slongo T: Operative treatment of clavicle fractures in children: a review of 21 years. J Pediatr Orthop 22:736–739, 2002. *Selected readings.

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15. Nordqvist A, Petersson C, Redlund-Johnell I: The natural course of lateral clavicle fracture: 15 (11–21) year follow-up of 110 cases. Acta Orthop Scand 64:87–91, 1993. 16. Black GB, McPherson JA, Reed MH: Traumatic pseudodislocation of the acromioclavicular joint in children: a fi fteen year review. Am J Sports Med 19:644–646, 1991. 17. Ogden JA: Distal clavicular physeal injury. Clin Orthop 188:68–73, 1984. 18. Havranek P: Injuries of distal clavicular physis in children. J Pediatr Orthop 9:213–215, 1989. 19. Postacchini F, Gumina S, Cinotti G: Anterior shoulder dislocation in adolescents. J Shoulder Elbow Surg 9:470–474, 2000. 20. Obremskey W, Routt ML: Fracture-dislocation of the shoulder in a child: case report. J Trauma 36:137–140, 1994. 21. Deitch J, Mehlman CT, Foad SL, et al: Traumatic anterior shoulder dislocation in adolescents. Am J Sports Med 31:758–763, 2003. *22. Marans HJ, Angel KR, Schemitsch EH, et al: The fate of traumatic anterior dislocation of the shoulder in children. J Bone Joint Surg Am 74:1242–1244, 1992. 23. Hovelius L, Augustini BG, Fredin H, et al: Primary anterior dislocation of the shoulder in young patients: a ten-year prospective study. J Bone Joint Surg Am 78:1677–1684, 1996. 24. Adirim TA, Cheng TL: Overview of injuries in the young athlete. Sports Med 33:75–81, 2003. 25. Paterson PD, Waters PM: Shoulder injuries in the childhood athlete. Clin Sports Med 19:681–692, 2000. 26. Carson WG, Gasser SI: Little Leaguer’s shoulder: a report of 23 cases. Am J Sports Med 26:575–580, 1998. 27. Larsen CF, Kiaer T, Lindequist S: Fractures of the proximal humerus in children: nine-year follow-up of 64 unoperated on cases. Acta Orthop Scand 61:255–257, 1990. 28. Schmittenbecher PP, Blum J, David S, et al: The treatment of humeral shaft and subcapital fractures in children: consensus report of the child trauma section of the DGU. Unfallchirurgie 107:8–14, 2004. 29. Kohler R, Trillaud JM: Fracture and fracture separation of the proximal humerus in children: report of 136 cases. J Pediatr Orthop 3:326– 332, 1983. 30. te Slaa RL, Nollen AJ: A Salter type 3 fracture of the proximal epiphysis of the humerus. Injury 18:429–431, 1987. 31. Gregg-Smith SJ, White SH: Salter-Harris III fracture-dislocation of the proximal humeral epiphysis. Injury 23:199–200, 1992. 32. Beringer DC, Weiner DS, Noble JS, et al: Severely displaced proximal humeral epiphyseal fractures: a follow-up study. J Pediatr Orthop 18:31–37, 1998. 33. Baxter MP, Wiley JJ: Fractures of the proximal humeral epiphysis: their influence on humeral growth. J Bone Joint Surg Br 68:570–573, 1986. 34. Cheng JC, Ng BK, Ying SY, et al: A 10-year study of the changes in the pattern and treatment of 6,493 fractures. J Pediatr Orthop 19:344– 350, 1999. 35. Larsen LB, Barfred T: Radial nerve palsy after simple fracture of the humerus. Scand J Plast Reconstr Hand Surg 34:363–366, 2000. 36. Machan FG, Vinz H: Humeral shaft fracture in childhood. Unfallchirurgie 19:166–174, 1993. 37. Leventhal JM, Thomas SA, Rosenfield NS, et al: Fractures in young children: distinguishing child abuse from unintentional injuries. Am J Dis Child 147:87–92, 1993. 38. Shaw BA, Murphy KM, Shaw A, et al: Humerus shaft fractures in young children: accident or abuse? J Pediatr Orthop 17:293–297, 1997. 39. Landin LA, Danielsson LG: Elbow fractures in children: an epidemiological analysis of 589 cases. Acta Orthop Scand 57:309–312, 1986. 40. Houshian S, Mehdi B, Larsen MS: The epidemiology of elbow fractures in children: analysis of 355 fractures, with special reference to supracondylar humerus fractures. J Orthop Sci 6:312–315, 2001. 41. Wu J, Perron AD, Miller MD, et al: Orthopedic pitfalls in the ED: pediatric supracondylar humerus fractures. Am J Emerg Med 20:544– 550, 2002. 42. Farnsworth CL, Silva PD, Mubarak SJ: Etiology of supracondylar humerus fractures. J Pediatr Orthop 18:38–42, 1998. 43. De Boeck H: Flexion-type supracondylar elbow fractures in children. J Pediatr Orthop 21:460–463, 2001. 44. Gartland JJ: Management of supracondylar fractures of the humerus in children. Surg Gynecol Obstet 109:145–154, 1959.

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45. Lyons ST, Quinn M, Stanitski CL: Neurovascular injuries in type III humeral supracondylar fractures in children. Clin Orthop 376:62–67, 2000. 46. Brown IC, Zinar DM: Traumatic and iatrogenic neurological complications after supracondylar humerus fractures in children. J Pediatr Orthop 15:440–443, 1995. 47. Campbell CC, Waters PM, Emans JB, et al: Neurovascular injury and displacement in type III supracondylar humerus fractures. J Pediatr Orthop 15:47–52, 1995. 48. Pirone AM, Graham HK, Krajbich JI: Management of displaced extension-type supracondylar fractures of the humerus in children. J Bone Joint Surg Am 70:641–650, 1988. *49. Sabharwal S, Tredwell SJ, Beauchamp RD, et al: Management of pulseless pink hand in pediatric supracondylar fractures of humerus. J Pediatr Orthop 17:303–310, 1997. 50. Garbuz DS, Leitch K, Wright JG: The treatment of supracondylar fractures in children with an absent radial pulse. J Pediatr Orthop 16:594–596, 1996. 51. Wilkins KE: Supracondylar fractures: what’s new? J Pediatr Orthop 6:110–116, 1997. 52. Shaw BA, Kasser JR, Emans JB, et al: Management of vascular injuries in displaced supracondylar humerus fractures without arteriography. J Orthop Trauma 4:25–29, 1990. 53. Clement DA: Assessment of a treatment plan for managing acute vascular complications associated with supracondylar fractures of the humerus in children. J Pediatr Orthop 10:97–100, 1990. *54. Donnelly LF, Klostermeier TT, Klosterman LA: Traumatic elbow effusions in pediatric patients: are occult fractures the rule? AJR Am J Roentgenol 171:243–245, 1998. 55. Skaggs DL, Mirzayan R: The posterior fat pad sign in association with occult fracture of the elbow in children. J Bone Joint Surg Am 81:1429–1433, 1999. 56. Griffith JF, Roebuck DJ, Cheng JC, et al: Acute elbow trauma in children: spectrum of injury revealed by MR imaging not apparent on radiographs. AJR Am J Roentgenol 176:53–60, 2001. 57. Chacon D, Kissoon N, Brown T, et al: Use of comparison radiographs in the diagnosis of traumatic injuries of the elbow. Ann Emerg Med 21:895–899, 1992. 58. Kissoon N, Galpin R, Gayle M, et al: Evaluation of the role of comparison radiographs in the diagnosis of traumatic elbow injuries. J Pediatr Orthop 15:449–453, 1995. 59. The RM, Severijnen RS: Neurological complications in children with supracondylar fractures of the humerus. Eur J Surg 165:180–182, 1999. 60. Battaglia TC, Armstrong DG, Schwend RM: Factors affecting forearm compartment pressures in children with supracondylar fractures of the humerus. J Pediatr Orthop 22:431–439, 2002. 61. Ippolito E, Caterini R, Scola E: Supracondylar fractures of the humerus in children: analysis at maturity of fi fty-three patients treated conservatively. J Bone Joint Surg Am 68:333–344, 1986. 62. Choung W, Heinrich SD: Acute annular ligament interposition into the radiocapitellar joint in children (nursemaid’s elbow). J Pediatr Orthop 15:454–456, 1995. 63. Macias CG, Bothner J, Wiebe R: A comparison of supination/flexion to hyperpronation in the reduction of radial head subluxations. Pediatrics 102:e10, 1998. 64. Schutzman SA, Teach S: Upper-extremity impairment in young children. Ann Emerg Med 26:474–479, 1995. 65. Macias CG, Wiebe R, Bothner J: History and radiographic fi ndings associated with clinically suspected radial head subluxations. Pediatr Emerg Care 16:22–25, 2000. 66. Snyder HS: Radiographic changes with radial head subluxation in children. J Emerg Med 8:265–269, 1990 67. Ufberg J, McNamara R: Management of common dislocations. In Roberts JR, Hedges JR (eds): Clinical Procedures in Emergency Medicine, 4th ed. Philadelphia: Elsevier Saunders, 2004, pp 946–988. 68. Schunk JE: Radial head subluxation: epidemiology and treatment of 87 episodes. Ann Emerg Med 19:1019–1023, 1990 69. McDonald J, Whitelaw C, Goldsmith LJ: Radial head subluxation: comparing two methods of reduction. Acad Emerg Med 6:715–718, 1999. 70. DaSilva MF, Williams JS, Fadale PD, et al: Pediatric throwing injuries about the elbow. Am J Orthop 27:90–96, 1998. 71. Do T, Herrera-Soto J: Elbow injuries in children. Curr Opin Pediatr 15:68–73, 2003.

72. Skaggs D, Pershad J: Pediatric elbow trauma. Pediatric Emerg Care 13:425-434, 1997. 73. Kelly Am, Pappas AM: Shoulder and elbow injuries and painful syndromes. Adolesc Med 9:569–587, 1998. 74. David T: Missed upper extremity fractures in athletes. Curr Sports Med Rep 1:327–332, 2002. 75. Radomisli TE, Rosen AL: Controversies regarding radial neck fractures in children. Clin Orthop 353:30–39, 1998. 76. Leung AG, Peterson HA: Fractures of the proximal radial head and neck in children with emphasis on those that involve the articular cartilage. J Pediatr Orthop 20:7–14, 2000. 77. Flynn JM, Sarwark JF, Waters PM, et al: The surgical management of pediatric fractures of the upper extremity. Instr Course Lect 52:635– 645, 2003. 78. Beaty JH, Kasser JR: Fracture about the elbow. Instr Course Lect 44:199–215, 1995. 79. Mirsky EC, Karas EH, Weiner LS: Lateral condyle fractures in children: evaluation of classification and treatment. J Orthop Trauma 11:117–120, 1997. 80. Hutchinson MR, Ireland ML: Overuse and throwing injuries in the skeletally immature athlete. Instr Course Lect 52:25–36, 2003. 81. Rasool MN: Dislocations of the elbow in children. J Bone Joint Surg Br 86:1050–1058, 2004. 82. Case SL, Hennrikus WL: Surgical treatment of displaced medial epicondyle fractures in adolescent athletes. Am J Sports Med 25:682– 686, 1997. 83. Farsetti P, Potenza V, Caterini R, et al: Long-term results of treatment of fractures of the medial humeral epicondyle in children. J Bone Joint Surg Am 83:1299–1305, 2001. 84. Papandrea R, Waters PM: Posttraumatic reconstruction of the elbow in the pediatric patient. Clin Orthop 370:115–126, 2000. 85. Fowles JV, Slimane N, Kassab MT: Elbow dislocation with avulsion of the medial humeral epicondyle. J Bone Joint Surg Br 72:102–104, 1990. 86. Carlioz H, Abols Y: Posterior dislocation of the elbow in children. J Pediatr Orthop 1:8–12, 1984. 87. Adirim TA, Cheng TL: Overview of injuries in the young athlete. Sports Med 33:75–81, 2003. 88. Kaeding CC, Whitehead R: Musculoskeletal injuries in adolescents. Prim Care 25:211–223, 1998. 89. Hang DW, Chao CM, Hang YS: A clinical and roentgenographic study of little league elbow. Am J Sports Med 32:79–84, 2004. 90. Klingele KE, Kocher MS: Little league elbow: valgus overload injury in the paediatric athlete. Sports Med 32:1005–1015, 2002. *91. Khosla S, Melton LJ, Dekutoski MB, et al: Incidence of childhood distal forearm fractures over 30 years. JAMA 290:1479–1485, 2003. 92. Noonan KJ, Price CT: Forearm and distal radius fractures in children. J Am Acad Orthop Surg 6:146–156, 1998. 93. Younger AS, Tredwell SJ, Mackenzie WG: Factors affecting fracture position at cast removal after pediatric forearm fracture. J Pediatr Orthop 17:332–336, 1997. 94. Haddad FS, Williams RL: Forearm fractures in children: avoiding redisplacement. Injury 26:691–692, 1995. 95. McLauchlan GJ, Cowan B, Annan IH, et al: Management of completely displaced metaphyseal fractures of the distal radius in children. J Bone Joint Surg Br 84:413–417, 2002. 96. Flynn JM: Pediatric forearm fractures: decision making, surgical techniques, and complications. Instr Course Lect 51:355–360, 2002. 97. Goodwin RC, Kuivila TE: Pediatric elbow and forearm fractures requiring surgical treatment. Hand Clin 18:135–148, 2002. 98. Beaty JH: Elbow fractures in children and adolescents. Instr Course Lect 52:661–665, 2003. 99. Gleeson AP, Beattie TF: Monteggia fracture-dislocation in children. J Accid Emerg Med 11:192–194, 1994. 100. Kay RM, Skaggs DL: The pediatric Monteggia fracture. Am J Orthop 27:606–609, 1998. 101. Vorlat P, De Boeck H: Traumatic bowing and Galeazzi fracturedislocation—a report of 2 children. Acta Orthop Scand 73:234–237, 2002. 102. Shonnard PY, DeCoster TA: Combined Monteggia and Galeazzi fractures in a child’s forearm: a case report. Orthop Rev 23:755–759, 1994. 103. Walsh HP, McLaren CA, Owen R: Galeazzi fractures in children. J Bone Joint Surg Br 69:730–733, 1987.

Chapter 19 — Upper Extremity Trauma 104. Cheng JC, Shen WY: Limb fracture pattern in different pediatric age groups: a study of 3,350 children. J Orthop Trauma 7:15–22, 1993. 105. Worlock P, Stower M: Fracture patterns in Nottingham children. J Pediatr Orthop 6:656–660, 1986. 106. Symons S, Rowsell M, Bhowal B, et al: Hospital versus home management of children with buckle fractures of the distal radius. J Bone Joint Surg Br 83:556–560, 2001. 107. Plint AC, Perry JJ, Correll R, et al: A randomized, controlled trial of removable splinting versus casting for wrist buckle fractures in children. Pediatrics 117:691–697, 2006. 108. Davidson JS, Brown DJ, Barnes SN, et al: Simple treatment for torus fractures of the distal radius. J Bone Joint Surg Br 83:1173–1175, 2001. 109. Abraham A, Henman P: Interventions for treating wrist fractures in children (protocol). Cochrane Database Syst Rev (3):CD004576, 2004. 110. Overly F, Steele DW: Common pediatric fractures and dislocations. Clin Ped Emerg Med 3:106–117, 2002. 111. Huurman WW: Injuries to the wrist and hand. Adolesc Med 9:611– 625, 1998. 112. Peljovich AE, Simmons BP: Traumatic arthritis of the hand and wrist in children. Hand Clin 16:673–684, 2000. 113. Light TR: Carpal injuries in children. Hand Clin 16:513–522, 2000. 114. Fabre O, De Boeck H, Haentjens P: Fractures and nonunions of the carpal scaphoid in children. Acta Orthop Belg 67:121–125, 2001.

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115. Cook PA, Yu JS, Wiand W, et al: Suspected scaphoid fractures in skeletally immature patients: application of MRI. J Comput Assist Tomogr 21:511–515, 1997. 116. Albert MC, Barre PS: A scaphoid fracture associated with a displaced distal radial fracture in a child. Clin Orthop 240:232–235, 1989. 117. Bhende MS, Dandrea LA, Davis HW: Hand injuries in children presenting to a pediatric emergency department. Ann Emerg Med 22:1519–1523, 1993. *118. Fetter-Zarzeka A, Joseph MM: Hand and fi ngertip injuries in children. Pediatr Emerg Care 18:341–345, 2002. 119. Ljungberg E, Rosberg HE, Dahlin LB: Hand injuries in young children. J Hand Surg Br 28:376–380, 2003. 120. Nofsinger CC, Wolfe SW: Common pediatric hand fractures. Curr Opin Pediatr 14:42–45, 2002. 121. Hastings H, Simmons BP: Hand fractures in children: a statistical analysis. Clin Orthop 188:120–130, 1984. 122. Mahabir RC, Kazemi AR, Cannon WG, et al: Pediatric hand fractures: a review. Pediatr Emerg Care 17:153–156, 2001. 123. Leclercq C, Korn W: Articular fractures of the fi ngers in children. Hand Clin 16:523–534, 2000. 124. O’Shaughnessy M, McCann J, O’Connor TP, et al: Nail re-growth in fi ngertip injuries. Ir Med J 83:136–137, 1990. *125. Roser SE, Gellman H: Comparison of nail bed repair versus nail trephination for subungual hematomas in children. J Hand Surg Am 24:1166–1170, 1999.

Chapter 20 Lower Extremity Trauma Besh Barcega, MD, MBA and Lilit Minasyan, MD

Key Points A delayed diagnosis of slipped capital femoral epiphysis has a high likelihood of leading to avascular necrosis of the femoral head. A saline arthrogram is useful for identifying knee lacerations that penetrate the joint space. Tibia and fibula fractures place the child at risk for a compartment syndrome of the leg.

ful reduction has occurred, keeping the hips in abduction with a pillow or blankets between the thighs minimizes the risk of re-dislocation. Postreduction radiographs are indicated. Patients with traumatic hip dislocations are usually admitted to the hospital for spica casting or traction followed by early mobilization. Emergent orthopedic consultation is needed if initial reduction attempts are unsuccessful. A delay in diagnosis or successful reduction increases the risk of avascular necrosis of the femoral head. With prompt treatment, most children with traumatic hip dislocations do well and have minimal or no long-term sequelae.1 Slipped Capital Femoral Epiphysis

Selected Diagnoses Traumatic hip dislocation Slipped capital femoral epiphysis Femur fractures Knee injuries Osgood-Schlatter disease Tibia and fibula fractures Ankle injuries Foot injuries Toe injuries Approach to the special needs child

Discussion of Individual Diagnoses Traumatic Hip Dislocation Traumatic hip dislocations are relatively rare in children.1 The mechanisms of injury involve high-energy events such as falls from substantial heights and motor vehicle accidents. Children generally present with groin and thigh pain, flexion and external rotation of the involved hip, and apparent shortening of the lower extremity. A small percentage of children with hip dislocations will also have associated acetabular fractures.1 Posterior dislocations are the most common. Pain control and neurovascular assessment are important factors in the initial emergency department evaluation of these children. An anterior-posterior pelvis radiograph will usually confirm the diagnosis (Fig. 20–1). Closed reduction by the emergency physician is indicated. The use of procedurerelated sedation for this procedure is prudent. Once success182

A slipped capital femoral epiphysis (SCFE, usually pronounced “skiffy”) results from shearing forces through the proximal femoral physis. This is a type of Salter-Harris type I fracture (Fig. 20–2). SCFE is in the differential diagnosis of any child with a limp and no other constitutional symptoms.2-4 The most commonly affected age group includes older school-age children and younger adolescents. Bone age is probably more important than chronological age.5 There may be a history of relatively minor trauma. The onset may be sudden and rather obvious or indolent and subtle. The child may complain of groin, hip, or knee pain. In particular, an older school-age child who has seen multiple physicians for knee pain, has undergone multiple normal radiographs of the knee, and has a normal knee examination is a classic example of an indolent case of SCFE. More than 20% of children with SCFE will have bilateral disease at presentation or will develop SCFE on the contralateral side at some point in childhood.6 Obese children are at higher risk for bilateral disease.6 When SCFE is suspected, anterior-posterior and frog-leg lateral hip radiographs and an anterior-posterior pelvis radiograph are indicated. The key finding on radiographs is an abnormal position of the proximal femoral epiphysis in relation to the metaphysis. This has been referred to as “the ice cream falling off the cone.” When slippage is not obvious, evaluation of Klein’s line is useful.7 Klein’s line is drawn along the superior aspect of the femoral neck and should intersect the femoral epiphysis. Failure of Klein’s line to intersect the femoral epiphysis is supportive of the diagnosis of SCFE. Once SCFE is identified, orthopedic consultation is indicated. Operative stabilization is usually undertaken. The timing of this is controversial and is at the discretion of the orthopedist.8 If radiographs are normal yet the diagnosis of

Chapter 20 — Lower Extremity Trauma

SCFE remains likely, one reasonable plan is to discharge the patient home with crutches and instructions for non–weight bearing on the involved extremity. Arrangements can then be made for an outpatient magnetic resonance imaging (MRI) study of the hip within 1 to 2 weeks.9 Complications of SCFE include avascular necrosis of the femoral head and

183

osteoarthritis of the hip. A delayed diagnosis increases the risk of complications. Even with appropriate management, avascular necrosis occurs in as many as 14% of children diagnosed with SCFE.10 Femur Fractures Femur fractures are the most common traumatic orthopedic injuries requiring hospitalization.11 Most femur fractures result from a high-impact mechanism, and the patients present with obvious swelling, deformity, pain, and tenderness in the affected thigh. Shortening of the involved extremity will be evident on physical examination. Infants and nonverbal children with femur fractures may present with a history of refusing to crawl, excessive crying, and swelling over the thigh or tenderness over the fracture site. Although femur fractures in nonambulatory infants and children are suggestive of nonaccidental trauma, they are not pathognomonic for child abuse12 (see Chapter 119, Physical Abuse and Child Neglect). Emergency department management of femur fractures generally involves splinting, analgesia, and monitoring the neurovascular status of the involved extremity. Radiographs of femur fractures are seldom subtle. Unlike adults, isolated, closed femur fractures have not been found to be a significant cause of hypotension in children.13,14 If a child with a closed femur fracture is experiencing hemodynamic instability, alternative causes should be investigated. Orthopedic consultation in the emergency department is indicated for most

FIGURE 20–1. Radiograph of a traumatic hip dislocation.

Salter-Harris Classification of Growth Plate Fractures

Metaphysis Physis (growth plate) Epiphysis Normal

Non-displaced Type I fracture (Radiographically normal)

FIGURE 20–2. Salter-Harris classification of growth plate fractures. (Adapted from Salter RB, Harris WR: Injuries involving the epiphyseal plate. J Bone Joint Surg [Am] 45:587–622, 1963.)

Displaced Type I fracture

Type II fracture

Crush

Type III fracture

Type IV fracture

Type V fracture

184

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femur fractures as most infants and children under age 6 are treated with spica casting and those over 6 years are typically treated with open reduction and internal fi xation.11 In certain circumstances, children with femur fractures can be discharged home from the emergency department without orthopedic consultation. Examples of these fractures include a child with a torus fracture of the femoral metaphysis without significant displacement or angulation and an adolescent with an avulsion fracture of the lesser trochanter.15 Knee Injuries Urgent orthopedic consultation is seldom needed for knee injuries seen in the pediatric emergency department. Specific conditions managed by the emergency physician include patellar dislocations and injuries to the menisci and ligaments. In most patellar dislocations, the patella is displaced laterally. Reduction is straightforward and is accomplished by extending the knee. This reduction is somewhat painful, but mercifully brief and simple to perform. Procedural sedation is seldom needed. Prompt pain relief is expected. Discharge to home in a knee immobilizer is the usual disposition. Orthopedic or primary care follow-up for a gradual return to normal activities is appropriate. Meniscal and ligamentous injuries are frequently due to a forced twisting motion of the knee. Frequently, the patient will have joint swelling due to hemarthrosis. Joint line tenderness is expected in most of these injuries. Injuries to the ligaments will result in a degree of joint laxity in the direction supported by the injured ligament. However, if the knee is excessively tender and swollen, testing for joint laxity will not be feasible. Radiographs typically will not reveal a fracture unless ligamentous disruption has resulted in a small avulsion fracture. Discharge to home in a knee immobilizer with or without crutches is the usual disposition. Orthopedic follow-up with the expectation of an outpatient MRI is a reasonable plan under most circumstances.16,17 There has recently been some interest in using bedside ultrasound to evaluate ligamentous and meniscal injuries.18 The role for ultrasound for this purpose is unclear at this point. Traditionally, nearly all patients with injured knees underwent radiographs. Although obviously indicated in severe injuries, the utility of these radiographs on the less acute end of the continuum of injuries was frequently questionable at best. In an attempt to limit unnecessary knee radiographs, the Ottawa knee rules were developed19-21 (Table 20–1). Recent studies have validated the Ottawa knee rules for children.19-21 Unfortunately, relatively few young children were

included in these studies, thus limiting the applicability of the rules to younger children. Applying the Ottawa knee rules to older school-age children and adolescents is probably reasonable. Several conditions involving the knee require urgent orthopedic consultation. These include open fractures, displaced fractures involving the growth plate, penetrating injuries involving the joint space, significantly avulsed tibial spine fractures, and foreign bodies within the joint space.22 Another injury pattern requiring prompt orthopedic consultation is the “floating knee,” which results from ipsilateral femoral and tibial fractures. This fracture combination is relatively rare in children, arising in the setting of highenergy trauma such as occurs when pediatric pedestrians are struck by automobiles (i.e., “auto vs. pedestrian”). Children with floating knees present with pain, swelling, and obvious deformity over the fracture sites. There is substantial instability of the entire middle of the lower extremity. Bedside portable radiographs are usually sufficient to make the diagnosis. Emergent angiography, including assessment of the popliteal vessels, is indicated. The initial emergency department management of these injuries involves providing adequate analgesia, applying a posterior long-leg splint, and obtaining prompt orthopedic consultation. The defi nitive treatment is open reduction and internal fi xation.23,24 The knee is the most common joint to sustain a penetrating injury. Treatment of children is similar to that of adults. Plain radiographs can be obtained to evaluate for associated fracture, air in the joint space indicating a violation of the joint, and the presence of a radiopaque foreign body. In addition, vascular trauma must be diagnosed in a timely manner to assure appropriate treatment. Bynoe et al. found duplex ultrasonography to accurately locate vascular injuries.25 In appropriate hands, duplex ultrasonography may serve as a noninvasive alternative to arteriography. Deep lacerations in close proximity to the joint should raise suspicion for an open joint wound. This can be confirmed by performing an arthrogram of the joint. An arthrogram is performed by preparing a sterile field on a site distant from the laceration and inserting a relatively large-bore needle (e.g., 18 gauge) into the joint space. By infusing injectable, sterile normal saline (from a bag of normal saline used for intravenous infusion, not the saline used for wound irrigation) into the joint space until there is swelling, the emergency physician observes for fluid leakage from the wound. Fluid leakage suggests on open joint injury. This should prompt urgent orthopedic consultation for operative washout and repair. Osgood-Schlatter Disease

Table 20–1

Ottawa Knee Rules

Obtain knee radiographs if there is a history of acute knee injury and at least one of the following: • Inability to walk 4 steps immediately after the injury and in the emergency department (regardless of limp) • Tenderness over the patella • Tenderness of the head of the fibula • Inability to flex the knee to 90 degrees • Age greater than 55 yr Data from Khine H, Dorfman DH, Avner JR: Applicability of Ottawa knee rule for knee injury in children. Pediatr Emerg Care 17:401–404, 2001.

Osgood-Schlatter disease refers to osteochondrosis of the anterior tuberosity of the tibia.26 Osteochondrosis is a “disease of ossification centers in children that begins as a degeneration or necrosis followed by regeneration or recalcification.”26 Osgood-Schlatter disease is a relatively common condition in adolescents and is more common in boys.27 As many as 25% to 50% of cases are bilateral.27 There is some debate as to whether this disease is a form of tendonitis or a Salter-Harris type I fracture of the tibial tubercle28 (see Fig. 20–1). These patients often present with knee pain that is worse with activity and relieved with rest. The physical examination is generally diagnostic, with tenderness and a bony bulge at the site of the tibial tuberosity. Radiographs are seldom needed for

Chapter 20 — Lower Extremity Trauma

the diagnosis or management of suspected Osgood-Schlatter disease. The usual treatment is conservative and consists of rest, anti-inflammatory/analgesic medications (e.g., ibuprofen), and follow-up with a primary care physician. For serious athletes, follow-up with a sports medicine physician is ideal to allow for maximum participation balanced with sufficient rest to minimize pain. Tibia and Fibula Fractures Most fractures of the fibula occur in association with tibia fractures. Isolated fibula fractures are rare in children. The location of the injury is usually clear from the physical examination, in which crepitus, a palpable step-off, bruising, and tenderness are expected at the fracture site. Radiographs of the entire tibia and fibula tend to offer adequate visualization of clinically important fractures. The identification of a fracture of both the tibia and fibula is straightforward. Emergency department management with a posterior molded splint is also straightforward. However, because of the relatively “tight” compartments of the leg, compartment syndrome may develop due to swelling at the fracture site (see Chapter 22, Compartment Syndrome). Prolonged periods of elevation are indicated during the first day or two after the injury. Admission to an observation unit or to the hospital overnight after reduction and splinting is suggested. Selected patients likely to be very compliant with the elevation requirement are the best candidates for discharge home from the emergency department. A tibial fracture seen only in young children is the toddler’s fracture. Toddler’s fractures are oblique or spiral fractures in the middle or distal third of the tibia. These fractures are due to a twisting force. Classically, these fractures have no displacement and no angulation. The classic story is of a toddler limping or refusing to walk after getting the foot caught in something and falling while twisting about to release the foot. The child may present without a clear mechanism of injury, however. The physical examination findings may be subtle. If the child is able to tolerate the examination, pain may be elicited at the fracture site. There is typically little, if any swelling. The overlying skin usually appears normal. Toddler’s fractures are notoriously difficult to diagnose on plain radiographs: the fracture may appear to be a “nutrient vessel” with a dark, oblique line running through the tibial shaft without apparent violation of the cortex, or it may appear on only one view. The fracture may not be evident at all on initial radiographs, only appearing when repeat radiographs are obtained 7 to 10 days after the injury as callus formation becomes radiographically evident.29 Treatment for toddler’s fractures, both those clearly diagnosed and those merely suspected, is with a long-leg splint and close follow-up with a primary care physician or orthopedist in 7 to 10 days.30-33 Ankle Injuries Ankle injuries are common. The ankle is a flexible, multidirectional, narrow joint that must support the body’s entire weight while moving and changing direction over uneven surfaces. Ankle injuries can range from minor strains of the supporting ligaments to serious fractures requiring operative intervention. At the more serious end of the injury spectrum are the Tillaux fracture and the Maisonneuve fracture. The Tillaux

185

fracture is a Salter-Harris type III fracture of the lateral, distal tibia. This fracture appears to be unique to adolescents. The fracture pattern is thought to result from asymmetric closing of the growth plate with the medial aspect closing earlier than the lateral aspect. This fracture may be difficult to appreciate on plain radiographs. Computed tomographic (CT) scanning may be required to make the diagnosis.34 Open reduction and internal fi xation are usually required.35 The Maisonneuve fracture is actually two fractures. The fi rst is a medial malleolar fracture (of the distal tibia). The second is an oblique fracture of the proximal fibula. If the physical examination and plain radiographs focus exclusively on the ankle, this proximal fibula fracture might be missed. With most Maisonneuve fractures there is disruption of the interosseous membrane between the tibia and fibula. When this occurs, the ankle joint is unstable and subsequent diastasis of the joint is likely. Maisonneuve fractures typically require open reduction and internal fi xation.36 Along the more minor end of the spectrum of ankle injuries are ankle sprains and “occult” distal fibula fractures. Classic teaching has suggested that the ligaments of pediatric ankles are stronger than the growth plate of the distal fibula. If true, nondisplaced Salter-Harris type I fractures of the distal fibula would be expected to be more common than ankle sprains in children. For children who have sustained inversion injuries to the ankle and have normal radiographs, the treatment recommendations have typically focused on immobilization with a posterior molded splint and avoidance of weight bearing. The recommended follow-up plan is then to have a primary care physician or orthopedist reevaluate the child in about 10 days with the expectation of repeat radiographs to look for callus formation. Preliminary work with ultrasound suggests that it may be able to differentiate ankle sprains from occult distal fibula fractures.37 Further study is required before ultrasound can be recommended for this purpose. One area of controversy is the use of the Ottawa ankle rules for evaluating children with ankle injuries (Table 20–2). The Ottawa ankle rules were developed to minimize the use of unnecessary radiographs in the evaluation of relatively minor ankle injuries.38 A few studies have supported the use of the Ottawa ankle rules in children,39-41 and one study found the

Table 20–2

Ottawa Foot and Ankle Rules

Obtain ankle radiographs if there is acute ankle injury and at least one of the following: • Inability to bear weight (4 steps) immediately after the injury and in the emergency department regardless of limp • Tenderness to palpation over the posterior edge or tip of the lateral malleolus • Tenderness to palpation over the posterior edge or tip of the medial malleolus Obtain foot radiographs if there is a history of acute foot injury and at least one of the following: • Inability to bear weight immediately after the injury and in the emergency department • Tenderness to palpation over the base of the 5th metatarsal • Tenderness to palpation over the navicular bone Data from Stiell IG, McKnight RD, Greenberg GH, et al: Implementation of the Ottawa Ankle Rules. JAMA 271:827–832, 1994.

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Ottawa ankle rules inappropriate for children.42 Other decision rules have also been suggested for evaluating pediatric ankle injuries.43,44 The clinical application of any of these decision rules is dependent on the emergency physician’s tolerance for failing to identify a clinically insignificant ankle fracture. The use of radiograph-minimizing decision rules for children remains controversial. What is clear, however, is that skeletally mature adolescents with ankle injuries can be treated like adults with similar injuries.38 Foot Injuries Pediatric midfoot and hindfoot fractures are relatively common. In younger children, these fractures often present with a chief complaint of limp and may be mistakenly diagnosed as a toddler’s fracture or foot sprain as the initial radiographs may be normal at the time of the emergency department visit. In cases of subtle midfoot and hindfoot injuries, plain radiographs obtained 2 to 4 weeks after the initial visit will typically reveal sclerotic changes at the fracture sites.45,46 The most commonly seen of these fractures involve the calcaneus or cuboid. Because of the difficulty in diagnosing subtle midfoot and hindfoot fractures, bone scans have been advocated for the early evaluation of these fractures.45-47 However, the clinical outcomes of these injuries is generally excellent without any particular intervention suggesting that bone scans may only be indicated for serious athletes or other special groups. Displaced fractures of the calcaneus and the midfoot sustained under a high-impact mechanism require orthopedic consultation in the emergency department. Avascular necrosis is a serious complication of these fractures. Lisfranc-type injuries (tarsometatarsal joint injuries after a midfoot plantar-flexion injury) rarely occur in young children. Unlike adults and adolescents who require urgent orthopedic consultation in the emergency department, younger children with these injuries can be successfully managed with a short-leg walking cast for 3 to 7 weeks.48 One complication of Lisfranc-type injuries is compartment syndrome. Therefore, elevation of the injured foot and monitoring for the development of compartment syndrome are indicated for these injuries. Common foot injuries in all age groups are proximal fifth metatarsal fractures. These fractures arise from inversion injuries of the foot and may be missed if the physical examination and evaluation of the radiographs focuses exclusively on the ankle. This is reflected in the inclusion of these fractures in the Ottawa ankle rules (see Table 20–2). The location of the fracture determines the management and prognosis. The most proximal fractures are usually avulsion fractures and are often referred to as dancer’s fractures. These fractures can usually be treated in a hard-soled shoe for a few weeks and seldom lead to complications. Follow-up with a primary care physician is reasonable for these common fractures. More distal fractures are usually referred to as Jones fractures. There is not a well-defined distinction between dancer’s fractures and Jones fractures. In adults, dancer’s fractures are thought to occur within 1.5 cm from the proximal tip of the fifth metatarsal, while Jones fractures occur more distally. Jones fractures do not heal as well as dancer’s fractures and may require open reduction and internal fi xation if closed treatment fails. A short-leg, posterior molded splint and the avoidance of weight bearing are usually indicated for Jones fractures. Alternatively, a walking boot may

be used. Follow-up with an orthopedist is indicated for Jones fractures. The approach to the patient with a puncture wound to the plantar surface of the foot depends on the mechanism of injury, the timing of the injury, and the possibility of a retained foreign body (see Chapter 160, Wound Management). Plain radiographs can aid in documenting the presence of radiopaque foreign bodies such as glass and metal. For wooden foreign bodies, ultrasound, CT scanning, and MRI may be reasonable imaging studies depending on the individual circumstances.49-52 Lawnmower and bicycle spoke injuries can result in extensive bony and soft tissue damage and loss. Urgent orthopedic consultation is indicated. Toe Injuries Nondisplaced fractures of the toes are seldom serious and are generally treated with “buddy taping” the injured toe to the adjacent toe. For displaced fractures, closed reduction and buddy taping by the emergency physician is usually adequate. This is particularly important for fifth toe fractures. If reduction is not accomplished, the fifth toe will protrude laterally from the foot. This leads to the patient “catching” the toe on objects when walking barefoot at any point in the future. Orthopedic consultation in 1 to 2 weeks may be obtained on an outpatient basis for unstable fractures. Great toe injuries with bleeding around the nail bed are probably best treated as open fractures with irrigation and prophylactic antibiotics to minimize the risk of osteomyelitis.53 Cephalexin (25 mg/kg per dose three times per day for 7 days) is a reasonable antibiotic choice. Approach to the Special Needs Child Technology-dependent children and those who are not ambulatory frequently have osteopenia that places them at high risk for fractures. Certain conditions are well known to predispose children to fractures. Examples include osteogenesis imperfecta and Ehlers-Danlos syndrome. Fracture of the lower extremity is included in the differential diagnosis for the fussy special needs child, especially if the examination reveals redness, swelling, or possible tenderness to palpation of the lower extremity. There may be a recent history of physical therapy or pain during patient transfer (such as in and out of a specialized wheelchair), but no history of any significant trauma, such as a fall. Plain radiographs of the involved extremity from the hip to the toes may be needed to locate the injury. Fractures in the nonambulating special needs child generally can be treated with splinting and pain control. Closed reduction of significantly displaced fractures is prudent. Procedural sedation may be required to accomplish these reductions (see Chapter 159, Procedural Sedation and Analgesia). REFERENCES 1. Mehlman CT, Hubbard GW, Crawford AH, et al: Traumatic hip dislocation in children. Clin Orthopedics 376:68–79, 2000. *2. Kocher MS, Bishop JA, Weed B, et al: Delay in the diagnosis of slipped capital femoral epiphysis. Pediatrics 113:322–325, 2004. 3. Ledwith CA, Fleisher GR: Slipped capital femoral epiphysis without hip pain leads to missed diagnosis. Pediatrics 89:660–662, 1992.

*Selected readings.

Chapter 20 — Lower Extremity Trauma 4. Matava MJ, Patton CM, Luhmann S, et al: Knee pain as the initial symptom of slipped capital femoral epiphysis: an analysis of initial presentation and treatment. J Pediatr Orthop 19:455–460, 1999. 5. Loder RT, Starnes T, Dikos G: The narrow window of bone age in children with slipped capital femoral epiphysis: a reassessment one decade later. J Pediatr Orthop 26:300–306, 2006. *6. Bhatia NN, Pirpiris M, Otsuka NY: Body mass index in patients with slipped capital femoral epiphysis. J Pediatr Orthop 26:197–199, 2006. 7. Klein A, Joplin RJ, Reidy JA, et al: Roentgenographic features of slipped capital femoral epiphysis. Am J Roentgenol Radium Ther 66:361–374, 1951. 8. Kalogrianitis S, Tan CK, Kemp GJ, et al: Does slipped capital femoral epiphysis require urgent stabilization? J Pediatr Orthop B 16:6–9, 2007. 9. Umans H, Liebling MS, Moy L, et al: Slipped capital femoral epiphysis: a physeal lesion diagnosed by MRI with radiographic and CT correlation. Skeletal Radiol 27:139–144, 1998. 10. Krahn TH, Canale ST, Beaty JH, et al: Long-term follow-up of patients with avascular necrosis after treatment of slipped capital femoral epiphysis. J Pediatr Orthop 13:154–158, 1993. 11. Heyworth BE, Galano GJ, Vitale MA, et al: Management of closed femoral shaft fractures in children ages 6 to 10: national practice patterns and emerging trends. J Pediatr Orthop 24:455–459, 2004. 12. Scherl SA, Miller LM, Lively N, et al: Accidental and nonaccidental femur fractures in children. Clin Orthop 376:96–105, 2000. 13. Anderson WA: The significance of femoral fractures in children. Ann Emerg Med 11:174–177, 1982. 14. Ciarallo L, Fleisher G: Femoral fractures: are children at risk for significant blood loss? Pediatr Emerg Care 12:343–346, 1996. 15. Kim SS, Thomas M: A football player with thigh pain. Pediatr Emerg Care 17:267–268, 2001. 16. Stanitski CL: Correlation of arthroscopic and clinical examinations with magnetic resonance imaging fi ndings of injured knees in children and adolescents. Am J Sports Med 26:2–6, 1998. 17. Wessel LM, Scholz S, Rusch, M, et al: Hemarthrosis after trauma to the pediatric knee joint: what is the value of magnetic resonance imaging in the diagnostic algorithm? J Pediatr Orthop 21:338–342, 2001. 18. O’Reilly MA, O’Reilly PM, Bell J: Sonographic appearances of medial retinacular complex injury in transient patellar dislocation. Clin Radiol 58:636–641, 2003. *19. Bulloch B, Neto G, Plint A, et al: Validation of the Ottawa knee rule in children: a multicenter study. Ann Emerg Med 42:48–55, 2003. 20. Khine H, Dorfman DH, Avner JR: Applicability of Ottawa knee rule for knee injury in children. Pediatr Emerg Care 17:401–404, 2001. *21. Stiell IG, Greenburg GH, McKnight RD, et al: Decision rules for the use of radiography in acute knee injuries: refi nement and prospective validation. JAMA 269:1127–1132, 1994. *22. Salter RB, Harris WR: Injuries involving the epiphyseal plate. J Bone Joint Surg [Am] 45:587–622, 1963. 23. Arslan H, Kapukaya H, Kesemenli C, et al: Floating knee in children. J Pediatr Orthop 23:458–463, 2003. 24. Yue JJ, Churchill RS, Copperman DR, et al: The floating knee in the pediatric patient. Clin Orthop 376:124–136, 2000. 25. Bynoe RP, Miles WS, Bell RM, et al: Noninvasive diagnosis of vascular trauma by duplex ultrasonography. J Vasc Surg 3:346–352, 1991. 26. Anderson DM, Novak PD, Keith J, et al (eds): Dorland’s Illustrated Medical Dictionary, 30th ed. Philadelphia: WB Saunders, 2003, p 1333. 27. Osgood RB: Lesions of the tibial tubercle occurring during adolescence. Boston Med Surg J 148:114–117, 1903. 28. Rosenberg ZS, Kawelblum M, Cheung YY, et al: Osgood-Schlatter lesion: fracture or tendonitis? Scintigraphic, CT, and MR imaging features. Radiology 185:853–858, 1992.

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*29. Oudjhane K, Newman B, Oh KS, et al: Occult fractures in preschool children. J Trauma 28:858–860, 1988. 30. Englaro EE, Gelfand MJ, Paltiel HJ: Bone scintigraphy in preschool children with lower extremity pain of unknown origin. J Nucl Med 33:351–354, 1992. 31. John SD, Moorthy CS, Swischuk LE: Expanding the concept of the toddler’s fracture. Radiographics 17:367–376, 1997. 32. Mellick LB, Ressor K: Spiral tibial fractures of children: a common accidental spiral long bone fracture. Am J Emerg Med 8:234–237, 1990. 33. Tenenbein MH, Reed MH, Black GB: The toddler’s fracture revisited. Am J Emerg Med 8:208–211, 1990. 34. Horn BD, Crisci K, Krug M, et al: Radiologic evaluation of juvenile Tillaux fractures of the distal tibia. J Pediatr Orthop 21:162–164, 2001. 35. Koury SI, Stone CK, Harrell G, et al: Recognition and management of Tillaux fractures in adolescents. Pediatr Emerg Care 15:37–39, 1999. 36. Duchesneau S, Fallat LM: The Maisonneuve fracture. J Foot Ankle Surg 34:422–428, 1995. 37. Farley FA, Kuhns L, Jacobson JA, et al: Ultrasound examination of ankle injuries in children. J Pediatr Orthop 21:604–607, 2001. *38. Stiell IG, Greenburg GH, McKnight RD, et al: A study to develop clinical decision rules for the use of radiography in acute ankle injuries. Ann Emerg Med 21:384–390, 1992. 39. Chande VT: Decision rules of roentgenography of children with acute ankle injuries. Arch Pediatr Adolesc Med 149:255–258, 1995. 40. Libetta C, Burke D, Brennan P, et al: Validation of the Ottawa ankle rules in children. J Accid Emerg Med 16:342–344, 1999. *41. Plint A, Bulloch B, Osmond M, et al: Validation of the Ottawa ankle rules in children with ankle injuries. Acad Emerg Med 6:1005–1009, 1999. 42. Clark KD, Tanner S: Evaluation of the Ottawa ankle rules in children. Pediatr Emerg Care 19:73–78, 2003. 43. Boutis K, Komar L, Jaramillo D, et al: Sensitivity of a clinical examination to predict the need for radiography in children with ankle injuries: a prospective study. Lancet 358:2118–2121, 2001. 44. Dayan PS, Vitale M, Langsam D, et al: Derivation of clinical prediction rules to identify children with fractures after twisting injuries of the ankle. Acad Emerg Med 11:736–743, 2004. 45. Blumberg K, Patterson RJ: The toddler’s cuboid fracture. Radiology 179:93–94, 1991. 46. Schindler A, Mason DE, Allington NJ: Occult fracture of the calcaneus in toddlers. J Pediatr Orthop 16:201–205, 1996. 47. Lalotis N, Pennie BH, Carty H, et al: Toddler’s fracture of the calcaneum. Injury 24:169–170, 1993. 48. Buoncristiani AM, Manos RE, Mills WJ: Plantar-flexion tarsometatarsal joint injuries in children. J Pediatr Orthop 21:324–327, 2001. 49. Mizel MS, Steinmetz ND, Trepman E: Detection of wooden foreign bodies in muscle tissue: experimental comparison of computed tomography, magnetic resonance imaging, and ultrasonography. Foot Ankle Int 15:437–443, 1994. 50. Yanay O, Vaughan, DJ Brownstein, D, et al: Retained wooden foreign body in a child’s thigh complicated by severe necrotizing faciitis: a case report and a discussion of imaging modalities for early diagnosis. Pediatr Emerg Care 17:354–355, 2001. 51. Imoisili MA, Bonwit AM, Bulas DI: Toothpick puncture injuries of the foot in children. Pediatr Infect Dis J 23:80–82, 2004. *52. Inaba AS, Zukin DD, Perro M: An update on the evaluation and management of plantar puncture wounds and Pseudomonas osteomyelitis. Pediatr Emerg Care 8:38–44, 1992. 53. Kensiger DR, Guille JT, Horn BD, et al: The stubbed great toe: importance of early recognition and treatment of open fractures of the distal phalanx. J Pediatr Orthop 21:31–41, 2001.

Chapter 21 Pelvic and Genitourinary Trauma Peter S. Auerbach, MD

Key Points In children, mortality directly related to pelvic fractures is very low. “Routine” pelvic radiographs are no longer advocated. Approximately 10% of children with pelvic fractures also have injuries to the genitourinary system. The utility of a microscopic urinalysis is unclear. Blood seen at the penile meatus is a contraindication to blindly placing a Foley catheter.

Introduction and Background Pelvic fractures are relatively uncommon in children, occurring in 3% to 5% of children versus 6% to 10% of adult blunt trauma patients.1,2 When fractures of the pelvis do occur in children, they are usually associated with a severe mechanism and multiple associated injuries. Mortality from pelvic fractures is lower in children than in adults due to differences in the types of fractures sustained and the inherent fracture resistance of the bony and ligamentous structures of the pediatric pelvis. Although rarely life threatening, injuries to the genitourinary system often occur in children with pelvic trauma and are sometimes overlooked during the initial assessment due to the high incidence of higher priority, associated injuries. Lower genitourinary injuries (i.e., injuries to the bladder, urethra, and genitals) are seen in fewer than 5% of children with pelvic fractures.3 Urethral injuries are difficult to diagnose. Serious renal injuries are seldom missed because of the high frequency with which abdominal and pelvic computed tomographic (CT) scanning are performed on traumatized children.

Recognition and Approach The most common mechanism of injury resulting in pediatric pelvic fractures is a pedestrian struck by a motor vehicle.4-7 In contrast, adults who sustain pelvic fractures are more 188

likely to be the driver or passenger in a motor vehicle collision.1,2 The most common significant injury associated with pelvic fractures in children is a head injury. Intra-abdominal solid organ injuries are also commonly associated with pelvic fractures. The classification of pediatric pelvic fractures has not been standardized, which makes a direct comparison of published studies difficult. Of the classification systems used, the most widely accepted classifies pelvic fractures into three types based on structural integrity8 (Fig. 21–1). Type A fractures spare the posterior pelvic arch and are therefore mechanically stable. Commonly seen type A fractures include those of the pubic rami. Type B fractures involve incomplete disruption of the posterior arch, making the pelvic ring horizontally unstable but vertically stable. Type B pelvic fractures are frequently the result of anterior-posterior compression. Type C fractures involve complete disruption of the posterior arch, often through the sacroiliac joint, rendering the pelvic ring both horizontally and vertically unstable. Type C pelvic fractures are frequently the result of vertical forces resulting from a fall. Type B and C fractures are relatively rare in children.4,5 The pediatric genitourinary system differs from that of adults in several important ways. The kidneys are more easily injured in children because they are relatively larger in size and less well protected by the ribs. Children tend to have less perirenal fat, weaker abdominal muscles, and a flexible rib cage. In addition, pediatric kidneys are more likely to contain persistent fetal lobulations, which may predispose to parenchymal disruption during blunt trauma.9 The pediatric bladder is more susceptible to injury because it extends superiorly into the abdomen and is less well protected by the pelvic ring. The bladder wall musculature is weakest at the superior pole, where it lies in contact with the peritoneum, making intraperitoneal bladder rupture more likely. In boys, the urethra may also be more susceptible to injury because it is less elastic and less well protected by the prostate.10 Injuries may involve any portion of the genitourinary system. The kidney is the most commonly injured portion of the genitourinary system. The most widely accepted scoring system for kidney injuries is incorporated into the comprehensive Organ Injury Scoring and Scaling System11 (Table 21–1). Most pediatric kidney injuries identified are grade I. The bladder is the second most frequently injured component of the genitourinary system. There is some utility in

Chapter 21 — Pelvic and Genitourinary Trauma

Table 21–1 Grade I II

A

III

IV V

189

Kidney Injury Scoring

Description of Injury Contusion or Subcapsular hematoma Nonexpanding perirenal hematoma confined to the retroperitoneum or 1.0-cm renal parenchymal laceration without urinary extravasation or Collecting system involvement Laceration extending into the collecting system or Renal artery or vein injury with contained hemorrhage Shattered kidney or Avulsion of renal hilum, which devascularizes kidney

Adapted from the Organ Injury Scaling Committee of the American Association for the Surgery of Trauma.11

B

C FIGURE 21–1. Classification of pelvic fractures. Type A, Lesions sparing (or with no displacement of) the posterior pelvic arch. Type B, Incomplete disruption of the posterior arch (partially stable). Type C, Complete disruption of the posterior arch (unstable). (Images courtesy of the Orthopedic Trauma Association.)

separating bladder injuries into three general categories: bladder contusions, extraperitoneal bladder rupture, and intraperitoneal bladder rupture. Contusions are partial tears of the bladder mucosa. Extraperitoneal bladder rupture usually occurs as a result of a displaced pelvic fracture lacerating the bladder. Intraperitoneal bladder rupture usually results from significant blunt trauma to a full bladder. Intraperitoneal bladder rupture is the most serious type of bladder injury and is the most likely type of bladder injury to require operative repair. Bladder injuries almost always present with gross hematuria, difficulty with urination, or significant abdominal pain.3 The male urethra is susceptible to injury during pelvic and perineal trauma. The male urethra is anatomically divided into posterior and anterior segments by the urogenital diaphragm between the pubic rami. The posterior segment is proximal and the anterior segment is distal. The two segments of the male urethra have different patterns of

injury. Posterior urethral injuries result from high-energy blunt trauma and are often associated with pelvic fractures and bladder injuries (Fig. 21–2). In contrast, anterior urethral trauma usually results from straddle injuries. Anterior urethral injuries are associated with external genital injuries. Both types of urethral injuries almost always present with blood at the penile meatus. Accidental injuries to the female urethra are extremely rare and are almost always accompanied by pelvic fractures.12 Blunt trauma to the pelvis and perineum can also result in injury to the external genitalia. In males, the most common genital injuries occur to the testicles. Injuries to the testicle include testicular rupture, traumatic torsion, dislocation, hematomas, and hematoceles (see Chapter 87, Testicular Torsion). In females, the most common accidental injuries to the external genitalia involve minor vulvar lacerations from straddle injuries.

Evaluation The initial approach to a child with possible pelvic or genitourinary trauma should begin with an accurate description of the mechanism of injury. A history of significant deceleration is associated with renal injuries even in the absence of abnormal physical findings or gross hematuria.13-15 Physical examination findings associated with pelvic fractures include pelvic tenderness, instability on gentle compression, and ecchymoses or abrasions directly overlying the bony pelvis. In most children with serious pelvic injuries, CT scanning of the abdomen and pelvis is ostensibly performed for other indications (see Chapter 25, Abdominal Trauma). When CT scanning is performed, these images of the bony pelvis preclude the need for plain radiographs. If CT scanning is not planned, a single anterior-posterior pelvis radiograph may be obtained if indicated by the physical examination. Routine pelvis radiographs as part of a traditional “C-spine/chest/ pelvis” set of radiographs are no longer advocated. Several recent pediatric studies of blunt trauma patients have

190

A

SECTION II — Approach to the Trauma Patient

B

C

FIGURE 21–2. Retrograde urethrogram demonstrating posterior urethral tear in a 16-year-old boy. A, Immediate extravasation of contrast at the level of the prostatic urethra. B and C, Further retrograde dye injection demonstrates extravasation of nearly all contrast medium with no significant filling of the bladder.

demonstrated that the “routine” pelvis radiograph has extremely low yield and may be safely omitted in many patients. In particular, this is true for children with normal mental status, a normal physical examination of the pelvis, and no distracting injuries.16-18 Open pelvic fractures are rare in children but have a mortality rate of 20% or higher.19 Open pelvic fractures must therefore be excluded through a detailed examination of the overlying skin. Any laceration near a fracture site, as well as on the buttocks, perineum, or genital area, is suspicious for an open fracture. Although rectal examinations are seldom indicated otherwise,20,21 a careful rectal examination should be performed in patients with displaced pelvic fractures to exclude internal lacerations. Care must be taken by the examiner to avoid sustaining a finger laceration. These examinations may require procedural sedation or general anesthesia to be performed safely. Girls with displaced pelvic fractures should have a cautious manual vaginal examination. For prepubertal girls who are not comatose, it is prudent to perform these examinations with procedural sedation or under general anesthesia. The physical examination may suggest particular genitourinary injuries. Physical fi ndings suggestive of renal injury include flank or lateral abdominal tenderness, ecchymosis, hematomas, or a palpable mass. In the absence of such findings, gross hematuria alone is a highly sensitive sign of a serious renal injury and should prompt radiographic imaging. Patients with bladder or urethral injuries may complain of lower abdominal pain, urinary urgency, or the inability to void. Physical findings associated with lower genitourinary injuries include gross hematuria, blood at the penile meatus, suprapubic tenderness, and a palpable, tender bladder. Gross hematuria is seen in nearly all cases of lower genitourinary injuries, and its absence is enough to exclude significant bladder or urethral injury unless abnormal physical examination findings or multiple associated injuries are present.3,22 The finding of blood at the penile meatus is highly sensitive for urethral injury and is a contraindication to blind urethral catheterization, even if a patient is able to spontaneously void. If catheterization is inappropriately attempted, the

urinary catheter could convert a partial urethral tear into a complete tear. Historically, various degrees of microscopic hematuria have been used to screen for the presence of renal injury.23-29 There continues to be debate in the literature over how many red blood cells on microscopic urinalysis should be considered significant enough to prompt genitourinary imaging in the absence of other indications. The quest for this “magic number” of red blood cells has not led to a definitive result. Data from multiple recent pediatric studies suggest that isolated microscopic hematuria has a very low yield when used as the sole indication for genitourinary imaging.13-15,30-32 It is conceivable that the test characteristics of microscopic urinalysis for identifying genitourinary injuries are not good enough to advocate using microscopic hematuria for this kind of decision making. Contemporary options for imaging children at risk for genitourinary injuries include CT scanning, ultrasound, cystograms, and urethrograms. The studies selected reflect the anatomic area of concern and, to some extent, the overall hemodynamic stability of the patients. Historically, the intravenous pyelogram was used to image the kidneys and ureters,23,24 but CT scanning is now the imaging modality of choice. CT scanning leads to faster results, is more sensitive for identifying renal injuries, and can be used to identify injuries to other intra-abdominal and pelvic structures.13,33 Ultrasound has a sensitivity for renal injury of only 70%, but can be performed rapidly at the bedside and does not require the use of intravenous contrast or radiation.34 Ultrasound may have the greatest utility in pregnant girls and any child too hemodynamically unstable to tolerate CT scanning. Ultrasound is useful for follow-up imaging in patients with known injuries (Fig. 21–3). Ultrasound, particularly when Doppler flow is assessed, is also useful for evaluating testicular injuries. Bladder injuries can best be identified by performing a cystogram. Cystograms involve the retrograde injection of contrast material through the urethra into the bladder. Cystograms may be performed with plain radiographs or with CT scanning. Bladder rupture is diagnosed by observing extravasation of the contrast material. Urethral

Chapter 21 — Pelvic and Genitourinary Trauma

A

B

191

C

FIGURE 21–3. Renal laceration and perinephric hematoma in a 17-year-old boy. A, Computed tomography shows acute laceration of the left kidney with a large perinephric hematoma. B, Ultrasound image of same patient 3 weeks later shows resolving hematoma but does not reveal a laceration. C, Comparison view of right (normal) kidney ultrasound.

injuries are diagnosed in a similar manner by retrograde urethrogram. A urethrogram is performed by gently injecting a small amount of contrast material (usually 10 to 30 ml depending upon the size of the child) into the distal urethra under fluoroscopy or while obtaining a plain fi lm radiograph. If a complete urethral tear is present, extravasation of contrast material will be seen without fi lling of the urethra or bladder proximal to the injury (see Fig. 21–2). If the bladder fi lls but extravasation is present, the likely diagnosis is a partial tear of the urethra. If no extravasation occurs and the bladder fi lls, then the examination is negative for urethral disruption.

Management In general, the identification of pelvic fractures and genitourinary injuries takes place in the context of an evaluation for multisystem trauma (see Chapter 11, Approach to Multisystem Trauma). Treatments for specific pelvic and genitourinary injuries need to be incorporated into the overall management of the traumatized child. Pelvic Fractures If a pelvic fracture is closed and nondisplaced, and the pelvic ring is stable, then no immediate management of the fracture is indicated. In this circumstance, the priorities are analgesia and identification of associated injuries. Children rarely become hypotensive as a direct result of pelvic fractures, so children in shock should be presumed to have another source of bleeding. In the rare event that a severe pelvic fracture contributes to ongoing blood loss, immediate measures can be taken in the emergency department (ED) to stabilize the pelvis by reapproximating the fracture surfaces. This is most often necessary for “open book” pelvic fractures. The simplest means to reapproximate such fractures and control hemorrhage is to tighten a sheet around the pelvis. Commercial devices designed for this purpose may be inappropriately sized for most children. Urgent orthopedic consultation for internal or external fi xation is then needed. Embolization performed by a interventional radiologist may also be indicated. This may require transfer of the patient to a pediatric trauma center. Obvious or suspected open pelvic fractures require the prompt administration of intravenous antibiotics. Open pelvic fractures, particularly in children, are sufficiently rare

that no evidence-based recommendations on antibiotic selection can be made. In this context, the selection of antibiotics may be based on the degree of soft tissue injury and the likelihood of bowel perforation.35,36 Relatively clean, open fractures of the iliac wing, for example, may do well with intravenous cefazolin. Open pelvic fractures with more extensive soft tissue damage may do well with intravenous cefazolin and gentamicin. Injuries likely to involve bowel perforation may do best with traditional “triple antibiotics” (i.e., cefazolin, gentimicin, and metronidazole). Given that many pelvic fractures are associated with other internal injuries, most children with pelvic fractures will require hospitalization. Over 90% of pelvic fractures in children are treated nonoperatively.4-6,37 Children with minor pelvic fractures and no other injuries may be candidates for discharge from the ED with close outpatient follow-up. Renal and Ureteral Injuries Almost 90% of blunt renal injuries, including severe ones, can be managed nonoperatively by hospitalization with close observation of hemodynamics, urine output, and hematocrit.38,39 This may also be true for some penetrating renal injuries.40 Immediate complications associated with renal injury include infection, urinary obstruction, persistent bleeding, and urinary extravasation. Ureteral injuries are generally managed surgically, either by reanastomosis or stent placement. When a delay in the diagnosis of a ureteral injury occurs, urinary diversion with delayed repair is usually necessary. Bladder Injuries The management of bladder injuries depends on the type and severity of the injury. Children with simple bladder contusions can be discharged with outpatient urologic follow-up if they can spontaneously void and have no other indications for admission. Extraperitoneal bladder rupture generally requires external urinary drainage. This can be accomplished by placement of a Foley or suprapubic catheter. If a displaced fragment of bone from the pelvis remains in the bladder wall, however, surgical removal and repair may be necessary. Intraperitoneal bladder rupture requires surgical repair. These injuries require suprapubic urinary diversion. Complications of bladder rupture include infection, vesicular fistula formation, and poor healing with the need for delayed surgical repair.

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Urethral Injuries Damage to the urethra may be managed in a number of ways depending upon the location and severity of injury. Posterior urethral injuries are typically treated with endoscopic catheterization using a guidewire. The urethra is then allowed to heal over the catheter. Severe posterior injuries require urinary diversion (e.g., suprapubic cystostomy) with delayed surgical reanastomosis. Anterior urethral injuries are treated by either long-term catheter placement, which allows healing of the urethra over the catheter, or reanastomosis. If urologic consultation is not immediately available and a patient with a urethral injury cannot void, then a suprapubic urinary catheter can be placed by the emergency physician to empty the bladder. This is most easily accomplished using a kit designed for this purpose, which usually includes a guidewire, dilator, and introducer sheath. Young children may require a smaller catheter size than is provided in standard kits. Procedural sedation may be needed to facilitate this procedure. Complications of urethral injury include stricture formation, infection, and impotence. Testicular Injuries Testicular rupture and traumatic torsion both require immediate operative intervention (see Chapter 87, Testicular Torsion). Testicular salvage rates decrease with time. If dislocation is suspected, the missing testis will likely be palpable superior to the scrotum. Manual reduction is typically indicated. Intravenous analgesia or procedural sedation is prudent for this procedure. Urologic consultation is required if attempts at reduction by the ED physician are unsuccessful. Large testicular hematomas and hematoceles may require surgical treatment. Children who have small scrotal hematomas, skin ecchymosis, or superficial lacerations without evidence of injury to the testicle can be discharged home with outpatient follow-up and oral analgesia as needed. More significant scrotal injuries, and any injury involving the testes, typically require urologic consultation.

Summary Pelvic fractures are uncommon in children. Genitourinary injuries are more common, but seldom life threatening. Children with pelvic fractures and associated genitourinary injuries are usually also at risk for multisystem trauma. The prognosis of children with isolated pelvic fractures is generally excellent. Injuries to other anatomic systems usually dictate overall management and contribute strongly to the ultimate outcome. REFERENCES *1. Demetriades D, Karaiskakis M, Velmahos GC, et al: Pelvic fractures in pediatric and adult trauma patients: are they different injuries? J Trauma 54:1146–1151, 2003. *2. Ismail BN, Bellemare JF, Mollitt DL, et al: Death from pelvic fracture: children are different. J Pediatr Surg 31:82–85, 1996. 3. Tarman GJ, Kaplan GW, Lerman SL, et al: Lower genitourinary injury and pelvic fractures in pediatric patients. Urology 59:123–126, 2002. 4. Chia JP, Holland AJ, Little, D, et al: Pelvic fractures and associated injuries in children. J Trauma 56:83–88, 2004.

*Selected readings.

*5. Silber JS, Flynn JM, Koffler KM, et al: Analysis of the cause, classification, and associated injuries of 166 consecutive pediatric pelvic fractures. J Pediatr Orthop 21:446–450, 2001. 6. Grisoni N, Connor S, Marsh E, et al: Pelvic fractures in a pediatric level I trauma center. J Orthop Trauma 16:458–463, 2002. 7. Rieger H, Brug E: Fractures of the pelvis in children. Clin Orthop 336:226–239, 1997. 8. Fracture and dislocation compendium. Orthopaedic Trauma Association Committee for Coding and Classification. J Orthop Trauma 10(Suppl 1):v–ix, 1–154, 1996. 9. Brown SL, Elder JS, Spirnak JP: Are pediatric patients more susceptible to major renal injury from blunt trauma? A comparative study. J Urol 160:138–140, 1998. 10. Koraitim MM, Marzouk ME, Atta MA, et al: Risk factors and mechanism of urethral injury in pelvic fractures. Br J Urol 77:876–880, 1996. 11. Moore EE, Shackford SR, Pachter HL, et al: Organ injury scaling: spleen, liver and kidney. J Trauma 29:1664, 1989. 12. Okur H, Kucukaydin M, Kazez A, et al: Genitourinary tract injuries in girls. Pediatr Urol 78:446–449, 1996. 13. Perez-Brayfield MR, Gatti JM, Smith EA, et al: Blunt traumatic hematuria in children: is a simplified algorithm justified? J Urol 167:2543– 2547, 2002. 14. Santucci RA, Langenburg SE, Zachareas MJ: Traumatic hematuria in children can be evaluated as in adults. J Urol 171: 822–825, 2004. 15. Nguyen MM, Das S: Pediatric renal trauma. Urology 59:762–767, 2002. 16. Junkins EP, Furnival RA, Bolte RG: The clinical presentation of pediatric pelvic fractures. Pediatr Emerg Care 17:15–18, 2001. 17. Junkins EP, Nelson DS, Carroll KL, et al: A prospective evaluation of the clinical presentation of pediatric pelvic fractures. J Trauma 51:64– 68, 2001. 18. Rees MJ, Aickin R, Kolbe A, et al: The screening pelvic radiograph in pediatric trauma. Pediatr Radiol 31:497–500, 2001. 19. Mosheiff R, Suchar A, Porat S, et al: The “crushed open pelvis” in children. Injury 30(Suppl 2):B14–B18, 1999. *20. Esposito TJ, Ingraham A, Luchette FA, et al: Reasons to omit digital rectal exam in trauma patients: no fi ngers, no rectum, no useful information. J Trauma 59:1314–1319, 2005. *21. Guldner G, Babbitt J, Boulton M, et al: Deferral of the rectal examination in blunt trauma patients: a clinical decision rule. Acad Emerg Med 11:635–641, 2004. 22. Iverson AJ, Morey AF: Radiographic evaluation of suspected bladder rupture following blunt trauma: critical review. World J Surg 25:1588– 1591, 2001. 23. Fleisher G: Prospective evaluation of selective criteria for imaging among children with suspected blunt renal trauma. Pediatr Emerg Care 5:8–11, 1989. 24. Lieu TA, Fleisher GR, Mahboubi S, et al: Hematuria and clinical fi ndings as indications for intravenous pyelography in pediatric blunt renal trauma. Pediatrics 82:216–222, 1988. 25. Bass DH, Semple PL, Cywes S: Investigation and management of blunt renal injuries in children: a review of 11 years’ experience. J Pediatr Surg 26:196–200, 1991. 26. Hashmi A, Klassen T: Correlation between urinalysis and intravenous pyelography in pediatric abdominal trauma. J Emerg Med 13:255–258, 1995. 27. Miller KS, McAninch JW: Radiographic assessment of renal trauma: our 15-year experience. J Urol 154:352–355, 1995. 28. Eastham JA, Wilson TG, Ahlering TE: Radiographic evaluation of adult patients with blunt renal trauma. J Urol 148:266–267, 1992. 29. Stalker HP, Kaufman RA, Stedje K: The significance of hematuria in children after blunt abdominal trauma. AJR Am J Roentgenol 154:569– 571, 1990. 30. Morey AF, Bruce JE, McAninch JW: Efficacy of radiographic imaging in pediatric blunt renal trauma. J Urol 156:2014–2018, 1996. 31. Abou-Jaoude WA, Sugarman JM, Fallat ME, et al: Indicators of genitourinary tract injury or anomaly in cases of pediatric blunt trauma. J Pediatr Surg 31:86–90, 1996. 32. Brown SL, Haas C, Dinchman KH, et al: Radiographic evaluation of pediatric blunt renal trauma in patients with microscopic hematuria. World J Surg 25:1557–1560, 2001. 33. Porter JM, Singh Y: Value of computed tomography in the evaluation of retroperitoneal organ injury in blunt abdominal trauma. Am J Emerg Med 16:225–227, 1998. 34. Yen K: Ultrasound applications for the pediatric emergency department: a review of the current literature. Pediatr Emerg Care 18:226–234, 2002.

Chapter 21 — Pelvic and Genitourinary Trauma 35. Merritt K: Factors increasing the risk of infection in patients with open fractures. J Trauma 28:823–827, 1988. 36. Robinson D, On E, Hadas N, et al: Microbiologic flora contaminating open fractures: its significance in the choice of primary antibiotic agents and the likelihood of deep wound infection. J Orthop Trauma 3:283–286, 1989. 37. Blasier RD, McAtee J, White R, et al: Disruption of the pelvic ring in pediatric patients. Clin Orthop 376:87–95, 2000.

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38. Margenthaler JA, Weber TR, Keller MS: Blunt renal trauma in children: experience with conservative management at a pediatric trauma center. J Trauma 52:928–932, 2002. 39. Wessel LM, Scholz S, Jester I, et al: Management of kidney injuries in children with blunt abdominal trauma. J Pediatr Surg 35:1326–1330, 2000. 40. Wessells H, McAninch JW, Meyer A, et al: Criteria for nonoperative treatment of significant penetrating renal lacerations. J Urol 157:24–27, 1997.

Chapter 22 Compartment Syndrome Christian Vaillancourt, MD, MSc and Ian Shrier, MD, PhD

Key Points Acute compartment syndrome is a limb-threatening condition. This condition should be recognized early, before pulses are lost. Significant necrosis can occur within 3 to 4 hours of the injury. Compartment pressure should be measured when the diagnosis is clinically equivocal. Definitive therapy is surgical fasciotomy.

Introduction and Background Acute compartment syndrome is a limb-threatening condition in which increased pressure within closed tissue spaces compromises the nutrient blood flow to muscles and nerves such that necrosis will invariably occur if decompression is not performed.1-4 This is in contrast to chronic (or recurrent) compartment syndrome, in which the mechanism of injury is usually exertional, symptoms most often subside at rest, and the condition is managed conservatively initially and by elective surgery when warranted.5-8 Acute compartment syndrome was first described in 1881 by a German physician named Dr. Richard von Volkmann.9 He reported on many cases of clawhand resulting from elbow injuries in children, which initially became known as “Volkmann’s contracture.” A compartment is a functional unit usually containing muscles, nerves, veins, and arteries. Each compartment is surrounded by a thick fascia that lacks the ability to stretch. A limb can contain more than one compartment; the four leg compartments are depicted in Figure 22–1. Acute compartment syndrome is not limited to the extremities; for example, it has been reported in the orbit10 as well as in the abdominal cavity.11 When pressure increases inside a closed compartment, it compresses both arterioles and venules. The increased venous 194

resistance results in increased venular pressure, and presumably increased capillary pressure.12 This may explain why one observes more serious injuries in acute compartment syndrome–induced ischemia compared to that produced by tourniquet-induced ischemia alone, a condition associated with decreased venular pressure.13

Recognition and Approach As suggested by Matsen,14 the numerous acute compartment syndrome etiologies can be classified within two categories: increased compartmental content and decreased compartmental volume (Table 22–1). Acute compartment syndrome is a well-recognized complication of revascularization surgery,15,16 as well as pelvic surgery in the lithotomy position.17,18 It has been described in a variety of other conditions, such as steroid use,19 human immunodeficiency virus– induced myositis,20 post–diagnostic electromyography,21 and self-induced hand suction in children.22 Because such a variety of circumstances can lead to acute compartment syndrome, it is important to maintain a high level of suspicion and inquire about the mechanism of injury. Most patients will be young males, will be involved in a traumatic incident, and will often have an associated fracture.23,24 The leg compartments are most often involved in the adult population25 (Fig. 22–2). Perhaps because of their smaller stature or a different mechanism of injury, there seems to be a more equal distribution between upper and lower extremities in children.23,24

Evaluation The presence of a tight compartment on palpation should alert emergency physicians to the possibility of acute compartment syndrome.2 The hallmark presentation is that of pain out of proportion to the apparent injury (Table 22–2). Nerve structures are particularly sensitive to ischemia, leading to early paresthesia or paralysis. Particular attention should be given to agitated/uncooperative young patients, 23 those requiring increasing amounts of analgesia,23,26 or those receiving continuous epidural analgesia.27 The loss of peripheral pulses is a late and ominous sign; acute compartment syndrome should be diagnosed before pulses are lost. It is often clinically easier to exclude the diagnosis of acute compartment syndrome than it is to confirm it.28 While

195

Chapter 22 — Compartment Syndrome

Fascial Compartments of Leg Anterior compartment

Crural fascia

Tibialis anterior m. Anterior tibial a. and v. and deep peroneal n.

Tibia Greater saphenous v. and saphenous n.

Extensor hallucis longus m. Extensor digitorum longus m.

Deep posterior compartment Lateral compartment

Tibialis posterior m. Peroneal a. and v. Flexor hallucis longus m.

Superficial peroneal n. Peroneous brevis m. Peroneous longus m.

Flexor digitorum longus m. Posterior tibial a. and v. and tibial n.

Anterior intermuscular septum

Interosseus membrane

Posterior intermuscular septum

Crural fascia

Fibula Transverse intermuscular septum

Superficial posterior compartment

Lateral sural cutaneous n.

Plantaris tendon Gastrocnemius m. (medial head)

Crural fascia

Soleus m.

Peroneal communicating branch of lateral sural cutaneous n.

Gastrocnemius m. (lateral head)

Lesser saphenous v. FIGURE 22–1. Cross-section of a leg illustrating its four compartments and their respective contents.

Table 22–1

Classification of Acute Compartment Syndrome Etiologies

Table 22–2

Clinical Findings in Conscious Patients

Increased Content

Decreased Volume

Common Clinical Findings*

Bleeding Major vascular injuries Bleeding disorder or anticoagulants Increased capillary permeability Postischemic swelling Muscle contraction (exercise, seizure, tetany) Burns Intra-arterial drugs Envenomation Infiltrated infusion Nephrotic syndrome

Tight dressing or cast Military antishock trousers (MAST) Burn eschars Lying on a limb or localized external pressure Closure of fascial defects

Pain Neurologic abnormalities Pain on passive stretch

clinically obvious cases should be referred to an orthopedic surgeon without further delay,29,30 up to 50% of cases will remain equivocal despite a thorough clinical evaluation.25,31 Measurement of intracompartmental pressure can be achieved using one of three methods: the Stryker instrument, the manometric Intervenous Alarm Control (IVAC) pump, or the Whitesides method. The Stryker instrument is accurate and easy to use32 (Fig. 22–3). If this instrument is not available, the pressure can just as accurately be measured using a method described by Uppal et al.33 : (1) set up the

95% 53% 49%

*Pallor and pulselessness are late and ominous signs. Acute compartment syndrome should be diagnosed before they occur.

IVAC pump to manometric mode, (2) zero the IVAC pump with the pump placed at the same height as the limb compartment that is to be measured to ensure that there is no hydrostatic pressure gradient, (3) insert the 18-gauge needle into the compartment, (4) infuse 0.3 ml of normal saline, and (5) read the pressure measurement. The Whitesides method requires a complicated procedure that includes a mercury manometer and is not as reliable.34 When measuring the pressure, the needle should be inserted within 5 cm of a suspected fracture, and measurements may have to be repeated if clinical suspicion is high.35 While it is accepted that normal compartment pressure should be less than 10 mm Hg, the pressure threshold for diagnosis of acute compartment syndrome is more controversial. Many surgeons make the diagnosis when an absolute pressure measurement of 30 to 40 mm Hg is reached.31

196

SECTION II — Approach to the Trauma Patient

Tense, bulging anterior compartment

1

16

A 4 3

Dusky, devitalized anterior compartment

Anterior

Lateral

25

20

16

14

Superior posterior

Normal lateral compartment content

Deep posterior

1 FIGURE 22–2. Distribution of involved compartments in patients with acute compartment syndrome confirmed at time of surgery (n = 76, age range 1 to 80 years). Some patients had more than one compartment involved. Numbers represent the percentage of of the total number of involved compartments (n = 140). Most injuries occurred in the lower extremities. (From Vaillancourt C, Shrier I, Vandal A, et al: Acute compartment syndrome: how long before muscle necrosis occurs? Can J Emerg Med 6:147–154, 2004.)

B FIGURE 22–4. Acute compartment syndrome (A) immediately after anterolateral incision, anterior compartment is bulging and hard; and (B) after fasciotomy release of the anterior and lateral compartments, the lateral compartment content is normal and viable but the anterior compartment content is dusky and devitalized. (Images reproduced with permission from Dr. Steven Papp, Assistant Professor, Orthopedic Trauma, The Ottawa Hospital, University of Ottawa, Canada.)

Original work from McQueen and Court-Brown has shown that many unnecessary surgeries would result from using this absolute pressure measurement criterion, and that a differential pressure of 30 mm Hg (i.e., diastolic pressure— compartment pressure is < 30 mm Hg) is more appropriate and would have missed no case of acute compartment syndrome.36

Management

FIGURE 22–3. Using the Stryker instrument to measure the intracompartmental pressure: (1) assemble the needle, the diaphragm chamber, and the prefilled syringe on the pressure monitor as shown; (2) zero the Stryker instrument; (3) insert the needle in the compartment to be measured; (4) inject 0.3 ml of normal saline; and (5) read the pressure measurement. (Photo courtesy of the Stryker Corporation.)

The only accepted therapy for acute compartment syndrome is urgent fasciotomy2-4,29 ; this should only be second to adequate narcotic pain control. Delays in diagnosis and compartment decompression can result in tissue necrosis, disability, or loss of limb25,37-40 (Fig. 22–4). While basic science has determined that muscle can tolerate up to 3 hours of tourniquet-induced ischemia before necrosis occurs,41 laboratory and clinical data on acute compartment syndrome have shown that muscle necrosis can occur well within that presumably safe 3-hour period.13,25 In a recent review of 76 acute compartment syndrome cases, almost half suffered some level of muscle necrosis, 30% of those lost more than 25% of the muscle belly, and it is estimated that necrosis

Chapter 22 — Compartment Syndrome

197

REFERENCES Think of acute compartment syndrome

Diagnosis clinically excluded

Diagnosis clinically evident

Diagnosis clinically equivocal

Measure compartment pressure Pressure differential < 30 mm Hg

Pressure differential ≥30 mm Hg

Low

Clinical suspicion

Treat alternative condition

High

Consult orthopedic surgeon

Urgent surgical fasciotomy

FIGURE 22–5. Diagnostic and therapeutic algorithm for acute compartment syndrome.

occurred within 3 hours of the initial injury in 37% of cases.25 Repeated or continuous monitoring of compartment pressure36,42 should occur in suspected cases if the initial pressure measurement was normal, if the child’s ability to communicate is limited due to age or other injuries, or if the child is receiving frequent or continuous narcotic analgesia. In the meantime, it is controversial whether the limb should be elevated or not; in acute compartment syndrome, limb elevation could lead to decreased perfusion pressure and more tissue damage. A number of adjunct therapeutic modalities have been suggested. These include mannitol,2,43 octreotide,44 melatonin,45 and hyperbaric oxygen.46 Unfortunately, none of these measures can alleviate the need for a rapid surgical fasciotomy.

Summary Acute compartment syndrome is a limb-threatening disease that can rapidly lead to permanent disability or lost of limb. A high level of suspicion for acute compartment syndrome should be maintained in appropriate cases. When in doubt, emergency physicians can easily confirm the diagnosis using needle pressure measurements (Fig. 22–5). Repeated or continuous pressure measurements should be performed in cases where suspicion for acute compartment syndrome remains high. Orthopedic surgeons should be consulted early, and urgent fasciotomy should take place when the diagnosis is confirmed.

*1. McQueen M: Acute compartment syndrome. Acta Chir Belg 98:166– 170, 1998. 2. Mabee JR: Compartment syndrome: a complication of acute extremity trauma. J Emerg Med 12:651–656, 1994. *3. Gulli B, Templeman D: Compartment syndrome of the lower extremity. Orthop Clin North Am 25:677–684, 1994. *4. Matsen FA, Winquist RA, Krugmire R: Diagnosis and management of compartment syndromes. J Bone Joint Surg Am 62:286–291, 1980. 5. Fehlandt A Jr, Micheli L: Acute exertional anterior compartment syndrome in an adolescent female. Med Sci Sports Exerc 27:3–327, 1995. 6. Shrier I: Exercised-induced acute compartment syndrome: a case report. Clin J Sport Med 1:202–204, 1991. 7. Hurschler C, Vanderby R Jr, Martinez DA: Mechanical and biochemical analysis of tibial compartment fascia in chronic compartment syndrome. Ann Biomed Eng 22:272–279, 1994. 8. Turnipseed WD, Hurschler C, Vanderby R Jr: The effects of elevated compartment pressure on tibial arteriovenous flow and relationship of mechanical and biochemical characteristics of fascia to genesis of chronic anterior compartment syndrome. J Vasc Surg 21:810–816, 1995. 9. Von Volkmann R: Die Ischämischen Muskellähmungen und Kontracturen. Centralbl Chir 51:801–803, 1881. 10. Prodhan P, Noviski NN, Butler WE, et al: Orbital compartment syndrome mimicking cerebral herniation in a 12-yr-old boy with severe traumatic asphyxia. Pediatr Crit Care Med 4:367–369, 2003. 11. Tao J, Wang C, Chen L, et al: Diagnosis and management of severe acute pancreatitis complicated with abdominal compartment syndrome. J Huazhong Univ Sci Technol 23:399–402, 2003. 12. Shrier I, Magder S: Pressure-flow relationships in in vitro model of compartment syndrome. J Appl Physiol 79:214–221, 1995. 13. Heppenstall RB, Scott R, Sapega A, et al: A comparative study of the tolerance of skeletal muscle to ischemia: tourniquet application compared with acute compartment syndrome. J Bone Joint Surg 68:820– 828, 1986. 14. Matsen FA: Compartment syndromes. Hosp Pract 15:113–117, 1980. 15. Quinn RH, Ruby ST: Compartment syndrome after elective revascularization for chronic ischemia: a case report and review of the literature. Arch Surg 127:865–866, 1992. 16. Scott DJ, Allen MJ, Bell PR, et al: Does oedema following lower limb revascularisation cause compartment syndromes? Ann R Coll Surg Engl 70:372–376, 1988. 17. Meyer RS, White KK, Smith JM, et al: Intramuscular and blood pressures in legs positioned in the hemilithotomy position: clarification of risk factors for well-leg acute compartment syndrome. J Bone Joint Surg Am 84:1829–1835, 2002. 18. Peters P, Baker SR, Leopold PW, et al: Compartment syndrome following prolonged pelvic surgery. Br J Surg 81:1128–1131, 1994. 19. Bahia H, Platt A, Hart NB, Baguley P: Anabolic steroid accelerated multicompartment syndrome following trauma. Br J Sports Med 34:308–309, 2000. 20. Lam R, Lin PH, Alankar S, et al: Acute limb ischemia secondary to myositis-induced compartment syndrome in a patient with human immunodeficiency virus infection. J Vasc Surg 37:1103–1105, 2003. 21. Farrell CM, Rubin DI, Haidukewych GJ: Acute compartment syndrome of the leg following diagnostic electromyography. Muscle Nerve 27:374–377, 2003. 22. Shin AY, Chambers H, Wilkins KE, Bucknell A: Suction injuries in children leading to acute compartment syndrome of the interosseous muscles of the hand: case reports. J Hand Surg Am 21:675–678, 1996. *23. Bae DS, Kadiyala RK, Waters PM: Acute compartment syndrome in children: contemporary diagnosis, treatment, and outcome. J Pediatr Orthop 21:680–688, 2001. *24. McQueen MM, Gaston P, Court-Brown CM: Acute compartment syndrome: who is at risk? J Bone Joint Surg Br 82:200–203, 2000. *25. Vaillancourt C, Shrier I, Vandal A, et al: Acute compartment syndrome: how long before muscle necrosis occurs? Can J Emerg Med 6:147–154, 2004. 26. Kadiyala RK, Waters PM: Upper extremity pediatric compartment syndromes. Hand Clin 14:467–475, 1998.

*Selected readings.

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27. Tang WM, Chiu KY: Silent compartment syndrome complicating total knee arthroplasty: continuous epidural anesthesia masked the pain. J Arthroplasty 15:241–243, 2000. 28. Ulmer T: The clinical diagnosis of compartment syndrome of the lower leg: are clinical fi ndings predictive of the disorder? J Orthop Trauma 16:572–577, 2002. 29. Lagerstrom CF, Reed RL, Rowlands BJ, Fischer RP: Early fasciotomy for acute clinically evident posttraumatic compartment syndrome. Am J Surg 158:36–39, 1989. 30. Vaillancourt C, Shrier I, Falk M, et al: Quantifying delays in the recognition and management of acute compartment syndrome. Can J Emerg Med 3:26–30, 2001. 31. Sterk J, Schierlinger M, Gerngross H, Willy C: [Intracompartmental pressure measurement in in acute compartment syndrome: results of a survey of indications, measuring technique and critical pressure value]. Unfallchirurg 104:119–126, 2001. 32. Uliasz A, Ishida JT, Fleming JK, Yamamoto LG: Comparing the methods of measuring compartment pressures in acute compartment syndrome. Am J Emerg Med 21:143–145, 2003. 33. Uppal GS, Smith RC, Sherk HH, Mooar P: Accurate compartment pressure measurement using the Intervenous Alarm Control (IVAC) Pump: report of a technique. J Orthop Trauma 6:87–89, 1992. 34. Whitesides TE Jr, Haney TC, Harada H, et al: A simple method for tissue pressure determination. Arch Surg 110:1311–1313, 1975. 35. Menetrey J, Peter R: Syndrome de loge aigu de jambe post-traumatique. Rev Chir Orthop Reparatrice Appar Mot 84:272–280, 1998. 36. McQueen MM, Court-Brown CM: Compartment monitoring in tibial fractures: the pressure threshold for decompression. J Bone Joint Surg Br 78:99–104, 1996.

37. Fitzgerald AM, Gaston P, Wilson Y, et al: Long-term sequelae of fasciotomy wounds. Br J Plast Surg 53:690–693, 2000. 38. Furulund OK, Hove LM: [Acute compartment syndrome—a clinical follow-up study]. Tidsskr Nor Laegeforen 120:3380–3382, 2000. 39. Giannoudis PV, Nicolopoulos C, Dinopoulos H, et al: The impact of lower leg compartment syndrome on health related quality of life. Injury 33:117–121, 2002. *40. Hope MJ, McQueen MM: Acute compartment syndrome in the absence of fracture. J Orthop Trauma 18:220–224, 2004. 41. Sapega AA, Heppenstall RB, Chance B, et al: Optimizing tourniquet application and release times in extremity surgery: a biochemical and ultrastructural study. J Bone Joint Surg 67:303–314, 1985. 42. Tiwari A, Haq AI, Myint F, Hamilton G: Acute compartment syndromes. Br J Surg 89:397–412, 2002. 43. Daniels M, Reichman J, Brezis M: Mannitol treatment for acute compartment syndrome. Nephron 79:492–493, 1998. 44. Kacmaz A, Polat A, User Y, et al: Octreotide improves reperfusioninduced oxidative injury in acute abdominal hypertension in rats. J Gastrointest Surg 8:113–119, 2004. 45. Sener G, Kacmaz A, User Y, et al: Melatonin ameliorates oxidative organ damage induced by acute intra-abdominal compartment syndrome in rats. J Pineal Res 35:163–168, 2003. 46. Wattel F, Mathieu D, Neviere R, Bocquillon N: Acute peripheral ischaemia and compartment syndromes: a role for hyperbaric oxygenation. Anaesthesia 53(Suppl 2):63–65, 1998.

Chapter 23 Spinal Trauma Andrew Wackett, MD and Peter Viccellio, MD

Key Points

concepts: the unique pediatric anatomy, Denis’ three-column system, and Daffner’s “fingerprints” of vertebral trauma.1-3

The management of a child with a potential spinal injury begins with the assessment of airway, breathing, and circulation while maintaining spinal immobilization.

Pediatric Spinal Anatomy

Children are more susceptible to upper cervical spine injuries, which bring a greater risk for airway compromise. Spinal cord injury without radiologic abnormality (SCIWORA) presentation ranges from subtle to obvious and may be delayed. Neurogenic shock is characterized by hypotension and bradycardia, but it is a diagnosis that should be entertained only after hemorrhagic shock has been excluded. Although controversial, steroid use in spinal cord injuries has become a standard of care in the United States.

Pediatric vertebral and spinal injuries have unique characteristics. Specifically, the type and distribution of vertebral injuries in young children, up to 8 to 12 years of age, are different from those of adolescents and adults. The fulcrum of cervical motion occurs at the C5-6 level in adolescents and adults, and it occurs at the C2-3 level in children, due to the relatively larger mass of the head. Thus the majority of spinal injuries in children involve the upper cervical spine and the craniovertebral junction, and the associated mortality is higher in children.1 Compared to adults, children have much more laxity in their spinal ligaments, weaker musculature, and more horizontally angled facet joints. Children can have significant spinal cord injuries without spinal fractures. This injury is referred to as a spinal cord injury without radiologic abnormality (SCIWORA). The reported incidence of SCIWORA is 16% to 19% in children compared to 0.2% in adults.4 During assessment of infants and children, including radiographic examination, clinicians must be aware of anatomic variation and age-related normal development (Tables 23–1 and 23–2). Vertebral Functional Columns

Introduction and Background The National Head and Spinal Cord Injury Survey indicates that there are approximately 11,200 new cases of acute spinal cord injury in the United States each year. Children account for 1065 (10%) of these cases. The mortality among spineinjured children is estimated at 25% to 32%. Costs of medical treatment for all spinal cord injury are estimated to be in excess of $380 million/year. Motor vehicle collisions are the most common etiology. They account for 36% to 54% of cases. Falls, diving injuries, sports-related injuries, birth injuries, penetrating injuries (knife and gunshot wounds), and child abuse account for the remaining precipitants.1

The vertebrae can be divided into three distinct functional columns. The anterior column extends from the anterior longitudinal ligament to a line drawn vertically through the center of the vertebral body. The middle column begins at this line and extends to the posterior longitudinal ligament. The posterior column extends from the posterior longitudinal ligament to the supraspinous ligament (Fig. 23–1). All the major support structures for the vertebrae are contained within the middle and posterior columns. Thus any disruption extending through all three columns will produce an unstable injury.3 Mechanisms of Spine Injury Spine injury mechanisms include flexion, extension, shearing, and rotational injuries.2

Recognition and Approach

Flexion Injuries

There are several vertebral injury patterns that present in children. These patterns are best understood by three unifying

Flexion injuries can be further divided into simple, burst, distraction, and dislocation patterns (Fig. 23–2). Simple 199

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flexion injuries demonstrate anterior compression of the superior aspect of the vertebral body. These injuries occur due to an anterior flexion force. There may or may not be narrowing of the disk space above the level of injury; however, the posterior vertebral body line and posterior ligamentous structures must remain intact. With up to 50% compression, the posterior and middle elements are not involved, thus leaving the injury both mechanically and neurologically stable. Greater than 50% compression should raise suspicion for posterior injury. Burst injuries show a vertebra comminuted by compressive forces with retropulsion of fragments. The mechanism of injury involves an axial load. These fractures involve both the anterior and middle columns and are therefore usually unstable, especially when the middle column is retropulsed into the spinal canal. Distraction injuries demonstrate widening of the interspinous and interfacet distance. Seat belt fractures, also known as Chance fractures, are examples of these injuries. These

Table 23–1

Normal Cervical Spine Variants in Infants and Children

Age

Feature

500 WBCs/mm3 in lavage effluent • >175 IU/dl amylase in lavage effluent • >6 IU/dl alkaline phosphatase in lavage effluent • Gram stain of lavage effluent positive for bacteria *Blunt trauma. Abbreviations: RBCs, red blood cells; WBCs, white blood cells.

The procedure is difficult for the inexperienced physician, and is best performed by the surgical consultant. The criteria for DPL to be deemed positive for bleeding or peritonitis are shown in Table 25–4. Imaging Studies Beyond the early identification of free intraperitoneal gas and subclinical pelvic fractures, the adjunctive supine chest and abdominal roentgenograms performed as part of the primary survey add little to the detection of abdominal injuries. However, they can occasionally reveal important clues to the differential diagnosis, particularly if there are physical signs of intra-abdominal injury, such as pelvic tenderness, eccyhmosis or abrasions, hematuria or difficulty voiding, or abdominal distention.33 They can also identify most rib, vertebral, and pelvic fractures, detect the presence of gastric dilation, and confirm the correct placement of gastric tubes. The abdominal roentgenogram can also suggest the presence of intraperitoneal or retroperitoneal blood or urine (groundglass appearance of the abdominal cavity, blurring of psoas shadows), splenic laceration or hematoma (medial displacement of the lateral border of the stomach, as marked by the gastric tube, especially if the fundic mucosa has a sawtooth appearance, indicative of bleeding from the short gastric vessels), renal injury (scoliosis, obliteration of the nephric outlines and psoas shadows, in association with fractures of the lower ribs), and pancreatic contusion or hematoma (inferiorly displaced transverse colon). Unfortunately, the diagnosis of transmural duodenal injury (small retroperitoneal or perinephric gas bubbles or shadows on the right side of the abdomen, slightly below the liver) and duodenal or proximal jejunal hematoma (paucity of gas in the distal small intestine) are quite difficult, and the diagnosis of ileal, colonic, or vesical injury essentially impossible. Even so, the role of upper gastrointestinal contrast fluoroscopy, using air or sterile intravenous contrast administered perorally or via a gastric tube, is extremely limited, and reserved for stable patients suspected of duodenal or proximal jejunal injury, since extraluminal extravasation of contrast does not universally occur once it is given. Intravenous urography, also known as intravenous pyelography, although largely supplanted by newer techniques, is still occasionally useful, and has two primary indications.

The first is in penetrating abdominal injury, when a “oneshot” intravenous urogram is obtained immediately prior to operative intervention in conjunction with the abdominal or pelvic roentgenogram, to confirm the presence of two kidneys and detect extravasation of urine from the kidneys, ureters, and bladder. The second is in blunt abdominal injury in which the presentation is delayed, and manifested only by significant hematuria (>20 red blood cells per high-power field [RBCs/hpf] on microscopic urinalysis). In this situation, it is still acceptable to obtain an intravenous urogram rather than CT to decrease radiation exposure, provided that the patient is otherwise stable. Retrograde cystourethrography is a vitally important test for male patients in whom pelvic instability, blood at the urinary meatus, perineal or scrotal hematoma, or, in adolescents, a high-riding prostate precludes safe insertion of a urinary (Foley) catheter when indicated. It is typically performed by mixing half-strength intravenous contrast with sterile lubricating jelly, which is then injected retrograde into the urethra as a plain roentgenogram is obtained. If the urethra is demonstrated to be intact, the treating physician may safely proceed with insertion of the urinary catheter. If not, suprapubic cystostomy may be needed, depending upon the physiologic status of the patient and the advice of a urology consultant experienced in the management of injured children. Double (peroral and intravenous) and triple (per rectum as well, if clinically indicated by the possibility of rectosigmoid or desending colonic perforation) contrast-enhanced CT has become the “gold standard” for definitive diagnosis of intra-abdominal injuries in stable patients. It is a better test for detection and quantification of abnormal collections of air or blood in the lower chest or in the abdomen (which are often missed on supine chest and abdominal roentgenography).34 It is also more accurate for inclusion or exclusion of contusion, laceration, disruption, or extravasation of intravenous contrast from solid organs, such as “splenic blush” (which indicates persistent bleeding from the spleen or its hilum, the clinical significance of which remains uncertain in the pediatric population), and intraperitoneal or retroperitoneal contrast seepage from the upper or lower tracts of the collecting system (which indicates urinary leak, and has the same clinical significance in children as it does in adults).35 Finally, it is especially good for documenting the positions of tubes and catheters (which on abdominal roentgenography requires an additional lateral view that often proves difficult to obtain during initial evaluation and resuscitation). Unfortunately, it cannot predict the need for operation, as this judgment is made on clinical grounds.36 Moreover, while it is more sensitive than plain roentgenography and contrast fluoroscopy for the diagnosis of duodenal and proximal jejunal injury, contrast-enhanced CT cannot definitively exclude such injuries, since leakage of contrast from the intestine may or may not occur.37 Yet, while it provides far greater sensitivity and specificity in the detection of most abdominal trauma than most other tests, its greater diagnostic accuracy must be weighed not only against its effect on the clinical management and outcome in potentially labile patients (recognizing that the patient must be physiologically stable in terms of both cardiorespiratory and hemodynamic status to safely undergo CT, since it takes up to 1 hour for peroral contrast to suffuse through the entire intestine), but

Chapter 25 — Abdominal Trauma

Table 25–5

Doses of Peroral and Intravenous Contrast Agents for Computed Tomography

Peroral Contrast Meglumine diatrizoate (Hypaque), 1.5%, by mouth or via gastric tube • Birth–2 yr: 60 ml • 3–5 yr: 120 ml • 6–9 yr: 180 ml • >9 yr: 300–400 ml Intravenous Contrast Meglumine diatrizoate (Hypaque), 60%, by vein • Step 1: Small intravenous test dose • Step 2: Intravenous bolus, 2 ml/kg, maximum 50 ml • Step 3: Intravenous infusion, 50–100 ml, during scanning

also against its potential long-term radiologic side effects in terms of late development of malignant neoplasia (especially when the potential diagnostic benefits from CT are marginal).38-40 Such risks are now being actively studied, and should lead to derivation and promulgation of a clinical decision rule that ascertains exactly which patients in whom the benefits exceed the risks. The preferred doses for peroral and intravenous contrast agents are shown in Table 25–5. Abdominal ultrasonography also has a key role in the diagnosis of intra-abdominal injury in children. Not to be confused with FAST, abdominal ultrasonography, in the hands of a skilled ultrasonographer, is nearly as sensitive and specific as CT, and may be preferred for static imaging of the pancreas and kidneys. However, while it is both more time efficient than CT (when considering the added time for contrast suffusion), and obviates the need for administration of peroral or intravenous contrast (especially useful in patients with allergies to shellfish or iodinated contrast agents), it is more difficult for the novice physician to perform or read, and is less accurate than CT, although it is increasingly being used serially to follow healing of solid organ injuries.41 Laboratory Studies Hematologic tests are of limited utility for the early diagnosis and treatment of abdominal injuries in childhood. Hemoglobin concentration and hematocrit are likely to be misleading during the initial phases of resuscitation, as dilutional anemia from endogenous fluid shifts and exogenous fluid administration will not as yet have occurred, although both tests will be useful as a baseline for further measurements. Similarly, arterial blood gases will serve as an initial indicator of core organ perfusion, but are more useful in terms of their trend, although they are more invasive than vital signs and urinary output.42 However, blood type and crossmatch are routinely obtained in all children with significant injury, especially those with hepatic, splenic, or, rarely, renal injuries likely to require transfusion in lieu of, or in addition to, operative management. After blood type and crossmatch, the most important biochemical test is urinalysis. The presence of blood in the urine (>20 RBCs/hpf on microscopic urinalysis, to ensure that failure to pursue microscopic hematuria does not result in failure to detect potential congenital anomalies or renal tumors) mandates CT if the child presents early (to exclude

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potential associated injuries as well as renal injuries), or intravenous urogram if the child presents late (for reasons noted earlier). However, some have argued that the standard used for adults (>50 RBCs/hpf) can also be applied to children.43 Still others have suggested that CT may not be necessary at all if injuries appear minor.44 The serum electrolytes (Na+, K+, Cl−, HCO3 −), blood urea nitrogen, and serum creatinine are valuable tests of renal function, and while they are virtually always normal in children with no previous history of kidney disease, they also serve as a baseline for management of fluids during and after resuscitation. Hepatic and pancreatic enzymes (serum aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, total and direct bilirubin, and alkaline phosphatase, as well as amylase and lipase) also play an important role in the diagnosis of blunt abdominal injury in childhood. Hepatic enzymes can detect a subclinical hepatic contusion or biliary leak, while pancreatic enzymes can detect unsuspected pancreatic injury, and by inference, since the tail of the pancreas extends into the hilum of the spleen, possible splenic injury as well, although the latter do not appear cost effective.45,46

Management Major Abdominal Injuries Abdominal injuries pose an immediate threat to the integrity of the breathing (via associated gastric dilation) and circulation (via associated intra-abdominal hemorrhage), hence to ventilation, oxygenation, and perfusion of core organs and body tissues, thence to vital functions. As such, resuscitation must proceed simultaneously with assessment. Abnormalities of the airway, breathing, and circulation are therefore treated in sequence, as soon as they are recognized, both to restore flow of oxygen through the series circuit composed of the tracheobronchial tree, the lungs, and the bloodstream, and to ensure accurate assessment of downstream segments of this circuit. Of the three major functions—ventilation, oxygenation, and perfusion—evaluated during the primary survey, deficits of perfusion, although uncommon, are the most detrimental. Since most of these perfusion deficits are caused by intra-abdominal hemorrhage, the approach to resuscitation of the child with intra-abdominal injury must be timely, precise, and vigorous. It is therefore vital that the stepwise pathophysiologic assessment of airway, breathing, and circulation advocated by the ATLS Course of the American College of Surgeons Committee on Trauma be followed in detail.4 The key immediately life-threatening abdominal condition, intraabdominal hemorrhage due to solid organ injury or unstable pelvic fracture, is recognized and treated during the primary survey. The key potentially life-threatening abdominal conditions, minor hemorrhage due to minor solid organ injuries, frank peritonitis due to gastrointestinal disruption, are recognized and treated during the secondary survey. Meticulous attention to the early detection and optimal management of these injuries is the ideal way to ensure effective restoration of core organ perfusion, thus the best chance the seriously injured child has of a full and complete physical and neurologic recovery. With the sole exception of massive gastric dilation that significantly impairs the airway (by causing pulmonary aspiration of acidic gastric contents), the breathing (by limiting

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diaphragmatic excursion), and the circulation (by markedly increasing vagal tone, thereby causing reflex bradycardia in the infant and young child), immediately life-threatening intra-abdominal injuries result in intra-abdominal hemorrhage (hence deranged tissue perfusion), and require emergent volume resuscitation prior to definitive treatment. However, major pediatric trauma is chiefly a disease of the airway and breathing (due to severe traumatic brain injury), rather than the circulation (due to ongoing major intra-abdominal hemorrhage), owing to the top-heavy body habitus of the infant and young child, which makes head injuries more common and torso injuries less common. Therefore, volume resuscitation must be guided by physical and laboratory signs of poor tissue perfusion: increased pulse rate; decreased pulse volume; pale, cool, skin that is mottled in infants and young children or clammy in older children and adolescents; increased capillary refi ll time; electrolytes that reveal high anion gap metabolic acidosis; arterial blood gases that reveal significant base deficit; and elevated serum lactate. In other words, the goal of volume resuscitation is not aggressive fluid administration, but appropriate fluid administration, since excessive water intake can significantly increase cerebral edema, and ultimately, intracranial pressure, complicating treatment of traumatic brain injury. Volume resuscitation is administered via the intravenous or, in infants or young children in whom intravenous access is difficult, the anterior tibial intraosseous routes, unless the latter is contraindicated by ipsilateral lower extremity fracture. Intravenous access should always be attempted first (due to the serious, if rare, complications of intraosseous access such as osteomyelitis), using large-bore over-theneedle plastic catheters wide enough to rapidly deliver fluid or blood, but narrow enough to fit inside the preferred intravenous access site (either the median cubital veins in the antecubital fossae, or the greater saphenous veins just anterior to the medial malleoli). Insertion of two large-bore catheters above the diaphragm is preferred, although other sites may be used if these are unavailable. In general, peripheral intravenous access is favored over central venous access, although femoral venous access may be employed if there is no other option. Volume resuscitation is initiated using an isotonic balanced salt solution, such as lactated Ringer’s solution, in continuously infused aliquots or “boluses” of 20 ml/ kg (equivalent to 25% of the circulating blood volume of the infant or young child, the smallest volume reduction that typically results in systolic hypotension, defined by the formula, 70 + 2 × age in years). These boluses may repeated twice (administered thrice) before red blood cells must be transfused (in accordance with the 3 : 1 rule, which states that isotonic balanced salt solutions are only one third as effective as red blood cells as a plasma expander). Although no data are available in pediatric patients, permissive hypotension has been employed with limited success in adult patients, provided blood pressure is adequate to maintain cerebral perfusion, and definitive surgical management is readily available. The pneumatic antishock garment (PASG), or military antishock trousers (MAST), are no longer used for treatment of decompensated shock, except in selected hypotensive patients with unstable pelvic fractures, among whom the device is used not to correct abnormal hemodynamics, but to stabilize fracture fragments.47,48

However, as crucial as volume resuscitation may be in children with intra-abdominal hemorrhage, the importance of stopping the bleeding cannot be sufficiently emphasized. Volume resuscitation may transiently restore core organ perfusion, but dilutional anemia is too often the result, particularly when bleeding patients are held in the emergency department in a futile attempt to achieve hemodynamic stability. If volume resuscitation must be employed in the absence of a surgeon, packed red blood cells (type specific if available, or type O, ideally Rh negative, if not) in continuous aliquots of 10 ml/kg should be administered as soon as possible to patients who are hypotensive on arrival in the emergency department, or who do not respond immediately to 40 to 60 ml/kg of lactated Ringer’s solution, rapidly infused, as stated, in continuous aliquots of 20 ml/kg. Use of an autotransfuser should be considered for patients with massive, ongoing intra-abdominal hemorrhage, but this is no substitute for emergent surgical consultation and intervention. Detection of peritonitis is also vital to abdominal examination in the child. There is no test for peritonitis other than physical examination. Mild direct tenderness may indicate minor damage to an underlying organ, but does not indicate peritonitis. Marked direct tenderness, especially when associated with direct or referred rebound tenderness, are the key clinical signs of peritonitis, and together are called peritoneal irritation. The classic “boardlike” rigidity described in adult patients with peritonitis is rarely felt in pediatric patients. Instead, they present with involuntary guarding, termed spasm, which differs from boardlike rigidity in that the treating physician can displace the abdominal wall. Regardless, true peritoneal irritation always reflects an intra-abdominal catastrophe, and mandates emergent laparotomy, usually for repair of a ruptured hollow viscus. Uncontrolled hemorrhage and frank peritonitis are the two main indications for emergent operative intervention in abdominal trauma, in children as well as adults. The former connotes solid visceral injury, and the latter hollow visceral injury. Other conditions mandate urgent laparotomy or laparoscopy as the situation warrants. The general indications for operative management in abdominal trauma are shown in Table 25–6. Solid Organs Modern management of nearly all solid organ injuries in childhood is nonoperative. Yet it is not nonsurgical, because operation is needed in a high proportion of pediatric trauma patients, and since, as with appendicitis, mature surgical judgment is required to decide whether, or when, operation may be indicated.49,50 As a general rule, children with liver, spleen, and kidney injuries will not require operative intervention for hemorrhage control unless the transfusion requirement exceeds half the blood volume (40 ml/kg) within the first postinjury day. However, this statement is somewhat misleading, since most patients who require operation declare themselves in the first few hours after injury, while patients whose transfusion requirement slowly approaches this limit 24 hours after injury are unlikely to rebleed later. This has led in recent years to reconsideration of the traditional approach to nonoperative management of solid organ injuries in childhood, such that extended stays in the pediatric intensive care unit are no longer the norm across North

Chapter 25 — Abdominal Trauma

Table 25–6

General Indications for Operative Management of Abdominal Organ Injuries

Blunt Trauma • Hemodynamic instability despite adequate volume resuscitation • Decompensated shock on admission • Transfusion requirement > 40 ml/kg • Physical signs of peritonitis • Positive findings on diagnostic peritoneal lavage (if so decided by the trauma surgeon) • Radiologic evidence of pneumoperitoneum • Radiologic evidence of intraperitoneal bladder rupture • Radiologic evidence of renovascular pedicle injury Penetrating Trauma • All gunshot wounds • All stab wounds associated with: • Physical signs of shock or peritonitis • Blood in the stomach, urine, or rectum • Evisceration • Radiologic evidence of intraperitoneal or retroperitoneal gas • Positive findings on diagnostic peritoneal lavage (if so decided by the trauma surgeon) • All suspected thoracoabdominal injuries

America, provided that nonoperative management is conducted in a hospital with a pediatric intensive care unit and ready access to a pediatric surgeon, a pediatric anesthesiologist, and ample blood products to ensure their availability when needed.51-53 There is little doubt that general trauma surgeons with significant pediatric experience can successfully manage children with solid organ injuries using nonoperative treatment protocols.54 However, neither a general trauma surgeon nor a pediatric trauma surgeon should attempt such management absent the availability of appropriate pediatric support, in terms of a pediatric intensive care unit and, most important, trained pediatric nursing. If these cannot be locally accomplished, and the injured child is stable enough for transfer to a pediatric-capable trauma center, transfer should be initiated as soon as possible after the primary survey has been completed, in accordance with preexisting transfer agreements well known to the treating physician. The time before transfer is effected is used to continue resuscitation, and to perform the secondary survey, without taking extra time to obtain imaging studies that will further delay transfer. However, if the child is unstable, operative management is appropriate. It is far better for such a child to safely remove a seriously damaged organ, even if likely salvageable under ideal circumstances, than to risk nonoperative management in an environment that is unprepared for it. Liver injuries are suspected based upon clinical evaluation, and confirmed by abdominal CT. Upper abdominal tenderness, more right than left sided, may or may not be present. As stated, volume resuscitation is the foundation of early care, since nonoperative management will be successful in 90% of children with hepatic injuries. Operation is indicated in pediatric blunt trauma patients who are frankly hypotensive on arrival in the emergency department, or who respond only transiently to volume resuscitation, since patients with severe injuries, especially AAST OIS grade V injuries, have a poor outcome.55 Urgent surgical consultation should be

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obtained on patient arrival in the emergency department, but in no case should it be delayed beyond defi nitive diagnosis by CT. It should also be obtained in patients who present after “successful” nonoperative management, since, as with splenic injuries, delayed bleeding is known to occur.56 Operation is nearly always indicated in penetrating trauma. Spleen injuries are likewise suspected based on clinical evaluation, and confirmed by abdominal CT. Left upper quadrant tenderness and left shoulder pain (Kehr’s sign) may or may not be present. Once again, volume resuscitation is the foundation of early care, nonoperative management being successful in 95% of children with splenic injuries. The presence of a splenic blush on CT is not yet well studied in pediatric patients, but preliminary experience suggests that, as with FAST, it may add little to management of blunt trauma patients, since current treatment is physiologically based, and linked to transfusion requirement.35 In the rare situation in which emergent operation is indicated, prior administration of multivalent pneumococcal vaccine could theoretically decrease the low incidence of overwhelming postsplenectomy infection, but there are no data proving this is so. Operation is nearly always indicated for penetrating trauma. Kidney injuries are managed nonoperatively in virtually all instances. As with liver and spleen injuries, the diagnosis is suspected based on clinical evaluation, and confirmed by CT obtained on clinical grounds or for significant hematuria.57 Renal injuries are typically minor, so volume resuscitation is needed only for severe injuries. This is also true of operative management, which is usually required for intraperitoneal leak from the collecting system, massive upper tract bleeding presenting as gross hematuria, severe disruption or shattering, and renal pedicle avulsion. Most blunt injuries with urinary leaks are managed nonoperatively, or by percutaneous nephrostomy, while most penetrating injuries with urinary leaks are managed by direct surgical repair. One-shot intravenous urography is mandatory whenever emergent surgical intervention is required and abdominal CT has not been, or should not, be obtained. Operation is needed in penetrating trauma only in severe cases (AAST OIS grade III–V). Pancreatic injuries in children are also managed nonoperatively in virtually all instances. The diagnosis is suspected typically on clinical grounds, and confirmed by CT or ultrasonography and appropriate laboratory tests. Traumatic pancreatitis presents with epigastric pain, and is managed conservatively, giving nothing by mouth and administering intravenous fluids until pain disappears and biochemical abnormalities are resolved. Pancreatic pseudocysts present with soft but tender epigastric masses, and are also managed conservatively, substituting total parenteral nutrition for intravenous fluids if the pseudocyst is well established. Operative intervention is rarely required for blunt trauma, and is associated with complication rates that are significantly higher than nonoperative care, even in severe cases associated with transection of the pancreatic head, body, tail, or duct.58-60 Operation is nearly always indicated for penetrating trauma. Hollow Organs Gastrointestinal tract injuries require operative intervention only if transmural disruption is present.61 Unfortunately, it

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is prohibitively difficult to identify such injuries without an operation. Neither CT nor contrast fluoroscopy is sufficient valid and reliable to exclude the diagnosis, although risk is increased if more than one organ is found to be injured.62 Thus the treating physician must wait for signs of peritoneal irritation to develop, or perform DPL, which can itself confound the abdominal examination if negative, and is no more accurate than CT or contrast fluoroscopy in ruling out intestinal perforation or laceration. Thus, in the absence of frank indications for laparotomy, serial abdominal examination, seeking signs of peritoneal information, is likely the most valid and reliable test available to the treating physician for diagnosis of gastrointestinal disruption. It is certainly the most cost effective. Gastrointestinal tract disruption is uncommon in blunt trauma but common in penetrating trauma. Signs of peritonitis always mandate urgent laparotomy. Genitourinary injuries exclusive of the kidneys require organ-specific management. Ureteric injuries are detected by CT or intravenous urography, and require stented repair when involving the supravesical component or reimplantation when involving the intravescial component. Vesical injuries are detected by similar means, and confirmed by voiding cysturethrogram. Intraperitoneal injuries to the dome of the urinary bladder require direct operative repair. Extraperitoneal injuries to the base of the urinary bladder require catheter drainage. Injuries to the male and female genital tracts are rarely associated with blunt trauma, with the exception of urethral injury in boys, for which a transurethral stent, ideally a urinary catheter, is required. Injuries to the male and female genital tracts seldom occur in penetrating trauma, but require surgical repair. Great vessel injuries always require operative repair, and are nearly universally detected at emergent laparotomy performed for massive, ongoing intra-abdominal hemorrhage that typically presents with decompensated shock.63,64 No preoperative tests are necessary, practical, or desirable, save for the one-shot intravenous urogram obtained for penetrating trauma whenever feasible. Survival is dependent upon immediate repair. Bony Pelvis Unstable fractures of the bony pelvis are detected clinically as described previously, and confirmed by pelvic roentgenography. Clinically unstable pelvic fractures require a pelvic sling, or similar device, to decrease pelvic volume and stabilize fracture fragments in an attempt to limit bleeding in the emergent phase of treatment. As stated, unstable pelvic fractures associated with hypotension may benefit from application and inflation of a PASG or MAST device, but are used in this situation to stabilize fracture fragments, hence limit further bleeding. Most pelvic fractures in childhood are simple and stable, and rarely require volume resuscitation. However, complex pelvic fractures, though rare, are both biomechanically and hemodynamically unstable, and require massive volume resuscitation. Closed pelvic fractures, via tamponade, will limit the ultimate amount of blood lost, provided operative intervention, which opens tissue planes and counteracts this tamponade, is not required for other reasons. Open pelvic fractures present an extraordinary management challenge, for which interven-

tional radiology and external fi xation are typically both required. Abdominal Compartment Syndrome A recent development in trauma surgery has been the recognition of abdominal compartment syndrome. Presumed to be due to reperfusion injury after prolonged operative treatment and resuscitation, and mediated by superoxide radicals, abdominal compartment syndrome results in massive edema of all intra-abdominal organs in the afflicted patient, impeding ventilation and oxygenation via upward pressure on the diaphragm, and impeding perfusion of intra-abdominal organs via compromised circulation. Rarely observed in the emergency department, the condition is recognized by intravesical pressures that exceed 25 cm H2O, and treated by release of pressure, typically by reoperation for placement of a Bogota bag, much as a Silon pouch is used for neonates undergoing delayed primary closure of gastroschisis or omphalocele, until such time as edema resolves and delayed primary closure can be safely effected. It is mentioned here because some emergency departments may rarely receive patients with abdominal compartment syndrome in transfer from other hospitals. Trauma Laparotomy It is axiomatic that optimal stabilization of the trauma patient frequently requires surgical intervention. Contemporary surgical management of abdominal injuries therefore relies heavily on “damage control.” A midline incision is swiftly made, and all four quadrants are packed. A rapid but careful inspection is then made for sources of bleeding and soilage. Sources of bleeding that can be readily controlled by repair or ligation are then addressed, leaving packing in place to apply direct pressure to other bleeding sites. Sources of soilage are then similarly readily controlled by stapling or ligation, after which the abdomen is speedily irrigated with warm saline solution, and temporarily closed with towel clips or Bogota bag. The patient is then fully resuscitated either in the operating room or the intensive care unit, until such time as normal body temperature is restored, metabolic derangements are corrected, and hematologic deficiencies are addressed, both in terms of oxygen-carrying capacity and with respect to blood clotting factors, which are adversely affected by hypothermia, hypocalcemia, dilution, and consumption. Once the patient is fully stabilized, defi nitive operation can proceed, and needed repairs can be performed. Trauma Laparoscopy The role of trauma laparoscopy is in evolution. To date, it has mostly been employed to determine whether abdominal penetration has occurred in questionable cases, and for diagnosis, and occasionally diaphragmatic repair, of potential or actual thoracoabdominal injuries. Theoretically, its application to trauma surgery is limited only by the speed and skill of the operating surgeon. However, at this point, its uses are limited to cases in which good visibility is assured, and active bleeding and soilage are not encountered. Minor Abdominal Injuries Minor abdominal injuries are those confined to the soft tissues of the abdominal wall, and which in cases of penetrat-

Chapter 25 — Abdominal Trauma

ing trauma do not violate the parietal peritonuem. They are noteworthy chiefly because of their frequency. Blunt injury to the abdominal wall typically results in superficial contusions to the skin and subcutaneous tissues, although occasionally the rectus muscles also, and does not require treatment beyond the symptomatic relief provided by warm compresses and oral analgesics. Penetrating injury to the abdominal wall is rarely associated with intra-abdominal injury absent signs of compensated or decompensated shock or parietal peritoneal irritation, but great care is warranted during exploration of an apparently superficial penetrating wound, since it is all too easy to explore a wound to such a depth that the abdomen is entered. Wounds that penetrate the transversalis fascia may require surgical exploration in the operating room, either by laparotomy or by laparoscopy. Likewise, contaminated wounds may also benefit from operative débridement by means of pulse jet irrigation prior to formal closure. Otherwise, superficial lacerations may be repaired in the emergency department, closing the wound in a minimum of two layers whenever possible. Tetanus prophylaxis is indicated for all contaminated wounds.

Table 25–7

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Triage Guidelines for Emergency Management of Abdominal Trauma

Blunt Trauma* Hemodynamically stable patient • Negative indications for CT → acute care area • Positive indications for CT → CT negative → acute care area • Positive indications for CT → CT positive → PICU vs. OR Hemodynamically unstable patient • Responds well to volume resuscitation → CT negative → PICU • Responds well to volume resuscitation → CT positive → PICU vs. OR • Responds poorly to volume resuscitation → OR Penetrating Trauma* • Gunshot wound → OR • Stab wound → OR vs. PICU vs. acute care area • Hypotension or peritonitis → OR • Blood in the stomach, rectum, or urine → OR • Evisceration → OR • Thoracoabdominal wounds → OR *If signs of peritoneal irritation, a laparotomy or OR is indicated. Abbreviations: CT, computed tomography; OR, operating room; PICU, pediatric intensive care unit.

Penetrating Injuries When first encountered, all penetrating injuries to the abdomen must be considered to have violated the parietal peritoneum. Great care must be taken during exploration of the wound to avoid such violation if it has not yet occurred. All penetrating gunshot wounds to the abdomen require exploratory laparotomy, as do those stab wounds associated with shock, peritonitis, evisceration, or blood in the stomach, urine, or rectum on insertion of a gastric tube or urinary catheter or digital examination. The remainder may be observed via serial physical examination. All penetrating abdominal injuries must be deemed contaminated, and must be thoroughly cleansed and débrided prior to suture repair, in addition to appropriate antibiotic and tetanus prophylaxis as indicated. As with abusive injuries, the history obtained following penetrating trauma is likely to be inaccurate. As such, hospital admission is warranted, both to ensure that the child receives a full course of antibiotics, and to allow full involvement of social work and pastoral care services, whose skills are critical in determining the circumstances surrounding the injury and minimizing the likelihood of recidivism. Finally, all gunshot and stab wound injuries in children must be reported to the police, and to local child protective services as well, if there is any hint that the injuries may have resulted from parental abuse or neglect. Thoracoabdominal Injuries Thoracoabdominal injuries are penetrating injuries that traverse the diaphragm. They must be suspected whenever a penetrating injury is found anywhere between the nipples and the umbilicus. All potential thoracoabdominal injuries mandate immediate chest roentgenography, to identify possible intrathoracic air or blood, followed by insertion of a chest tube if present. All such injuries will also require exploratory laparotomy or laparoscopy, both to determine whether and where diaphragmatic penetration may have occurred, and to exclude other intra-abdominal injuries that also require operative repair.

Summary Serious abdominal injuries occur in nearly 1 in 10 cases of major childhood trauma, and follow only central neuraxis injuries and intrathoracic injuries in their lethality. Most pediatric abdominal injuries are initially managed nonoperatively, although major abdominal injuries typically coexist with immediately or potentially life-threatening injuries to other body regions. A high index of suspicion for abdominal injuries is always warranted, since derangements of ventilation, oxygenation, and perfusion resulting from injury to intra-abdominal organs that affect the integrity of the airway, breathing, and circulation substantially worsen the prognosis of associated injuries, particularly central neuraxis injuries, due to inadequate delivery of blood to damaged brain tissue. A physiologic approach to the emergent management of abdominal trauma best serves the needs of the injured child, whose vigorous hemodynamic compensation but limited circulatory reserves call for both rapid restoration and meticulous maintenance of circulating volume, so cellular respiration is supported and irreversible shock is avoided (Table 25–7). REFERENCES 1. Pigula FA, Wald SL, Shackford SR, et al: The effect of hypotension and hypoxia on children with severe head injuries. J Pediatr Surg 28:310– 316, 1993. 2. Cooper A, Barlow B, DiScala C: Vital signs and trauma mortality: the pediatric perspective. Pediatr Emerg Care 16:66, 2000. 3. Cooper A, Barlow B, DiScala C, et al: Mortality and truncal injury: the pediatric perspective. J Pediatr Surg 29:33–38, 1994. 4. Subcommittee on Advanced Trauma Life Support, American College of Surgeons Committee on Trauma: Advanced Trauma Life Support for Doctors Student Manual, 7th ed. Chicago: American College of Surgeons, 2004. 5. Subcommittee on Pediatric Resuscitation, American Heart Association Committee on Emergency Cardiovascular Care: Textbook of Pediatric

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6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31.

32.

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Advanced Life Support, 4th ed. Dallas: American Heart Association, 2006. Haller JA: Injuries of the gastro-intestinal tract in children: notes on recognition and management. Clin Pediatr 5:476–480, 1966. Peng RY, Bongard FS: Pedestrian versus motor vehicle accidents: an analysis of 5,000 patients. J Am Coll Surg 189:343–348, 1999. Orsborn R, Haley K, Hammond S, et al: Pediatric pedestrian versus motor vehicle patterns of injury: debunking the myth. Air Med J 18:107–110, 1999. Campbell DJ, Sprouse LR, Smith LA, et al: Injuries in pediatric patients with seatbelt contusions. Am Surg 69:1095–1099, 2003. Grisoni ER, Pillai SB, Volsko TA, et al: Pediatric airbag injuries: the Ohio experience. J Pediatr Surg 35:160–163, 2000. Erez I, Lazar L, Gutermacher M, et al: Abdominal injuries caused by bicycle handlebars. Eur J Surg 167:331–333, 2001. Winston FK, Shaw KN, Kreshak AA, et al: Hidden spears: handlebars as injury hazards to children. Pediatrics 102:596–601, 1998. Lallier M, Bouchard S, St-Vil D, et al: Falls from heights among children: a retrospective review. J Pediatr Surg 34:1060–1063, 1999. Wang MY, Kim KA, Griffith PM, et al: Injuries from falls in the pediatric population: an analysis of 729 cases. J Pediatr Surg 36:1528–1534, 2001. Cvijanovich NZ, Cook LJ, Mann NC, et al: A population-based assessment of pediatric all-terrain vehicle injuries. Pediatrics 108:631–635, 2001. Lin PH, Barr V, Bush RL, et al: Isolated abdominal aortic rupture in a child due to all-terrain vehicle accident: a case report. Vasc Endovasc Surg 37:289–292, 2003. DiScala C, Sege R, Li G, et al: Child abuse and unintentional injuries: a 10-year retrospective. Arch Pediatr Adolesc Med 154:16–22, 2000. Cooper A, Floyd T, Barlow B, et al: Fifteen years’ experience with major blunt abdominal trauma due to child abuse. J Trauma 28:1483–1487, 1988. Peery CL, Chendrasekhar A, Paradise NF, et al: Missed injuries in pediatric trauma. Am Surg 65:1067–1069, 1999. Jacobs LM, Gross R, Luk S (eds): Advanced Trauma Operative Management. Woodbury, CT: Ciné-Med, Inc., 2004. Hackam DJ, Potoka D, Meza M, et al: Utility of radiographic hepatic injury grade in predicting outcome for children after blunt abdominal trauma. J Pediatr Surg 37:386–389, 2002. Potoka DA, Schall LC, Ford HR: Risk factors for splenectomy in children with blunt splenic trauma. J Pediatr Surg 37:294–299, 2002. Ismail NH, Bellemare JF, Mollitt DL, et al: Death from pelvic fracture: children are different. J Pediatr Surg 31:82–85, 1996. Holmes JF, Sokolove PE, Land C, et al: Identification of intraabdominal injuries in children hospitalized following blunt torso trauma. Acad Emerg Med 6:799–806, 1999. Patel JC, Tepas JJ: The efficacy of focused abdominal sonography for trauma (FAST) as a screening tool in the assessment of injured children. J Pediatr Surg 34:44–47, 52–54, 1999. Mutabagani KH, Coley BD, Zumberge M, et al: Preliminary experience with Focused Abdominal Sonography in Trauma (FAST) in children: is it useful? J Pediatr Surg 34:48–54, 1999. Corbett SW, Andrews HG, Baker EM, et al: ED evaluation of the pediatric trauma patient by ultrasonography. Am J Emerg Med 18:244–249, 2000. Soudack M, Epelman M, Maor R, et al: Experience with focused abdominal sonography for trauma (FAST) in 313 pediatric patients. J Clin Ultrasound 32:53–61, 2004. Holmes JF, London KL, Brant WE, et al: Isolated intraperitoneal fluid on abdominal computed tomography in children with blunt trauma. Acad Emerg Med 7:335–341, 2000. Rathaus V, Zissin R, Werner M, et al: Minimal pelvic fluid in blunt abdominal trauma in children: the significance of this sonographic fi nding. J Pediatr Surg 36:1387–1389, 2001. Holmes JF, Brant WE, Bond WF, et al: Emergency department ultrasonography in the evaluation of hypotensive and normotensive children with blunt abdominal trauma. J Pediatr Surg 36:968–973, 2001. Pershad J, Gilmore B: Serial bedside emergency ultrasound in a case of pediatric blunt abdominal trauma with severe abdominal pain. Pediatr Emerg Care 16:375–376, 2000.

33. Kevill K, Wong AM, Goldman HS, et al: Is a complete trauma series indicated for all pediatric trauma victims? Pediatr Emerg Care 18:75– 77, 2002. 34. Holmes JF, Brant WE, Bogren HG, et al: Prevalence and importance of pneumothoraces visualized on abdominal computed tomographic scan in children with blunt trauma. J Trauma 50:516–520, 2001. 35. Lutz N, Mahboubi S, Nance ML, et al: The significance of contrast blush on computed tomography in children with splenic injuries. J Pediatr Surg 39:491–494, 2004. 36. Sievers EM, Murray JA, Chen D, et al: Abdominal computed tomography scan in pediatric blunt abdominal trauma. Am Surg 65:968–971, 1999. 37. Strouse PJ, Close BJ, Marshall KW, et al: CT of bowel and mesenteric trauma in children. Radiographics 19:1237–1250, 1999. 38. Brenner D, Elliston C, Hall E, et al: Estimated risks of radiationinduced fatal cancer from pediatric CT. AJR Am J Roentgenol 176:289– 296, 2001. 39. Brenner DJ: Estimating cancer risks from pediatric CT: going from the qualitative to the quantitative. Pediatr Radiol 32:228–231, 2002. 40. Jindal A, Velmahos GC, Rofougaran R: Computed tomography for evaluation of mild to moderate pediatric trauma: are we overusing it? World J Surg 26:13–16, 2002. 41. Minarik L, Slim M, Rachlin S, et al: Diagnostic imaging in the followup of nonoperative management of splenic trauma in children. Pediatr Surg Int 18:429–431, 2002. 42. Parish RA, Watson M, Rivara FP: Why obtain arterial blood gases, chest x-rays, and clotting studies in injured children? Experience in a regional trauma center. Pediatr Emerg Care 2:218–222, 1986. 43. Perez-Brayfield MR, Gatti JM, Smith EA, et al: Blunt traumatic hematuria in children: is a simplified algorithm justified? J Urol 167:2543– 2547, 2002. 44. Brown SL, Haas C, Dinchman KH, et al: Radiologic evaluation of pediatric blunt renal trauma in patients with microscopic hematuria. World J Surg 25:1557–1560, 2001. 45. Puranik SR, Hayes JS, Long J, et al: Liver enzymes as predictors of liver damage due to blunt abdominal trauma in children. South Med J 95:203–206, 2002. 46. Adamson WT, Hebra A, Thomas PB, et al: Serum amylase and lipase alone are not cost-effective screening methods for pediatric pancreatic trauma. J Pediatr Surg 38:354–357, 2003. 47. Cooper A, Barlow B, DiScala C, et al: Efficacy of MAST use in children who present in hypotensive shock. J Trauma 33:151, 1992. 48. Garcia V, Eichelberger M, Ziegler M, et al: Use of military antishock trouser in a child. J Pediatr Surg 16:544–546, 1981. 49. Green SM, Rothrock SG: Is pediatric trauma really a surgical disease? Ann Emerg Med 39:537–540, 2002. 50. Tepas JJ, Frykberg ER, Schinco MA, et al: Pediatric trauma is very much a surgical disease. Ann Surg 237:775–781, 2003. 51. Mehall JR, Ennis JS, Saltzman DA, et al: Prospective results of a standardized algorithm based on hemodynamic status for managing pediatric solid organ injury. J Am Coll Surg 193:347–353, 2001. 52. Stylianos S: Evidence-based guidelines for resource utilization in children with isolated spleen or liver injury. J Pediatr Surg 35:164–169, 2000. 53. Stylianos S: Compliance with evidence-based guidelines in children with isolated spleen or liver injury: a prospective study. J Pediatr Surg 37:453–456, 2002. 54. Jacobs IA, Kelly K, Valenziano C, et al: Nonoperative management of blunt splenic and hepatic trauma in the pediatric population: significant differences between adult and pediatric surgeons? Am Surg 67:149–154, 2001. 55. Pryor JP, Stafford PW, Nance ML: Severe blunt hepatic trauma in children. J Pediatr Surg 36:974–979, 2001. 56. Fisher JC, Moulton SL: Nonoperative management and delayed hemorrhage after pediatric liver injury: new issues to consider. J Pediatr Surg 39:619–622, 2004. 57. Wessel LM, Scholz S, Jester I, et al: Management of kidney injuries in children with blunt abdominal trauma. J Pediatr Surg 35:1326–1330, 2000. 58. Shilyansky J, Sen LM, Kreller M, et al: Nonoperative management of pancreatic injuries in children. J Pediatr Surg 33:343–345, 1998.

Chapter 25 — Abdominal Trauma 59. Kouchi K, Tanabe M, Yoshida H, et al: Nonoperative management of blunt pancreatic injury in children. J Pediatr Surg 34:1736–1738, 1999. 60. Wales PW, Shuckett B, Kim PCW: Long-term outcome of nonoperative management of complete traumatic pancreatic transection in children. J Pediatr Surg 36:823–827, 2001. 61. Canty TG Sr, Canty TG Jr, Brown C: Injuries of the gastrointestinal tract from blunt trauma in children: a 12-year experience at a designated pediatric trauma center. J Trauma 46:234–240, 1999.

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62. Nance ML, Keller MS, Stafford PW: Predicting hollow visceral injury in the pediatric blunt trauma patient with solid visceral injury. J Pediatr Surg 35:1300–1303, 2000. 63. Harris LM, Hordines J: Major vascular injuries in the pediatric population. Ann Vasc Surg 17:266–269, 2003. 64. Cox CS, Black CT, Duke JH, et al: Operative treatment of truncal vascular injuries in children and adolescents. J Pediatr Surg 33:462–467, 1998.

Chapter 26 Burns Nicholas Tsarouhas, MD and Paula Agosto, RN, MHA

Key Points Proper management of the burn patient requires the clinician to be comfortable with the classification of burns by both depth and body surface area. It is crucial to anticipate and be able to manage the possibility of fulminant airway edema in the burn patient. The profound fluid needs of the burn patient with circulatory impairment require familiarity with weight-based and body surface area–based calculations. The goal of burn wound management is to reduce the risk of infection while minimizing the likelihood of an adverse cosmetic outcome. The decision to admit and/or transfer a child to a burn center depends on many factors, including the risk of infection, cosmetic and functional outcomes, pain control, complexity of wound care, age, associated morbidities, underlying medical conditions, and social concerns.

Causes The leading causes of burns in children are scalds, flame burns, and electrical injuries.3 Children less than 5, especially boys, are the highest risk group. In toddlers, scald burns from hot liquids account for 80% of all thermal injuries.3 Toddlers also are commonly burned from touching hot metals such as stoves, grills, and home space heaters. School-age children often sustain thermal burns from play with dangerous equipment such as matches and cigarette lighters. Teenagers are more commonly burned from risk-taking activities, fireworks, and careless use of flammable substances. Household fires caused by unattended cigarettes or candles are a major contributor to pediatric burn injuries and death in all age groups. Cigarettes alone are responsible for 35% of the fatal house fires in the United States.4 Anatomy and Physiology The skin is the organ most visibly affected by burns. It consists of two main layers: the epidermis and the dermis. The epidermis (the outer layer of skin) is formed from several layers of stratified epithelium. The dermis is composed of connective tissue, which is tough and elastic. The nerve endings concerned with the sensation of touch and temperature are located in the dermis. Structures within the skin include sweat glands, hair follicles, and sebaceous glands. A layer of subcutaneous fat separates the skin from underlying structures. In addition to its cosmetic importance, the skin protects the body against infection, regulates body temperature, and serves as a barrier to prevent fluid loss. Pathophysiology

Introduction and Background Epidemiology Burns continue to be a major source of morbidity and mortality in the pediatric population. In the United States in 2001, there were more than 181,000 fire- and burn-related injuries, and 672 deaths in children up to age 19 years.1 In children 1 to 9 years old, burns rank third among injuryrelated deaths.2 Most pediatric deaths occur as a result of house fires. Lower socioeconomic areas account for the highest death rates. While the incidence of burns continues to drop in the United States, it is important to remember that many burns are not reported; therefore, most data underestimate the true scope of this public health issue.3 246

Thermal Burns The thinner skin of young children accounts for deeper burns as compared to adults. Thermal energy damages skin in proportion to intensity and duration. Once tissue is damaged, blood supply and cellular activity increase in the injured area, causing heat and redness. The damaged tissue and mast cells ooze various enzymes and histamine, which trigger vasodilation and increased capillary permeability. Swelling and edema then develop as the capillary walls leak inflammatory exudate (containing plasma, antibodies, and some red blood cells and white blood cells) into the surrounding tissue. Macrophage cells begin to arrive at the wound site to defend against bacteria and help clear blood clots, damaged tissue, and other debris.5

Chapter 26 — Burns

Inhalation Injury While thermal burns account for major fire-related morbidity, mortality is intimately tied to inhalation injury and carbon monoxide (CO) poisoning. Inhalation of toxins associated with flame smoke accounts for 80% of burn-related deaths.6 Direct thermal injury may lead to upper airway edema and obstruction. Some combustion of soot particles continues, and these small particles may be carried into the lung. Additional clinical consequences include systemic capillary leak, bronchospasm from aerosolized irritants, small airway occlusion from sloughed endobronchial debris, impaired ciliary clearance, loss of surfactant, increased dead space and intrapulmonary shunting from alveolar flooding, decreased lung compliance from interstitial and alveolar edema, decreased thoracic compliance from chest wall burns, and, later, infection of the denuded tracheobronchial tree (tracheobronchitis) or pulmonary parenchyma (pneumonia).7 The evaluation and management of smoke inhalation is covered in detail in Chapter 143 (Inhalations and Exposures). Carbon Monoxide Poisoning Smoke inhalation is commonly associated with CO poisoning, as levels of CO may reach 10% in house fires.8 CO impairs oxygen delivery and utilization. It binds tightly to hemoglobin with an affinity 250 times that of oxygen. CO also binds to cytochrome oxidase, thus interfering with cellular oxidative energy metabolism.9 The net result of this impairment in the delivery, release, and use of oxygen is tissue and cellular hypoxia. The evaluation and management of CO poisoning is covered in detail in Chapter 143 (Inhalations and Exposures). Electrical Injury Electrical burns result in over 1500 deaths per year10 and 2% to 3% of all admissions to hospital burn centers.11 Electrical burns result from thermal energy that is produced as an electrical current passes through the body. The amount of thermal energy produced is directly proportional to the degree of the electric current. Nerves, muscles, and blood vessels have low electrical resistance, so electricity will preferentially flow through these structures. Alternating current, which is found in household electricity, produces muscle tetany caused by the continual contraction and relaxation of the muscle with each cycle. One of the most common pediatric electrical injuries occurs as a result of a child biting an electrical cord.

Table 26–1

247

Direct current, found in lightning, poses its greatest risk when the current traverses the heart, resulting in ventricular fibrillation or asystole. While 70% to 80% of those struck by lightning survive,12 100 fatalities occur in the United States each year.13 The major cause of arrest in these patients is the result of dysrhythmias, myocardial damage, or respiratory arrest with asphyxia. The evaluation and management of electrical injuries is covered in detail in Chapter 142 (Electrical Injury). Chemical Burns Nearly 100,000 chemical burns are reported in the United States each year.11 Fortunately, the overwhelming majority of these prove to be relatively benign. In most cases, the burn is a result of a direct chemical injury. Acid burns result in coagulation necrosis, which usually limits the depth and penetration of the burn. Common household products that contain acids include drain cleaners (sulfuric acid or hydrochloric acid), toilet cleaners (hydrochloric acid or phosphoric acid), and car batteries (sulfuric acid).14 Alkalis produce liquefactive necrosis, thus causing deeper penetration and a more significant burn. Alkalis include lye (sodium hydroxide), fertilizers (anhydrous ammonia), oven and drain cleaners (sodium or potassium hydroxide), paint strippers (sodium hydroxide), and various detergents.15 Consultation with a poison control center should be considered when evaluating children with chemical burns, to assess the possibility of associated systemic toxicities in addition to the cutaneous burn. The evaluation and management of chemical burns is covered in detail in Chapter 143 (Inhalations and Exposures).

Recognition and Approach Classification of Thermal Burns Depth Traditionally, burns have been classified as first, second, third, and even fourth degree. Many experts now recommend that this nomenclature be replaced by the designations of superficial, superficial partial thickness, deep partial thickness, and full thickness (Table 26–1). It is often difficult to correctly identify the depth of the burn, however, and it is common to have several depths exhibited in one injury. The center usually has a higher degree of burn than the periphery. First-degree or superficial burns are limited to the epidermis. They are characterized by painful, erythematous,

Classification of Burns by Depth

Burn Type

Histology

Appearance

Pain?

Healing

Scarring?

Superficial/first degree Superficial partial thickness/second degree Deep partial thickness/ second degree

Epidermis only

Painful, erythematous, nonblistered Erythematous, blistering, moist

Painful

3–5 days

None

Painful

2 wk

Possible

Paler, drier, blistering

May be less painful

Several weeks

Likely

Pale and white, or charred and leathery

May be painless

Months

Always

Full thickness/third degree

Complete destruction of epidermis and 50% of dermis Complete destruction of epidermis and dermis

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SECTION II — Approach to the Trauma Patient

nonblistered areas of inflammation. An example is a severe sunburn. Importantly, when body surface area (BSA) calculations are performed to estimate the amount of burn, firstdegree burns are not included. Generally, these burns heal within 3 to 5 days with no scarring. Second-degree or partial-thickness burns extend into the dermis. Superficial partial-thickness burns result in the complete destruction of the epidermis and less than 50% of the dermis. These burns are erythematous, blistering, moist, and painful. There is pain because intact sensory nerve receptors are still exposed. These usually heal in 2 weeks, though scars are possible. Deep partial-thickness burns result in the complete destruction of the epidermis and greater than 50% of the dermis. They are often paler and drier, and may be less painful as there is some destruction of cutaneous nerves. These take many weeks to heal, and scars are likely. Third-degree or full-thickness burns extend into the subcutaneous tissues. Full-thickness burns result in the complete destruction of the epidermis and the dermis. Their appearance may be pale and white, or charred and leathery. These are usually nontender as there is widespread destruction of cutaneous nerves. Healing is slow, and skin grafting is usually needed. Some experts add an additional category of fourth-degree burns. These involve destruction of the underlying structures such as muscles, tendons, nerves, and bones. Severe electrical burns are an example of this type. Body Surface Area BSA estimates are important in the initial evaluation and management of burns. These calculations help guide volume resuscitation, decisions to admit, transfer to burn centers, and prognosis. Importantly, only second- and third-degree burns are included in the BSA calculation, because superficial burns have little impact on patient care and outcome. The “rule of nines” (Table 26–2) is a convenient and rapid method of estimating the extent of BSA burned in adolescents. It divides the surface area of the body into areas of 9%. When all body areas of these 9% segments are summed, 1% remains, which is assigned to the genitalia and perineum. It is inaccurate for children, however, as they have relatively larger heads and smaller extremities. The rule of nines is good for a quick estimate in children older than 9 years. For patients who are 9 years and younger, a more precise method of burn size estimation should ultimately be used. The Lund and Browder chart16 (Fig. 26–1) subdivides body areas into segments and assigns a propor-

Table 26–2

Classification of Burns by Body Surface Area: “Rule of Nines”*

Body Area

Relative Percent Burn

Head and neck Anterior/posterior torso Lower extremity Upper extremity Genitalia/perineum Total

9% 18% each (36%) 18% each (36%) 9% each (18%) 1% 100%

*Note: Less accurate for children 9 years and younger, who have relatively larger heads and smaller extremities.

tionate percentage of body surface to each area, based on age. The lower extremity is divided into upper leg, lower leg, and foot, rather than being considered as a whole. The head of a baby is proportionately much larger than any other area of the body. As a child grows, the head becomes relatively smaller as compared with the rest of the body, and the lower extremities assume more BSA. Another method of estimating burn injury extent uses the size of the child’s hand. The BSA represented by the hand is set at 1%. Some experts advocate including the fingers, while others do not. A better estimate of the palm itself may be 0.5%17; one study estimated the palm at 0.4%, and the entire hand at 0.8%.18 This method is both quick and useful for areas of irregular or nonconfluent burns. Recognition of Child Abuse Between 10% and 20% of burns in children are intentionally inflicted.11 Most inflicted burns are scald or contact burns that have recognizable patterns (Table 26–3). Toddlers submerged in hot water, particularly as punishment for toilet training misfortunes, present with a characteristic scald burn to the buttocks, perineum, thighs, and feet (see Chapter 119, Physical Abuse and Neglect). The primary care provider needs to have a high index of suspicion when the history of the injury does not match the pattern of the burn, or is not consistent with the child’s developmental age. While the burn needs to be promptly treated, the provider is mandated to report all suspicious injuries to the appropriate social services and child protective agencies.

Evaluation Immediate Emergency Department Evaluation Airway Assessment Inhalation of hot gases can burn the airway, and lead to rapidly progressive airway edema and obstruction. The child’s airway is exquisitely sensitive to swelling, as airway resistance increases as the fourth power of the radius. Thus even small degrees of edema may have catastrophic airway implications. Every emergent evaluation, regardless of the injury, begins with an airway assessment. The evaluation commences with an “across the room” inspection of the child’s airway patency. The crying child, at the very least, is able to maintain the airway at that point in time. The child who is quiet or exhibiting signs of distress is more ominous. The usual signs and symptoms of airway compromise should be sought: stridor, hoarseness, drooling, gagging, coughing, and increased work of breathing. Additional signs of concern include burns to the face, singed facial hairs, and carbonaceous sputum. Table 26–3 • • • • • •

Recognizable Patterns of Intentionally Inflicted Burns

Triangular shape from the tip of an iron Linear parallel lines from a radiator Hot water submersion burns to buttocks, thighs, feet Symmetric, well-demarcated stocking/glove burns to feet/hands Splash burns when a hot liquid is thrown Deep, small, circular cigarette burns

Chapter 26 — Burns

249

A

2

2

13

11/2

2

11/2

11/2

11/2 21/2

1

11/2

11/2 B

B

C

C

13/4

2

13

21/2

11/2

11/2 B

B

C

C

13/4

13/4

13/4

soles of feet

FIGURE 26–1. Classification of burns by body surface area: the Lund and Browder chart. (Adapted from Thermal injury. In Barkin RM [ed]: Pediatric Emergency Medicine, 2nd ed. St. Louis: Mosby, 1997, p 490.)

< 1 yr

1 yr

5 yr

10 yr

15 yr

Adult

A half of head

9 1/2%

8 1/2%

6 1/2%

5 1/2%

4 1/2%

3 1/2%

B half of thigh

2 3/4%

3 1/4%

4%

4 1/4%

4 1/2%

4 3/4%

C half of leg

2 1/2%

2 1/2%

2 3/4%

3%

3 1/4%

3 1/2%

head

19%

17%

13%

11%

9%

neck

2%

2%

2%

2%

2%

half of trunk (ant or post)

13%

13%

13%

13%

13%

one buttock

2.5%

2.5%

2.5%

2.5%

2.5%

genitalia

1%

1%

1%

1%

1%

upper (3) or lower (4) arm

3-4%

3-4%

3-4%

3-4%

3-4%

one hand (2.5) or foot (3.5)

2.5-3.5%

2.5-3.5%

2.5-3.5%

2.5-3.5%

2.5-3.5%

one thigh

5%

6.5%

8.5%

9%

9.5%

one leg (below knee)

5%

5%

5.5%

6%

6.5%

It is important to remember that cervical spine trauma may be present. Often, patients have jumped or have fallen from burning buildings. If the history is unclear or unknown, patients must be cervically immobilized until clinical or radiographic assessment and clearance is completed.

Breathing Assessment Bronchospasm is very common from the extreme irritative properties of inhaled smoke and toxic gases. Once again, the patient in respiratory distress should be obvious at the onset. Tachypnea, retractions, grunting respirations, coughing, and

250

SECTION II — Approach to the Trauma Patient

nasal flaring are all clues to the severity of the distress. Concerning lung ausculatory sounds include wheezing, rales, and decreased breath sounds. Cyanosis is a late sign of critical compromise. A pulse oximeter reading of oxygen saturation is useful in many cases, but it is crucial to remember that victims of CO poisoning will look pink and have a normal oxygen saturation, despite being hypoxemic. An arterial blood gas with co-oximetry is mandatory. Equally important is the fact that the initial chest radiograph may be normal. Over the course of a few hours, infi ltrates, and even complete opacification may develop. Circulation Assessment Burn patients may experience profound circulatory impairment (“burn shock”). Shock may develop in children with 15% to 20% BSA burns.11 Large burns release vasoactive mediators that result in systemic capillary leakage. Cardiac output is decreased by circulating factors that depress myocardial function, which may lead to shock. Important indicators of circulatory integrity include mental status, skin color and temperature, capillary refi ll, pulses, heart rate, and blood pressure. While hypotension is a late and ominous sign of circulatory failure in children, hypertension is also seen in severely burned children. Other important parameters to guide fluid management include urine output and, in some cases, central venous pressures. Basic metabolic chemistries and blood gases for pH are also important to assist in the fluid management of these patients. Mental Status Assessment Alteration in mental status should prompt a thorough assessment for the underlying etiology. Possible life-threatening etiologies include anoxia from asphyxiation, hypercarbia from hypoventilation, CO intoxication, hypovolemia with resultant cerebral hypoperfusion, traumatic brain injury, and seizures. Other causes may include pain, anxiety, drugs, and alcohol. Children with large burns, although alert in the first hours after injury, may become obtunded secondary to fluid shifts, pain medication, sleep deprivation, and exhaustion.19 Nevertheless, computed tomography scans should be obtained when the etiology of the mental status aberration is unknown, to exclude occult head injury. Blood gases with co-oximetry, electrolytes, and toxicologic screens also add useful information.

The most common burn infection is a cellulitis. This usually occurs in the first few days after the burn. Any progressively expanding area of erythema, induration, and tenderness around a burn’s margins should raise suspicion of a cellulitic infection. Unfortunately, the inflammatory response that ensues after a burn also may easily be confused with a cellulitis. Moreover, fever, which is common with cellulitis, is often seen in the setting of an uninfected burn, as an expected physiologic inflammatory response. While laboratory studies are occasionally helpful, close clinical observation for progression is crucial. Invasive burn wound infections also occur. A rapid proliferation of bacteria in burn eschar may proceed to invade underlying viable tissues. Clinical signs of an invasive burn wound infection include (1) a change in color of the wound; (2) a dark brown, black, or violaceous discoloration of the wound; (3) hemorrhagic discoloration of subeschar tissue; (4) conversion of a burn from partial thickness to full thickness; (5) new drainage; and (6) a foul odor.22 Additionally, fever and other systemic signs of toxicity may be present. Gram-positive organisms, typically Staphylococcus aureus and group A β-hemolytic streptococcus (GABHS), are the predominate pathogens in early burn infections (Table 26–4). Gram-negative organisms, especially Pseudomonas aeruginosa, colonize the eschar and should be considered when infections develop after a week. P. aeruginosa infection classically presents with the green pigment pyocyanin. Ecthyma gangrenosum should also raise suspicion for P. aeruginosa infection. These deep cutaneous erosions, usually seen in immunocompromised patients, often begin as vesicles, which pustulate, and then progress rapidly to gangrenous ulcers. Sepsis is common. Bacteroides and other anaerobic bacteria are occasional isolates from serious burn infections. In extensively burned patients who develop late infections, Candida and other fungi should be considered.20 Viral infections of burns, most commonly herpes simplex virus (HSV) or cytomegalovirus, are usually heralded by a vesicular eruption. Systemic Inflammatory Response Syndrome Systemic inflammatory response syndrome may follow severe burns. The common presentation is fever, tachypnea, tachycardia, shock, and multisystem organ failure. The hyperactive immune response causes a generalized inflammation that damages healthy tissue as well as infected burn wounds. Microvascular permeability leads to decreased tissue oxygenation, and blood flow is reduced due to microthrombi. During

Life-Threatening Complications Infection Infection remains the leading cause of morbidity and mortality in burn patients.20 The overall reported incidence of infections in burned children is 13.6%.21 Necrosis of burned tissue produces a protein-rich medium that encourages bacterial growth. Inevitably, all burns become colonized by skin flora and potentially pathogenic organisms that may invade this breached epithelial barrier and lead to infectious complications. Inhalation injury to the respiratory tract may lead to lethal pulmonary disease. Importantly, seriously burned children also have a global immunosuppression that compounds their infection susceptibility.7

Table 26–4

Pathogens Responsible for Burn Infections

Early Infections Staphylococcus aureus Group A β-hemolytic streptococcus (GABHS) Late Infections Pseudomonas aeruginosa and other gram negatives Bacteroides and other anaerobic bacteria Candida and other fungi Herpes simplex virus, cytomegalovirus, and other viruses

Chapter 26 — Burns

this reaction, the intestinal and, possibly, the respiratory barriers to infection are damaged, allowing the entry of additional bacteria into the circulation.6 Aggressive supportive care remains the therapeutic mainstay. Myoglobinuria Myoglobinuria secondary to muscle breakdown and widespread cell death (rhabdomyolysis) is seen when BSA burns approach 30%. Myoglobin accumulates in the kidneys at alarming rates and may lead to fulminant renal failure. Strict attention to the urine output, urinalysis, and fluid therapy is crucial. Special Considerations Eye Burns Serious corneal burns are generally obvious on physical examination, with the cornea having a clouded appearance. More subtle injuries can be detected after topical fluorescein application. In general, any burns of the eyes or eyelids require urgent ophthalmologic consultation. Ear Burns The most important aspect of managing deeply burned ears is to prevent auricular chondritis. This serious complication results from the poor blood supply of the cartilage of the external ear. The prevention of infection is paramount as infected cartilage liquefies, losing its structural integrity. Topical mafenide acetate has been shown to sharply reduce the incidence of auricular chondritis.23 Hand Burns Preservation of the functional integrity of the hand mandates specialized attention. Hand surgery consultation is mandatory. During the first 24 to 48 hours, adequate blood flow must be ensured. The adequacy of perfusion can be judged by temperature and the presence of pulsatile flow detectable by Doppler in the digital pulp. If there is any question, escharotomy or fasciotomy should be done. Subsequently, the hands should be splinted in a position of function, with the metacarpophalangeal joints at 70 to 90 degrees, the interphalangeal joints in extension, the first web space open, and the wrist at 20 degrees of extension.23

Management Emergency Stabilization Airway Humidified oxygen (100%) should be administered immediately to all burn patients. As burn patients may also have cervical spine trauma, the head should be maintained in neutral position, and any airway manipulation should presume the presence of a cervical spine injury. The jaw thrust should be the airway opening maneuver of choice, as opposed to the chin lift, which could extend the neck and damage the spinal cord. Endotracheal intubation should only occur with the assistance of someone maintaining in-line cervical stabilization. Because the airway is so precarious, experts recommend early intubation, as edema and obstruction can develop rapidly.24 In anticipation of a distorted and edematous airway,

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endotracheal tubes (ETTs) with smaller diameter than usual for age should be readily available. Once the tube is in place, it should be very carefully secured, as reintubation may be impossible if it is dislodged. One safe method of securing the ETT in the burn patient is to tape both under and over the ears.25 Breathing Once the airway is secure and oxygen is being delivered, attention turns to the adequacy of oxygenation and ventilation. The clinical assessment is augmented by electronic end-tidal CO2 monitoring and pulse oximetry. It is vital to remember, however, that in the presence of elevated carboxyhemoglobin levels (common with smoke inhalation) pulse oximetry overestimates the true oxyhemoglobin saturation.26 Thus, arterial blood gas determination (with co-oximetry) is mandatory. If the patient’s breathing is judged to be suboptimal, ventilatory support is necessary. Hand ventilation with a bagvalve-mask apparatus should be employed initially while preparations are made for endotracheal intubation. Ideally, an anesthesia (Mapleson) bag should be used to manually ventilate, as it allows one to assess lung compliance, which is often compromised in the setting of smoke inhalation. The bronchospasm that commonly accompanies smoke inhalation should be treated with aerosolized β2-agonists (albuterol, levalbuterol), terbutaline, and/or epinephrine. Corticosteroids have not been shown to be of benefit in decreasing the tracheobronchial inflammation induced by smoke inhalation.27 If endotracheal intubation and mechanical ventilation are required, there are a few important medication selection considerations. The most common sedative choices are thiopental, midazolam, ketamine, and etomidate. Because thiopental is associated with hypotension, it should be avoided in the burn patient with circulatory insufficiency or shock. While etomidate and midazolam are fine choices, ketamine has the added benefit of being a bronchodilator, which may be useful in the setting of smoke-induced bronchospasm. The muscle relaxants of choices are usually the nondepolarizers (vecuronium, pancuronium, rocuronium). Nondepolarizing muscle relaxants are preferred over succinylcholine for burns that are more than 48 hours old. Once mechanical ventilation is initiated, air trapping should be anticipated. Adequate expiratory times should be ensured, and one should be alert for dynamic hyperinflation.28 Inflating pressures to greater than 40 cm H2O should be avoided, unless there is severely impaired chest wall compliance.7 Circulation/Fluid Therapies Adequate vascular access is required to support the resuscitation needs of the severely burned patient. Peripheral vascular access can be difficult to secure in hypovolemic burn patients, especially young children. When necessary, it is acceptable to place an intravenous (IV) line through the burn wound.29 Central access is generally required in children with large burn injuries.7 The intraosseous route should be used in the unstable child needing fluid therapy in whom rapid vascular access is not easily obtained. Burns greater than 15% to 20% BSA will produce hypovolemic shock unless appropriately managed with crystalloid

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Environmental

fluid replacement. Burns less than 15% are not associated with massive capillary leak; therefore, formal fluid resuscitation is not required.30 Isotonic saline, most commonly lactated Ringer’s solution, is recommended for resuscitation in the first 24 hours after a significant burn.7 Lactated Ringer’s solution contains physiologic concentrations of major electrolytes. The lactate serves as a buffer, which may lessen the propensity for hyperchloremic acidosis.30 Normal saline, however, is an acceptable alternative. An initial fluid bolus of 20 ml/kg is recommended. Large volumes of fluid are needed, however, for proper resuscitation, because only 20% to 30% of the isotonic fluid remains in the intravascular space.31 The initial fluids should not contain potassium, as cell breakdown (common to massive burns) releases a large amount of intracellular potassium. This hyperkalemia could have devastating effects on both the heart and kidneys. Albumin also should be avoided initially, as edema may be increased by albumin use in the first 24 hours because of capillary leak. Once capillary integrity is restored and intravascular volume is replete, colloid may be helpful for volume expansion and preservation of serum oncotic pressure. Some experts have recommended the use of 3% sodium chloride solution during resuscitation. The theory is that the hypertonic saline might preserve intravascular volume and decrease edema. However, other experts disagree. One particular study found that hypertonic sodium resuscitation was associated with renal failure and death.32 The Parkland formula33 and its variations have become the standard method for calculating the initial fluid requirements of severely burned patients. During the initial 24 hours after injury, the patient receives 4 ml/kg/%BSA burn of lactated Ringer’s solution in addition to maintenance fluids. Half of this total is given in the first 8 hours after injury, and the remainder is given in the subsequent 16 hours. It is universally acknowledged that the Parkland formula, while quick and easy to use, underestimates the needs of young children, as it is strictly based on weight. Weight-based formulas are suboptimal because BSA correlates imprecisely with weight in growing children. Using weight-related formulas may lead to the administration of less than maintenance fluids to smaller children. Thus, maintenance fluids should be added to the Parkland calculation for children younger than 5 years. An alternative is to use a surface area–related formula, such as the one devised by Carvajal.34 The Carvajal formula recommends that, in the first 24 hours, in children less than 5 years old, the following formula be used: 5000 ml/m2/%BSA burn, plus 2000 ml/m2. As with the Parkland formula, half of this total is given in the first 8 hours after injury, and the remainder is given in the subsequent 16 hours.

Prophylactic systemic antibiotics are contraindicated in burn care, as their use has been shown to increase the risk of more virulent and resistant organisms.29,35,37,38 Antibiotic therapy should be initiated only if the clinical suspicion for an infected burn is high. A progressively expanding burn cellulitis should be treated with topical mafenide acetate and a systemic semisynthetic penicillin to cover for GABHS and S. aureus, or a broad-spectrum β-lactam antibiotic if culture results are unavailable.22 Invasive burn wound infections can be life threatening, and generally require treatment with a combination of surgery and antibiotics.23 Topical antifungal agents (clotrimazole) are used for localized fungal infections, but any suspicion of disseminated fungal infection should be aggressively treated with IV amphotericin B, possibly with the addition of 5-flucytosine.22 Topical acyclovir (5%) may be used in patients with documented localized HSV infections, but similarly, any suspicion of disseminated HSV infection should prompt treatment with IV acyclovir.22 Routine use of topical antibacterials, such as silver sulfadiazine and mafenide acetate, is discussed later.

Dextrose

Nasogastric Tube

Smaller children (1 to 2 cm) should be broken and débrided.35,42 These experts believe that leaving blisters intact may interfere with assessment and with joint mobility.44 Still others advocate relieving uncomfortable pressure by aspirating the burn fluid from tense blisters, leaving the epithelium to act as a biologic dressing.45,46 Topical Antibiotics After the burn has been cleaned and débrided, attention must be given to controlling bacterial density and decreasing the likelihood of a burn wound infection. A number of agents are effective as topical antimicrobials in burn wound care. They are generally divided into potent agents that are designed to prevent burn wound invasion (silver sulfadiazine, mafenide acetate, and silver nitrate), and milder agents (bacitracin, Neosporin, Polysporin, and mupirocin) that are used to treat small or superficial wounds. The more potent agents may delay epithelialization and should be reserved for use in managing more extensive and deeper burns. The milder agents, when used in combination with nonadherent gauze, provide a comfortable, protective environment that promotes epithelialization of the wound.35

The use of light occlusive dressings is generally believed to prevent bacterial infection and enhance the rate at which wounds epithelialize. Additionally, optimal dressings should absorb exudates, prevent the wound from further damage, and cause minimal pain upon removal. Many centers use petroleum or mesh gauze as the first layer on the wound. This provides a moist environment that promotes healing, and doesn’t stick to the wound upon removal. This gauze is then covered with multiple layers of absorbent padding to better protect the wound from additional trauma. While not a standard for emergency department use, Biobrane, a bilaminar temporary skin substitute, is sometimes used. This biosynthetic wound dressing is constructed of a silicon fi lm with a nylon fabric partially embedded in the fi lm. The fabric presents to the wound bed a complex, three-dimensional structure of trifi lament threads to which collagen has been chemically bound.47 One prospective study found that the treatment of partial-thickness burns with Biobrane was superior to topical therapy with 1% silver sulfadiazine.48 While different uses have been advocated for this dressing, its use in partial-thickness burns has remained controversial. One of the concerns that has been raised against the use of Biobrane in this setting is infection. Infection rates from 5% to 22.6% have been reported.49-51 Disposition Indications for Admission It is often difficult to decide the disposition of pediatric burn patients. While many guidelines exist that define specific BSA percentages, as well as wound severity, these alone cannot be the sole determinants. The risk of infection,

Chapter 26 — Burns

Table 26–6

Indications for Admission

Burn Depth/Body Surface Area (BSA) Full thickness >2% BSA Partial thickness >10% BSA Burn Location Face Perineum and genitalia Hands, feet, joints Circumferential Burn Mechanism Inhalation Electrical/high voltage Chemical Associated Issues Serious trauma Underlying medical problems Social concerns Very young age Social/Environmental Issues Neglect Abuse Unable to care for self

cosmetic and functional outcomes, pain control, complexity of wound care, age, associated morbidities, underlying medical conditions, and social concerns all must be factored into this complicated decision. Table 26–6 lists some useful parameters to assist with this decision making. Indications for Transfer to a Burn Center Most experts agree that burn centers have improved survival and reduced morbidity in burn patients. Many publications list factors to consider when deciding which children should be transferred to a burn center.52 Many of these parallel the indications to admit noted previously. For example, burn patients with preexisting medical disorders often require transfer, as issues related to these disorders could complicate management, prolong recovery, and affect mortality. While trauma is often cited as a reason to transfer, the burned patient initially should be stabilized in a trauma center before being transferred to a burn center. Burned children in hospitals without qualified personnel or equipment should be transferred. Transfer should be considered in all children who will require special social, emotional, or long-term rehabilitative care. Importantly, these factors should be considered as guidelines, rather than rigid protocols. Out-of-Hospital Care Emergency Medical Services providers follow many of the management strategies outlined earlier. Most importantly, they must be cognizant of the risk of impending airway compromise; therefore, they must always be vigilant about the need for early endotracheal intubation. Oxygen (100%) should be administered and breathing should be supported, while maintaining cervical spine immobilization as necessary. At least one, but preferably two peripheral IV lines should be started in patients with significant burns. Lactated Ringer’s solution should be infused, usually in boluses of 20 ml/kg. Great care must be taken to ensure that the patient’s body temperature is maintained, as hypothermia is an important problem in young children with large burns.

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Discharge Care Medications Acetaminophen or ibuprofen are commonly used analgesics at discharge. Narcotics, such as codeine or hydrocodone, however, may be necessary in cases of larger, painful burns. As burns are pruritic, medications such as hydroxyzine, diphenhydramine, and newer antihistamines may be helpful, especially when used in conjunction with moisturizing creams or lotions.35 Wound Infection The parents should be advised to return with the patient if there are signs of infection: redness, swelling, tenderness, and purulent discharge. Of course, many of these signs are normal in the course of burn healing, so it is not always easy to distinguish a burn infection from a normally healing burn wound. It is common for Silvadene-treated burns to form a greenish serous drainage that is easily mistaken for purulence. Furthermore, while many associate the development of a fever with an infection, it is important to remember that burn patients may develop low-grade fevers a day or two after the burn—even in the absence of infection. Wound Care The parents should be instructed to keep the wound clean and dry. They can clean the wound with soap and lukewarm water. Some recommend saline solutions. The parents may débride loose nonviable tissue, and wash off accumulated exudates and topical antibiotic residues. After the wound has been cleaned, topical antibiotic ointments or creams may be applied. These topical antibiotics, typically Silvadene or Polysporin, are usually applied twice daily until the wound has completely reepithelialized. This process usually takes 5 to 10 days for superficial wounds and 10 to 14 days for medium-depth wounds.35 It is important to use clean, but not necessarily sterile technique when performing burn wound care at home.53 The wound is dressed with a light, nonadherent dressing following the application of the topical antibiotic. Most experts recommend twice-daily dressing changes.53 On smaller wounds, however, once daily should suffice.37 Follow-up Care Follow-up care of all partial- and full-thickness burns is extremely important. The wound should be examined by a clinician every 2 to 3 days. The parents and patient should be instructed to return 4 to 6 weeks later to assess for hypertrophic scar and pigment changes. Patients should also be instructed to avoid ultraviolet light exposure (i.e., sunlight) during the time of wound maturation because the wound may become permanently hyperpigmented. The use of a sun block (>30 sun protection factor) is recommended for at least 1 year for any patient whose wounds are exposed to sunlight.35 Approach to the Child and Family An important component to the management of the severely burned child centers around the psychosocial trauma that this injury has on the family. Parents may be experiencing

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feelings of guilt, anger, anxiety, and fear. These feelings are often sensed by the child. Gentle reassurance in a calm, quiet manner will assist in soothing those involved. The age of the child will dictate the specific approach. For the child younger than 2 years, communication is most effective through the parents. Children of this age have little understanding of what is happening, but usually feel a sense of security when a parent is present. For the 2- to 7-year-old child, careful reassurance and explanation in words that the child can understand are vital, as these children often believe that injury, discomfort, and painful procedures are a punishment for bad behavior. For the 7- to 11-year-old, clear, simple explanations are required. Children who are ill or in pain often regress. They should be reassured that that it is acceptable to cry when they feel pain, otherwise they might feel ashamed and uncomfortable. Above 11 years, children are able to comprehend the outcome of their injuries, and will want precise information, particularly regarding potential scarring.54 The parents, also, will want clear information about what to expect. Parents often feel that they lose control of their child’s well-being in the clinical environment. Including them in the care of their child, ensures partnership, and helps to give them control in the child’s care.

Summary Prognosis A study looking at burn survival rates in children from 1974 to 1980, versus from 1991 to 1997, concluded that survival rates after burns have improved significantly for all children. Furthermore, even children with large burns should survive today.55 Importantly, the large majority of those who survive serious burns have favorable long-term outcomes.56-59 Even those who survive massive injuries can be expected to have a satisfying quality of life.60-63 Advances in resuscitation, intensive care, mechanical ventilation, vascular access, antimicrobials, analgesia, nutrition, surgical intervention, and wound care have all contributed to improvements in survival and quality of life.55 Prevention During the past two decades, fire-related deaths have declined. This is due to improved fire-fighting techniques, enhanced emergency medical services, and widespread educational programs aimed at both children and adults.64 For example, the use of home smoke detectors has dramatically reduced the severity of burn injuries, resulting in an estimated 80% reduction in mortality and a 74% decrease in injuries from residential fires.64,65 The use of flame-resistant childhood sleepwear has further contributed to these reductions. Lowering the temperature of the water on the thermostats of water heating units has also made a significant impact. The contact time for a scald burn drops significantly as water temperature rises above 120° F. For this reason, it is recommended that hot water heaters be set at or below 120° F. A water temperature of greater than 140° F (common in hot water heaters) causes severe burns in less than 5 seconds in children.66 The bath water temperature should always be checked first by an adult.

Parents and caregivers should be warned of the common summertime burn dangers from fireworks, barbecue grills, and campfires. Even excessive sun exposure can lead to sunburns with serious consequences. Winter burn threats include wood stoves and electric and kerosene space heaters. Advances in our abilities to evaluate patients and manage their burn-related morbidities have led to dramatic improvements in the overall care of burned children. Nevertheless, prevention remains our first defense against these tragedies. Research should continue to focus on creative new strategies to ensure the safety of our children. REFERENCES 1. Centers for Disease Control and Prevention, National Center for Injury Prevention and Control, WISQUARS: Overall fi re/burn nonfatal injuries and rates per 100,000 and fi re/burn deaths and rates per 100,000. Available at http://webapp.cdc.gov/cgi-bin/broker.exe 2. Centers for Disease Control and Prevention: Ten leading causes of injury death by age group—2001 highlighting unintentional injury deaths. Available at ftp://ftp.cdc.gov/pub/ncipc/10LC-2001/PDF/101c *3. Passaretti D, Billmire D: Management of pediatric burns. J Craniofac Surg 14:713–718, 2003. 4. McLoughlin E, McGuire A: The causes, cost and prevention of childhood burn injuries. Am J Dis Child 144:677–683, 1990. *5. Taylor K: The management of minor burns and scalds in children. Nursing Standard 16(11):45–52, 54, 2001. 6. Klein G, Herndon D: Burns. Pediatr Rev 25:411–417, 2004. *7. Sheridan RL: Burns. Crit Care Med 30:S500–S514, 2002. 8. Thom S, Keim L: Carbon monoxide poisoning: a review—epidemiology, pathophysiology, clinical fi ndings and treatment options including hyperbaric oxygen therapy. Clin Toxicol 27:141, 1989. 9. Ryan C, Shankowsky H, Tredget E: Profi le of the pediatric burn patient in a Canadian burn center. Burns 18:267–272, 1992. 10. Zubair M, Besner GE: Pediatric electrical burns: management strategies. Burns 23:413–420, 1997. *11. Reed J, Pomerantz W: Emergency management of pediatric burns. Pediatr Emerg Care 21:118–129, 2005. 12. Otherson H: Burns and scalds. Pediatr Ann 12:753–760, 1983. 13. Thompson J, Ashwal K: Electrical burns in children. Am J Dis Child 137:231–235, 1983. 14. Bates N: Acid and alkali injury. Emerg Nurse 7(8):21–26, 2000. 15. Smith ML: Pediatric burns: management of thermal, electrical, and chemical burns and burn-like dermatologic conditions. Pediatr Ann 29:367–378, 2000. 16. Lund C, Browder N: The estimate of areas of burns. Surg Gynecol Obstet 79:352, 1944. 17. Sheridan RL, Petras L, Basha G, et al: Planimetry study of the percent of body surface represented by the hand and palm: sizing irregular burns is more accurately done with the palm. J Burn Care Rehabil 16:605–606, 1995. 18. Morgan E, Bledsoe S, Barker J: Practical therapeutics: ambulatory management of burns. Am Fam Physician 62:2015–2026, 2000. 19. Cohen BJ, Jordan MH, Chapin SD, et al: Pontine myelinolysis after correction of hyponatremia during burn resuscitation. J Burn Care Rehabil 12:153–156, 1991. *20. Das A, Kim K: Infections in burn injury. Pediatr Infect Dis J 19:737– 738, 2000. 21. Weber JM, Sheridan RL, Pasternack MS, Tompkins RG: Nosocomial infections in pediatric patients with burns. Am J Infect Control 25:195–201, 1997. 22. Pruitt BA Jr, McManus AT, Kim SH, Goodwin CW: Burn wound infections: current status. World J Surg 22:135–145, 1998. 23. Sheridan RL: Evaluating and managing burn wounds. Dermatol Nurs 12:17, 18, 21–28, 2000. 24. Grande C, Stene J, Bernhard W: Airway management: considerations in the trauma patient. Crit Care Clin 6:37–59, 1990. 25. Mlcak RP, Helvick B: Protocol for securing endotracheal tubes in a pediatric burn unit. J Burn Care 8:233–237, 1987. 26. Buckley RG, Aks SE, Eshorn JL, et al: The pulse oximetry gap in carbon monoxide intoxication. Ann Emerg Med 24:252, 1994. *Selected readings.

Chapter 26 — Burns 27. Nieman GF, Clark WR, Hakim T: Methylprednisolone does not protect the lung from inhalation injury. Burns 17:384,1991. 28. Parker JC, Hernandez LA, Peevy KJ: Mechanisms of ventilator-induced lung injury. Crit Care Med 21:131–143, 1993. 29. Finkelstein J, Schwartz S, Madden M, et al: Pediatric emergency medicine. Pediatric burns: an overview. Pediatr Clin North Am 39:1145– 1163, 1992. 30. Sheridan RL: The seriously burned child: resuscitation through reintegration—1. Curr Probl Pediatr 28:105–127, 1998. 31. Monafo WW: Initial management of burns. N Engl J Med 335:1581– 1586, 1996. 32. Huang PP, Stucky FS, Dimick AR, et al: Hypertonic sodium resuscitation is associated with renal failure and death. Ann Surg 221:543, 1995. 33. Warden GD: Burn shock resuscitation. World J Surg 16:16–23, 1992. 34. Carvajal HF: Fluid resuscitation of pediatric burn victims: a critical appraisal. Pediatr Nephrol 8:357–366, 1994. 35. Kagan RJ, Smith SC: Evaluation and treatment of thermal injuries. Dermatol Nurs 12:334–350, 2000. 36. Hedderich R, Ness T: Analgesia for trauma and burns. Crit Care Clin 15:167–184, 1999. 37. Kao CC, Garner WL: Acute burns. Plast Reconstr Surg 101:2482–2493, 2000. 38. Palmieri T, Greenhalgh D: Topical treatment of pediatric patients with burns: a practical guide. Am J Clin Dermatol 3:529–534, 2002. 39. McDonald WS, Sharp CW, Deitch EA: Immediate enteral feeding in burn patients is safe and effective. Ann Surg 213:177–183, 1991. 40. Mainous MR, Block EF, Deitch EA: Nutritional support of the gut: how and why. New Horiz 2:193–201, 1994. 41. Deitch EA: The management of burns. N Engl J Med 323:1249–1253, 1990. 42. Schonfeld N: Outpatient management of burns in children. Pediatr Emerg Care 6:249–253, 1990. 43. Edwards-Jones V, Shawcross SG: Toxic shock syndrome in the burned patient. Br J Biomed Sci 54:110–117, 1997. 44. Bosworth C: Burns Trauma: Management and Nursing Care. London: Bailliere Tindall, 1997. 45. Flanagan M, Graham J: Should burn blisters be left intact or debrided? J Wound Care 10:41–45, 2001. 46. Gowar J, Lawrence J: The incidence, causes and treatment of minor burns. J Wound Care 4:71–74, 1995. 47. Kao CC, Garner W: Acute burns. Plast Reconstruct Surg 105:2482– 2493, 2000. 48. Barret JP, Dziewulski P, Ramzy P, et al: Biobrane versus 1% silver sulfadiazine in second-degree pediatric burns. Plast Reconstruct Surg 105:62–65, 2000.

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49. Demling RH: Use of Biobrane in management of scalds. J Burn Care Rehabil 16:329, 1995. 50. Phillips LG, Robson MC, Smith DJ: Uses and abuses of a biosynthetic dressing for partial-skin thickness burns. Burns 15:846, 1989. 51. Ou LF, Lee SY, Chen YC, et al: Use of Biobrane in pediatric scald burns: experience in 106 children. Burns 24:49, 1998. 52. Committee on Trauma, American College of Surgeons: Guidelines for the operations of burn units. In Resources for Optimal Care of the Injured Patient: 1999. Chicago: American College of Surgeons, 1999, pp 55–62. 53. Sheridan RL: The seriously burned child: resuscitation through reintegration—2. Curr Probl Pediatr 28:139–167, 1998. 54. Morgan M: Nursing management of the injured child in the A&E department. In Mead DM, Sibert JR (eds): The Injured Child: An Action Plan for Nurses. London: Scutari Press, 1991, pp 45–52. 55. Sheridan RL, Remensnyder JP, Schnitzer JJ, et al: Current expectations for survival in pediatric burns. Arch Pediatr Adolesc Med 154:245–249, 2000. 56. Andreasen NJ, Norris AS, Hartford CE: Incidence of long-term psychiatric complications in severely burned adults. Ann Surg 174:785–793, 1971. 57. Blades BC, Jones C, Munster AM: Quality of life after major burns. J Trauma 19:556–558, 1979. 58. Abdullah A, Blakeney P, Hunt R, et al: Visible scars and self-esteem in pediatric patients with burns. J Burn Care Rehabil 15:164–168, 1994. 59. Moore P, Blakeney P, Broemeling L, et al: Psychologic adjustment after childhood burn injuries as predicted by personality traits. J Burn Care Rehabil 14:80–82, 1993. 60. Herndon DN, LeMaster J, Beard S, et al: The quality of life after major thermal injury in children: an analysis of 12 survivors with greater than or equal to 80% total body, 70% third-degree burns. J Trauma 26:609–619, 1986. 61. Powers PS, Cruse CW, Daniels S, Stevens B: Posttraumatic stress disorder in patients with burns. J Burn Care Rehabil 15:147–153, 1994. 62. Tarnowski KJ, Rasnake LK, Linscheid TR, Mulick JA: Behavioral adjustment of pediatric burn victims. J Pediatr Psychol 14:607–615, 1989. 63. Sawyer MG, Minde K, Zuker R: The burned child: scarred for life? A study of the psychosocial impact of a burn injury at different developmental stages. Burns Incl Therm Inj 9:205–213, 1983. 64. Mallonee S, Istre GR, Rosenberg M, et al: Surveillance and prevention of residential-fi re injuries. N Engl J Med 335:27, 1996. 65. Marshall SW, Runyan CK Bangdiwala SI, et al: Fatal residential fi res: who dies and who survives? JAMA 279:1633–1637, 1998. 66. American Burn Association: The Advanced Burn Life Support Course, Chicago: American Burn Association, 2000.

Chapter 27 Neurovascular Injuries Isabel Barata, MD

Key Points Emergency department management of vascular or nerve injuries require a meticulous and expeditious workup in order to prevent long-term morbidities. Blunt and penetrating extremity injuries require different clinical approaches. Diagnostic studies to evaluate the presence of a vascular or nerve injury should not delay the transfer of a patient to the operating room.

complete transection, contusion, laceration, and arteriovenous fistula formation. Indirect injuries can be more subtle in presentation and include vessel spasm, external compression, mural contusion, thrombosis, and aneurysm formation. Peripheral vascular injuries to extremity tissues can be tolerated without ischemia when collateral vascular flow is present and adequate. This may not always be the situation, depending on the mechanism, location, and extent of injury and on the patient’s baseline circulation to the involved extremity. In general, extremity tissues tolerate 4 to 6 hours of ischemia before irreversible injury occurs.

Evaluation Vascular and Nerve Injury Upper Extremity Injuries

Introduction and Background Traumatic injury disproportionately affects the young and is the leading cause of death and disability in the pediatric age group; however, vascular injuries in pediatric patients are rare. The majority of vascular injuries that occur in children are extremity injuries related to fractures1 or broken glass.2 Motor vehicle accidents, heavy machinery–related injuries, and falls cause a small proportion of blunt vascular injuries secondary to decelerating or crushing forces. Vascular injuries are usually caused by penetrating trauma from glass, bullets, and knives. Penetrating peripheral vascular injuries secondary to gunshots or stab wounds are more common in males than in females.

Recognition and Approach Blunt trauma causes vascular injury due to either tensile or shear strain. Tensile strain leads to longitudinal forces causing vessel or intimal rupture, which exposes flowing blood to a large surface area rich in thrombogenic substances, resulting in a local thrombosis. Shear strain is secondary to lateral forces acting on the vessel wall and can result in partial or complete transection. Penetrating injuries cause damage to vascular structures by direct injury secondary to stab or low-velocity missile wounds and/or high-velocity injury. Velocity and mass will influence the missile’s destructive power. These types of injuries can cause severe damage, even in the absence of direct vascular trauma. Direct vascular injury can lead to partial or 258

FRACTURES

Approximately 75% of all fractures sustained by children occur in the upper extremities and frequently occur during a fall with an outstretched hand. Most of these injuries involve the wrist and forearm. The elbow accounts for approximately 3% to 7% of all fractures in children.3 The majority of elbow fractures in children are supracondylar fractures of the humerus4 (Fig. 27–1). Elbow fractures are challenging due to the high potential for limb-threatening damage to neurovascular structures. The neurovascular examination is often difficult in a crying and frightened child; however, it must be done before the child is sent for radiographs. Pulses, capillary refi ll, and skin temperature of the extremity being evaluated should be checked. A brief overview of the sensorimotor evaluation of the hand is outlined in Table 27–1.5,6 No one test has been accepted as the standard procedure for the evaluation of sensation. The various sensory tests available for patient assessment will yield different information regarding the integrity of the quickly and slowly adapting sensory receptors. Tests such as provocative maneuvers and sensory thresholds (cutaneous and vibration) will be more sensitive in the evaluation of patients with nerve compression, and will yield better functional information in patients with nerve injury. In adult patients, one of the preferred methods to assess sensation is two-point discrimination, which may be of limited value in children depending on the age and degree of cooperation. When diagnosis of vascular trauma is uncertain, the following signs and symptoms may indicate peripheral ischemia:

Chapter 27 — Neurovascular Injuries

I

Table 27–1

Radial nerve

II A II B FIGURE 27–1. Modified Gartland grading of supracondylar fractures of the humerus in children.

Neurovascular Examination of the Upper Extremity Sensory

Motor

Dorsal thumb web space

Raise the thumb (give “thumbs-up” sign) or raise the wrist Flex the thumb or index finger (make an “O” with the thumb and index finger) Move the index finger medially and laterally, or flex the tip of the fifth finger

Median nerve

Volar tip of the index finger

Ulnar nerve

Volar tip of the lateral border of the small finger

pain, pallor, paresthesias, pulselessness (palpable pulse does not exclude diagnosis), prolonged capillary refill, and paralysis (the 6 Ps). Increased pain and decreasing sensation are cardinal signs that a compartment syndrome is beginning.7 Vascular injury to the brachial artery and neural injury to the median, radial, and ulnar nerves can occur from stretching, entrapping, or disrupting the neurovascular structures. The incidence of neural and vascular injuries associated with humeral supracondylar fracture has been reported as nerve injury only in 6% to as high as 16% of patients,8,9 vascular compromise only in 2.9% of patients, and combined nerve and vascular injury in 2.9%.9 Median nerve injuries accounted for 58.9% of nerve injuries, followed by radial (26.4%) and ulnar (14.7%).9 The supracondylar fracture of the humerus in children can be due to an extension-type fracture, in which the condylar complex shifts posterolaterally or posteromedially, or, in a smaller number of cases, a flexion-type fracture in which the condylar complex shifts anterolaterally.10 Posterolateral fracture displacement correlates with median nerve and vascular compromise.11 Up to 80% of median nerve injuries involve the anterior intereosseous nerve.9,12-14 Posteromedial fracture displacement correlates with radial nerve injury. Anterolateral fracture displacement in a flexion-type fracture is more frequently associated with ulnar nerve damage15,16 (Table 27–2). Secondary injuries can also occur in two primary ways: (1) during manipulation of the fracture, the nerves and/or vessels can be stretched or entrapped between the fracture ends; and (2) treatment in the hyperflexed position (used when only closed reduction is performed) can compromise the vascu-

Table 27–2

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III

Supracondylar Fracture Displacement Direction and Associated Nerve Injuries

Fracture Displacement

Nerve Injury (Most Common)

Posterolateral

Median nerve: Up to 80% Anterior interosseous nerve Radial nerve Ulnar nerve

Posteriomedial Anterolateral

larity of the forearm, eventually resulting in Volkmann’s contracture. The rate of iatrogenic nerve injury has been reported to be 2% to 3%.17 The radial pulse is reported to be absent before reduction in 7% to 12% of all fractures and in up to 19% in displaced fractures. After reduction, the pulse is restored in 80% of cases. Injury to the nerves can also exist due to swelling of the tissues around the elbow irrespective of the treatment. A wide variety of treatments has been recommended for displaced supracondylar fractures, ranging from nonoperative treatment through closed reduction and percutaneous Kirschner wire transfi xation to open reduction with more or less stable internal fi xation. The management is determined by the difficulty in obtaining and maintaining reduction and by the involvement of neurovascular structures. BLUNT INJURIES

Blunt extremity vascular injury associated with blasts (e.g., fireworks) can be associated with fractures, amputations, dislocations, and digit neurovascular injury.18 PENETRATING INJURIES

A study of penetrating injuries of the upper extremity in which the mechanism of injury was stabbing in 39%, bullet in 51%, pellets in 4%, and dog bites in 6% found that the proximity of the injury to neurovascular bundles was a poor predictor of arterial injury, and long-term morbidity was mainly associated with nerve injuries.19 Injuries to the upper extremity due to gunshot wounds are common.20 The extent of soft tissue disruption and the type of fracture depends on the energy of the gunshot. Injuries resulting from low-energy gunshot wounds are more likely to have less soft tissue, bone, and neurovascular disruption. High-energy gunshot wounds cause more soft tissue disruption, bone loss, complex comminuted and unstable fractures, and neurovascular injuries.21

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SECTION II — Approach to the Trauma Patient

In high-energy gunshot-induced fractures, the first choice for initial stabilization is the use of external fi xation, providing stability for vascular repair and access to the wound for débridement and subsequent soft tissue surgery.21 Small laceration injuries to the upper extremity have the potential to conceal an underlying deep injury. In patients with injuries from glass and knife lacerations, it was found that extensor tendons were more commonly injured and that patients had the following injuries: a single tendon injury in 92.5%, a single deep structure injury in 59.3%, a single nerve injury in 18.7%, a single artery injury in 14.9%, and a combination of tendon, nerve, and artery injuries in up to 14.9%.22 Lower Extremity Injuries Fractures of the femoral supracondylar region are common in adolescents and middle-aged adults. Most often they are the result of high-energy blunt trauma such as motor vehicle collisions or industrial injuries. These fractures are usually associated with injuries to the neurovascular bundle. Blunt vascular injuries in the lower extremities occur most commonly in the anteroposterior tibial arteries.23 The neurovascular injuries are even more complex when they are the result of penetrating trauma such as missile injuries.24,25 Peripheral nerve injuries can result from either blunt or penetrating trauma with resulting injuries of the femoral, sciatic, peroneal, or tibial nerves. On physical examination, patients with femoral neuropathy demonstrate weakness on knee extension and sensory deficit in the area just superior and medial to the patella, with diminished or absent knee deep tendon reflexes. Findings in sciatic neuropathy are weakness of the hamstring muscle and all muscles below the knee, sensory loss in the posterior thigh and most of the leg below the knee, and absent or diminished ankle deep tendon reflexes. Peroneal nerve injuries are associated with weakness of the extensor hallucis longus muscle, with inability to dorsiflex the foot or move the toes, and sensory loss in the first toe and first web space (Table 27–3).

the distal femoral or proximal tibial epiphysis, or displaced tibial tuberosity fractures, may be especially susceptible to neurovascular problems.26 Important neurovascular structures are in close proximity to the knee joint. The femoral artery moves from medial to posterior in the popliteal fossa as it courses through the adductor canal just proximal to the distal femoral metaphysis. The popliteal artery bifurcates just proximal to the articular surface of the knee. The posterior tibial nerve lies adjacent to the popliteal artery. The peroneal nerve courses around the lateral aspect of the fibular head. Distal femoral fractures account for approximately 7% of all physeal fractures.27 A common mechanism of injury is hyperextension causing an anterior displacement of the epiphysis. Displacement of the fracture in the sagittal plane may be associated with neurovascular injury in the popliteal fossa and instability on closed reduction. Physeal fracture displacement in the coronal plane is not associated with other injuries, and the joint may be stable after closed reduction.28 Clinically, the thigh may appear angulated and shortened compared with the contralateral thigh. The pain, knee effusion, and soft tissue swelling usually are severe. The Salter-Harris (SH) classification system (Fig. 27–2) provides general guidelines regarding the risk of growth disturbance, but there are no clinical methods for quantifying the true extent of physeal damage in an acute injury. Hemarthrosis may be more severe in SH III and SH IV fractures, and vascular examinations may reveal diminished or absent distal pulses. Neurologic symptoms also may be evident dis-

Table 27–3

Sensory

Motor

Femoral nerve

Area superior and medial to the patella

Sciatic nerve

Posterior thigh and leg below the knee

Peroneal nerve

First toe and first web space

Weakness on knee extension Diminished or absent knee deep tendon reflexes Weakness of the hamstring muscle and all muscles below the knee Absent or diminished ankle deep tendon reflexes Inability to dorsiflex foot and move toes

FRACTURES

Traumatic forces applied to the immature knee result in fracture patterns different from those in adults. Trauma that would result in a ligament injury in an adult is likely to cause in a child or adolescent an injury to the growth plate (physis) as well as the adjacent areas of the femur, tibia, or patella. The relative abundance of cartilage in the knee of the growing child may make the diagnosis of certain injuries more challenging. Certain fractures, such as hyperextension injuries to

Type I

Type II

Type III

Neurovascular Examination of the Lower Extremity

Type IV

FIGURE 27–2. Classification of epiphyseal fractures according to the Salter-Harris system.

Type V

Chapter 27 — Neurovascular Injuries

tally due to disruption of the posterior tibial and common peroneal nerve distributions. Treatment for distal femoral physeal fractures varies according to severity of injury. Displaced SH I or SH II fractures are treated with closed reduction and splinting with a hip spica cast. SH III and SH IV injuries usually require anatomic reduction, which cannot be obtained with closed reduction, and are very often unstable. Operative treatment is required since even slight residual displacement can result in formation of a bone bar that causes limb-length discrepancy and angular deformity. Whereas fractures involving the tibia and fibula are the most common lower extremity pediatric fractures, those involving the proximal tibial epiphysis are among the most uncommon, comprising less than 2% of all physeal injuries,29 but have the highest rate of complications. The injury is usually due to anterior-posterior forces with increased risk of neurologic and/or vascular compromise, with the potential for the development of a compartment syndrome as well. When displacement occurs, the popliteal artery is vulnerable. At the tibial metaphysis, the artery is just posterior to the popliteus muscle. SH I injuries occur at an earlier age (average age 10 years). Half of SH I injuries are nondisplaced and diagnosed by stress radiographs only. SH II are the most common type, and one third are nondisplaced. SH III injuries are often associated with lateral condyle fractures or medial collateral ligament injuries. SH IV injuries are often associated with angular deformity. SH V injuries are usually diagnosed retrospectively. Anterior physis closure can cause significant genu recurvatum. Complications of these injuries include vascular insufficiency and peroneal nerve palsy.28 PENETRATING INJURIES

In a study of penetrating injuries, caused by gunshot wounds in 58.3% of patients and fragments of mines or other explosive devices in 41.7%, it was found that 18% of the injuries were supracondylar fractures, with associated neurovascular bundle injuries in 38% and vascular injuries in 34%. Patients required external fi xation in 86% of cases and primary reconstruction of large blood vessels in 32% of limbs.25 A similar study looking at injuries resulting from infantry weapon missiles in 70.7% of patients and explosive devices in 29.3% found that associated neurovascular bundle injuries were present in 26.8% of patients.24 Nerve and tendon lacerations of the foot and ankle region are relatively common. Acute nerve and tendon injuries should be repaired with appropriate techniques at the time of initial wound exploration. Primary nerve repair may help minimize the risk of painful neuroma formation; primary tendon repair can lead to better functional results than delayed repair.30 Compartment Syndrome Acute compartment syndrome is a potentially devastating condition in which the pressure within an osseofascial compartment rises to a level that decreases the perfusion gradient across tissue capillary beds, leading to cellular anoxia, muscle ischemia, and death (see Chapter 22, Compartment Syndrome). A variety of injuries and medical conditions may initiate acute compartment syndrome, including fractures, contusions, bleeding disorders, burns, trauma, postischemic swelling, and gunshot wounds. Diagnosis is primarily clinical (pain out of proportion to the injury or

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physical findings), supplemented by compartment pressure measurements. Nerve blocks and other forms of regional and epidural anesthesia may contribute to a delay in diagnosis. Basic science data suggest that the ischemic threshold of normal muscle is reached when pressure within the compartment is elevated to 20 mm Hg below the diastolic pressure or 30 mm Hg below the mean arterial blood pressure.31 On diagnosis of impending or true compartment syndrome, immediate measures must be taken. Complete fasciotomy of all compartments involved is required to reliably normalize compartment pressures and restore perfusion to the affected tissues. Recognizing compartment syndromes requires having and maintaining a high index of suspicion, performing serial examinations in patients at risk, and carefully documenting changes over time. In a retrospective study of upper extremity fasciotomy at a level I trauma center, it was found that the mechanism of injury was penetrating trauma (gunshot wounds in 37% and stab wounds in 11%), blunt or crush in 33%, and burns in 18% of cases. Fifty-six percent of patients had vascular injuries and 33% of patients had fractures. The decision to perform fasciotomy was clinical in 75% of patients, and only 22% of patients had compartment pressures measured (range, 40 to 87 mm Hg; mean, 52).32 Thoracic/Abdominal Injuries Pediatric truncal vascular injuries are rare, but the reported mortality is high (35% to 55%) and similar to that in adults.33 Thoracic injuries are primarily due to blunt rupture, which accounts for 85% of cases, 75% being motor vehicle collision related.34 In contrast, penetrating thoracic injuries are rare in children less than 13 years old.35 The most common thoracic vascular injury is to the aorta. Studies have shown that concomitant injuries such as traumatic brain injury, pulmonary contusion, rib fractures, hemothorax, cervicothoracic spine injury, femur fracture, and other orthopedic injuries occurred with 83% of thoracic aortic injuries and multiple vascular injuries occurred in 25% of cases.32 Abdominal vascular injuries were primarily due to a penetrating mechanism, and the vessel most commonly involved was the inferior vena cava, followed by the aorta and less commonly the iliac artery/vein, superior mesenteric artery/vein, hepatic vein, portal vein, splenic artery/vein, and renal artery/vein.33 Concomitant injuries associated with abdominal vascular injuries included small bowel, spleen, pancreas, large bowel, stomach, duodenum, liver, kidney, bile duct, bladder, diaphragm and orthopedic injuries. The survival and subsequent complications of patients with vascular injuries, regardless of which body cavity or vessel was injured, were related to the initial hemodynamic status. Patients presenting with blood pressure of less than 90 mm Hg had 100% mortality rate, and all patients with blood pressure greater than 90 mm Hg survived.33,36 For further information on specific evaluation and management, see Chapter 24 (Thoracic Trauma) and Chapter 25 (Abdominal Trauma). Neck Vascular injuries of the neck are not as common in children as in adults; however, a delayed diagnosis of injury to a major cervicothoracic vessel from blunt trauma may cause significant adverse sequelae. The presence of cervicothoracic “seat belt sign” has been reported in the adult population to be

262

SECTION II — Approach to the Trauma Patient

Zone I

Zone I

Zone II

Zone II

Zone III

Zone III

Hyoid bone

Jugular vein Carotid artery

Vertical plane at level of mandibular angle

FIGURE 27–3. Anatomic divisions of the face into three areas for penetrating injuries: Zone I, above the angle of the mandible to the base of the skull; Zone II, from the angle of the mandible to the cricoid; and Zone III, below the cricoid to the suprasternal notch/clavicles.

associated with blunt vascular injury in anywhere from 0.24% to 3% of cases.37,38 The presence of vascular injury was strongly associated with a Glasgow Coma Scale score less than 14, an Injury Severity Score greater than 16, and the presence of a clavicle and/or fi rst rib fracture in adult patients. Pediatric patients have a higher incidence of seat belt sign as compared to adult patients; however, vascular injuries and cervical spine fractures are rare.37 Penetrating neck trauma in children may lead to potentially life-threatening injuries. Several studies of penetrating trauma to the head and neck in children have found that the risk for vascular and neurologic injuries is high.33,39,40 The most commonly affected vessel is the carotid artery, followed by the vertebral artery, internal jugular vein, and facial artery. The immediate threats to life with neck injury are loss of airway due to expanding hematomas or laryngotracheal injuries, massive arterial bleed from neck or associated mediastinal/chest bleed, associated tension pneumothorax, and disruption of cerebral perfusion resulting in a cerebrovascular accident. The pediatric approach to patients with neck injuries emphasizes the selective approach to neck exploration.39 Hemodynamically unstable patients, patients with expanding hematomas, air bubbling from a wound, or respiratory distress, and patients with suspected tracheal or esophageal injuries need emergency surgical exploration. Children who are hemodynamically stable should have an appropriate preoperative diagnostic evaluation followed by clinical observation. Nonoperative observation of penetrating zone II neck injuries (Fig. 27–3) is safe if active observation can be performed and the facilities for immediate operative intervention are available.41,42 Diagnostic Evaluation Extremities Careful neurologic (Table 27–4; see also Table 27–1) and vascular evaluation is important since many nerves and

Table 27–4

Orthopedic Injuries and Associated Nerve Injuries

Orthopedic Injury

Nerve Injury

Elbow supracondylar fracture Acetabulum fracture Hip dislocation Femoral shaft fracture Femoral distal physeal fracture Knee dislocation Proximal tibial physeal fracture

Median, radial, or ulnar Sciatic Femoral Peroneal Tibial or peroneal Tibial or peroneal Peroneal

arteries run within the same bundle. If a peripheral nerve injury is present, there is a good chance that the artery is also injured. Physical examination, as already mentioned, should look for the 6 Ps. However, the physical examination alone is often inadequate for predicting arterial trauma. Patients with a history of severe hemorrhage at the scene, diminished or unequal pulses, nonpulsatile hematoma, and decreased twopoint discrimination in an anatomic nerve distribution should have a Doppler examination for pulses and arterial pressure index (API). The API can be used as a screening tool for clinically significant arterial compromise.43-46 It is obtained by measuring systolic blood pressure in the injured and uninjured extremity and calculating brachial-brachial or ankle-ankle blood pressure ratios to detect penetrating vascular injury.43-45 It can also be used in patients with blunt vascular injury.43,46 If none of the hard signs of vascular injury, such as pulsatile hemorrhage, a palpable thrill or audible bruit, or a pulseless limb, is present, the cutoff for imaging is an API less than 0.9 between sides, which has a sensitivity of 95% to 97% and a negative predictive value of 99%.43-45 This ratio is only useful for injuries proximal to the elbow or knee, as distal injuries do not require repair if hard signs are absent due to division of the blood supply

Chapter 27 — Neurovascular Injuries

into two main arteries with collateralization. Also, an API may be difficult to determine in certain injuries that preclude cuff placement at the wrist or ankle or in patients with hypovolemia. The API combined with physical examination was used in a study of penetrating extremity trauma to decide which patients needed angiography. In this study, 4% of patients with hard signs of vascular injury went to the operating room, 17% without vascular compromise underwent operative procedures or were admitted for other injuries, 23% with nonproximity wounds were discharged, and 55.7% with a negative physical examination and normal API were discharged from the emergency department. The authors concluded that angiography is only indicated for symptomatic patients or asymptomatic patients with abnormal APIs.45 Also, the API can be used in patients with blunt trauma; an ankle-brachial index less than 0.9 suggests vascular injury.46 Plain radiographs help diagnose fractures, foreign bodies, or missiles that may be responsible for neurovascular compromise. If plain radiographs fail to reveal a fracture, a stress radiograph, computed tomography scan, or magnetic resonance imaging study may help to establish the diagnosis. Duplex ultrasonography images the vessel and measures blood flow and velocity. Color flow duplex scanning has been shown to be useful postoperatively to manage children who have undergone various procedures to establish a radial pulse after type 3 supracondylar fractures of the humerus.47 It is a noninvasive alternative to angiography in monitoring occult injuries. It may be particularly advantageous in small children since it can be performed serially at the bedside; however, it is an operator-dependent test. Digital subtraction angiography is more sensitive than angiography in detecting extravasation of contrast material48 ; however, it is very sensitive to motion artifact. It involves manual contrast injection followed by immediate radiography.49 It is rapid and accurate, and does not require transportation of an unstable patient to an angiography suite. Digital subtraction angiography is currently used in young children, as formal angiography is difficult to obtain in an uncooperative patient. Multidetector-row helical computed tomographic arteriography (MDCTA) is emerging as a new way to study arterial anatomy. It is noninvasive and allows evaluation of different body areas simultaneously. In one study of adult patients, MDCTA adequately demonstrated the nature and location of all arterial injuries when compared with conventional arteriography or surgical exploration.50 MDCTA is a reliable technique for the detection and characterization of traumatic extremity arterial injuries in adult patients; however, it has not been studied in children. Angiography in pediatric patients under 5 years of age poses the risk of iatrogenic injury due to the small caliber of the vessels. In addition, arterial spasm is more common in the pediatric patient and can complicate the use of angiography. Therefore, angiography should be reserved for patients with suspected arterial injury with an equivocal vascular examination (decreased pulse, abnormal API, abnormal ankle-brachial index, and bruits).51 Patients with obvious vascular injuries (bleeding or ischemia) should go to the operating room. In summary, in the evaluation of blunt or penetrating vascular injury of the extremity, the following approach is

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indicated. If the patient has hard signs of vascular injury, such as pulsatile hemorrhage, an expanding hematoma, a palpable thrill or audible bruit, or a pulseless limb, the patient requires immediate surgical exploration and vascular repair. Patients with no hard signs but either soft signs (e.g., history of large blood loss, decreased two-point discrimination, decreased or unequal pulses, and nonpulsatile hematoma) or injuries that are known to be associated with a high incidence of arterial damage should be screened with an API. If the API is greater than 0.9, a serial clinical evaluation should be performed. If the API is less than 0.90, further evaluation is indicated with either duplex ultrasonography or MDCTA, if studies show the latter evaluation to be useful in children. If these diagnostic tests are abnormal, then angiography is indicated. In patients with low likelihood of vascular injury (proximity injury, penetrating wound in proximity to vascular structures without clinical findings to suggest vascular compromise), duplex ultrasonography follow-up may be used. Compartment Syndrome If the history and physical examination suggest compartment syndrome, an orthopedic consultation should be obtained, and compartment pressures measured with commercially available monitors. The patient should be carefully followed with serial examinations and pressure measurements (see Chapter 22, Compartment Syndrome). Neck Traumatic injury to the major vessels of the head and neck can result in potentially devastating neurologic sequelae. Carotid duplex ultrasound is a noninvasive, rapid screening test for arterial injury. Conventional angiography has been the primary imaging modality used to evaluate these often challenging patients with both bunt neck trauma and penetrating wounds in zone I or zone III (see Fig. 27–3), carotid bruit, large hematoma, and suspected arterial injury. The absence of hemorrhage, expanding hematoma, bruit, thrill, or neurologic (hard signs) deficit reliably excludes surgically significant vascular injuries in penetrating zone III neck trauma, suggesting that angiography is not necessary.52 Hard signs in stable patients should mandate angiography because these vascular injuries may be amenable to endovascular therapy.52 Advances in cross-sectional imaging have improved the ability to screen for these lesions, which have been found to be more common than previously thought.53 MDCTA screening increases the detected incidence of blunt vascular neck injury eightfold, with rates similar to angiographybased screening protocols. MDCTA screening significantly decreases blunt vascular neck injury–related morbidity and mortality in an efficient manner, underscoring its utility in the early diagnosis of this injury.54 Other studies of blunt and/or penetrating neck injuries showed that MDCTA is adequate for the initial evaluation and triage of patients to conventional angiography or surgery for appropriate treatment, and as a guide to conservative management when appropriate.55,56 In summary, if hard signs of vascular injury are present, the unstable patient requires operative management and the stable patient angiography. If the patient does not have hard signs of vascular injury, then MDCTA can be used as screening tool to guide further evaluation and intervention.

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SECTION II — Approach to the Trauma Patient

Management After initial stabilization, a more detailed secondary evaluation is conducted to assess for vascular injury. Fractures are splinted and dislocations reduced since anatomic repositioning and splinting may help restore circulation in dislocations or fractures. If penetrating injuries, particularly highvelocity injuries, are near major vascular structures, the clinician should assume there is damage to those structures. It is important to control hemorrhage with direct pressure; however, blindly clamping a blood vessel should be avoided. Vascular status must be frequently reassessed and popliteal artery injuries carefully monitored because of minimal collateral circulation present in the lower extremity. Obvious vascular injury with evidence of ischemia is an indication for emergent surgical exploration. Prompt consultation with the trauma team is routine at most major urban trauma centers. If isolated peripheral vascular injury is present, the vascular surgeon should be consulted early in the management of the patient. Also, early intravenous antibiotics and tetanus immunization (if indicated) should be provided. If surgical consultation and appropriate diagnostic evaluation tools are not available at the primary institution, the patient must be transferred as quickly as possible after stabilization.

Summary The goals in management of children with neurovascular injuries are stabilization of the patient and minimization of ischemic time. A thorough neurovascular examination is more difficult in young children. However, it should be performed and carefully documented. Children have a higher risk of developmental abnormalities secondary to ischemia. Prompt consultation, early intravenous antibiotics, and tetanus immunization if indicated are also important aspects of management. Prognosis depends upon ischemic time and number and extent of associated injuries. Associated nerve damage occurs in a large percentage of vascular injuries; 45% of those result in permanent deficits. After initial stabilization, if surgical consultation is not available, the clinician should arrange for transfer. REFERENCES 1. Richardson JD, Fallat M, Nagaraj HS, et al: Arterial injuries in children. Arch Surg 116:685–690, 1981. *2. Wolf YG, Reyna T, Schropp KP, Harmel RP: Arterial trauma of the upper extremity in children. J Trauma 30:903–905, 1990. 3. Landin LA: Fracture patterns in children: analysis of 8,682 fractures with special reference to incidence, etiology and secular changes in a Swedish urban population 1950–1979. Acta Orthop Scand Suppl 202:1– 109, 1983. 4. Landin LA, Danielsson LG: Elbow fractures in children: an epidemiological analysis of 589 cases. Acta Orthop Scand 57:309, 1986. 5. Townsend DJ, Bassett GS: Common elbow fractures in children. Am Fam Physician 53:2031–2041, 1996. 6. Skaggs D, Pershad J: Pediatric elbow trauma. Pediatr Emerg Care 13:425–434, 1997. 7. Weinmann M: Compartment syndrome. Emerg Med Serv 32(9):36, 2003. 8. Culp RW, Osterman, AL, Davidson RS, et al: Neural injuries associated with supracondylar fractures of the humerus in children. J Bone Joint Surg Am 72:1211–1215, 1990.

*Selected readings.

*9. Lyons ST, Quinn M, Stanitski CL: Neurovascular injuries in type III humeral supracondylar fractures in children. Clin Orthop Relat Res (376):62–67, 2000. 10. Farnsworth CL, Silva PD, Mubarak SJ: Etiology of supracondylar humerus fractures. J Pediatr Orthop 18:38–42, 1998. 11. Rasool MN, Naidoo KS: Supracondylar fractures: posterolateral type with brachialis muscle penetration and neurovascular injury. J Pediatr Orthop 19:518–522, 1999. 12. Campbell CC, Waters PM, Emans JB, et al: Neurovascular injury and displacement in type III supracondylar humerus fractures. J Pediatr Orthop 15:47–52, 1995. 13. Cramer KE, Green NE, Devito DP: Incidence of anterior interosseous nerve palsy in supracondylar humerus fractures in children. J Pediatr Orthop 13:502–505, 1993. 14. Jones ET, Louis DS: Median nerve injuries associated with supracondylar fractures of the humerus in children. Clin Orthop Relat Res (150):181–186, 1980. 15. Wilkins KE: Residuals of elbow trauma in children. Orthop Clin North Am 21:291–314, 1990. 16. Wilkins KE: The operative management of supracondylar fractures. Orthop Clin North Am 21:269–289, 1990. 17. Rasool MN: Ulnar nerve injury after K-wire fi xation of supracondylar humerus fractures in children. J Pediatr Orthop 18:686–690, 1998. 18. Moore RS, Tan V, Dormans JP, Bozentka DJ: Major pediatric hand trauma associated with fireworks. J Orthop Trauma 14:426–428, 2000. 19. Degiannis E, Levy RD, Sliwa K, et al: Penetrating injuries of the brachial artery. Injury 26:249–252, 1995. *20. Hahn M, Strauss E, Yang EC: Gunshot wounds to the forearm. Orthop Clin North Am 26:85–93, 1995. 21. Johnson EC, Strauss E: Recent advances in the treatment of gunshot fractures of the humeral shaft. Clin Orthop Relat Res (408):126–132, 2003. 22. Tuncali D, Yavuz N, Terzioglu A, Aslan G: The rate of upper-extremity deep-structure injuries through small penetrating lacerations. Ann Plast Surg 55:146–148, 2005. 23. Rozycki GS, Tremblay LN, Feliciano DV, et al: Blunt vascular trauma in the extremity: diagnosis, management, and outcome. J Trauma 55:814–824, 2003. 24. Nikolic D, Jovanovic Z, Turkovic G, et al: Subtrochanteric missile fractures of the femur. Injury 29:743–749, 1998. 25. Nikolic DK, Jovanovic Z, Turkovic G, et al: Supracondylar missile fractures of the femur. Injury 33:161–166, 2002. 26. Zionts LE: Fractures around the knee in children. J Am Acad Orthop Surg 10:345–355, 2002. 27. Mann DC, Rajmaira S: Distribution of physeal and nonphyseal fractures in 2,650 long-bone fractures in children aged 0-16 years. J Pediatr Orthop 10:713–716, 1990. 28. Beaty JH, Kumar A: Fractures about the knee in children. J Bone Joint Surg Am 76:1870–1880, 1994. 29. Donahue JP, Brennan JF, Barron OA: Combined physeal/apophyseal fracture of the proximal tibia with anterior angulation from an indirect force: report of 2 cases. Am J Orthop 32:604–607, 2003. 30. Thordarson DB, Shean CJ: Nerve and tendon lacerations about the foot and ankle. J Am Acad Orthop Surg 13(3):186–196, 2005. 31. Gulli B, Templeman D: Compartment syndrome of the lower extremity. Orthop Clin North Am 25:677–684, 1994. 32. Dente CJ, Feliciano DV, Rozyck, GS, et al: A review of upper extremity fasciotomies in a level I trauma center. Am Surg 70:1088–1093, 2004. *33. Cox CS, Black CT, Duke JH, et al: Operative treatment of truncal vascular injuries in children and adolescents. J Pediatr Surg 33:462– 467, 1998. 34. Cooper A: Thoracic injuries. Semin Pediatr Surg 4:109–115, 1995. 35. Meller JL, Little AG, Shermeta DW: Thoracic trauma in children. Pediatrics 74:813–819, 1984. 36. Sirinek KR, Gaskill HV, Root HD, Levine BA: Truncal vascular injury—factors influencing survival. J Trauma 23:372–377, 1983. 37. Rozycki GS, Gaskill HV, Root HD, et al: A prospective study for the detection of vascular injury in adult and pediatric patients with cervicothoracic seat belt signs. J Trauma 52:618–623; discussion 623–624, 2002. 38. Fabian TC, Patton JH, Croce MA, et al: Blunt carotid injury: importance of early diagnosis and anticoagulant therapy. Ann Surg 223:513–522; discussion 522–555, 1996. 39. Cooper A, Barlow B, Niemirska M, et al: Fifteen years’ experience with penetrating trauma to the head and neck in children. J Pediatr Surg 22:24–27, 1987.

Chapter 27 — Neurovascular Injuries 40. Martin WS, Gussack GS: Pediatric penetrating head and neck trauma. Laryngoscope 100:1288–1291, 1990. *41. Kim MK, Buckman R, Szeremeta W: Penetrating neck trauma in children: an urban hospital’s experience. Otolaryngol Head Neck Surg 123:439–442, 2000. 42. Hall JR, Reyes HM, Meller JL: Penetrating zone-II neck injuries in children. J Trauma 31:1614–1617, 1991. 43. Levy BA, Zlowodzki MP, Graves M, Cole PA: Screening for extremity arterial injury with the arterial pressure index. Am J Emerg Med 23:689–695, 2005. *44. Johansen K, Lynch K, Paun M, Copass M: Non-invasive vascular tests reliably exclude occult arterial trauma in injured extremities. J Trauma 31:515–519; discussion 519–522, 1991. 45. Conrad MF, Patton JH, Parikshak M, Kralovich KA: Evaluation of vascular injury in penetrating extremity trauma: angiographers stay home. Am Surg 68:269–274, 2002. 46. Mills WJ, Barei DP, McNair P: The value of the ankle-brachial index for diagnosing arterial injury after knee dislocation: a prospective study. J Trauma 56:1261–1265, 2004. 47. Sabharwa S, Tredwell SJ, Beauchamp RD, et al: Management of pulseless pink hand in pediatric supracondylar fractures of humerus. J Pediatr Orthop 17:303–310, 1997. 48. Sibbitt RR, Palmaz JC, Garcia F, Reuter SR: Trauma of the extremities: prospective comparison of digital and conventional angiography. Radiology 160:179–182, 1986.

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*49. Itani KM, Rothenberg SS, Brandt ML, et al: Emergency center arteriography in the evaluation of suspected peripheral vascular injuries in children. J Pediatr Surg 28:677–680, 1993. 50. Busquets AR, Acosta JA, Colon E, et al: Helical computed tomographic angiography for the diagnosis of traumatic arterial injuries of the extremities. J Trauma 56:625–628, 2004. 51. de Virgilio C, Mercado PD, Arnell T, et al: Noniatrogenic pediatric vascular trauma: a ten-year experience at a level I trauma center. Am Surg 63:781–784, 1997. 52. Ferguson E, Dennis JW, Vu JH, Frykberg ER: Redefi ning the role of arterial imaging in the management of penetrating zone 3 neck injuries. Vascular 13:158–163, 2005. 53. Stallmeyer MJ, Morales RE, Flanders AE: Imaging of traumatic neurovascular injury. Radiol Clin North Am 44:13–39, 2006. 54. Schneidereit NP, Simons R, Nicolaou S, et al: Utility of screening for blunt vascular neck injuries with computed tomographic angiography. J Trauma 60:209–215; discussion 215–216, 2006. *55. Stuhlfaut JW, Barest G, Sakai O, et al: Impact of MDCT angiography on the use of catheter angiography for the assessment of cervical arterial injury after blunt or penetrating trauma. AJR Am J Roentgenol 185:1063–1068, 2005. 56. Woo K, Magner DP, Wilson MT, et al: CT angiography in penetrating neck trauma reduces the need for operative neck exploration. Am Surg 71:754–758, 2005.

Chapter 28 Apparent Life-Threatening Events Andrew DePiero, MD

Key Points The term apparent life-threatening event does not refer to a single diagnosis, but identifies a heterogeneous group of conditions with a common clinical presentation. Potentially life-threatening conditions may present as apparent life-threatening events. Infants who have experienced an apparent lifethreatening event do not usually appear ill on presentation to the emergency department. There is no standardized approach to the emergency department evaluation or management of infants who have experienced apparent life-threatening events.

Introduction and Background Infants commonly present to the emergency department (ED) for evaluation of a possible apparent life-threatening event (ALTE). The term apparent life-threatening event does not refer to a single diagnosis, but identifies a heterogeneous group of conditions with a common clinical presentation. A formal definition from the National Institutes of Health in 1986 defined an ALTE as “an episode that is frightening to the observer and that is characterized by some combination of apnea (central or occasionally obstructive), color change (usually cyanotic or pallid but occasionally erythematous or plethoric), marked change in muscle tone (usually marked limpness), choking or gagging. In some cases the observer fears that the infant has died.”1 The term apparent lifethreatening event replaces the previously used terms, “aborted crib death” and “near-miss SIDS,” to avoid implying a close association with sudden infant death syndrome (SIDS).1 Despite this consensus definition of ALTE, controversy remains. Varying definitions lead to heterogeneity in clinical studies. Varying upper limits on age have been used. There are no generally accepted criteria for either the general appearance or the clinical stability of infants suspected of having experienced an ALTE. Some have proposed that the definition of ALTE be amended to include the lack of obvious

physical examination findings.2 An infant who is in moderate respiratory distress may fit some definitions of ALTE, whereas only well-appearing infants with an entirely normal physical examination fit other definitions. Practitioners and researchers continue to struggle with what constitutes an ALTE (Table 28–1). Substantial variability exists with respect to age and clinical presentation. The absence of a reproducible, widely accepted clinical defi nition complicates any interpretation of the existing literature on this topic. Therefore, basing clinical practice on available evidence is problematic. Nonetheless, the varied definitions of ALTE are sufficiently similar to offer information on which to base a reasonable approach to these infants when they present to the ED.3-7

Recognition and Approach ALTEs are relatively uncommon. Limited epidemiologic data suggest the incidence is between 0.6 and 2.5 per 1000 live births.7,8 Historically, ALTEs were thought to be episodes that would have resulted in SIDS if someone had not intervened. The link between SIDS and ALTEs is unclear. In particular, the “back to sleep” campaign aimed at increasing the number of infants placed supine to sleep appears to have decreased the incidence of SIDS, but not ALTEs.9

Clinical Presentation An ALTE is most often identified from historical data provided by caregivers. Cyanosis, apnea, and difficulty breathing are the most frequently reported symptoms.10,11 Other reported symptoms include abnormal movements, loss of consciousness, vomiting, choking, color change other than cyanosis (e.g., gray, red, or pale), gagging, and change in tone (i.e., limp or stiff). The episodes may occur while awake or asleep. Interventions by care providers range from vigorous stimulation to cardiopulmonary resuscitation. These events frighten most parents and care providers. In the ED, personnel should obtain a history of the event, including a description of any associated symptoms and an account of any recent changes in the patient’s health (e.g., fever, upper respiratory tract symptoms). The past medical history should focus on any prior unusual episodes or behaviors, a perinatal history, and a description of any respiratory symptoms or symptoms associated with gastroesophageal reflux (see Chapter 35, Vomiting, Spitting Up, and Feeding Difficulties). The clinician should inquire about a family 269

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SECTION III — Approach to Unique Problems of Infancy

Table 28–1

Varying Definitions of Apparent Life-Threatening Events Age Range of Study Subjects

Working Definition Apparent Life-Threatening Event (ALTE)—“An episode that is frightening to the observer and that is characterized by some combination of apnea (central or occasionally obstructive), color change (usually cyanotic or pallid but occasionally erythematous or plethoric), marked change in muscle tone (usually marked limpness), choking or gagging”1 “sudden occurrence of one or more of the following: breathing irregularity (e.g., apnea, labored or shallow breathing, choking and gagging), color change indicative of decreased oxygenation (e.g., cyanosis, pallor), altered muscle tone or mental status (e.g., hypotonia, hypertonia, clonic movements, and unresponsiveness)”11 “apnea monitor alarm or an episode associated with two or more of the following factors: apnea, color change, change in muscle tone, choking/gagging or the performance of CPR at the time of the episode . . . . single episode within the previous 24 hours and presenting with stable vital signs”13 “one or more symptoms of apnea, color change, choking or abnormal limb movements and provided this has caused sufficient concern in the observer to seek medical attention”10 “unexpected change in behavior that alarmed the caregiver. The initial episodes can occur during sleep, awake or while Not defined feeding . . . some combination of apnea, color change, marked change in muscle tone, choking or gagging . . . . In most cases . . . prompt intervention was associated with normalization of the child’s appearance.”24 “episodes of cyanosis or pallor for which vigorous stimulation had been given by the caregivers”3 “a cessation of breathing, cyanosis or change in the level of consciousness”18 “apneic episodes accompanied by one or more of the following manifestations: cyanosis, hypotonia, loss of consciousness necessitating vigorous stimulation or resuscitation”4 “an event of prolonged apnea, hypotonia and cyanosis or pallor”14 “attack of an infant who, during presumed sleep, is found not breathing, cyanotic or pale, often limp and who has to be vigorously stimulated or ventilated mouth-to-mouth to be resuscitated”5

Not defined 38° C

Age

Evaluation

Management

0–28 d

1. Detailed history and complete physical exam 2. Laboratory evaluation for sepsis: • Blood: CBC w/ diff and culture • Urine: cath urinalysis and culture • CSF: cell count, protein, glucose, gram stain, culture • Chest radiograph (if indicated) • Stool for heme test and culture (if indicated) • Consider HSV and enteroviral PCR for CSF

29–60 d

1. Detailed history and complete physical exam 2. Laboratory evaluation for sepsis: as for ≤28 d 3. Determine if patient is low-risk for SBI by meeting ALL criteria listed here: • Non-toxic appearance • No focus of infection on exam (except OM) • No known immunodeficiency • WBC , late or holosystolic

Grade I+II and mid-systolic

If asymptomatic, workup complete

FIGURE 67–2 Evaluation of undiagnosed cardiac murmurs. (Adapted from Braunwald E, Perloff JK: Physical examination of the heart and circulation. In Zipes DP [ed]: Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine, 7th ed. Philadelphia: Elsevier, 2005, p 103.)

Table 67–5

If symptomatic or clinical features of cardiac disease, endocarditis, embolic disease or syncope

Echocardiography

Cardiology consult if any pathology found or if non-valvular cardiac cause for symptoms suspected

Pathologic Murmurs17-19,21-23,26

Valvular Lesion

Clinical Presentation

Physical Examination

Auscultation

ECG/CXR

Aortic stenosis

Acyanotic, pulmonary edema

Harsh, medium-pitched, crescendo-decrescendo systolic murmur; paradoxically split S2, ejection click and S4 gallop Harsh crescendodecrescendo ejection systolic murmur heard best at the upper left sternal border, radiates to back or left infraclavicular area; ejection click, split S2 Low-pitched, rumbling, diastolic murmur over apex; opening snap

ECG: Left ventricular hypertrophy CXR: Dilated ascending aorta, cardiomegaly

Mitral stenosis

History of bicuspid valve Infants: CHF, shock Older children: Syncope, chest pain, sudden death, exercise intolerance Infants: Cyanosis, poor feeding, tachypnea, cardiac shock Children: Exertional dyspnea, exercise intolerance, chest pain, right-sided heart failure Dyspnea, rarely hemoptysis

Aortic regurgitation

Exercise intolerance, CHF, chest pain

Wide pulse pressure, bounding arterial pulses

Decrescendo mid-diastolic high-pitched murmur over the 3rd or 4th ICS; S1 diminished

Mitral regurgitation

History of rheumatic fever

High-pitched, blowing, pan-systolic murmur at the apex and radiating to left axilla; widely split S2

Mitral valve prolapse

Adolescents: Palpitations, chest pain, syncope

Acute MR: acute pulmonary edema and evidence of rightsided heart failure Chronic MR: minimal symptoms Healthy appearing

Pulmonary stenosis

Cyanosis, tachypnea, dependent edema, and organomegaly (spleen, liver)

Pulmonary edema

Midsystolic click, late systolic murmur

ECG: Right axis deviation, right ventricular hypertrophy CXR: cardiomegaly, prominence of the main and left pulmonary artery ECG: Left atrial enlargement, right ventricular hypertrophy CXR: Left atrial enlargement, prominent pulmonary vasculature, pulmonary congestion ECG: Left ventricular hypertrophy in severe AR; PVCs CXR: Cardiomegaly, dilation of ascending aorta, pulmonary congestion ECG: Left ventricular hypertrophy, left atrial enlargement CXR: Left ventricular hypertrophy, left atrial enlargement ECG: Dysrhythmias— SVT, premature atrial or ventricular contractions

Abbreviations: AR, aortic regurgitation; CHF, congestive heart failure; CXR, chest radiography; ECG, electrocardiogram; ICS, intercostal space; MR, mitral regurgitation; PVCs, premature ventricular contractions; SVT, supraventricular tachycardia.

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SECTION IV — Approach to the Acutely Ill Patient

often depends on a left-to-right shunt across a patent foramen ovale and a right-to-left shunt across the patent ductus arteriosus.14 Infants with severe AS usually present with cardiomegaly, vascular congestion, or cardiogenic shock. The clinical picture may be difficult to distinguish from overwhelming sepsis with low cardiac output. Even asymptomatic infants with AS identified in the neonatal period may have rapid disease progression, which appears to occur independently of the severity of the initial obstruction.15 Children with mild to moderate AS are usually asymptomatic. However, valvular disease progression usually manifests with the unmasking or exacerbation of symptoms with exercise. Children with more severe AS present with exercise intolerance, chest pain, syncope, or even sudden death.16 Importantly, chest pain or syncope during exertion should always prompt consideration of AS or idiopathic hypertrophic subaortic stenosis (IHSS) in the differential diagnosis. On physical examination, patients with valvular AS are acyanotic but may have signs of pulmonary edema. The murmur of AS is classically a harsh, medium-pitched, crescendo-decrescendo–shaped systolic murmur heard over the aortic valve area. Other heart sounds may include a diminished, paradoxically split S2, an ejection click, and an S4 gallop. The ECG can be normal or may reveal left ventricular hypertrophy. Chest radiography occasionally may show cardiomegaly, but the only abnormal finding may be dilation of the ascending aorta. As the child grows and cardiac output increases, the pressure gradient across the valve increases. This natural progression of disease eventually leads to ventricular dysfunction and congestive heart failure.17,18 Supravalvular and subvalvular aortic stenosis are less prevalent. Patients with the idiopathic form of diffuse subaortic stenosis, also referred to as IHSS, will present with many symptoms similar to those with valvular aortic stenosis. Clinical and echocardiographic findings will distinguish these entities. Pulmonary Stenosis Lesions that cause PS also may be valvular, supravalvular, or subvalvular. Abnormalities of the pulmonary leaflets are the cause of valvular PS. Supravalvular PS is characterized by stenosis of the main pulmonary artery, while subvalvular PS involves the infundibulum and is often associated with tetralogy of Fallot. Infants with critical PS will depend on a patent ductus to provide pulmonary blood flow and an interatrial shunt to direct most of the systemic venous return. Clinically, during the postnatal period these infants will have varying degrees of cyanosis depending on the blood flow through the patent ductus and the interatrial shunt. They may have symptoms of poor feeding and tachypnea that can progress to cardiac shock as the ductus closes. Children with mild PS are generally asymptomatic, but as stenosis progresses, they may develop exertional dyspnea and increased exercise intolerance. Children with severe PS can have chest pain and heart failure. The harsh, medium-pitched, crescendo-decrescendo ejection-type systolic murmur of PS, best heard over the upper left sternal border, may be associated with an ejection click and split S2. It radiates to the back or to the left infraclavicular area. The ECG may be normal in patients with mild PS, but with increased severity of stenosis, right axis deviation and right ventricular hypertrophy

develop. With progression of PS, chest radiography will reveal cardiomegaly and prominence of the main and left pulmonary artery due to post-stenotic dilation. On chest radiography, pulmonary vascular markings are normal or slightly diminished.18,19 Obstruction to Flow Across the Atrioventricular Valves Stenosis of the atrioventricular valves, as seen in mitral stenosis (MS) and tricuspid stenosis (TS), causes passive pulmonary and systemic vascular congestion without an effect on ventricular function. However, impaired fi lling of the left ventricle will lead to decreased cardiac output. Mitral Stenosis Congenital MS can occur as an isolated valvular lesion or in association with other congenital cardiac defects. Acquired MS, almost always due to rheumatic fever, is rare in the United States. Thickening of the leaflets, fusion of the commissures, or “parachute mitral valve” obstructs flow from the left atrium, resulting in increases in atrial pressure and eventually pulmonary venous congestion. The clinical presentation of MS includes the signs and symptoms of pulmonary edema and pulmonary hypertension, which reflect the severity of stenosis. Congenital MS is usually severe, presenting in early infancy. On physical examination, patients have a lowpitched, rumbling, diastolic murmur appreciated over the apex. A diastolic opening snap may rarely be heard. The ECG demonstrates left atrial enlargement and right ventricular hypertrophy. Atrial fibrillation as a manifestation of left atrial dilation and hypertrophy is rare in children. The chest radiograph shows left atrial enlargement and prominent pulmonary vasculature and interstitial edema reflective of pulmonary congestion.20-22 Tricuspid Stenosis Congenital tricuspid valve disease is usually due to valvular atresia or Ebstein’s anomaly. Isolated congenital TS is rare. Tricuspid stenosis is almost always rheumatic in origin, and symptoms rarely present in childhood. Signs and symptoms of systemic venous obstruction due to TS include peripheral edema with passive congestion and enlargement of organs such as the liver and spleen.23 Regurgitant Flow Across the Cardiac Valves Cardiac valves that allow retrograde or regurgitant flow across the valve result in volume overload and dilation of the cardiac chamber or great vessel on either side of the valve. Significant chronic regurgitation or acutely developing regurgitation manifests clinically as congestive heart failure. Commonly recognized valvular regurgitant lesions are mitral regurgitation (MR) and aortic regurgitation (AR). Hemodynamically significant pulmonary and tricuspid regurgitation are much rarer clinical entities. Patients with late-stage obstructive or regurgitant valvular dysfunction will present to the emergency department with shock or pulmonary edema. Aortic Regurgitation AR in childhood is most commonly associated with a bicuspid valve. Incomplete closure or prolapse of the bicuspid valve may lead to isolated regurgitation or a combination of

Chapter 67 — Valvular Heart Disease

stenosis and regurgitation.24 AR is associated with many clinical entities, including dilation of the aortic root as seen in Marfan syndrome, destruction of the semilunar cusps due to endocarditis, ventricular septal defects, and rheumatic fever. Mild AR is generally asymptomatic, but disease progression can result in exercise intolerance and eventual congestive heart failure. Chest pain, multiple premature ventricular contractions, and congestive heart failure are ominous signs. However, these symptoms are usually not evident until well into adulthood. Acute AR, as seen in infectious endocarditis or trauma, presents with rapid onset of heart failure symptoms and even sudden cardiovascular collapse. The murmur of AR is a decrescendo, mid-diastolic, high-pitched murmur best heard at the third or fourth left intercostal space. S1 is abnormally diminished. A wide pulse pressure and bounding arterial pulses are often present with severe chronic AR. In more severe AR, the ECG will show left ventricular hypertrophy. Chest radiographs may reveal left ventricular cardiomegaly, dilation of the ascending aorta, and pulmonary venous congestion.21,23 Mitral Regurgitation Congenital MR is most frequently diagnosed in the context of other congenital heart defects. Isolated congenital MR is extremely rare. MR is the common manifestation of valvular dysfunction in children with rheumatic heart disease.25 Other major causes of MR include infectious endocarditis, collagen vascular disorders, primary abnormalities of the valve, myocardial ischemia (e.g., anomalous left coronary artery, Kawasaki disease), and cardiomyopathy. Patients with chronic MR are relatively asymptomatic until adulthood, when progression of disease leads to decreased cardiac output and eventually heart failure. Patients with acute MR, as seen in infectious endocarditis, acute dysfunction of the papillary muscle, or chordae tendineae, present with symptoms of acute pulmonary edema and right-sided heart failure. A regurgitant, high-pitched, blowing pan-systolic murmur is appreciated at the apex and radiates to the left axilla. The S2 is widely split because the aortic valves close early, with the decreased stroke volume ejected from the left ventricle. The ECG may show left ventricular and left atrial hypertrophy. The chest radiograph may reveal left ventricular hypertrophy and left atrial enlargement in chronic MR and pulmonary edema in acute MR.21,23,26 Mitral Valve Prolapse Mitral valve prolapse (MVP) is the most common valvular problem seen in practice and is the most common cause of MR in the United States. It is more commonly seen in adolescents. Most cases of MVP are considered a normal variant whereby the posterior or anterior leaflet bulges into the left atrium. MVP is often recognized in children with congenital heart defects, Marfan syndrome, or other connective tissue disorders. Children are usually asymptomatic but may present with palpitations, chest pain, or rarely syncope. The natural history of uncomplicated MVP is not well understood, and cardiovascular complication of arrhythmias, progression of MR, overt congestive heart failure, chordae tendineae rupture, and even sudden death have been described.16,27 On auscultation, patients with mitral regurgitation may have a midsystolic click followed by a late systolic murmur (click-murmur syndrome). ECG rarely may reveal

527

arrhythmias such as supraventricular tachycardias or premature atrial or ventricular contractions.21 Cardinal Systemic Manifestations of Valvular Heart Disease Patients with valvular heart disease present with a constellation of systems determined by age and progression of valvular disease pathology. The cardinal symptoms of valvular heart disease include congestive heart failure, chest pain, palpitations, syncope, and neurologic deficits. Congestive heart failure results from volume or pressure overload. Time of onset of congestive heart failure due to congenital heart disease can be reliably predicted. Severe pulmonary or tricuspid atresia will result in symptoms of volume overload at birth. Patients with critical AS or PS will likely become symptomatic during the first few weeks of life. However, complex congenital heart disease, episodes of supraventricular tachycardia, congenital heart block, hydrops fetalis, and bonchopulmonary dysplasia also cause congestive heart failure in the neonatal period and must be distinguished from isolated critical AS/PS. AR, MS, and MR leading to congestive heart failure will have highly variable presentations ranging from early childhood to late adulthood. The onset of acquired valvular heart disease will be less predictable and must be distinguished from other disease processes such as sepsis, viral myocarditis, infi ltrative or hypertrophic cardiomyopathy, and recurrent bouts of “pneumonia.”28 Children who present to the emergency department with chest pain rarely have serious valvular disease.29 However, patients with severe valvular pathology (e.g., AS, IHSS) occasionally develop chest pain due to ventricular hypertrophy, increased wall stress, and resultant unmet oxygen demand. Similar to angina pectoris, patients may develop exertional chest pain that usually resolves with rest. Other conditions causing chest pain must be considered, including coronary artery anomalies, arrhythmias, cardiovascular disease, hypertrophic obstructive cardiomyopathy, cocaine abuse, pericarditis, and myocarditis30 (see Chapter 62, Chest Pain). Cardiac arrhythmias clinically perceived as palpitations are associated with all cardiac valvular lesions. Supraventricular rhythms (e.g., paroxysmal supraventricular tachycardia, atrial fibrillation, and atrial flutter) are frequently associated with MS and MR. In all patients presenting with palpitations, thorough evaluation for valvular causes is warranted. Specifically, MVP has been associated with atrial and ventricular premature contractions, paroxysmal supraventricular tachycardias, and ventricular tachyarrhythmias.31 Patients with severe obstructive cardiac lesions such as AS, PS, or IHSS may have syncope (see Chapter 61, Syncope). Clinically, these patients often present with exercise-induced syncope. The demand for cardiac output is not met, resulting in decreased cerebral perfusion and syncope. Furthermore, patients with valvular disease may experience syncope due to arrhythmias resulting from the underlying valve pathology.32-35 In the absence of signs and symptoms consistent with endocarditis, systemic embolization manifested as an acute neurologic deficit in a young patient warrants thorough investigation for left-sided valvular lesions or right-sided lesions associated with an interatrial communication36 (see Chapter 44, Central Nervous System Vascular Disorders).

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SECTION IV — Approach to the Acutely Ill Patient

Important Clinical Features and Considerations Endocarditis and Antibiotic Prophylaxis Valvular heart disease causes significant pressure gradients and turbulent blood flow, which predispose to endothelial damage and thrombus formation. This environment of vascular damage and overlying thrombus formation produces a nidus for bacterial growth. Any focal infection (e.g., pyelonephritis, pneumonia, skin abscess) or procedures performed on patients can lead to bacteremia. This combination of factors produces the milieu for development of endocarditis. The onset of illness is usually insidious and is suspected when there are signs and symptoms of fever, chills, sweats, malaise, fatigue, and cardiac murmur. Endocarditis can be lifethreatening. The emergency physician must be cognizant of the patient’s underlying valve disease because special considerations need to be exercised to prevent development of infectious endocarditis. Recommended antibiotic prophylaxis regimens for endocarditis developed by the American Heart Association depend on the level of risk associated with the procedure and the cardiac lesions (see Chapter 64, Pericarditis, Myocarditis, and Endocarditis).37,38

studies) and catherization, the results of which will direct further management to include medical therapy, valvuloplasty, or surgery. The asymptomatic child with potential cardiac valvular pathology requires referral to a pediatric cardiologist. The child with symptoms such as chest pain and syncope or symptoms suggestive of congestive heart failure will require an expedited evaluation. Indications and timing of interventions such as balloon valvuloplasty or surgery are based on the symptoms of the patient and evaluation of Doppler gradients across the affected valve, peak systolic pressure gradients, and calculated effective area of the valve orifice determined during echocardiography and catheterization. Patients with valvular heart disease may experience complications resulting from their medical management. Drug interactions and potential toxicities of cardiac medications warrant consideration. Patients presenting to the emergency department with problems unrelated to their valvular disease may need endocarditis prophylaxis for conditions or procedures that may cause bacteremia (see Chapter 64, Pericarditis, Myocarditis, and Endocarditis). These patients may also be more susceptible to other illnesses such as gastrointestinal bleeding or pulmonary infections.18,21,42

Rheumatic Heart Disease

Summary

Acute rheumatic fever is a common cause of heart disease in underdeveloped countries, but is rarely seen in the United States except for occasional localized outbreaks.39 Valvular lesions are believed to be caused by antibodies against the group A streptococcus that cross-react with antigen in various components of the heart. The revised Jones criteria are used to diagnose acute rheumatic fever (see Chapter 95, Musculoskeletal Disorders in Systemic Diseases). Carditis occurs in 50% of patients and invariably is associated with the murmurs of valvulitis (MR or AR).40 Permanent damage to heart valves often results from the carditis, leading to chronic valvular disease affecting predominantly the aortic and mitral valves. Recurrent episodes of rheumatic fever increase the valvular pathology. Patients with a history of rheumatic fever must receive antibiotic prophylaxis.41

One of the most important roles of the emergency physician in caring for pediatric patients with valvular heart disease is to first consider the diagnosis. A thorough history and physical examination with minimal testing will enable the physician to guide management and disposition. Patients with findings consistent with innocent murmurs can appropriately be followed by the primary physician. Asymptomatic patients who potentially have a pathologic murmur can usually be referred for outpatient evaluation by the pediatric cardiologist. Symptomatic patients will require acute management and disposition by the emergency physician augmented by a pediatric cardiologist. If an infant or child with known valvular heart disease presents to the emergency department, the clinician must consider whether symptoms are suggestive of complications of the valvular disease or if antibiotic prophylaxis is needed to prevent complications such as endocarditis.

Management The initial stabilization and management of the newborn with cardiac valvular disease is dictated by the underlying valvular pathology and severity of symptoms. The critically ill infant or child will require emergent medical treatment and coordination of management with the pediatric cardiac specialist (see Chapter 7, The Critically Ill Neonate; and Chapter 30, Congenital Heart Disease). Newborns with critical right-sided obstruction to pulmonary outflow, causing cyanosis, or left-sided obstruction to systemic outflow, causing shock, benefit temporarily from prostaglandin E1 infusion, which reopens the ductus arteriosus. Vasodilators should be avoided in the treatment of ventricular failure due to AS, but their use should be considered in the treatment of MR to maintain the forward flow state. Symptoms of pulmonary venous congestion due to severe MS are treated with diuretics. The pediatric cardiologist will help coordinate further diagnostic procedures as indicated, including echocardiography (M-mode, two-dimensional, and Doppler

REFERENCES 1. McLaren M, Lachman A, Pocock WA, Barlow JB: Innocent murmurs and third heard sounds in black school children. Br Heart J 43:67–73, 1980. 2. Park M: Basic tools in routine evaluation of cardiac patients: history taking. In Pediatric Cardiology for Practitioners, 4th ed. St. Louis: Mosby, 2002, pp 3–9. 3. Park M: Basic tools in routine evaluation of cardiac patients: physical examination. In Pediatric Cardiology for Practitioners, 4th ed. St. Louis: Mosby, 2002, pp 10–33. 4. McCrindle B, Shaffer K, Kan JS, et al: Cardinal clinical signs in the differentiation of heart murmurs in children. Arch Pediatr Adolesc Med 150:169–174, 1996. 5. Pelech A: The cardiac murmur: when to refer? Pediatr Clin North Am 45:107–122, 1998. 6. Braunwald E, Perloff JK: Physical examination of the heart and circulation. In Zipes DP (ed): Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine, 7th ed. Philadelphia: Elsevier, 2005, pp 77–106. 7. Danford D: Decision analysis in pediatric cardiology outcomes research. Prog Pediatr Cardiol 7:67–75, 1997.

Chapter 67 — Valvular Heart Disease 8. Birkebaek N, Hansen LK, Elle B, et al: Chest roentgenogram in the evaluation of heart defects in asymptomatic infants and children with a cardiac murmur: reproducibility and accuracy. Pediatrics 103:e15, 1999. 9. Danford D, Gumbiner C, Martin AB, et al: Effects of electrocardiography and chest radiograph on the accuracy of preliminary diagnosis of common congenital cardiac defects. Pediatr Cardiol 21:334–340, 2000. 10. Smythe J, Teixeira OH, Vlad P, et al: Initial evaluation of heart murmurs: are laboratory tests necessary? Pediatrics 86:497–500, 1990. 11. Danford D, Nasir A, Gumbiner C: Cost assessment of the evaluation of heart murmurs in childhood. Pediatrics 91:365–368, 1993. 12. Yi M, Kimball TR, Rsevat J, et al: Evaluation of heart murmurs in children: cost-effectiveness and practical implications. J Pediatr 141:504–511, 2002. 13. Danford D, Martin AB, Fletcher SE, Gumbiner CH: Echocardiographic yield in children when innocent murmur seems likely but doubts linger. Pediatr Cardiol 23:410–414, 2002. 14. Westmoreland D: Critical congenital cardiac defects in the newborn. J Perinat Neonatal Nurs 12(4):67–87, 1999. 15. Yetman A, Rosenberg H, Joubert G: Progression of asymptomatic aortic stenosis identified in the neonatal period. Am J Cardiol 75:636– 637, 1995. 16. Basso C, Corrado D, Thiene G: Cardiovascular causes of sudden death in young individuals including athletes. Cardiol Rev 7:127–135, 1999. 17. Freed M: Aortic stenosis. In Allen H, Clark E, Gutgesell H, Driscoll D (eds): Moss and Adams’ Heart Disease in Infants, Children and Adolescents, Including the Fetus and Young Adult, 6th ed. Philadelphia: Lippincott Williams & Williams, 2001, pp 970–987. 18. Park M: Obstructive lesions. In Pediatric Cardiology for Practitioners, 4th ed. St. Louis: Mosby, 2002, pp 155–165. 19. Latson L, Priesto L: Pulmonary stenosis. In Allen H, Clark E, Gutgesell H, Driscoll D (eds): Moss and Adams’ Heart Disease in Infants, Children and Adolescents, Including the Fetus and Young Adult, 6th ed. Philadelphia: Lippincott Williams & Williams, 2001, pp 820–844, 2002. 20. Okubo S, Nagata S, Masuda Y, et al: Clinical features of rheumatic heart disease in Bangladesh. Jpn Circ J 48:1345–1349, 1984. 21. Park M: Valvular heart disease. In Pediatric Cardiology for Practitioners, 4th ed. St. Louis: Mosby, 2002, pp 311–320. 22. Baylen B: Mitral inflow obstruction. In Allen H, Clark E, Gutgesell H, Driscoll D (eds): Moss and Adams’ Heart Disease in Infants, Children and Adolescents, Including the Fetus and Young Adult, 6th ed. Philadelphia: Lippincott Williams & Williams, 2001, pp 924–937. 23. Bonow RO, Braunwald E: Valvular heart disease. In Zipes ZD (ed): Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine, 7th ed. Philadelphia: Elsevier, 2005, pp 1553–1615. 24. Roberts W, Morrow A, McIntosh C, et al: Congenitally bicuspid aortic valve causing severe, pure aortic regurgitation without superimposed infective endocarditis. Am J Cardiol 47:206–209, 1981. 25. Marcus R, Sareli P, Pocock WA, Barlow JB: The spectrum of severe rheumatic mitral valve disease in a developing country: correlations

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among clinical presentation, surgical pathologic fi ndings, and hemodynamic sequelae. Ann Intern Med 120:177–183, 1994. 26. Boudoulasa H, Wooley C: The floppy mitral valve, mitral valve prolapse and mitral valvular regurgitation. In Allen H, Clark E, Gutgesell H, Driscoll D (eds): Moss and Adams’ Heart Disease in Infants, Children and Adolescents, Including the Fetus and Young Adult, 6th ed. Philadelphia: Lippincott Williams & Wilkins, 2001, pp 947–969. 27. Kamei F, Nakaharan N, Yuda S, et al: Long-term site-related differences in the progression and regression of the idiopathic mitral valve prolapse syndrome. Cardiology 91:161–168, 1999. 28. Park M: Congestive heart failure. In Pediatric Cardiology for Practitioners, 4th ed. St. Louis: Mosby, 2002, pp 399–401. 29. Selbst S, Rudy R, Clark B: Chest pain in children: follow-up of patients previously reported. Clin Pediatr (Phila) 29:374–377, 1990. 30. Park M: Child with chest pain. In Pediatric Cardiology for Practitioners, 4th ed. St. Louis: Mosby, 2002, pp 441–448. 31. Boudoulas H, Kolibash A Jr, Baker P, et al: Mitral valve prolapse and the mitral valve prolapse syndrome: a diagnostic classification and pathogenesis of symptoms. Am Heart J 118:796–818, 1989. 32. Park M: Syncope. In Pediatric Cardiology for Practitioners, 4th ed. St. Louis: Mosby, 2002, pp 449–459. 33. Benditt D, Lurie K, Fabian W: Clinical approach to diagnosis of syncope: an overview. Cardiol Clin 15:165–176, 1997. 34. Linzer M, Yang E, Estes N III, et al: Diagnosing syncope, Part 1. Value of history, physical examination, and electrocardiography. Clinical Efficacy Assessment Project of the American College of Physicians. Ann Intern Med 126:989–996, 1997. 35. Linzer M, Yang E, Estes N III, et al: Diagnosing syncope, Part 2. Unexplained syncope. Clinical Efficacy Assessment Project of the American College of Physicians. Ann Intern Med 127:76–86, 1997. 36. Cerrato P, Grasso M, Imperiale D, et al: Stroke in young patients: etiopathogenesis and risk factors in different age classes. Cerebrovasc Dis 18:154–159, 2004. 37. Karchmer AW: Infectious endocarditis. In Zipes DP (ed): Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine, 7th ed. Philadelphia: Elsevier, 2005, pp 1633–1658. *38. Dajani AS, Taubert KA, Wilson W, et al: Prevention of bacterial endocarditis: recommendations by the American Heart Association. JAMA 277:1794–1801, 1997. 39. Centers for Disease Control: Acute rheumatic fever—Utah. MMWR Morb Mortal Wkly Rep 36:108–110, 115, 1987. 40. Stollerman GH: Rheumatic fever. Lancet 349:935–942, 1997. 41. Park M: Acute rheumatic fever. In Pediatric Cardiology for Practitioners, 4th ed. St. Louis: Mosby, 2002, pp 304–310. *42. Bonow R, Carabello B, de Leon A Jr, et al: ACC/AHA guidelines for the management of patients with valvular heart disease: executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 98:1949–1984, 1998. *Selected readings.

Chapter 68

Infectious Disease

Bacteremia Elizabeth R. Alpern, MD, MSCE

Key Points Occult bacteremia is the risk of bacteremia in a wellappearing young child with a fever without an identifiable source of infection. Recent immunization innovations have drastically changed the etiology and lowered the prevalence of occult bacteremia. Risk of serious invasive disease associated with occult bacteremia is present but extremely low in an immunized child. Bacteremia may be associated with identifiable focal bacterial infections common in childhood, such as pneumonia, but is a different clinical entity than that of occult bacteremia.

Introduction and Background Occult bacteremia is the presence of pathogenic bacteria in the blood of a well-appearing febrile child who lacks a focal bacterial source of infection. Occult bacteremia carries a risk of progressing to focal infection, meningitis, or sepsis; therefore, a patient’s risk, methods for early identification, and treatment options for this entity have been widely studied. The population at risk has been identified as those children 2 to 24 months of age (some studies included children up to 36 months of age) with fever. It is an important concept for the emergency physician to differentiate children at risk for occult bacteremia from those children at risk for “nonoccult” bacteremia. Certainly young children with signs or symptoms of invasive disease, underlying immunodeficiencies, or evidence of systemic infection stemming from focal bacterial infections have an important and known risk of bacteremia. This bacteremia is not occult and therefore is a different entity from that described in this chapter.

Recognition and Approach As with every clinical entity, identification of the at-risk population is the first step to diagnosis and treatment. Occult 530

bacteremia, by definition, affects healthy, well-appearing children from 2 to 24 or 36 months of age.1-8 This chapter is thus limited to those healthy children considered immunocompetent hosts. In most cases, the patient’s medical history will establish this prerequisite condition, which is vitally important to ascertain. The patient should not have a known underlying oncologic process, acquired or inborn immunodeficiency, sickle cell anemia, congenital heart disease, or indwelling medical device. Children who fall into those categories are certainly at risk for bacteremia; however, this is not the population that comprises those at risk for occult bacteremia. In addition, immunization status and concurrent antibiotic use may influence the risk of occult bacteremia (as discussed later in detail), and therefore should be identified. Although fever is typically recognized as a temperature above 38.5° C, for purposes of population definition, most studies use 39° C as a cutoff for fever in children at risk for occult bacteremia.2-5,7,8 Another prerequisite condition for considering the diagnosis of occult bacteremia is a well-appearing child without evidence of focal bacterial infection (other than otitis media) that may predispose to bacteremia, such as pneumonia or urinary tract infections (see Chapter 33, Urinary Tract Infection in Infants; Chapter 58, Pneumonia/Pneumonitis; and Chapter 86, Urinary Tract Infections in Children and Adolescents). Some researchers believe that, if a child appears ill enough to warrant assessment with a lumbar puncture based on physical examination at initial evaluation, then he or she should not be included in the at-risk population for occult bacteremia, though he or she may certainly be at risk for nonoccult bacteremia.3 Historically, the most common etiologic organisms for occult bacteremia were Streptococcus pneumoniae and Haemophilus influenzae type b.2,4,6,7 Other common causative organisms included Salmonella species, H. influenzae nontype b, group A streptococci, Enterococcus species, and Neisseria meningitidis.3,5 Recent innovations in childhood immunizations have had the opportunity to dramatically change the prevalence and causative organisms of occult bacteremia. The H. influenzae type b (Hib) vaccine was introduced in 1987. Since that time, in the population at large, there has been a 94% decrease in the incidence of Hib meningitis and a shift in the median age of Hib meningitis from 15 months to 25 years of age.9,10 Prior to the licensure of the Hib vaccine, studies reported the prevalence of occult bacteremia to be between 3% and 11%.2,4,6,11,12 However, since the

Chapter 68 — Bacteremia

widespread use of the Hib vaccine, two studies have reported the overall rate of occult bacteremia to be between 1.6% and 1.9%.3,5 The conjugate pneumococcal vaccine was licensed in 2000, with subsequent impressive declines in invasive pneumococcal disease.13-16 There are 90 pneumococcal serotypes, and the current conjugate pneumoccocal vaccine licensed in the United States is a heptavalent vaccine. The seven serotypes covered by the current vaccine, however, accounted for 98% of cases of occult pneumococcal bacteremia in a recent study.17 The results of a single study since the introduction of the conjugate pneumoccocal vaccine indicate that the overall prevalence of the disease has decreased to less than 1% of children at risk.8 Occult bacteremia is of concern to the clinician due to the risk of possible progression from bacteremia to sepsis or death via hematogenously spread focal infection. This risk of invasive disease associated with occult bacteremia is dependent on the causative organism of the bacteremia. Prior to the Hib vaccine era, the risk of invasive disease associated with identified H. influenzae type b bacteremia was 25% to 44%.2,18 However, occult pneumococcal bacteremia is associated with a significantly decreased risk of invasive disease, estimated at less than 1%.2,18 Subsequent to the use of Hib vaccine, but prior to the introduction of the conjugate pneumococcal vaccine, the risk of meningitis or death in children considered to be at risk for occult bacteremia was approximately 0.03%.3

Clinical Presentation The diagnosis of occult bacteremia is dependent upon a complete history, including immunization status, and a thorough physical examination. There are several findings on the physical examination of the at-risk child that influence the probability that the patient has occult bacteremia. The incidence of occult bacteremia remains constant between 6 and 24 months of age.3,5,19 There is a lower incidence from 3 to 6 months of age hypothesized to be due to presence of maternal antibody after birth. However, selection bias in the studies performed (i.e., younger children may have undergone more invasive evaluations, and focal infections were identified at a higher rate) may have influenced results. The risk of occult bacteremia increases with increasing temperature and is more than two times the risk once temperature rises above 40° C.3,19 However, a patient’s response to antipyretics does not reflect the risk of underlying occult bacteremia; a patient whose appearance improves after antipyretics does not have a lowered risk of bacteremia.20-22 The risk of occult bacteremia with certain concomitant diseases has also been studied. Children with identified otitis media have the same overall risk of occult bacteremia as those without ear infections.3,18 Children presenting with simple febrile seizures without focal identifiable infections also have rates of occult bacteremia comparable to those of all children at risk.23 Children with particular viral illnesses, such as bronchiolitis, croup, and stomatitis, however, have a lower risk of occult bacteremia associated with those febrile illnesses.7,24,25 The final diagnosis of occult bacteremia is contingent upon a positive blood culture. However, an inherent limitation of this test is the delay until growth of the organism indicating a positive culture. In a continuously monitored

531

carbon dioxide detection pediatric blood culture system, approximately 94% of pathogenic cultures became positive within 18 hours.3,26 The majority of contaminated cultures are not positive until after that time point. As the rate of occult bacteremia declines due to improved immunization practices, the rate of truly positive pathogenic cultures approximates that of contaminated cultures.3,8 Many laboratory studies have been evaluated as screening tools for the identification of occult bacteremia. However, due to the overall low rate of occult bacteremia, their usefulness for the emergency medicine physician is limited by their positive predictive value. The complete blood count is the most widely studied laboratory screening test for occult bacteremia.2,5,6,8,12,19,27 If a white blood cell count of 15,000/mm3 or greater is used for a “positive” screen for occult bacteremia, the current positive predictive value of that test is between 3% and 5%.5,8 In other words, approximately 3% of children with white blood cell counts ≥ 15,000/mm3 will have occult bacteremia. An absolute neutrophil count of ≥ 10,000/ mm3 has predicted approximately 8% of patients with occult bacteremia.19 Therefore, although an increased white blood cell count or neutrophil count is associated with an increased risk of occult bacteremia, the vast majority of patients with a “positive” screen will not have occult bacteremia. The emergency physician must balance the risk of not identifying a small percentage of cases of occult bacteremia with the ubiquitous use of screening tests that add time and invasive testing to the emergency department (ED) visit of a young child. C-reactive protein has also been studied as a screen for serious bacterial infections, including pneumonia, urinary tract infections, and occult bacteremia.28,29 The positive predictive value of C-reactive protein, depending on the cutoff for positivity, is between 30% and 65% for identification of all patients at risk for “serious bacterial infections.”28,29 However, when applied solely to patients with occult bacteremia, approximately 3% of at-risk children with a C-reactive protein level ≥ 4.4 have occult bacteremia. Thus the same considerations apply to the use of C-reactive protein as a screening tool for occult bacteremia. The risk of occult urinary tract infection far outweighs the risk of occult bacteremia in some at-risk children, especially febrile well-appearing boys under 6 months of age and uncircumcised boys or any girls prior to toilet training. Therefore, assessment for occult urinary tract infections is extremely important (see Chapter 33, Urinary Tract Infection in Infants; and Chapter 86, Urinary Tract Infections in Children and Adolescents).

Important Clinical Features and Considerations There are several important misconceptions or problem areas regarding the evaluation and treatment of occult bacteremia. Emergency physicians must be aware of these issues so the correct strategy is applied to febrile children who are at risk for both occult and nonoccult bacteremia (Table 68–1). The evaluation and treatment of young, febrile, wellappearing children at risk for occult bacteremia has long been a topic of controversy in pediatrics and emergency medicine. In response to one of the many studies of occult

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SECTION IV — Approach to the Acutely Ill Patient

Table 68–1

Misconceptions or Problem Areas Regarding the Evaluation and Treatment of Occult Bacteremia in Children

Misconception/Problem Area

Clarification/Appropriate Action

Applying the approach to the wrong population (i.e., those who are not at risk for occult bacteremia) Performing a lumbar puncture on an ill-appearing child and, if normal, considering the child to be at risk for occult bacteremia Believing that screening tests will be able to identify patients at greater risk of occult bacteremia Failure to appreciate the risk or prevalence of occult urinary tract infection

Identify host factors and exclude those children with oncologic process, immune disorders, sickle cell disease, congenital heart disease, or indwelling medical device. If a child appears ill enough to warrant a lumbar puncture, then he or she should not be included in the at-risk population for occult bacteremia; however, he or she may still be at risk for nonoccult bacteremia. Due to the overall low prevalence of occult bacteremia, screening tests have been shown to have a very low positive predictive value in these patients.

Failure to arrange close outpatient follow-up Failure to understand the laboratory methods used to identify positive blood cultures and their impact on the interpretation of the culture result

The risk of occult urinary tract infection far outweighs the risk of occult bacteremia in selected populations; therefore, screening for urinary tract infection in young febrile children is extremely important. Follow-up care is imperative for any child with persistent fever or other symptoms regardless of emergency department evaluation as focal bacterial sources may become evident at a later date. In a continuously monitored system, the vast majority of pathogenic blood cultures will turn positive within 18 hr; the vast majority of contaminants will turn positive after that time point.

infections in young children, an insightful editorial summarized this controversy as follows.30 Physicians typically approach the workup and treatment of the young child at risk for occult bacteremia in one of two basic ways: as a “riskminimizer” or a “test-minimizer.”30 If the physician leans more toward minimizing any possible risk of adverse outcome, then a “structured, methodical, laboratory intensive” strategy, including obtaining a blood culture, is often used to identify and treat all patients at risk for occult bacteremia (risk minimizer).30 Alternatively, if the physician leans toward “careful clinical examination, close follow-up, and avoiding invasive testing” (test minimizer), then he or she likely believes that the risk of adverse outcome is so low as to not justify broad-spectrum antibiotics in all possible patients at risk.30 Physicians in this group are likely to avoid ordering blood cultures on patients at risk for occult bacteremia. Recognition of where one stands on this continuum at different points in one’s career as a physician is as important as understanding the studies of possible evaluation and treatment strategies of children at risk for occult bacteremia.

Management Due to the difficult nature of the process of diagnosing occult bacteremia without some delay in test results, expectant antibiotic use has been advocated by some to decrease the risk of adverse outcomes such as meningitis or sepsis. However, as the risk of occult bacteremia and subsequent adverse sequelae have changed due to immunization innovations, with resultant changes is causative organisms, many advocate treating only patients identified to have documented bacteremia, not all those at risk. There are also risks associated with expectant antibiotic therapy, including adverse and allergic reactions and increasing the prevalence of drug-resistant organisms. Several large studies have evaluating the benefits of expectant antibiotics. In the pre-Hib vaccine era, three studies evaluated antibiotic treatment of patients at risk for occult bacteremia.2,4,12 In a trial of amoxicillin versus placebo, there

was no statistical difference between the antibiotic group and the placebo group in the incidence of major infectious morbidity.4 In a study of amoxicillin/clavulanate versus ceftriaxone, there was no difference in serious adverse outcomes in patients treated with either drug.12 The third study examined the difference in risk of focal infections of patients treated with ceftriaxone versus amoxicillin.2 Ceftriaxone was noted to decrease the risk of “definite” focal infections but was not effective in decreasing the risk of acquiring a “definite or probable” focal infection.2,31 In this particular study, H. influenzae and Salmonella species were the only causes of subsequent meningitis in patients with occult bacteremia. Several meta-analyses have also evaluated expectant antibiotic treatment of patients at risk for occult bacteremia.32-34 These studies concluded that expectant antibiotics do not prevent serious bacterial infections in all children at risk for occult bacteremia, especially in light of the extremely low risk of meningitis or death associated with pneumococcal bacteremia.32-34 A review of the risk of serious bacterial illness associated with occult bacteremia when antibiotics are reserved for only culture-proven bacteremia showed that the risk of adverse outcome associated with reserved treatment was exactly the same as the risk associated with treatment with expectant antibiotics published in prior literature.35 In addition, a costeffectiveness analysis indicated that, as the rates of occult bacteremia and meningitis decline with epidemiologic changes, empirical testing with complete blood counts and use of expectant antibiotic will become significantly less cost effective.36 Whichever treatment plan is instituted for an individual patient, follow-up within 24 to 36 hours with the child’s primary care provider or alternative site of care is imperative for any child with persistent fever or other symptoms as focal bacterial infections may become evident after the ED visit. The emergency physician is likely to see children return or referred to the ED for evaluation and treatment following a “positive” blood culture obtained at a prior visit to the ED or primary care provider. If the blood culture becomes

Chapter 68 — Bacteremia

533

Reevalutation for positive blood culture

Fever, ill appearing, or New focal infection identified

Afebrile Well appearing Asymptomatic

Blood cuIture, complete blood count, urinalysis, urine culture, chest X-ray, consider lumbar puncture (especially if prior antibiotic treatment)

FIGURE 68–1. Reevaluation for positive blood culture.

Admit IV antibiotics

positive within 18 to 24 hours utilizing a continuously monitored carbon dioxide detection system, the risk that this represents a true pathogenic culture is high.3,26 Cultures that become positive after this time period are most probably contaminants; however, they still have a small risk of representing more uncommon pathogens. Although S. pneumoniae is currently the most common causative organism of occult bacteremia and has a very high spontaneous resolution rate, there is still a risk of seeding deep infection. Therefore, a systematic approach to the patient who returns or is “recalled” due to a positive blood culture is recommended.37 Patients with a positive blood culture and resolution of fever and lack of signs or symptoms of focal infection on reevaluation can be safely treated as outpatients after a repeat blood culture is obtained (Fig. 68–1). However, patients with positive cultures who are persistently febrile and/or ill appearing need a full evaluation to assess for new focal infections, including meningitis. If no prior antibiotics have been prescribed, physical examination by an experienced practitioner may reliably indicate the presence or absence of a focal infection. Complete blood count, urinalysis and culture, chest radiograph, and lumbar puncture should all be considered in the ill-appearing febrile child with known occult bacteremia. Admission and broad-spectrum intravenous antibiotic treatment are indicated.

Summary Occult bacteremia is an entity that affects well-appearing febrile children without an identifiable focus of infection. The prevalence of and risks associated with occult bacteremia have changed significantly over the past decades as immunizations have targeted the most common etiologic organisms. Although there is a risk of serious bacterial illness associated with occult bacteremia, now that S. pneumoniae is the most common cause, this risk has greatly decreased. The impact of the pneumococcal conjugate vaccine is yet to be fully determined. Due to the decreasing prevalence of the disease, evaluation of children at risk for occult bacteremia with complete blood counts and treatment with

Prior antibiotic treatment

Without prior antibiotic treatment

Repeat blood culture Assess for partially treated focal infection including meningitis

Consider repeat blood culture Outpatient follow-up

expectant antibiotics now has limited impact. Outpatient follow-up for all persistently febrile children is also a crucial step in the management of patients at risk for occult bacteremia. REFERENCES *1. American College of Emergency Physicians Clinical Policies Subcommittee on Pediatric Fever: Clinical policy for children younger than three years presenting to the emergency department with fever. Ann Emerg Med 42:530–545, 2003. 2. Fleisher GR, Rosenberg N, Vinci R, et al: Intramuscular versus oral antibiotic therapy for the prevention of meningitis and other bacterial sequelae in young, febrile children at risk for occult bacteremia. J Pediatr 124:504–512, 1994. *3. Alpern ER, Alessandrini EA, Bell LM, et al: Occult bacteremia from a pediatric emergency department: current prevalence, time to detection, and outcome. Pediatrics 106:505–511, 2000. 4. Jaffe D, Tanz R, Davis T, et al: Antibiotic administration to treat possible occult bacteremia in febrile children. N Engl J Med 317:1175–1180, 1987. 5. Lee GM, Harper MB: Risk of bacteremia for febrile young children in the post-Haemophilus influenzae type B era. Arch Pediatr Adolesc Med 152:624–628, 1998. 6. McGowan J, Bratton L, Klein J, Finland M: Bacteremia in febrile children seen in a “walk-in” pediatric clinic. N Engl J Med 288:1309-1312, 1973. 7. Kuppermann N, Bank DE, Walton EA, et al: Risks for bacteremia and urinary tract infections in young febrile children with bronchiolitis. Arch Pediatr Adolesc Med 151:1207–1214, 1997. *8. Stoll ML, Rubin LG: Incidence of occult bacteremia among highly febrile young children in the era of the pneumococcal conjugate vaccine. Arch Pediatr Adolesc Med 158:671–675, 2004. 9. Centers for Disease Control and Prevention: Progress toward elimination of Haemophilus influenzae type B disease among infants and children—United States, 1987–1995. MMWR Morb Mortal Wkly Rep 45:901–906, 1996. 10. Schuchat A, Robinson K, Wenger J, et al: Bacterial meningitis in the United States in 1995. N Engl J Med 337:970–976, 1997. 11. Teele DW, Pelton SI, Grant MJ, et al: Bacteremia in febrile children under 2 years of age: results of cultures of blood of 600 consecutive febrile children seen in a “walk-in” clinic. J Pediatr 87:227–230, 1975. 12. Bass J, Steele R, Wittler R, et al: Antimicrobial treatment of occult bacteremia: A multicenter cooperative study. Pediatr Infect Dis J 12:466–473, 1993.

*Selected readings.

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13. Kaplan SL, Mason EO Jr, Wald ER, et al: Decrease of invasive pneumococcal infections in children among 8 children’s hospitals in the United States after the introduction of the 7-valent pneumococcal conjugate vaccine. Pediatrics 113:443–449, 2004. *14. Whitney CG, Farley MM, Hadler J, et al: Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine. N Engl J Med 348:1737–1746, 2003. 15. Black S, Shinefield H, Fireman B, et al: Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Northern California Kaiser Permanente Vaccine Study Center Group. Pediatr Infect Dis J 19:187–195, 2000. 16. Lin PL, Michaels MG, Janosky J, et al: Incidence of invasive pneumococcal disease in children 3 to 36 months of age at a tertiary care pediatric center 2 years after licensure of the pneumococcal conjugate vaccine. Pediatrics 111:896–899, 2003. 17. Alpern ER, Alessandrini EA, Bell LM, et al: Serotype prevalence of occult pneumococcal bacteremia. Pediatrics 108:e23, 2001. 18. Schutzman S, Petrycki S, Fleisher G: Bacteremia with otitis media. Pediatrics 87:48–53, 1991. 19. Kuppermann N, Fleisher GR, Jaffe DM: Predictors of occult pneumococcal bacteremia in young febrile children. Ann Emerg Med 31:679– 687, 1998. 20. Baker MD, Fosarelli PD, Carpenter RO: Childhood fever: correlation of diagnosis with temperature response to acetaminophen. Pediatrics 80:315–318, 1987. 21. Bonadio WA, Bellomo T, Brady W, Smith D: Correlating changes in body temperature with infectious outcome in febrile children who receive acetaminophen. Clin Pediatr (Phila) 32:343–346, 1993. 22. Torrey SB, Henretig F, Fleisher G, et al: Temperature response to antipyretic therapy in children: relationship to occult bacteremia. Am J Emerg Med 3:190–192, 1985. 23. Shah SS, Alpern ER, Zwerling L, et al: Low risk of bacteremia in children with febrile seizures. Arch Pediatr Adolesc Med 156:469–472, 2002. *24. Levine D, Platt S, Dayan P, et al; Multicenter RSV-SBI Study Group for the Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics: The risk of serious bacterial infection in young febrile infants with respiratory syncytial virus infections. Pediatrics 113:1728–1734, 2004.

25. Greenes DS, Harper MB: Low risk of bacteremia in febrile children with recognizable viral syndromes. Pediatr Infect Dis J 18:258–261, 1999. 26. Neuman MI, Harper MB: Time to positivity of blood cultures for children with Streptococcus pneumoniae bacteremia. Clin Infect Dis 33:1324–1328, 2001. 27. Jaffe D, Fleisher G: Temperature and total white blood cell count as indicators of bacteremia. Pediatrics 87:670–674, 1991. 28. Isaacman DJ, Burke BL: Utility of the serum C-reactive protein for detection of occult bacterial infection in children. Arch Pediatr Adolesc Med 156:905–909, 2002. 29. Pulliam PN, Attia MW, Cronan KM: C-reactive protein in febrile children 1 to 36 months of age with clinically undetectable serious bacterial infection. Pediatrics 108:1275–1279, 2001. *30. Green SM, Rothrock SG: Evaluation styles for well-appearing febrile children: are you a “risk minimizer” or a “test minimizer”? Ann Emerg Med 33:211–214, 1999. 31. Long SS: Antibiotic therapy in febrile children: “best-laid schemes.” J Pediatr 124:585–588, 1994. 32. Rothrock SG, Harper MB, Green SM, et al: Do oral antibiotics prevent meningitis and serious bacterial infections in children with Streptococcus pneumoniae occult bacteremia? A meta-analysis. Pediatrics 99:438– 444, 1997. 33. Bulloch B, Craig WR, Klassen TP: The use of antibiotics to prevent serious sequelae in children at risk for occult bacteremia: a metaanalysis. Acad Emerg Med 4:679–683, 1997. 34. Rothrock SG, Green SM, Harper MB, et al: Parenteral vs oral antibiotics in the prevention of serious bacterial infections in children with Streptococcus pneumoniae occult bacteremia: a meta-analysis. Acad Emerg Med 5:599–606, 1998. 35. Bandyopadhyay S, Bergholte J, Blackwell CD: Risk of serious bacterial infection in children with fever without a source in the post-Haemophilus influenzae era when antibiotics are reserved for culture-proven bacteremia. Arch Pediatr Adolesc Med 156:512–517, 2002. 36. Lee GM, Fleisher GR, Harper MB: Management of febrile children in the age of the conjugate pneumococcal vaccine: a cost-effectiveness analysis. Pediatrics 108:835–844, 2001. 37. Bachur R, Harper MB: Reevaluation of outpatients with Streptococcus pneumoniae bacteremia. Pediatrics 105:502–509, 2000.

Chapter 69 Human Immunodeficiency Virus Infection and Other Immunosuppressive Conditions Marina Catallozzi, MD

Key Points Human immunodeficiency virus infection and acquired immunodeficiency syndrome have different manifestations in children and adults. Early anticipation and aggressive management of overwhelming postsplenectomy infection are vital to outcome. Patients with asplenia of any etiology should be considered at high risk for invasive and life-threatening bacterial and parasitic infection and should be managed aggressively. Neutropenic patients can present with severe infections without localizing signs or symptoms. Since it is not possible to determine which immunocompromised patients are or are not infected on presentation to the emergency department, empirical antibiotics should be given to all such patients.

Selected Diagnoses Human immunodeficiency virus and acquired immunodeficiency syndrome Asplenia: congenital, splenectomy, and functional Primary immunodeficiencies Immunosuppression

Discussion of Individual Diagnoses Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome The perinatally acquired human immunodeficiency virus (HIV) epidemic peaked in the 1980s and 1990s. The United

States has seen a dramatic decrease in the number of new cases of perinatal HIV transmission since 1995, when voluntary HIV testing in pregnant women and antiretroviral therapy for HIV-positive women during pregnancy and delivery became routine. Reducing mother-to-child HIV transmission, institution of appropriate prophylaxis of opportunistic infections (OIs), and offering antiretroviral therapy when indicated have all contributed to decreases in OIs in children with HIV and/or acquired immunodeficiency syndrome (AIDS).1 However, in 2005 there were still an estimated 68 cases of AIDS reported in children under age 13, and 9112 estimated cumulative cases of AIDS in children under 13.2 Thus, OIs are still a cause for concern in the pediatric HIV-infected population. Additionally, HIV-positive women with OIs are more likely to transmit infections congenitally to both HIV-exposed but uninfected children and those with HIV infection.3 In contrast to OIs in adults, children do not have reactivation of latent pathogens, but primary infection with pathogens. Thus clinicians should be aware that the clinical manifestations and treatment differ from that in adults with OIs. The Centers for Disease Control and Prevention estimates that approximately half of all new HIV infections in the United States are among people less than 25 years of age.2 A disproportionate number of 13- to 24-year-olds with newly diagnosed HIV infection are racial and ethnic minorities, and most are infected sexually, either young men who have sex with men or young women who have sex with men. In 2005, there were an estimated 2546 new cases of AIDS and a cumulative estimated 41,311 cases of AIDS in 13- to 24-yearolds.2 In seeing patients in this age group, clinicians must be aware of the acute seroconversion syndrome in people at risk for acquiring HIV, and presentations of illness in those who do and do not know their HIV status. Many 13- to 24-yearolds infected with HIV are unaware of their status. Additionally, not all patients who are prescribed antiretroviral therapy have a good response to therapy. Reasons for this include poor adherence to regimens, drug toxicity, drug interactions, and initial infection with resistant HIV. Thus OIs in the HIVinfected adolescent must be considered.4 535

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Clinical Presentation Children and adolescents with HIV with signs and symptoms of acute illness will most commonly have OIs. These infections cause a varied array of clinical findings, including most commonly fever, respiratory distress, gastrointestinal symptoms, mucocutaneous manifestations, and neurologic syn-

Table 69–1

dromes. Table 69–1 presents the differential diagnosis to consider, clinical manifestations to recognize, and diagnostic tests to order when approaching these patients. For children and adolescents on antiretroviral therapy, drug toxicity must also be considered, with the most common presentations including rash, gastrointestinal symptoms, and fever. Additionally, pain is a common complaint in children

Differential Diagnosis of Acute Illness in Children and Adolescents with HIV/AIDS

Diagnosis

Clinical Presentation

Diagnostic Tests

Bacterial infections, invasive

Children: febrile illness, pneumonia, meningitis, sepsis, UTI, sinusitis, otitis osteomyelitis, septic arthritis, abscess Adolescents: pneumonia with fever, chest pain, productive cough Children: oral thrush, diaper dermatitis, esophagitis; rarely invasive but more common in those with advanced disease, central lines Adolescents: oral thrush, esophagitis, vulvovaginitis Children: fever, respiratory distress, lymphadenopathy, headache, wasting Adolescents: disseminated disease (fever, lymphadenopathy, skin manifestations), meningitis Children: meningoencephalitis (fever, headache, altered mental status more common than meningismus, photophobia, focal neurologic signs), disseminated cryptococcosis (cutaneous lesions resembling molluscum), pulmonary cryptococcosis (fever, nonproductive cough, mediastinal lymphadenopathy) Adolescents: meningitis (can see clinical presentation of meningitis), meningoencephalitis Children: fever and vomiting, nonbloody watery diarrhea, dehydration, weight loss; presents as any other acute gastroenteritis; can present with fever, right upper quadrant pain if infects the bile duct Adolescents: watery diarrhea, abdominal cramping; can see nausea & vomiting; cholangitis, and pancreatitis; in rare cases, microsporidia can cause eye infections, encephalitis, and disseminated infection Children: febrile illness, retinitis, mono-like illness, colitis, pneumonitis, encephalitis, congenital manifestations Adolescents: retinitis, colitis, esophagitis Children: asymptomatic or clinical hepatitis Adolescents: asymptomatic or clinical hepatitis (fever, nausea, vomiting, jaundice) Congenital: disseminated multiorgan disease; localized CNS, skin, eye, or mouth disease Children: orolabial disease with dissemination and visceral involvement in severely immunocompromised; esophagitis, genital Adolescents: skin, eye, or mouth disease, genital lesions Children: fever, fatigue, weight loss, nonproductive cough, cutaneous nodules Adolescents: interstitial pneumonitis, meningitis Children: recurrent fever, weight loss, night sweats, diarrhea, abdominal pain, lymphadenopathy Adolescents: usually disseminated disease with fever, night sweats, weight loss, diarrhea Neonates: congenital, nonspecific, failure to thrive, symptoms, pneumonia, meningitis Children: no symptoms or nonspecific, fever, failure to thrive, acute pneumonia, extrapulmonary disease Adolescents: fever, cough, wasting, lymphadenopathy Children: fever, respiratory distress, cough, hypoxia Adolescents: fever, SOB, cough, hypoxia

Blood culture, urine culture, CBC, CXR, LP if indicated; radiologic testing based on localizing signs Blood culture, CXR, sputum culture

Candida infections

Coccidiomycosis

Cryptococcosis

Cryptosporidiosis/ Microsporidiosis

Cytomegalovirus (CMV) Hepatitis B and C Herpes simplex virus (HSV)

Histoplasmosis Mycobacterium avium complex disease Mycobacterium tuberculosis

Pneumocystis jiroveci

Physical exam, KOH prep, fungal culture, barium swallow or endoscopy, blood culture; if fungemic, retinal exam, abdominal CT or US, bone scan if osteomyelitis suspected Blood culture, sputum culture, LP for CSF culture, serum antibody testing Cryptococcal antigen (serum and CSF), LP (for cell count, glucose, protein, opening pressure); fungal cultures of CSF, sputum, and blood; BAL; biopsy of pulmonary or skin lesions

Stool for ova and parasites; endoscopy if indicated

Dependent on presentation, CMV serum and urine antigen, CMV antibody titers, CMV PCR, endoscopy, CXR, LP, head imaging, eye exam Hepatitis B surface antigen, hepatitis C virus PCR, LFTs Clinical diagnosis based on seeing vesicles and ulcers, viral culture from lesions, direct immunofluorescence for HSV antigen from lesions; Tzanck preparation from lesions no longer recommended because nonspecific; CSF for HSV PCR if indicated Blood culture (takes up to 6 wk to grow); antigen in serum, urine, CSF, BAL Blood culture (for AFB, can take up to 6 wk to grow), biopsy specimens, CBC (neutropenia, anemia, thrombocytopenia), LFTs (evidence of infiltrative liver disease) CXR, skin testing (anergy testing not indicated), history of contact with infected adult, AFB stain of morning gastric aspirate (children), sputum, or BAL Low alveolar-arterial oxygen gradient on arterial blood culture, elevated lactate dehydrogenase; CXR can appear normal (early on) or have diffuse parenchymal infiltrates; visualization of the organism on histopathology or direct fluorescent antibody of BAL or sputum (in adolescents)

Chapter 69 — HIV Infection and Other Immunosuppressive Conditions

Table 69–1

537

Differential Diagnosis of Acute Illness in Children and Adolescents with HIV/AIDS (Continued)

Diagnosis

Clinical Presentation

Diagnostic Tests

Progressive multifocal leukoencephalopathy

Focal neurologic signs, seizures, cognitive dysfunction

Syphilis

Congenital: if no symptoms at birth, can see symptoms within the first 6 mo of life; organomegaly, jaundice, rash, nasal discharge, mucocutaneous lesions, anemia, pseudoparalysis

Radiographic findings (demyelination) on CT or MRI, CSF, or PCR for JC virus support diagnosis; brain biopsy may be indicated In infants, cannot rely on antibody testing because reflects mother’s immunoglobulins; diagnosis made by combination of physical, radiologic, serologic, and direct microscopic exam; CBC, CSF for VDRL; if indicated can check CXR, long bone radiograph, eye exam Nontreponemal antibody tests (VDRL or RPR), treponemal tests if former are positive (DFA-TP or FTA-ABS). LP should be considered in HIV-positive patients with serologic evidence of syphilis to rule out neurosyphilis; consider diagnosis if high-risk sexual activity (MSM, other STDs) Toxo-specific serum IgM, IgA, IgE, IgG (after 6 mo), head imaging (CT with multiple ring-enhancing lesions)

Adolescents: primary (painless genital ulcer), secondary (skin lesions— generalized and on palms and soles, lymphadenopathy, fever, HA, aseptic meningitis), late syphilis (dementia, aortitis) Toxoplasmosis

Varicella-zoster virus (VZV)

Congenital: maculopapular rash, lymphadenopathy, organomegaly, jaundice, pancytopenia, CNS disease (seizures, microcephaly, hydrocephalus) Children: fatigue, fever, sore throat, mono-like syndrome, rash, cervical lymphadenopathy Adolescents: fever, headache, confusion, seizures, encephalitis Congenital: skin scarring, lymph hypoplasia, neurologic manifestations (seizures, microcephaly, etc.) Children: generalized pruritic vesicular rash, fever; zoster with typical dermatomal distribution, but can see more disseminated rash; retinitis; encephalitis Adolescents: zoster/shingles (dermatomal, rarely disseminated if immunocompromised); retinal necrosis

Clinical diagnosis based on typical appearance of generalized vesicular rash and fever or painful vesicular rash in dermatomal pattern; direct immunofluorescence for VZV antigen on cells collected from skin, conjunctiva, or mucosa. Tzanck preparation is nonspecific (see giant cells with HSV as well). VZV isolation from culture of vesicular fluid; eye exam

Abbreviations: AFB, acid-fast bacilli; BAL, bronchoalveolar lavage; CBC, complete blood count; CNS, central nervous system; CSF, cerebrospinal fluid; CT, computed tomography; CXR, chest radiograph; DFA-TP, direct fluorescent antibody–treponemal test; FTA-ABS, fluorescent treponemal antibody absorption test; HA, headache; HIV, human immunodeficiency virus; Ig, immunoglobulin; KOH, potassium hydroxide; LFTs, liver function tests; LP, lumbar puncture; MRI, magnetic resonance imaging; MSM, men who have sex with men; PCR, polymerase chain reaction; RPR, rapid plasma reagent test; SOB, shortness of breath; STDs, sexually transmitted diseases; US, ultrasound; UTI, urinary tract infection; VDRL, Venereal Disease Research Laboratory test. Adapted from Mofenson LM, Oleske J, Serchuck L, et al.3 and Benson CA, Kaplan JE, Masur H, et al.4

with HIV infection secondary to systemic manifestations such as cardiomyopathy, myositis, drug reactions, and other secondary infections.5 In adolescents engaging in high-risk behaviors (unprotected sex, young men who have sex with men, history of a sexually transmitted disease, known HIV-positive sexual contact or forced sex within the 4 weeks prior to presentation), a diagnosis of acute HIV seroconversion must be considered when patients present with symptoms such as fever, fatigue, lymphadenopathy, pharyngitis, generalized rash, or, in general, a mononucleosis-like syndrome. While HIV antibody testing is not helpful in this acute setting, a baseline test should be obtained. Diagnostic testing should include a measurement of plasma viremia (by HIV polymerase chain reaction), with viral loads of greater than 50,000 copies/ml diagnostic of HIV seroconversion in the setting of a negative HIV antibody test.6-8 In the acute setting, the most common diagnoses to recognize in HIV-infected children and adolescents include invasive bacterial infections (bacteremia and pneumonia in particular), Pneumocystis jiroveci (PCP; formerly Pneumocystis carinii) pneumonia, herpes zoster, esophageal candidiasis, and disseminated Mycobacterium avium complex. Studies of opportunistic infections in perinatally infected children prior to antiretroviral therapy showed that bacterial infec-

tions were the most common infections, with pneumonia, bacteremia, and urinary tract infections the most common manifestations.3 One explanation for this finding is that, in children, infection with HIV occurs before primary immune function against common bacterial infections develops (specifically B-cell and humoral responses). While Streptococcus pneumoniae was found to be the most important bacterial pathogen in this group, this pattern may change given the institution of pneumococcal conjugate vaccinations as part of the primary vaccine series. While bacteremia with grampostitive organisms is more common than gram-negative bacteremia, gram-negative bacteremia is observed in children with advanced diseased, those with central lines, and those less than 5 years of age with less severe immunosuppression.9 Typical gram-negative organisms include Pseudomonas aeruginosa, nontyphoidal salmonellae, Escherichia coli, and Haemophilus influenzae. In the absence of bacteremia, acute pneumonia is presumed to be bacterial in the setting of a febrile child with pulmonary symptoms and an abnormal chest radiograph. Lymphoid interstitial pneumonitis (LIP) is common in pediatric AIDS. LIP or any underlying chronic lung disease makes development of acute pneumonia more likely.10 The clinical presentation of bacterial infections is based on the type of infection, as HIV-infected children will most likely present

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with signs and symptoms similar to those of children without HIV (fever, increased white blood cell count). However, severely immunocompromised patients may not be able to produce either fever or an elevated white blood cell count. PCP is still the most common AIDS-defining disease in the pediatric population, with the incidence peaking in the first year of life, between 3 and 6 months. In contrast to children over 1 year of age and to adults, in whom PCP occurs when CD4 cell counts are less than 200/mm3, low CD4 cell counts are not a risk factor for disease in infants as many infected with PCP have CD4 counts over 1500/mm3. This is why PCP prophylaxis is recommended in infants of HIV-positive mothers until the absence of HIV infection is proven. As in adults, the presentation of PCP can be either sudden, with classic symptoms of fever, tachypnea, and cough, or more subtle, with mild cough, dyspnea, and poor feeding.3,11 Mucocutaneous manifestations and infections that are rare in immunocompetent children are more common in perinatally infected HIV-positive children with moderate (defined as CD4 percentage of 15 to 24) and severe (defined as CD4 percentage of 1 to 14) immunosuppression. One study found that fungal infections were most common, notably oral candidiasis with Candida albicans. Viral infections were the second most common. As in HIV-infected adults, herpes zoster is more common in children with AIDS than in uninfected childen. Herpes simplex virus (HSV) stomatitis occurs with greater frequency and severity. Presentations can be atypical, and more than one mucocutaneous manifestation can present in the same patient.12 Management When invasive bacterial infection is suspected in the emergency department (ED), treatment regimens should take into consideration local resistance patterns to common infectious agents (e.g., penicillin-resistant S. pneumoniae or methicillin-resistant S. aureus) and any recent use of prophylactic or therapeutic medications by the patient. HIV-infected children who are severely immunocompromised require broad-spectrum antibiotic treatment for a range of organisms (resistant and nonresistant); those who are neither immunocompromised nor neutropenic can be treated as HIV-negative patients. An HIV-infected pediatric patient (non-neonatal) with suspected bacteremia, bacterial pneumonia, or meningitis should be treated with broad-spectrum cephalosporins such as ceftriaxone (80 to 100 mg/kg in one or two divided doses with a maximum dose of 4 g daily) or cefotaxime (200 mg/kg divivded in three or four doses with a maximum dose of 8 to 10 g daily) until an organism can be identified. In HIV-infected pediatric patients with fever and an indwelling catheter, both gram-negative and grampositive organisms should be treated with a regimen with pseudomonal and methicillin-resistant S. aureus coverage, such as ceftazidime and vancomycin.3,4 Treatment for PCP should be initiated if the diagnosis is suspected, and not withheld pending the diagnosis. Bronchoalveolar lavage is positive for at least 72 hours after PCP treatment has been initiated. In the absence of allergy, trimethoprim-sulfamethoxazole (TMP-SMX) can be started at 15 to 20 mg/kg of body weight per day (TMP component; 75 to 100 mg/kg of SMX) in three to four divided doses for patients older than 2 months of age and adults. It should be given

intravenously (IV) over 1 hour. Once the acute phase has passed, the TMP-SMX can be administered orally in the same dose to complete the 21-day course of treatment. If patients are not able to take TMP-SMX, pentamidine may be given (4 mg/kg as a single daily dose given IV over 60 to 90 minutes for 14 to 21 days). If pentamidine cannot be used, alternative oral regimens can be initiated, but are poorly studied in children. Early initiation of corticosteroids (within 72 hours of diagnosis) can be beneficial in moderate or severe cases of PCP. This is usually defined as the presence of hypoxemia with a partial pressure of arterial oxygen less than 70 mm Hg or an alveolar-arterial gradient greater than 35 mm Hg. Recommended initial doses include prednisone 40 mg twice a day, prednisone or IV methylprednisolone 1 mg/kg twice a day, or IV methylprednisolone 1 mg/kg every 6 hours.3,4,11 Uncomplicated oropharyngeal candidiasis can usually be treated with topical therapy such as clotrimazole troches used at 10 mg orally four to five times a day for 14 days or regimens utilizing nystatin suspension at 400,000 to 600,000 U/ml four times daily for 7 to 14 days. Since many of the topical therapies fail, some providers choose to begin therapy with an oral azole in severe cases, either fluconazole (best tolerated and most effective; 3 to 6 mg/kg by mouth once a day for 14 days), itraconazole, or ketoconazole. The patient’s liver function should be assessed prior to beginning this therapy. Interactions with other medications (particularly antiretrovirals) that utilize the cytochrome P-450 system should also be considered.3,4 Acyclovir is the first-line treatment for HIV-infected children with primary varicella and zoster. With primary varicella, IV acyclovir is recommended because of the risk of disseminated and life-threatening illness (fever, numerous or deep and hemorrhagic skin lesions, moderate or severe immunosuppression). Neonatal HSV disease should be treated with high-dose IV acyclovir (20 mg/kg of body weight per dose three times daily) administered for 21 days for central nervous system and disseminated disease and for 14 days for skin, eye, and mouth disease. The dose for children less than 1 year of age is 10 mg/kg over 1 hour every 8 hours for 21 days. Oral acyclovir at 20 mg/kg per dose given four times a day should be reserved for children with normal CD4 counts or for those with very mild disease. Acyclovir is also first-line treatment for HIV-infected children with zoster. Intravenous acyclovir should be used in children who are very immunosuppressed if there is risk of eye involvement (trigeminal nerve distribution), or multidermatomal distribution. Renal function should be checked with a baseline serum creatinine so the dose can be adjusted for renal impairment if necessary.3 Asplenia: Congenital, Splenectomy, and Functional Patients without a spleen or with functional hyposplenism are at risk for life-threatening infection. Congenital asplenia is associated with very low survival rates past 1 year of age and usually seen in conjunction with cardiac abnormalities and biliary atresia. Surgical splenectomies are performed secondary to trauma, cysts, malignancy, or other hematologic conditions (Hodgkin’s disease, hemolytic anemia, and idiopathic thrombocytopenic purpura).13 While some surgeons attempt to retain splenic tissue or autotransplant splenic

Chapter 69 — HIV Infection and Other Immunosuppressive Conditions

tissue, there is no good evidence that this helps to preserve splenic function. Functional asplenia occurs from other primary medical conditions that result in degrees of hyposplenism: sickle cell disease (hemoglobin SC, hemoglobin SE, β-thalassemia), thrombocytopenia, malignant histiocytosis, gastrointestinal causes (celiac disease, dermatitis herpetiformis, ulcerative colitis), liver disease (portal hypertension), immunologic disorders (systemic lupus erythematosus, rheumatoid arthritis, Graves' disease, polyarteritis nodosum), infi ltrative diseases (amyloidosis, sarcoidosis), and other miscellaneous causes (Bartonella infection, HIV infection, graft-versus-host disease, post–bone marrow transplantation, total parenteral nutrition, cancer therapy that includes either high-dose steroids or splenic irradiation).13 Important Clinical Features and Considerations The spleen plays a critical role in responding to antigens both by antigen clearance and antibody production, as well as through fi ltering, phagocytosis, and opsonization of cells. This places asplenic patients at higher risk for sepsis caused by bacteria, particularly encapsulated organisms such as Strep. pneumoniae, H. influenzae, and Neisseria meningitidis. While Strep. pneumoniae is the most common pathogen, other important causes of infection include gram-negative bacteria (associated with high mortality rates) such as E. coli and P. aeruginosa. Other bacteria include group B stretococcus, Staphylococcus aureus, Salmonella species, Enterococcus species, Bacteroides species, Bartonella, and Plesiomonas. Unusual organisms such as Capnocytophaga carnimorsus (also implicated after dog bites) and protozoa (e.g., those causing babesiosis, malaria, and ehrlichiosis) have also been implicated in asplenic patients. These infections must be considered in patients with asplenia with recent travel.14,15 Overwhelming postsplenectomy infection (OPSI) risk is thought to be highest in children, people undergoing splenectomy for hematologic conditions, and patients who are immunosuppressed for other reasons. While the risk of infection has been found to be highest in the first 2 years after splenectomy, lifetime risk of OPSI remains at 5% and carries a mortality rate of 38% to 69%.15 Despite preventive measures to reduce the risk of OPSI—immunization again Strep. pneumoniae, H. influenzae type b, and N. meningitides; prophylactic antibiotics; standby antibiotics (to be used if the patient becomes acutely febrile or ill and does not have quick access to a medical center)—asplenic patients remain at risk for OPSI, and no studies have specifically shown the efficacy of these measures. Also, it cannot be assumed that asplenic patients have been counseled regarding the risk of infection or the importance of compliance with daily prophylaxis.14 Streptococcus pneumoniae is the most important pathogen in asplenic pediatric patients, and has been implicated in over 50% of invasive infections.14 Prior to the institution of vaccination with conjugate pneumococcal vaccine, the median time to come to medical attention was 24 hours. Presenting signs and symptoms include fever, shock, petechiae or purpura, disseminated intravascular coagulopathy, and respiratory distress. Types of illnesses in these children include bacteremia (with or without other focal infections), meningitis, and osteomyelitis. While there are studies to support an overall decline in invasive pneumococcal disease after the introduction of the conjugate vaccine, approxi-

539

mately 19% of invasive pneumococcal disease has been caused by serotypes not included in the conjugate pneumococcal vaccine. Thus protection against pneumococcus cannot be presumed.16,17 OPSI does not always have a focus of infection. One possible explanation for the lack of localizing findings is that nasal carriage and colonization may lead to later invasive infection.13 Patients may present with septic shock, but often the presentation is more protean—viral-type symptoms such as fever, fatigue, headache, vomiting, and abdominal pain. OPSI must be suspected and therapy must be instituted very early as the disease can progress very quickly. The overall mortality rate of OPSI is between 50% and 70%. Other morbidities can include hearing loss, gangrene, skin grafts, and amputations. Early anticipation of OPSI and aggressive management are vital.13,16 Management The best way to improve survival is to recognize the risk for the illness before the full clinical picture of sepsis emerges. Sepsis should be aggressively treated, and empirical therapy should take precedence over any diagnostic testing. Ideally, blood cultures would be drawn prior to the administration of antibiotics, but should never delay treatment. Even though Pneumococcus is the most common pathogen, IV antibiotics should be administered that cover the spectrum of possible bacterial etiologies. Combination antibiotics should cover penicillin-resistant pneumococci, gram-negative organisms, β-lactamase–resistant organisms, and any other local resistance issues. Consultation should be sought with infectious disease specialists in areas where both penicillin and cephalosporin resistance is known, or when patients have multiple allergies. Proposed regimens include ceftriaxone (50 to 75 mg/kg IV per dose every 12 hours; adult dose 2 g IV per dose every 12 to 24 hours) or cefotaxime (25 to 50 mg/kg IV per dose every 6 hours; adult dose 2 g IV per dose every 8 hours) plus gentamycin (2.5 mg/kg IV per dose every 8 hours; adult dose 5 to 7 mg/kg IV per dose every 24 hours) or vancomycin (10 to 15 mg/kg per dose every 6 hours; adult dose 2 to 3 g per day in divided doses every 6 to 12 hours). Some authors also suggest the addition of rifampin in initial management.13,14 While some authors suggest steroids or immunoglobulin, there are no clear recommendations or data to support these measures. Patients with asplenia or splenectomy are at high risk for OPSI after animal or bite wounds and should be treated with prophylactic antibiotics, either ampicillin-sulbactam or amoxicillin–clavulinic acid by mouth depending on the severity of the wound. Particular attention to the possibility of malaria (whether or not the patient was on prophylaxis), babesiosis, or ehrlichiosis should be considered in asplenic patients who travel to endemic regions.14 Diagnostic workup (before or after the initiation of IV antibiotics), depending on the clinical scenario, should include blood culture, urine culture, sputum culture (in older children and adolescents), lumbar puncture if indicated, complete blood count, chemistry, and chest radiograph. Primary Immunodeficiencies Primary immunodeficiencies (PIs) are a group of disorders in which the primary defect is intrinsic to one or more of the

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SECTION IV — Approach to the Acutely Ill Patient

four components of the immune system: B lymphocytes, T lymphocytes, phagocytes, and complement. The World Health Organization classifies PIs on a molecular basis as Tand B-cell immunodeficiencies; predominantly antibody deficiencies; other well-defined immunodeficiency syndromes; diseases of immune dysregulation; congenital defects of phagocyte number, function, or both; defects in innate immunity; autoinflammatory disorders; and complement deficiencies. For the purposes of this chapter, PIs are discussed in terms of the components of the immune system affected.18,19 Clinical Presentation In the ED, children with PIs may present with known diagnoses, as overwhelming infections representing the fi rst sign of a PI, or with recurrent infections indicating an underlying PI. It is helpful to approach the disorders in terms of types of infections with which they are likely to present.18,19 B-lymphocyte defects are the most common PIs (approximately 70%) and manifest as an impaired antibody response.20-22 Those patients affected are more susceptible to bacterial infections, particularly encapsulated pyogenic bacteria such as H. influenzae, Strep. pneumoniae, and staphylococci, but also infections with other bacteria (P. aeruginosa, Mycoplasma hominis, and Ureaplasma urealyticum) as well as enteroviruses. Most of the B-lymphocyte defects (except common variable immunodeficiency, which presents between 20 and 30 years of age) present after 3 to 6 months when maternal antibodies wane. Types of bacterial infection include pneumonia, otitis, sinusitis, and bacteremia.20-22 T-lymphocyte defects usually present at birth or in early infancy. While T-cell disorders are thought of as cellular immunodeficiencies, these patients are also at risk for pneumococcal disease because of impaired antibody

Table 69–2

Management Whether or not the underlying immunologic defect is known, acute management should be guided by the patient’s clinical situation. In the ED, supportive and resuscitative management and coverage with broad-spectrum antibiotic therapy are always appropriate until further diagnostic workup can be pursued. PIs are an important group of disorders in the pediatric population. Careful attention to overwhelming or recurrent infection is the key to guiding diagnosis and man-

Examples of Primary Immunodeficiences20-23

Affected Part of the Immune System B lymphocytes

T lymphocytes Combined B and T lymphocytes

Phagocytes

responses.20,21,23 Patients with T-cell defects are primary thought to be at high risk for OIs secondary to viruses (severe respiratory infections caused by parainfluenza or respiratory syncytial virus; herpesvirus infections such as HSV, varicella-zoster virus, or cytomegalovirus), and PCP. They may also be at risk for infections with bacterial pathogens as seen in B-lymphocyte defects. These children are also more prone to fungal and mycobacterial disease.20,21,23 Phagocyte defects (affecting neutrophils and macrophages) present in early childhood and display very specific infections with pyogenic bacteria (Pseudomonas, Serratia marcescans, Staph. aureus) and fungi (Aspergillus fumigatus and Candida). They do not typically cause infection with PCP, pneumococcus, or viruses. Infections of the skin and reticuloendothelial system frequently occur.21,24 Complement defects are rare, but can occur in nearly every component of the complement system—the classical pathway, alternative pathway, and membrane attack complex. This defect predisposes patients to encapsulated bacterial infections, most notably pneumococcal infections. Clinical presentations include bacteremia or meningitis. Defects of the terminal components (C5 to C9) predispose to infection with Neisseria species.20,21 Table 69–2 contains examples of primary immunodeficiencies in each part of the immune system.

Examples

Typical Presentation

X-linked agammaglobulinemia Autosomal recessive agammaglobulinemia Hyper-IgM syndrome IgA deficiency Common variable immunodeficiency IgG subclass deficiencies Selective antipolysaccharide antibody deficiencies DiGeorge syndrome Purine nucleoside phosphorylase deficiency

First year of life with infection from encapsulated bacteria such as Pneumococcus, Giardia, or enteroviruses

Severe combined immunodeficiency Wiskott-Aldrich syndrome (X-linked recessive) Ataxia-telangiectasia (autosomal recessive) Progressive cerebellar ataxia Oculocutaneous telangiectasia Recurrent lung infections Chronic granulomatous disease (defect of the nicotinamide adenine dinucleotide phosphatase oxidase pathway) Leukocyte adhesion defect Chédiak-Higashi syndrome

Abbreviations: Ig, immunoglobulin; PCP, Pneumocystis jiroveci pneumonia.

Thymic hypoplasia, hypocalcemia secondary to hypoparathyroidism, and congenital cardiac anomalies; classic facies associated Failure to thrive, chronic diarrhea, oral thrush, skin rash, pneumonia, sepsis, PCP, severe pneumonias due to several possible etiologies; fatal without intervention, bone marrow transplantation Eczema, thrombocytopenia, and recurrent infections Recurrent and often life-threatening infection with catalase-positive bacteria and fungi most often in the skin, lung, lymph nodes, and liver; excessive granuloma formation

Chapter 69 — HIV Infection and Other Immunosuppressive Conditions

agement. Knowledge of an already diagnosed PI also helps to guide therapy. Immunosuppression Immunodeficiencies can be either primary or secondary and can affect any component of the immune system. Causes of secondary immunosuppression include cancer and transplantation (bone marrow or solid organ). Risk of infection in cancer is high because of the underlying disease process or organ involved, chemotherapeutic agents utilized in treatment, degree of neutropenia, alteration of mucosal immunity, and frequent need for an indwelling catheter. Infection risk in bone marrow transplantation is high for the reasons mentioned, and because of the need for immunosuppressive medications, risk of infection with cytomegalovirus, and graft-versus-host disease. Solid organ transplantation is associated with infection risk at the site of the transplanted organ, an underlying disease process for which the patient received the transplant, poor nutritional status of the patient prior to transplantation due to chronic disease, and the need for immunosuppressive medications. All of these factors make the initial evaluation and treatment of the immunosuppressed patient crucial to outcome.25 Clinical Presentation Fever can often be the only sign of a serious infection in an immunocompromised patient. Half of febrile neutropenic patients with cancer have an occult infection.25 The Infectious Diseases Society of America Fever and Neutropenia Guidelines Panel defines fever as a single oral temperature of greater than 38.3° C (101° F) or a temperature of greater than 38.0° C (100.4° F) for more than 1 hour. They define neutropenia as a neutrophil count of less than 500 cells/mm3 or a count of less than 1000 cells/mm3 with the likelihood that the count will decrease to less than 500 cells/mm3. Increased risk of infection is associated with lower neutrophil count, prolonged neutropenia, and a low nadir of neutrophil count.25,26 If pathogens are able to be isolated, bacteria are most common and include gram-positive, gram-negative, and anaerobic organisms. Fungi are common in patients with a history of exposure to broad-spectrum antibiotics. Neutropenic patients can present with severe infections without localizing signs or symptoms (i.e., induration, erythema) due to lack of ability to mount a local inflammatory response. Body fluids may not always reflect a pleocytosis.25,26 A careful history and physical examination is paramount, and attention should be focused on common sites of infection—the oral cavity, including the teeth, gums, and oropharynx; the lungs; the gastrointestinal tract (with special attention to the perineum and anus); the eyes and fundi; the skin (focus on any access sites, bone marrow aspirate sites), and soft tissue (particularly around the nails).25,26 If the patient is hemodynamically stable, the following diagnostic evaluation should be obtained prior to empirical treatment with antibiotics: blood culture (from both the peripheral vein and catheter lumen) for bacterial and fungal culture; Gram stain and culture (for bacteria, fungi and, if the lesion is chronic, mycobacteria) of any fluid draining from the indwelling catheter site; urinalysis and urine culture; and chest radiograph. Other studies (such as cerebrospinal fluid) are dependent on the patient’s clinical status.

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A complete blood count and serum chemistry (electrolytes, blood urea nitrogen, creatinine, liver function tests) should also be obtained. Workup for fungal infection can be pursued at a later date or if the patient does not respond to initial antimicrobial therapy.25,26 Management As with patients with asplenia, infection in neutropenic patients can progress rapidly, and all febrile and neutropenic patients should be presumed to have an invasive infection until proven otherwise. Empirical therapy should include coverage for both gram-positive and gram-negative bacteria. The antibiotic choice should be dependent on the susceptibility and resistance patterns of a given institution as well as the patient’s allergies or organ impairment. Suggested management can include monotherapy with a third- or fourth-generation cephalosporin (cefepime, ceftazidime), or carbapenem, or two-drug therapy (an aminoglycoside and either an antipseudomonal penicillin or cefepime, ceftazidime, or carbapenem).25,26 Vancomycin should be added if local rates of gram-positive infections are high, if the infection is suspected to be catheter related, if the patient is know to be colonized with resistant bacteria, if the patient was recently treated for gram-positive bacteremia, if the patient received chemotherapy that is known to cause severe mucosal impairment, or the patient is hypotensive or clinically unstable.25,26 Other coverage should be based on the patient’s clinical examination and findings. Empirical antifungal coverage is almost never initiated in the ED unless the patient is known to have fungal disease. Central indwelling catheters should stay in place unless there is a clear indication for removal (tunnel infection, recurrent infections), and that decision is usually not made in the ED. For well-appearing low-risk patients, some institutions manage fever and neutropenia in the outpatient setting with oral antibiotics, but this must be in consultation with the oncologist and with assurance that the patient has a reliable social situation, ability to return to the hospital for worsening status, and prearranged close follow-up.25,26 Fever is a common presenting symptom in immunocompromised, neutropenic patients and is usually indicative of an underlying infection. Since it is not possible to determine which patients are or are not infected on presentation to the ED, empirical antibiotics should be given to all such patients. REFERENCES 1. Graham SM: HIV and respiratory infections in children. Curr Opin Pulm Med 9:215–220, 2003. *2. Centers for Disease Control and Prevention: HIV/AIDS Surveillance Report, 2005 (Vol. 17). Atlanta: Centers for Disease Control and Prevention, 2007. http://www.cdc.gov/hiv/topics/surveillance/resources/ reports *3. Mofenson LM, Oleske J, Serchuck L, et al: Treating opportunistic infections among HIV-exposed and infected children: recommendations from CDC, the National Institutes of Health, and the Infectious Diseases Society of America. MMWR Recomm Rep 53(RR-14):1–100, 2004. 4. Benson CA, Kaplan JE, Masur H, et al: Treating opportunistic infections among HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association/Infectious Diseases Society of America. MMWR Recomm Rep 53(RR-15):1–120, 2004.

*Selected readings.

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5. National Institutes of Health: Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection. Supplement II: Managing Complications of HIV Infection in HIV-Infected Children on Antiretroviral Therapy. Bethesda, MD: National Institutes of Health, 2006. 6. Bisno AL: Acute pharyngitis. N Engl J Med 344:205–211, 2001. 7. Vanhems P, Dassa C, Lambert J, et al: Comprehensive classification of symptoms and signs reported among 218 patients with acute HIV-1 infection. J Acquir Immune Defic Syndr 21:99–106, 1999. 8. Kahn JO, Walker BD: Acute human immunodeficiency virus type 1 infection. N Engl J Med 339:33–39, 1998. 9. Dankner WM, Lindsey JC, Levin MJ; Pediatric AIDS Clinical Trials Group Protocol Teams: Correlates of opportunistic infections in children infected with the human immunodeficiency virus managed before highly active antiretroviral therapy. Pediatr Infect Dis J 20:40– 48, 2001. 10. Gonzalez CE, Samakoses R, Boler AM, et al: Lymphoid interstitial pneumonitis in pediatric AIDS: natural history of the disease. Ann N Y Acad Sci 918:358–361, 2000. *11. Thomas CF, Limper AH: Pneumocystic pneumonia. N Engl J Med 350:2487–2498, 2004. 12. Wananukul S, Deekajorndech T, Panchareon C, Thisyakorn U: Mucocutaneous fi ndings in pediatric AIDS related to degree of immunosuppression. Pediatr Dermatol 20:289–294, 2003. *13. Bridgen ML, Patullo AL: Prevention and management of overwhelming postsplenectomy infection—an update. Crit Care Med 27:836–842, 1999. 14. Davidson RN, Wall RA: Prevention and management of infections in patients without a spleen. Clin Microbiol Infect 7:657–660, 2001. 15. Bisharat N, Omari H, Lavi I, Raz R: Risk of infection and death among post-splenectomy patients. J Infect 43:182–186, 2001.

16. Schutze GE, Mason, EO Jr, Barson WJ, et al: Invasive pneumococcal infections in children with asplenia. Pediatr Infect Dis J 21:278–282, 2002. 17. Whitney CG, Farley MM, Hadler J, et al; Active Bacterial Core Surveillance of the Emerging Infections Program Network: Decline in invasive pneumococcal disease after the introduction of proteinpolysaccharide conjugate vaccine. N Engl J Med 348:1737–1746, 2003. *18. Notarangelo L, Casanova JL, Fischer A, et al; International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee: Primary immunodeficiency diseases: an update. J Allergy Clin Immunol 114:677–687, 2004. 19. Bonilla FA, Geha RS: Primary immunodeficiency diseases. J Allergy Clin Immunol 111(Suppl):S571–S581, 2001. 20. Picard C, Puel A, Bustamante J, et al: Primary immunodeficiencies associated with pneumococcal disease. Curr Opin Allergy Clin Immunol 3:451–459, 2003. 21. Buckley RH: Pulmonary complications of primary immunodeficiencies. Paediatr Respir Rev 5(Suppl A):S225–S233, 2004. 22. Ballow M: Primary immunodeficiency disorders: antibody deficiency. J Allergy Clin Immunol 109:581–591, 2002. 23. Buckley RH: Primary cellular immunodeficiencies. J Allergy Clin Immunol 109:747–757, 2002. 24. Rosenzweig SD, Holland SM: Phagocyte immunodeficiencies and their infections. J Allergy Clin Immunol 113:620–626, 2004. *25. Pizzo PA: Fever in immunocompromised patients. N Engl J Med 341:893–900, 1999. *26. Hughes WT, Armstrong D, Bodey GP, et al: 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis 34:730–751, 2002.

Chapter 70 Sexually Transmitted Infections Cynthia J. Mollen, MD, MSCE

Key Points Evaluation for sexually transmitted diseases in adolescent females can often be done without the speculum examination, if nucleic acid amplification techniques are available for organism identification Empirical treatment is generally recommended when suspicion of a sexually transmitted infection (STI) is high, in order to reduce the risk of complications and shorten infectivity. Confidentiality and consent issues should be considered for all adolescent patients presenting for evaluation of a possible STI.

Selected Diagnoses Pelvic inflammatory disease Cervicitis Vaginitis Genital ulcers Herpes genitalis Syphilis Lymphogranuloma venereum Chancroid Genital growths Human papillomavirus Molluscum contagiosum Urethritis and epididymitis Neonatal infections

Discussion of Individual Diagnoses The rates of many sexually transmitted infections (STIs) are highest among adolescents, due at least in part to increased frequency of unprotected intercourse when compared to adults. In addition, adolescents are biologically more susceptible to infection, often have short-term serial relationships, and may have barriers to access to health care. Clinicians can make an impact on future acquisition of STIs by discussing risk factors and healthy sexual behaviors with the adolescent

patient. Of paramount importance is obtaining an accurate sexual history in private, in a nonjudgmental fashion, in order to assess risk for the infections discussed in this chapter. Pelvic Inflammatory Disease Pelvic inflammatory disease (PID) is a polymicrobial infection of the upper genital tract, and is one of the most common infections in sexually active young women. A range of inflammatory disorders can be classified as PID, including endometritis, salpingitis, oophoritis, perihepatitis, and tubo-ovarian abscess (TOA). Adolescents are at approximately 10-fold higher risk for acquiring PID when compared to adult women (women under 25 years old account for 70% of cases); this increased risk is due to a number of factors, including lower levels of secretory immunoglobulin A in adolescents and differences in the epithelial cells of young women when compared to adults, which allow pathogens to cause infection more easily. In addition, adolescents may be more likely to be exposed to bacterial and viral causes of STIs as they tend to have short-term serial intimate relationships and most likely are less effective users of condoms than adults.1,2 PID usually begins as an STI, often caused by Neisseria gonorrhoeae or Chlamydia trachomatis. However, PID is a polymicrobial infection that often involves other organisms as well, including anaerobes. Once the lower genital tract is infected, bacteria ascend to the upper genital tract and cause symptoms of PID.1 In addition to age, other risk factors for PID include previous episodes of PID, use of an intrauterine device, vaginal douching, and bacterial vaginosis. The use of condoms and oral contraceptives is a protective factor; oral contraceptives cause thickening of the cervical mucus and decrease cervical dilation, uterine contraction, and blood flow during menses, all of which are mechanisms that support ascension of bacteria to the upper genital tract.2 Clinical Presentation Patients can present with a wide variety of symptoms and signs, and the presentation can be subtle, particularly with mild disease. Therefore, it is important to consider PID in the differential of any young women presenting to the emergency department (ED) with the complaint of abdominal pain. The clinical diagnosis of PID is imprecise; studies suggest that the clinical diagnosis of symptomatic PID has a positive predictive value for salpingitis of only 65% to 90% when compared to laparoscopy, which is considered to be the best diagnostic tool for PID.3,4 Clearly laparoscopy is not 543

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Table 70–1

Diagnosis of Pelvic Inflammatory Disease

Minimum Criteria (at least one)

Additional Supporting Criteria

Uterine tenderness Adnexal tenderness Cervical motion tenderness

Oral temperature >101° F (38.3° C) Abnormal cervical or vaginal mucopurulent discharge Elevated erythrocyte sedimentation rate Elevated C-reactive protein Laboratory documentation of cervical infection with N. gonorrhoeae or C. trachomatis Presence of abundant numbers of WBC on saline microscopy of vaginal secretions

From Centers for Disease Control and Prevention: Sexually transmitted diseases treatment guidelines—2006. MMWR Recomm Rep 55(RR-11):1–100, 2006.

indicated for the majority of patients with suspected PID, so a clinical diagnosis is usually necessary (Table 70–1). Most patients presenting with PID will complain of abdominal pain, abnormal vaginal bleeding, or vaginal discharge. Patients may report a history of fever, and may complain of nausea and vomiting, although gastrointestinal symptoms are usually not the primary complaint. Major diagnoses to consider in adolescent patients presenting with abdominal pain, in addition to PID, include appendicitis, constipation, cholecystitis, ovarian torsion, ovarian tumor, pregnancy and associated complications, pyelonephritis, and nephrolithiasis. When assessing an adolescent for the possibility of PID, it is crucial to obtain an accurate social history. This is best obtained by interviewing the patient alone. One approach is to establish a practice of interviewing all adolescents without a parent present, in order to maintain consistency and limit the possibility of missing important information. This approach will also minimize the possibility of missing the diagnosis of PID in a patient who “seems” unlikely to be sexually active, such as the patient with a chronic medical condition or special health care needs. It is important to outline the limits of confidentiality for both the parent and the patient (suicidal or homicidal ideation, or an indication of abuse) (see also Chapter 151, Issues of Consent, Confidentiality, and Minor Status). Because there is no laboratory or radiologic test that can make a definitive diagnosis of PID, the physical examination is of the utmost importance. In addition to a general physical examination, the pelvic examination provides key information. The pelvic examination, which consists of three traditional components (external inspection, speculum examination, and bimanual examination), is generally associated with a significant amount of anxiety for the adolescent patient.5 According to the Centers for Disease Control and Prevention (CDC) 2006 Sexually Transmitted Diseases Treatment Guidelines, the diagnosis of PID should be considered in all patients at risk for an STI who have either uterine or adnexal or cervical motion tenderness on physical examination, if no other explanation for the findings can be found.3 Furthermore, a recent study suggests that the most sensitive physical examination finding for diagnosing PID is adnexal tenderness.6 Both of these physical examination criteria can

be assessed through the bimanual examination, without the use of a speculum. In addition, recent advances in diagnostic testing techniques for N. gonorrhoeae and C. trachomatis have helped pave the way for a reduction in the use of the speculum.7 Urine-based and vaginal swab nucleic acid amplification techniques have been shown to be at least as sensitive as endocervical culture. Cervical culture for gonorrhea has a sensitivity of 87% to 94%, compared with a sensitivity of 92% to 96% for urine-based tests and up to 100% for vaginal swab–based tests. Similarly, while cervical culture for chlamydia has a sensitivity of only 77% to 84%, urine-based tests have a sensitivity of 88% to 95%, and vaginal swab–based tests have a sensitivity of 91% to 93%. Furthermore, urinebased and vaginal swab–based tests for both organisms have specificities of 100%.8-16 Therefore, in healthy, nonpregnant adolescents being evaluated in the ED for possible PID, a speculum examination can be avoided in most cases. A key exception to this is the patient with profuse vaginal bleeding. A variety of symptoms, signs, and laboratory values support the diagnosis of PID (see Table 70–1). None of these criteria requires the use of a speculum. The presence of a cervical discharge is not necessary for the diagnosis; the presence of a mucopurulent discharge in the vagina, whether originating from the cervix or the vagina, is an adequate supportive finding. Most patients with PID have either a mucopurulent discharge or evidence of white blood cells (WBCs) on microscopic evaluation of a saline preparation of vaginal fluid; if neither of these findings is present, another explanation for the patient’s findings should be sought. Transvaginal ultrasound may be helpful in diagnosing some patients.17 Patients with suspected PID should have urine or vaginal swabs sent for detection of N. gonorrhoeae or C. trachomatis. Vaginal swabs should be sent for a wet preparation to evaluate for Trichomonas vaginalis and a Gram stain. To obtain adequate specimens, two Dacron-tipped specimen swabs should be simultaneously inserted about 1 inch into the vagina, and remain for approximately 30 seconds. In addition, a complete blood count, erythrocyte sedimentation rate, and C-reactive protein level can all be helpful in making the diagnosis. Depending on the local prevalence of syphilis, a rapid plasma reagin test may be done as well. Important Clinical Features and Considerations An important consideration for the patient diagnosed with PID is the concern for the presence of a TOA, which is the most serious acute complication of PID. Studies suggest that the prevalence of TOA among hospitalized patients may approach 20%, and that it is difficult to assess clinically whether or not a patient has a TOA.18-20 Based on these findings, some adolescent experts recommend pelvic ultrasound (the most specific and sensitive test for TOA) for all patients diagnosed with PID. To date, there are no clear guidelines to indicate which patients are at highest risk of TOA. A review of the literature suggests that, at a minimum, ultrasound should be obtained on patients in whom other diagnoses cannot be excluded (such as appendicitis), patients who are ill appearing or have elevated inflammatory markers, or patients who are not responding to therapy. Decisions about imaging should be based on the individual patient, and should take into account the patient’s ability to follow up with a health care provider within a few days.

Chapter 70 — Sexually Transmitted Infections

Perihepatitis (Fitz-Hugh–Curtis syndrome) is another complication of salpingitis. Signs and symptoms include right upper quadrant pain and tenderness, fever, nausea, and vomiting. Signs and symptoms of salpingitis are usually present, but not in all cases. The ED physician should remember to keep PID on the differential diagnosis list of any adolescent female presenting with abdominal pain; it is important to treat mild disease, so therapy should be instituted even if the diagnosis is not certain. One common misperception is that patients with cervicitis (discussed later) can have abdominal pain; this is generally not the case, so if a patient with vaginal discharge also has abdominal pain that is not explained by an additional diagnosis, the patient should be treated for PID rather than cervicitis. Other complications of PID include ectopic pregnancy, infertility, recurrent and chronic PID, chronic abdominal pain, and pelvic adhesions. Management Any patient meeting the minimum criteria for the diagnosis of PID (see Table 70–1), if no other diagnosis is apparent, should be treated empirically (Table 70–2). Up-to-date treatment recommendations can be found on the CDC website (http://www.cdc.gov/STD/). Of note, single-dose therapy of azithromycin has not been shown to be adequate treatment for PID.3 The decision about whether or not to admit a patient for inpatient therapy can be difficult. The CDC recommends inpatient treatment for patients in whom surgical emergen-

Table 70–2

Treatment of Pelvic Inflammatory Disease

Parenteral Regimen A* Cefotetan 2 g IV q12h or Cefoxitin 2 g IV q6h Plus Doxycycline 100 mg orally q12h Parenteral Regimen B Clindamycin 900 mg IV q8h Plus Gentamicin loading dose IV or IM (2 mg/kg) followed by a maintenance dose (1.5 mg/kg) q8h

Outpatient Regimen A Ofloxacin† 400 mg orally bid × 14 days or Levofloxacin† 500 mg orally qd × 14 days With or without Metronidazole 500 mg orally bid × 14 days Outpatient Regimen B Ceftriaxone 250 mg IM once or Cefoxitin 2 g IM once and probenecid 1 g orally once Plus Doxycycline 100 mg orally bid × 14 days With or without Metronidazole 500 mg orally bid × 14 days

*Parenteral therapy can be discontinued 24 hours after clinical improvement, and the patient should complete a 14-day course of doxycycline (100 mg twice daily). When tubo-ovarian abscess is present, clindamycin or metronidazole is used with doxycyline to provide more effective anaerobic coverage. † Fluoroquinolones are not recommended for use in patients younger than 18 years old; however, no joint damage has been observed in patients treated with prolonged courses of ciprofloxacin, so the CDC has stated that children who weigh more than 45 kg can be treated with any regimen. Abbreviations: IM, intramuscularly; IV, intravenously. From Centers for Disease Control and Prevention: Sexually transmitted diseases treatment guidelines—2006. MMWR Recomm Rep 55(RR-11):1–100, 2006.

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cies cannot be excluded; for pregnant patients; for patients not responding to oral therapy or who are unable to follow or tolerate an outpatient oral regimen; for patients with severe illness, nausea and vomiting, or high fever; and for patients with TOA. In addition, many adolescent experts recommend hospitalizing patients who are 14 years old or younger and patients for whom follow-up within 72 hours cannot be arranged. One randomized, controlled trial comparing inpatient to outpatient therapy for mild to moderate PID has been performed,21 which concluded that there was no difference in reproductive outcomes between women treated as inpatients compared with those treated as outpatients. However, that trial did not involve many adolescents, making it difficult to generalize the results to that population. Any patient treated as an outpatient should have clinical follow-up 3 days after beginning treatment. For adolescents, who may have issues with particular compliance or access to health care, it is important to ensure that the prescribed regimen will be completed and that follow-up can be arranged. In addition, male sex partners should be treated if they have had sexual contact with the patient within 60 days of the onset of symptoms. Options for partner treatment include self-referral and patient-delivered treatment. When determining the best treatment strategy for the adolescent with PID, it is important to keep issues of confidentiality in mind. Patients under the age of 18 years are able to seek care for treatment of sexually transmitted diseases without parental consent.22 It is important to engage the adolescent in a discussion about disclosing the diagnosis, and, whenever possible, it is helpful to involve the parent in treatment plans in order to improve compliance and follow-up. However, the patient has the right to confidential treatment, although some states allow the physician to notify the patient’s parents.23 If the patient chooses not to inform a parent, it can be helpful to obtain private numbers (such as a cell phone or beeper number) in order to communicate culture results or to follow up the patient’s clinical status. Summary PID is a difficult clinical diagnosis. It is important to consider the diagnosis of PID in any adolescent patient at risk for an STI in whom the minimum clinical criteria are met. All patients diagnosed with PID who are treated on an outpatient basis should have follow-up arranged within 72 hours. Adolescents may require more intensive education and follow-up than adult patients. Therefore, treatment decisions should be individualized and should take into account follow-up options, support systems at home, and the resources available on an outpatient or inpatient basis. Cervicitis Gonorrhea and chlamydia are among the most frequently reported infectious diseases in the United States. In fact, chlamydia is the most commonly reported bacterial STI, with 834,555 cases reported in 200224 ; because patients are often not tested before being treated, and because underreporting remains a problem, the CDC estimates that 2.8 million Americans are infected with chlamydia each year. The CDC estimates that there are approximately 700,000 people newly infected with gonorrhea yearly.25 While both of these infections are often asymptomatic, they can both present with mucopurulent cervicitis (MPC).

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Clinical Presentation MPC is characterized by a purulent endocervical discharge, which is often noted by the patient as a thick vaginal discharge. Patients with uncomplicated lower genital tract infection will not have abdominal pain or adnexal or cervical motion tenderness; conversely, patients who present only with vaginal discharge may have subclinical upper genital tract infection.26,27 Patients may complain of dyspareunia or postcoital spotting. Differential diagnoses to consider for the patient presenting with vaginal discharge include vaginitis (described later); cervicitis due to organisms other than N. gonorrhoeae and C. trachomatis, such as Candida species or herpes simplex virus; foreign body; and physiologic discharge. Laboratory testing for patients with vaginal discharge should include testing for N. gonorrhoeae and C. trachomatis. As mentioned earlier, vaginal swab–based and urine-based tests are sensitive and specific, and may obviate the need for a speculum examination in the adolescent patient. Additional testing includes vaginal swabs for Gram stain and wet preparation, as described previously. Recent studies suggest that women with vaginal polymorphonuclear cells (PMNs) noted on examination of their vaginal discharge are more likely to have subclinical PID; therefore, the finding of many PMNs on Gram stain may alter treatment.26,27 However, there are no clear guidelines as to whether or not these women need to be treated similarly to patients with clinical PID. The diagnosis of cervicitis is fairly straightforward, and should be considered in any patient with an abnormal vaginal discharge. Although it can be difficult to distinguish with certainty between cervicitis and vaginitis without a speculum examination, because most etiologies of vaginitis can be diagnosed quickly with laboratory tests (as described later) the clinician can usually determine which patients are likely to benefit from empirical treatment for infection with N. gonorrhoeae and C. trachomatis. In many cases of MPC, neither organism is identified. Other infections in females caused by N. gonorrhoeae include urethritis, which is characterized by dysuria, urinary frequency, exudate from the urethra or periurethral glands, and suprapubic pain; bartholinitis and bartholin gland abscess; pharyngitis, which usually resolves spontaneously; rectal infection; conjunctivitis; and otitis externa. Although pharyngeal infection is generally self-limited, patients should be treated to limit the spread of the organism and to limit the possibility of dissemination.28 Patients with gonorrheal infection can also develop disseminated disease, characterized by arthritis/arthralgia, tenosynovitis, and dermatitis. Other sites of disseminated disease include perihepatitis, meningitis, myopericarditis, endocarditis, osteomyelitis, and pneumonia. C. trachomatis can also cause urethritis, which is often asymptomatic but can be associated with dysuria. Newborns of infected mothers are at risk for ophthalmia neonatorum, scalp abscess at the site of fetal monitors, rhinitis, pneumonia, and anorectal infections. Management The CDC recommends that patients suspected of being infected with N. gonorrhoeae and C. trachomatis should be treated empirically if the prevalence of these infections is high in the patient population, and if the patient might be difficult to locate for treatment after test results are available.

Table 70–3

Treatment of Cervicitis

Chlamydial Infection

Gonococcal Infection

Azithromycin 1 g orally once or Doxycycline 100 mg orally bid × 7 days

Cefixime 400 mg orally once or Ceftriaxone 125 mg intramuscularly once or Ofloxacin 400 mg orally once or Levofloxacin 250 mg orally once Treatment for chlamydia if chlamydia infection not ruled out

Erythromycin base 500 mg orally qid × 7 days Erythromycin ethylsuccinate 800 mg orally qid × 7 days Ofloxacin* 300 mg orally bid × 7 days Levofloxacin* 500 mg orally qd × 7 days

*For quinolones, children who weigh more than 45 kg can be treated with any regimen recommended for adults. From Centers for Disease Control and Prevention: Sexually transmitted diseases treatment guidelines—2006. MMWR Recomm Rep 55(RR-11):1–100, 2006.

For most adolescents, empirical treatment is warranted because of the difficulty with locating teenagers after an ED visit combined with potential problems with maintaining confidentiality once the patient has left the ED. Patients should be treated for both gonorrhea and chlamydia infections (Table 70–3). For chlamydial infection, single-dose azithromycin therapy has been shown in randomized, controlled trials to be equally efficacious when compared with 7 days of doxycycline.29 Although treatment with azithromycin is more expensive, this should be weighed against the benefit of providing complete treatment during the ED visit. Ofloxacin is also efficacious, but is not recommended as first-line therapy because of increased cost. Although erythromycin is an alternative treatment, it is not as effective as the others and the gastrointestinal side effects can affect compliance. In order to maximize compliance, particularly with the adolescent population, it can be useful to dispense the entire treatment course at the time of the ED visit and to observe the first dose. All sex partners within 60 days should be treated, and the most recent sex partner should be evaluated even if the most recent contact was more than 60 days prior to the patient’s presentation. Patients should abstain from sexual intercourse until 7 days after the onset of treatment. Currently, there is no need for a patient to be retested once therapy is complete. For pregnant patients, azithromycin is thought to be safe and effective. The preferred treatment for gonococcal infection is ceftriaxone.30 Strains of N. gonorrhoeae resistant to quinolones are becoming more common. In fact, the CDC recommends that patients with gonorrhea who live in Hawaii and California not be treated with a quinolone; in addition, there have been recent increases in fluoroquinolone-resistant gonococci in Massachusetts, Michigan, New York City, and Seattle.31 In areas where resistance is a concern, ceftriaxone should be used as primary therapy. With the exception of cefi xime, which at present is available sporadically and only as an oral suspension, other oral cephalosporin regimens have not been shown to be effective for the treatment of N. gonorrhoeae. Similarly, a 1-g dose of azithromycin is also not effective;

Chapter 70 — Sexually Transmitted Infections

although a 2-g dose of azithromycin is effective, due to cost and a high frequency of gastrointestinal side effects it is also not a recommended treatment.3 Pregnant patients can be treated with ceftriaxone or spectinomycin intramuscularly (a single 2-g dose). Patients with isolated cervicitis can be treated as outpatients, with follow-up within 5 to 7 days to assess for resolution of symptoms. Patients being treated for cervicitis should be counseled about the signs and symptoms of PID. In addition, patients with persistent symptoms after appropriate therapy should be rescreened for infection, as in most situations this represents a new infection rather than treatment failure. Some experts recommend that adolescents be screened every 3 to 4 months, even if asymptomatic, because of the risk of acquiring a new chlamydia infection. For the treatment of sex partners, one study suggests that patientdelivered treatment is comparable to self-referral, and so should be considered for some patients.32 Vaginitis The three most common infectious causes of vaginitis are Candida albicans, Trichomonas vaginalis, and bacterial vaginosis (BV). Herpes simplex virus can also cause vaginitis; it is discussed in detail later. It is estimated that up to 75% of women will experience at least one episode of vulvovaginal candidiasis (VVC) in their lifetimes.33 Patients at particularly high risk include pregnant women, patients using corticosteroids or broad-spectrum antibiotics, and patients with diabetes mellitus. Although VVC is generally due to overgrowth of a patient’s own organisms, the infection can be sexually transmitted. Approximately 15% of asymptomatic women may harbor Candida species during their reproductive years.34 T. vaginalis is the most common treatable STI. The CDC estimates there are approximately 7.4 million new cases of trichomoniasis diagnosed each year in women and men.35 Women can contract trichomoniasis from penis-vagina contact or from vulva-vulva contact; men usually contract trichomoniasis from infected women.36

Table 70–4

547

BV is the most common cause of vaginal discharge in women of childbearing age, and is diagnosed in approximately 15% of pregnant women in the United States.37 The infection is characterized by an overgrowth of predominantly anaerobic organisms (Gardnerella vaginalis, Mycoplasma hominis, and Prevotella and Mobiluncus species), which replace the normal lactobacilli and increase the vaginal pH from less than 4.5 to as high as 7.0. It is more common in black women, in those who smoke, and in those who use intrauterine devices. Although sexual activity, particularly with multiple partners, is a risk factor for BV, it is unclear what role sexual activity plays in acquiring the infection. Studies suggest that exposure to a new sexual partner is a more important risk factor than frequency of sexual encounters38,39 ; however, questions remain about the role of sexual activity in the acquisition of BV, particularly because partner treatment shows no benefit. It is thought that frequent episodes of BV are more likely to be relapsed infections rather than reinfection.39 Clinical Presentation Women with vaginitis generally present with some combination of vulvar irritation and itching, edema or erythema of the genitalia, and excessive or malodorous vaginal discharge. VVC, trichomoniasis, and BV all have specific clinical characteristics that can help narrow the differential diagnosis and guide laboratory evaluation (Table 70–4). Thick, curdy discharge, the classic description of vaginal discharge caused by VVC, is a specific but not very sensitive finding.33 The classic frothy yellow discharge occurs in approximately 10% to 30% of women with Trichomonas.36 Studies suggest that trichomoniasis infection is generally not associated with lower abdominal pain and dysuria.40 BV is asymptomatic in up to 50% of infected women; symptomatic women generally present with a homogeneous white discharge without signs of inflammation.37 Adolescents presenting with an abnormal vaginal discharge should have a Gram stain of the vaginal discharge as

Common Causes of Vaginitis

Etiology

Vulvovaginal Candidiasis

Trichomoniasis

Bacterial Vaginosis

Symptoms/Signs

Vulvar itching and soreness Vaginal discharge Superficial dyspareunia Vulvar erythema, edema Fissures, excoriations Satellite lesions Saline microscopy 10% KOH microscopy Gram stain Culture if previously treated, question about species Fluconazole 150 mg orally once (not in pregnant patients) or Multiple topical azoles; 1-, 3-, and 7-day treatment options

Yellow or purulent vaginal discharge Vulvar itching Vulvar erythema Vaginal erythema

Vaginal discharge No signs of inflammation

Saline microscopy Rapid test (some labs) Culture pH > 4.5

No, unless partner symptomatic

Yes

Amsel criteria (at least 3) • homogeneous, white d/c • clue cells • fishy odor with 10% KOH • pH > 4.5 Metronidazole 500 mg orally bid × 7 days or Metronidazole gel 0.75%, one full applicator (5 g) intravaginally qd × 5 days or Clindamycin cream 2%, one full applicator (5 g) intravaginally at bedtime for 7 days No

Diagnosis

Treatment

Partner Treatment

Metronidazole 2 g once or Metronidazole 500 mg bid × 7 days

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well as microscopy to help distinguish between the likely causative agents. Symptoms alone should not be used to guide therapy.41 Gram stain has a sensitivity of 65% for detecting pseudohyphae; microscopy with 10% potassium hydroxide (KOH) has a sensitivity of 70%.34 Of note, KOH is toxic to T. vaginalis, so additional microscopy with saline is necessary to detect trichomonads. The saline wet preparation has a sensitivity of 60% to 80% for detecting trichomoniasis. The use of spun urine can improve the detection of T. vaginalis in patients with suspected trichomoniasis who have negative wet preparations,42 and some laboratories can perform a rapid nucleic acid detection test. If necessary, culture for T. vaginalis can be performed, which has a sensitivity of approximately 95%.36 Determining the pH of the vaginal fluid can also be helpful, as both trichomoniasis and BV are associated with a pH greater than 4.5. Culture of vaginal discharge is generally not helpful, with the exception of cases of recurrent VVC or to definitively diagnose a suspected case of trichomoniasis in the setting of a negative wet preparation. BV can be diagnosed using clinical criteria (proposed by Amsel et al.)43 or by Gram stain (using a scoring system introduced by Nugent et al.).44 The two diagnostic methods have been shown to be relatively similar; in a multicenter study comparing Gram stains of vaginal smears to the standard criteria of Amsel et al. for the diagnosis of BV, the sensitivity of the Gram stain method was 89%, with a specificity of 83%.45 Although the Gram stain method is more objective, the clinical criteria are more practical in many settings. The clinical criteria require three of the following: (1) a homogeneous, white, noninflammatory discharge that smoothly coats the vaginal walls, (2) the presence of clue cells on microscopic examination (clue cells are irregularly bordered squamous epithelial cells whose cell outlines are obliterated by sheets of small bacteria; they are seen in saline, not KOH, preparations), (3) a vaginal fluid pH of greater than 4.5, and (4) a fishy odor of vaginal discharge before or after addition of 10% KOH. Definitive diagnosis can be made by Gram stain demonstrating few or no lactobacilli with a predominance of Gardnerella vaginalis plus other organisms resembling gram-negative Bacteroides species, anaerobic gram-positive cocci, or curved rods. The differential diagnosis for patients with vaginitis includes urinary tract infection and cervicitis, as well as noninfectious irritation of the vulva (e.g., mechanical, chemical, or allergic). In patients at risk for an STI who are diagnosed with vaginitis, it is important to consider concomitant treatment for cervicitis after specimens are sent for N. gonorrhoeae and C. trachomatis. If these specimens can be obtained without a speculum examination (i.e., urine or vaginal swab), there is generally no indication for a speculum examination in adolescents with vaginitis.46 Important Clinical Features and Considerations It is important to consider the diagnosis of VVC in any patient with vaginal discharge and irritation, even if the discharge is not described as the “classic” thick, curdy discharge. Patients who have four or more episodes of VVC a year are defined as having recurrent VVC; the pathogenesis of this is not well understood, and most women with recurrent VVC do not have an apparent predisposing condition. Vaginal cultures should be obtained in these patients to identify unusual

species.3,34 Patients can also present with severe VVC, characterized by extensive vulvar erythema, edema, excoriation, and fissure formation.3 VVC during pregnancy is associated with an increased risk of neonatal oral thrush. Other potential complications of vaginitis include recurrent infections as well as pregnancy-related complications, such as chorioamnionitis, particularly with trichomonas and BV. BV is also associated with premature rupture of membranes, preterm labor, and postpartum endometritis. Finally, BV is associated with an increased risk of infection with N. gonorrhoeae and C. trachomatis, as well as upper genital tract infection.47,48 Patients who are at risk for an STI can present with more than one infection, so all causes of vaginitis should be considered for every sexually active adolescent. It is possible for patients to be diagnosed with any combination of VVC, trichomoniasis, and BV; therefore, regardless of the characteristics of the vaginal discharge, laboratory evaluation for all three infections should be included as standard workup for the sexually active adolescent presenting with vaginal discharge. Management Patients with VVC can be treated either orally, with a single dose of fluconazole,49 or with a variety of topical azole therapies (see Table 70–4). For patients with recurrent VVC, although each individual episode usually responds well to short-term azole therapy, experts generally recommend a longer course of topical therapy (7 to 14 days) or, if treating orally, repeating a 150-mg dose of fluconozole on day 3. Patients with recurrent VVC benefit from suppressive maintenance therapy, which is usually continued for 6 months. Similarly, patients with severe VVC should also be treated with a 7- to 14-day course of topical therapy or two doses of oral fluconazole, 72 hours apart. Infection with T. vaginalis is treated with metronidazole, either as a single dose or a 7-day course. Because of compliance issues, most adolescents should be treated with the single dose. Metronidazole gel is not recommended because, as a topical preparation, it is unlikely to achieve therapeutic levels in the urethra or perivaginal glands.3 Some strains of T. vaginalis have decreased susceptibility to metronidazole; however, these strains usually respond to higher doses, so patients who remain symptomatic after either regimen should be treated with 500 mg twice a day for 7 days. A third course of antibiotics, using 2 g daily for 3 to 5 days, can also be used. If the patient remains symptomatic after three courses of metronidazole, the CDC recommends consultation with a specialist; CDC specialists can be reached by telephone (770-488-4115). All women with symptomatic BV should be treated, with the goal of relieving vaginal symptoms and signs of infection and to reduce the risk for other infections, such as human immunodeficiency virus (HIV) and PID.38 In the pregnant patient, treatment of BV is particularly important. Recommended treatment for BV is with oral metronidazole for 7 days, intravaginal metronidazole gel, or intravaginal clindamycin cream; the clindamycin cream is thought to be less effective than the metronidazole regimens. Other alternative treatments include metronidazole in a single 2-g dose and oral clindamycin for 7 days; these regimens are also less effective than the other metronidazole regimens. Intravaginal preparations are not recommended for pregnant patients.

Chapter 70 — Sexually Transmitted Infections

Patients with isolated vaginitis generally do very well with appropriate therapy. Follow-up for uncomplicated VVC, trichomonas, and BV is unnecessary for patients unless symptoms persist. Nucleic acid amplification tests are under development for Trichomonas, which may in the future aid in diagnosis. BV is a difficult diagnosis, particularly in the acute care setting; if uncertainty about the diagnosis exists and the patient is not pregnant, it is appropriate to arrange follow-up without providing treatment. Genital Ulcers Herpes Genitalis Genital herpes, caused by either herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2), is the second most prevalent STD in the United States, affecting at least 50 million people.50 HSV-2 is believed to be the most common cause of genital herpes, although recent studies suggest that HSV-1 may account for more than the 30% of infections previously attributed to HSV-2, particularly in certain populations. Specifically, sexually acquired HSV-1 is more common in younger age groups, in women, and in men who have sex with men.51 The two strains of herpesvirus have very different natural histories, so determining the particular type of infection can be important for treatment and counseling.52 HSV initially causes epithelial infection, and then establishes latency in sacral neuronal ganglia. Once latency is established, there is no cure for the disease, and reactivation of the virus causes recurrent disease. CLINICAL PRESENTATION

Patients with either type of HSV usually present with multiple painful 1- to 2-mm vesicles on an erythematous base. The eruption of ulcers is often preceded by paresthesias or burning sensations in the genital area. The early lesions then erode to become shallow ulcers, and may coalesce. Patients are at risk for secondary infection as well. Primary infections tend to be more severe than recurrences, and patients with a primary infection can also present with systemic symptoms such as fever, malaise, and myalgias. In addition, patients may complain of dysuria, urinary retention, and dyspareunia. Systemic symptoms peak within 3 to 4 days and then improve; pain and irritation are maximal between days 7 and 11, and lesions can persist for about 2 weeks. The total duration of a primary episode, including healing, is about 3 weeks. In contrast, recurrent infections generally present with fewer lesions that are smaller in size, with a total duration from onset to resolution of about 1 week. After the first year, recurrences tend to decrease in frequency, and recurrence of disease caused by HSV-1 is much less common than recurrence of disease caused by HSV-2. In fact, some studies suggest that the recurrence rate of HSV-1 is just 20% of the rate of HSV-2, and that recurrence after the first year with HSV-1 is very uncommon.52 The differential diagnosis of patients presenting with genital ulcers includes early syphilis, chancroid, lymphogranuloma venereum (LGV), contact dermatitis, molluscum contagiosum, and genital lesions of Behçet’s syndrome. Because the prognoses for infection with HSV-1 and HSV2 differ dramatically, most experts recommend testing both to confirm the diagnosis of herpes genitalis and to identify the viral serotype. Multiple testing strategies for HSV exist.53,54

549

Isolation of HSV in cell culture is the preferred test, although the sensitivity of culture declines as lesions begin to heal. A culture specimen can be obtained when intact vesicles are present by aspirating the vesicle fluid using a fine-gauge needle, or unroofing a vesicle and swabbing the fluid using a cotton or Dacron swab. If pustules are present, a specimen can be obtained by unroofing the pustule, washing away purulent material with sterile saline, and swabbing the base of the lesion. For ruptured vesicles or ulcers, or for crusted lesions, a specimen can be obtained by washing away any necrotic material with sterile saline and swabbing the base of the lesion. Cervical Papanicolaou smears and Tzanck tests of genital lesions are both insensitive (30% to 70%) and nonspecific, and so should not be used routinely. Immunfluoresence techniques can differentiate between the two serotypes, and are very sensitive and specific, and rapid. Because of the possibility of false-positive tests, repeat or confirmatory testing (with an immunoblot assay) may be indicated in some patients.53 Although the classic presentation of herpes genitalis is unmistakable, many patients present with less classic symptoms. Therefore, it is important to consider other causes of genital ulcers in most patients. Complications of infection with HSV include significant psychological distress; local complications such as secondary bacterial infection, phimosis, labial adhesions, urinary retention, and constipation; proctitis, particularly in men who have sex with men; herpes keratitis; and encephalitis and meningitis. Furthermore, infants born to women with genital herpes infection are at risk for neonatal infection. MANAGEMENT

Sitz baths or tap water compresses can provide some symptomatic relief, and petroleum jelly may also relieve some discomfort from crusting and fissuring. Three systemic antiviral medications have been shown in randomized, controlled trials to provide clinical benefit for first clinical episodes, for recurrent episodes, and as suppressive therapy: acyclovir, valacyclovir, and famciclovir.55-58 Topical antiviral therapy has little proven benefit and is not recommended.3 For the first clinical episode, antivirals used within 6 days of the onset of lesions have been shown to shorten viral shedding by 10 days, to dramatically reduce the number of new lesions, to decrease pain by about 25%, and to reduce time to healing by 4 to 9 days. Episodic therapy for recurrences reduces viral shedding and healing time by about 1 day; a more dramatic effect in healing time has been noted when patients initiate therapy early in the recurrence. In order to be effective, therapy should begin within 1 day of lesion onset. Suppressive therapy can reduce the frequency of recurrent infections by more than 75% in patients with six or more recurrences per year.59,60 All three medications have an excellent safety profi le and are well tolerated. For patients with severe disease or complications that require hospitalization, such as disseminated infection, pneumonitis, hepatitis, encephalitis, or meningitis, intravenous acyclovir should be used3 (Table 70–5). The safety of systemic acyclovir, valacyclovir, and famciclovir therapy in pregnant patients has not been well established, although studies suggest that there is not an increased risk for major birth defects compared with the general population for women exposed to acyclovir during the first

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Table 70–5

Treatment for Herpes Genitalis

First Clinical Episode Treat for 7–10 days, longer if healing incomplete Recurrent Episodes Treat for 5 days, unless using valacyclovir 500 mg orally twice a day; then 3 days is sufficient Suppressive Therapy Valacyclovir 500 mg regimen may be less effective than the other regimens in patients with ≥10 episodes per year

Acyclovir 400 mg orally tid or Acyclovir 200 mg orally 5 times a day or Famciclovir 250 mg orally tid or Valacyclovir 1 g orally bid Acyclovir 400 mg orally tid or Acyclovir 200 mg orally 5 times a day or Acyclovir 800 mg orally bid or Famciclovir 125 mg orally bid or Valacyclovir 500 mg orally bid or Valacyclovir 1 g orally qd Acyclovir 400 mg orally bid or Famciclovir 250 mg orally bid or Valacyclovir 500 mg orally qd or Valacyclovir 1 g orally qd

From Centers for Disease Control and Prevention: Sexually transmitted diseases treatment guidelines—2006. MMWR Recomm Rep 55(RR-11):1–100, 2006.

trimester. Some experts recommend acyclovir therapy, particularly late in pregnancy, in order to reduce the risk of recurrences. Approximately 90% of patients with HSV-2 will experience at least one recurrence; up to 40% can have at least six recurrences in the first year. Recurrence with HSV-1 infection is much less likely. Patients should refrain from sexual intercourse until the lesions are healed, and should be counseled that transmission can occur even in the absence of symptoms. Counseling about the disease is an important aspect of treatment, although many patients benefit more from counseling once the acute episode has resolved. The CDC has a National STD/HIV Hotline (800-227-8922), and a useful website is http://www.ashastd.org. Follow-up in 1 week is recommended, particularly to reinforce the implications of the diagnosis and to address psychological concerns. Vaccines for HSV are currently under development.61 Syphilis Syphilis, a systemic disease caused by Treponema pallidum, is becoming much less common in the United States, due at least in part to the fact that in 1998 the CDC launched a national plan to eliminate the disease. However, despite an 80% decrease in the number of cases of syphilis reported to the CDC since 1990, syphilis continues to be among the top 10 reportable diseases, and in 2000 affected almost 6000 people.62 In adolescents, syphilis is more common among females. The disease in adolescents has been linked to cocaine use and drug-related sexual behavior. Real and perceived barriers to health care access likely also contribute to the rate of syphilis in this population due to delayed treatment and prolonged infectivity.63 CLINICAL PRESENTATION

Syphilis can be divided into three stages: primary, secondary, and tertiary. In addition, latent infections (which can be early or late) are detected by serology in the absence of clinical symptoms. Primary syphilis presents with an ulcer or chancre at the infection site. The site of infection is usually the ano-

genital area or the mouth; breasts and fingers are less common sites. In fact, 95% of chancres are located on the external genitalia. Single lesions are common, but multiple lesions do occur; lesions that touch each other across folds of skin are referred to as “kissing lesions.” The chancre is usually 1 to 2 cm in diameter, and begins as a painless papule that erodes into an indurated, painless ulcer. Regional firm, nontender lymphadenopathy can accompany the lesion. Secondary syphilis develops about 4 to 10 weeks after the chancre, and is characterized most commonly by a general skin eruption with a predilection for the palms and soles. The eruption involves mucous membranes, is bilateral and symmetric, and tends to follow lines of cleavage. Individual lesions are sharply demarcated, up to 2 cm in diameter, and have a reddish brown hue. The rash is usually macular, papular, or papulosquamous; vesicular and pustular rashes are rare. The eruption may last anywhere from several weeks to up to a year. Other manifestations of secondary syphilis include general or regional lymphadenopathy (nonpainful, rubbery, discrete nodes) and a flulike syndrome, most often with sore throat and malaise but also with headaches, lacrimation, nasal discharge, arthralgias, weight loss, and fever. Other rare manifestations of secondary syphilis include syphilis alopecia (moth-eaten appearance of the scalp and eyebrows), arthritis or bursitis, hepatitis, iritis and anterior uveitis, and glomerulonephritis. Tertiary syphilis, which occurs 2 to 10 years after initial exposure in untreated patients, is rare in adolescents. Tertiary syphilis presents with cardiovascular symptoms (usually 10 to 30 years after exposure) and with gummas, which are granulomatous lesions that involve skin, soft tissue, viscera, or bones. The lesions are few in number, asymmetric, and not contagious. Neurosyphilis is also rare in adolescents; most cases in this age group are asymptomatic or present as acute syphilitic meningitis. Acute syphilitic meningitis has signs and symptoms similar to those of other causes of acute meningitis, including fever, headache, photophobia, and meningismus. Cranial nerve palsies are present in about 40% of cases. DIAGNOSIS

The differential diagnosis of primary syphilis includes sexually transmitted causes of genital ulcers, such as herpes, chancroid, and LGV, as well as non–sexually transmitted causes of ulcers, including traumatic lesions, fi xed drug reaction, Candida, Behçet’s syndrome, psoriasis, lichen planus, and erythema multiforme. Also in the differential diagnosis is cancer, which is very rare in adolescents. Other etiologies with presentations similar to secondary syphilis include pityriasis rosea, drug eruptions, tinea versicolor, lupus erythematosus, scabies, pediculosis, rosacea, infectious mononucleosis, and condyloma acuminatum. Although the clinical history and appearance of the lesions can often distinguish these etiologies, serology tests for syphilis should be performed if there is any doubt about the diagnosis. Darkfield microscopic examination and direct fluorescent antibody (DFA) tests of lesion exudate or tissue are the definitive methods for diagnosing primary syphilis, according to the CDC. Darkfield examination is simple and fairly reliable, with a sensitivity of 73% to 79%.64 Some experts recommend repeating the examination on 3 separate days before determining that the test is negative. Failure to detect the organ-

Chapter 70 — Sexually Transmitted Infections

ism using this technique does not ensure that the patient does not have syphilis; in addition, technical factors, such as too little or too much fluid on the slide, can affect the results. Darkfield microscopy should not be performed on samples of lesions on the mouth or anus, areas where nonpathogenic treponemes are often present. DFA is performed at some reference laboratories and some state health departments, and has a slightly better sensitivity than darkfield microscopy (73% to 100%).64 A presumptive diagnosis of syphilis can be made using two types of serologic tests: (1) nontreponemal tests, including the Venereal Disease Research Laboratory (VDRL) and the rapid plasma reagin (RPR) tests; and (2) treponemal tests, including the fluorescent treponemal antibody, absorbed (FTA-Abs) and the T. palladium particle agglutination (TPPA) tests.64,65 Nontreponemal tests are used for screening and to monitor therapy. The VDRL is the test of choice for evaluating for neurosyphilis, and has a slightly higher specificity when compared to the RPR (96% to 99% compared to 93% to 99%), resulting in fewer false-positive tests. However, the RPR has a slightly better sensitivity (86% compared to 78% for primary syphilis), and so is most often used for screening. Both tests have 100% sensitivity for secondary syphilis; the RPR is slightly more sensitive than the VDRL for detecting tertiary syphilis (73% vs. 71%) and latent syphilis (98% vs. 95%). Many disorders can result in false-positive nontreponemal tests, including acute infections (such as viral infections, chlamydial infections, Lyme disease, Mycoplasma infections, and nonsyphilitic spirochetal infections), autoimmune diseases, narcotic addiction, sarcoidosis, lymphoma, cirrhosis, and aging. Therefore, all positive nontreponemal tests need to be confirmed with a treponemal test. Presumptive diagnosis of primary or secondary syphilis can be made based on a positive nontreponemal test with a titer of at least 1:8 (for primary syphilis) or a titer that rises more than two dilutions, combined with a positive treponemal test. Adolescents with a positive darkfield examination should be treated, as well as adolescents with a typical lesion and a positive serologic test. Routine lumbar puncture is not indicated for patients with primary syphilis; this test should be limited to patients with clinical signs and symptoms of neurologic involvement. Adolescents suspected of having secondary syphilis who have atypical findings or a nontreponemal titer of less than 1:16 should have a second nontreponemal test and a treponemal test performed. The titer results of an RPR and a VDRL cannot be compared. The diagnosis of neurosyphilis can be difficult, because although the cerebrospinal fluid (CSF) VDRL is highly specific, it is somewhat insensitive (60% to 70%).3,64 Other laboratory findings in neurosyphilis include an elevated CSF leukocyte count (>5 WBCs/mm3) and increased CSF protein. The CSF FTA-Abs is less specific than the CSF VDRL, but is much more sensitive; some experts believe that a negative CSF FTA-Abs excludes neurosyphilis. In addition to patients with neurologic symptoms, evaluation for neurosyphilis should be performed in patients with ophthalmologic symptoms (e.g., uveitis), in patients who have treatment failure, in patients who have serum nontreponemal test titers of ≥1:32 unless disease duration is known to be less than 1 year, and in patients in whom nonpenicillin therapy is planned, unless disease duration is known to be less than 1 year.

551

If latent syphilis is a concern, both an RPR/VDRL and an FTA-Abs test should be performed, because the nontreponemal tests have a sensitivity of about 70%. The adolescent should be treated if the FTA-Abs is positive and there is no documentation of prior treatment. The diagnosis of syphilis should be considered in any sexually active patient with a genital ulcer or a generalized rash. The clinical presentation of syphilis can manifest in many different ways, and can mimic other diagnoses such as pityriasis rosea. One of the most difficult aspects of diagnosing syphilis is interpreting the various serologic tests. As mentioned earlier, many other disorders can result in a falsepositive nontreponemal test. False-negative nontreponemal tests can occur in early or late syphilis. False-negative and false-positive treponemal tests are rare. However, both types of tests can be negative if sexual contact with an infected individual occurred within the preceding 90 days. Most treated patients continue to have positive treponemal tests for life; persistently positive nontreponemal tests usually indicate inadequately treated disease. The complications of syphilis, which result from untreated early disease, can be prevented with timely therapy. MANAGEMENT

The treatment of choice for syphilis is penicillin G, administered parenterally (Table 70–6). Penicillin is the only proven therapy for neurosyphilis and syphilis during pregnancy. Penicillin-allergic patients in these categories should undergo desensitization prior to treatment. Although there are some data indicating that oral azithromycin may prove to be an effective therapy, currently that drug is not recommended.66 The Jarisch-Herxheimer reaction occurs within 2 hours after treatment in 50% of patients with primary syphilis, 90% of patients with secondary syphilis, and 25% of patients with early latent syphilis. Fever and chills, myalgias, headache, elevated neutrophil count, and tachycardia characterize the reaction. The symptoms last 12 to 24 hours, and treatment is reassurance, bed rest, and antipyretics. The reaction can produce uterine contractions in pregnant women; however, this is not a contraindication to treatment.3 Syphilis is spread from person to person only when mucocutaneous lesions are present, which are rare after 1 year of infection. However, anyone who has been exposed sexually to a patient with syphilis should be evaluated. Patients exposed to someone with primary, secondary, or latent syphilis within the last 90 days should be treated presumptively; if exposure occurred more than 90 days ago but follow-up is uncertain, the patient should also be treated presumptively. For the purposes of partner notification and presumptive treatment, patients with syphilis of unknown duration who have high nontreponemal serologic test titers (i.e., at least 1:32) can be considered to have early syphilis. However, the titer should not be used to differentiate early from late latent syphilis for the purposes of treatment. Long-term sex partners of patients with latent syphilis should be evaluated clinically and serologically; treatment can be based on the results of this evaluation. Adolescents diagnosed with syphilis require close followup to monitor the results of therapy. Some experts recommend HIV testing for all patients diagnosed with syphilis. Consultation with an infectious disease expert should be considered.

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Table 70–6

Treatment for Syphilis Primary/Secondary

Early Latent

Late Latent

Tertiary

Neurosyphilis

Recommended

Benzathine PCN G 2.4 million units IM once

Benzathine PCN G 2.4 million units IM once

Benzathine PCN G 2.4 million units IM weekly × 3 doses

Benzathine PCN G 2.4 million units IM weekly × 3 doses

Possible alternatives (nonpregnant patients)

Doxycycline 100 mg orally bid × 14 days or Tetracycline 500 mg qid × 14 days

Doxycycline 100 mg orally bid × 14 days or Tetracycline 500 mg qid × 14 days

Potentially effective (close followup necessary)

Ceftriaxone 1 g qd IM or IV × 10 days or Azithromycin 2 g orally once

Doxycycline 100 mg orally bid × 14 days or Tetracycline 500 mg qid × 14 days

Aqueous PCN G 3–4 million units IV q4h × 10–14 days or Procaine PCN 2.4 units IM qd plus probenecid 500 mg orally qid × 10–14 days Ceftriaxone 2 g qd × 10–14 days

Abbreviations: IM, intramuscularly; IV, intravenously; PCN, penicillin. From Centers for Disease Control and Prevention: Sexually transmitted diseases treatment guidelines—2006. MMWR Recomm Rep 55(RR-11):1–100, 2006.

Lymphogranuloma Venereum LGV is rare in the United States; there were 113 known cases in 1997, although this number likely represents a falsely low prevalence due to underreporting and misdiagnosis. LGV is caused by serovars L1, L2, and L3 of C. trachomatis. The peak incidence of the disease is in people ages 15 to 40 years, and males account for about 75% of cases. CLINICAL PRESENTATION

After an incubation period of 3 to 30 days, the primary stage of LGV is characterized by a small, painless papule at the site of the inoculation. The lesion may ulcerate, and is self-limiting. It is often not noticed by the patient. An associated mucopurulent discharge of the urethra or cervix can also be present. The secondary stage occurs several weeks later, and chiefly involves the inguinal lymph nodes; the anus or rectum can also be involved, particularly in women or in men who have sex with men. In women, the deep iliac or perirectal nodes can be involved, which may result in low back pain or abdominal pain. Painful regional adenopathy is the most common manifestation of secondary disease; nodes are typically enlarged and unilateral, and can become infected and develop necrotic abscesses. The characteristic bubo is produced when the lymph nodes become matted and fluctuant. The buboes may rupture in as many as one third of patients, but most buboes heal without problems. Most men present during this phase, but only one third of women do, since women tend not to develop inguinal lymphadenopthy. Patients may also complain of constitutional symptoms such as headache, fever, chills, and myalgias. The third phase is a genitoanorectal syndrome, which is uncommon but occurs more commonly in women who were asymptomatic earlier in the disease.67 Differential diagnosis considerations for a genital-inguinal lesion include syphilis, HSV, chancroid, granuloma inguinale, pyogenic infection, and cat-scratch fever. For patients

with rectal fistulas, inflammatory bowel disease, chronic rectal infections such as gonorrhea and amebiasis, and granuloma inguinale should be considered. The diagnosis of LGV is made serologically and by excluding other causes of inguinal lymphadenopathy or genital ulcers. Clinically, it can be difficult to distinguish LGV from chancroid. It is important to keep LGV in the differential diagnosis for patients presenting with genital ulcers or inguinal adenopathy, particularly if the patient has had sexual contact with a person in or from Asia or Africa, where the disease is much more common. Late-stage disease can be complicated by elephantiasis of the genitalia, rectal strictures, and rectal fissures. MANAGEMENT

The preferred treatment is doxycycline 100 mg orally twice a day for 21 days. Alternatively, erythromycin base, 500 mg orally four times a day for 21 days, can be used. Buboes may require aspiration or incision and drainage to prevent the formation of inguinal/femoral ulcerations. Sexual contacts within 30 days before the onset of the patient’s symptoms should be examined, tested for urethral or cervical chlamydial infection, and treated. Pregnant women should be treated with erythromycin.3,67 Treatment cures the infection and prevents ongoing tissue damage, although scarring can result from tissue reaction. Rectovaginal fistulas, bowel obstruction, and extensive genital destruction require surgical treatment. Patients should be followed clinically until signs and symptoms have resolved. Chancroid Chancroid is a genital ulcer infection caused by Haemophilus ducreyi. It is endemic in some parts of the United States, and occurs in discrete outbreaks as well. In 2000, 78 cases of chancroid were reported to the CDC; like LGV, however,

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chancroid is likely very underreported because of the difficulty of culturing the organism as well as the fact that the diagnosis is not often considered.68 Using new DNA amplification methods, the CDC has identified this infection in cities where it was previously not diagnosed. About 10% of patients in the United States with chancroid are co-infected with T. pallidum or HSV, and chancroid is a cofactor for transmission of HIV.3

diagnosis if initial tests are negative. Patients should be reexamined 3 to 7 days after initiation of therapy; ulcers generally improve symptomatically within 3 days and objectively within 7 days. Sex partners should be examined and treated if they had contact with the patient within the 10 days preceding the onset of symptoms.

CLINICAL PRESENTATION

Human Papillomavirus

After an incubation period of 3 days to 2 weeks, a small inflammatory papule or pustule develops at the inoculation site. Within days the papule erodes to form a very painful, deep ulceration, usually 3 to 20 mm in diameter, that is soft, friable, and nonindurated. A foul-smelling, yellow-gray exudative covering is usually present, along with surrounding erythema. Men often have a single ulcer, while women often have several. Within several weeks, up to 60% of patients will develop unilateral, painful inguinal lymphadenopathy, which can develop into a suppurative bubo. Fever and malaise may occur. Extragenital sites are rare. Other forms include transient chancroid, which consists of an ulcer that rapidly resolves in less than a week and is followed by suppurative inguinal lymphadenitis; follicular chancroid, which has ulcerations in hair-bearing areas; the dwarf variety, which manifests as one or more herpetiform ulcerations; and giant chancroid, which consists of multiple small ulcerations that rapidly expand and coalesce to form a single large ulceration. A painful ulcer and tender inguinal adenopathy, combined with suppurative inguinal adenopathy, is almost pathognomonic for chancroid.69 The differential diagnosis is similar to that for LGV: herpes genitalis, primary syphilis, Behçet’s syndrome, traumatic lesions, or fi xed drug eruptions. In adolescents, the most common causes of ulcerative lesions are, in descending order, herpes, nonspecific trauma, syphilis, and chancroid. A definitive diagnosis of chancroid can be made using a special culture medium for H. ducreyi; however, this medium is not widely available, and culture has a sensitivity of only 80%.70 A probable diagnosis can be made if all of the following criteria are met69 : (1) the patient has one or more painful genital ulcers, (2) the patient has no laboratory evidence of syphilis at least 7 days after the onset of the ulcers, (3) the clinical presentation is consistent with chancroid, and (4) a test for HSV performed on ulcer exudate is negative. It is important to keep chancroid in the differential for patients with genital ulcers; the diagnosis can be easily missed because it is not very common.

Human papillomavirus (HPV) is the most prevalent STI in the United States among adolescent and young adult women. More than 30 types of HPV can infect the genital tract; most infections are asymptomatic, subclinical, or go unrecognized. HPV types 6 and 11 are the usual etiologies for visible genital warts and can cause respiratory papillomatosis in infants and children, although the risk is less than 0.04%. Major risk factors are related to sexual behavior, and include multiple sex partners, first intercourse within 18 months after menarche, increased frequency of sexual intercourse, and, for men, failure to use a condom.72,73 The relationship between condom use and the acquisition of HPV by women is less clear.

MANAGEMENT

Recommended treatments are azithromycin 1 g orally in a single dose; ceftriaxone 250 mg intramuscularly (IM) in a single dose; ciprofloxacin 500 mg orally twice a day for 3 days; or erythromycin base 500 mg orally three times a day for 7 days. Ciprofloxacin should not be used in pregnant or lactating women.69,71 Treatment cures the infection, leads to resolution of clinical symptoms, and prevents transmission to others. Patients who are uncircumcised or who have HIV infection may not respond as well as other patients to therapy. The CDC recommends that all patients diagnosed with chancroid be tested for HIV, and retested for syphilis and HIV 3 months after the

Genital Growths

CLINICAL PRESENTATION

There are four major types of warts caused by HPV. Condylomata acuminatum is the classic cauliflower-shaped growth with a granular surface. Papular warts are flesh-colored, smooth, dome-shaped papules that are 1 to 4 mm in size. Keratotic warts have a thick, crustlike layer, and resemble common skin warts. Flat-topped warts are macular or slightly raised and are invisible to the naked eye. The lesions occur most commonly on the cervix of women (70%) and the inner surface of the prepuce of men (70%); circumcised males are more likely to have involvement of the shaft of the penis. Other sites include the vulva (25%), the anus (20%), the vagina (10%), and the urethra (5%) for women. Up to 25% of males can have involvement of the urethral meatus. Lesions are usually asymptomatic, but can cause itching, burning, fissuring, pain, or bleeding. The differential diagnosis for HPV includes condylomata lata (secondary syphilis), molluscum contagiosum, granuloma inguinale, seborrheic keratosis, neoplasia, and, in males, pink pearly papules (parallel rows of lesions at the corona of the penis that are normally present in about 15% of the population). In most cases, external genital warts can be diagnosed clinically. If the diagnosis is uncertain, if the lesions do not respond to therapy, or if the disease worsens during therapy, biopsy can be used to confirm the diagnosis. All women with external genital warts should undergo a speculum examination to look for the presence of disease internally. Although genital HPV is sexually transmitted, it is possible to contract external condylomata by autoinoculation or inoculation with HPV from skin warts. In addition, virus can be passed to an infant during delivery. The HPV types that cause skin warts can be transmitted by fomites, and virus has been recovered from sauna benches, underwear, examination gloves, and tanning couches. It is unclear whether or not fomites are an important source of infection for transmission of genital HPV. Any pediatric patient presenting with genital warts should be evaluated for evidence of sexual abuse.

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MANAGEMENT

The primary goal of treating visible warts is symptomatic treatment, although some patients with asymptomatic lesions will want to be treated for cosmetic or psychological reasons. If left untreated, some warts will resolve spontaneously, although there is no way to predict which patients will experience spontaneous resolution. Some patients may choose to wait and see how the lesions progress prior to initiating therapy. Current data suggest that treating warts may reduce infectivity, but probably does not completely eliminate it. There are quite a few acceptable treatment regimens; selection of treatment should be based on the preference of the patient, the available resources, and the experience of the health care provider (Table 70–7). All therapies are cytodestructive, except for topical 5% imiquimod cream and intralesional interferons, which are immunotherapies. Treatments are rarely administered in the ED. Patients should be referred to a gynecologist or primary care physician for definitive therapy. Complications from therapy are rare when the treatments are employed properly. Persistent hypo- or hyperpigmentation is common after ablation. Other complications include depressed or hypertrophic scars or, rarely, chronic pain syndromes. Local inflammatory reactions are common with the use of podofi lox and imiquimod. Pain and sometimes necrosis and blistering can occur after application of liquid nitrogen. Imiquimod, podophyllin, and podofilox should not be used during pregnancy. Patients should be counseled that recurrences, particularly within the first 3 months, might occur. Sex partners of patients with genital warts should be examined, because selfor partner examination has not been evaluated as a diagnostic method, and patients may miss lesions. However, there is no indication for treating in order to prevent future transmission, since the role of treatment in affecting infectivity is unknown. In addition, there is no indication that reinfection plays a role in recurrences. Many young women will become negative for HPV within 24 months of diagnosis.73 There is no evidence that the presence of external genital warts is associated with the development of cervical cancer. Molluscum Contagiosum Molluscum contagiosum is a viral infection that is becoming increasingly common in sexually active adolescents. In ado-

Table 70–7

lescents and adults, molluscum is most commonly transmitted by sexual contact, although it can be transmitted by casual contact, fomites, or self-inoculation.74 In sexually active adolescents, the lesions are commonly seen on the genital and pubic areas. The lesions are firm, flesh-colored, waxy, dome-shaped, globular nodules with central umbilication. There are usually between 1 and 20 lesions between 3 and 7 mm in diameter, which occur in clusters. The lesions are usually asymptomatic, although inflammatory changes can occur. Some patients may experience pruritis or tenderness. Differential diagnosis includes condylomata acuminata and vulvar syringoma for multiple small lesions, and squamous or basal cell carcinoma for large, solitary lesions. The diagnosis is usually made clinically, although several techniques can aid in the diagnosis. For example, spraying the lesion with ethyl chloride produces a distinct central area of darkness that is not found in warts, and unroofing the lesion with a 27-gauge needle reveals the presence of a white “pearl.” Biopsy is rarely necessary. Most molluscum lesions will resolve spontaneously, although this process can take 6 months to 5 years. Many experts recommend treatment of genital molluscum lesions to reduce the risk of transmission and to prevent autoinoculation, as well as to improve the patient’s quality of life. Treatment modalities are similar to those for external genital warts, and include physician-administered (electrosurgery, curettage, cryosurgery, trichloroacetic acid [TCA] application, and podophyllin) and patient-administered (podofi lox, retinoic acid, and imiquimod 1% or 5% cream) modalities. The physical and chemical ablation techniques are associated with pain, irritation, and mild scarring; because of the caustic nature of TCA and podophyllin, only a small area can be treated at one time. Several open-label and randomized, controlled trials indicate that imiquimod cream is well tolerated and effective for the treatment of molluscum lesions, providing a novel treatment, particularly for patients who do not tolerate other therapies or in whom other therapies are not effective.3,74-76 Patients should be followed up in 30 days in order to assess for new lesions that may have been incubating at the time of treatment. Sex partners require treatment only if lesions are present.

Treatment of Genital Warts

Patient Administered

Provider Administered

Podofilox 0.5% solution or gel, applied with a cotton swab (solution) or finger (gel) to warts twice a day for 3 days, then no therapy for 4 days. Can repeat for up to 4 cycles. Limit to 10 cm2 of area and 0.5 ml of podofilox. Imiquimod 5% cream, applied once daily at bedtime, 3 times a week for up to 16 weeks. The treatment area should be washed 6–10 hr after the application.

Cryotherapy; can repeat every 1–2 wk.

Podophyllin resin 10% –25% in a compound tincture of benzoin, applied to each wart and allowed to air dry. Can repeat weekly. Limit to 10 cm2 of area and ≤0.5 ml of podophyllin. BCA/TCA 80% –90%, with a small amount applied only to warts. A white “frosting” will develop. If excess acid is applied, remove with talc, baking soda, or liquid soap. Can repeat weekly. Surgical removal with tangential scissor excision, tangential shave excision, curettage, or electrosurgery.

Abbreviations: BCA, bichloroacetic acid; TCA, trichloroacetic acid. From Centers for Disease Control and Prevention: Sexually transmitted diseases treatment guidelines—2006. MMWR Recomm Rep 55(RR-11):1–100, 2006.

Chapter 70 — Sexually Transmitted Infections

Urethritis and Epididymitis STIs in males include urethritis, epididymitis, and orchitis. Orchitis is discussed in Chapter 89 (Penile/Testicular Disorders). Urethritis is the most common manifestation of N. gonorrhoeae and C. trachomatis infection in males. Other etiologies of nongonococcal urethritis include Ureaplasma urealyticum and Mycoplasma genitalium, as well as T. vaginalis and HSV. Clinical Presentation Urethritis presents with urethral discharge and inflammation. Spontaneous discharge is often noted in the morning, after holding urine overnight. Dysuria and pruritis can also be present. Infection with C. trachomatis is often asymptomatic; when symptoms are present, they tend to be more mild than those associated with gonococcal infection. Even without symptoms, however, males infected with C. trachomatis usually have evidence of urethral inflammation on laboratory evaluation of secretions or urine.77-79 The presence of mucopurulent urethral discharge is adequate to make the diagnosis of urethritis; if in doubt, a Gram stain of the urethral secretions demonstrating ≥5 WBCs per oil immersion field can confirm the diagnosis. Gram stain is the preferred diagnostic test, because it has high sensitivity and specificity, and can also identify gonococcal infection by the presence of intracellular diplococci. Alternatively, a positive leukocyte esterase test on fi rst-void urine or microscopic examination of first-void urine demonstrating ≥10 WBCs per high-power field supports the diagnosis. Definitive tests for N. gonorrhoeae and C. trachomatis should also be sent; either cultures from the urethra or nucleic acid amplification tests, using a urine specimen, are appropriate.80 Testing for T. vaginalis is generally reserved for patients who do not respond to therapy, or to patients with a known infected contact. The differential diagnosis of urethritis includes the

Table 70–8

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infectious etiologies noted previously, as well as allergic inflammation, trauma, and foreign body. Gonococcal infection can spread and cause prostatitis, epididymitis, seminal vesiculitis, and infection of Cowper’s and Tyson’s glands. Epididymitis is characterized by urethral discharge, dysuria, scrotal pain and tenderness that is usually unilateral, scrotal swelling and erythema, pain/tenderness/ swelling of the lower pole of the epididymis, and swelling and pain of the spermatic cord. Prostatitis can be asymptomatic; when symptoms are present, they include chills, fever, malaise, rectal pain, lower back pain, lower abdominal pain, and urinary symptoms such as dysuria, frequency, and acute urinary retention. Like females, males are also at risk for pharyngitis, rectal infection, conjunctivitis, otitis externa, and disseminated disease. Proctitis has become much less common over the last decade, but is still important to consider in the differential of any sexually active patient with gastrointestinal symptoms. Chlamydial infection can also cause epididymitis, which is often a more indolent infection than that caused by N. gonorrhoeae. Other complications include proctitis as well as Reiter’s syndrome, which is characterized by conjunctivitis, dermatitis, urethritis, and arthritis. Some patients can have isolated arthritis or reactive tenosynovitis without the other characteristics of Reiter’s syndrome. The role of C. trachomatis in prostatitis is unclear. Management Patients with confirmed uncomplicated gonococcal infection of the urethra or rectum should be treated with ceftriaxone or a fluoroquinolone, preferably administered during the ED visit (Table 70–8). Although there has been some concern about the use of fluoroquinolones in children younger than 18 years, the CDC has stated that, because no joint injury has been documented in children treated with prolonged

Treatment for Other Gonococcal* and Chlamydial Infections

Infection

Treatment†

Uncomplicated gonococcal infection of the urethra or rectum

Ceftriaxone 125 mg IM once or Ciprofloxacin 500 mg orally once or Ofloxacin 400 mg orally once or Levofloxacin 250 mg orally once Azithromycin 1 g orally once or Doxycycline 100 mg orally bid × 7 days Metronidazole 2 g orally once plus erythromycin base 500 mg orally qid for 10 days Ceftriaxone 250 mg IM once plus doxycycline 100 mg orally bid × 10 days Or, if allergy Ofloxacin 300 mg orally bid × 10 days or Levofloxacin 500 mg orally qd × 10 days Ceftriaxone 125 mg IM once or Ciprofloxacin 500 mg orally once Ceftriaxone 1 g IM once; saline lavage of the affected eye(s) Ceftriaxone 1 g IM q24h or Ciprofloxacin 400 mg IV q12h or Levofloxacin 250 mg IV daily Ceftriaxone 1–2 g q12h for 10–14 days (meningitis) or at least 4 wk (endocarditis)

Nongonococcal urethritis Recurrent/persistent urethritis Epididymitis

Uncomplicated gonococcal infections of the pharynx Gonococcal conjunctivitis Disseminated gonococcal infection: therapy should continue for 24–48 hr after improvement; then be switched to oral therapy to complete 7 days treatment Gonococcal meningitis or endocarditis

*Patients with gonococcal infections should generally be treated for concomitant chlamydial infection. The reader is referred to the CDC Sexually Transmitted Diseases web site (http://www.cdc.gov/STD/) for additional regimens. Abbreviation: IM, intramuscularly. From Centers for Disease Control and Prevention: Sexually transmitted diseases treatment guidelines—2006. MMWR Recomm Rep 55(RR-11):1–100, 2006. †

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ciprofloxacin regimens, any patient weighing over 45 kg can be treated with any of the recommended regimens. Treatment for gonococcal pharyngitis is either ceftriaxone 125 mg IM in a single dose, or ciprofloxacin 500 mg orally in a single dose. Patients with gonococcal conjunctivitis should be treated with ceftriaxone 1 g IM once, as well as one lavage of the eye with normal saline. Patients with epididymitis can usually be treated as outpatients, although hospitalization is recommended when severe pain suggests other diagnoses, such as torsion, or if the patient is febrile. For all infections, if chlamydial infection is not ruled out, dual therapy is recommended.3 Patients with disseminated gonococcal infection should be hospitalized for treatment, particularly if compliance is questionable, the diagnosis is uncertain, or purulent synovial effusions or other complications are present. Cure rates for uncomplicated gonococcal and chlamydial infections are high. If symptoms recur, patients should be re-treated with the original regimen if compliance is in doubt or if the patient has been reexposed to an infected partner. Patients with nongonococcal urethritis that is not due to C. trachomatis have relapse rates of up to 50% after 2 months; some cases are caused by tetracycline-resistant U. urealyticum. Patients with gonococcal infection who have persistent symptoms after treatment should be evaluated by culture in order to assess sensitivities of the organism.3 Patients with epididymitis who do not improve after 3 days of therapy should be re-evaluated to assess for other causes, such as tumor, abscess, infarction, tuberculosis, and fungal infection. All sex partners within 60 days, as well as the patient’s most recent sex partner if more than 60 days ago, should be treated whether or not they are symptomatic. Patients should refrain from sexual intercourse for 7 days after treatment is completed and until symptoms have resolved. Neonatal Infections3,81,82 Both N. gonorrhoeae and C. trachomatis can cause ophthalmia neonatorum, which generally presents in patients less than 30 days old. Prophylaxis with erythromycin eye drops helps prevent gonococcal disease, but does not affect the incidence of chlamydia.3 Therefore, gonococcal ophthalmia should be considered in patients who did not receive prophylaxis and in children of mothers who did not receive prenatal care or who have a history of STIs. Other gonococcal infections include scalp abscess and disseminated disease with bacteremia, arthritis, or meningitis. C. trachomatis can also cause pneumonia. Clinical Presentation Infants born to mothers with a history of HSV can present with a variety of clinical syndromes; in addition, neonatal herpes can be present in infants born to mothers without a clear history of HSV, as well as in infants born via cesarean section. Infections have been documented despite presumed intact membranes. The risk to an infant born to a mother with a primary HSV infection is 33% to 50%; risk to infants of mothers with reactivated infection is less than 5%.83 Infections usually present within the first 4 weeks of life. Most cases of congenital syphilis are diagnosed through routine prenatal and antenatal screening of the mother. However, a small number of patients may present to the ED during the neonatal period.

Infants with gonococcal ophthalmia generally present with a hyperpurulent eye discharge and very injected conjunctivae, although symptoms can be more subtle. Other causes of conjunctivitis in this age group include chemical conjunctivitis (often from prophylactic eyedrops, which presents in the first 3 days of life), other bacterial causes, and viral causes. Any infant with a purulent eye discharge should have a Gram stain of the discharge to evaluate for intracellular diplococci, as well as a viral culture of conjunctival cells (obtained via conjunctival scraping with a Dacrontipped swab) to evaluate for Chlamydia. Culture of the eye discharge alone is not adequate to diagnose chlamydial infection. A limited number of nonculture tests are licensed by the Food and Drug Administration for conjunctival specimens.84 Patients with intracellular diplococci on Gram stain should be treated presumptively for gonococcal infection until culture results are available. Culture is important for definitive diagnosis because other species of Neisseria can be indistinguishable from N. gonorrhoeae on Gram stain. Blood cultures and lumbar puncture can be reserved for patients with other signs of systemic disease, such as fever. Infants with chlamydia pneumonia generally present with a staccato cough, tachypnea, and hyperinflation and bilateral diffuse infi ltrates on chest radiograph. Specimens for Chlamydia testing should be obtained from the nasopharynx. Neonatal HSV can present with disseminated disease, most often involving the lung and the liver; with localized central nervous system disease, with meningitis and focal seizures; or with disease localized to the skin, eyes, and mouth. Infants with HSV often present without skin lesions. Lesions can be evaluated for HSV as described earlier; if CSF is obtained, an HSV polymerase chain reaction test is available in many laboratories. In addition, serum can be sent for culture for the systemically ill infant. Infants with congenital syphilis who are symptomatic can present with hepatosplenomegaly, snuffles, lymphadenopathy, mucocutaneous lesions, edema, rash, hemolytic anemia, or thrombocytopenia. Testing for syphilis in the neonate is similar to that described earlier; diagnosis is likely if the patient has clinical features consistent with syphilis and either a serum quantitative nontreponemal serologic titer that is fourfold greater than the mother’s titer, or a positive darkfield or FTA-Abs test of body fluids. Patients with proven or highly probable disease should have a lumbar puncture and a complete blood count, and other tests, such as longbone radiographs and liver function tests, as clinically indicated. Important Clinical Features and Considerations Because of the severe sequelae of gonococcal ophthalmia, infants with eye discharge should be assumed to have this infection until proven otherwise. Untreated, the infection can progress to corneal ulceration and to globe rupture within 24 hours of infection. Topical therapy is not adequate for either gonococcal or chlamydial ophthalmia neonatorum. Given the high morbidity and mortality of neonatal herpes infection, this should be considered in any neonate with fever, irritability, and abnormal CSF results. A careful physical examination is necessary to identify skin lesions, particularly in the scalp and near the eyebrows.

Chapter 70 — Sexually Transmitted Infections

Evaluation for congenital syphilis in the ED setting is limited to patients with clinical symptoms. There is no indication for routine screening in this setting. Management Patients with presumed gonococcal ophthalmia should be treated with ceftriaxone, 25 to 50 mg/kg intravenously (IV) or IM in a single dose (maximum 125 mg), and should be admitted to the hospital for frequent saline lavage of the eye until the discharge clears. These patients should be evaluated by an ophthalmologist. Patients with scalp abscesses or disseminated infection should be treated for 7 days, or for 10 to 14 days if meningitis is present. Patients with chlamydial ophthalmia neonatorum or pneumonia should be treated with erythromycin base or ethylsuccinate 50 mg/kg per day orally, in four divided doses, for 14 days. Infants treated with erythromycin for chlamydial infection should be followed up to determine treatment effectiveness; about 20% of these patients fail initial therapy and require a second course. Infants with HSV should be treated with acyclovir 20 mg/ kg IV every 8 hours for 14 days for skin disease, and for 21 days for meningitis. Infants with ocular involvement should also receive a topical ophthalmic drug, such as 1% to 2% trifluridine, and be evaluated by an ophthalmologist. Infants with symptomatic congenital syphilis should be treated with aqueous penicillin G 50,000 units/kg per dose IV every 12 hours for the first 7 days of life and every 8 hours thereafter, for a total of 10 days, or procaine penicillin G 50,000 units/kg per dose IM daily for 10 days. All infants with congenital syphilis require close follow-up and repeat testing. REFERENCES 1. Brook I: Microbiology and management of polymicrobial female genital tract infections in adolescents. J Pediatr Adolesc Gynecol 15:217–226, 2002. 2. Washington AE, Aral SO, Wolner-Hanssen P: Assessing risks for pelvic inflammatory disease and its sequelae. JAMA 266:2581–2586, 1991. *3. Centers for Disease Control and Prevention: Sexually transmitted diseases treatment guidelines—2006. MMWR Recomm Rep 55(RR-11): 1–100, 2006. 4. Simms I, Warburton F, Westrom L: Diagnosis of pelvic inflammatory disease: time for a rethink. Sex Transm Infect 79:491–494, 2003. 5. Millstein SG, Adler NE, Irwin CE Jr: Sources of anxiety about pelvic examinations among adolescent females. J Adolesc Health Care 5:105– 111, 1984. *6. Peipert JF, Ness RB, Blume J, et al: Clinical predictors of endometritis in women with symptoms and signs of pelvic inflammatory disease. Am J Obstet Gynecol 184:856–864, 2001. 7. Blake DR, Fletcher K, Joshi N, Emans SJ: Identification of symptoms that indicate a pelvic examination is necessary to exclude PID in adolescent women. J Pediatr Adolesc Gynecol 16:25–30, 2003. 8. Bryant DK, Fox AS, Spigland I, et al: Comparison of rapid diagnostic methodologies for chlamydia and gonorrhea in an urban adolescent population: a pilot study. J Adolesc Health 16:324–327, 1995. 9. Carroll KC, Aldeen WE, Morrison M, et al: Evaluation of the Abbott LCx ligase chain reaction assay for detection of Chlamydia trachomatis and Neisseria gonorrhoeae in urine and genital swab specimens from a sexually transmitted disease clinic population. J Clin Microbiol 36:1630–1633, 1998. 10. Hook EW 3rd, Ching SF, Stephens J, et al: Diagnosis of Neisseria gonorrhoeae infections in women by using the ligase chain reaction on patient-obtained vaginal swabs. J Clin Microbiol 35:2129–2132, 1997.

*Selected readings.

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11. Hook EW 3rd, Smith K, Mullen C, et al: Diagnosis of genitourinary Chlamydia trachomatis infections by using the ligase chain reaction on patient-obtained vaginal swabs. J Clin Microbiol 35:2133–2135, 1997. 12. Johnson RE, Newhall WJ, Papp JR, et al: Screening tests to detect Chlamydia trachomatis and Neisseria gonorrhoeae infections—2002. MMWR Recomm Rep 51(RR-15):1–38, 2002. 13. Lee HH, Chernesky MA, Schachter J, et al: Diagnosis of Chlamydia trachomatis genitourinary infection in women by ligase chain reaction assay of urine. Lancet 345:213–216, 1995. 14. Thomas BJ, Pierpoint T, Taylor-Robinson D, et al: Sensitivity of the ligase chain reaction assay for detecting Chlamydia trachomatis in vaginal swabs from women who are infected at other sites. Sex Transm Infect 74:140–141, 1998. 15. Newhall WJ, Johnson RE, DeLisle S, et al: Head-to-head evaluation of five chlamydia tests relative to a quality-assured culture standard. J Clin Microbiol 37:681–685, 1999. 16. Van Dyck E, Leven M, Pattyn S, et al: Detection of Chlamydia trachomatis and Neisseria gonorrhoeae by enzyme immunoassay, culture, and three nucleic acid amplification tests. J Clin Microbiol 39:1751–1756, 2001. 17. Molander P, Sjoberg J, Paavonen J, et al: Transvaginal power Doppler fi ndings in laparoscopically proven acute pelvic inflammatory disease. Ultrasound Obstet Gynecol 17:233–238, 2001. 18. Golden N, Cohen H, Gennari G, et al: The use of pelvic ultrasonography in the evaluation of adolescents with pelvic inflammatory disease. Am J Dis Child 141:1235–1238, 1987. 19. Golden N, Neuhoff S, Cohen H: Pelvic inflammatory disease in adolescents. J Pediatr 114:138–143, 1989. 20. Slap GB, Forke CM, Cnaan A, et al: Recognition of tubo-ovarian abscess in adolescents with pelvic inflammatory disease. J Adolesc Health 18:397–403, 1996. *21. Ness RB, Soper DE, Holley RL, et al: Effectiveness of inpatient and outpatient treatment strategies for women with pelvic inflammatory disease: results from the Pelvic Inflammatory Disease Evaluation and Clinical Health (PEACH) Randomized Trial. Am J Obstet Gynecol 186:929–937, 2002. 22. English A: Understanding legal aspects of care. In Neinstein LS (ed): Adolescent Health Care: A Practical Guide, 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2002, pp 186–198. 23. Guttmacher Institute State Center: State Policies in Brief: Minors’ Access to STD Services, 2006. Available at http://www.guttmacher.org/ statecenter/spibs/spib_MASS.pdf 24. Centers for Disease Control and Prevention: Chlamydia—CDC Fact Sheet, 2006. Available at http://www.cdc.gov/STD/Chlamydia/ STDFact-Chlamydia.htm 25. Centers for Disease Control and Prevention: Gonorrhea—CDC Fact Sheet, 2006. Available at http://www.cdc.gov/STD/Gonorrhea/STDFactgonorrhea.htm 26. Wiesenfeld HC, Hillier SL, Krohn MA, et al: Lower genital tract infection and endometritis: insight into subclinical pelvic inflammatory disease. Obstet Gynecol 100:456–463, 2002. 27. Yudin MH, Hillier SL, Wiesenfeld HC, et al: Vaginal polymorphonuclear leukocytes and bacterial vaginosis as markers for histologic endometritis among women without symptoms of pelvic inflammatory disease. Am J Obstet Gynecol 188:318–323, 2003. 28. Hutt DM, Judson FN: Epidemiology and treatment of oropharyngeal gonorrhea. Ann Intern Med 104:655–658, 1986. 29. Martin DH, Mroczkowski TF, Dalu ZA, et al; The Azithromycin for Chlamydial Infections Study Group: A controlled trial of a single dose of azithromycin for the treatment of chlamydial urethritis and cervicitis. N Engl J Med 327:921–925, 1992. 30. Moran JS, Levine WC: Drugs of choice for the treatment of uncomplicated gonococcal infections. Clin Infect Dis 20:S47–S65, 1995. 31. Centers for Disease Control and Prevention: Fluoroquinolone resistance in Neisseria gonorrhoeae, Hawaii, 1999, and decreased susceptibility to azithromycin in N. gonorrhoeae, Missouri, 1999. MMWR Morb Mortal Wkly Rep 49:833–837, 2000. 32. Schillinger JA, Kissinger P, Calvet H, et al: Patient-delivered partner treatment with azithromycin to prevent repeated Chlamydia trachomatis infection among women: a randomized, controlled trial. Sex Transm Dis 30:49–56, 2003. 33. Eckert LO, Hawes SE, Stevens CE, et al: Vulvovaginal candidiasis: clinical manifestations, risk factors, management algorithm. Obstetr Gynecol 92:757–765, 1998.

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34. Association of Genitourinary Medicine and the Medical Society for the Study of Venereal Diseases, Clinical Effectiveness Group: National guideline for the management of vulvovaginal candidiasis. Sex Transm Infect 75:S19–S20, 1999. 35. Centers for Disease Control and Prevention: Trichomoniasis—CDC Fact Sheet, 2004. Available at http://www.cdc.gov/STD/Trichomonas/ STDFact-Trichomoniasis.htm 36. Association of Genitourinary Medicine and the Medical Society for the Study of Venereal Diseases, Clinical Effectiveness Group: National guidelines for the management of Trichomonas vaginalis. Sex Transm Infect 75:S21–S23, 1999. 37. Association of Genitourinary Medicine and the Medical Society for the Study of Venereal Diseases, Clinical Effectiveness Group: National guideline for the management of bacterial vaginosis. Sex Transm Infect 75:S16–S18, 1999. 38. Joesoef MR, Schmid GP, Hillier SL: Bacterial vaginosis: review of treatment options and potential clinical indications for therapy. Clin Infect Dis 28(Suppl 1):S57–S65, 1999. 39. Wilson J: Managing recurrent bacterial vaginosis. Sex Transm Dis 80:8–11, 2004. 40. Wolner-Hanssen P, Krieger JN, Stevens CE, et al: Clinical manifestations of vaginal trichomoniasis. JAMA 261:571–576, 1989. 41. Landers DV, Wiesenfeld HC, Heine RP, et al: Predictive value of the clinical diagnosis of lower genital tract infection in women. Am J Obstet Gynecol 190:1004–1010, 2004. 42. Blake DR, Duggan A, Joffe A: Use of spun urine to enhance detection of Trichomonas vaginalis in adolescent women. Arch Pediatr Adolesc Med 153:1222–1225, 1999. 43. Amsel R, Totten PA, Spiegel CA, et al: Nonspecific vaginitis: diagnostic criteria and microbial and epidemiologic associations. Am J Med 74:14–22, 1983. 44. Nugent RP, Krohn MA, Hillier SL: The reliability of diagnosing bacterial vaginosis is improved by a standardized method of Gram stain interpretation. J Clin Microbiol 29:297–301, 1991. 45. Schwebke JR, Hillier SL, Sobel JD, et al: Validity of the vaginal Gram stain for the diagnosis of bacterial vaginosis. Obstet Gynceol 88:573– 576, 1996. *46. Blake DR, Duggan A, Quinn T, et al: Evaluation of vaginal infections in adolescent women: can it be done without a speculum? Pediatrics 102:939–944, 1998. 47. Peipert JF, Montagno AB, Cooper AS, Sung CJ: Bacterial vaginosis as a risk factor for upper genital tract infection. Am J Obstet Gynecol 177:1184–1187, 1997. 48. Wiesenfeld HC, Hillier SL, Krohn MA, et al: Bacterial vaginosis is a strong predictor of Neisseria gonorrhoeae and Chlamydia trachomatis infection. Clin Infect Dis 36:663–668, 2003. 49. Sobel JD, Brooker D, Stein GE, et al; Fluconazole Vaginitis Study Group: Single oral dose fluconazole compared with conventional clotrimazole topical therapy of Candida vaginitis. Am J Obstet Gynecol 172:1263–1268, 1995. 50. Centers for Disease Control and Prevention: Herpes—CDC Fact Sheet, 2004. Available at http://www.cdc.gov/STD/Herpes/STDFact-Herpes. htm 51. Roberts CM, Pfister JR, Spear SJ: Increasing proportion of herpes simplex virus type 1 as a cause of genital herpes infection in college students. Sex Transm Dis 30:797–800, 2003. 52. Engelberg R, Carrell D, Krantz E, et al: Natural history of genital herpes simplex virus type 1 infection. Sex Transm Dis 30:174–177, 2003. *53. Ashley RL: Sorting out the new HSV type specific antibody tests. Sex Transm Infect 77:232–237, 2001. 54. Turner KR, Wong EH, Kent CK, Klausner JD: Serologic herpes testing in the real world: validation of new type-specific serologic herpes simplex virus tests in a public health laboratory. Sex Transm Dis 29:422–425, 2002. 55. Bryson YJ, Dillon M, Lovett M, et al: Treatment of fi rst episodes of genital herpes simplex virus infection with oral acyclovir: a randomized double-blind controlled trial in normal subjects. N Engl J Med 308:916–921, 1983. 56. Corey L, Wald A, Patel R, et al; Valacyclovir HSV Transmission Study Group: Once-daily valacyclovir to reduce the risk of transmission of genital herpes. N Engl J Med 350:11–20, 2004. 57. Strand A, Patel R, Wulf HC, Coates KM; International Valacyclovir HSV Study Group: Aborted genital herpes simplex virus lesions: fi ndings from a randomized controlled trial with valacyclovir. Sex Transm Infect 78:435–439, 2002.

58. Wald A: New therapies and prevention strategies for genital herpes. Clin Infect Dis 28(Suppl 1):S4–S13, 1999. 59. Douglas JM, Critchlow C, Benedetti J, et al: A double-blind study of oral acyclovir for suppression of recurrences of genital herpes simplex virus infection. N Engl J Med 310:1551–1556, 1984. 60. Mertz GJ, Jones CC, Mills J, et al: Long-term acyclovir suppression of frequently recurring genital herpes simplex virus infection: a multicenter double-blind trial. JAMA 260:201–206, 1988. 61. Stanberry LR, Cunningham AL, Mindel A, et al: Prospects for control of herpes simplex virus disease through immunization. Clin Infect Dis 30:549–566, 2000. 62. Centers for Disease Control and Prevention: Syphilis Elimination Key Facts, November 28, 2001. Available at http://www.cdc.gov/std/media/ SyphElimKeyFacts.htm 63. Shew ML, Fortenberry JD: Syphilis screening in adolescents. J Adolesc Health 13:303–305, 1992. *64. Wicher K, Horowitz HW, Wicher V: Laboratory methods of diagnosis of syphilis for the beginning of the third millennium. Microbes Infect 1:1035–1049, 1999. 65. Augenbraun M, Rolfs R, Johnson R, et al; Syphilis and HIV Study Group: Treponemal specific tests for the serodiagnosis of syphilis. Sex Transm Dis 25:549–552, 1998. 66. Hook EW 3rd, Martin DH, Stephens J, et al: A randomized, comparative pilot study of azithromycin versus benzathine penicillin G for treatment of early syphilis. Sex Transm Dis 29:486–490, 2002. 67. Mabey D, Peeling RW: Lymphogranuloma venereum. Sex Transm Infect 78:90–92, 2002. 68. Centers for Disease Control and Prevention: Other sexually transmitted diseases. In STD Surveillance 2000: National Profi le, 2001. Available at http://www.cdc.gov/std/stats00/2000OtherSTDs.htm 69. Lewis DA: Chancroid: clinical manifestations, diagnosis, and management. Sex Transm Infect 79:68–71, 2003. 70. Lewis DA: Diagnostic tests for chancroid. Sex Transm Infect 76:137– 141, 2000. 71. Schmid GP: Treatment of chancroid, 1997. Clin Infect Dis 28(Suppl 1): S14–S20, 1999. 72. Gunter J: Genital and perianal warts: new treatment opportunities for human papillomavirus infection. Am J Obstet Gynecol 189:S3–S11, 2003. 73. Moscicki AB, Shiboski S, Broering J, et al: The natural history of human papillomavirus infection as measured by repeated DNA testing in adolescent and young women. J Pediatr 132:277–284, 1998. *74. Ting PT, Dytoc MT: Therapy of external anogenital warts and molluscum contagiosum: a literature review. Dermatol Ther 17:68–101, 2004. 75. Tyring SK: Molluscum contagiosum: the importance of early diagnosis and treatment. Am J Obstet Gynecol 189:S12–S16, 2003. 76. Syed TA, Goswami J, Ahmadpour OA, Ahmad SA: Treatment of molluscum contagiosum in males with an analog of imiquimod 1% in cream: a placebo-controlled, double-blind study. J Dermatol 25:309– 313, 1998. *77. Richens J: Main presentations of sexually transmitted infections in men. BMJ 328:1251–1253, 2004. 78. Sherrard J, Barlow D: Gonorrhoea in men: clinical and diagnostic aspects. Genitourin Med 72:422–426, 1996. 79. Burstein GR, Zenilman JM: Nongonococcal urethritis—a new paradigm. Clin Infect Dis 28:S66–S73, 1999. 80. Palladino S, Pearman JW, Kay ID, et al: Diagnosis of Chlamydia trachomatis and Neisseria gonorrhoeae genitourinary infections in males by the Amplicor PCR assay of urine. Diagn Microbiol Infect Dis 33:141–146, 1999. 81. Pickering LK (ed): Red Book: 2006 Report of the Committee on Infectious Diseases, 27th ed. Elk Grove Village, IL: American Academy of Pediatrics, 2006. 82. O’Hara MA: Ophthalmia neonatorum. Pediatr Clin North Am 40:715– 725, 1993. 83. American Academy of Pediatrics: In Pickering LK (ed): Red Book: 2006 Report of the Committee on Infectious Diseases, 27th ed. Elk Grove Village, IL: American Academy of Pediatrics, 2006, pp 301–309. 84. American Academy of Pediatrics: In Pickering LK (ed): Red Book: 2006 Report of the Committee on Infectious Diseases, 27th ed. Elk Grove Village, IL: American Academy of Pediatrics, 2006, pp 361–371.

Chapter 70 — Sexually Transmitted Infections

USEFUL WEBSITES The American Academy of Pediatrics Committee on Infectious Diseases Red Book: http://aapredbook.aappublications.org/ The Centers for Disease Control and Prevention Sexually Transmitted Diseases Treatment Guidelines: http://www.cdc.gov/std/treatment/

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The Centers for Disease Control and Prevention website (for information on any sexually transmitted infection): http://www.cdc.gov/std The American Social Health Association home page, with information and hotline access: http://www.ashastd.org

Chapter 71 Selected Infectious Diseases Robert P. Olympia, MD

Key Points Lyme disease, the leading cause of vector-borne infectious illness in the United States, is associated with three distinct clinical stages: early localized, early disseminated, and late disseminated. “Food-borne illness” refers to an acute onset of symptoms, ranging from vomiting, diarrhea, and abdominal pain/cramping to potential life-threatening complications, caused by the ingestion of contaminated food. Onset and duration of symptoms vary, depending on the specific cause. Distinguishing between diseases associated with foreign travel can be difficult since many present with fever associated with constitutional symptoms such as headache, myalgias, malaise, anorexia, and vomiting/ diarrhea. Young children with infectious mononucleosis are often asymptomatic, although they may present with low-grade fever, pharyngitis, lymphadenopathy, splenomegaly, malaise, rash, headache, anorexia, nausea, chills, and myalgias.

Selected Diagnoses Tick-borne illnesses Lyme disease Ehrlichiosis Food-borne illness Diseases associated with foreign travel Infectious mononucleosis Severe acute respiratory syndrome

Discussion of Individual Diagnoses Tick-borne Illnesses Lyme Disease Lyme disease is the leading cause of vector-borne infectious illness in the United States, with 23,000 cases reported in 560

2002. It is caused by the spiral-shaped bacterium Borrelia burgdorferi. The bacterium is transmitted to humans via the bite of an infected deer tick, of which there are two types: the western black-legged tick (Ixodes pacificus), causing disease on the Pacific coast, and the black-legged tick (Ixodes scapularis), causing disease in the northeastern and north-central United States. The reservoirs for these ticks are the whitefooted mouse and deer. Transmission is based on the length of attachment of the tick, with low risk of transmission associated with less than 24 to 48 hours of attachment. Lyme disease is commonly found in the northeastern mid-Atlantic and midwestern portions of the United States, as well as several counties in northwestern California. Outside the United States, the disease can be found in Spain, France, Austria, Germany, Russia, and Japan. Clinical manifestations of Lyme disease may present year-round, with a higher incidence during late spring to summer (May to August). CLINICAL PRESENTATION

Lyme disease is associated with three distinct clinical stages: early localized, early disseminated, and late disseminated (Table 71–1). Clinical findings are based on time from the initial exposure (bite of the infected tick). The classic rash of Lyme disease is erythema migrans (EM), commonly found on the head or neck in young children or the extremities of older children. The lesion begins as a small red maculae or papule at or adjacent to the site of the bite, which enlarges in an annular centrifugal fashion to approximately 10 to 15 cm in diameter, resembling a “bull’s eye.” EM is commonly associated with nonspecific symptoms such as fever, fatigue, malaise, headache, myalgias, and arthralgias. EM, found in only two thirds of humans bitten by an infected tick, appears typically 14 days after the initial exposure. The rash and constitutional symptoms are typically self-limited and not dependent on treatment with antibiotics. If untreated, early disseminated Lyme disease may occur weeks to months following initial exposure. Of those cases that progress, 20% develop neurologic manifestations (cranial neuropathy, radiculoneuropathy, aseptic meningitis/encephalitis),1 10% develop cardiac manifestations (myopericarditis, atrioventricular [AV] block, or cardiomyopathy), and 20% develop multiple EM. The most common cranial neuropathy associated with Lyme disease is Bell’s palsy (peripheral VII nerve palsy), which may be unilateral or bilateral. While commonly confused with viral meningitis, Lyme meningitis is more often associated with Bell’s palsy,

Chapter 71 — Selected Infectious Diseases

Table 71–1

Clinical Findings and Treatment* in Lyme Disease

Stage (Time from Initial Exposure)

Treatment†

Early Localized (7–14 days) Erythema migrans

Amoxicillin 50 mg/kg/day divided bid or Doxycycline‡ 100 mg bid × 14–21 days Early Disseminated (days to weeks) Multiple erythema migrans Amoxicillin (as above) × 21–28 days Neurologic Cranial neuropathy Amoxicillin (as above) × 21–28 days (Bell’s palsy) Radiculoneuritis Amoxicillin (as above) × 21–28 days Aseptic meningitis/ Ceftriaxone 75–100 mg/kg/day × encephalitis 14–28 days or 30–60 days depending on clinical response Cardiac Myopericarditis Ceftriaxone (as above) × 14–21 days Atrioventricular block Cardiology consult Cardiomegaly Cardiology consult Musculoskeletal Arthralgias Supportive care Myalgias Supportive care Late Disseminated (weeks to months) Arthritis Amoxicillin (as above) × 28 days Chronic polyneuropathy Supportive care Chronic encephalopathy§ Supportive care *Treatment for Lyme disease may have different recommendations from different sources; consultation with an infectious disease expert should be considered. † Cefuroxime axetil or erythromycin can be used for penicillinallergic patients. ‡ Only in children 8 years or older. § Sleep disturbance, fatigue, mood changes, concentration difficulty, and memory loss.

papilledema, longer duration of symptoms prior to lumbar puncture, lack of fever at time of diagnosis, and cerebrospinal fluid (CSF) pleocytosis (especially neutrophils).2 Late disseminated Lyme disease is associated with oligoarthritis (most common manifestation), chronic polyneuropathy, and chronic encephalopathy (commonly manifesting as sleep disturbance, fatigue, mood changes, concentration difficulty, memory loss).3 The arthritis associated with late disseminated disease is often limited to large weight-bearing joints.4 The diagnosis of Lyme disease can be made clinically, serologically, or by polymerase chain reaction (PCR) (Table 71– 2). The clinical diagnosis can be made simply by identifying the classic EM rash, or by identifying one clinical manifestation (arthritis, cranial neuropathy, AV block, aseptic meningitis, or radiculoneuritis) and isolation of or serologic evidence of B. burgdorferi infection. Enzyme-linked immunosorbent assay (ELISA) or Western blot techniques, both of which detect immunoglobulin M (IgM) and immunoglobulin G (IgG), are serologic tests that can confirm the diagnosis. In Lyme disease, IgM peaks approximately 4 weeks and IgG approximately 6 weeks after initial exposure. The Centers for Disease Control and Prevention recommends the use of ELISA as the initial screening test, and confirmation with the Western blot if the ELISA is positive (due to cross reactivity

Table 71–2

561

Diagnosis of Lyme Disease

Erythema migrans or at least one manifestation (arthritis, cranial neuropathy, AV block, aseptic meningitis, radiculoneuritis) and isolation or serologic evidence of Borellia burgdorferi infection Serologic evidence Perform enzyme-linked immunosorbent assay (ELISA) first If positive, confirm with Western immunoblot Polymerase chain reaction (PCR)—may be used on blood, CSF fluid, or synovial fluid Supportive Elevated WBC count, sedimentation rate, AST, complement C3/C4 Joint fluid with 25,000–125,000 WBCs/mm3 with polymorphonuclear predominance CSF with mild pleocytosis (60% of cases), children may have been seen late in their disease course, and it is uncertain if the Pediatric Appendicitis Score’s test characteristics will be as accurate if applied to a less ill emergency department population. Imaging Studies In general, plain abdominal radiographs are not helpful for diagnosing uncomplicated appendicitis in children. Commonly cited findings of rightward scoliosis, soft tissue changes, localized ileus, and “free peritoneal fluid” occur in children with and without appendicitis.44 Radiographs in children with appendiceal perforation may show bowel obstruction, a right lower quadrant mass, or a calcified appendicolith.12,45 Of these radiographic fi ndings, a calcified appendicolith is the most specific for appendicitis, present in 10% to 20% of young children with perforated appendicitis, in less than 10% with uncomplicated appendicitis, and in only 1% to 2% of children without appendicitis.45-47 However, plain radiographs are normal or nonspecific in over three quarters of children with appendicitis, and this modality, in general, should not be used to exclude or diagnose this disorder.46-48 Ultrasonography has been studied extensively in children with suspected appendicitis. Experienced centers have found ultrasound to be nearly 90% sensitive and greater than 95% specific for diagnosing appendicitis, while others have reported a sensitivity as low as 44% to 48%.49-52 Ultrasonographic findings diagnostic of nonperforated appendicitis include an appendiceal diameter greater than 6 mm, a “target sign” with five concentric layers, distention or obstruction of the appendiceal lumen, and muscular wall thickness greater than 2 mm. Ultrasonographic accuracy is diminished in perforated cases as the appendix may no longer be enlarged, and nonspecific features of absent peristalsis or a pericecal or perivesical mass may be the only fi ndings. The primary advantages of ultrasound are noninvasiveness, lack of radiation exposure, and high specificity. Retrospective studies have found its use to be associated with increased cost, increased time to surgery, and increased length of hospitalization without altering complication rates.53 Due to limited experience and reported poor sensitivity, many centers do not perform ultrasound on children with suspected appendicitis. For those sites performing ultrasound, a negative examination should not be relied upon to exclude appendicitis due to its limited sensitivity. CT is an accurate test for diagnosing appendicitis. CT has superior sensitivity to ultrasonography.51,52,54,55 Moreover, radiologists are more confident in their interpretation of CT for appendicitis compared to ultrasound.56 The most accurate CT studies have employed a standardized, focused helical technique with narrow collimation (3 to 5 mm) and narrow reconstructed images (every 1 to 3 mm) starting at the top of L3 or the iliac crest and extending distally to the acetabular roof or pubic symphysis. Using these techniques,

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sensitivities ≥ 95% have been achieved in children.51,52,54,57-60 Some experts recommend rectal contrast for improved visualization of the cecum and pericecal structures, and to opacify the lumen of uninflammed, unobstructed appendices.7,51,58-60 Administration of rectal contrast requires a cooperative patient who can retain the material (e.g., age > 3 to 4 years, no mental disability, and absent diarrhea). Others recommend intravenous contrast to improve bowel wall visualization. A single study found unenhanced CT to be accurate in children.52,54,57 Sensitivity of CT is substantially lower (53% to 84%) when nonstandarzied techniques are used, CT is not helical, or narrow collimation and narrow reconstructed images are not employed.55,61,62 False-negative CT scans also may be related to diminished pericecal fat at in children less than 10 years old, use of adult diagnostic criteria (e.g., 6-mm wall-to-wall appendiceal diameter), and lack of radiologic experience.7,63 The most common CT abnormalities, found in more than 90% of appendicitis cases, are an appendiceal wall-to-wall diameter greater than 6 mm and periappendiceal fat stranding.7,63,64 Other less common findings include focal cecal wall thickening adjacent to an inflamed appendix, an abscess, adenopathy, and right lower quadrant or pelvic fluid.7,63,64 An appendicolith is identified on CT in 65% of children with appendicitis and in 14% of nondiseased appendices.65 Alternate diagnoses in children without appendicitis are found in 30% to 34% of cases (e.g., nephrolithiasis, pyelonephritis, ovarian cyst or mass, ovarian torsion, inflammatory bowel disease, Meckel’s diverticulum).59,66 The main concern with CT scanning is radiation exposure.

Important Clinical Features and Considerations An important reason that it is difficult to diagnose appendicitis at younger ages is the multitude of more common nonsurgical disorders that cause similar symptoms. In fact, gastroenteritis and upper respiratory tract infections are the most common misdiagnoses in infants and children ultimately diagnosed with appendicitis6 (Table 73–3).

Management During evaluation, it is appropriate to control pain with short-acting intravenous analgesics. Providing analgesics to children with acute abdominal pain does not affect diagnostic accuracy or alter the clinical outcome of these children.67-69 Pediatric surgeons are significantly less likely to provide analgesia before definitive diagnosis compared to emergency physicians.70 To address their concerns, it may be appropriate to devise a policy whereby the surgeons are given a short window of opportunity to evaluate the patient. After their evaluation or if they are unable to see the patient in an expeditious manner, analgesics are administered. A reasonable initial medication is 0.05 mg/kg of intravenous morphine sulfate.68 Intravenous volume replacement should be administered to all children with suspected appendicitis and evidence of dehydration or sepsis. Maintenance fluids are indicated because children suspected of having appendicitis should be kept nil per os (NPO). Children with sepsis or evidence of perforation (e.g., temperature > 100.4° F, diffuse peritonitis,

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Table 73–3

Most Common Misdiagnoses in Children with Appendicitis

Initial Misdiagnosis Gastroenteritis Upper respiratory tract infection* Pneumonia Sepsis Urinary tract infection Encephalitis/encephalopathy Febrile seizure Blunt abdominal trauma Unknown

Percentage of Cases 42 18 4 4 4 2 2 2 22

*Includes otitis media, sinusitis, pharyngitis, and upper respiratory tract infection. From Rothrock SG, Skeoch G, Rush JJ, et al: Clinical features of misdiagnosed appendicitis in children. Ann Emerg Med 20:45–50, 1991.

ill appearance, symptoms duration > 36 to 48 hours) require broad-spectrum intravenous antibiotics. A single study found that use of ticarcillin/clavulanate plus gentamicin was associated with quicker defervesence and fewer infectious complications compared to traditional therapy of ampicillin and gentamicin plus clindamycin.71 Small studies have shown that monotherapy with cefoxitin, piperacillin/tazobactam, imipenem/cilastin, or ampicillin/sulbactam is equivalent to traditional multiple-drug therapy in preventing infectious complications from ruptured appendicitis.72 A meta-analysis also suggests that antibiotics are effective in preventing postoperative complications in children with uncomplicated appendicitis.73 However, antibiotics were effective whether they were given pre- or postoperatively in uncomplicated appendicitis.73 For this reason, antibiotic decisions in uncomplicated appendicitis can be deferred to the admitting surgeon. Definitive therapy of acute appendicitis is appendectomy prior to perforation. Unfortunately, a large of number of children develop perforation prior to diagnosis. For these patients, immediate fluid resuscitation and antibiotic therapy are required. A subset of children with perforated appendicitis and an appendiceal abscess may undergo delayed (interval) appendectomy 4 to 8 weeks following an initial course of intravenous antibiotics, depending upon the clinical presentation and initial response to intravenous antibiotics.74,75

Summary Most children who receive appropriate treatment for appendicitis do well. While a retrospective audit of adult patients with appendicitis who underwent interhospital transfer concluded no harm came to low-risk patients, no such studies have been performed in children.76 Children with appendicitis suffer more morbidity than adults, and transferring for economic reasons alone is inappropriate. Children with complicated appendicitis have a better outcome when cared for by pediatric surgeons.77 With this in mind, it may be appropriate to transfer a subset of complicated cases that do not require immediate surgery in addition to cases in which the general surgeon is inexperienced with children and unable to provide appropriate care (see Chapter 150, Emergency Medical Treatment and Labor Act [EMTALA]).

REFERENCES *1. Rothrock SG, Pagane J: Acute appendicitis in children: emergency department diagnosis and management. Ann Emerg Med 36:39–51, 2000. 2. Reynolds SL, Jaffe DM: Children with abdominal pain in a pediatric emergency department. Pediatr Emerg Care 6:8–12, 1990. 3. Reynolds SL, Jaffe DM: Diagnosing abdominal pain in a pediatric emergency department. Pediatr Emerg Care 8:126–128, 1992. 4. Scholer SJ, Pituch K, Orr DP, et al: Clinical outcomes of children with acute abdominal pain. Pediatrics 98:680–685, 1996. 5. Lin Y, Lee C: Appendicitis in infancy. Pediatr Surg Int 19:1–3, 2003. 6. Rothrock SG, Skeoch G, Rush JJ, et al: Clinical features of misdiagnosed appendicitis in children. Ann Emerg Med 20:45–50, 1991. 7. Grayson DE, Wettlaufer JR, Dalrymple NC, et al: Appendiceal CT in pediatric patients: relationship of visualization to amount of peritoneal fat. AJR Am J Roentgenol 176:497–500, 2001. 8. Bax NM, Pearse RG, Dommering N, et al: Perforation of the appendix in the neonatal period. J Pediatr Surg 15:200–202, 1980. 9. Bryant LR, Trinkle JK, Noon JA, et al: Appendicitis and appendiceal perforation in neonates. Am Surg 36:523–525, 1970. 10. Buntain WL, Krempe RE, Kraft JW: Neonatal appendicitis. Alabama J Med Sci 21:295–298, 1984. 11. Shaul WL: Clues to the early diagnosis of neonatal appendicitis. J Pediatr 98:473–476, 1981. 12. Alloo J, Gerstle T, Shilyansky J, Ein SH: Appendicitis in children less than 3 years of age: a 28-year review. Pediatr Surg Int 19:777–779, 2004. 13. Barker AP, Davey RB: Appendicitis in the fi rst three years of life. Aust N Z J Surg 58:491–494, 1988. 14. Bartlett RH, Eraklis AJ, Wilkinson RH: Appendicitis in infancy. Surg Gynecol Obstet 130:99–105, 1970. 15. Grosfeld JL, Weinberger M, Clatworthy HW: Acute appendicitis in the fi rst two years of life. J Pediatr Surg 8:285–292, 1973. 16. Horwitz JR, Gursoy M, Jaksic T, et al: Importance of diarrhea as a presenting symptom of appendicitis in very young children. Am J Surg 173:80–82, 1997. 17. Puri P, O’Donnell B: Appendicitis in infancy. J Pediatr Surg 13:173– 174, 1978. 18. Daehlin L: Acute appendicitis during the fi rst three years of life. Acta Chir Scand 148:291–294, 1982. 19. Graham JM, Pokorny WJ, Harbery FJ: Acute appendicitis in preschool age children. Am J Surg 139:247–250, 1980. 20. Golladay ES, Sarrett JR: Delayed diagnosis in pediatric appendices. South Med J 81:38–41, 1988. 21. Williams N, Kapila L: Acute appendicitis in the under five year old. J R Coll Surg Edinb 39:168–170, 1994. 22. Williams N, Kapila L: Acute appendicitis in the preschool child. Arch Dis Child 66:1270–1272, 1991. 23. Siegal B, Hyman E, Lahat E, et al: Acute appendicitis in early childhood. Helv Paediatr Acta 37:215–219, 1982. 24. Wilson D, Sinclair S, McCallion WA, et al: Acute appendicitis in young children in the Belfast urban area: 1985–1992. Ulster Med J 63:3–7, 1994. 25. Rasmussen OO, Hoffman J: Assessment of the reliability of the symptoms and signs of acute appendicitis. R Coll Surg Edinb 36:372–377, 1991. 26. Williams NM, Johnstone JM, Everson NW: The diagnostic value of symptoms and signs in childhood abdominal pain. J R Colle Surg Edinb 43:390–392, 1998. *27. Samuel M: Pediatric appendicitis score. J Pediatr Surg 37:877–881, 2002. 28. Gauderer MWL, Crane MM, Green JA, et al: Acute appendicitis in children: the importance of family history. J Pediatr Surg 36:1214–1217, 2001. 29. Basta M, Morton NE, Mulvhill JJ, et al: Inheritance of acute appendicitis: familial aggregation in the United States. Am J Epidemiol 132: 910–924, 1990. 30. Brender JD, Marcuse EK, Weiss NS, et al: Is childhood appendicitis familial? Am J Dis Child 139:338–340, 1985. 31. Andersson N, Griffith H, Murphy J, et al: Is appendicitis familial? Br Med J 2:697–698, 1979.

*Selected readings.

Chapter 73 — Appendicitis 32. Doriaswamy NW: Pregress of acute appendicitis: a study in children. Br J Surg 65:877–879, 1978. 33. Dickson JA, Jones A, Telfer S, et al: Acute abdominal pain in children. Scand J Gastroenterol Suppl 144:43–46, 1988. 34. Rothrock SG, Green SM, Dobson M, et al: Misdiagnosis of appendicitis in non-pregnant women of child bearing age. J Emerg Med 24:1–9, 1995. 35. Eriksson S, Granstrom L, Olander B, Wretlind B: Sensitivity of interleukin-6 and C-reactive protein concentrations in the diagnosis of acute appendicitis. Eur J Surg 161:41–45, 1995. 36. Eriksson S, Granstrom L, Carlstrom A: The diagnostic value of repetitive preoperative analysis of C-reactive protein and total leucocyte count in patients with suspected appendicitis. Scand J Gastroenterol 29:1145–1149, 1994. 37. Anderson RE, Hugander A, Ravn H, et al: Repeated clinical and laboratory examinations in patients with equivocal diagnosis of appendicitis. World J Surg 24:479–485, 2000. 38. Thompson MM, Underwood MJ, Dookeran KA, et al: Role of sequential leucocyte counts and C-reactive protein measurements in acute appendicitis. Br J Surg 79:822–824, 1992. 39. Lyons D, Waldron R, Ryan T, et al: An evaluation of the clinical value of the leucocyte count and sequential counts in suspected acute appendicitis. Br J Clin Pract 41:794–796, 1987. 40. Arnbjornsson E: Bacturia in appendicitis. Am J Surg 155:356–358, 1988. 41. Bond GR, Tully SG, Chan LS, Bradley RL: Use of the MANTRELS score in childhood appendicitis: a prospective study of 187 children with abdominal pain. Ann Emerg Med 19:1014–1018, 1990. 42. Owen TD, Williams H, Stiff G, et al: Evaluation of the the Alvarado score in acute appendicitis. J R Soc Med 85:87–88, 1992. 43. Gwynn LK: The diagnosis of acute appendicitis: clinical assessment versus computed tomography evaluation. J Emerg Med 21:119–123, 2001. 44. Bakha RK, McNair MM: Useful radiologic signs in acute appendicitis in children. Clin Radiol 28:193–196, 1977. 45. Johnson JF, Coughlin WF, Stark P: The sensitivity of plain fi lms for detecting perforation in children with appendicitis. ROFO Fortschr Geb Rontgenstr Nuklearmed 149:619–623, 1988. 46. Rothrock SG, Green SM, Harding M, et al: Plain abdominal radiography in the detection of acute medical and surgical disease in children: a retrospective analysis. Pediatr Emerg Care 7:281–285, 1991. 47. Rothrock SG, Green SM, Hummel CB: Plain abdominal radiography in the detection of major disease in children. Ann Emerg Med 21:1423– 1429, 1992. 48. Boleslawski E, Panis Y, Benoist S, et al: Plain abdominal radiography as a routine procedure for acute abdominal pain of the right lower quadrant: prospective evaluation. World J Surg 23:264–266, 1999. 49. Hahn HB, Hoepner FU, Kalle T, et al: Sonography of acute appendicitis in children: 7 years experience. Pediatr Radiol 28:147–151, 1998. 50. Schulte B, Beyer D, Kaiser C, et al: Ultrasonography in suspected acute appendicitis in childhood—report of 1285 cases. Eur J Ultrasound 8:177–182, 1998. *51. Garcia Pena BM, Mandl KD, Kraus SJ, et al: Ultrasonography and limited computed tomography in the diagnosis and management of appendicitis in children. JAMA 282:1041–1046, 1999. 52. Sivit CJ, Applegate KE, Stallion A, et al: Imaging evaluation of suspected appendicitis in a pediatric population: effectiveness of sonography versus CT. AJR Am J Roentgenol 175:977–981, 2000. 53. Roosevelt GE, Reynolds SL: Does the use of ultrasonography improve the outcome of children with appendicitis? Acad Emerg Med 5:1071– 1075, 1998. 54. Kaiser S, Frenckner B, Jourlf HK: Suspected appendicitis in children: US and CT—a prospective randomized study. Radiology 223:633–638, 2002.

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55. Karakas SP, Guelfuat M, Leonidas JC, et al: Acute appendicitis in children: comparison of clinical diagnosis with US and CT imaging. Pediatr Radiol 30:94–98, 2000. 56. Garcia Pena BM, Taylor GA: Radiologists’ confidence in interpretation of sonography and CT in suspected pediatric appendicitis. AJR Am J Roentgenol 175:71–74, 2000. 57. Lowe LH, Penney MW, Stein SM, et al: Unenhanced limited CT of the abdomen in the diagnosis of appendicitis in children: comparison with sonography. AJR Am J Roentgenol 176:31–35, 2001. 58. Mullins ME, Kircher MF, Ryan DP, et al: Evaluation of suspected appendicitis in children using limited helical CT and colonic contrast material. AJR Am J Roentgenol 176:37–41, 2001. 59. Sivit CJ, Dudgeon DL, Applegate KE, et al: Evaluation of suspected appendicitis in children and young adults: helical CT. Radiology 216:430–433, 2000. 60. Stephen AE, Segev DL, Ryan DP, et al: The diagnosis of acute appendicitis in a pediatric population: to CT or not to CT. J Pediatr Surg 38:367–371, 2003. 61. Patrick DA, Janik JE, Janik JS, et al: Increased CT scan utilization does not improve the diagnostic accuracy of appendicitis in children. J Pediatr Surg 38:659–662, 2003. 62. Reich JK, Brogdon B, Ray WE, et al: Use of CT scan in the diagnosis of pediatric acute appendicitis. Pediatr Emerg Care 16:241–243, 2000. 63. Callahan MJ, Rodriguez DP, Taylor GA: CT of appendicitis in children. Radiology 224:325–332, 2002. 64. Friedland JA, Siegel MJ: CT appearance of acute appendicitis in childhood. AJR Am J Roentgenol 168:439–442, 1997. 65. Lowe LH, Penney MW, Scheker LE, et al: Appendicolith revealed on CT in children with suspected appendicitis: how specific is it in the diagnosis of appendicitis? AJR Am J Roentgenol 175:981–984, 2000. 66. Lowe LH, Perez R, Scheker LE, et al: Appendicitis and alternate diagnoses in children: fi ndings on unenhanced limited helical CT. Pediatr Radiol 31:569–577, 2001. 67. Kim MK, Strait RT, Sato TT, Hennes HM: A randomized clinical trial of analgesia in children with acute abdominal pain. Acad Emerg Med 9:281–287, 2002. 68. Green R, Bulloch B, Kabani A, et al: Early analgesia for children with acute abdominal pain. Pediatrics 116:978–983, 2005. 69. Goldman RD, Crum D, Bromberg R, et al: Analgesia administration for acute abdominal pain in the pediatric emergency department. Pediatr Emerg Care 22:18–21, 2006. 70. Kim MK, Galustyan S, Sato TT, et al: Analgesia for children with acute abdominal pain: a survey of pediatric emergency physicians and pediatric surgeons. Pediatrics 112:1122–1126, 2003. 71. Rodriguez JC, Buckner D, Schoenike S, et al: Comparison of two antibiotic regimens in the treatment of perforated appendicitis in pediatric patients. Int J Clin Pharmacol Ther 38:492–499, 2000. 72. Kaplan S: Antibiotic usage in appendicitis in children. Pediatr Infect Dis J 17:1047–1048, 1998. *73. Andersen BR, Kallehave FL, Andersen HK: Antibiotics versus placebo for prevention of postoperative infection after appendicectomy. Cochrane Database Syst Rev (2):CD001439, 2003. 74. Gillick J, Velayudham M, Puri P: Conservative management of appendix mass in children. Br J Surg 88:1539–1542, 2001. 75. Weber TR, Keller MA, Bower RJ, et al: Is delayed operative treatment worth the trouble with perforated appendicitis in children? Am J Surg 186:685–688, 2003. 76. Norton VC. Schriger DL: Effect of transfer on outcome of patients with appendicitis. Ann Emerg Med 29:467–473, 1997. 77. Alexander F, Magnusion D, DiFiore J, et al: Specialty versus generalist care of children with appendicitis: an outcome comparison. J Pediatr Surg 36:1510–1513, 2001.

Chapter 74 Intussusception Jonathan I. Singer, MD

Key Points The diagnosis of intussusception should be considered in any infant or child with severe, episodic abdominal pain. The combination of rhythmic abdominal pain, vomiting, blood in the stool, and an abdominal mass is absent in most patients with intussusception. An atypical clinical pattern (e.g., atypical age, absence of pain, nonbloody diarrhea, altered mental status) is common in intussusception. Prolonged history, in the face of a normal examination, should not exclude the diagnosis of intussusception. A normal plain abdominal radiograph cannot exclude the diagnosis of intussusception.

Introduction and Background Intussusception is an invagination (or telescoping) of one segment of the intestinal tract into another. The invagination may be within the same portion of gastrointestinal (GI) tract (intragastric, jejunojejunal, colocolic), or a proximal portion of the intestine can invaginate into a distal adjacent part (duodenal-jejunal, ileocolic, sigmoid-rectal). More than 90% of cases of intussusception that occur in infants and children are ileocolic.1 The telescoped bowel causes bowel wall ischemia and edema and leads to abdominal pain and other associated features of intussusception.2

Recognition and Approach Intussusception may occur at any age (Fig. 74–1). Cases have been described in preterm infants, throughout childhood, and into adulthood.3 Neonates constitute less than 1% of all reported pediatric cases. In large series, most intussusceptions occur prior to age 2. A majority of this subgroup have occurred between the fifth and ninth month of life. Of late, more cases have been depicted in children beyond the fifth 582

year of age. Intussusception historically has been described in well-nourished children, but institutional reviews from the past decades have substantiated encounters in undernourished children.4 Intussusception affects males two times more frequently than females. While most cases are sporadic, occasional familial associations have been reported.5,6 The cause of intussusception is unknown in 90% of pediatric cases. There is no recognized etiology for an abnormal peristaltic wave that leads to the invagination. Venous and lymphatic flow from the intussuscepted segment is interrupted. Obstructed venous drainage produces edema of the bowel wall. Epithelium may be sloughed and mixed with stool, leading to bloody, mucus-fi lled stools. If the intussusception is undiagnosed, compromised arterial blood flow may lead to bowel necrosis with bowel perforation. In 10% of cases an identifiable cause for intussusception is found.7 Intussusceptions that occur within the first month of life are more often associated with an abnormal congenital malformation.8,9 An abnormal “lead point” (pathologic lesion) for intussusception is common in children older than 4 years, and may be due to various infections, inflammatory disease states, posttraumatic events, and surgical procedures (Table 74–1). Beyond the 14th year of life, intussusception is uniformly associated with a lead point.7 The tempo of intussusception may be variable. Most children have an abrupt onset of symptoms, and parents seek medical attention within 24 hours of onset. This acute presentation results from complete intestinal obstruction or release of neuroactive GI tract hormones.10 Some children have symptoms that are prolonged from days to weeks (chronic intussusception).11 A longer duration of symptoms is more characteristic of patients beyond 2 years of age and in those who have an incomplete (nonstrangulating, nonischemic) intussusception.

Clinical Presentation The pain of intussusception can produce a sudden screaming fit in a child, with doubling of the thighs onto the abdomen. Pain may last several minutes. After an asymptomatic interval, repeated paroxysms will cause the child to cry out again. The child may be inconsolable or may seem comfortable in a knee-chest position in the arms of the caregiver. Vomiting tends to occur shortly after the initial painful episode. Children typically vomit only gastric contents. Occasionally, the emesis may be bilious, fecal, or bloody. Bowel movements

30 25 20 15 10 5

ye ar s >5

ye ar s 5

ye ar s 3

ye ar s 2

3

1

ye ar

0 m on th s 6 m on th s 9 m on th s

Cases per 10,000 patients per year

Chapter 74 — Intussusception

Patient age FIGURE 74–1. Annual incidence of intussusception at different ages.2,42-45

Table 74–1

Risk Factors and Pathologic Lead Points for Intussusception

Cystic fibrosis Foreign body ingestion Gastrojejunal feeding tube Hemangiomas Hemophilia Henoch-Schönlein purpura (intussusception develops in 3–5% with this disorder) Intestinal duplications Intestinal lymphoma Intestinal polyps (e.g., juvenile polyps, Peutz-Jeghers syndrome) Meckel’s diverticulum Neurofibromatosis Peyer’s patch hypertrophy (postviral or parasitic enteritis) Rotavirus vaccine Surgical procedures (especially retroperitoneal surgery, as in Wilms’ tumor removal) Trauma with bowel wall edema or hemorrhage

vary from formed to liquid. Within 3 to 24 hours, stool is passed that has a gelatinous, mucus-like consistency. The presence of blood in fecal material may be trace to copious.12 While the classic triad of intussusception is colicky, intermittent severe abdominal pain, vomiting, and rectal bleeding, this combination of features is found in less than one third of all patients.13 Between 85% and 92% of children manifest colicky abdominal pain, while 60% to 80% of patients experience vomiting.1,4 Gross blood is present in the stools of 40% to 50% of patients.12,14 “Current jelly” stools, which are mucoid, bloody, and maroon in color, account for a minority of bloody stools.12 Of those children without gross blood in the stool, 75% have occult blood on rectal examination.14 The child with intussusception is often well perfused, hydrated, and alert despite apparent discomfort.13 The abdomen is flat, nondistended, and occasionally scaphoid. The abdomen is typically soft and nontender except in the region of the intussusception, where voluntary guarding may be seen. A sausage-shaped, sometimes ill-defined, and variably tender mass may be present on palpation of the right upper quadrant or right midabdomen. The combination of a right upper quadrant mass and a scaphoid right lower

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abdomen is termed Dance’s sign and is highly suggestive of an intussusception. In some cases, rectal examination may reveal a mass. Classic signs are often absent in infants and children with intussusception, and no single or combination of examination features can reliably exclude this disorder.13,15 Atypical symptoms and signs may lead to misdiagnosis or a delay in diagnosis.16-18 Clinicians need to be aware of the broad range of atypical presentations that occur in intussusception (Table 74–2). When patients present with typical clinical features (e.g., intermittent severe pain, an abdominal mass, and bloody stool), the diagnosis is readily apparent. When the picture is less complete, and atypical manifestations dominate, other diagnoses may be entertained.19 The differential diagnosis is broad and based on the wide variety of pediatric disorders causing pain, vomiting, an abdominal mass, and rectal bleeding (Table 74–3). Diagnostic Evaluation Several laboratory tests should be undertaken when there is suspicion of intussusception. Following a rectal examination, the stool should be tested for occult blood. A negative guaiac test does not exclude the diagnosis, but decreases the likelihood that intussusception is present.14 When the duration of symptoms is brief, and the child is without dehydration, hyperthermia, or peritoneal irritation, blood chemistries and complete blood count are not useful diagnostically. However, these tests are of utility in the face of significant bleeding, shock, or dehydration. Cultures of blood, urine, and stool are appropriate for the septic-appearing child.20 The child with altered mental status requires a bedside estimate of blood sugar. One of several imaging procedures should be undertaken when there is a suspicion of intussusception. Diagnostic emergency imaging may take the form of plain abdominal radiography, ultrasonography (US), or computed tomography (CT). Plain abdominal radiographs usually constitute the first imaging test when intussusception is suspected. A supine and upright or supine and left lateral decubitus film of the abdomen can be obtained. The most important role of plain abdominal radiography is to uncover contraindications to contrast enema. Patients with radiographic evidence of a high-grade bowel obstruction, intraperitoneal air, or pneumatosis intestinalis should not be subjected to contrast enema. The secondary function of plain radiographs is to see if intussusception is likely. The radiographic findings suggestive of intussusception include minimal intestinal gas, minimal fecal content in the colon, mass lesion, inability to visualize the liver tip, localized air-fluid levels, and dilated small bowel loops.21 In fact, intussusception may be the most common cause of bowel obstruction under the age of 2 years.22 The diagnosis can be confirmed only when plain fi lm shows the head of the intussusception within the bowel lumen.22 It is important to recognize that fi lms may be normal in up to 25% to 26% of cases, with another 53% of plain fi lms having nonspecific or equivocal findings.23,24 Due to nonspecificity of plain fi lms, radiologists agree on the radiographic findings in as few as 12% of cases.24 Ultrasonography may also be useful in establishing the diagnosis of intussusception and, when it is discovered, may dictate the optimum mode of reduction. Ultrasonography tends to be of greater utility in patients with a nonspecific

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SECTION IV — Approach to the Acutely Ill Patient

Table 74–2

Atypical Clinical Features in Intussusception1,11,13,15,17,40,46-52

Age Absent pain Chronic and transitory pain Vomiting Diarrhea Nonbloody stool Altered mental status Nonspecific prodrome Prior surgery

Vital signs Neurologic findings Abdominal mass Rectal examination

Table 74–3

While the most common age range is 5–9 mo, cases of intussusception are reported in older children, adolescents, and even adults. 8–18% of infants and children have painless intussusception. Others may have a single paroxysm of pain without rhythmic, periodic pain. Individuals with subacute and chronic presentations may be overlooked. Many cases of intussusception are ultimately diagnosed in individuals who have had symptomology from weeks to months. Cases of transient (self-reducing) intussusception have been reported. Vomiting is the chief complaint in 40% of children who present to the emergency department. Vomiting may be the first identified complaint, preceding pain by many hours. While vomiting is usually nonbilious, occasional infants have presented with bilious vomiting. Nonbloody diarrhea is a prominent complaint, occurring in up to 19% of cases. Only half of all patients have gross rectal bleeding. Of the remaining patients, 25% have heme-negative stool. Depressed consciousness with obtundation or coma state may be the primary manifestation or dominant concern of the caregiver. Respiratory manifestations, fever, and nonspecific complaints such as anorexia, nausea, and constipation may precede the readily diagnosed symptom complex. Previous abdominal surgery, particularly retroperitoneal dissection (e.g., Wilms’ tumor removal), is a risk factor for intussusception. Intussusception of the appendiceal stump is a known complication of appendectomy. The interval from operation to onset of intussusception may be as long as 5 years. Gastrojejunal tubes predispose to intussusception. Tachycardia, fever, hypertension, or apnea may be seen early in the course of intussusception. Hypotension, poor perfusion with pallor, and diaphoresis may be seen in the context of prolonged symptomology, excessive blood loss, and ischemic bowel with secondary sepsis. Apathy, miosis, decreased motor tone, seizure, or opisthotonic posturing may occur as the initial indication of illness or well after gastrointestinal signs are present. Between bouts of invagination, an abdominal mass may be absent. During invagination, the mass may pass into the hepatic flexure and may be difficult or impossible to feel. Despite only a brief history of illness, the intussusception may protrude through the anus.

Differential Diagnosis of Intussusception Physical Features Prominent Symptoms

Abdominal Mass

Abdominal Pain

Vomiting or Diarrhea

Altered Mental Status

Congenital

Acquired

Rectal Bleeding

Appendicitis

Malrotation with midgut volvulus Appendicitis Bowel obstruction Incarcerated hernia

Metabolic derangement Endocrinopathy Diabetic ketoacidosis Drug intoxication

Teratoma

Wilms’ tumor

Dysgerminoma Yolk sac tumor Embryonal carcinoma

Pheochromocytoma Lymphoma*

Ischemic bowel due to shock Rectal prolapse Meckel’s diverticulum* Juvenile polyp*

Infectious enterocolitis Pseudomembranous colitis or invasive bacterial enteritis

Closed head injury

Epiploic appendicitis Primary peritonitis Torsion, ovary/testicle Mesenteric ischemia

Adenocarcinoma

Fissure

*These disorders can also serve as a lead point and cause intussusception.

history, normal physical examination, or atypical clinical pattern. Sonographic findings of intussusception are a large sonolucent target, a bull’s-eye or donut sign on the transverse (cross) section, and a sleeve or pseudo–kidney sign on the longitudinal section.25 When either plain fi lms or US exhibits positive findings that are nonspecific or highly suggestive, an air or barium contrast enema should be undertaken to reduce the intussusception if no contraindications exist. A contrast enema with barium or air under fluoroscopic or sonographic guidance is the procedure of choice for diagnosing intussuception. Moreover, these techniques can successfully reduce the intussusception in 65% to 90% of cases.26-28 Success rates are highest for individuals who have had symptoms for less than 24 hours.13 Neonates and patients beyond age 4 are less likely to experience reduction and more likely to require surgical exploration. Rare complications of

air and barium contrast studies include bleeding and perforation.29 Additional risks include the reduction of necrotic bowel or reduction without detecting a pathologic lead point.7,30 Spiral CT has occasionally been employed to diagnose equivocal cases, although this technique is not routinely recommended. CT findings include a distended bowel loop with a thickened, edematous wall and an eccentric, crescentic or wedge-shaped, low-density intraluminal mass that represents the invaginated mesentery.11

Important Clinical Features and Considerations An unusual type of intussusception is a small bowel intussusception (SBI), accounting for less than 2% of all cases.31

Chapter 74 — Intussusception

Children with this variant are older than typical cases (mean age 4 to 4.5 years) and have a longer duration of symptoms prior to initial presentation (mean 76 hours).31,32 In contrast to typical ileocolic cases, an SBI can be located in the left side of the abdomen. Ultrasound may miss this disease in up to 24% of cases since the outer diameter of the intussusception is smaller than for ileocolic cases and the location is often atypical.31,32 Due to its proximal location, air contrast and barium enema are not useful for diagnosis or reduction of SBI.32 Diagnosis is often made by CT or during laparotomy when other surgical disorders are suspected.31,32 Controversy exists as to the exact sequence of radiologic procedures needed in suspected intussusception. Some centers with extensive US experience rely on a normal scan to exclude the diagnose in patients with a moderate to low clinical suspicion, only obtaining contrast studies if the US is positive or equivocal.33 Since US misses up to 5% of ileocolic cases (and 24% of SBI cases), close observation is required for patients with a negative US. If a high clinical suspicion is present, contrast enema is still required.33-35 Use of US in this manner can decrease the radiation risk and exposure to an invasive procedure. Moreover, US can be used to direct the hydrostatic reduction and improve the reduction rates with contrast enemas.36,37 Ultrasound-guided hydrostatic reduction is less successful if the intussusception is left sided or contains entrapped fluid (edema). One study of US-guided reduction analyzed the thickness of the hypoechogenic external layer of the intussusceptum to determine its association with successful reduction. The authors found that reduction was 100% successful if this layer was less than 7.2 mm thick, 68% successful if it was 7.5 to 12 mm thick, and never successful if the bowel wall was greater than 14 mm thick.38 During evaluation or reduction of intussusception, clinicians may be tempted to administer sedatives. However, infants and children must be able to perform a Valsalva maneuver during contrast studies, and administration of these medications may reduce the successful reduction rates.33

Management The uncomplicated patient does not require airway intervention or either respiratory or circulatory support. Monitoring that is appropriate for the degree of patient instability should be initiated. Intravenous lines are inserted in all patients, and a fluid bolus is administered to all individuals with either excessive diarrhea or blood loss from ischemia or frank hemorrhage. A normal saline bolus is administered at a rate of 20 ml/kg over a brief time frame and repeated until the patient becomes hemodynamically stable. All patients should be placed on “nothing by mouth” status. Although not universally performed, pending surgical consultation and imaging procedures, a nasogastric tube is recommended. Following resuscitation, a decision must be made concerning whether there are contraindications to nonoperative attempts at reduction of the intussusception. For patients without contraindications, the radiologist and surgical consultant can determine whether air insufflation or barium reduction is employed.29 If pneumatic or hydrostatic pressure techniques fail to reduce the intussusception, a repeated effort at nonoperative reduction from 30 minutes to 24 hours

585

later is an option.26,39 With failure of reduction, operative therapy must be employed. About 60% of cases that could not be reduced nonoperatively are successfully reduced at surgery without resection.26

Summary Patients who require surgical reduction of intussusception generally have an uncomplicated postoperative course. Those who undergo surgical reduction experience a recurrence rate between 2% and 5%.25 Individuals who have successful nonoperative reduction who had been stabilized before undergoing the contrast enema have prompt return of intestinal function. Their vital signs, if altered, return to normal within hours. Patients who have presented with altered mental status have abrupt return to alertness following reduction.40 Patients who have had nonoperative reduction have a 2% to 20% rate of recurrence.30 Recurrence may occur up to 1 year following the initial intussusception. However, most cases occur within 1 to 3 days following pneumatic or hydrostatic reduction. It is not possible to establish which patients are likely to have recurrent intussusception based on presenting signs and symptoms, age, or sex.41 Some facilities admit the child to the hospital for a 24-hour time frame. Other institutions observe the child in the emergency department for less than a 24hour time frame prior to discharge home.27 Otherwise healthy children who have a successful enema reduction suffer no adverse outcomes when discharged from the emergency department.39 If observation within the emergency department is carried out, at discharge the emergency physician must ascertain if parents understand the indications that warrant a return for further medical attention (i.e., recurrent symptoms, vomiting, new or different pain, or GI bleeding). REFERENCES 1. Bergdahl S, Hugosson C, Lauren T, Soderlund S: Atypical intussusception. J Pediatr Surg 7:700–705, 1972. 2. O’Ryan M, Lucero Y, Pena A, Valenzuela MT: Two year review of intestinal intussusception in six large public hospitals of Santiago, Chile. Pediatr Infect Dis J 22:717–721, 2003. 3. Martinez Biarge M, Garcia-Alix A, Luisa del Hoyo M, et al: Intussusception in a preterm neonate: a very rare, major intestinal problem— systematic review of cases. J Perinat Med 32:190–194, 2004. 4. Luks FI, Yazbeck S, Perreault G, Desjardins JG: Changes in the presentation of intussusception. Am J Emerg Med 10:574–576, 1992. 5. Stringer MD, Holmes SJ: Familial intussusception. J Pediatr Surg 27:1436–1437, 1992. 6. McGovern CM: Intussusception in twins. Am J Emerg Med 18:742– 743, 2000. 7. Blakelock RT, Beasley SW: The clinical implications of non-idiopathic intussusception. Pediatr Surg Int 14:163–167, 1998. 8. Patriquin HB, Afshani E, Effman E, et al: Neonatal intussusception: report of 12 cases. Radiology 125:463–466, 1977. 9. Wang NL, Yeh ML, Chang PY, et al: Prenatal and neonatal intussusception. Pediatr Surg Int 13:232–236, 1998. *10. Conway EE Jr: Central nervous system fi ndings and intussusception: how are they related? Pediatr Emerg Care 9:15–18, 1993. 11. Schulman H, Laufer L, Kurzbert E, et al: Chronic intussusception in childhood. Eur Radiol 8:1455–1456, 1998. *12. Yamamoto LG, Morita SY, Boychuk RB, et al: Stool appearance in intussusception: assessing the value of the term “currant jelly.” Am J Emerg Med 15:293–298, 1997. 13. Fanconi S, Berger D, Rickham PP: Acute intussusception: a classic clinical picture? Helv Paediatr Acta 37:345–352, 1982. *Selected readings.

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*14. Losek JD, Fiete RL: Intussusception and the diagnostic value of testing stool for occult blood. Am J Emerg Med 9:1–3, 1991. 15. Ravitch M: Considerations of errors in the diagnosis of intussusception. Am J Dis Child 84:17, 1952. 16. Teitelbaum JE, Fishman SJ, Leichtner AM, Tunnessen WW: “Read my lips”: abdominal pain in a 14-year-old. Contemp Pediatr 16:31–41, 1999. 17. Shteyer E, Koplewitz BZ, Gross E, Granot E: Medical treatment of recurrent intussusception associated with intestinal lymphoid hyperplasia. Pediatrics 111:682–685, 2003. 18. Pollack CV Jr, Pender ES: Unusual cases of intussusception. J Emerg Med 9:347–355, 1991. 19. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 24-1997: a six-year-old boy with bouts of abdominal pain, vomiting, and a left-sided abdominal mass. N Engl J Med 337:329–336, 1997. 20. McCabe JB, Singer JI, Love T, Roth R: Intussusception: a supplement to the mnemonic for coma. Pediatr Emerg Care 3:118–119, 1987. 21. Daneman A, Alton DJ: Intussusception: issues and controversies related to diagnosis and reduction. Radiol Clin North Am 34:743–756, 1996. 22. Lazar L, Rathaus V, Erez I, Katz S: Interrupted air column in the large bowel on plain abdominal fi lm: a new radiological sign of intussusception. J Pediatr Surg 30:1551–1553, 1995. 23. Eklof O, Hartelius H: Reliability of the abdominal plain fi lm diagnosis in pediatric patients with suspected intussusception. Pediatr Radiol 9:199–206, 1980. 24. Sargent MA, Babyn P, Alton DJ: Plain abdominal radiography in suspected intussusception: a reassessment. Pediatr Radiol 24:17–20, 1994. 25. Harrington L, Connolly B, Hu X, et al: Ultrasonographic and clinical predictors of intussusception. J Pediatr 132:836–839, 1998. 26. Sandler AD, Ein SH, Connolly B, et al: Unsuccessful air-enema reduction of intussusception: is a second attempt worthwhile? Pediatr Surg Int 15:214–216, 1999. 27. Le Masne A, Lortat-Jacob S, Sayegh N, et al: Intussusception in infants and children: feasibility of ambulatory management. Eur J Pediatr 158: 707–710, 1999. 28. Peh WC, Khong PL, Lam C, et al: Reduction of intussusception in children using sonographic guidance. AJR Am J Roentgenol 173:985– 988, 1999. 29. Daneman A, Navarro O: Intussusception, Part 2: an update on the evolution of management. Pediatr Radiol 34:97–108, 2004. 30. Eshel G, Barr J, Heiman E, et al: Incidence of recurrent intussusception following barium versus air enema. Acta Paediatr 86:545–546, 1997. 31. Ko SF, Lee TY, Ng SH, et al: Small bowel intussusception in symptomatic pediatric patients: experiences with 19 surgically proven cases. World J Surg 26:438–443, 2002. 32. Kim JH: US features of transient small bowel intussusception in pediatric patients. Kor J Radiol 5:178–184, 2004. 33. Henrikson S, Blane CE, Koujok K, et al: The effect of screening sonography on the positive rate of enemas for intussusception. Pediatr Radiol 33:190–193, 2003.

34. Rohrschneider WK, Troger J: Hydrostatic reduction of intussusception under US guidance. Pediatr Radiol 25:530–534, 1995. 35. del-Pozo G, Albillos JC, Tejedor D, et al: Intussusception in children: current concepts in diagnosis and enema reduction. Radiographics 19:299–319, 1999. 36. Crystal P, Hertzanu Y, Farber B, et al: Radiographically guided hydrostatic reduction of intussusception in children. J Clin Ultrasound 30: 343–348, 2002. 37. Grant RL, Piotto L: Benefits of sonographic hydrostatic reduction as opposed to air reduction in a case of intussusception due to lymphoma. Australas Radiol 48:264–266, 2004. 38. Mirilas P, Koumanidou C, Vakaki M, et al: Sonographic features indicative of hydrostatic reducibility of intestinal intussusception in infancy and early childhood. Eur Radiol 11:2576–2580, 2001. 39. Gonzalez-Spinola J, Del Pozo G, Tejedor D, Blanco A: Intussusception: the accuracy of ultrasound-guided saline enema and the usefulness of a delayed attempt at reduction. J Pediatr Surg 34:1016–1020, 1999. 40. Singer J: Altered consciousness as an early manifestation of intussusception. Pediatrics 64:93–95, 1979. 41. Champoux AN, Del Beccaro MA, Nazar-Stewart V: Recurrent intussusception: risks and features. Arch Pediatr Adolesc Med 148:474–478, 1994. *42. Bajaj L, Roback MG: Postreduction management of intussusception in a children’s hospital emergency department. Pediatrics 112(6 Pt 1):1302–1307, 2003. 43. Parashar UD, Holman RC, Cummings KC, et al: Trends in intussusception association hospitalizations and deaths among US infants. Pediatrics 106:1413–1421, 2000. 44. Perez-Schael I, Escalona M, Salinas B, et al: Intussusception associated hospitalization among Venezuelan infants during 1998 through 2001: anticipating rotavirus vaccines. Pediatr Infect Dis J 22:234–239, 2003. *45. Fischer TK, Bihrmann K, Perch M, et al: Intussusception in early childhood: a cohort study of 1.7 million children. Pediatrics 114:782– 785, 2004. 46. Birkhahn R, Fiorini M, Gaeta TJ: Painless intussusception and altered mental status. Am J Emerg Med 17:345–347, 1999. 47. Losek JD: Intussusception: don’t miss the diagnosis! Pediatr Emerg Care 9:46–51, 1993. 48. Orenstein J: Update on intussusception. Contemp Pediatr 17:180–191, 2000. 49. Ein SH, Stephens CA: Intussusception: 354 cases in 10 years. J Pediatr Surg 6:16–27, 1971. 50. La Salle AJ, Andrassy RJ, Page CP, et al: Intussusception of the appendiceal stump. Clin Pediatr (Phila) 19:432–435, 1980. 51. Barton LL, Chundu K: Intussusception associated with transient hypertension. Pediatr Emerg Care 4:249–250, 1988. 52. Goetting MG, Tiznado-Garcia E, Bakdash TF: Intussusception encephalopathy: an underrecognized cause of coma in children. Pediatr Neurol 6:419–421, 1990.

Chapter 75 Gastrointestinal Bleeding Jeffrey S. Blake, MD and Stephen J. Teach, MD, MPH

Key Points Most gastrointestinal bleeding in children is selflimited and not life threatening. The presence of significant gastrointestinal bleeding usually can be identified clinically. Emergency department evaluation should prioritize early recognition and management of active bleeding and hemorrhagic shock. Severe gastrointestinal bleeding requires rapid volume resuscitation and consultation with a gastroenterologist or surgeon to identify and control the source of hemorrhage. Establishing a definitive diagnosis in the emergency department is not always possible, but making a presumptive diagnosis may be acceptable once lifethreatening disorders are excluded.

Introduction and Background Many causes of gastrointestinal (GI) bleeding are unique to infants and children (e.g., necrotizing enterocolitis, formula intolerance, midgut volvulus). The frequency of specific causes depends on both the age of the patient and the location of bleeding1 (Tables 75–1 and 75–2). Fortunately, mortality is low in infants and children with GI bleeding since most causes are benign and comorbid conditions (e.g., atherosclerosis, coronary artery disease) are rare.

Recognition and Approach While GI bleeding in children occurs frequently in the intensive care setting,2 this complaint is not commonly seen in infants and children presenting to an emergency department (ED). In fact, GI bleeding only accounts for 0.3% of children presenting to a pediatric ED.3 Moreover, only 4% of these cases have a serious cause for their disorder, and mortality is less than 1%.3

Bleeding from the GI tract is never normal and can signify serious disease or common benign disorders. At any age, swallowed blood may be misinterpreted as gastrointestinal bleeding. Neonates can ingest blood at the time of birth or may ingest blood while nursing from a nipple that has nearby maternal bleeding. Swallowed blood from a nosebleed or intraoral source can be mistaken for GI bleeding, especially if bleeding is heavy and triggers hematemesis that consists of swallowed blood. Food and drinks may contain red dye that turns the stool, red but the stool will be heme negative when tested for occult blood. Clinicians must be able to differentiate between disorders that mimic bleeding, benign causes of bleeding, serious causes of bleeding, and surgical disorders that require acute intervention.

Clinical Presentation Initial evaluation is directed at assessing the hemodynamic stability of infants and children with GI bleeding. Assessment is also directed at determining whether or not there is ongoing bleeding (Table 75–3). This assessment is based on heart rate, palpation of central and peripheral pulses, blood pressure, mental status, respiratory rate and pattern, and signs of cutaneous perfusion. Although tachycardia is a sensitive indicator of acute, significant GI bleeding in children, children have an impressive ability to increase their systemic vascular resistance and to maintain a normal blood pressure in response to hypovolemia (compensated shock). Therefore, hypotension is considered a late finding in progression of shock (decompensated shock). Quantifying the amount of bleeding requires visual inspection or a historical description of the bleeding. Importantly, children may present with fatigue, syncope, weakness or other alteration in mental status without any bleeding noted from the GI tract.4 Confirming the presence of bleeding is an important evaluation step since true GI bleeding can easily be confused with hemoptysis, hematuria, vaginal bleeding, or swallowed blood from the nose, mouth, or oropharynx. Several “mimickers” of true GI bleeding include foods and medications that make vomitus appear red (food coloring, tomatoes, fruit juices), stools appear red (food coloring, beets, ampicillin), or stools appear black (licorice, spinach, iron supplements). Testing stool and emesis or gastric aspirates for occult blood is usually sufficient to confirm or rule out true GI bleeding in these cases. There are a large number of reasons for false positive and false negative stool testing5 (Tables 75–4 and 75–5). 587

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Table 75–1

Causes of Acute Upper Intestinal Bleeding*

Common Newborn and Infant Swallowed maternal blood Human milk During delivery Esophagitis Older Child Esophagus Esophagitis Acid reflux Pill induced Mallory-Weiss tear

Stomach

Duodenum

Other

Gastritis Prolapse gastropathy Aspirin Nonsteroidal antiinflammatory drug Stress ulcer/gastritis

Duodenitis Crohn disease

Swallowed blood Oral/nasal pharynx

Uncommon Gastric ulcer Bleeding diathesis

Esophagitis Viral (herpes, cytomegalovirus) Allergic Fungal Caustic ingestion Varices Dieulafoy lesion Foreign body Duplication cyst Gastritis Crohn’s disease Portal hypertension Helicobacter pylori infection Ulcer Zollinger-Ellison syndrome Cushing’s ulcer Leiomyoma Varices Vascular malformation Dieulafoy disease Ulcer Helicobacter pylori infection Curling’s ulcer Vascular malformation Foreign body Lymphoid hyperplasia Varices Dieulafoy disease Duplication cyst Hemobilia Swallowed blood Munchausen syndrome by proxy Pulmonary hemorrhage

Table 75–2

Causes of Lower Intestinal Bleeding*

Common

Uncommon

Newborn and Infant Allergic colitis Anal fissure Milk protein intolerance Necrotizing enterocolitis (premature) Swallowed maternal blood Infectious diarrhea Older Child Anal fissure Intussusception Infectious enterocolitis Salmonella Shigella Campylobacter Escherichia coli O157:H7 Yersinia enterocolitica Clostridium difficile Inflammatory bowel disease (>4 yr of age) Meckel’s diverticulum Perianal streptococcal cellulites Juvenile/inflammatory polyp

Juvenile polyp Vascular lesions Hirschsprung’s enterocolitis Meckel’s diverticulum Intestinal duplication Intussusception Infectious enterocolitis Inflammatory bowel disease (38.5° C)41 during the week before the initial evaluation than those

with transient synovitis. Children with septic arthritis have significantly higher temperatures (mean 37.7° C to 38.7° C) than children with transient synovitis (mean 36.6° C to 37.4° C).42-44 However, one third of the children have peak temperatures less than 38.3° C.33,38 Thus fever may not always be present. This is especially true in neonates with septic arthritis, in whom fever may be absent in most cases.45,46 There is some evidence that a recent upper respiratory infection33,37 or traumatic injury37 may predispose a child to septic arthritis. A history of immune deficiency or systemic disease may also predispose children to developing septic arthritis. Recent antibiotic use may make the diagnosis of septic arthritis a more difficult task. In one series, approximately one third of the patients had received an antibiotic in the week prior to admission.33 The infected joint is usually swollen, warm, and tender to palpation. Both active and passive motion of the joint are extremely painful and therefore limited.31 An effusion may be present. Joint dislocation may be observed.36 The affected joint is usually held in a position that allows for maximum joint distention. If the hip is involved, the leg may be abducted and externally rotated, while knee involvement leads to slight flexion, and ankle involvement manifests with plantar flexion. There is a wide range of possible presentations, from the child with septic arthritis who presents moribund in septic shock, to the well-appearing child with a limp who is afebrile. As there is no single diagnostic test that can diagnose septic arthritis, clinical evaluation in combination with test results can help guide management. The peripheral leukocyte count may be elevated in septic arthritis (mean 13,200/ mm3 vs. mean 11,200/mm3 in transient synovitis),37,43 thereby providing a means to differentiate septic arthritis from transient synovitis of the hip.42-44 Other studies have described a white blood cell count of greater than 11,000/mm3 to 12,000/ mm3 to be an independent predictor of acute septic arthritis.43,44 However, the peripheral leukocyte counts are not reliable indicators. In one series,46 only 23% of patients had a leukocyte count greater than 15,000/mm3. Similarly, another described only one third of the septic arthritis cohort with leukocytosis.7 The ESR is a nonspecific marker of inflammation or infection that has been used to aid in the diagnosis of septic arthritis and in monitoring response to treatment. The ESR is elevated (>20 mm/hr) in 85% to 90% of children with septic arthritis at the time of admission.33,38,47 It has also been recommended as a tool in combination with other factors to differentiate septic arthritis of the hip from toxic synovitis,42-44 and is a more sensitive indicator of septic arthritis of the hip than temperature or leukocyte count.46 It does not appear to correlate with the duration, severity, or final outcome of the disease. Furthermore, the ESR does not rise until 24 to 48 hours after the onset of symptoms or signs of infection and stays elevated 3 to 4 weeks after resolution of the infection.48,49 CRP, another acute-phase reactant, has gained favor because it is a rapid indicator of inflammation, rising within 6 hours of the triggering stimulus.40,50 Therefore, it has been recommended as a more accurate independent predictor of septic arthritis than the ESR.51 In one study, only 13% of children with suspected joint infection and a CRP of less than 1.0 mg/dl had septic arthritis.51 It has also been recommended as an adjunct screening test with the ESR in septic

Chapter 96 — Bone, Joint, and Spine Infections

arthritis because it increases and decreases much more quickly than the ESR.52 It may also be useful in detecting potential complications sooner than other laboratory indices (e.g., ESR).52 In this regard, it has been shown to be useful in the identification of concurrent septic arthritis in children who have acute osteomyelitis.49 Lastly, it may be of greater value than the ESR in determining resolution of inflammation.40,49,50 Although many studies have attempted to incorporate several of these combined variables into predication models that distinguish septic arthritis of the hip from transient or toxic synovitis,41-44,51,53 (Table 96–2) most clinical prediction models have failed to demonstrate sufficient validity outside of the originating institution.53 Septic arthritis must be differentiated from other causes of limb pain in children, including fractures, sprain, strains, neoplasms (metastatic disease, Ewing’s and osteogenic sarcoma), ischemia or infarction from hemoglobinopathies, slipped capital femoral epiphysis, Legg-Calvé-Perthes disease, transient synovitis, cellulitis, myositis, bursitis, and osteomyelitis. In general, these disorders do not cause the same degree of joint pain, joint swelling, and limited joint range of motion compared to septic arthritis. It also must be distinguished from other causes of arthritis, including reactive arthritis, rheumatic fever, juvenile rheumatoid arthritis, Lyme disease, serum sickness, lupus erythematosus, Henoch-Schönlein purpura, parvovirus, mumps, rubella, hepatitis B, and fungal causes. The presence of specific diagnostic features and arthrocentesis are required to differentiate these disorders from septic arthritis. Blood cultures should be obtained on all patients with possible septic arthritis. They are positive in 30% to 40% of

Table 96–2

709

patients.33,34,38,54 Although the yield may be relatively low, the ease of obtaining the culture can be instrumental in isolating an etiologic organism and enabling the most effective treatment. Furthermore, in as many as 20% of cases of septic arthritis, there is a positive blood culture in the presence of a negative synovial fluid culture.33-35 The most important diagnostic test is direct aspiration of the joint and subsequent fluid analysis. Others have provided extensive detail regarding the techniques for aspiration of specific joints for diagnostic purposes (Table 96–3).54a Gram stain should always be performed and will yield a presumptive diagnosis in about one third of patients.34 A joint fluid leukocyte count greater than 80,000 to 100,000/ml with greater than 70% to 75% polymorphonuclear neutrophils is consistent with a septic joint. However, one study of 126 cases with a known bacterial etiology34 demonstrated that 55% had joint cell counts ≤ 50,000 cells/mm3 and 34% had counts ≤ 25,000 cells/mm3. A low glucose (less than one third of serum value) is also consistent with a septic joint, yet in that same study of 126 children with proven bacterial septic arthritis, glucose levels were above 40 mg/dl in 44 specimens and reduced in only 41 specimens.34 The confirmatory study is a positive synovial fluid culture, present in 50% to 70% of patients.33-36,54 A significant number of children with septic arthritis have persistently negative cultures even without receiving antibiotics prior to diagnosis. Culture-negative cases have been shown to have clinical and synovial similarities to those with positive cultures. Therefore, the same aggressive therapy is recommended in those cases with or without identification of a causative organism.55 In septic arthritis, plain radiography may show joint space widening, disruption of the normal fat planes (which may

Predictors of Septic Arthritis of the Hip in Children Operator Characteristics of Predictors

Author

Predictors 43

Del Beccaro et al Jung et al42

Kocher et al44

Kunnamo et al41 Levine et al54 53

Luhmann et al

ESR > 20 mm/hr Temperature > 37.5° C ESR > 30 mm/hr Temperature > 37° C ESR > 20 mm/hr CRP > 1.0 mg/dl WBC > 11,000 cells/mm3 Joint space distance > 2 mm on radiograph History of fever Non–weight bearing ESR > 40 mm/hr WBC > 12,000 cells/mm3 CRP > 2 mg/dl Temperature >38.5° C CRP ≥ 1.0 mg/dl ESR ≥ 25 mm/hr History of fever Non–weight bearing ESR > 40 mm/hr WBC > 12,000 cells/mm3

Sensitivity*

Specificity†

PPV

NPV

97%

86%

46%

2%

71% NR

86% NR

68% 99.1%

12% 0.1%

NR

NR

99.8%

0.1%

100%

87%

46%

100%

90% 92% NR

29% 22% NR

34% 35% 59%

87% 86% NR

*Sensitivity if any one of the listed features was present. † Specificity if any one of the listed features was present. Abbreviations: CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; NPV, negative predictive value, or probability of disease if none of features is present; NR, not reported; PPV, positive predictive value, or probability of disease if all features are present; WBC, white blood cell count.

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Table 96–3 Clarity Color WBC count/ml PMNs (%) Glucose* Culture Disease

Analysis of Joint Fluid Noninflammatory

Inflammatory

Septic

Hemorrhagic

Clear Yellow 50,000 >75% 50% Septic arthritis

Bloody Red/brown 97th percentile for age • Long thin face, narrow maxilla • Ectopic lentis, myopia, blue sclera • Pectus excavatum or carinatum • Long, thin fingers that are hyperextensible • Steinberg thumb sign (see Fig. 97–2) • Walker-Murdoch wrist sign • Skin hyperelasticity • Fragile skin (scarring and poor healing) • Fragile blood vessels (easily bruised) • Joint hypermobility • Muscle weakness, hypotonia • Short stature • Abnormal facies • Skin hyperpigmentation • Skin thickening/tightness • Myalgias, fatigue, weight loss • Raynaud’s phenomenon • Pulmonary fibrosis • Cardiomyopathy, pericardial effusion • Reflux, esophagitis, malabsorption • Proximal > distal muscle weakness with high CPK, LDH and abnormal electromyogram • Stiff and sore muscles • Arthralgias, dysphagia, dysphonia • Nonpitting edema • Heliotrope (violaceous erythematous) rash— especially eyelids • Scaly, red, atrophic skin over extensor surface of joints • Subcutaneous calcinosis

• Aorta and aortic root dilation with aortic valve disorder and aortic dissection • Lens dislocation • Spontaneous pneumothorax • Pulmonary blebs • Scoliosis • Recurrent temporomandibular joint dislocations • Dental caries • Arterial aneurysms • Mitral valve prolapse • Spontaneous pneumothorax • Joint dislocations • Visceral perforations • Spontaneous vessel ruptures (abdominal and splenic) • Accelerated hypertension • Renal failure • Pulmonary hypertension and respiratory failure

• Gastrointestinal bleeding or perforation • Respiratory infection/failure • Extremity contractures

Abbreviations: CPK, creatine phosphokinase; LDH, lactate dehydrogenase.

patients have an upper segment–to–lower segment ratio of less than 0.86 (with the lower segment measured from the symphysis pubis to the floor) or an armspan-to-height ratio of greater than 1.05.2 Arachnodactyly can be identified by the Steinberg thumb sign, in which the entire thumbnail projects beyond the ulnar border of the hand, and the WalkerMurdock wrist sign, in which the thumb and fifth finger overlap around the wrist.2 Other skeletal abnormalities that may be evident on physical examination include pectus excavatum or pectus carinatum and scoliosis. Diagnostic imaging may be required to evaluate for protrusio acetabuli and dural ectasia. The major ocular abnormality that occurs in patients with Marfan syndrome is lens dislocation. This can occur as early

as infancy, and clinical findings of megalocornea or iridodonesis may be helpful clues. Slit-lamp examination aids in the diagnosis. Other complications include retinal detachment and acute glaucoma. The cardiovascular manifestations that occur contribute to both morbidity and mortality. Progressive mitral valve prolapse can cause substantial morbidity with the development of arrhythmias, heart failure, thromboemboli, or endocarditis. Mitral regurgitation is common, with approximately 50% of patients younger than 20 years of age affected. Dilation of the aortic valve and ascending aorta leading to aortic valve incompetence typically occurs as the patient ages, with 90% of patients having some aortic root dilation by age 20 years. Aortic dissection is a life-threatening complication of

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Table 97–2

Ghent Criteria for Diagnosis of Marfan Syndrome

Skeletal System A major skeletal criterion is assigned when at least four of the following are present: • Pectus carinatum • Pectus excavatum requiring surgery • Upper segment–to–lower segment ratio < 0.86 or armspan-toheight ratio >1.05 • Wrist and thumb signs: both signs should be present to diagnose arachnodactyly according to the Ghent criteria • Scoliosis > 20 degrees or spondylolisthesis • Reduced elbow extension (2 cm) in load-bearing areas of joints. Osgood-Schlatter Disease (Tibial Tubercle Apophysitis) Osgood-Schlatter disease or tibial tubercle apophysitis is one of the most frequently diagnosed overuse injuries in children. Repeated contraction of the quadriceps muscle results in injury of the tibial tubercle.7 It occurs in children 10 to 15 years old, with onset in girls preceding that of boys by approximately 2 years.4,12 Signs and symptoms include pain, tenderness, and swelling over the tibial tubercle. Pain may worsen with jumping sports, climbing stairs, or rising from a seated position.7 Radiographs are not needed but may show soft tissue swelling or fragmentation of the tibial tubercle (Fig. 98–3). Treatment includes local pressure, anti-inflammatory medications, ice, and rest. Severe pain may require a 1- to 2week period of knee immobilization. Resolution may be slow, often taking 12 to 18 months.12 Once the growth plate is closed, persistent pain may indicate a residual ossicle. Surgical excision of the tubercle may relieve pain.13 Although the disease is generally self-limited, patients with the disease may go on to experience some level of disability with sports activity later in life.14 Sinding-Larsen-Johansson Disease and Jumper’s Knee Sinding-Larsen-Johansson (SLJ) disease is an apophysitis that typically occurs in children 10 to 13 years old. Its cause is repetitive tensile stress at the junction of the patella and patellar tendon with subsequent calcification and ossification of the inferior aspect of the patella. Patients may describe a subtle onset of pain and demonstrate palpable pain isolated to the inferior pole of the patella (allowing it to be easily distinguished from Osgood-Schlatter disease). Pain occurs during jumping, climbing, or kneeling or with direct trauma to the area. Radiographs may show fragmentation of the distal pole of the patella, but imaging is not needed for diagnosis. Treatment includes rest, anti-inflammatory medica-

727

16 years old

B

tions, and quadriceps flexibility exercises.15 Resolution typically occurs in 6 to 12 months.12 Although commonly combined in the category of SLJ, patellar tendonitis or “jumper’s knee” is thought to occur from partial thickness tears of the patella tendon.4 It is characterized by proximal patellar tendon pain and tenderness on palpation. This entity may result in long-lasting symptoms.16 A progressive exercise plan for drop squats and quadricep extension and hamstring exercises has been reported to successfully reduce pain at 12 weeks.17 Occasionally, surgical repair may be necessary to relieve symptoms.18 Illiotibial Band Syndrome The illiotibial band extends from the tensor fascia lata and inserts on the lateral aspect of the proximal tibia. This band changes position during knee extension, snapping forward over the lateral condyle from its posterior location behind the lateral epicondyle when the knee is flexed. The movement is only detectable when there is inflammation. Running with a high step (e.g., up and down stairs) elicits pain. A positive Noble test is diagnostic: the physician places a thumb over the lateral femoral epicondyle and actively flexes and extends the knee with the patient supine. Pain over the epicondyle is reproduced when the knee is in 20 to 30 degrees of flexion.2 Radiographs are generally not necessary. Treatment includes rest, anti-inflammatory medications, and reduction of all activities that involve heavy weight bearing. Local corticosteroid injection has been described in adults with recent onset of symptoms, but is not well described in children.19 Sever’s Disease (Calcaneal Apophysitis) This overuse injury occurs at the insertion of the Achilles tendon into the secondary ossification center of the calcaneus from repetitive traction, subsequent inflammation, and fragmentation. Whether the injury represents a true metaphyseal trabecular stress fracture or an apophysitis is controversial.20 The patient typically complains of heel pain that worsens during activity. Physical examination is remarkable for pain that is elicited by lateral and medial pressure on the calcaneus. Radiographs often show fragmentation and sclerosis

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SECTION IV — Approach to the Acutely Ill Patient

with MTSS complain of diffuse pain along the middle and distal third of the posteromedial aspect of the tibia. Initially the pain resolves with exercise and returns with rest, but, as the problem persists, the pain will increase with activity. Pain can be elicited with ankle plantar flexion against resistance, by having the patient stand on the toes, or by asking the patient to jump in place. The pain of MTSS is diffuse in contrast to that of stress fractures, which is localized with point tenderness over the bone. The location of pain in addition to the adjunct of normal radiographs and a normal neurovascular examination assure the diagnosis. Treatment includes ice and rest (generally for a 3- to 4-week period).24 MTSS can progress to a stress fracture, so athletes should not be allowed to “work through the pain.” Many variables contribute to the development of MTSS; therefore, preventative measures, including proper shoes, evaluation of running surfaces, and stretching and strengthening exercises, are useful in preventing further injury.7 Köhler’s Disease

FIGURE 98–4. Sever’s disease in an 11-year-old male with fragmentation of the calcaneal apophysis. (From Green NE, Swiontkowski MF [eds]: Skeletal Trauma in Children, 3rd ed. Philadelphia: WB Saunders, 2003, p 540.)

of the secondary ossification center (Fig. 98–4). A return to sports can be expected in approximately 2 months if patients adhere to a treatment regimen that includes rest, anti-inflammatory medications, Achilles tendon stretching exercises, and orthotics.21

Also known as tarsal navicular osteochondritis, this disease affects younger children (50 degrees).32 Operative spinal correction is only necessary with progressive thoracic kyphosis.

Summary Musculoskeletal pain in the young athlete should never be overlooked. The diagnosis of most overuse injuries is suggested by the history of the offending activity and the risk factors associated with various sports activities. Conservative management with rest, ice, and nonsteroidal analgesia is adequate acute treatment for most overuse injuries in children. A plan for initial rest with gradual return of activity, and educating families on developmentally appropriate training programs, equipment, and facilities, should be addressed with all overuse injuries. The earlier most overuse injuries are diagnosed and treated, the better the prognosis. REFERENCES *1. Andrish JT: Upper extremity injuries in the skeletally immature athlete. In Nicholas JA, Hershman EB (eds): The Upper Extremity in Sports Medicine. St. Louis: Mosby, 1990, pp 676–678. 2. Dugan S, Weber K: Selected topics in sports medicine. Dis Mon 48:572–616, 2002.

*Selected readings.

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3. Gómez JE: Upper extremity injuries in youth sports. Pediatr Clin North Am 49:593–626, 2002. *4. Hogan KA, Gross RH: Overuse injuries in pediatric athletes. Orthop Clin North Am 34:405–415, 2003. 5. Walter KD, Congeni JA: Don’t let Little League shoulder or elbow sideline your patient permanently. Contemp Pediatr 21:69–88, 2004. 6. Carson WG Jr, Gasser SI: Little Leaguer’s shoulder: a report of 23 cases. Am J Sports Med 26:575–580, 1998. 7. Christopher NC, Congeni J: Overuse injuries in the pediatric athlete: evaluation, initial management, and strategies for prevention. Clin Pediatr Emerg Med 3:118–128, 2002. 8. Singer KM, Roy SP: Osteochondrosis of the humeral capitellum. Am J Sports Med 12:351–360, 1984. 9. Kobayashi K, Burton KJ, Rodner C, et al: Lateral compression injuries in the pediatric elbow: Panner’s disease and osteochondritis dissecans of the capitellum. J Am Acad Orthop Surg 12:246–254, 2004. 10. Carr KE: Musculoskeletal injuries in young athletes. Clin Fam Pract 5(2):1–21, 2003. 11. Hefti F Bequiristain J, Krauspe R, et al: Osteochondritis dissecans: a multicenter study of the European Pediatric Orthopedic Society. J Pediatr Orthop B 8:231–245, 1999. 12. Stahelli LT: Fundamentals of Pediatric Orthopedics, 3rd ed. Philadelphia: Lippincott Williams & Wilkins, 2003, pp 58–70. 13. Flowers MJ, Bhadreshwar DR: Tibial tuberosity excision for symptomatic Osgood-Schlatter disease. J Pediatr Orthop 15:292–297, 1995. 14. Ross MD, Villard D: Disability levels of college-aged men with a history of Osgood-Schlatter disease. J Strength Cond Res 17:659–663, 2003. 15. Medlar RC, Lyne ED: Sinding-Larsen-Johansson disease: its etiology and natural history. J Bone Joint Surg Am 60:1113–1116, 1978. 16. Kettunen JA, Kvist M, Alanen E, Kujala UM: Long-term prognosis for jumper’s knee in male athletes: a prospective follow-up study. Am J Sports Med 30:689–692, 2002. 17. Cannell LJ, Taunton JE, Clement DB, et al: A randomised clinical trial of the efficacy of drop squats or leg extension/leg curl exercises to treat clinically diagnosed jumper’s knee in athletes: pilot study. Br J Sport Med 35:60–64, 2001. 18. Ferretti A, Conteduca F, Camerucci E, Morelli F: Patellar tendinosis: a follow-up study of surgical treatment. J Bone Joint Surg Am 84:2179– 2185, 2002. 19. Gunter P, Schwellnus MP: Local corticosteroid injection in iliotibial band friction syndrome in runners: a randomised controlled trial. Br J Sports Med 38:269–272, 2004. 20. Ogden JA, Ganey TM, Hill JD, Jaakkola JI: Sever’s injury: a stress fracture of the immature calcaneal metaphysis. J Pediatr Orthop 24:488– 492, 2004. 21. Micheli LF, Ireland ML: Prevention and management of calcaneal apophysitis in children: an overuse syndrome. J Pediatr Orthop 7:34– 38, 1987. 22. De Garceau D, Dean D, Requejo SM, Thordarson DB: The association between diagnosis of plantar fasciitis and Windlass test results. Foot Ankle Int 24:251–255, 2003. 23. DiGiovanni BF, Nawoczenski DA, Lintal ME, et al: Tissue-specific plantar fascia-stretching exercise enhances outcomes in patients with chronic heel pain: a prospective, randomized study. J Bone Joint Surg Am 85:1270–1277, 2003. 24. Metzl JD, Metzl JA: Shin pain in an adolescent soccer player: a case based look at shin splints. Contemp Pediatr 21:36–48, 2004. 25. Borges JL, Guille JT, Bowen JR: Köhler’s bone disease of the tarsal navicular. J Pediatr Orthop 15:596–598, 1995. *26. Waicus KM, Smith BW: Back injuries in the pediatric athlete. Curr Sports Med Rep 1(1):52–58, 2002. 27. Soler T, Calderon C: The prevalence of spondylolysis in the Spanish elite athlete. Am J Sports Med 28:57–62, 2000. 28. Miller SF, Congeni J, Swanson K: Long-term functional and anatomical follow-up of early detected spondylolysis in young athletes. Am J Sports Med 32:928–933, 2004. 29. d’Hemecourt PA, Zurakowski D, Kriemler S, Micheli LJ: Spondylolysis: returning the athlete to sports participation with brace treatment. Orthopedics 25:653–657, 2002. 30. Reitman CA, Esses SI: Direct repair of spondylolytic defects in young competitive athletes. Spine J 2:142–144, 2002. 31. Lim MR, Yoon SC, Green DW: Symptomatic spondylolysis: diagnosis and treatment. Curr Opin Pediatr 16:37–46, 2004. 32. Riddle EC, Bowen JR, Shah SA, et al: The duPont kyphosis brace for the treatment of adolescent Scheuermann kyphosis. J South Orthop Assoc 12:135–140, 2003.

Chapter 99 Rhabdomyolysis Nicole S. Sroufe, MD, MPH and Rachel M. Stanley, MD, MHSA

Key Points The classic triad of rhabdomyolysis includes myalgias, muscle weakness, and dark urine (myoglobinuria). Elevations in creatine kinase are diagnostic of rhabdomyolysis, but are not prognostic. A urinalysis positive for blood with the absence of red blood cells occurs in rhabdomyolysis. The mainstay of therapy for rhabdomyolysis is aggressive hydration, alkalinization of the urine, and adequate diuresis to prevent the development of acute renal failure.

Introduction and Background Rhabdomyolysis is a potentially lethal syndrome that occurs after skeletal muscle injury with release of intracellular myocyte contents into extracellular fluid, resulting in elevations of serum myoglobin, creatine kinase (CK), lactate dehydrogenase (LDH), aldolase, aspartate aminotransferase, and alanine aminotransferase.1-7 Rhabdomyolysis was defined by Gabow as any condition resulting in a fivefold or greater rise in serum CK (in the absence of brain or heart disease).1,8 However, others have defined rhabdomyolysis by elevations of CK from at least 3- to more than 100-fold, the upper limit of normal.8 As a result of skeletal muscle injury with loss of integrity of the myocyte, several physiologic alterations occur, including hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia, metabolic acidosis, hypoalbuminemia, and myoglobinuria.1,2,8,9 These electrolyte derangements contribute to the multiple complications that occur in patients with rhabdomyolysis. Many complications may arise in patients with rhabdomyolysis, including acute renal tubular necrosis, myoglobinuric renal failure, severe muscle necrosis, cardiac arrhythmias resulting in arrest, disseminated intravascular coagulation (DIC), lactic acidosis, and compartment syndrome.2,5,9-13 730

Recognition and Approach Epidemiologic information regarding rhabdomyolysis in the pediatric population is limited given that no large case series have been reported. The list of disorders causing rhabdomyolysis is extensive (Table 99–1). Rhabdomyolysis may occur in isolation, or in combination with other features diagnostic of specific syndromes. Heat stroke is defined by altered mental status in patients with core temperatures of 39.5° C or more, leading to multisystem organ failure, including circulatory collapse, liver failure, neurologic dysfunction, DIC, renal failure, and rhabdomyolysis.14 In malignant hyperthermia, an autosomal dominant disorder of skeletal muscle, susceptible patients develop a potentially fatal hypermetabolic reaction with hyperthermia, muscle rigidity, tachycardia, metabolic acidosis, and rhabdomyolysis when exposed to depolarizing muscle relaxants and inhalation anesthetics, as well as extreme stress in the form of heat or exercise.15-17 When neuroleptic malignant syndrome develops as an adverse effect of antipsychotic medication, patients experience muscle rigidity, hyperthermia, altered mental status, autonomic dysfunction, and rhabdomyolysis.18 Rhabdomyolysis may also develop in patients with propofol infusion syndrome, characterized by the sudden onset of refractory bradycardia progressing to asystole, lipemia, fatty infi ltration of the liver with hepatomegaly, and severe metabolic acidosis.19,20 Rhabdomyolysis may develop acutely in otherwise healthy children, or intermittently in children affected by myopathies, muscular dystrophies, and metabolic derangements.10 Many acquired illnesses, including infections secondary to viral or bacterial agents, have resulted in the development of rhabdomyolysis.3,4,11,12,21-25 Medications, exposure to toxins, and the use of drugs of abuse have also resulted in the development of rhabdomyolysis.7,9,15-20,26-38 Traumatic injury with insult to muscle tissue secondary to nonaccidental trauma, immobilization, crush injury, electrical injury, burns, and ischemic injury may also result in rhabdomyolysis10,13,39-42 (see Chapter 26, Burns; Chapter 119, Physical Abuse and Child Neglect; and Chapter 142, Electrical Injury). Conditions resulting in hyperthermia predispose patients to the development of rhabdomyolysis, as does exertion in the untrained/unconditioned athlete or in individuals with sickle cell trait.2,14-18,43,44 Metabolic derangements, including diabetic ketoacidosis, nonketotic hyperosmolar coma, hypothyroidism/

Chapter 99 — Rhabdomyolysis

Table 99–1

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Nonexhaustive List of Precipitating Factors of Rhabdomyolysis in Children

Viral Infections Coxsackie virus Echovirus Epstein-Barr virus Influenza virus types A and B Varicella-zoster virus Bacterial Infections Clostridium tetani Coxiella burnetti Group B streptococcus Mycoplasma pneumoniae Neisseria meningitides Salmonella enteritidis Staphylococcus aureus Medications Acetaminophen Amoxapine Amphotericin B Anticholinergics Antipsychotics Barbiturates Benzodiazepines Colchicine Corticosteroids Cyclosporine Diphenhydramine Diuretics Haloperidol Inhalation anesthetics Isoniazid Ketamine Lithium Loxapine Narcotics Pemoline Phenytoin Propofol Serotonin antagonists Statins Succinylcholine Suxamethonium Sympathomimetics Tacrolimus Theophylline Tricyclic antidepressants Trimethoprim-sulfamethoxazole Drugs of Abuse Caffeine Cocaine Ecstasy Ethanol Heroin Methamphetamine Phencyclidine

hyperthyroidism, and electrolyte imbalances, may also precipitate rhabdomyolysis10,41,42,45,46 (see Chapter 105, Diabetic Ketoacidosis; Chapter 109, Thyrotoxicosis; Chapter 110, Dehydration and Disorders of Sodium Balance; Chapter 111, Metabolic Acidosis; and Chapter 114, Hyperkalemia). Children with disorders of metabolism and myopathies often present with intermittent rhabdomyolysis and myoglobinuria.1,5,11,15,35,41,45,47 A 3-year retrospective study of neurology consultations at the University of California, San Diego, demonstrated an

Withdrawal Syndromes Alcohol Intrathecal baclofen Sedative-hypnotics Toxic Substances Barium Carbon monoxide poisoning Cyanide Hydrogen sulfide Rattlesnake venom Strychnine Trauma Crush injury Electrical injury/lightning strikes Immobilization Ischemic injury Nonaccidental trauma/child abuse Third-degree burns Traumatic positioning Hyperthermia Heatstroke Malignant hyperthermia Neuroleptic malignant syndrome Exertion Exercise-induced (running or weight training) Exertion in patients with sickle cell trait Metabolic/Endocrine Diabetic ketoacidosis Electrolyte imbalances (hypernatremia/hyponatremia, hypokalemia, hypophosphatemia, hypocalcemia) Hyperthyroidism/hypothyroidism Nonketotic hyperosmolar coma Genetic Disorders of carbohydrate metabolism Disorders of fatty acid metabolism (carnitine palmitoyltransferase I or II deficiency, very-long-chain acyl-coenzyme A dehydrogenase deficiency, medium-chain acyl-coenzyme A dehydrogenase deficiency) Muscular dystrophies Miscellaneous Adrenoleukodystrophy Dermatomyositis Hypothermia Idiopathic Polymyositis

incidence of childhood rhabdomyolysis of 0.26% of hospital admissions.11 A retrospective review of children admitted to the Medical College of Virginia during an 8-year period identified 19 cases of rhabdomyolysis (excluding intermittent/ relapsing rhabdomyolysis) with causes ranging from trauma (5 cases), nonketotic hyperosmolar coma (2 cases), viral myositis (2 cases), dystonia (2 cases) and malignant hyperthermia–related conditions (2 cases), and additional cases resulting from hypernatremia, polymyositis, hypothermia, and muscle exertion.10

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SECTION IV — Approach to the Acutely Ill Patient

Clinical Presentation Rhabdomyolysis is characterized by the classic triad of myalgias, muscle weakness, and darkened urine, although a broad spectrum of symptoms and disease severity can occur.5,7,43 Myoglobin released from myocytes after cell injury is partially excreted by the kidneys, resulting in the dark brown pigmentation of the urine.7,8 Patients may report localized or diffuse muscle tenderness, weakness, and stiffness, and may develop muscle edema, skin changes consistent with pressure necrosis, or compartment syndrome.2,5,10,12,19,43 Systemic symptoms including fever, malaise, nausea, and vomiting may be present, dependent on the underlying cause of muscle injury.10,19 Early in the disease course, patients may present only with myalgias and weakness without darkened urine, given that 100 g of muscle tissue must be injured before serum proteins become saturated and patients develop myoglobinuria.7,8 As additional muscle is injured, serum myoglobin increases and myoglobinuria develops. Therefore, patients may be misdiagnosed as having merely a viral syndrome with myalgias. Conversely, patients presenting late in the disease course may present in acute, fulminant renal failure.7 Patients presenting with lethargy or coma or as victims of severe trauma may be diagnosed with rhabdomyolysis much further into their disease course.7,10 Serum CK is the most sensitive biochemical indicator of myocyte injury, and should be measured to assess for rhabdomyolysis.1,5,43,48 The MM fraction of CK reflects skeletal muscle injury; CK begins to rise within 2 hours of myocyte injury, peaks within 12 to 36 hours, and decreases by 40% each day after the insult to muscle tissue ceases.1,5,7,43 Rhabdomyolysis may be present with elevations of CK from as little as 3- to more than 100-fold the upper limit of normal.8 Although CK is highly sensitive for identifying myocyte injury, elevations of CK are not predictive of disease severity, or of progression to myoglobinuric renal failure.1,10,48 Additional laboratory studies provide support for the diagnosis of rhabdomyolysis, but are not diagnostic. Careful evaluation of the dipstick urinalysis can provide valuable clues indicative of myocyte injury. A positive urine dipstick for blood with no, or very few, red blood cells visualized with microscopy is suggestive of myoglobinuria, and should prompt an investigation for the presence of rhabdomyolysis.7,10,12,43 Myoglobinuria can be confirmed with direct measurement of myoglobin in the urine. Myoglobin may also be quantitated in serum, increasing quickly after myocyte injury, and normalizing within 1 to 6 hours of the cessation of cellular injury.10 Given the short half-life of myoglobin, it is not reliable in confirming the diagnosis of rhabdomyolysis. In fact, nearly 50% of patients with rhabdomyolysis do not have myoglobinuria on presentation.5,7 Myoglobinuria may be the only feature that cues the clinician to consider the diagnosis of rhabdomyolysis. However, myoglobinuria is not predictive of the development of renal failure.1 Serum electrolytes, LDH, aminotransferases, and creatinine should be assessed in the evaluation for rhabdomyolysis, as myocyte injury results in the release of potassium, phosphorus, purines, and LDH from muscle tissue.7,8,12,19,43 Serum aldolase is also elevated.7,8,12 Additionally, renal function should be evaluated, given that myoglobinuria results in acute tubular necrosis with potential for renal failure.3,5,9-11,43

Additional disorders of muscle tissue may present with myalgias and weakness, including autoimmune disorders, genetic defects of metabolism, and dermatomyositis, requiring further investigation based on clinical suspicion5 (see Chapter 95, Musculoskeletal Disorders in Systemic Disease; and Chapter 97, Muscle and Connective Tissue Disorders). Additionally, inflammatory conditions in localized muscle tissue may present with muscle pain. Myositis, inflammation of muscle secondary to infection of deep fascial and muscle planes, and pyomyositis, a bacterial infection of skeletal muscle resulting in abscess formation, should be differentiated from rhabdomyolysis, which is a noninflammatory condition.3,49

Important Clinical Features and Considerations Early recognition of rhabdomyolysis is paramount to prevent potentially fatal complications. The most common and potentially devastating complication of rhabdomyolysis is acute renal failure. The incidence of acute renal failure in children ranges from 5–42%.1,10,50 A recent retrospective review of 191 children with rhabdomyolysis reported that the risk of acute renal failure in this series was much less than the risk reported for adults.50 Renal failure develops as a result of myoglobin casts obstructing renal tubules, decreased glomerular fi ltration rate, and the direct nephrotoxic effects of myoglobin by-products.3,5,7,9-11,43 In an acidic milieu, with a pH less than 5.6, myoglobin dissociates into ferrihemate and globin.5 Ferrihemate is directly nephrotoxic, impairs renal tubular transport, and produces additional renal injury secondary to the production of free hydroxyl radicals.7,43 Patients with urinary pH less than 5.6, hypovolemia, and metabolic acidosis are at greater risk for the development of renal failure. The release of intracellular potassium from myocytes results in hyperkalemia. Hypocalcemia develops due to the deposition of calcium in injured tissues and is exaggerated by the formation of calcium-phosphorus precipitants resulting from hyperphosphatemia.2,5,7,11,43 These electrolyte imbalances place patients at risk for cardiac arrhythmias and arrest.2,5,7,10,43,50 Interestingly, patients with rhabdomyolysis secondary to heatstroke are less likely to develop hyperkalemia given the presence of a respiratory alkalosis, increased sweating, and overproduction of aldosterone.14 These patients commonly present with normal serum potassium levels or hypokalemia.14 DIC may develop in patients with rhabdomyolysis, further complicating their course and management.2,5,7 Compartment syndrome also may develop as a result of fluid accumulation in muscle tissue secondary to intracellular fluid shifts.7

Management Standard protocols for the management of rhabdomyolysis do not exist, and no randomized controlled trials have been carried out to evaluate the efficacy of current recommended therapies. Attention should be focused on primary resuscitation efforts, ensuring adequate ventilation and circulation.5,7,43 All patients require continuous cardiac monitoring, frequent assessment of vital signs, and monitoring of

Chapter 99 — Rhabdomyolysis

urine output. An appropriate evaluation to determine the cause of muscle injury must be completed to identify and treat potential causes of myocyte destruction (hyperthermia/ hypothermia, electrolyte abnormalities, metabolic derangements, toxins, hypovolemia)5,7,43 (see Chapter 111, Metabolic Acidosis; Chapter 114, Hyperkalemia; and Chapter 139, Hyperthermia). The mainstay of therapy for rhabdomyolysis is aggressive hydration with isotonic saline to restore intravascular volume, induce diuresis, and prevent renal failure.5,9,11,43 Urine output must be closely monitored and adequate urine output maintained (>2 to 3 ml/kg per hour) to reduce the risk of acute tubular necrosis. Sodium bicarbonate administration is recommended to alkalinize the urine to a pH greater than 6.0 to prevent the breakdown of myoglobin into ferrihemate, preventing ferrihemate precipitation in the renal tubules.7-9,14,43,50 To further induce diuresis and prevent oliguric renal failure, osmotic agents are recommended.9,11,14,43 Mannitol (0.5 to 1 g/kg intravenously [IV] initially, followed by 0.25 to 0.5 g/kg IV every 4 to 6 hours) and furosemide (1 mg/kg IV every 6 hours) have been used successfully to induce diuresis in patients with rhabdomyolysis.9,11,14,43 In addition to ensuring adequate hydration and renal perfusion, electrolyte disturbances that occur secondary to muscle injury must be aggressively treated. Treatment of hyperkalemia must be a priority, and appropriate therapy should be instituted promptly (see Chapter 114, Hyperkalemia).5,11,43 If oliguric renal failure or persistent electrolyte disturbances develop, dialysis may be required.43 However, dialysis does not prevent acute renal failure as myoglobin is not a dialyzable substance.11 Early consultation with a pediatric nephrologist is encouraged when managing rhabdomyolysis in patients with renal insufficiency and failure. Additional therapy may be required, specific to the complications that develop from rhabdomyolysis. DIC must be treated aggressively with platelets, coagulation factors, and other blood products to prevent further complications,5 and the development of compartment syndrome will require appropriate surgical consultation with the potential need for fasciotomy.7 If malignant hyperthermia (autosomal dominant patients with muscle rigidity after succinylcholine or anesthetic) or neuroleptic malignant syndrome are considerations, dantrolene (2 to 3 mg/kg IV) should be administered (see Chapter 139, Hyperthermia).

Summary Rhabdomyolysis results from various insults to skeletal muscle via direct or indirect means. Given the potentially fatal complications, patients with rhabdomyolysis require aggressive treatment in an inpatient setting. The primary treatment goal is to prevent further skeletal muscle breakdown and the development of acute renal failure.11 Additional data are needed in the pediatric population to better define the most appropriate approach to the management and care of children with rhabdomyolysis. Given the limited data available in pediatric populations, the mortality secondary to rhabdomyolysis is not well defined. However, patients with myoglobinuric renal failure tend to have a better prognosis if hypotension is minimized and cortical necrosis avoided.5 Some authors report a return of full muscle mass and function within 1 to 6 weeks of the

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initial insult, with variable degrees of residual weakness observed.11 REFERENCES *1. Gabow P, Kaehny W, Kelleher S: The spectrum of rhabdomyolysis. Medicine 61:141–152, 1982. 2. Walsworth M, Kessler T: Diagnosing exertional rhabdomyolysis: a brief review and report of two cases. Mil Med 166:275–277, 2001. 3. Singh U, Scheld W: Infectious etiologies of rhabdomyolysis: three case reports and review. Clin Infect Dis 22:642–649, 1996. 4. Minami K, Maeda H, Yanagawa T, et al: Rhabdomyolysis associated with Mycoplasma pneumoniae infection. Pediatr Infect Dis J 22:291– 293, 2003. 5. Will M, Hecker R, Wathen P: Primary varicella-zoster induced rhabdomyolysis. South Med J 89:915–920, 1996. 6. Osamah H, Finkelstein R, Brook J: Rhabdomyolysis complicating acute Epstein-Barr virus infection. Infection 23:119–120, 1995. 7. Coco T, Klasner A: Drug-induced rhabdomyolysis. Curr Opin Pediatr 16:206–210, 2004. *8. Ng Y, Johnston H: Clinical rhabdomyolysis. J Paediatr Child Health 36:397–400, 2000. 9. Bush S, Jansen P: Severe rattlesnake envenomation with anaphylaxis and rhabdomyolysis. Ann Emerg Med 25:845–848, 1995. *10. Watemberg N, Leshner R, Armstrong B, et al: Acute pediatric rhabdomyolysis. J Child Neurol 15:222–227, 2000. *11. Chamberlain M: Rhabdomyolysis in children: a 3 year retrospective study. Ped Neurol 7:226–228, 1991. 12. Swaringen J, Seiler J, Bruce R: Influenza A induced rhabdomyolysis resulting in extensive compartment syndrome. Clin Orthop Relat Res 375:243–249, 2000. 13. Malinoski D, Slater M, Mullins R: Crush injury and rhabdomyolysis. Crit Care Clin 20:171–192, 2004. 14. Wang A, Li P, Lui S, et al: Renal failure and heatstroke. Ren Fail 17:171–179, 1995. 15. Pedrozzi N, Ramelli G, Tomasetti R, et al: Rhabdomyolysis and anesthesia: a report of two cases and review of the literature. Pediatr Neurol 15:254–257, 1996. 16. Kozack J, MacIntyre D: Malignant hyperthermia. Phys Ther 81:945– 952, 2001. 17. Wappler F, Fiege M, Steinfath M, et al: Evidence for susceptibility to malignant hyperthermia in patients with exercise-induced rhabdomyolysis. Anesthesiology 94:95–100, 2001. 18. Yoshikawa H, Watanabe T, Abe T, et al: Haloperidol-induced rhabdomyolysis without neuroleptic malignant syndrome in a handicapped child. Brain Dev 22:256–258, 2000. 19. Kang T: Propofol infusion syndrome in critically ill patients. Ann Pharmacother 36:1453–1456, 2002. 20. Hanna J, Ramundo M: Rhabdomyolysis and hypoxia associated with prolonged propofol infusion in children. Neurology 50:301–303, 1998. 21. Goebel J, Harter H, Boineau F, et al: Acute renal failure from rhabdomyolysis following influenza A in a child. Clin Pediatr 36:479–481, 1997. 22. Brook I: Tetanus in children. Pediatr Emerg Care 20:48–52, 2004. 23. Carrascosa M, Pascual F, Victoria M, et al: Rhabdomyolysis associated with acute Q fever. Clin Infect Dis 25:1243–1244, 1997. 24. Berger R, Wadowksy R: Rhabdomyolysis associated with infection by Mycoplasma pneumoniae: a case report. Pediatrics 105:433–436, 2000. 25. Karis C, Triantafyllidis G: Index of suspicion. Pediatr Rev 23:25, 27–28, 2002. 26. Stucka K, Mycyk M, Leikin J, et al: Rhabdomyolysis associated with unintentional antihistamine overdose in a child. Pediatr Emerg Care 19:25–26, 2003. 27. Cassidy J, Bolton D, Haynes S, et al: Acute rhabdomyolysis after cardiac transplantation: a diagnostic conundrum. Paediatr Anaesth 12:729– 732, 2002. 28. Nakamura H, Blumer J, Reed M: Pemoline ingestion in children: a report of five cases and review of the literature. J Clin Pharmacol 42:275–282, 2002. 29. Panganiban L, Makalinao I, Cortes-Maramba N: Rhabdomyolysis in isoniazid poisoning. J Toxicol Clin Toxicol 39:143–151, 2001.

*Selected readings.

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30. Chattopadhyay I, Shetty H, Routledge P, et al: Colchicine induced rhabdomyolysis. Postgrad Med J 77:191–192, 2001. 31. Kalaria D, Wassenaar W: Rhabdomyolysis and cerivastatin: was it a problem of dose? CMAJ 167:737, 2002. 32. Halachanova V, Sansone R, McDonald S: Delayed rhabdomyolysis after ecstasy use. Mayo Clin Proc 76:112–113, 2001. 33. McCann B, Hunter R, McCann J: Cocaine/heroin induced rhabdomyolysis and ventricular fibrillation. Emerg Med J 19:264, 2002. 34. Johnson C, VanTassell V: Acute barium poisoning with respiratory failure and rhabdomyolysis. Ann Emerg Med 20:1138–1142, 1991. 35. Frankowski G, Johnson J, Tobias J: Rapacuronium administration to two children with Duchenne’s muscular dystrophy. Pediatr Anesth 91:27–28, 2000. 36. Gronert G: Cardiac arrest after succinylcholine: mortality greater with rhabdomyolysis than receptor upregulation. Anesthesiology 94:523– 529, 2001. 37. Hibi S, Misawa A, Tamai M, et al: Severe rhabdomyolysis associated with tacrolimus. Lancet 346:702, 1995. 38. Carroll R, Hall E, Kitchens C: Canebrake rattlesnake envenomation. Ann Emerg Med 30:45–48, 1997. 39. DiGiacomo J, Frankel H, Haskell R: Unsuspected child abuse revealed by delayed presentation of periportal tracking and myoglobinuria. J Trauma Injury Infect Crit Care 49:348–350, 2000. 40. Schwengel D, Ludwig S: Rhabdomyolysis and myoglobinuria as manifestations of child abuse. Pediatr Emerg Care 1:194–197, 1985.

41. Sauret J, Marinides G, Wang G: Rhabdomyolysis. Am Fam Physician 65:907–912, 2002. 42. Alshanti M, Eledrisis M, Jones E: Rhabdomyolysis associated with hyperthyroidism. Am J Emerg Med 19:317, 2001. 43. Moghtader J, Brady W, Bonadio W: Exertional rhabdomyolysis in an adolescent athlete. Pediatr Emerg Care 13:382–385, 1997. 44. Sherry P: Sickle cell trait and rhabdomyolysis: case report and review of the literature. Mil Med 155:59–61, 1990. 45. Hollander A, Olney R, Blackett P, et al: Fatal malignant hyperthermialike syndrome with rhabdomyolysis complicating the presentation of diabetes mellitus in adolescent males. Pediatrics 111:1447–1452, 2003. 46. Pena D, Vaccarello M, Neiberger R: Severe hemolytic uremic syndrome associated with rhabdomyolysis and insulin-dependent diabetes mellitus. Child Nephrol Urol 11:223–227, 1991. 47. Straussberg R, Harel L, Varsano I, et al: Recurrent myoglobinuria as a presenting manifestation of very long chain acyl coenzyme A dehydrogenase deficiency. Pediatrics 99:894–896, 1997. 48. Lappalainen H, Tiula E, Uotila L, et al: Elimination kinetics of myoglobin and creatine kinase in rhabdomyolysis: implications for followup. Crit Care Med 30:2212–2215, 2002. 49. Falasca G, Reginato A: The spectrum of myositis and rhabdomyolysis associated with bacterial infection. J Rheumatol 21:1932–1937. 50. Mannix R, Tan ML, Wright R, Baskin M: Acute pediatric rhabdomyolysis: causes and rates of renal failure. Pediatrics 118:2119–2125, 2006. 51. Savage D, Forbes M, Pearce G: Idiopathic rhabdomyolysis. Arch Dis Child 46:594–607, 1971.

Chapter 100 Diseases of the Hip Ronald I. Paul, MD

Key Points Hip disease should be considered in any child with thigh, groin, or knee pain. Although specific hip disorders are more common in specific age ranges, there is a considerable amount of overlap. The absence of hip ossification centers makes the diagnosis of developmental dysplasia of the hip difficult in young infants.

Selected Diagnoses Developmental dysplasia of the hip Legg-Calvé-Perthes disease Slipped capital femoral epiphysis Transient synovitis of the hip

Discussion of Individual Diagnoses Developmental Dyspasia of the Hip Developmental dysplasia of the hip (DDH) describes a spectrum of diseases that result from abnormal formation of the hip joint during fetal development and the first few months of life. The term replaces the older and more traditional designation, “congenital dislocation of the hip,” which was too narrow in its description. Many cases are not dislocated at the time of diagnosis, and not all cases are congenital. Although most cases are detected during routine newborn and early infancy examinations by a primary care physician, some cases either are not discovered early or have a delayed presentation. Clinical Presentation DDH is variable in its presentation, depending on the severity and age at diagnosis. Some newborn hip joints are simply loose or slide in the acetabulum and are referred to as being subluxatable. Other hip joints lie within the acetabulum, but are dislocatable as they can be manually displaced with an audible “click” or palpable “clunk.” The least common but

more severe form of DDH includes hips that are dislocated while at rest. They may or may not be able to be reduced with simple measures. The incidence of hip dysplasia in neonates is thought to be 1%, with 0.1% dislocated.1 However, routine ultrasonography of babies in England has shown up to a 6% incidence of abnormal hips, although 90% of these return to normal by 9 weeks of age.2 DDH is found more often in white and less often in African American infants.1 Female gender and family history of DDH are risk factors, and up to 25% of DDH infants are born breech.2,3 Because of the variability in presentation of DDH, clinical findings and appropriate diagnostic tests depend on the severity of dysplasia and patient age. Initially, parents may report difficulty in diapering an infant whose hips resist abduction. If not detected prior to walking, parents may notice gait asymmetry due to leg length differences. Eventually, pain in the hips and increasing limp will be noticed by the parent, patient, or physician. The Ortolani and Barlow maneuvers have been the standard examination techniques used by physicians4 (Fig. 100– 1). Both techniques should be performed on calm infants as a crying infant’s muscle tone may inhibit the subtle changes in DDH. In the Barlow maneuver, each hip should be flexed to 90 degrees while one hand stabilizes the other hip or pelvis. The thumb is placed on the medial thigh and the index and middle fingers are placed on the greater trochanter. The thigh is adducted and then pressure is applied longitudinally in a posterior direction in an attempt to dislocate the hip. A palpable clunk or audible click may occur with dislocation. The Ortolani maneuver is used to detect a hip that is dislocated by trying to reduce the dislocation. The thigh is flexed and abducted and the femoral head is lifted anteriorly into the acetabulum. If reduction is possible, the relocation will be felt as a clunk, not heard as a click. Loose hips may be detected by increased laxity in the hip joint. Ortolani or Barlow maneuvers become more difficult to detect as the infant ages beyond 4 to 6 months because soft tissue contractures develop as the hip becomes more fi xed in place. After this time, the infant may have a hip dislocation with severe limitations of abduction along with other signs, including leg-length discrepancy and asymmetric thigh skinfolds. Although most cases are diagnosed clinically, radiographs and ultrasonography (US) have been helpful in confirming the diagnosis.5 Some centers recommend routine US of all 735

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FIGURE 100–1. Ortolani (right) and Barlow (left) tests for detecting development dysplasia of the hip.

FIGURE 100–2. Radiograph of a 17-month-old infant with congenital dislocation of the right hip. There is delayed ossification of the femoral epiphysis and an abnormal position of the femoral metaphysis.

infants for DDH. However, US is not routinely performed in the United States since it may be too sensitive for mild hip dyplasia, and many cases will resolve spontaneously.1,2,5 Therefore, clinical examination is the primary method of diagnosis until 4 to 6 weeks of age. Ultrasound may be helpful at that time if clinical examination results warrant it. Plain radiographs of the pelvis are helpful, but only after the femoral head starts to ossify at about 4 months of age.5 Prior to 4 months of age, plain radiographs may be difficult to interpret and falsely reassuring. Abnormal position or delayed

ossification of the femoral head may be seen in older patients with DDH (Fig. 100–2). The differential diagnosis of DDH is broad. Consideration should be given to causes of abnormal hip movement or abnormal resting position of hips. The list includes trauma, septic joints, and contractures caused by cerebral palsy (see Chapter 20, Lower Extremity Trauma; Chapter 21, Pelvic and Genitourinary Trauma; Chapter 46, Disorders of Movement; and Chapter 47, Peripheral Neuromuscular Disorders). An older child who presents with unrecognized DDH and a limp

Chapter 100 — Diseases of the Hip

should be investigated for metatarsus adduction, internal tibial torsion, Legg-Calvé-Perthes (LCP) disease, slipped capital femoral epiphysis, and transient synovitis of the hip. The workup will depend on patient age and other associated symptoms and physical findings. Management Once the diagnosis is made, management is directed by orthopedic consultants. Treatment is more successful when DDH is recognized earlier in its course. Mild laxity that is recognized in the first few days of life may not need therapy if the follow-up examination becomes normal. If symptoms persist, the main therapy is a Pavlik harness, which splints the leg in flexion and abduction. The splint prevents hip extension and limits adduction. If unsuccessful, a hip spica cast may be necessary. Infants older than 6 months may need closed reduction of a dislocated hip under general anesthesia. If unsuccessful, open reduction or femoral osteotomies may be needed. Prognosis is excellent if diagnosed early in the newborn period. Untreated patients are at risk for osteoarthritis, gait disturbances, leg-length discrepancies, and chronic pain. Legg-Calvé-Perthes Disease LCP disease, named after the three physicians who first described this disorder in the early 1900s, is a sequence of events that includes ischemic hip degeneration and subsequent regeneration that takes place in young children over several years. Although the disease is self-limited and usually has a benign outcome during childhood and adolescence, many patients develop significant osteoarthritis later in life. The etiology of LCP disease is unclear, and the disease may have a hormonal or an abnormal blood viscosity or clotting origin.6,7 The end result is an ischemic insult to the developing femoral head resulting in necrosis. The disease occurs in a young age group, with 80% of patients between 4 and 9 years of age, and an outer range of 2 to 13 years of age.8 The disease is more common in males than females and there is an increased incidence in siblings.7 Birth weight below 2.5 kg, short stature, and delayed skeletal maturation have also been shown to be risk factors. About 10% of patients will develop bilateral disease.

FIGURE 100–3. Radiograph of an 8-year-old boy with left hip pain. There is fragmentation of the left femoral head demonstrating Legg-Calvé-Perthes disease.

737

Clinical Presentation Children with this disease generally present with pain or a limp. Pain may be localized to the hip, groin, thigh, or knee. Parents may relate the pain or limp to minor trauma. Pain onset is usually not abrupt, but develops over days to months. Physical examination may show a limp (antalgic gait) secondary to either pain or a leg-length discrepancy. The length of both legs should be measured and compared in the supine position by measuring from the anterior superior iliac spine to the medial malleolus. The patient may also have pain with external hip rotation, and limited internal rotation and abduction. Radiographs are the most common method for confirming a diagnosis. The diseased hip joint will progress through several stages, and radiographs will demonstrate different findings. Initially, anteroposterior and frog-leg lateral pelvic radiographs will demonstrate a smaller femoral head compared to the contralateral normal hip. A widened joint space may also be apparent. Within several months, a crescentshaped radiolucent line may appear in the femoral head as it becomes more radiopaque. Following this, the epiphysis becomes fragmented (Fig. 100–3). Finally, reossification takes place, which may leave a residual deformity in both the femoral head and corresponding acetabulum. The entire process may take 2 to 4 years. Magnetic resonance imaging (MRI) has been used to evaluate children with LCP disease. With MRI, cartilaginous and metaphyseal abnormalities can be seen. The thickness of the articular cartilage of the femoral head has been shown to be increased in LCP disease and may be associated with loss of containment of the femoral head. Importantly, MRI has been shown to be more sensitive than radiography for the determination of subluxation of the femoral head during the active phase of LCP disease.9 The differential diagnosis of patients with LCP disease is large and includes inflammatory disorders, trauma, neoplasias, and congenital abnormalities. DDH also may occur in this age group, especially if it is unrecognized in infancy. Management Since the disease is self-limiting and resolves in 2 to 4 years, initial treatment is aimed at reducing pain. This may be

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accomplished with nonsteroidal anti-inflammatory drugs and reduction of activity. Occasionally, non–weight-bearing, braces, casting, and osteotomies are utilized to decrease pain and improve femoral head reossification in a normal spherical shape.10 Orthopedic outpatient referral is appropriate for most cases. Long-term outcome studies show that most patients are active and pain free for 20 to 40 years postdiagnosis. However, beyond 40 to 50 years, over 50% of patients develop degenerative joint disease and osteoarthritis.6,10 The largest prognostic risk factors for long-term morbidity are age at diagnosis and the extent of residual femoral head deformity.6 Patients who are diagnosed at an earlier age (under 6 years of age) do better than older children. Patients with more residual deformity in the femoral head are at risk for earlier onset of degenerative joint disease. Slipped Capital Femoral Epiphysis Slipped capital femoral epiphysis (SCFE) is defined as displacement of the femoral epiphysis (femoral head) on the femoral metaphysis (femoral neck). The slippage initially occurs in a posterior and medial direction, and occurs most frequently during adolescent growth spurts. Due to the potential for damage to the tenuous vascular supply of the femoral head, the process is an important one to diagnose as delays in implementing treatment can lead to further slippage and increased morbidity. Most practitioners now classify SCFE into two categories, stable and unstable.11,12 Clinically, a stable SCFE is one in which the patient can bear weight with or without crutches and an unstable SCFE is when the child cannot walk, even with crutches. An older classification based on duration of symptoms (chronic vs. acute) is no longer recommended as it has less prognostic capabilities. The vast majority of patients present with a stable SCFE, which carries a better prognosis if recognized early. Although SCFE is usually associated with overweight children, it can also occur in nonobese patients. It is thought that obesity causes increased shear forces across an already weak and vertically oriented physis, resulting in slippage.12 It occurs more often in African Americans compared to whites, and 60% of patients are male.13 SCFE usually occurs in adolescents during prepubescent growth. Therefore, it occurs earlier in females (average 12 years) than males (average 13.5 years) and rarely occurs after menarche in females.12,14 Between 25% and 40% of children with SCFE have bilateral involvement, with 50% of these presenting with simultaneous involvement and the others develop symptoms on the contralateral side within 18 months of initial diagnosis.12 Clinical Presentation Children present with a variety of symptoms, including a limp and pain. Symptoms are usually present for several weeks before diagnosis and may be initially attributed to minor injuries or “growing pains.” Patients may have pain in the hip, thigh, groin, or knee. The absence of hip pain and the presence of thigh pain have been associated with a missed diagnosis.15 Errant diagnoses by physicians have included Osgood-Schlatter disease, bursitis, growing pains, chondromalacia, thigh contusions, muscle strains, stress fractures, and tendonitis. Because delayed diagnosis can result in further slippage, it is important for practitioners to include

SCFE in their differential diagnosis whenever evaluating patients with thigh, groin, or knee pain. In addition to pain, children may have an antalgic gait or loss of internal rotation of the hip. As slippage increases, there will be a worsening gait abnormality and decreased internal rotation of the hip. Unstable SCFE presents with extreme pain and can be thought of as an acute Salter-Harris type I fracture.16 Minor trauma, as in slipping off a curb edge or simply twisting in bed, may immediately precede an unstable SCFE. In addition to severe pain, patients with an unstable SCFE will resist any motion at the hip. The hip is usually held in flexion and external rotation. Gentle passive hip flexion usually leads to external rotation of the hip. No attempts at reduction should be made in the emergency department as this can cause further damage to the femoral head’s vascular supply.17 All patients with symptoms compatible with a stable SCFE should have anteroposterior and frog-leg lateral pelvic radiographs. Because early slippage is posterior and inferior, initial radiographic findings may only be seen on the lateral radiographs, revealing minimum posterior step-off at the physeal plate. Klein’s line represents a line drawn along the femoral neck on an anteroposterior film that should bisect the lateral portion of the femoral head. In patients with mild slippage, the line will be flush with or lateral to the lateral edge of the epiphysis (Fig. 100–4). As the slippage continues, there is further inferior and posterior movement of the epiphysis relative to the metaphysis, and radiographs will eventually show the typical picture similar to a scoop of ice cream slipping off a cone. Patients suspected of having an unstable SCFE should not be forced into a frog-leg lateral position, but should have a lateral hip radiograph taken instead. A lateral view or frog-leg lateral view of the opposing leg should be taken for comparison and to detect mild slippage in bilateral cases. The differential diagnosis for patients with SCFE includes other processes that can cause pain in the hip and lower leg. LCP disease usually occurs in younger children, but there is overlap in the age distribution. Patients with transient synovitis, septic hip, osteomyelitis, and muscle or ligamentous injuries of the thigh or hip may also present with similar symptoms (see Chapter 20, Lower Extremity Trauma; Chapter 21, Pelvic and Genitourinary Trauma; Chapter 95, Musculoskeletal Disorders in Systemic Disease; and Chapter 96, Bone, Joint, and Spine Infections). Because hip pathology often presents with knee pain, acute or chronic injuries of the knee, including Osgood-Schlatter disease and chondromalacia, should be considered. However, the knee examination is usually normal in patients with SCFE. Management All patients with SCFE need orthopedic referral as surgery is needed in all cases. Patients with unstable SCFE will need immediate orthopedic referral. Children with stable SCFE can be made non–weight bearing with crutches and seen promptly as outpatients. The most common surgical procedure for stable SCFE is a single central screw to maintain the femoral head in its current location until the physis is closed.12 No attempts are made to reduce the slippage. Once physeal closure occurs, the patient is able to return to running and contact sports. Surgical treatment for unstable SCFE is controversial and may involve closed reduction, single or multiple screws, or osteotomies, and will depend on the degree of slippage and the preference of the orthopedic surgeon.18

Chapter 100 — Diseases of the Hip

739

FIGURE 100–4. Radiograph of a 12-year-old with left hip pain. There is mild slippage of the left femoral epiphysis. Klein’s line, drawn along the femoral neck, does not bisect the left femoral epiphysis as it does on the normal right hip.

Patients with stable SCFE usually do very well with minimal complications or morbidity, especially when diagnosed early. Complications of unstable SCFE include avascular necrosis of the femoral head, occurring in up to 35% of cases, and chondrolysis or loss of cartilage in the femoral head and acetabulum.10,15,17 Chondrolysis also develops more often as the degree of slippage increases and underscores the need to avoid missed or delayed diagnoses. Transient Synovitis of the Hip The most common cause of painful hips in children is transient synovitis of the hip (TSH). While the etiology of TSH is unknown, there is usually no long-term morbidity from this disorder. Importantly, clinicians must be able to differentiate this disorder from serious disorders causing a painful hip, including septic hip, osteomyelitis, LCP disease, SCFE, and neoplasias. Although cases have been described in infants as young as 9 months and children as old as 18 years, the average age of children with TSH is 6 years, with a typical range of 3 to 10 years.19,20 This range overlaps with other causes of hip disease, including LCP disease and SCFE. The disorder is found more often in males, with a male:female ratio of between 1.5 : 1 and 2.6 : 1.19,21,22 Over 95% of children present with unilateral involvement, with an even distribution between right and left hips.20 Clinical Presentation Many patients have pain or limp for less than 24 hours, and two thirds have symptoms for less than 1 week.20 Most others have symptoms for less than 1 month. A preceding or concurrent respiratory infection is found in 50% of patients with TSH, leading some to believe there is an infectious or postinfectious etiology. Most patients will either be afebrile or have a low temperature elevation,20,22 although temperatures as high as 40° C have been reported.20 Patients may report pain of the hip, thigh, or knee, and have a mild limp or refuse to bear weight. Infants and children are not ill appearing and have a varying degree of restriction of hip movement and pain elicited at extremes of rotation. The evaluation of patients suspected of having TSH should include a white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) level,

and a blood culture to differentiate this disorder from septic arthritis.21-25 The WBC count is usually normal to mildly elevated, with a mean count between 8600/mm3 and 11,200/ mm3.20,21 However, some patients may have a WBC count greater than 20,000/mm3. The mean ESR is less than 20 mm/ hr but may be greater than 20 mm/hr in as many as 25% of cases.22 CRP is usually less than 1 mg/dl but may be greater than 2 mg/dl in up to 14% of cases.22 Radiographs may be normal or may show signs consistent with a joint effusion, with widening of the joint space or displacement or obliteration of periarticular fat planes. All patients with TSH will have an abnormal US showing mild or moderate effusion, with a small percentage showing severe effusion22,26,27 (Fig. 100–5). Joint aspiration is performed by orthopedic consultants and is reserved for patients in whom septic arthritis is still considered as a possible diagnosis after review of the clinical examination findings and other less invasive laboratory studies. Joint fluid should be sterile in TSH, with no bacteria seen on Gram stain and negative synovial fluid culture. Although many etiologies have to be considered in the differential diagnosis of a child with a painful hip, radiographs can usually reveal abnormalities associated with LCP disease, SCFE, and trauma. Clinicians must be able to differentiate TSH from a septic hip. Several studies have found that the historical features and diagnostic adjuncts differ statistically between the two diseases: mean WBC count, ESR, CRP, temperature, joint space differences, history of fever, and an inability to bear weight.21-25 A combination of several factors, including temperature greater than 37° C to 38° C, WBC count greater than 11,000/mm3, ESR greater than 20 mm/hr, CRP greater than 1 mg/dl, joint space difference of greater than 2 mm on radiographs, and a history of fever or non–weight bearing, is more predictive of patients at increased risk of septic hip and therefore in need of a hip aspiration. If none of these features is present, the probability of septic arthritis is less than 1%22-25 (see Chapter 96, Bone, Joint, and Spine Infections). The more abnormal factors present, the greater likelihood the patient has a septic hip and not TSH.22-25 Limited studies have found MRI to be helpful in differentiating between the two entities, although there should be no delay in confirming the diagnosis of septic hip.28 If septic arthritis is suspected after initial imaging and

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FIGURE 100–5. Ultrasound of a 5-year-old with right hip pain. Hip effusion is demonstrated with widening of the intracapsular space, especially when compared with normal left hip.

laboratory evaluation, orthopedic specialists should be consulted for hip joint aspiration. Management Most patients with TSH have rapid resolution of symptoms with bed rest. While most patients can be treated at home, some with more severe symptoms are treated in the hospital with traction for pain management. Recurrence of symptoms after initial resolution is unusual but may occur in 4% of cases.19 Follow-up US examinations or radiographs in 6 months may reveal a small number of patients who develop LCP disease,19,20,22 although it is unclear if TSH increases the risk for LCP disease, or the LCP cases were simply not recognized during the initial presentation. Because of the reported association with LCP disease, patients with TSH should be considered for repeat US examinations or radiographs if recurrent symptoms develop several months later. Unlike septic arthritis and SCFE, no long-term complications or morbidity is associated with TSH. REFERENCES 1. French LM, Dietz FR: Screening for developmental dysplasia of the hip. Am Fam Physician 60:177–184, 1999. 2. Marks DS, Clegg J, al-Chalabi AN: Routine ultrasound screening for neonatal hip instability: can it abolish late-presenting congenital dislocation? J Bone Joint Surg Br 76:534–538, 1994. 3. Barlow TG: Early diagnosis and treatment of congenital dislocation of the hip. J Bone Joint Surg Br 44:292–301, 1962. 4. Novacheck TF: Developmental dysplasia of the hip. Pediatr Clin North Am 43:829–848, 1996. 5. Donaldson JS, Feinstein KA: Imaging of developmental dysplasia of the hip. Pediatr Clin North Am 44:591–614, 1997. 6. Weinstein SL: Natural history and treatment outcomes of childhood hip disorders. Clin Orthop 344:227–242, 1997. 7. Wenger DR, Ward WT, Herring JA: Current concepts review. Legg-Calvé-Perthes disease. J Bone Joint Surg Am 73:778–788, 1991. 8. Koop S, Quanbeck D: Three common causes of childhood hip pain. Pediatr Clin North Am 43:1053–1066, 1996. 9. Hubbard AM: Imaging of pediatric hip disorders. Radiol Clin North Am 39: 721–732, 2001. 10. Herring JA: Current concepts review. The treatment of Legg-CalvéPerthes disease: a critical review of the literature. J Bone Joint Surg Am 76:448–458, 1994.

11. Loder RT: Unstable slipped capital femoral epiphysis. J Pediatr Orthop 21:694–699, 2001. 12. Loder RT: Slipped capital femoral epiphysis. Am Fam Physician 57:2135–2142, 1998. 13. Loder RT: The demographics of slipped capital femoral epiphysis: an international multicenter study. Clin Orthop Relat Res 322:8–27, 1996. 14. Swiontkowski MF, Gill EA: Slipped capital femoral epiphysis. Am Fam Physician 33:167–171, 1986. 15. Ledwith CA, Fleisher GR: Slipped capital femoral epiphysis without hip pain leads to missed diagnosis. Pediatrics 89:660–662, 1992. 16. Stanitski CL: Acute slipped capital femoral epiphysis. J Am Acad Orthop Surg 2:96–106, 1994. 17. Maeda S, Kita A, Funayama K, Kokubun S: Vascular supply to slipped capital femoral epiphysis. J Pediatr Orthop 21:664–667, 2001. 18. Rattey T, Piehl F, Wright JG: Acute slipped capital femoral epiphysis: review of outcomes and rates of avascular necrosis. J Bone Joint Surg Am 78:398–402, 1996. 19. Landin LA, Damielsson LG, Wattsgard C: Transient synovitis of the hip: its incidence, epidemiology and relation to Perthes’ disease. J Bone Joint Surg Br 69:238–242, 1987. 20. Haueisen DC, Weiner DS, Weiner S: The characterization of “trans-ient synovitis of the hip” in children. J Pediatr Orthop 6:11–17, 1986. 21. Del Beccro MA, Champoux AN, Bockers T, Mendelman PM: Septic arthritis versus transient synovitis of the hip: the value of screening laboratory tests. Ann Emerg Med 21:1419–1422, 1992. 22. Eich GF, Superti-Furga A, Umbricht FS, Willi UV: The painful hip: evaluation of criteria for clinical decision making. Eur J Pediatr 158:923–928, 1999. 23. Kocher MS, Zurakowski D, Kasser JR: Differentiating between septic arthritis and transient synovitis of the hip in children: an evidencebased clinical prediction algorithm. J Bone Joint Surg Am 81:1662– 1670, 1999. 24. Kocher, MS, Mandiga R, Zurakowski D, et al: Validation of a clinical prediction rule for the differentiation between septic arthritis and transient synovitis of the hip in children. J Bone Joint Surg Am 86:1629–1635, 2004. 25. Jung ST, Rowe SM, Moon EU, et al: Significance of laboratory and radiologic fi ndings for differential between septic arthritis and transient synovitis of the hip. J Pediatr Orthop 23:368–372, 2003. 26. Terjesen T, Osthus P: Ultrasound in the diagnosis and follow-up of transient synovitis of the hip. J Pediatr Orthop 11:608–613, 1991. 27. Eggl H, Drekonja T, Kaiser B, Dorn U: Ultrasonography in the diagnosis of transient synovitis of the hip and Legg-Calvé-Perthes disease. J Pediatr Orthop 8:177–180, 1999. 28. Lee SK, Suh JK, Ryeom HK, et al: Septic arthritis versus transient synovitis at MR imaging: preliminary assessment with signal intensity alterations in bone marrow. Radiology 211:459–465, 1999.

Immunologic/Allergic

Chapter 101

Serum Sickness Lee S. Benjamin, MD

Key Points Serum sickness is now rare in the United States due to the substitution of newer medications for those historically made from animal serum. A condition with a clinical presentation similar to serum sickness, known as “serum sickness–like reaction,” is sometimes referred to as “serum sickness.” This intermingling of terms likely leads to some confusion. The signs and symptoms of serum sickness are fever, arthralgia, skin eruptions, lymphadenopathy, nephritis, edema, and neuritis. The signs and symptoms of serum sickness-like reactions, in contrast, may include fever and lymphadenopathy, but are otherwise confined to the skin and joints. Antibiotics are the most common medications to cause serum sickness–like reactions. A latent period of 2 to 17 days is expected between antigen exposure and the onset of serum sickness–like reactions.

Introduction and Background Serum sickness is an uncommon clinical syndrome associated with exposure to animal serum. The typical symptoms include fever, arthralgias, skin eruptions that can include palpable purpura or urticaria, lymphadenopathy, nephritis, edema, and neuritis.1,2 Historically, antisera derived from horse serum were the most common causes of serum sickness. These antisera were used to treat snake bites, botulism, and pneumococcal, meningococcal, and streptococcal infections, and to immunize patients against diphtheria, tetanus, and rabies.3-7 Refinements and advances in treatments for these conditions have substantially mitigated the risk of serum sickness for patients in recent years. Serum sickness–like reactions are more common than cases of serum sickness. Serum sickness–like reactions have

some clinical signs and symptoms in common with serum sickness. These include rash and joint pains.8-11 The rash may include urticaria or erythema multiforme, or be morbilliform. The child may exhibit arthralgias or clinically appreciable arthritis. The presence of fever or lymphadenopathy is variable. Unlike serum sickness, serum sickness–like reactions are not associated with circulating immune complexes. Therefore, palpable purpura, nephritis, edema, and neuritis are not expected in cases of serum sickness–like reactions. Oral antibiotics are currently the most common cause of serum sickness–like reactions.9 Even though they share some clinical features, it is unknown if serum sickness–like reactions and serum sickness are different points along a single continuum. Unfortunately, the term serum sickness is sometimes applied to cases of serum sickness–like reactions.12 This intermingling of terms likely leads to confusion.

Recognition and Approach There are no recent epidemiologic studies reporting the incidence, but clinical experience suggests serum sickness presenting to the emergency department is rare. Serum sickness is a type III hypersensitivity reaction to foreign proteins that leads to the development of circulating immune complexes that deposit in small vessels, activation of complement, and recruitment of granulocytes.1,3,13-15 The deposition of the circulating immune complexes is thought to be the dominant pathophysiologic derangement. Children with serum sickness–like reactions are rare, but relatively more common than those with serum sickness. Population-based epidemiologic data are not available. The pathophysiology of serum sickness–like reactions remains elusive.8,10,16 Circulating immune complexes are inconsistently identified. The vast majority of cases of serum sickness– like reactions occur in children younger than 5 years.10-12 A history of taking a new antibiotic or other medication is nearly universal12 (Table 101–1). In particular, the use of oral cefaclor has been implicated in cases of serum sickness– like reactions.8,9,12 Prior sensitization to medication is not a prerequisite.8,10

Clinical Presentation Children may present to the emergency department for evaluation of possible serum sickness or a serum sickness–like reaction. A history of exposure to horse serum makes the 741

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Table 101–1

Medications Associated with Serum Sickness–like Reactions

Bupropion Carbamazepine Cephalosporins Ciprofloxacin Fluoxetine Griseofulvin Metronidazole NSAIDs Penicillins Phenytoin Propranolol Rifampin Streptomycin Sulfa medications Tetracyclines Thiouracil Abbreviation: NSAIDs, nonsteroidal anti-inflammatory drugs.

diagnosis of serum sickness quite likely. However, the history is seldom so straightforward. It is more likely to include some vague symptoms arising after treatment with a new medication has begun. The temporal relationship between starting the new medication and symptom onset is sometimes helpful. For both serum sickness and serum sickness–like reactions, the onset of symptoms is usually delayed several days from the exposure to the inciting antigen. The exact time span is not known. Rough estimates based on limited data suggest the symptoms of serum sickness arise 1 to 2 weeks after antigenic exposure and the symptoms of serum sickness–like reactions arise 2 to 17 days after drug exposure.10,13,14 The most common symptoms include rash and arthralgia.8,9,11,12,17 A history of neurologic symptoms or dark urine is most consistent with a diagnosis of serum sickness. A history of recently beginning a course of oral cefaclor suggests a serum sickness–like reaction.8,9,12,18,19 Physical examination findings in cases of serum sickness and serum sickness–like reactions are often nonspecific. In both conditions, a rash is expected. In both conditions, the rash may be urticarial or morbilliform.8,9,11 In cases of serum sickness, but not serum sickness–like reactions, the rash may include petechiae and palpable purpura. In both conditions, the physical examination may reveal swollen, tender joints consistent with an acute arthritis. Fever and lymphadenopathy are characteristic of serum sickness, but variably seen in cases of serum sickness–like reactions.8,9,12-14 Facial edema and an abnormal neurologic examination may be seen in cases of serum sickness, but not cases of serum sickness–like reactions.20 A child with acute nephritis associated with serum sickness may be hypertensive. Laboratory tests have modest utility in the evaluation of a child with possible serum sickness or a serum sickness–like reaction. For cases suggestive of serum sickness–like reactions, no routine laboratory tests are indicated. The history of initiating a new medication, particularly an antibiotic, 2 to 17 days prior to presentation and the presence of a nonpetechial rash and joint pains with or without fever are likely diagnostic. For cases in which serum sickness is likely, testing is generally directed at the overall differential diagnosis. For example, for children with a petechial rash or purpura, a

measurement of platelets (usually obtained as part of a complete blood count) and a prothrombin time are probably indicated. A microscopic urinalysis is helpful for identifying acute nephritis. A measurement of blood urea nitrogen and creatinine is also indicated if serum sickness is suspected. Other laboratory tests are indicated on a case-by-case basis, guided by signs and symptoms. The child’s primary care physician may request other tests to guide him or her in the outpatient management of serum sickness.

Important Clinical Features and Considerations The differential diagnosis of the signs and symptoms associated with children suspected of having serum sickness or serum sickness–like reactions is broad. The differential diagnosis includes conditions such as bacterial, viral, and parasitic infections, as well as vasculitis, connective tissue disease, syphilis, atopic disease, inflammatory bowel disease, sarcoidosis, cystic fibrosis, Behçet’s syndrome, pemphigus, bullous pemphigoid, and allergic vasculitis.21

Management Discontinuation of the offending agent is the mainstay of treatment and is usually curative.17 There is no evidence on which to base management decisions. Although systemic steroids have been recommended, their utility is uncertain, particularly given that the vast majority of children will have spontaneous resolution of their symptoms with the removal of the offending agent as the sole intervention.11,17 Other treatments are supportive and symptomatic. These include acetaminophen for fever and analgesia, antihistamines for allergic-type symptoms such as urticaria, and nonsteroidal anti-inflammatory medications such as ibuprofen for joint inflammation and pain. In general, children with serum sickness or serum sickness–like reactions can be managed as outpatients. Uncertainty in the diagnosis may warrant hospital admission or transfer to a tertiary pediatric center to work through the differential diagnosis. The most common reason for admission to the hospital in cases of serum sickness–like reactions is for uncontrollable joint pains.11 In general, the emergency physician should recommend that the family avoid giving the offending agent to the child in the future. One pair of authors recommends avoiding the entire class of medications to which the offending agent belongs.22 There is no evidence to support this recommendation. Others have noted no significant cross reactivity within the same class of medications.11,23

Summary A history of antigen exposure is very helpful in evaluating a child suspected of possibly harboring serum sickness or a serum sickness–like reaction to a new medication. The presence of palpable purpura, nephritis, edema, and neuritis helps differentiate serum sickness from a serum sickness–like reaction. Removing the offending agent is the mainstay of treatment. Most children do well with symptomatic treatment and recover uneventfully. Avoidance of the offending agent in the future is prudent.

Chapter 101 — Serum Sickness

REFERENCES *1. Roujeau JC, Stern RS: Severe adverse cutaneous reactions to drugs. N Engl J Med 331:1272–1285, 1994. 2. Parker CW: Drug allergy. N Engl J Med 292:511–514, 1975. 3. von Pirquet CF, Schick B: Serum Sickness. Baltimore: Williams & Wilkins, 1951. 4. Bielory L, Kemeny DM, Richards D, et al: IgG subclass antibody production in human serum sickness. J Allergy Clin Immunol 85:573–577, 1990. 5. Corrigan P, Russell FE, Wainschel J: Clinical reactions to antivenin. Toxicon 16(1 Suppl):457–465, 1978. 6. Karliner JS, Belaval GS: Incidence of reactions following administration of antirabies serum; study of 526 cases. JAMA 193:359–362, 1965. 7. Moynihan NH: Serum-sickness and local reactions in tetanus prophylaxis: a study of 400 cases. Lancet 269:264–267, 1955. 8. Levine LR: Quantitative comparison of adverse reactions to cefaclor vs. amoxicillin in a surveillance study. Pediatr Infect Dis 4:358–361, 1985. *9. Parshuram CS, Phillips RJ, Nash MC: Serum sickness in a paediatric emergency department: the role of cefaclor. J Paediatr Child Health 35:223–224, 1999. 10. Kearns GL, Wheeler JG, Childress SH, et al: Serum sickness-like reactions to cefaclor: role of hepatic metabolism and individual susceptibility. J Pediatr 125:805–811, 1994. 11. Vial T, Pont J, Pham E, et al: Cefaclor-associated serum sickness-like disease: eight cases and review of the literature. Ann Pharmacother 26:910–914, 1992. *Selected readings.

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12. Heckbert SR, Stryker WS, Coltin KL, et al: Serum sickness in children after antibiotic exposure: estimates of occurrence and morbidity in a health maintenance organization population. Am J Epidemiol 132:336– 342, 1990. 13. Bielory L, Gascon P, Lawley TJ, et al: Human serum sickness: a prospective analysis of 35 patients treated with equine anti-thymocyte globulin for bone marrow failure. Medicine 67:40–47, 1988. 14. Lawley TJ, Bielory L, Gascon P, et al: A prospective clinical and immunologic analysis of patients with serum sickness. N Engl J Med 311:1407–1413, 1984. 15. Lawley TJ, Bielory L, Gascon P, et al: A study of human serum sickness. J Invest Dermatol 85(1 Suppl):129s–132s, 1985. *16. King BA, Geelhoed GC: Adverse skin and joint reactions associated with oral antibiotics in children: the role of cefaclor in serum sicknesslike reactions. J Paediatr Child Health 39:677–681, 2003. 17. Hebert AA, Sigman ES, Levy ML: Serum sickness-like reactions from cefaclor in children. J Am Acad Dermatol 25:805–808, 1991. 18. Parshuram CS, Phillips RJ: Retrospective review of antibioticassociated serum sickness in children presenting to a paediatric emergency department. Med J Aust 169:116, 1998. 19. Platt R, Dreis MW, Kennedy DL, et al: Serum sickness-like reactions to amoxicillin, cefaclor, cephalexin and trimethoprimsulfamethoxazole. J Infect Dis 158:474–477, 1988. 20. Tatum AJ, Ditto AM, Patterson R, et al: Severe serum sickness-like reaction to oral penicillin drugs: three case reports. Ann Allergy Asthma Immunol 86:330–334, 2001. 21. Van Es LA, Daha MR, Valentijn RM, et al: The pathogenetic significance of circulating immune complexes. Neth J Med 27:350–358, 1984. 22. McCullough H, Grammar LC: Cefaclor serum sickness. JAMA 275:1152–1153, 1996. 23. Ackley AM Jr, Felsher J: Adverse reactions to cefaclor. South Med J 74:1550, 1981.

Chapter 102 Vaccination-Related Complaints and Side Effects Franz E. Babl, MD, MPH and Stuart Lewena, MBBS

Key Points Most vaccination-related complaints are mild and self-limited. The probability that a given problem is related to a recent vaccination can be predicted by knowing which vaccines were given and the timing of the administration of the vaccines in relation to the emergency department visit. Knowledge of the immunization schedule is useful for determining which vaccines a child is likely to have received. This is particularly helpful when the parents cannot reliably identify which vaccines were given during a recent office visit. Due to the low incidence of some events and the high rate of vaccination in the developed world, it is difficult or impossible to determine if some very rare adverse events are causally related to immunizations or merely temporally associated with them.

Selected Diagnoses Allergic reactions and anaphylaxis Rash Fever Encephalitis and encephalopathy Generalized weakness Seizures Syncope Hypotonic-hyporesponsive episodes (shocklike state) Protracted, inconsolable crying Arthralgias and arthritis Extensive limb swelling Thrombocytopenia 744

Discussion of Individual Diagnoses Allergic Reactions and Anaphylaxis Vaccine-related allergic reactions, particularly serious reactions such as anaphylaxis, are rare.1 The measles vaccine, diphtheria and tetanus toxoids and pertussis vaccine (DTP) and hepatitis B vaccine (HepB) are the most commonly identified vaccine-related causes of anaphylaxis.2 The rates of anaphylaxis are 1.8 per 1 million doses for measles vaccine (0.00018%) and 1.6 per 1 million doses for HepB (0.00016%).1,3 Serious allergic reactions due to other vaccines are even rarer.4 Vaccines contain various additives and other components that may cause allergic reactions in children sensitive to these agents. The measles and mumps vaccines (most commonly combined in the measles-mumps-rubella vaccine [MMR]) are derived from chick embryo fibroblast tissue and contain very small amounts of egg protein. Children with an egg allergy are at increased risk of having an allergic reaction to these immunizations, but the risk is exceedingly small. In contrast, the influenza vaccine contains a greater amount of egg protein and places children at such a great risk for allergic reactions that it is recommended that this vaccine be withheld from children with egg allergies.5 Inactivated poliovirus vaccine (IPV) contains trace quantities of neomycin, streptomycin, and polymyxin B. Children with allergies to any of these antimicrobials are at risk for allergic reactions to IPV. The MMR and varicella vaccines contain trace amounts of neomycin and gelatin. Children allergic to neomycin or gelatin can develop allergic reactions, including delayed-type local reactions manifesting as erythematous, pruritic papules 48 to 96 hours after vaccination.3,6,7 Yeast protein is present in HepB, and children with yeast allergies can have reactions to this vaccine.6 The timing of allergic reactions, including anaphylaxis, in relation to vaccine administration is an important factor in determining whether or not the vaccine could be the cause. Parents may not be able to list the vaccines given during a recent office visit or may provide inaccurate information.8 Because of this, it is helpful for emergency physicians to have some familiarity with the recommended schedule of immunizations to allow for a reasoned guess as to what vaccinations were likely given based on the child’s age (Table 102–1).

Chapter 102 — Vaccination-Related Complaints and Side Effects

Table 102–1

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Simplified Pediatric Immunization Schedule Vaccines

Age Birth 2 mo 4 mo 6 mo 12 mo 15 mo 4–6 yr 11–12 yr

HepB ✓ ✓ ✓

DTaP

Tdap

✓ ✓ ✓ ✓ ✓

✓

Hib

IPV

PCV

✓ ✓ ✓ ✓

✓ ✓ ✓

✓ ✓ ✓ ✓

✓

Influenza*

✓

MMR

Varicella

✓

✓

✓

✓

Rota

MCV4

HPV†

✓

✓

✓ ✓ ✓

*Influenza vaccine is given yearly thereafter up to age 5 years. † HPV is administered as a series of 3 immunizations given over 6 months. Abbreviations: DTaP, diphtheria and tetanus toxoids and acellular pertussis vaccine; HepB, hepatitis B vaccine; Hib, Haemophilus influenzae type b conjugate vaccine; HPV, human papillomavirus vaccine; IPV, inactivated poliovirus vaccine; MCV4, meningococcal conjugate vaccine; MMR, measles-mumps-rubella vaccine; PCV, pneumococcal conjugate vaccine; Rota, rotavirus vaccine; Tdap, tetanus and diphtheria toxoids and acellular pertussis vaccine. Adapted from American Academy of Pediatrics Committee on Infectious Diseases. Recommended immunization schedules for children and adolescents—United States, 2007. Pediatrics 119:207–208, 3 p following 208, 2007.

In general, anaphylaxis, if it develops, does so shortly after immunization. In a review of 366 patients with adverse reactions to DTaP, 34 patients developed anaphylaxis and 76 developed urticaria.7 Most cases of anaphylaxis manifested within 15 minutes of vaccine administration, and none occurred after 60 minutes. In contrast, urticaria developed up to 24 hours after immunization. In another study of adverse events after 3 million MMR vaccinations, 30 (0.001%) anaphylaxis-like reactions appeared, 29 within 20 minutes of immunization.9 None of these cases was fatal. The management of vaccine-related allergic reactions and anaphylaxis does not differ from that for cases due to other causes (see Chapter 14, Anaphylaxis/Allergic Reactions). Rash The vaccines most commonly associated with rashes are the varicella and MMR vaccines. A localized injection site rash develops in 4% of children receiving the varicella vaccine.10 Most varicella vaccine–related rashes become apparent 9 to 16 days after immunization. Most of these cases involve mild, localized, papular lesions. Some children manifest what appears to be a mild case of varicella with a handful of the characteristic vesicular lesions and crusting in approximately the same time frame as the papular rashes. Based on the virology, at least some of these cases are due to varicella infection and not the varicella vaccination. In a polymerase chain reaction analysis of 70 post–varicella vaccine rashes, 61% of cases had the wild-type varicella virus strain and 31% showed the Oka-type vaccine strain.11 Disseminated varicella due to the vaccine strain may occur in previously undiagnosed immune-compromised patients.12 MMR is associated with transient rashes in 5% of those vaccinated. This rash is fairly nonspecific in appearance and typically occurs 7 to 10 days after immunization.4,13 This MMRassociated rash is associated with transient lymphadenopathy in some cases. Fever Many childhood vaccines have been associated with causing fever after vaccination.6 Febrile episodes occur at low rates, and within the first 1 to 2 days postvaccination, after admin-

istration of HepB, influenza virus vaccine, Haemophilus influenzae type b conjugate vaccine, and pneumococcal conjugate vaccine (PCV). Fever due to MMR, however, usually occurs 7 to 12 days after immunization. Approximately 5% of children develop a fever of ≥39.4° C (103° F) after MMR vaccination.13,14 In some ways, fever is so common in children that most are expected to develop fever at some point after an immunization. Attributing fever to an immunization is fraught with problems if the time course is drawn out. For example, the incidence of fever within 42 days after the fi rst dose of varicella vaccine is 15%, which is similar to the incidence seen in children who received placebo.10,15 Very high fevers may be seen within 48 hours of the administration of DTP.6 Temperatures ≥40.5° C (104.8° F) are seen in 0.3% of children receiving DTP.6 Following the introduction of the acellular pertussis vaccine into DTP (designated as DTaP), the incidence of fever has been much lower.6 It is prudent to consider alternative diagnoses in children who manifest fever that is temporally associated with vaccines. In one study, 80% of children who experienced fever after receiving the varicella vaccine harbored another illness10 (see Chapter 32, Fever in the Well-Appearing Young Infant). Encephalitis and Encephalopathy Encephalopathy refers to any acute or chronic acquired abnormality of the function of the brain. Encephalitis refers to an encephalopathy caused by an inflammatory response in the brain usually manifested by pleocytosis (i.e., white blood cells in the cerebrospinal fluid).2 Encephalitis with resultant residual permanent encephalopathy develops in approximately 1 in 1000 people (0.1%) infected with the measles virus.13 There is not enough evidence to accept or reject a causal relationship between immunization with live measles vaccine virus and encephalitis or encephalopathy.2 In the United States, 166 cases of encephalopathy occurring 6 to 15 days after measles vaccine were identified over 30 years through a number of passive surveillance systems.13,16 In other words, the incidence of encephalopathy possibly due to measles vaccines is approximately 1 in 2 million (0.00005%). This incidence is so low and the percentage of the population who receives vaccinations is so high, it is essentially

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SECTION IV — Approach to the Acutely Ill Patient

impossible to perform a study to determine if encephalitis can be caused by the measles component of MMR. So, although measles (the disease) can cause encephalitis, it is not clear if the measles vaccine can cause encephalitis. A 10year follow-up of a study from the United Kingdom on vaccination-related encephalopathy showed no evidence of a risk of long-term neurological damage associated with measles vaccine.17 Some strains of the mumps component of MMR can cause aseptic meningitis. However, the strain used in the United States does not.2,13 DPT might cause acute encephalopathy, but with an incidence of 0 to 10 cases per million vaccinations (0 to 0.001%).1,18 There is no difference in the management of children presenting with acute encephalopathy or acute encephalitis temporally associated with vaccines and that of other children with a similar presentation (see Chapter 11, Altered Mental Status/Coma). Generalized Weakness The two main types of weakness associated with vaccines are paralytic poliomyelitis and the Guillain-Barré syndrome. The oral poliovirus vaccine (OPV) has been causally linked with paralytic poliomyelitis.2 The case definition of vaccineassociated poliomyelitis is acute flaccid paralysis in a vaccine recipient 7 to 30 days after receiving OPV, with no sensory or cognitive loss, and with paralysis still present 60 days after the onset of symptoms. The risk is low at 1 case per 2.4 million doses (0.00004%).19 In the United States, the routine childhood immunization schedule has replaced OPV with IPV which is not associated with paralytic poliomyelitis. However, outside the United States, OPV is still widely used. The Guillain-Barré syndrome has been associated with a number of vaccines, but there are inadequate data to determine if a causal relationship exists.2,4,19 This is another example of a very rare event occurring in the context of a very high incidence of vaccination. Seizures The two vaccines associated with high fevers, MMR and DTP, are also associated with febrile seizures. The available data are difficult to reconcile. For example, the risk of febrile seizures following MMR vaccination has been reported to range from 1 in 100,000 (0.001%) up to 1 in 3000 (0.03%).9,20 Case definitions likely cause these differences. The timing of the febrile seizures correlates with the timing of peak postvaccination temperatures.21 There is no evidence that MMR is associated with an increased risk of epilepsy.2 The change from DTP (with the whole-cell pertussis adsorbed component, also referred to as DTwP) to DTaP (with an acellular pertussis component) vaccine has dramatically decreased the risk of fever and also febrile seizures. The incidence of febrile seizures associated with DTaP is 0.5 events per 100,000 vaccinations (0.0005%).22 The treatment of febrile seizures associated with vaccinations is no different than that of children with febrile seizures thought to be due to other causes (see Chapter 40, Seizures). Syncope Syncope can occur after any of the routine childhood vaccinations.23 Syncope can be preceded by symptoms such as light-headedness, dizziness, diaphoresis, and visual changes. Syncope associated with vaccinations is typically brief. Adolescent girls are the most common population to experience

syncope following vaccination.23,24 In a review of 697 cases of syncope after vaccination, 57% occurred within 5 minutes of administration, 80% occurred within 15 minutes, and 88% within 30 minutes. Like other causes of syncope, 24% of the children experiencing syncope manifested some brief seizurelike movements.23 In most cases, postvaccination syncope is neurocardiogenic. The approach to children who experience syncope following vaccination is the same as that of other children who experience syncope (see Chapter 61, Syncope). Hypotonic-Hyporesponsive Episodes (Shocklike State) Hypotonic-hyporesponsive episodes have been associated with DTP vaccines. Although the highest rates occur after immunization with the older DTwP, episodes may occur after DTaP administration.25 These events occur with an incidence of 0 to 140 cases per 100,000 doses (0 to 0.14%).4,18,26 Hypotonic-hyporesponsive episodes have been defined as limpness or hypotonia, reduced responsiveness, and pallor or cyanosis occurring within 48 hours of immunization and lasting from 1 minute to 48 hours in children younger than 10 years of age.27 The etiology and pathophysiology of these events is unknown. By the time patients present for medical attention, symptoms have often resolved. In a series of 215 cases of hypotonic-hyporesponsive episodes, the median age was 4 months (range, 1 month to 8.9 years) and the median interval from the time of vaccination to onset of symptoms was 3.5 hours (range, 1 minute to 2 days).28 None of the events was fatal, and 99% of children returned to their prevaccination state with a median time to return of 6 hours (range, 1 minute to 4 months). The three children reported as not returning to baseline were diagnosed with conditions not known to be causally associated with immunizations. Assessment of a child with a possible hypotonic-hyporesponsive episode should exclude other known causes of sudden onset of hypotonia, hyporesponsiveness, or pallor. Evidence of preceding seizure activity or a postictal state, or evidence of urticaria, wheezing, or other signs and symptoms of anaphylaxis should be assessed. Other considerations in the setting of immunizations that are painful are syncope and breath-holding spells. There are no known residual effects from having a hypotonic-hyporesponsive episode.27,28 Protracted, Inconsolable Crying Protracted, inconsolable crying has been recognized as an adverse event causally related to DTP.18 It has been defi ned as persistent, severe, inconsolable screaming or crying for 3 or more hours observed within 48 hours of DTP vaccination.6 The incidence of this syndrome is 1 in 100 (1%) doses administered for DTP vaccines containing the whole-cell pertussis component (DTwP) and significantly less with newer acellular pertussis vaccines (DTaP).6,17,29 The significance or cause of protracted inconsolable crying is unknown.6 There are no specific management recommendations for children with protracted inconsolable crying following immunization. Serious sequelae have not been described (see Chapter 31, Excessive Crying). Arthralgias and Arthritis Joint symptoms such as arthralgias (i.e., joint pains) and arthritis (i.e., joint redness and swelling) are associated with

Chapter 102 — Vaccination-Related Complaints and Side Effects

the rubella component of MMR. Acute arthralgia or arthritis after vaccination with the rubella vaccine strain used in the United States occurs rarely in children. In contrast, 26% of young women develop acute arthralgias and 11% develop acute arthritis after rubella vaccination.30-32 Joint symptoms generally begin 1 to 3 weeks after vaccination, persist for 1 day to 3 weeks, and rarely recur. Although many different joints can be involved in the reaction to rubella vaccines, knees and fingers are the most common. The hips are seldom involved. The question of whether rubella vaccine can cause chronic arthritis in adult women is controversial.18 Recent data from a prospective, randomized, placebo-controlled trial of 546 seronegative women receiving rubella vaccine show a small excess risk of developing chronic joint pain.33 There is no evidence that vaccine-related joint problems should be managed differently from non–vaccine-related arthralgias or arthritis (see Chapter 95, Musculoskeletal Disorders in Systemic Diseases). Extensive Limb Swelling Extensive limb swelling is defined as edema extending at least to the elbow or knee in a vaccinated limb. In a 13-year review of reports to the Vaccine Adverse Events Reporting System (VAERS), 418 cases of extensive limb swelling were identified.34 A broad range of vaccines have been implicated, with those most frequently cited being the PCV, DTaP, and adult tetanus and diphtheria toxoids (Td) vaccines. In most cases the swelling develops within 24 hours after vaccination and is limited to the proximal half of the extremity. Associated erythema, warmth, or pain was reported in more than 70% of cases, and constitutional symptoms such as fever were reported in 20% to 25%. Children younger than 2 years had associated agitation or crying in 32% of cases of extensive limb swelling. Adolescents and adults had influenza-like symptoms in 10% to 18% of cases.34 Extensive limb swelling has been associated with booster doses of DTaP.35 Extensive thigh swelling was reported in 2% of patients after the fourth dose of this vaccine; most cases were associated with erythema and pain. The etiology of extensive limb swelling is unknown.34,35 Extensive limb swelling after vaccination appears to be selflimited and resolves without sequelae. There are no specific management recommendations for patients with extensive limb swelling. Thrombocytopenia MMR is associated with thrombocytopenia. The risk of thrombocytopenia is estimated to be 1 in 35,000 doses (0.003%).2 It is unknown which vaccine component is responsible for the development of thrombocytopenia. The presentation is similar to cases of idiopathic thrombocytopenic purpura (ITP)36,37 (see Chapter 122, Petechiae and Purpura). Vaccine-associated thrombocytopenia typically presents within 6 weeks of MMR immunization, with the highest incidence between 15 and 28 days after vaccination.38 Compared to cases of ITP that are not temporally associated with vaccine administration, vaccine-associated cases tend to be milder and have higher platelet counts.37 There is no evidence to suggest that vaccine-associated thrombocytopenia should be evaluated and managed differently from other cases of thrombocytopenia.

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REFERENCES 1. Centers for Disease Control and Prevention: Update: vaccine side effects, adverse reactions, contraindications, and precautions. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 45(RR-12):1–35, 1996. 2. Stratton KR, Howe CJ, Johnston RB (eds): Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: National Academy Press, 1994. 3. Pool V, Braun MM, Kelso JM, et al: Prevalence of anti-gelatin IgE antibodies in people with anaphylaxis after measles-mumps-rubella vaccine in the United States. Pediatrics 110:e71, 2002. *4. Chen RT, Mootrey G, DeStefano F: Safety of routine childhood vaccinations: an epidemiological review. Paediatr Drugs 2:273–290, 2000. 5. Centers for Disease Control and Prevention: Key facts about influenza (flu) vaccine. Available at www.cdc.gov/flu/protect/keyfacts.htm (Accessed December 20, 2006). 6. Pickering LK, Baker CJ, Long SS, et al (eds): Red Book: 2006 Report of the Committee on Infectious Disease, 27th ed. Elk Grove Village, IL: American Academy of Pediatrics, 2006. 7. Nakayama T, Aizawa C, Kuno-Sakai H: A clinical analysis of gelatin allergy and determination of its causal relationship to the previous administration of gelatin-containing acellular pertussis vaccine combined with diptheria and tetanus toxoid. J Allergy Clin Immunol 103:321–325, 1993. 8. Goldstein KP, Kviz FJ, Daum RS: Accuracy of immunization histories provided by adults accompanying preschool children to a pediatric emergency department. JAMA 270:2190–2194, 1993. 9. Patja A, Davidkin I, Kurki T, et al: Serious adverse events after measlesmumps-rubella vaccination during a fourteen year prospective followup. Pediatr Infect Dis J 19:1127–1134, 2000. 10. Ngai A, Staehle BO, Kuter BJ, et al: Safety and immunogenicity of one vs. two injections of Oka/Merck varicella vaccine in healthy children. Pediatr Infect Dis J 15:49–54, 1996. 11. Wise RP, Salive ME, Braun M, et al: Postlicensure safety surveillance for varicella vaccine. JAMA 284:1271–1279, 2000. 12. Kramer JM, LaRussa P, Tsai W et al: Disseminated vaccine strain varicella as the acquired immune deficiency syndrome defi ning illness in a previously undiagnosed child. Pediatrics 108:e39, 2001. 13. Centers for Disease Control and Prevention: Measles, mumps, and rubella—vaccine use and strategies for elimination of measles, rubella and congenital rubella syndrome and control of mumps: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 47(RR-8):1–57, 1998. 14. Peltola H, Heinonen OP: Frequency of true adverse ractions to measles-mumps-rubella vaccine: a double blind placebo controlled trial in twins. Lancet 1:939–940, 1986 15. Weibel RE, Neff BJ, Kuter BJ, et al: Live attenuated varicella virus vaccine: efficacy trial in healthy children. N Engl J Med 310:1409–1415, 1984. 16. Weibel RE, Caserta V, Benor DE, et al: Acute encephalopathy followed by permanent brain injury or death associated with further attenuated measles vaccines: a review of claims submitted to the National Vaccine Injury Compensation program. Pediatrics 101:383–387, 1998. 17. Miller D, Wadsworth J, Diamond J, et al: Measles vaccination and neurological events. Lancet 349:729–730, 1997. 18. Howson CP, Howe CJ, Finberg HV (eds): Adverse Events of Pertussis and Rubella Vaccines. Washington, DC: National Academy Press, 1991. 19. Centers for Disease Control and Prevention: Poliomyelitis prevention in the United States: introduction of a sequential vaccination schedule of inactivated polio virus vaccine followed by oral polio virus vaccine. MMWR Recomm Rep 46(RR-3):1–25, 1997. 20. Farrington CP, Pugh S, Colville A, et al: A new method for active surveillance of adverse events from diptheria/tetatus/pertussis and measles/mumps/rubella vaccines. Lancet 345:567–569, 1995. 21. Griffi n MR, Ray WA, Mortimer EA, et al: Risk of seizures after measlesmumps-rubella immunization. Pediatrics 88:881–885, 1991. 22. Rosenthal S, Chen R, Hadler S: The safety of acellular pertussis vaccine vs whole-cell pertussis vaccine: a postmarketing assessment. Arch Pediatr Adolesc Med 150:457–460, 1996.

*Selected readings.

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*23. Braun MM, Patriarca PA, Ellenberg SS: Syncope after immunization. Arch Pediatr Adolesc Med 151:255–259, 1997. 24. Centers for Disease Control and Prevention: General recommendations on immunizations. MMWR Recomm Rep 51(RR-02):1–36, 2002. 25. LeSaux N, Barrowman NJ, Moore DL, et al: Decrease in hospital admissions for febrile seizures and reports of hypotonic-hyporesponsive episodes presenting to hospital emergency departments since switching to acellular pertussis vaccine in Canada: a report from IMPACT. Pediatrics 112:e348, 2003. 26. Brown F, Greco D, Mastrantonio P, et al: Pertussis vaccine trials. Dev Biol Stand 89:1–407, 1997. 27. Braun MM, Teracciano G, Salive ME, et al: Report of a US Public Health Service Workshop on hypotonic-hyporesponsive episode (HHE) after pertussis immunization. Pediatrics 102:e1201, 1998. 28. DuVernoy TS, Braun MM; the VAERS Working Group: Hypotonichyporesponsive episodes reported to the Vaccine Adverse Events Reporting System (VAERS), 1996–1998. Pediatrics 106:e52, 2000. 29. Decker MD, Edwards KM, Steinhoff MC, et al: Comparison of 13 acellular pertussis vaccines: adverse reactions. Pediatrics 96:557–566, 1995. 30. Freestone DS, Prydie J, Smith SG, et al: Vaccination of adults with Wistar RA 27/3 rubella vaccine. J Hygiene 69:471–477, 1971.

31. Polk BF, Modlin JF, White JA, et al: A controlled comparison of joint reactions among women receiving one of two rubella vaccines. Am J Epidemiol 115:19–25, 1982. 32. Centers for Disease Control and Prevention: Epidemiology and Prevention of Vaccine Preventable Diseases, 7th ed. Atlanta: Centers for Disease Control and Prevention, 2002. 33. Tingle A, Mitchell L, Grace M, et al: Randomized, double-blind placebo-controlled study of adverse events of rubella immunization in seronegative women. Lancet 349:1277–1281, 1996. 34. Woo EJ, Burwen DR, Gatumu SN, et al: Extensive limb swelling after immunization: reports to the Vaccine Adverse Event Reporting System. Clin Infect Dis 37:351–358, 2003. *35. Rennels MB, Deloria MA, Pichichero ME, et al: Extensive swelling after booster doses of acellular pertussis-tetanus-diphtheria vaccines. Pediatrics 105:e12, 2000. 36. Vlacha V, Forman EN, Miron D: Recurrent thrombocytopenic purpura after repeated measles-mumps-rubella vaccination. Pediatrics 97:738– 739, 1996. 37. Drachtman RA, Murphy S, Ettinger LJ: Exacerbation of chronic idiopathic thrombocytopenic purpura following measles-mumps-rubella immunization. Arch Pediatr Adolesc Med 148:326–327, 1994. 38. Miller E, Waight P, Farrington CP, et al: Idiopathic thrombocytopenic purpura and MMR vaccine. Arch Dis Child 84:227–229, 2001.

Chapter 103 Tetanus Prophylaxis Fredrick M. Abrahamian, DO and David A. Talan, MD

Key Points Tetanus in children in the United States is rare. Children at higher risk for developing tetanus in the United States include those who are not completely vaccinated (including those children whose parents choose not to immunize them), adolescent injectiondrug users, and immigrants from outside North America or Western Europe. The decision to initiate postexposure prophylaxis is dependent on the wound characteristics and the child’s vaccination history. Wounds at higher risk for tetanus include contaminated wounds (e.g., with dirt, feces, soil, or saliva), puncture wounds, avulsions, wounds resulting from missiles, crush injuries, burns, frostbite, and those with neurovascular compromise. The two important factors to determine about a patient’s vaccination history are whether or not the patient has had a primary immunization series (i.e., at least three doses of adsorbed tetanus toxoid) and the elapsed time period since the last vaccination dose.

Introduction and Background Although the global incidence of tetanus is high and continues worldwide to claim thousand of lives annually, it remains a rare disease in the United States and other developed countries.1 Implementation of large-scale tetanus immunization programs, widespread availability of tetanus toxoid vaccine and immune globulin, and improved wound care management and childbirth practices have all contributed to the dramatic decline in the incidence of tetanus in developed countries. Although no active immunization practice is considered 100% effective, tetanus immunization has shown to be one of the most effective immunization practices ever developed.2,3

Recognition and Approach In the United States, tetanus occurs primarily in adults, although internationally, neonatal tetanus accounts for the majority of cases.1 During 1998–2000, a total of 130 cases of tetanus were reported to the Centers for Disease Control and Prevention (CDC).4 The majority were males (60%) between the ages of 20 and 59 years (55%). Twelve (9%) of the cases involved children younger than 20 years of age, including one neonate. Of the 130 cases identified, the outcome was known for only 113 patients. Twenty of these patients died. None of the deaths occurred in children or adults younger than 30 years of age. From a review of tetanus cases reported to the CDC from 1987 to 2000, the majority of the cases had an acute injury identified prior to the onset of illness.4-8 Puncture wounds were the most frequent type of acute injury, followed by lacerations and abrasions. A common circumstance for a puncture wound was stepping on a nail. Other puncture wounds included splinters, tattooing, and animal bites. The sites of antecedent injury were, in order of decreasing frequency, a lower extremity, an upper extremity, the head, and the trunk. Tetanus surveillance reports indicate that the populations relevant to pediatric emergency medicine that are at highest risk for developing tetanus in the United States are children who are not completely vaccinated, adolescent injection-drug users,4-9 and immigrants from outside North America or Western Europe.10-12 Parental objections to immunizations are a key risk factor for children who develop tetanus in the United States. Neonates born to parents who object to and do not receive vaccinations, due to either religious or philosophical reasons, are at higher risk of developing tetanus. During 1992–2000, 13 cases of non-neonatal tetanus in children younger than 15 years were reported. Of those, 11 (85%) were not protected due to parental objections to immunizations.13 Similarly, the three reported neonatal tetanus cases in the United States during 1989–2000 were associated with absent or incomplete maternal vaccination.5,7,13,14

Evaluation The decision to initiate postexposure prophylaxis is dependent on the wound characteristics and the patient’s vaccination history. Regarding tetanus postexposure prophylaxis, 749

750

SECTION IV — Approach to the Acutely Ill Patient

the Advisory Committee on Immunization Practices (ACIP) of the CDC categorizes wounds as either clean, minor wounds, or “all other wounds.” Examples of “all other wounds” include contaminated wounds (e.g., with dirt, feces, soil, or saliva), puncture wounds, avulsions, wounds resulting from missiles, crush injuries, burns, and frostbite. These wounds are at higher risk for harboring Clostridium tetani since they have occurred in an environment in which C. tetani spores are prevalent or they are the type of tissue injury that provides low oxygen tension conducive for anaerobic conditions allowing C. tetani spore germination and proliferation.15,16 Children who have not received at least three doses of adsorbed tetanus toxoid are also at increased risk for tetanus.13 In clinical practice, some parents are uncertain if their child has received a complete primary immunization series.17 Current tetanus prophylaxis guidelines recommend considering a child as not having had any previous tetanus vaccinations if the history of past immunizations is unknown or uncertain.15,16 Fortunately, young adults who have served in the military and children who have attended public schools in North America or Western Europe are likely to have completed a primary immunization series. Immigrants from outside North America or Western Europe and adults who do not have an education level beyond grade school are more likely to lack primary immunization.10

Management The primary immunization series ensures adequate baseline levels of tetanus antibody and future anamnestic response to booster injections. Since immunity to tetanus with vaccination declines with time, booster doses are required to keep the antitoxin levels in a protective range. Periodic injections of tetanus toxoid result in sequentially higher peak responses, higher residual antitoxin levels, and longer periods during which antibodies are detected.2 Primary immunization is

Table 103–1

recommended beginning in infancy with intramuscular (IM) injections of diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP)18-20 (Table 103–1). A catch-up tetanus immunization schedule and minimum intervals between doses for children and adolescents who start late or who are more than 1 month behind is also available18 (Table 103–2). At age 19 and greater, a booster dose of tetanus and diphtheria toxoids vaccine (adult) (Td) administered every 10 years provides adequate protection for clean, minor, uncontaminated wounds. For all high-risk wounds that are also associated with a shorter tetanus incubating period, to make certain there is rapid attainment of adequate antibody levels, a booster dose is recommended if the preceding tetanus toxoid was given greater than 5 years prior15,16,21 (Table 103– 3). Since the ACIP regularly updates the recommended childhood and adolescent immunization schedules, we recommend reviewing the latest immunization recommendation by contacting local or state health departments, by accessing the CDC’s National Immunization Program web site at http://www.cdc.gov/nip, or by calling the National Immunization Information Hotline at 800-232-2522 (English) or 800-232-0233 (Spanish). Active Immunization Active immunization is provided by the administration of tetanus toxoid, which is provided in various preparations22 (Table 103–4). DTaP is indicated for primary and booster vaccinations against diphtheria, tetanus, and pertussis for children 6 weeks to 7 years (i.e., prior to the seventh birthday). DTaP is preferred over diphtheria and tetanus toxoids and whole-cell pertussis vaccine adsorbed (DTwP) due to its lower incidence of local and systemic adverse reactions and improved efficacy.23 DTaP is given as a 0.5-ml IM injection into the anterolateral aspect of the thigh (for infants) or the deltoid muscle of the upper arm (for children). The most frequently encountered adverse events include local reactions such as injection site tenderness, redness, induration, and

Routine Diphtheria, Tetanus, and Pertussis Vaccination Schedule Summary for Children and Adolescents

Dose

Customary Age

Primary 1 Primary 2 Primary 3 First booster Second booster

2 mo 6 wk old or older 4 mo 4–8 wk after first dose 6 mo 4–8 wk after second dose 15–18 mo‡ 6–12 mo after third dose 4–6 yr old, before entering kindergarten or elementary school (not necessary if fourth dose [first booster] is administered after fourth birthday) Recommended at age 11–12 yr if at least 5 yr have elapsed since the last dose of tetanus and diphtheria toxoid–containing vaccine. Ages 13–18 yr should serve as a catch-up interval for those who were not immunized at ages 11–12 yr. Subsequent routine Td boosters are recommended every 10 yr

Additional boosters

Age/Interval*

Product DTaP† DTaP† DTaP† DTaP† DTaP† Tdap

*Prolonging the interval does not require restarting the series. Use diphtheria and tetanus toxoids vaccine adsorbed (pediatric) (DT) if encephalopathy has occurred after administration of a previous dose of pertussis-containing vaccine. If the child is ≥1 year of age at the time that primary dose three is due, a third dose 6 to 12 months after the second dose completes primary vaccination with DT. ‡ The fourth dose of DTaP may be administered at age 12 months provided that 6 months have elapsed since the third dose and the child is unlikely to return at age 15 to 18 months. The final dose in the series should be given at age 4–6 years. Abbreviations: DTaP, diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed; Tdap, tetanus and diphtheria toxoids and acellular pertussis vaccine adsorbed formulated for use in adolescents and adults ≤64 years of age (Boostrix® approved for use in persons aged 10–18 years; Adacel™ approved for use in persons aged 11–64 years); Td, tetanus and diphtheria toxoids vaccine adsorbed (minimum age: 7 years). This immunization schedule is based on information in references 18, 19, 20, and 34. †

Chapter 103 — Tetanus Prophylaxis

Table 103–2

751

Catch-up Tetanus Immunization Schedule and Minimum Intervals between Doses for Children and Adolescents Who Start Late or Who Are More Than or Equal to 1 Month Behind—United Sates, 2007 Catch-up Schedule for Children Ages 4 mo–6 yr Minimum Interval between Doses

Dose 1 (Minimum Age)

Dose 1 to Dose 2

Dose 2 to Dose 3

4 wk

4 wk

DTaP (6 wk)

Catch-up Schedule for Children Ages 7–18 yr Minimum Interval between Doses

Dose 3 to Dose 4

Dose 4 to Dose 5

6 mo

6 mo*

†

Dose 1 to Dose 2

Dose 2 to Dose 3

Dose 3 to Dose 4

4 wk

8 wk: If first dose administered at age < 12 mo. 6 mo: If first dose administered at age ≥ 12 mo.

6 mo: If first dose administered at age < 12 mo.

Note: There is no need to restart a vaccine series regardless of the time that has elapsed between doses. *The fifth dose is not necessary if the fourth dose was given after the fourth birthday. Minimum age for DTaP administration is 6 weeks and maximum age is 6 years. † Tdap should be substituted for a single dose of Td in the primary catch-up series or as a booster if age appropriate. Td should be used for all other doses. A 5-year interval from the last Td dose is encouraged when Tdap is used as a booster dose. Abbreviations: DTaP, diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed; Tdap, tetanus and diphtheria toxoids and acellular pertussis vaccine adsorbed formulated for use in adolescents and adults ≤ 64 years of age; Td, tetanus and diphtheria toxoids vaccine adsorbed. Data from Centers for Disease Control and Prevention: Recommended immunization schedules for persons aged 0–18 years—US, 2007. MMWR Morb Mortal Wkly Rep 55(51&52):1–4, 2007.

Table 103–3

Current Summary Guide to Tetanus Prophylaxis in Routine Wound Management Clean, Minor Wounds

All Other Wounds*

History of Adsorbed Tetanus Toxoid (Doses)

Td or Tdap†

TIG

Td or Tdap†

TIG

Unknown or 15,000/mm3), hemoglobin ( 8 yr old Selective indications in children; expert infectious disease advice helpful Gram-negatives, Pseudomonas, Aeromonas; no anaerobes, poor MSSA MSSA, GABHS; no MRSA; reserve for penicillin allergy MSSA, CA-MRSA, HA-MRSA, GABHS, penicillinresistant Pneumococcus Synergy against MSSA, CA-MRSA, HA-MRSA Used in combinations for synergy versus staphylococci, enterococci, Pseudomonas, gram-negative enterics

Abbreviations: GABHS, group A β-hemolytic streptococcus; CA-MRSA, community-acquired methicillin-resistant Staphylococcus aureus; HA-MRSA, hospital-acquired methicillin-resistant Staphylococcus aureus; MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-sensitive Staphylococcus aureus.

on the antimicrobial susceptibility pattern of the patient’s isolate in attempts to decolonize patients. Data are not currently sufficient to allow recommendation of such approaches as routine care. The emergency physician should seek infectious disease expertise in these situations. Patients who do not respond to therapy or worsen despite use of effective antimicrobial agents, or continue to have significant recurrent disease, may have an underlying predisposing condition. S. aureus disease is most troublesome to patients with neutropenias (familial, cyclic, acquired), neutrophil disorders (oxidative burst deficiencies, myeloperoxidase deficiency, glucose-6-phosphate dehydrogenase deficiency, chemotactic disorders, leukocyte adhesion defects),

HIV-related immune deficiency, hyperimmunoglobulinemia E syndrome, and common variable immune deficiency. Hidradenitis Suppurativa Hidradenitis suppurativa is a chronic, often progressive, severe inflammatory disease of apocrine glands mainly in intertigenous areas such as the axillae, groin, perineum, and rectum. Disease severity is often cyclic and remitting; flareups can be debilitating. The spectrum of disease ranges from inflammatory nodules to nodules with draining wounds and sinus tracts. With each cycle of inflammation the extent of the lesions increases. The condition is commonly confused with furuncles and carbuncles, progressive folliculitis, and

Chapter 120 — Skin and Soft Tissue Infections

Table 120–5

833

Organisms Associated with Unusual Domesticated and Wild Animal Bite Wounds

Animal

Organism

Treatment Should Include*

Horses Pig/sheep Rat Ferret/gerbil Monkeys Coyote Wolf Cougar Panther Lion Tiger

Similar to dog and cat Dog/cat flora + Francisella tularensis and others Dog/cat flora + Streptobacillus moniliformis, Leptospira Rat flora + Acinetobacter anitratus Human flora + herpesvirus B Francisella tularensis Pasteurella multocida Pasteurella multocida Pasteurella multocida Pasteurella multocida, Staphylococcus aureus, Escherichia coli Pasteurella multocida, Acinetobacter, Escherichia coli, streptococci, staphylococci Rabies Rabies Rabies Rabies Pasteurella multocida Francisella tularensis

Amoxicillin/clavulanate Amoxicillin/clavulanate, gentamycin Amoxicillin/clavulanate Antipseudomonal penicillin Antiviral therapy Gentamycin Amoxicillin/clavulanate Amoxicillin/clavulanate Amoxicillin/clavulanate Amoxicillin/clavulanate Amoxicillin/clavulanate

Skunks Raccons Bats Foxes Opossum Squirrel

RIG, HDCV RIG, HDCV RIG, HDCV RIG, HDCV Amoxicillin/clavulanate Gentamycin

*Consult with infectious disease specialist for total management strategy. Abbreviations: HDCV, human diploid cell rabies vaccine; RIG, rabies immune globulin.

Table 120–6

Prophylactic Antimicrobial Strategy for Mammalian Bite Wounds (Domesticated Animals and Humans)

Commonly Associated Organisms Empirical therapy for most bites Dog bites

Cat bites

Human bites

Pasteurella multocida Streptococcus species Staphylococcus aureus Neisseria species Anaerobes: Bacteroides, Fusobacterium Other: Eikenella, Capnocytophaga canimorsus Pasteurella multocida Streptococcus species Staphylococcus aureus Neisseria species Anaerobes: Bacteroides, Fusobacterium Other: Eikenella, Capnocytophaga canimorsus Many aerobic/anaerobic bacteria, esp. Streptococcus, Staphylococcus, Eikenella corrodens, Corynebacterium, Bacteroides, Clostridium

First Choice

Other Choices †

Penicillin-Allergic Patient*

Amoxicillin/clavulanate 25–40 mg/kg bid

Cefuroxime 50 mg/kg divided bid or Ceftriaxone† 50–75 mg/kg IM qd × 2–3 days

Clindamycin 15–25 mg/kg divided tid plus Trimethoprim/sulfamethoxazole 6–12 mg/kg divided bid or Doxycycline‡ 50–100 mg bid Clindamycin plus trimethoprim/ sulfamethoxazole or Doxycycline‡

Amoxicillin/clavulanate

Penicillin V 25–50 mg/kg divided tid–qid or Amoxicillin 40 mg/kg divided tid §

Amoxicillin/clavulanate

Penicillin and/or dicloxicillin 25–50 mg/kg, divided qid for both

Clindamycin plus trimethoprim/ sulfamethoxazole or Doxycycline‡

Amoxicillin/clavulanate

Penicillin and/or dicloxicillin

Clindamycin plus trimethoprim/ sulfamethoxazole or Doxycycline‡ or Erythromycin¶ or Macrolide

*Should consult with infectious disease expert. Effective against S. aureus, anaerobes, E. corrodens, and P. multocida. ‡ Not for use in prepubertal children or pregnant women. § Lower incidence of P. multocida. ¶ Pasturella multocida only moderately sensitive, with known treatment failures; Eikenella with slightly increased sensitivity. †

834

SECTION IV — Approach to the Acutely Ill Patient

epidermoid or dermoid cysts. Hidradenitis suppurativa is differentiated from these other conditions by its chronicity, cyclic presentation, and progressive nature. Differentiation of perianal hidradenitis from perianal complications associated with inflammatory bowel disease may be difficult. Acne conglobata is similar in appearance to hidradenitis suppurativa but lacks cyclic features. Over 98% of hidradenitis suppurativa cases present after the age of 11 years, and hormonal influences may play an important role. Oral contraceptives, pregnancy, and the latter portion of the menstrual cycle are known to worsen disease in females. Hidradenitis is more common in patients with a variety of endocrinopathies, including diabetes mellitus and adrenal gland diseases. The etiology of hidradenitis suppurativa remains largely undefined; however, apocrine gland duct obstruction and superinfection play roles in pathogenesis. A variety of organisms have been isolated from wound drainage, including Staphylococcus species, Streptococcus species, Escherichia coli, Klebsiella species, Proteus species, Corynebacteria, and anaerobes.58,59 Treatment of patients with flare-ups of hidradenitis involves warm baths, local antisepsis, and cleansing with mild antibacterial agents. Oral and topical antistaphyloccocal antimicrobial agents are commonly prescribed, with anaerobic coverage added in cases of perianal disease. Topical clindamycin or an oral tetracycline has some efficacy.60 Oral clindamycin has also been used. Cultures should guide the ultimate antibiotic choice. There are no data to support a recommendation for chronic, suppressive antimicrobial therapy. Patients should be advised to wear loose-fitting clothes that will not rub and traumatize affected areas. Incision and drainage of lesions or unroofing of closed lesions to encourage marsupialization may speed healing, but has no effect on recurrence, prognosis, or disease severity. Referral to a dermatologist or surgeon is necessary since treatment with retinoids or immunemodulating medications such as cyclosporin, or local to wide surgical incision and even skin grafting, may be warranted. Lymphangitis Lymphangitis is an inflammatory process of the lymphatic system that drains an area of infection. Regional lymph nodes are often involved and may become suppurative at later stages. Physical examination reveals tender, erythematous streaks extending from the primary site of infection and along the tracts of the lymphatics. Group A streptocococcus is the leading cause, with S. aureus implicated in most other cases; however, infection with a variety of other organisms may also present in a similar fashion. For example, lymphangitis may be seen with puncture and contaminated wound infections. Wound and blood cultures are recommended in children due to the risk of bacteremia and sepsis, especially when febrile. Therapy is directed against the primary infection and stratified by the general approach to soft tissue infections (see Table 120–2). REFERENCES 1. Ambati B, Ambati J, Azar N, et al: Periorbital and orbital cellulitis before and after the advent of Haemophilus influenzae type b vaccination. Ophthalmology 107:1450–1453, 2000. 2. Patel M, Athrens JC, Moyer J, et al: Pneumococcal soft tissue infections: a problem deserving more recognition. Clin Infect Dis 19:149– 151, 1994.

3. Newell PM, Norden CW: Value of needle aspiration in bacteriologic diagnosis of cellulitis in adults. J Clin Microbiol 26:401–404, 1988. 4. Sachs MK: Cutaneous cellulitis. Arch Dermatol 127:493–496, 1991. 5. Sigurdsson AF, Gudmundsson S: The etiology of bacterial cellulitis as determined by fi ne-needle aspiration. Scand J Infect Dis 21:537–542, 1989. 6. Lebre C, Girard-Pipau F, Roujeau JC, et al: Value of fine-needle aspiration in infectious cellulitis. Arch Dermatol 132:842–843, 1996. 7. Salgado CD, Farr BM, Calfee DP: Community acquired methicillinresistant Staphylococcus aureus: a meta-analysis of prevalence and risk factors. Clin Infect Dis 36:131–139, 2003. 8. Howe PM, Eduardo-Fajardo J, Orcutt MA: Etiologic diagnosis of cellulitis: comparison of aspirates obtained from the leading edge and the point of maximal inflammation. Pediatr Infect Dis J 6:685–686, 1987 9. Sadow KB, Chamberlain JM: Blood cultures in the evaluation of children with cellulitis. Pediatrics 101:e4, 1998. 10. Frank AL: Clindamycin treatment of methicillin-resistant Staphylococcus aureus infections in children. Pediatr Infect Dis J 21:530–534, 2002. 11. Centers for Disease Control and Prevention: Four pediatric deaths from community-acquired methicillin-resistant Staphylococcus aureus: Minnesota and North Dakota, 1997–1999. MMWR Morb Mortal Wkly Rep 37:2858–2862, 1999. 12. Herold BC, Immergluck LC, Maranan MC, et al: Community-acquired methicillin-resistant Staphylococcus aureus in children with no predisposing risk. JAMA 279:593–598, 1998. 13. Wible K, Tregnaghi M, Bruss J, et al: Linezolid versus cefadroxil in the treatment of skin and skin structure infections in children. Pediatr Infect Dis J 22:315–322, 2003. 14. Kaplan SL: Use of linezolid in children. Pediatr Infect Dis J 21:870–872, 2002. 15. Day S, Klein BL: Popsicle panniculitis. Pediatr Emerg Care 8:91–93, 1992. 16. Unkel JH, McKibben DH, Fenton SJ, et al: Comparison of odontogenic and nonodontogenic facial cellulitis in a pediatric hospital population. Pediatr Dent 19:476–479, 1997. 17. Zimbelman J, Palmer A, Todd J: Improved outcome of clindamycin compared with beta-lactam antibiotic treatment for invasive Streptococcus pyogenes infection. Pediatr Infect Dis J 18:1096–1100, 1999. 18. Mogielnicki NP, Schwartzman JD, Elliott JA: Perineal group A streptococcal disease in a pediatric practice. Pediatrics 106:276–281, 2000. 19. Nowicki MH, Bishop PR, Parker PH: Digital desquamation—a new fi nding in perianal streptococcal dermatitis. Clin Pediatr 39:237–239, 2000. 20. Paradisi M, Cianchini G, Angelo C: Efficacy of topical erythromycin in treatment of perianal streptococcal dermatitis. Pediatr Dermatol 10:297–298, 1993. 21. Montemarano AD, James WD: Staphylococcus aureus as a cause of perianal dermatitis. Pediatr Dermatol 10:259–262, 1993. 22. Hirschfeld AJ: Two family outbreaks of perianal cellulitis associated with group A beta-hemolytic streptococci. Pediatrics 46:799–802, 1970. 23. Keene WE, Markum AC, Samadpour M: Outbreak of Pseudomonas aeruginosa infections caused by commercial piercing of upper ear cartilage. JAMA 291:981–985, 2004. 24. Lyon M, Doehring MC: Blistering distal dactylitis: a case series in children under nine months of age. J Emerg Med 26:421–423, 2004. 25. Norcross MC Jr, Mitchell DF: Blistering distal dactylitis caused by Staphylococcus aureus. Cutis 51:353–354, 1993. 26. Zirn JR, Tompkins SD, Huie C, et al: Rapid detection and distinction of cutaneous herpesvirus infections by direct immunofluorescence. J Am Acad Dermatol 33:724–728, 1995. 27. Midani S, Rathore M: Chromobacterium violaceum infection. South Med J 91:464–466, 1998. 28. Vally H, Whittle A, Cameron S, et al: Outbreak of Aeromonas hydrophila wound infections associated with mud football. Clin Infect Dis 38:1084–1089, 2004. 29. Peterson JJ, Bancroft LW, Kransdorf MJ: Wooden foreign bodies: imaging appearance. AJR Am J Roentgenol 178:557–562, 2002. 30. Jacobs RF, McCarthy RE, Elser JM: Pseudomonas osteochondritis complicating puncture wounds of the foot in children: a 10-year evaluation. J Infect Dis 160:657–661, 1989. 31. Fustes-Morales A, Gutierrez-Castrellon P, Duran-McKinster C, et al: Necrotizing fasciitis: report of 39 pediatric cases. Arch Dermatol 138:893–899, 2002.

Chapter 120 — Skin and Soft Tissue Infections 32. Miron D, Lev A, Colodner R, et al: Vibrio vulnificus necrotizing fasciitis of the calf presenting with compartment syndrome. Pediatr Infect Dis J 22:666–668, 2003. 33. Zerr DM, Alexander ER, Duchin JS, et al: A case-control study of necrotizing fasciitis during primary varicella. Pediatrics 103:783–790, 1999 34. Laupland KB, Davies HD, Low DE, et al: Invasive group A streptococcal disease in children and association with varicella-zoster virus infection. Ontario Group A Streptococcal Study Group. Pediatrics 105: e60, 2000 35. Aronoff DM, Bloch KC: Assessing the relationship between the use of nonsteroidal antiinflammatory drugs and necrotizing fasciitis caused by group A streptococcus. Medicine 82:225–235, 2003 36. Bisno AL, Cockerill FR 3rd, Bermudez CT: The initial outpatientphysician encounter in group A streptococcal necrotizing fasciitis. Clin Infect Dis 31:607–608, 2000 37. Hsieh T, Samson LM, Jabbour M, et al: Necrotizing fasciitis in children in eastern Ontario: a case-control study. CMAJ 163:393–396, 2000. 38. Wong C-H, Khin L-W, Heng K-S, et al: The LRINEC (Laboratory Risk Indicator for Necrotizing Fasciitis) score: a tool for distinguishing necrotizing fasciitis from other soft tissue infections. Crit Care Med 32:1535–1541, 2004. 39. Yen ZS, Wang HP, Ma HM, et al: Ultrasonographic screening of clinically-suspected necrotizing fasciitis. Acad Emerg Med 9:1448–1451, 2002. 40. Walshaw CF, Deans H: CT fi ndings in necrotising fasciitis—a report of four cases. Clin Radiol 51:429–432, 1996. 41. Schmid MR, Kossman T, Duewell S: Differentiation of necrotizing fasciitis and cellulitis using MR imaging. AJR Am J Roentgenol 170:615–620, 1998. 42. Majeski J, Majeski E: Necrotizing fasciitis: improved survival with early recognition by tissue biopsy and aggressive surgical treatment. South Med J 90:1065–1068, 1997. 43. Moss RL, Musemeche CA, Kosloske AM: Necrotizing fasciitis in children: prompt recognition and aggressive therapy improve survival. J Pediatr Surg 31:1142–1146, 1996 44. Lille ST, Sato TT, Engrav LH, Jurkovich GJ: Necrotizing soft tissue infections: obstacles in diagnosis. J Am Coll Surg 182:7–11, 1996. 45. Cawley MJ, Briggs M, Haith LR Jr, et al: Intravenous immunoglobulin as adjunctive treatment for streptococcal toxic shock syndrome associated with necrotizing fasciitis: case report and review. Pharmacotherapy 19:1094–1098, 1999. 46. Sattler CA, Mason EO, Kaplan SL: Prospective comparison of risk factors and demographic and clinical characteristics of communityacquired, methicillin-resistant versus methicillin-susceptible Staphylococcus aureus infection in children . Pediatr Infect Dis J 21:910–917, 2002.

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47. Rist T, Parish LC, Capin LR, et al: A comparison of the efficacy and safety of mupirocin cream and cephalexin in the treatment of secondarily infected eczema. Clin Exp Dermatol 27:14–20, 2002. 48. Wollenberg A, Wetzel S, Burgdorf WH, et al: Viral infections in atopic dermatitis: pathogenic aspects and clinical management. J Allergy Clin Immunol 112:683–685, 2003 49. Syed TA, Goswami J, Ahmadpour OA, et al: Treatment of molluscum contagiosum in males with an analog of imiquimod 1% in cream: a placebo-controlled, double-blind study. J Dermatol 25:309–313, 1998. 50. Iyer S, Jones DH: Community-acquired methicillin-resistant Staphylococcus aureus skin infection: a retrospective analysis of clinical presentation and treatment of a local outbreak. J Am Acad Dermatol 50:854–858, 2004. 51. Lina G, Piemont Y, Godail-Gamot F, et al: Involvement of PantonValentine leukocidin-producing Staphylococcus aureus in primary skin infections and pneumonia. Clin Infect Dis 29:1128–1132, 1999. 52. Centers for Disease Control and Prevention: Methicillin-resistant Staphylococcus aureus infections among competitive sports participants—Colorado, Indiana, Pennsylvania, and Los Angeles County, 2000–2003. MMWR Morb Mortal Wkly Rep 52:793–795, 2003. 53. Lindenmayer JM, Schoenfeld S, O’Grady R, et al: Methicillin-resistant Staphylococcus aureus in a high school wrestling team and the surrounding community. Arch Intern Med 158:895–899, 1998. 54. Kazakova SV, Hageman JC, Matava M: A clone of methicillin-resistant Staphylococcus aureus among professional football players. N Engl J Med 352:468–475, 2005. 55. Lee MC, Rios AM, Aten MF: Management and outcome of children with skin and soft tissue abscesses caused by community-acquired methicillin-resistant Staphylococcus aureus. Pediatr Infect Dis J 23:123– 127, 2004. 56. Harbarth S, Dharan S, Liassine N, et al: Randomized, placebocontrolled, double-blind trial to evaluate the efficacy of mupirocin for eradicating carriage of methicillin-resistant Staphylococcus aureus. Antimicrob Agent Chemother 43:1412–1416, 1999. 57. Watanakunakorn C, Axelson C, Bota B, et al: Mupirocin ointment with and without chlorhexidine baths in the eradication of Staphylococcus aureus nasal carriage in nursing home residents. Am J Infect Control 23:306–309, 1995. 58. Highet AS, Warren RE, Weekes AJ: Bacteriology and antibiotic treatment of perineal suppurative hidradenitis. Arch Dermatol 124:1047– 1051, 1988. 59. Brook I, Frazier EH: Aerobic and anaerobic microbiology of axillary hidradenitis suppurativa. J Med Microbiol 48:103–105, 1999. 60. Jemec GB, Wendelboe P: Topical clindamycin versus systemic tetracycline in the treatment of hidradenitis suppurativa. J Am Acad Dermatol 39:971–974, 1998.

Chapter 121 Erythema Multiforme Major and Minor Antonio E. Muñiz, MD

Key Points Erythema multiforme consists of “target” skin lesions and may have involvement of one mucous membrane, usually the oral mucosa. The diagnosis of Stevens-Johnson syndrome requires that at least two mucous membranes are affected in addition to the “target” skin lesions. Ophthalmologic consultation is required if there is ocular mucosa involvement. Stevens-Johnson syndrome requires hospitalization, intravenous fluid and electrolyte replacement, and meticulous skin care.

Introduction and Background Erythema multiforme (EM) and Stevens-Johnson syndrome (SJS) are hypersensitivity syndromes that can be caused by infections, drugs, vaccinations, malignancy, and connective tissue disorders. EM is defined as an acute, self-limiting vesiculobullous disorder characterized by the formation of symmetrically distributed erythematous macules and papules, some of which evolve into the classic “target” lesions (Table 121–1).1 On occasion it can involve one mucosal surface, particularly the oral mucosa.2 It is seen most commonly in the second to fourth decade of life, but 20% of cases occur in children. SJS is a potentially life-threatening condition with mortality up to 15%. By definition, it requires involvement of at least two mucous membranes, most often the conjunctivae and oropharynx, although the nasal, urethral, vaginal, and rectal mucosa can also be affected3 (Table 121–2). The respiratory and gastrointestinal tracts are occasionally involved. As opposed to EM, mucosal and cutaneous involvement in SJS is severe with extensive necrosis. For many years EM was classified into minor and major forms, the major variant being SJS. However, recent consensus states that SJS is best 836

regarded as a different entity than EM, despite clinical and histologic similarities.1,4 In addition, no one has been able to demonstrate that EM evolves into SJS.4,5

Recognition and Approach The pathogenesis of EM is unknown, but it is considered to be a delayed hypersensitivity immune response to a number of different stimuli, particularly the herpes simplex virus (HSV) antigen in children.6-8 Cytotoxic effector cells (CD8+ T lymphocytes in the epidermis) induce apoptosis of scattered keratinocytes, which leads to cell necrosis. The diagnosis is often made by clinical assessment but can be confirmed by biopsy of a typical lesion, which shows T-lymphocyte infi ltration. Unlike EM, in SJS there is an excessive overexpression of tumor necrosis factor-α in the epidermis.8,9 This may account for the greater degree of epidermal necrosis seen in SJS. Skin biopsy is characterized by a perivascular mononuclear infi ltrate with some eosinophils in the dermis, variable hydrops degeneration of the basilar layer, and subepidermal blister formation in severe cases. The list of putative trigger factors for EM and SJS in adults is an extensive one, but in children it seems that the majority of cases of EM are the result of a preceding recrudescence of HSV.1,10 SJS in adults is usually drug induced, but in children it is associated with infections, especially Mycoplasma pneumoniae, as well as drugs, most notably antibiotics, anticonvulsants, and nonsteroidal anti-inflammatory drugs.1,10-13

Clinical Presentation Erythema Multiforme EM is often preceded by a herpes simplex infection, usually localized to the face but potentially occurring in any location. Prodromal symptoms are absent or mild and may consist of low-grade fever, cough, and anorexia. Myalgias or arthralgias are rare accompanying symptoms. Typically, crops of lesions develop over a few days in acral regions, especially the palms and dorsa of the hands, wrists, feet, and extensor surfaces of elbows and knees, and occasionally on the face. EM may manifest Koebner’s phenomenon—target lesions appearing within areas of cutaneous trauma such as

Chapter 121 — Erythema Multiforme Major and Minor

Table 121–1

Clinical Features of Erythema Multiforme

• Benign, self-limited, and occasionally recurrent disorder • Cutaneous lesions consisting of symmetric, fixed macules or papules evolving into “target” lesions • Mucous membrane absent or limited only to the oral cavity • Minimal or no prodromal symptoms • Supportive treatment (antihistamines, acyclovir)

Table 121–2

Table 121–4

837

Differential Diagnosis for StevensJohnson Syndrome

Burns or scalds Staphylococcal scalded skin syndrome (SSSS) Toxic epidermal necrolysis (TEN) Kawasaki disease Toxic shock syndrome Acute graft-versus-host disease Paraneoplastic pemphigus

Clinical Features of StevensJohnson Syndrome

• • • •

Prodromal symptoms Severe mucous membrane involvement (at least two) Much larger cutaneous involvement Treatment includes fluid and electrolyte replacement and meticulous skin care • Other treatment may include corticosteroids and immune globulin • Life threatening (mortality up to 15%)

Table 121–3

Differential Diagnosis of Erythema Multiforme

FIGURE 121–1. Typical target lesions in erythema multiforme.

Giant urticaria Drug reactions Bullous pemphigoid Chronic bullous dermatosis of childhood (CBDC) Polymorphic light reaction Systemic lupus erythematosus (SLE) Urticarial vasculitis Erythema annulare centrifugum

scratches.13,14 The cutaneous eruption of EM generally resolves in 1 to 2 weeks, but occasionally may be present for 4 weeks. EM in childhood is frequently initially misdiagnosed as urticaria14,15 (Table 121–3). The lesions in urticaria are transient and migratory and have a clear central zone, not a dusky one. In addition urticarial lesions will resolve with the administration of subcutaneous epinephrine, and EM will not.14,15 Stevens-Johnson Syndrome SJS is usually preceded by a prodromal illness lasting up to 2 weeks and consisting of high fever, cough, coryza, sore throat, headache, chest pains, malaise, arthralgias, myalgias, vomiting, and diarrhea. Toxicity and generalized lymphadenopathy are common. Occasionally the child has hepatosplenomegaly or evidence of hepatitis. Myocarditis, pneumothorax, nephritis, and gastrointestinal bleeding are rare complications. After 1 to 14 days, the rash starts suddenly and occurs in the face, trunk, and limbs. Mucous membrane involvement, especially of the oral, conjunctival, and urethral mucosa, is typical and often severe. Oral mucous lesions may be confused with aphthous ulcers, herpes simplex infection, pemphigus, bullous pemphigoid, epidermolysis bullosa, and paraneoplastic pemphigus, and the differential diagnosis for SJS involves these and other serious disorders (Table 121–4).

FIGURE 121–2. Concentric rings of target lesion in erythema multiforme.

Important Clinical Features and Considerations Cutaneous lesions start as dull red macules or maculopapules, which may increase in size up to 3 cm in diameter within 24 to 48 hours. The lesions are usually asymptomatic, but some patients complain of itching. The lesions may evolve into target-shaped (or iris) plaques, which are the hallmark of EM4 (Fig. 121–1). The target lesions consist of two or three concentric rings (Fig. 121–2). The central portion starts as a dusky red or purple macule before evolving into tense bullae with clear or hemorrhagic contents. There is usually a middle pale zone of edematous skin and an outer halo of well-demarcated erythema. As the name implies, there may be a variable pattern of lesions ranging from necrotic macules to an exclusively blistering disorder, but most have approximately 100 lesions16 (Fig. 121–3). In SJS, depending on the severity, the

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A

FIGURE 121–4. Large desquamation in Stevens-Johnson syndrome.

B FIGURE 121–3. A, Close-up of extensive erythema multiforme. B, Stevens-Johnson syndrome demonstrating extensive skin lesions.

epidermis begins to separate from the basal layer as a result of very minor frictional forces (Nikolsky’s sign), and large flaccid blisters that resemble scalds rupture, leaving sheets of necrotic epidermis with a moist erythematous base (Fig. 121–4). Complications that occur with large areas of skin sloughing include fluid and electrolyte losses, secondary bacterial infections, scarring, and dyspigmentation.1,17 The primary oral lesion consists of an erythematous macule that evolves centrally into a thick-walled vesicle or bulla. The blisters last a brief period and, after rupture, leave the characteristic irregularly shaped ulcer with indistinct margins and a yellow necrotic base. Unlike EM, mucosal involvement in SJS is confluent and widespread. The lips are often covered with hemorrhagic crusts (Fig. 121–5). These lesions are extremely painful and may become covered with a pseudomembrane prior to healing. In severe cases, erosion of the pharynx and esophagus leads to necrotizing esophagitis (Fig. 121–6). Swallowing is so painful that dehydration is a common sequela. Genital involvement induces urethritis, balanitis, and vulvovaginitis, which are associated with dysuria and purulent discharge (Fig. 121–7). The skin eruption consists of symmetric red macules that progress to central blister formation and extensive areas of epidermal necrosis. Erosions may also bleed. Genitourinary lesions may be so painful that urinary retention occurs. On occasion the rectal mucosa is also inflamed and ulcerated. Complications such as adhesions may develop.18

FIGURE 121–5. Hemorrhagic crusts of oral mucosa in Stevens-Johnson syndrome.

FIGURE 121–6. Extensive painful necrotic lesions of Stevens-Johnson syndrome.

Ocular lesions constitute the most severe mucous membrane involvement. The early phase consists of a mucopurulent conjunctivitis with inflamed, edematous papillae and photophobia (Fig. 121–8). Focal ulcerations can occur and lead to formation of pseudomembranes and synechiae between the eyelids and conjunctiva. Other reported complications include entropion, keratitis, symblepharon,

Chapter 121 — Erythema Multiforme Major and Minor

FIGURE 121–7. Penile mucosal involvement in Stevens-Johnson syndrome.

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correction of dehydration from transepidermal fluid losses, replacement of electrolytes, maintenance of nutrition, and pain control. These patients are best managed in a burn unit or pediatric intensive care unit with meticulous skin care for prevention of secondary bacterial infection, which can lead to sepsis, a leading cause of mortality. In addition, sulfonamide-containing ointments should be avoided since they have been implicated in causing these disorders.18,25 Surgical débridement and whirlpool therapy to remove necrotic epidermis are recommended. Prompt withdrawal of the causative agent should be a priority since the course of the illness may be shortened.26 Immediate ophthalmologic evaluation is mandatory if there are conjunctival lesions. Frequently applied lubrication with artificial tears and ophthalmic antibiotic drops or ointments (not containing sulfonamide) are necessary, with daily blunt disruption of synechiae. The controversy over whether systemic corticosteroids should be used to attenuate progression of disease is still unresolved, since there are no large prospective, doubleblind, multicenter controlled trials.17,27 In small trials, corticosteroids have been shown to decrease the duration of fever and lesions.27-29 Systemic corticosteroids do increase the risk of infection; however, their advocates suggest tapering the dose quickly once disease progression has ceased, and perhaps combining their use with a prophylactic antibiotic. Highdose intravenous immune globulins have been shown to improve some cases, with faster resolution of fever and skin lesions and shortened hospital stays.30-33

Summary

FIGURE 121–8. Involvement of the conjunctiva in Stevens-Johnson syndrome.

trichiasis, corneal pannus, uveitis, panophthalmos, and stricture of the lacrimal puncta.19,20 Severe involvement may lead to loss of vision and even blindness.21 There are no specific laboratory abnormalities in EM, but SJS has been associated with elevated sedimentation rate, leukocytosis, eosinophilia, anemia, elevated hepatic transaminases, proteinuria, and hematuria.1,22

Management Patients with EM require only symptomatic care, in addition to withdrawing any drugs suspected of initiating the eruption. If pruritus is prominent, oral antihistamines, calamine lotion, or oatmeal baths may be useful. Painful oral lesions may be treated with topical analgesic mouthwash (equal mixture of Maalox, 60 ml, and diphenhydramine, 15–30 ml), which is placed on the lesions with a Q-Tip. Viscous xylocaine should not be included since as little as 1–2 ml can be toxic to young children. HSV-associated EM does not usually respond to acyclovir, but prophylactic acyclovir, if given early enough, can prevent recurrences.2,23,24 Those patients with more extensive skin involvement, such as those with SJS, must be hospitalized for intravenous fluids,

In EM, disease tends to be mild and attacks tend to subside within 1 to 3 weeks, usually without sequelae, except for an occasional pigmentary change. A follow-up visit in 24 to 48 hours is advisable to determine the progress of EM. In SJS, prognosis depends on prompt diagnosis and meticulous care for patients with extensive disease. Mortality is generally less for children than adults, but may be as high as 15%, and is worse with increasing body surface area involvement. In most cases recovery occurs within 3 to 6 weeks. REFERENCES *1. Lèautè-Labréze C, Lamireau T, Chawki D, et al: Diagnosis, classification and management of erythema multiforme and Stevens-Johnson syndrome. Arch Dis Child 83:347–352, 2000. 2. Weston WL, Morelli JG, Rogers M: Target lesions on the lips: childhood herpes simplex associated with erythema multiforme mimics Stevens-Johnson syndrome. J Am Acad Dermatol 37:848–850, 1997. 3. Wong KC, Kennedy PJ, Lee S: Clinical manifestations and outcomes of 17 cases of Stevens-Johnson syndrome and toxic epidermal necrolysis. Aust J Dermatol 40:131–134, 1999. 4. Assier H, Bastuji-Garin S, Revuz J, Roujeau JC: Erythema multiforme with mucous membrane involvement and Stevens-Johnson syndrome are clinically different disorders with distinct causes. Arch Dermatol 131:539–543, 1995. 5. Brice SL, Huff JC, Weston WL: Erythema multiforme minor in children. Curr Probl Dermatol 11:3–26, 1990. 6. Weston WL, Stockert SS, Jester J, et al: Herpes simplex virus in childhood erythema multiforme. Pediatrics 89:32–34, 1992. 7. Darragh TM, Egbert BM, Berger TG: Identification of herpes simplex virus DNA in lesions of erythema multiforme by the polymerase chain reaction. J Am Acad Dermatol 24:23–26, 1991.

*Selected readings.

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8. Paquet P, Nikkels A, Arrese JE, et al: Macrophages and tumor necrosis factor alpha in toxic epidermal necrolysis. Arch Dermatol 130:605– 608, 1994. 9. Ng PP, Sun YJ, Tan HH, Tan SH: Detection of herpes simplex virus genomic DNA in various subsets of erythema multiforme by polymerase chain reaction. Dermatology 207:349–353, 2003. 10. Aurelian L, Ono F, Burnett J: Herpes simplex virus (HSV)-associated erythema multiforme (HAEM): a viral disease with an autoimmune component. Dermatol Online J 9:1, 2003. 11. Tay YK, Huff JC, Weston WL: Mycoplasma pneumoniae infection is associated with Stevens-Johnson syndrome, not erythema multiforme (von Hebra). J Am Acad Dermatol 35:757–760, 1996. 12. Sullivan JR, Shear NH: The drug hypersensitivity syndrome: what is the pathogenesis? Arch Dermatol 137:357–364, 2001. 13. Huff JC, Weston WL: Isomorphic phenomenon in erythema multiforme. Clin Exp Dermatol 8:409–413, 1983. 14. Weston WL: What is erythema multiforme? Pediatr Ann 25:106–109, 1996. 15. Weston JA, Weston JL: The overdiagnosis of erythema multiforme. Pediatrics 89:802, 1992. 16. Huff JC, Weston WL: Recurrent erythema multiforme. Medicine 68:133–140, 1989. 17. Prendiville JS, Hebert AA, Greenwald MJ, et al: Management of Stevens-Johnson syndrome and toxic epidermal necrolysis. J Pediatr 115:881–887, 1989. 18. Hart R, Minto C, Creighton S: Vaginal adhesions caused by StevensJohnson syndrome. J Pediatr Adolesc Gynecol 15:151–152, 2002. 19. Ginsburg CM: Stevens-Johnson syndrome in children. Pediatric Infect Dis 1:155–158, 1982. 20. Lehman SS: Long-term ocular complications of Stevens-Johnson syndrome. Clin Pediatr 38:425–427, 1999. 21. Kompella VB, Sangwan VS, Bansal AK, et al: Ophthalmic complications and management of Stevens-Johnson syndrome at a tertiary eye care center in south India. Indian J Ophthalmol 50:283–286, 2002.

22. Wong KC, Kennedy PJ, Lee S: Clinical manifestations and outcomes of 17 cases of Stevens-Johnson syndrome and toxic epidermal necrolysis. Australas J Dermatol 40:131–134, 1999. 23. Schofield JK, Tatnall FM, Leigh IM: Recurrent erythema multiforme: clinical features and treatment in a large series of patients. Br J Dermatol 128:542–545, 1993. 24. Tatnall FM, Schofield JK, Leigh IM: A double-blind, placebocontrolled trial of continuous acyclovir therapy in recurrent erythema multiforme. Br J Dermatol 132:267–270, 1995. 25. Roujeau JC: Treatment of severe drug eruptions. J Dermatol 26:718– 722, 1999. 26. Garcia-Doval I, LeCleach L, Bocquet H, et al: Toxic epidermal necrolysis and Stevens-Johnson syndrome: does early withdrawal of causative drugs decrease the risk of death? Arch Dermatol 136:323–327, 2000. 27. Kakourou T, Klontza D, Soteropoulou F, Kattamis C: Corticosteroid treatment of erythema multiforme major (Stevens-Johnson syndrome) in children. Eur J Pediatr 156:90–93, 1997. 28. Ayangco L, Rogers RS 3rd: Oral manifestations of erythema multiforme. Dermatol Clin 21:195–205, 2003. *29. Prendiville JS: Erythema multiforme and steroids. Pediatr Dermatol 17:75–83, 2000. 30. Morici MV, Galen WK, Shetty AK, et al: Intravenous immunoglobulin therapy for children with Stevens-Johnson syndrome. J Rheumatol 27:2494–2497, 2000. 31. Metry DW, Jung P, Levy ML: Use of intravenous immunoglobulin in children with Stevens-Johnson syndrome and toxic epidermal necrolysis: seven cases and review of the literature. Pediatrics 112:1430–1436, 2003. 32. Prins C, Vittorio C, Padilla RS, et al: Effect of high-dose intravenous immunoglobulin therapy in Stevens-Johnson syndrome: a retrospective, multicenter study. Dermatology 207:96–99, 2003. 33. Bachot N, Revuz J, Roujeau JC: Intravenous immunoglobulin treatment for Stevens-Johnson syndrome and toxic epidermal necrolysis: a prospective noncomparative study showing no benefit on mortality or progression. Arch Dermatol 139:33–36, 2003.

Chapter 122 Henoch-Schönlein Purpura Antonio E. Muñiz, MD

Key Points Palpable petechiae or purpura symmetrically distributed over the buttocks and extensor surfaces of the legs is the characteristic rash distribution of Henoch-Schönlein purpura. In children with severe colicky abdominal pain, an ileoileal intussusception must be excluded. Major morbidity is due to renal involvement, which may lead to chronic renal disease. Treatment is supportive with nonsteroidal antiinflammatory drugs and occasionally systemic corticosteroids or cytotoxic drugs.

Introduction and Background Henoch-Schönlein purpura (HSP), also known as anaphylactoid purpura or allergic vasculitis, is the most prevalent cause of leukocytoclastic vasculitis in children, particularly between 3 and 10 years of age. It can occur in adults but is associated with a worse prognosis, more renal involvement, and increased use of aggressive therapeutic regimens, including corticosteroids and cytotoxic drugs.1,2 The disorder is characterized by a tetrad consisting of a distinctive purpuric rash, colicky abdominal pain, athralgias or arthritis, and in some cases renal disease.

Recognition and Approach A history of an antecedent upper respiratory tract infection preceding the onset of illness, seen in up to 75% of cases, suggests a hypersensitivity reaction to a virus resulting in vascular damage. Other entities implicated in the pathogenesis have included drugs, foods, insect bites, immunizations, cold exposure, tumors, pregnancy, and chemical toxins.3-5 The disorder appears to be initiated by deposition of immune complexes on the basement membrane, mainly of the immunoglobulin A (IgA) class, which activates complement leading to systemic inflammation of small vessels in the

upper dermis, gastrointestinal tract, synovial membranes, renal glomeruli, and occasionally the lungs and central nervous system.6-8 The deposition of IgA occurs as a consequence of abnormal glycosylation of O-linked oligosaccharides of IgA1.9

Clinical Presentation The eruption is frequently preceded by a prodrome consisting of fever, headache, malaise, nausea, and vomiting. Subsequently a characteristic rash, abdominal pain, and/or joint symptoms occur. In most children, HSP is a self-limited illness with no significant sequelae; however, in a small minority renal disease can occur. The major diagnostic feature is that of palpable petechiae or purpura. Individual lesions vary in size from 2 to 10 mm in diameter. They are most commonly found in a symmetric distribution over the buttocks and extensor surfaces of the legs (Figs. 122–1, 122–2, and 122–3). Children younger than 2 years of age have lesions in atypical locations, such as the face, upper extremity, and trunk (Fig. 122–4). Individual lesions occur in successive crops, tend to fade after 5 days, and eventually are replaced by areas of brownish pigmentation, purpura, or ecchymosis. New crops of lesions frequently occur over the next 2 to 4 weeks over the fading lesions of a previous episode, thereby giving a polymorphous appearance to the disorder. Less than 5% of patients have associated edema of the hands, feet, or face, and few have lesions consisting of urticaria.10 The differential diagnosis of HSP is variable3,4,11 (Table 122–1).

Important Clinical Features and Considerations Fifty percent to 80% of affected children also have involvement of joints, gastrointestinal tract, and kidneys, with lesser involvement of the cardiopulmonary, genitourinary, and central nervous system (Table 122–2). The diagnosis of HSP is made by clinical features. Confirmation of the diagnosis of HSP requires evidence of tissue deposition of IgA in the skin or kidney by IgA immunofluorescence microscopy. Biopsy of skin lesions demonstrates a leukocytoclastic vasculitis, or white blood cells surrounding dermal blood vessels. These are more prominent in the postcapillary venules. 841

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FIGURE 122–3. Typical purpuric lesions of the buttocks.

FIGURE 122–1. Typical purpuric lesions of the lower extremity.

FIGURE 122–4. Atypical location of purpuric lesions in a young child.

Table 122–1

FIGURE 122–2. Typical purpuric lesions of the knee.

Differential Diagnosis of HSP

Juvenile rheumatoid arthritis (JRA) Disseminated intravascular coagulation (DIC) Acute glomerulonephritis Idiopathic thrombocytopenic purpura (ITP) Inflammatory bowel disease Meningococcemia Infectious mononucleosis Systemic lupus erythematosus (SLE) Thrombotic thrombocytopenic purpura (TTP) Rocky Mountain spotted fever (RMSF) Churg-Strauss syndrome Chronic urticaria Atypical measles Staphylococcal sepsis Pseudomonas sepsis Subacute bacterial endocarditis Gonococcemia Mixed cryogobulinemia Hypersensitivity vasculitis Antiphospholipid syndrome Wegener’s granulomatosis Trauma (including child abuse)

Chapter 122 — Henoch-Schönlein Purpura

Table 122–2

Organ Systems Affected by HSP

Associated Features

Description

Joints (80%)

Warm, tender, and painful swelling of joints, with or without overlying purpura11 Primarily in knees and ankles, but may be seen in elbows, hands, and feet Joint symptoms generally last a few days but have a high recurrence rate Symptoms from edema of the bowel wall, hemorrhage as a result of vasculitis, and thrombosis of the microvasculature Typically occur 1 wk after the rash but may precede in 14% –36%31 Colicky abdominal pain, vomiting, visceral infarction or perforation, pancreatitis, cholecystitis, hydrops of the gallbladder, colitis, protein-losing enteropathy, appendicitis, pseudomembranous colitis, chronic intestinal obstruction with ileal stricture, intussusception, hemorrhage (melena or hematochezia), or shock18,32-37 Location of intussusception is usually ileoileal and is diagnosed initially by ultrasound (“donut” or “pseudokidney” sign); may require surgical reduction but spontaneous reduction has occurred with conservative therapy, consisting of nasogastric drainage, corticosteroids, and intravenous fluids38-40 Most serious cause of morbidity Occurs few days to 1 mo after onset May present with gross or, more commonly, microscopic hematuria, with or without casts and proteinuria Often self-limited; if proteinuria persists, may progress to advanced glomerular disease and acute or chronic renal failure Chronic renal disease in up to 15% with hematuria and proteinuria; if evidence of nephritis or nephrotic syndrome, end-stage renal disease in up to 50% 41 Overall, 1.7% of all patients develop chronic renal failure.42 Children at higher risk for renal disease include those with hypertension, proteinuria > 1 g/L, elevations of serum blood urea nitrogen and creatinine, decreased fibrin-stabilizing factor (factor XIII) activity, glomerular crescents on biopsy, and rash greater than 1 month’s duration.41,43-48 Headache, diplopia, cerebral or cerebellar hemorrhage, subarachnoid hemorrhage, seizures, focal neurologic deficit, mononeuropathy, and coma49-52 Asymptomatic pulmonary infiltrate or recurrent episodes of pulmonary hemorrhage53,54 Cardiac involvement is rare; may include myocarditis, coronary artery vasculitis resulting in acute myocardial ischemia or infarction, and cardiac tamponade48,55,56 Scrotal hemorrhage may cause intense pain from severe scrotal swelling57,58 Rare report of a simultaneous torsion of the testes; ultrasound or nuclear scan is recommended59,60

Gastrointestinal symptoms (75%)

Kidney (25–50%)

Central nervous system Cardiopulmonary Genitourinary (20%)

843

Management Complete recovery occurs in 94% of children; therefore, most receive no specific therapy.2 Bed rest and general supportive care are helpful. Analgesia with nonsteroidal antiinflammatory drugs may reduce joint and soft tissue discomfort. For significant gastrointestinal hemorrhage, fluids and blood should be replaced as required. The degree to which diagnostic testing is performed in the emergency department depends on symptoms, but in all cases a urinalysis is warranted as a screening test for possible renal complications. Need for hospitalization is also dictated by severity of symptoms and the presence of complications. Most children can be managed as outpatients, but parents should be counseled that symptoms may wax and wane for several weeks before remitting entirely, and can be debilitating. The efficacy of corticosteroids is controversial.12-15 Although there is little evidence that corticosteroids alter the prognosis of HSP, they suppress and improve the acute manifestations, and hence may be justified for short periods in severe cases, especially those with significant gastrointestinal complications (except bleeding, perforation, intussuception) or chronic glomerulonephritis.16,17 In this setting, a regimen of phased intravenous methylprednisolone followed by oral prednisone for 3 months may be beneficial.18 This regimen is useful in reversing the anti-inflammatory process but not the IgA deposition. Dapsone, azathioprine, cyclophosphamide, cyclosporine, methothrexate, intravenous immune globulins, plasmapheresis, anticoagulation, and dipyridamole have been tried with varying success in severe and refractory cases.8,19-28 Renal transplantation can be performed in those

patients who progress to end-stage renal disease; however, recurrent disease can occur.29,30 A pediatric nephrologist or rheumatologist should be consulted for guidance on the use of steroids and other medications.

Summary HSP generally subsides within a few days to weeks, with some patients having recurrent attacks lasting weeks or months. The prognosis for most patients with HSP is excellent, with full recovery without sequelae in most cases. In children younger than 2 years of age, the disease is generally milder and of shorter duration, with fewer systemic complications. Patients should be hospitalized if complications develop, such as significant bleeding, intussusception, renal disease (especially with hypertension), and pulmonary or central nervous system hemorrhages. All patients with an abnormal urinalysis should be referred for urgent follow-up so that the urine may continue to be frequently monitored. REFERENCES 1. Garcia-Porra C, Calvino MC, Llorca J, et al: Henoch-Schönlein purpura in children and adults: clinical differences in a defi ned population. Semin Arthritis Rheum 32:149–156, 2002. 2. Blanco R, Martinez-Taboada VM, Rodriguez-Valverde V, et al: HenochSchönlein purpura in adulthood and childhood: two different expressions of the same syndrome. Arthritis Rheum 40:859–864, 1997. 3. Harper L, Ferreira MA, Howie AJ, et al: Treatment of vasculitic IgA nephropathy. J Nephrol 13:360–366, 2000. 4. Scott DG, Watts RA: Systemic vasculitis: epidemiology, classification and environmental factors. Ann Rheum Dis 59:161–163, 2000.

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5. Campanile G, Hautmann G, Lotti TM: The etiology of cutaneous necrotizing vasculitis. Clin Dermatol 17:505–508, 1999. 6. Saulsbury FT: Henoch-Schönlein purpura. Pediatr Dermatol 1:195– 201, 1984. 7. Saulsbury FT: IgA rheumatoid factor in Henoch-Schönlein purpura. J Pediatr 108:71–76, 1986. 8. Tarshish P, Bernstein J, Edelmann CM: Henoch-Schönlein purpura nephritis: course of disease and efficacy of cyclophosphamide. Pediatr Nephrol 19:51–56, 2003. 9. Saulsbury FT: Henoch-Schönlein purpura in children: report of 100 patients and review of the literature. Medicine 78:395–409, 1999. 10. Nussinovitch M, Prais D, Finkelstein Y, Varsano I: Cutaneous manifestations of Henoch-Schönlein purpura in young children. Pediatr Dermatol 15:426–428, 1998. 11. Sorenson SF, Slot O, Tvede N, Petersen J: A prospective study of vasculitis patients collected in a five year period: evaluation of the Chapel Hill nomenclature. Ann Rheum Dis 59:478–482, 2000. 12. Huber AM, King J, McLaine P, et al: A randomized, placebo controlled trial of prednisone in early Henoch-Schönlein purpura. BMC Med 2:7, 2004. 13. Mollica F, Li Volti S, Garozzo R, Russo G: Effectiveness of early prednisone therapy in preventing the development of nephropathy in anaphylactoid purpura. Eur J Pediatr 151:140–144, 1992. 14. Flynn JT, Smoyer WE, Bunchman TE, et al: Treatment of HenochSchönlein purpura glomerulonephritis in children with high-dose corticosteroids plus oral cyclophosphamide. Am J Nephrol 21:128–133, 2001. 15. Wyatt RJ, Hogg RJ: Evidence-based assessments of treatment options for children with IgA nephropathies. Pediatr Nephrol 16:156–167, 2001. 16. Rosenblum ND, Winter HS: Steroid effects in the course of abdominal pain in children with Henoch-Schönlein purpura. Pediatrics 79:1018– 1021, 1987. 17. Niaudet P, Habib R: Methylprednisolone pulse therapy in the treatment of severe forms of Schönlein-Henoch purpura nephritis. Pediatr Nephrol 12:238–243, 1998. 19. Harries MJ, McWhinney P, Melsom R: Recurrent Henoch-Schönlein purpura controlled with cyclosporin. J R Soc Med 97:184–185, 2004. 20. Ronkainen J, Autio-Harmainen H, Nuutinen M: Cyclosporin A for the treatment of severe Henoch-Schönlein glomerulonephritis. Pediatr Nephrol 18:1138–1142, 2003. 21. Singh S, Devidayal, Kumar L, et al: Severe Henoch-Schönlein nephritis: resolution with azathioprine and steroids. Rheumatol Int 22:133– 137, 2002. 22. Nakahata T, Tanaka H, Suzuki K, Ito E: Successful treatment with leukocytapheresis in refractory Henoch-Schönlein purpura: case report. Clin Rheumatol 22:248–250, 2003. 23. Tanaka H, Suzuki K, Nakahata T, et al: Early treatment with oral immunosuppresants in severe proteinuric purpura nephritis. Pediatr Nephrol 18:347–350, 2003. 24. Rettig P, Cron RQ: Methotrexate used as a steroid-sparing agent in non-renal chronic Henoch-Schönlein purpura. Clin Exp Rheumatol 21:767–769, 2003. 25. Bergstein J, Leiser J, Andreoli SP: Response of crescentic HenochSchönlein purpura to corticosteroid and azathioprine therapy. Clin Nephrol 49:9–14, 1998. 26. Oner A, Tinaztepe K, Erdogan O: The effect of triple therapy on rapidly progressive type of Henoch-Schönlein nephritis. Pediatr Nephrol 9:6–10, 1995. 27. Iijima K, Ito-Kariya S, Nakamura H, Yoshikawa N: Multiple combined therapy for severe Henoch-Schönlein nephritis in children. Pediatr Nephrol 12:244–248, 1998. 28. Hattori M, Ito K, Konomoto T, et al: Plasmapheresis as the sole therapy for rapidly progressive Henoch-Schönlein purpura nephritis in children. Am J Kidney Dis 33:427–433, 1999. 29. Nast CC, Ward HJ, Koyle MA, Cohen AH: Recurrent HenochSchönlein purpura following renal transplantation. Am J Kidney Dis 9:39–43, 1987. 30. Hasegawa A, Kawamura T, Ito H, et al: Fate of renal grafts with recurrent Henoch-Schönlein purpura nephritis in children. Transplant Proc 21:2130–2133, 1989. 31. Hattori M, Ito K, Konomoto T, et al: Plasmapheresis as the sole therapy for rapidly progressive Henoch-Schönlein purpura nephritis in children. Am J Kidney Dis 33:427–433, 1999.

32. Lombard KA, Shah PC, Thrasher TV, Grill BB: Ileal stricture as a late complication of Henoch-Schönlein purpura. Pediatrics 77:396–398, 1986. 33. Chen SY, Kong MS: Gastrointestinal manifestations and complications of Henoch-Schönlein purpura. Chang Gung Med J 27:175–181, 2004. 34. Lippl F, Huber W, Werner M, et al: Life-threatening gastrointestinal bleeding due to a jejunal lesion of Henoch-Schönlein purpura. Endoscopy 33:811–813, 2001. 35. Cho CS, Min JK, Park SH, et al: Protein losing enteropathy associated with Henoch-Schönlein in a patient with rheumatoid arthritis. Scand J Rheumatol 25:334–336, 1996. 36. Kumon Y, Hisatake K, Chikamori M, et al: A case of vasculitis cholecystitis associated with Schonlein-Henoch purpura in an adult. Gastroenterol Jpn 23:68–72, 1988. 37. Branski D, Gross V, Gross-Kieselstein E, et al: Pancreatitis as a complication of Henoch-Schönlein purpura. J Pediatr Gastroenterol Nutr 1:275–276, 1982. 38. Sonmez K, Turkyilmaz Z, Demirogullari B, et al: Conservative treatment for small intestinal intussusception associated with HenochSchönlein’s purpura. Surg Today 32:1031–1034, 2002. 39. Connolly B, O’Halpin D: Sonographic evaluation of the abdomen in Henoch-Schonlein purpura. Clin Radiol 49:320–323, 1994. 40. Choong CK, Beasley SW: Intra-abdominal manifestations of Henoch-Schönlein purpura. J Paediatr Child Health 34:405–409, 1998. 41. Koskimies O, Mir S, Rapola J, Viska J: Henoch-Schönlein nephritis: long-term prognosis of unselected patients. Arch Dis Child 56:482– 484, 1981. 42. Loirat C, Ehrich JH, Geerlings W, et al: Report on management of renal failure in children in Europe, XXIII, 1992. Nephrol Dial Transplant 1(Suppl):26–40, 1994. 43. Coppo R, Mazzucco G, Cagnoli L, et al: Long-term prognosis of Henoch-Schönlein nephritis in adults and children. Italian Group of Renal Immunopathology Collaborative Study on Henoch-Schönlein Purpura. Nephrol Dial Transplant 12:2277–2283, 1997. 44. Niaudet P, Murcia I, Beaufi ls H, et al: Primary IgA nephropathies in children: prognosis and treatment. Adv Nephrol Necker Hosp 22:121– 140, 1993. 45. Riagnte D, Candelli M, Federico G, et al: Predictive factors of renal involvement or relapsing disease in children with Henoch-Schönlein purpura. Rheumatol Int 25:45–48, 2005. 46. Goldstein AR, White RH, Akuse R, Chantler C: Long-term followup of childhood Henoch-Schönlein nephritis. Lancet 339:280–282, 1992. 47. Rai A, Nast C, Adler S: Henoch-Schönlein purpura nephritis. J Am Soc Nephrol 10:2637–2644, 1999. 48. Kawasaki Y, Suzuki J, Sakai N, et al: Clinical and pathological features of children with Henoch-Schönlein purpura nephritis: risk factors associated with poor prognosis. Clin Nephrol 60:153–160, 2003. 49. Belman AL, Leicher CR, Moshe SL, Mezey AP: Neurologic manifestations of Schoenlein-Henoch purpura: report of three cases and a review of the literature. Pediatrics 75:687–692, 1985. 50. Chen CL, Chiou YH, Wu CY, et al: Cerebral vasculitis in HenochSchönlein purpura: case report with sequential magnetic resonance imaging changes and treated with plasmapheresis alone. Pediatr Nephrol 15:276–278, 2000. 51. Paolini S, Ciappetta P, Piattella MC, Domenicucci M: HenochSchönlein syndrome and cerebellar hemorrhage: report of an adolescent case and literature review. Surg Neurol 60:339–342, 2003. 52. Imai T, Okada H, Nanba M, et al: Henoch-Schönlein purpura with intracerebral hemorrhage. Brain Dev 24:115–117, 2002. 53. Chaussain M, de Boissieu D, Kalifa G, et al: Impairment of lung diffusing capacity in Schönlein-Henoch purpura. J Pediatr 121:12–16, 1992. 54. Besbas N, Duzova A, Topalogu R, et al: Pulmonary haemorrhage in a 6-year-old boy with Henoch-Schönlein purpura. Clin Rheumatol 20:293–296, 2001. 55. Gulati T, Kumar P, Dewan V, Anand VK: Henoch Schonlein purpura with rheumatic carditis. Indian J Pediatr 71:371–372, 2004. 56. Agraharkar M, Gokhale S, Le L, et al: Cardiopulmonary manifestations of Henoch-Schönlein purpura. Am J Kidney Dis 35:319–322, 2000.

Chapter 122 — Henoch-Schönlein Purpura 57. Sakai N, Kawamoto K, Fukuoka H, et al: Acute scrotal swelling in Henoch-Schönlein purpura: a case report. Hinyokika Kiyo 46:739–741, 2000. 58. Ben-Sira L, Laor T: Severe scrotal pain in boys with Henoch-Schönlein purpura: incidence and sonography. Pediatr Radiol 30:125–128, 2000.

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59. Turkish VJ, Traisman HS, Belman AB, et al: Scrotal swelling in the Schönlein-Henoch syndrome. J Urol 115:317–319, 1976. 60. Crosse JE, Soderdahl DW, Schamber DT: “Acute scrotum” in HenochSchönlein syndrome. Urology 7:66–67, 1976.

Chapter 123 Classic Viral Exanthems Antonio E. Muñiz, MD

Key Points Measles causes a prodrome, Koplik’s spots, and a 10day maculopapular rash.

respiratory syncytial virus, and influenza virus).2,3 In general, most nonspecific exanthems occurring in the warmer months are caused the enteroviruses, and those occurring during the winter months by the respiratory viruses.

Rubella usually is a benign disease, but can result in thrombocytopenia and arthralgias.

Discussion of Individual Diagnoses

Roseola infantum may present as febrile seizure.

Classic features of measles include a prodrome of fever, cough, coryza, conjunctivitis, and Koplik’s spots, followed by an exanthematous phase. During the entire course of the illness, the child appears quite ill. Despite active immunization in the United States, outbreaks continue to occur.4 Measles is caused by an RNA virus, Paramyxovirus, that is highly contagious and is spread by direct contact with infectious droplets or, less commonly, by airborne spread. The incubation period, as defined by days prior to appearance of the rash, is 8 to 12 days. It is contagious 1 to 2 days before the prodrome and 4 days after the rash develops. It is most prevalent in late winter and spring. With the recommended two-dose vaccination schedule, first at 12 to 15 months and the second at 4 to 6 years of age, the incidence of measles in the United States has decreased to 100 cases per year.5,6 Up to 67% are caused by importation of the virus from other countries.7 Typical measles infects the epithelial cells of the respiratory tract and binds to a cell surface glycoprotein, CD46.8,9 This is followed by spread to lymphoid tissue, where it replicates, and eventually a primary viremia occurs. The virus disseminates to multiple sites, including skin, the liver, and the gastrointestinal tract tract.10 Infection of the oral mucosa leads to the enanthem. The cutaneous eruption is related to the presence of the measles virus within keratinocytes and endothelial cells of the superficial dermal vessels.11 The virus replicates within keratinocytes, leading to multinucleated giant cells, called Warthin-Finkeldey cells.11 The clinical lesions are believed to be due to the host response to the virus within the skin.

Fifth disease can result in aplastic anemia in patients with shortened life span or abnormal red blood cells. Gingivostomatitis is the primary presentation of herpes simplex virus infection in children.

Selected Diagnoses Measles (rubeola, first disease) Rubella (German measles, third disease) Roseola infantum (exanthem subitum, sixth disease) Erythema infectiosum (fifth disease, human parvovirus B19) Herpes simplex (human herpesvirus 1 and human herpesvirus 2) Varicella-zoster virus (human herpesvirus 3) Coxsackievirus (hand-foot-and-mouth disease)

Introduction and Background Any generalized cutaneous erythematous eruption associated with an acute viral syndrome is known as a viral exanthem. If the mucosa is involved, it is called an enanthem. The exact incidence of viral exanthems is unknown, and the most common are caused by enteroviruses.1 A majority of childhood exanthems are nonspecific and cannot be accurately assigned to a discrete etiologic diagnosis. These exanthems are usually self-limited, resolving spontaneously in 1 week without long-term sequelae, and require only symptomatic therapy. Multiple viral agents are capable of causing a nonspecific exanthem, including nonpolio enteroviruses (i.e., cosackievirus, echovirus, and enterovirus) and respiratory viruses (i.e., rhinovirus, adenovirus, parainfluenza virus, 846

Measles (Rubeola, First Disease)

Clinical Presentation A prodrome occurs for 3 to 5 days of high fever, chills, systemic toxicity, headache, malaise, anorexia, and the “three Cs” (cough, coryza, and conjunctivitis). The cough is described as brassy or barking, and an initial diagnosis of croup or bronchitis may be made. The conjunctivitis is characterized by severe lacrimation with mild photophobia. The

Chapter 123 — Classic Viral Exanthems

Table 123–1

847

Differential Diagnosis of Morbilliform Rashes

Differential Diagnosis

Causes

Viruses

Measles Rubella Roseola infantum Erythema infectiosum Infectious mononucleosis Pityriasis rosea HIV (primary) Infectious hepatitis Scarlet fever Rocky Mountain spotted fever Syphilis Ampicillin, penicillin Nonsteroidal anti-inflammatory drugs Salicylic acid Phenytoin, barbiturates Phenothiazines Thiazide diuretics Isoniazid Guttate psoriasis Graft-versus-host disease Urticaria Papular urticaria Erythema multiforme Henoch-Schönlein purpura Kawasaki disease

Bacterial infections Drug eruptions FIGURE 123–1. Koplik’s spots on buccal mucosa seen in measles.

Papulosquamous disorders Reactive erythemas

Abbreviation: HIV, human immunodeficiency virus.

FIGURE 123–2. Erythematous macules and papules in measles.

coryza consists of copious mucopurulent discharge. Enlarged cervical and preauricular lymph nodes are present. The exanthem follows the prodrome but is preceded by an enanthem. The enanthem is composed of intense erythema of the mucous membranes with focal 1- to 3-mm punctuate white-gray papules (Koplik’s spots) usually adjacent to the lower premolars. These resemble a grain of salt on a red background (Fig. 123–1). The exanthem begins at the hairline and behind the ears as blotchy erythema and spreads centrifugally and in a cephalocaudad direction to involve the face, trunk, and extremities, with multiple discrete macules and papules (Fig. 123–2). These gradually coalesce, and, by the third day, the entire body is involved and lesions are intensely erythematous, and at times purpuric (morbilliform). Usually by the fourth day, the rash begins to fade, with a coppery-brown discoloration

and desquamation, in the same order as it appeared. The rash fades by the 10th day (“10-day rash”). Complications of measles are infrequent but may be life threatening, especially in children less than 1 year of age, patients who are immunosuppressed, or the elderly.12 Bacterial otitis media, bacterial pneumonia, bronchitis, laryngotracheobronchitis, diarrhea, myocarditis, and encephalitis may complicate measles.1,13 Severe pneumonia and encephalitis are primary causes of death and are more likely to complicate measles in young infants and malnourished or immunocompromised children. Other rarely reported complications include thrombocytopenia, Stevens-Johnson syndrome, gangrenous stomatitis, appendicitis (lymphoid hyperplasia), hepatitis, laryngotracheal bronchitis, acute glomerulonephritis, pericarditis, lymphadenitis, and subacute sclerosing panencephalitis.14 Mortality related to measles in the United States is estimated to be 1 per 1000.4 Low vitamin A levels have been implicated in the severity of measles.15 The differential of morbilliform exanthems is vast and include viruses, bacterial infections, drug eruptions, papulosquamous disorders, and reactive erythema (Table 123–1). The typical features of measles are easily recognized. When the diagnosis is in doubt, viral isolation from mucosa or the nasopharynx, although difficult, will distinguish measles from other morbilliform exanthems. Acute and convalescent sera, obtained at 1 week and 3 weeks after the onset of the illness, showing a fourfold rise in immunoglobulin G antibodies assist with a retrospective diagnosis.16 Laboratory diagnosis can be accomplished by serologic assays, including complement fi xation, hemagglutination-inhibition (HAI) titer, direct immunofluorescence, and enzyme-linked immunosorbent assay (ELISA).17 Leukocytosis is common.

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SECTION IV — Approach to the Acutely Ill Patient

Management No specific treatment is available, only supportive therapy in most cases. Using two doses of vitamin A (200,000 IU) on consecutive days is associated with a reduction in the risk of mortality in children under the age of 2 years as well as a reduction in the risk of pneumonia-specific mortality.18 Those with suspected vitamin A deficiency should have a second dose on the following day and at 4 weeks. Others who should receive vitamin A include immunosuppressed or malnourished patients or those with impaired intestinal absorption, or patients recently emigrated from an area with high mortality due to measles. Vitamin A reduces mortality in hospitalized children up to 60%.19 If bacterial pneumonia or otitis media occurs, appropriate antibiotics are indicated. Children with significant pulmonary symptoms or central nervous system (CNS) involvement should be hospitalized. In areas where other patients are not immunized against measles, any patient with measles should be isolated during the contagious period, from onset of respiratory symptoms through the fourth day of the exanthem. Postexposure prophylaxis in susceptible individuals includes measles vaccine, if given within 72 hours of exposure, and immune globulin (0.25 ml/kg intramuscularly [IM]), which can be given up to 6 days following exposure to prevent disease or modify its course. Immune serum globulin should be administered to unimmunized infants less than 1 year of age or to those who are immunosuppressed at a dose of 0.5 ml/kg IM (maximum 15 ml) as soon as possible after exposure. Outbreaks should be reported to local public health authorities. Measles virus is susceptible in vitro to ribavirin, which has been given to patients with severe infection and immunocompromised children. Close follow-up should be arranged to observe for the development of severe pneumonia or encephalitis. Parents should be advised to return immediately if there is fever recurrence, headache, or a change in mental status, or if seizures or motor deficits develop. Rubella (German Measles, Third Disease) Rubella is a viral illness characterized by a maculopapular rash and enlargement of the posterior occipitocervical lymph nodes. Rubella is caused by an RNA virus, Rubivirus, that is transmitted by contact with aerosolized particles from an infected person. It can also be transmitted transplacentally. Rubella occurs most commonly in late winter and early spring, and the incubation period ranges from 14 to 21 days. The patient is contagious a few days before illness and up to 1 week after the onset of the rash. The primary site of infection is the nasopharynx, followed by spread to regional lymphatics and eventually viremia. Virus replicates in the reticuloendothelial system. The rash appears as the serum antibody titer is rising, suggesting a potential contribution of antigen-antibody interactions in the skin. Clinical Presentation Classic rubella is a mild illness in most children and usually not diagnosed unless an epidemic exists.20 Rubella acquired postnatally in infants and children is accompanied by few or no prodromal symptoms, and up to 50% of rubella infections may be asymptomatic.20,21 In children with clinical symptoms (10%), rubella presents insidiously with a mild prodrome of headache, low-grade fever, malaise, sore throat,

FIGURE 123–3. Rose-pink macular and papular eruption in rubella.

anorexia, conjunctivitis, cough, and coryza. These are more common in adolescents or adults.20,21 Mild lymphadenopathy may precede the exanthem by several days and occurs in the occipital, posterior auricular, and posterior cervical lymph nodes. An enanthem characterized by erythematous and petechial macules on the soft palate (Forschheimer spots) may be present. The rash occurs 1 to 5 days after onset of illness. A faint rose-pink, macular or papular eruption appears first on the face and spreads downward to the trunk and proximal extremities (Fig. 123–3). Within 48 hours, the face and trunk rash has faded and the eruption involves the distal extremities. Rarely, petechiae or purpura may be seen. In cases of extensive eruption, a fine, flaky desquamation may occur. The eruption is usually completely resolved by the third day (“3-day measles”), but occasionally may last 5 days. As opposed to measles, the child appears well. A monoarticular arthritis or arthralgia may accompany rubella, especially in adolescent girls.20,21 The fingers, wrists, and knees are most often affected, and symptoms resolve by 1 month. Occasionally the elbows, shoulders, and spine are involved. It may present as the so-called STAR (sore throat, arthritis, rash) complex.22 Other viruses associated with the STAR complex include human parvovirus B19, hepatitis B, adenovirus, echovirus, coxsackievirus, and Epstein-Barr virus. Other less common complications include encephalitis, myocarditis, pericarditis, hemolytic anemia, thrombocytopenic purpura, and hepatitis. In distinguishing rubella from measles, the clinician should look for the absence of fever and toxicity. It may be difficult to distinguish rubella from enterovirus exanthems, infectious mononucleosis, cytomegalovirus, reovirus,

Chapter 123 — Classic Viral Exanthems

adenovirus, measles, scarlet fever, roseola infantum, parvovirus B19, syphilis, toxoplasmosis, or mild drug reactions.23 The diagnosis may be made from recovery of the organism from the nasal mucosa, blood, urine, or cerebrospinal fluid, but such tests are superfluous in most cases. Serologic diagnosis can be performed with the HAI titer, latex agglutination, direct immunofluorescence, ELISA, and passive HAI antibody test or by serologic acute and convalescent titers.17 In infants with congenital rubella, the virus may be recovered from peripheral blood leukocytes, stool, or urine for months to years after birth. Leukopenia is common. Rubella acquired during the first trimester of pregnancy may result in intrauterine transmission, and congenital rubella is seen 10% to 20% of cases.23-25 The earlier in the pregnancy that the transmission occurs, the greater the risk to the fetus. The skin manifestations include purpura and petechiae from thrombocytopenia, and may recur any time during the first 5 years of life. Other features include sensorineural hearing loss, congenital heart defects (i.e., patent ductus arteriosus, pulmonary stenosis), cataract, retinopathy, glaucoma, pigmentary retinopathy, growth retardation, behavioral disorders, meningoencephalitis, pneumonia, intrauterine growth retardation (IUGR), psychomotor retardation, hepatosplenomegaly, hepatitis with jaundice, and “blueberry muffin” spots.20,23-25 Management There is no specific treatment for rubella. If the patient is febrile, fever control measures will suffice. Oatmeal baths and antihistamines are helpful for pruritus. Nonsteroidal anti-inflammatory agents may be prescribed for arthritis. Administration of the rubella vaccine after exposure has not been demonstrated to ameliorate illness. When a pregnant women is exposed to rubella, a serum specimen should be obtained and tested for rubella antibody. If antibody is present, there is no risk of infection. If no rubella antibody is detectable, a second blood specimen should be obtained 2 or 3 weeks later. If antibody is present in the second specimen and not the first, infection is presumed to have occurred, and termination of pregnancy may be considered. If termination of pregnancy is not an option, serum immune globulin (0.55 ml/kg IM) should be given. Roseola Infantum (Exanthem Subitum, Sixth Disease) Roseola occurs predominantly in infants 6 months to 3 years of age, with a peak age of 6 to 7 months.26-29 It is characterized by 2 to 3 days of sustained fever in an infant who otherwise appears well, after which the infant becomes afebrile and a pink, morbilliform exanthem appears transiently and fades within a few days. Roseola is caused by human herpesvirus 6 (HHV-6), a double-stranded DNA virus, and occasionally by human herpesvirus 7 (HHV-7).30,31 It can occur at any time of the year, but is more common in the spring.32 The incubation period is 5 to 15 days. Transmission is airborne and from contact with infected respiratory droplets and, rarely, transplacentally.33 Clinical Presentation The illness begins with high fever that lasts 3 to 7 days, cough, and otitis media, but patients appear well.26,27,34 Mild edema of the eyelids and posterior cervical lymphadenopathy

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FIGURE 123–4. Rose-pink macules and papules in roseola infantum.

are occasionally seen. A seizure with the onset of fever is noted in 25% to 36% of cases.27,29,35 A bulging fontanelle is also a common physical finding. An enanthem of erythematous papules on the mucosa of the soft palate and uvula (Nagayama’s spots) may be seen in 65% of cases.32 The rash of roseola usually coincides with cessation of fever, or may follow it by 1 to 2 days. It is characterized by rose-pink macules and papules, and occurs predominantly on the neck and trunk, but occasionally involves the face and proximal extremities (Fig. 123–4). The eruption fades over a few days, rarely persisting for up to a week. Differential diagnosis may include other viruses (Table 123–2). HHV-6 can be recovered from cultures of peripheral blood leukocytes, by serology with a fourfold increase in HHV-6 immunoglobulin G antibodies, by antigen detection by polymerase chain reaction (PCR) or immunofluorescence studies, or from skin lesions by molecular diagnosis.34 Leukopenia with relative lymphocytosis develops on day 3 of illness. Complications are uncommon and include seizures, hyperpyrexia, vomiting, diarrhea, cough, fulminant hepatitis, thrombocytopenia, disseminated infection, and hepatosplenomegaly. Rarely encephalitis or encephalopathy occurs.36 Management There is no specific treatment for roseola. Antipyretics can be used for fever. Patients with severe disease or immunocompromised hosts may benefit from administration of ganciclovir, foscarnet, or cidofovir.37,38 If an infant presents with a febrile seizure and the appropriate diagnostic studies reveal no source, it is prudent to inform parents that the child may have the roseola exanthem after the fever subsides. Erythema Infectiosum (Fifth Disease) Erythema infectiosum (fifth disease) is a viral infection caused by human parvovirus B19, which causes an intense,

850

SECTION IV — Approach to the Acutely Ill Patient

Table 123–2

Differential Diagnosis of Roseola Infantum

Echovirus 16 Epstein-Barr virus Adenovirus Cytomegalovirus Parvovirus B19 Rubella Measles Parainfluenza virus

confluent erythema on both cheeks, followed by a lacy rash on the rest of the body.39 Human parvovirus B19, a singlestranded DNA virus, has been isolated within the skin lesions of patients with erythema infectiosum.39 The organism replicates in erythroid bone marrow cells, accounting for its role in red-cell aplasia of immunodeficient patients or those with chronic hemolytic anemia.40 It occurs more frequently in winter and spring. It can present at any age but is most common in children 4 to 10 years of age.41 Transmission is via respiratory droplets or blood products, or vertically from mother to fetus. The incubation period is 6 to 14 days but can be as long as 21 days, and patients are contagious prior to the start of the eruption and up to 7 days posteruption.

FIGURE 123–5. Slapped-cheek appearance of erythema infectiosum.

Table 123–3

Differential Diagnosis of Erythema Infectiosum

Differential Diagnosis

Causes

Viruses

Echovirus Rubella Epstein-Barr virus Measles Coxsackievirus Dengue Hepatitis Scarlet fever

Clinical Presentation In most patients the first reported manifestation is the characteristic rash. Prodromal symptoms may occasionally occur, and include low-grade fever, coryza, headache, sore throat, chills, nausea, myalgias, and malaise. The exanthem of erythema infectiosum is divided into three stages. Initially a bright, fiery red macular erythema appears on the cheeks (“slapped-cheek” or “sunburned” appearance) (Fig. 123–5). It is often associated with a rim of sparing around the nose and mouth (“circumoral pallor”). The second stage occurs 1 to 4 days later when the rash may spread to involve the arms, legs, chest, and abdomen. It consists of a pink to dull red macular eruption. Fading of the central portion gives a lacy, reticulate pattern. Pruritus is unusual.42 The third stage varies in duration from 1 week to several weeks and is characterized by waxing and waning intensity of the eruption. The exanthem generally lasts from 3 to 5 days, but may last up to 4 months.39,40 The rash increases in intensity from vigorous exercise, overheating of the skin, sun exposure, or crying. Occasionally, morbilliform, vesicular, or purpuric skin eruptions are seen. A purpuric hand and foot eruption (purpuric gloves-and-socks syndrome) may develop.39,43 The differential diagnosis may include drug reactions, other viral entities, and collagen vascular diseases (Table 123–3). Diagnosis can be confirmed by analysis of serum obtained within 30 days of the onset of illness for the presence of immunoglobulin M B19 antibodies via ELISA or radioimmunoassay.44 For immunocompromised hosts with chronic infection, nucleic acid hybridization or PCR assays are recommended.45 Symmetric arthritis of the hands, wrists, or knees has been described, especially in adolescent and adult females.22,40,46 The STAR complex is caused by parvovirus B19 as often as by rubella.22 Joint symptoms usually resolve by 1 to 2 months. Joint involvement worsens over the day.

Bacteria Drug eruption Collagen vascular disease

Polyarteritis nodosa Lupus erythematosus Juvenile rheumatoid arthritis

Unusual complications may include encephalopathy, aseptic meningitis, neuropathy, cerebellar ataxia, seizures, myocarditis, and hepatitis.47 In children with acquired or hereditary hemolytic anemias or any condition that results in red blood cell destruction (i.e., hereditary spherocytosis, sickle cell disease, glucose-6-phosphate dehydrogenase deficiency, pyruvate kinase deficiency) or decreased red blood cell production (i.e., iron deficiency anemia or thalassemia), parvovirus B19 is associated with a poorer prognosis and results in transient aplastic crisis.40,48 It can occur under conditions of erythroid stress, such as during hemorrhage, during a state of iron deficiency anemia, and following kidney or bone marrow transplant. These episodes are accompanied by symptoms of anemia, such as dyspnea, lassitude, and confusion, and can last 10 to 15 days. Rarely congestive heart failure develops, which can be fatal. In immunocompromised patients, such as those with human immunodeficiency virus infection, congenital immunodeficiencies, acute leukemia, organ transplants, or systemic lupus erythematosus, or in infants less that 1 year old, parvovirus B19 can cause a serious, prolonged chronic anemia due to persistent lysis of red blood cell precursors and bone marrow suppression. In pregnant women, parvovirus B19 infection may result in fetal anemia, high-output cardiac failure,

Chapter 123 — Classic Viral Exanthems

851

pleural effusions, polyhydramnios, nonimmune hydrops fetalis, and fetal demise.48-50 Fetal loss occurs in 8% to 10% of pregnancies complicated by parvovirus and is highest if infection is acquired prior to 20 weeks’ gestation.51,52 Management There is no specific treatment for erythema infectiosum. Isolation for 2 weeks of patients at risk for complications, such as pregnant women, immunosuppressed patients, or patients with chronic hemolytic anemia, is recommended. Administration of intravenous (IV) immune globulins may be used in these high-risk groups,53 leading to a marked increase in reticulocyte counts and corresponding rise in hemoglobin. Blood transfusions may be required. Those with arthritis symptoms may gain relief with nonsteroidal anti-inflammatory drugs. The risk of exposure should be explained to pregnant females, and serologic testing offered. If acute infection is confirmed, serial fetal ultrasonography should be performed, assessing for congestive heart failure, IUGR, or fetal hydrops. Management of severely affected fetuses has included in utero blood transfusion.

FIGURE 123–6. Herpetic gingivostomatitis: vesicular lesions on the lips and oral mucosa from herpes simplex virus.

Herpes Simplex (Human Herpesvirus 1 and 2 Infections) Grouped vesicles on an erythematous base are the characteristic lesions of herpes simplex virus (HSV) in the skin, regardless of location.54 On mucous membranes, the blister roof is easily shed and an erosion is seen. The infection may be primary or recurrent.54 Initial infection is termed primary if it occurs in a host with no prior HSV infection or recurrent in a host previously infected with HSV. Recurrent infections represent reactivation of latent herpesvirus. Human herpesvirus 1 (HHV-1, or herpes simplex virus 1 [HSV-1]) and human herpesvirus 2 (HHV-2, or herpes simplex virus 2 [HSV-2]) are double-stranded DNA viruses. They are epidermotropic, and productive viral infection occurs within keratinocytes. Initial infection is characterized by viral replication at the initial site of contact, such as skin, mucous membranes, or eyes. The virus then travels along the regional nerves to the ganglia and establishes a latent infection, where it remains for life. The incubation period ranges from 2 days to 2 weeks. Transmission in neonates is during birth through contact with an infected maternal genital tract, or by direct contact with infected oral secretions or lesions. Clinical Presentation After initial exposure, HSV may persist in nerve ganglia and be reactivated by a number of factors, including fever, emotional disturbances, ultraviolet light, menses, and trauma.54,55 Once recurrent skin involvement appears, the disease is contagious and can be transmitted to other areas of the skin or to other persons. Sites of involvement vary, but the most common are the lips, eyes, cheeks, and hands.54,55 Regional lymphadenopathy may occur in all forms of herpes simplex. Distinct clinical features of the various types are listed in Table 123–4 and shown in Figures 123–6 through 123–9. Herpes virus may be recovered from vesicles during the first 24 hours after their appearance. Other locations for recovery include conjunctivae, nasopharynx, rectum, urine, cerebrospinal fluid, and blood.56 A Tzanck preparation (scraping from an intact blister treated with Geimsa or

FIGURE 123–7. Herpes labialis: grouped vesicles on the lips.

Wright stain) will show the characteristic epidermal giant cells. Rapid diagnostic tests using direct fluorescent antibody or dye-labeled monoclonal antibodies are 90% accurate.57 Some institutions may perform a PCR for detection of HSV DNA, especially in the setting of CNS infection.58 Many other viruses and diseases should be considered in the differential diagnosis of herpes simplex (Table 123–5). The most common complication is secondary bacterial superinfection. Immunosuppressed patients or pregnant patients may have disseminated disease involving multiple organs, including the liver, lung, brain, heart, and adrenal glands. It presents as a sepsis-like syndrome with jaundice, progressive hepatosplenomegaly, hepatitis, poor feeding, dyspnea, pneumonia, adrenal necrosis, hypothermia, seizures, encephalitis, evidence of disseminated intravascular coagulopathy, and death, which may occur in 48 to 96 hours. Management Oral acyclovir, famciclovir, valcyclovir, or penciclovir, foscarnet, or cidofovir are specific therapies for localized cutaneous herpes simple infections54 (Table 123–6). Antiviral

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Table 123–4

Clinical Features of Herpes Simplex Virus (HSV) Disease in Children

Forms of HSV

Clinical Features

Herpes Gingivostomatitis (caused by HSV-1)

Most frequent clinical presentation of primary HSV infection in children (6 mo–5 yr) Transmitted by infectious saliva Incubation: 2–12 days Primary form: fever, irritability, malaise, refusal to eat or drink Vesicular lesions on tongue, buccal mucosa, gingiva, and palate (Fig. 123–6) become eroded and ulcerated, appearing as 1- to 3-mm shallow gray ulcers on a red base; gums become mildly swollen, red, ulcerated, exudative, and friable. Tender submandibular and cervical lymphadenopathy are common. Dehydration is the most common complication.83 Acute disease lasts 3–7 days but may persist up to 3 wk. Fever, malaise, odynophagia, and headache Vesiculoulcerative lesions develop on tonsils and pharynx. Recurrent infection of the lip Occurs in up to 20% of infants and children54 Prodrome of pain, tingling, or itching Grouped vesicles on one portion of the lip, usually lower, typically follow an acute febrile illness or intense sun exposure. Lesions last up to 8 days. Corneal involvement in 12 yr) 1000 mg PO 1–2 times per day for 7–10 days Abbreviations: IV, intravenously; PO, orally.

FIGURE 123–8. Herpes keratitis: grouped vesicles with crusting.

FIGURE 123–9. Herpetic whitlow: superficial vesiculopustules.

Table 123–5

Differential Diagnosis of Herpes Simplex Infection

Differential Diagnosis

Causes

Viruses

Varicella-zoster virus Coxsackievirus (herpangina) Orf Influenza Echovirus Variola Vaccinia Erythema multiforme Aphthous ulcers Vincent’s infection Behçet’s syndrome Allergic contact dermatitis Impetigo Bacterial or other viral conjunctivitis Streptococcal blistering distal dactylitis Burns

Disease

agents given within 72 hours of the onset of the rash decrease severity or duration of the infection and are associated with less feeding difficulty and shorter duration of viral shedding. However, famciclovir, valcyclovir, foscarnet, and cidofovir are not approved for use in children. In neonatal HSV, IV acyclovir is efficacious. The dose for preterm infants of 34 to 36 weeks’ gestation is 10 mg/kg per dose IV every 8 hours, and that for premature infants less

than 34 weeks’ gestation, 10 mg/kg per dose IV every 12 hours. The dose for term infants is 20 mg/kg per dose IV every 8 hours for 14 days. For infants with encephalitis or disseminated HSV, recommended treatment is up to 21 days. Although most neonates with encephalitis survive, most have substantial neurologic sequelae. Approximately 25% of neonates with disseminated disease die despite treatment. Supportive measures, such as fever control, maintenance of fluid and electrolyte balance, and thermal regulation, should be instituted immediately. Infected patients must be isolated as they shed virus. Pain relief should be provided for gingivostomatitis with acetaminophen and an analgesic mouth wash (equal parts of aluminum hydroxide and diphenhydramine plus viscous xylocaine added when age appropriate, but this should be done with extreme caution since as little as 1–2 ml may be toxic in young children), which is applied with a cotton swab onto lesions or, in older children, rinsed and expectorated. Patients should avoid citrus fruits and spicy or hot liquids. Careful daily ophthalmologic follow-up is required for ocular keratitis. Corticosteroid therapy, either topical or systemic, should be avoided. Topical corticosteroids may be required after several days of antiviral therapy in patients with marginal ulcers or associated stromal disease, but these agents should be given only in consultation with an ophthalmologist. Antiviral agents may include trifluridine (1%) drops, vidarabine (3%) ointment, 0.1% iododeoxyuridine, or acyclovir ophthalmic ointment. In severe cases, oral or IV acyclovir or vidarabine and a cycloplegic may be required.59 Disseminated infections require hospitalization and intensive supportive therapy. Treatment of genital herpes consists of warm sitz baths, topical anesthetics, oral analgesics, wet compresses with aluminum acetate (Burow’s solution), and topical antibacterial ointment to prevent secondary infection. For severe cases, oral acyclovir can accelerate healing and shorten duration of symptoms and viral shedding.60 The majority of children with HSV require supportive care, and follow-up is indicated in cases in which the lesions persist or in patients who are hospitalized with severe disease. Varicella-Zoster Virus (Human Herpesvirus 3 Infections) Varicella-zoster virus (VZV) or human herpesvirus 3 (HHV3) is a double-stranded DNA virus producing an abrupt onset of crops of grouped vesicles.61,62 It is highly contagious, with an incubation period of 14 to 16 days (range 10 to 21 days)26 and occurs primarily in children from 2 to 8 years old, with 90% of cases occurring before the age of 14 years. It is most prevalent in late winter and early spring. The disease is spread through person-to-person contact and airborne spread, and occurs from 1 to 2 days before the onset of rash to 5 to 6 days

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after onset or when lesions have crusted.62 Transplacental infection may also occur. HHV-3 enters via the respiratory route and replicates in the lymph nodes. Viremia follows with entry into reticuloendothelial cells. A second viremia results in spread into the skin and organs. In keratinocytes, HHV-3 produces ballooning degeneration of cells and an interepidermal blister. Primary infection is known as chickenpox. After an initial varicella infection, the VZV remains dormant in cells of the dorsal root ganglia or cranial nerve ganglia until reactivation. Subsequent propagation of the virus along the nerve to the skin gives rise to grouped vesicles. The reactivation stage is known as herpes zoster or shingles.61,62 Reactivation may result from reexposure to varicella, physical trauma to the spinal column, radiation therapy, immunosuppressant drugs, cancer, leukemia, or Hodgkin’s lymphoma. Clinical Presentation A prodrome consists of low-grade fever, malaise, headache, anorexia, cough, coryza, and sore throat. In normal children, systemic symptoms are mild and serious complications are rare. In immunocompromised patients, the disorder is more likely to be characterized by an extensive eruption that is often hemorrhagic, severe constitutional symptoms, and occasionally pneumonia and death.63 Individual lesions begin as faint erythematous macules that progress to edematous papules and then to delicate vesicles (“dewdrop on a rose petal”) within 24 to 48 hours (Figs. 123–10 and 123–11). The exanthem usually begins on the scalp, face, and trunk and less commonly on the extremities. Intense pruritus commonly accompanies the vesicular stage of the rash. The vesicles develop moist crusts that dry and are shed, leaving a shallow erosion. Successive crops of lesions appear during the next 2 to 5 days, so that at any one time several stages of skin lesions can be seen concomitantly. The lesions spread centripetally. Lesions frequently involve mucous membranes, and isolated erosions may be seen in the conjunctiva, oral muscosa, or nasal cavity and occasionally in the vagina.62 Lesions may vary from as few as 10 to greater than 100. The lesions disappear in 7 to 10 days and usually heal without scarring. In patients with thrombocytopenia, lesions may appear hemorrhagic.64 While smallpox has been eradicated, there is still concern regarding its use as a biological terrorism agent. In contrast to varicella, it causes a vesicular rash that evolves at the same rate for all lesions as opposed to the successive crops that occur with chickenpox. Herpes zoster in prepubertal children is usually mild. Neuralgia, common in the elderly, is rarely seen in children and occasionally occurs in adolescents. Maternal varicella infection during pregnancy and varicella occurring in the newborn period represent risk factors for childhood herpes zoster. Malaise, headache, and fever may precede the rash, especially in young children. Herpes zoster is a unilateral eruption that involves one to three dermatomes, most commonly the thoracic and the ophthalmic branch of the trigeminal nerve (Fig. 123–12). Infection of the ophthalmic branch of the Vth cranial (trigeminal) nerve may involve the cornea with keratitis and uveitis and lead to permanent damage (zoster ophthalmicus). It is suspected when the nasociliary branch is involved and, accordingly, is present in those who have cutaneous involvement of the nose

FIGURE 123–10. Papules, vesicles, and pustules seen in varicella-zoster virus infection.

(Hutchinson’s sign). Involvement of the geniculate ganglion results in pain in the ear with vesicles on the pinnae, tongue, ear, and skin of the auditory canal. When accompanied by facial palsy and disturbances of hearing and equilibrium, it is part of the Ramsay Hunt syndrome (Fig. 123–13). In herpes zoster, grouped lesions appear within several adjacent dermatomes. They begin as macules and edematous papules and progress to vesicles on an erythematous base. Intense pruritus occurs during the vesicular stage. As the eruption resolves, vesicles open up, become crusted, and slowly heal. The eruption tends to appear first at a point nearest the CNS and extends peripherally along the course of the nerve, thus producing the characteristic bandlike distribution of lesions. Generally the eruption is unilateral, but it may cross the midline and, at times, may involve the contralateral side. Successive crops continue to appear from 5 to 7 days. They resolve by crusting over in the course of another 7 to 10 days, and occasionally up to 3 weeks. In children, rarely dermatomal pain may precede the eruption. Typical varicella is seldom confused with other illnesses, but some viruses may mimic the lesions (Table 123–7). HHV-3 may be recovered from the vesicles during the first 72 hours after the onset of the eruption. A Tzanck

Chapter 123 — Classic Viral Exanthems

Table 123–7

855

Differential Diagnosis of Varicella

Coxsackievirus (hand-foot-and-mouth disease) Herpes simplex virus Insect-bite reactions (popular urticaria) Erythema multiforme Parapsoriasis Rickettsialpox Dermatitis herpetiformis Smallpox (variola) Vaccinia

FIGURE 123–11. Different stages of lesions seen in varicella-zoster virus infection, consisting of macules, papules, vesicles (“dewdrop on a rose petal”), and crusting of vesicles.

FIGURE 123–12. Herpes distribution.

zoster

in

the

thoracic

dermatomal

preparation (scraping from an intact blister treated with Geimsa or Wright stain) will show the characteristic epidermal multinucleated giant cells containing intranuclear viral inclusions. Direct fluorescent antibody examination using a swab specimen taken from the base of a freshly opened lesion can distinguish HSV from HZV. Other laboratory tests include fluorescent antibody to membrane antigen, neutralization test, latex agglutination, ELISA, and demonstration of VZV DNA from vesicular fluid with PCR; identification of viral particles by direct electron microscopy; and serologic studies of acute and convalescent sera for VZV antibody.65 Laboratory abnormalities usually show leukocytosis and elevated hepatic transaminases. Secondary bacterial infection of varicella skin lesions is common.66 It is generally caused by Staphylococcus aureus or group A β-hemolytic streptococci. The presence of fever after 4 or 5 days of illness or unusually indurated skin lesion should alert the clinician to the possibility of cellulitis. Lifethreatening toxic shock syndrome, gangrenous cellulitis, and necrotizing fasciitis have all been described.67 Data suggest that the use of ibuprofen may be associated with necrotizing fasciitis.68 Pneumonia may complicate varicella, especially in adolescents. Other complications include otitis media, Reye’s syndrome, acute postinfectious cerebellar ataxia, encephalitis, aseptic meningitis, transverse myelitis, Guillain-Barré syndrome, arthritis, nephritis, carditis, myositis, appendicitis, orchitis, nephritis, hepatitis, purpura fulminans, and thrombocytopenia.69,70 In immunocompromised patients or those with Hodgkin’s lymphoma or leukemia, hematogenous spread of herpes zoster occurs 1 to 5 days after the dermatome infection begins.71 This results in a generalized eruption. Most children recover without sequelae, but visceral involvement can occur. Some may have severe disease with high fever, encephalitis, pneumonia, hepatitis, or disseminated intravascular coagulation.62 Congenital varicella syndrome occurs in 2% of infants in whom exposure to varicella occurred during the first or second trimester. It consists of IUGR, microcephaly, cortical atrophy, limb hypoplasia, microphthalmia, cataracts, micrognathia, chorioretinitis, and cutaneous scarring.72 Management

FIGURE 123–13. Ramsay Hunt syndrome with herpes zoster involving the ophthalmic branch of the trigeminal nerve.

Healthy children with varicella do not require specific therapy. Treatment is supportive and aimed at decreasing pruritus and minimizing the risk of secondary infection. Wet dressing, soothing baths, and calamine lotion with oral antihistamines will provide symptomatic relief of pruritus.73 Topical antihistamines containing diphenhydramine have the potential to cause sensitization and should probably be avoided. Acetaminophen can be used to control fever or pain; salicylates should be avoided due to the associated risk of

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Reye’s syndrome. Secondary bacterial infection is treated with antistaphylococcal drugs such as cephalexin, amoxicillin/clavulanate, or dicloxacillin. In penicillin-allergic patients, azithromycin, clarithromycin, or clindamycin can be used. In immunocompetent hosts, most viral replication stops 72 hours after the onset of the eruption; however, it is extended in immunocompromised hosts. Oral acyclovir is not recommended for routine use in otherwise healthy children with varicella. Systemic antiviral agents, such as acyclovir and vidarabine, have been used with success in children.74-76 If given within the first 24 hours of the exanthema, they can shorten the duration and magnitude of fever, accelerate healing time, and decrease the number of skin lesions. Since VZV is less sensitive to acyclovir than HSV, levels of acyclovir two to eight times greater are required. Oral acyclovir should be considered for patients at increased risk for moderate to severe varicella, such as those less than 6 months old or greater than 12 years old, those with chronic cutaneous or pulmonary disease, those on long-term salicylate therapy or corticosteroids, immunocompromised children, and children with ophthalmic involvement, Ramsay Hunt syndrome, disseminated zoster, and possible pregnancy. Children on corticosteroids or other immunosuppressive agents and exposed to varicella should have the dosages of these drugs reduced or discontinued whenever possible. Passive immunization with varicella-zoster hyperimmune globulin has been shown to modify or prevent illness in highrisk individuals if given with 48 to 72 hours of exposure.73,74 It is recommended for patients with immunodeficiencies, leukemia, or lymphoma, and in those receiving chemotherapy or other immunosuppressive agents, with seronegative pregnancy, or with disseminated disease. It is indicated for newborns whose mothers have developed primary varicella within 5 days before or 2 days after delivery and in neonates who develop varicella by the 10th day of life, as they are at increased risk of disseminated, fulminant infection. In the rare case of postherpetic neuralgia, treatment consists solely of analgesics. Analgesics used primarily in adults have included tricyclic antidepressants, gabapentin, lidocaine patch, opioids, and capsacin, but none of these has been studied for use in children.77 All patients with complications such as fasciitis, Reyes’s syndrome, pneumonia, or encephalitis should be hospitalized. The highly contagious nature of the infection should be emphasized, and child should be isolated until the lesions are crusted, which usually occurs 5 to 7 days after the eruption occurs. A follow-up visit within 48 hours should be scheduled for children who are discharged home from the emergency department to assess for any development of secondary bacterial infection. Children with disseminated zoster, ophthalmic zoster, or Ramsay Hunt syndrome should be seen daily until symptoms resolve.

excretion in feces persisting for 2 weeks. Coxsackievirus is transmitted transplacentally, by direct contact with nasal or oral secretions, through fecal material, or in aerosolized droplets. It is more prevalent during late summer or early fall. The virus enters the buccal or ileal mucosa and spreads to the lymph nodes. Viremia ensues with spread to the oral mucosa and skin. By day 7 after infection, serum antibody levels increase, and the virus disappears. Clinical Presentation A brief prodrome may occur, characterized by low-grade fever, anorexia, abdominal pain, cough, mouth soreness, and malaise, followed by the appearance of the enanthem and exanthem. The enanthem is the most characteristic finding and begins as small red macules that evolve into small vesicles, 1 to 3 mm to 2 cm in diameter, that rapidly rupture to leave behind erosions and ulcers superimposed on an erythematous base. They occur over the buccal mucosa and tongue as well as the palate, uvula, gingiva, and anterior tonsillar pillars (Fig. 123–14). These lesions are painful, and children refuse to eat or drink; therefore, dehydration is a common sequela. The exanthem is maculopapular at first, then evolves into gray-white vesiculopustules ranging from 3 to 7 mm in diameter, with variable amounts of associated erythema. They are thin walled and contain a clear fluid, sometimes coalesce to form bullae, and are occasionally tender or pruritic. Lesions are usually elliptical or football shaped and surrounded by a red areola, and are found most commonly on the palms and soles, less often on the dorsal or lateral surfaces of the hands and feet, and occasionally on the buttocks and perineum (Fig. 123–15). Lesions clear within 2 to 7 days. Children with coxsackievirus infection are generally not ill appearing. Other findings include occasional lymphadenopathy in submandibular and cervical regions. In the early nonvesicular stage, rubella and other morbilliform lesions must be considered, and in the vesicular stage the disease can be mistaken for varicella. The enanthem may be mistaken for several other entities (Table 123–8). Occasionally coxsackievirus infections may cause myocarditis, pneumonia, meningoencephalitis, and aseptic meningitis.79,80 In addition, there have been reports of fatal cases from enterovirus 71.81 Infection in the first trimester may lead to spontaneous abortion or IUGR.

Coxsackievirus (Hand-Foot-and-Mouth Disease) Abrupt onset of scattered papules that progress to oval or linear vesicles in an acral distribution with oral involvement suggests hand-foot-and-mouth disease. The epidemic form is almost always caused by coxsackievirus A16 or enterovirus 71, but coxsackieviruses A2, A4 through A7, A9, A10, B1 through B3, and B5 have also been isolated.78 The incubation period is 3 to 6 days, and patients are highly contagious from 2 days before to 2 days after onset of the eruption, with viral

FIGURE 123–14. Vesicles and erosions seen on the palate in coxsackievirus infection (hand-foot-and-mouth syndrome).

Chapter 123 — Classic Viral Exanthems

A

857

B FIGURE 123–15. Elliptical vesicles seen on the hands (A) and feet (B) in coxsackievirus infection (hand-foot-and-mouth syndrome).

Table 123–8

Differential Diagnosis of the Enanthem of Coxsackievirus Infection

Varicella Aphthous ulcers Erythema multiforme Herpes simplex virus Herpangina

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30. Yamanishi K, Okuno T, Shiraki K, et al: Identification of human herpesvirus 6 as a casual agent for exanthema subitum. Lancet 1:1065– 1067, 1988. 31. Tanaka K, Kondo T, Torigoe S, et al: Human herpesvirus 7: another casual agent for roseola (exanthema subitum). J Pediatr 125:1–5, 1994. 32. Asano Y, Yoshikawa T, Suga S, et al: Clinical features of infants with primary human herpesvirus 6 infection (exanthema subitum, roseola infantum). Pediatrics 93:104–108, 1994. 33. Adams O, Krempe C, Kogler G, et al: Congenital infections with human herpesvirus 6 infection in young children. N Engl J Med 326:1445–1450, 1992. 34. Teach SJ, Wallace HL, Evans MJ, et al: Human herpesvirus types 6 and 7 and febrile seizures. Pediatr Neurol 21:699–703, 1999. 35. Barone SR, Kaplan MH, Krilov LR: Human herpesvirus-6 infection in children with fi rst febrile seizures. J Pediatr 127:95–97, 1995. 36. Yoshikawa T, Nakashima T, Suga S, et al: Human herpesvirus-6 DNA in cerebrospinal fluid in a child with exanthema subitum and meningoencephalitis. Pediatrics 89:888–890, 1992. 37. Burns WH, Sandford GR: Susceptibility of human herpesvirus 6 to antivirals in vitro. J Infect Dis 162:634–637, 1990. 38. Safrin S, Cherrington J, Jaffe HS: Clinical uses of cidofovir. Rev Med Virol 7:145–156, 1997. 39. Seishima M, Kanoh H, Izumi T: The spectrum of cutaneous eruptions in 22 patients with isolated serological evidence of infection by parvovirus B19. Arch Dermatol 135:1556–1557, 1999. 40. Barton RB: Parvovirus B19: twenty-five years in perspective. Pediatr Develop Pathol 2:296, 1999. 41. Anderson LJ: Role of parvovirus B19 in human disease. Pediatr Infect Dis 6:711–718, 1987. 42. Stiefel L: Erythema infectiosum (fi fth disease). Pediatr Rev 16:474– 475, 1995. 43. Ongradi J, Becker K, Horvath, A, et al: Simultaneous infection by human herpesvirus 7 and human parvovirus B19 in papular-purpuric gloves-and-socks syndrome. Arch Dermatol 136:672, 2000. 44. Chen MY, Lee KL, Hung CC: Imunoglobulin M and G immunoblots in the diagnosis of parvovirus B19 infection. J Formos Med Assoc 99:24, 2000. 45. Cherry JD: Parvovirus infections in children and adults. Adv Pediatr 46:245–269, 1999. 46. Moore TL: Parvovirus-associated arthritis. Curr Opin Rheumatol 12:289–294, 2000. 47. Heegaard ED, Hornsleth A: Parvovirus: the expanding spectrum of disease. Acta Paediatr 84:109–117, 1995. *48. Heegaard ED, Brown KE: Human parvovirus B19. Clin Microbiol Rev 15:485–505, 2002. 49. Gilbert GL: Parvovirus B19 infection and its significance in pregnancy. Commun Dis Intell 24:69, 2000. 50. Anand A, Gray ES, Brown T, et al: Human parvovirus infection in pregnancy and hydrops fetalis. N Engl J Med 316:183–186, 1987. 51. Gratacos E, Torres PJ, Vidal J, et al: The incidence of human parvovirus B19 infection during pregnancy and its impact on perinatal outcome. J Infect Dis 171:1360–1363, 1995. 52. Miller E, Fairley CK, Cohen BJ, et al: Immediate and log term outcome of human parvovirus B19 infection in pregnancy. Br J Obstet Gynecol 105:174–178, 1998. 53. Koch WC, Massey G, Russell CE, et al: Manifestations and treatment of human parvovirus B19 infection in immunocompromised patients. J Pediatr 116:355–359, 1990. 54. Whitley RJ: Herpes simplex virus infection. Semin Pediatr Infect Dis 186(Suppl 1):S40–S46, 2002. 55. Jones VF, Badgett JT, Marshall GS: Repeated photoreactivation of herpes simplex virus type 1 in an extrafacial dermatomal distribution. Pediatr Infect Dis J 13:238, 1994. 56. Jacobs RF: Neonatal herpes simplex virus infections. Semin Perinatol 22:64–71, 1998. 57. Goodyear HM: Rapid diagnosis of cutaneous herpes simplex infections using specific monoclonal antibodies. Clin Exp Dermatol 19:294, 1994. 58. Troendle-Atkins J, Demmler GJ, Buffone GJ: Rapid diagnosis of herpes simplex virus encephalitis by using polymerase chain reaction. J Pediatr 123:376–380, 1993. 59. Flowers FB, Araujo OE, Turner LA: Recent advances in antiherpetic drugs. Int J Dermatol 27:612–616, 1988.

60. Mertz GJ, Critchlow CW, Benedetti J, et al: Double-blind placebocontrolled trial of oral acyclovir in first-episode genital herpes simplex virus infection. JAMA 252:1147–1151, 1984. 61. Takayama N, Takayama M, Takita J: Herpes zoster in healthy children immunized with varicella vaccine. Pediatr Infect Dis J 19:169, 2000. 62. Arvin AM: Chickenpox (varicella). Contrib Microbiol 3:96, 1999. 63. Feldman S, Hughes WT, Daniel CB: Varicella in children with cancer: seventy-seven cases. Pediatrics 56:388–397, 1975. 64. Charkes ND: Purpuric chickenpox: report of a case, review of the literature and classification by clinical features. Ann Intern Med 54:745, 1961. 65. Nahass GT, Goldstein BA, Zhu W-Y, et al: Comparison of Tzanck smear, viral culture, and DNA diagnostic methods in detection of herpes simplex and varicella-zoster infection. JAMA 268:2541, 1992. 66. Bullovwa JGM, Wishik SM: Complications of varicella. I. Their occurrence among 2,534 patients. Am J Dis Child 49:923, 1935. 67. Smith EWP, Garson A, Boyleston JA, et al: Varicella gangrenosa due to group A beta-hemolytic streptococcus. Pediatrics 57:306, 1976. 68. Zerr DM, Alexander ER, Duchin JS, et al: A case-control study of necrotizing fasciitis during primary varicella. Pediatrics 103:783–790, 1999. 69. Orlowski JP, Gilis J, Kilham HA: A catch in the Reye. Pediatrics 80:638–642, 1987. 70. Preblud SR, Orenstein WA, Bart KJ: Varicella: clinical manifestations, epidemiology and health impact in children. Pediatr Infect Dis 3:505, 1984. 71. Keiden SE, Mainwaring D: Association of herpes zoster with leukemia and lymphoma in children. Clin Pediatr 4:13–17, 1965. 72. Derrick CW Jr, Lord L: In utero varicella-zoster infections. South Med J 91:1064–1066, 1998. 73. Arvin AM: Management of varicella-zoster infections in children. Adv Exp Med Biol 458:167, 1999. 74. Lin F, Hadler JL: Epidemiology of primary varicella and herpes zoster hospitalization: the pre-varicella vaccine era. J Infect Dis 181:1897, 2000. 75. White R, Hilty M, Haynes R, et al: Vidarabine therapy of varicella in immunosuppressed patients. J Pediatr 101:125, 1982. 76. Prober CG, Kirk LE, Keeney RE: Acyclovir therapy of chickenpox in immunosuppressed children—a collaborative study. J Pediatr 101:622, 1982. 77. Dworkin RH, Schmader KE: Treatment and prevention of postherpetic neuralgia. Clin Infect Dis 36:877–882, 2003. 78. Lindenbaum JE, Van Dyck PC, Allen RG: Hand, foot and mouth disease associated with coxsackievirus group B. Scand J Infect Dis 7:161–163, 1975. 79. Tindall JP, Miller GD: Hand, foot and mouth disease. Cutis 9:457–463, 1972. 80. Wright HT Jr, Landing BH, Lenette EH, et al: Fatal infection in an infant associated with Coxsackie virus group A type 16. N Engl J Med 268:1041–1044, 1963. 81. Shimizu H, Utama A, Yoshii K, et al: Enterovirus 71 from fatal and nonfatal cases of hand, foot, and mouth disease epidemics in Malaysia, Japan, and Taiwan in 1997–1998. Jpn J Infect Dis 52:12, 1999. 82. Robart HA, McCracken GH, Whitley RJ, et al: Clinical significance of enteroviruses in serious summer febrile illnesses of children. Pediatr Infect Dis J 18:869–874, 1999. 83. Amir J, Harel L, Smetana Z, et al: The natural history of primary herpes simplex type 1 gingivostomatitis in children. Pediatr Dermatol 16:259– 263, 1999. 84. Dworkin MS, Shoemaker PC, Spitters C, et al: Endemic spread of herpes simplex virus type 1 among adolescent wrestlers and their coaches. Pediatr Infect Dis J 18:1108–1109, 1999. 85. ACOG practice bulletin: management of herpes in pregnancy. Clinical management guidelines for obstetrician-gynecologists. Int J Gynaecol Obstet 68:165–173, 2000. 86. Bale JF Jr: Human herpesvirus and neurological disorders of childhood. Semin Pediatr Neurol 6:278, 1999. 87. Kimberlin D: Herpes simplex virus, meningitis and encephalitis in neonates. Herpes 11(Suppl 2):65A–76A, 2004. 88. Kohl S: Neonatal herpes simplex virus infection. Clin Perinatol 24:129–150, 1997.

Chapter 124 Dermatitis Antonio E. Muñiz, MD

Key Points The main treatment for atopic dermatitis is topical corticosteroids. Diaper dermatitis of longer than 3 days’ duration is usually superinfected with Candida. Seborrheic dermatitis responds to tar shampoos and ketoconazole topically and only occasionally requires topical corticosteroids. Removal of the offending agent responsible for the eruption in contact dermatitis is curative, but symptomatic treatment includes corticosteroids and antihistamines.

AD occurs during the first year of life in 60% of patients, generally appearing at 2 to 6 months of age. Approximately 70% to 95% develop AD by the age of 5 years. The lifetime prevalence of AD is 5% to 20% in children and 1% to 3% in adults.1 There are three distinct phases of AD, in which both the location and morphology of the lesions change with age.2-5 The infantile phase occurs in children up to 2 years of age; the childhood phase from 2 years of age to puberty; and the adult phase from puberty onward. The etiology of AD is still unknown; however, atopic dry skin is characterized by a decrease in skin lipids, an altered water-binding capacity of the stratum corneum, and increased transepidermal water loss with marked skin dehydration.6 This impaired barrier function leads to increased skin irritability with subsequent scratching, which leads to the development of the typical lesions of AD. An immunologic etiology also has been suggested because many children with AD have chronic elevation of immunoglobulin E.6a Clinical Presentation

Selected Diagnoses Atopic dermatitis Diaper dermatitis Seborrheic dermatitis Contact dermatitis

Discussion of Individual Diagnoses Atopic Dermatitis Atopic dermatitis (AD) is a chronic, inherited, relapsing skin condition characterized by xerosis, pruritus, inflammation, and lichenification. Associated findings include a family history of AD, asthma, or allergic rhinitis. Eczema (“boiling over”) in the acute setting refers to a morphology of erythema, scaling, vesicles, and crusts. In the chronic state, eczema refers to a morphology of scaling, lichenification, and pigmentary changes (either hypo- or hyperpigmentation). Eczematous lesions are found in conditions other than AD, including seborrheic dermatitis, contact dermatitis, scabies, autosensitization reactions, tinea pedis, immunodeficiencies, nummular eczema, dyshidrotic eczema, and lichen simplex chronicus. Eczema is essentially the morphologic skin finding to a number of different stimuli.

INFANTILE PHASE

The quintessential feature and morbidity of AD is pruritus from dry skin, which may be unbearable and interferes with daily activity and normal sleep patterns. The eruption begins on the cheeks, forehead, scalp, and lateral aspects of the extensor surfaces of the legs6 (Fig. 124–1). The trunk may also be involved (Fig. 124–2). The lesions are symmetric and ill defined, and consist of scaly, erythematous papules, patches, or vesicles that are sometimes covered with areas of crusting and excoriation. It spares the tip of the nose and the perioral and periorbital regions. Generalized xerosis is a prominent feature. CHILDHOOD PHASE

The flexural areas are the sites of predilection. The antecubital and popliteal fossae are most affected, with the neck, flexural surfaces of the wrists and ankles, and buttock and thigh creases also commonly involved. The lesions are pruritic, ill-defined, scaly, erythematous patches, often covered with crusts and excoriations (Fig. 124–3). The childhood phase is when lichenification (thickening of the skin and accentuated skin markings) is first observed and is most prominent in the antecubital and popliteal fossae and around the wrists (Figs. 124–4 and 124–5). Nummular 859

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FIGURE 124–1. Symmetrical scaly, erythematous papules, patches, and vesicles on the cheeks seen in the infantile phase of atopic dermatitis.

FIGURE 124–4. Lichenification seen in atopic dermatitis.

FIGURE 124–2. Symmetrical scaly, erythematous papules, patches, and vesicles on the cheeks and trunk seen in the infantile phase of atopic dermatitis.

FIGURE 124–5. Lichenification seen in atopic dermatitis.

ADULT PHASE

After the child reaches puberty, the lesions are once again located on the face, neck, and body, with a more diffuse distribution with erythema and scaling, but with less exudation. Xerosis and lichenification are prominent features. The face continues to have a typical central pallor. ASSOCIATED FINDINGS AND DIFFERENTIAL DIAGNOSIS FIGURE 124–3. Scaly, erythematous patches covered with crusts and excoriations seen on childhood phase of atopic dermatitis.

(coin-shaped) exudative patches may be seen. The nails maybe shinny and buffed and the eyebrows sparse and broken off from constant rubbing. In dark skin, the lesions are more papular with follicular accentuation and hyperpigmentation.

There are many associated findings with AD7-12 (Table 124– 1). Children with AD also have a tendency to develop secondary viral and bacterial skin infections. Herpes simplex virus infection is known as eczema herpeticum or Kaposi’s varicelliform eruptions13 (Fig. 124–6). The child is usually febrile and develops small, grouped vesicular lesions in the area of eczema, which subsequently spreads to normal skin. These vesicles form small erosions that crust over 24 to 48

Chapter 124 — Dermatitis

Table 124–1

861

Associated Findings in Atopic Dermatitis (AD)

Findings

Descriptions

Ichthyosis vulgaris Dennie-Morgan fold

Extensor surfaces of the extremities are dry, scaly, and hyperkeratotic. Extra crease line found under the lower eyelid. Originally thought to be pathognomonic for AD, but may be seen with other inflammatory conditions around the eye or in Down syndrome. Lateral thinning of eyebrows from rubbing Hyperpigmentation under the eyes caused by chronic edema, lichenification, and postinflammatory hyperpigmentation Exaggerated linear nasal crease caused by frequent rubbing of the nose Keratoconjunctivitis, which may occur in a painful form known as vernal conjunctivitis. Other eye findings include cataracts, keratoconus (elongation of corneal surface), and retinal detachment. The lesions consist of asymptomatic hyperkeratotic follicular papules (“chicken-skin appearance”). It is found on extensor aspects of upper arms and anterior aspects of the thigh. It begins early in life and improves with age. In young children, the lateral aspects of the cheeks near the hairline are often involved, which may be mistaken for acne. Slightly scaly and dry hypopigmented patches on the cheeks and upper trunk. The lesions are ill defined and often misdiagnosed as tinea corporis. Mainly seen in children 6–12 years of age, especially in warm weather when the rest of the face is tanned. The lesions consist of small pruritic, multiloculated vesicles. These rupture, leaving crusts and scales with erythema. It affects the palms, soles, and sides of the fingers and toes and is associated with hyperhidrosis. Scaling, cracking, and painful fissuring on both feet that markedly improves in puberty

Hertoghe’s sign Allergic shiners “Nasal salute” Eye findings Keratosis pilaris

Pityriasis alba Dyshidrotic eczema Juvenile plantar dermatitis

FIGURE 124–7. Secondary impetigo infection.

Chronic infection may lead to osteomyelitis. Infection with the nephritogenic M strain of streptococcus may lead to the development of glomerulonephritis. The differential diagnosis of AD includes other eczematous disorders (Table 124–2). Management

FIGURE 124–6. Infection with herpes simplex virus (eczema herpeticum) in a child with atopic dermatitis.

hours. Tzanck smears and viral cultures will confirm the diagnosis. Ninety-three percent of patients with AD have significant Staphylococcus aureus colonization of the skin.14 On occasion impetigo can occur in areas of eczema (Fig. 124–7). Widespread honey-colored crusting, erosions, oozing, follicular pustules, and furuncles suggest staphylococcal infection.

Effective management of AD hinges upon good rapport with the affected child and parents and education about the nature of the disease, potential aggravating factors to avoid, and treatment strategies.15 Bubble baths and excessive exposure to soap, shampoo, and detergents aggravate dryness and should be discouraged. However, daily bathing is no longer considered to be harmful for atopic dry skin. Bathing in lukewarm water for 5 to 15 minutes rehydrates the stratum corneum, although benefits are only seen if an emollient is applied immediately after leaving the water to prevent evaporation.16,17 Bathing once or twice daily is soothing during an acute flare, helps reduce bacterial counts, and aids in penetration of topical steroids applied after the bath. Soaps should be mild and unscented with a neutral pH (Dove, Oil of Olay, Caress, Camay, Aveeno, and Purpose). If soaps are too

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Table 124–2

Differential Diagnosis of Atopic Dermatitis

Scabies Seborrheic dermatitis Contact dermatitis Psoriasis Acrodermatitis enteropathica Agammaglobinemia Ataxia-telangiectasia Gluten-sensitive enteropathy Langerhans cell histiocytosis Hurler’s syndrome Hartnup syndrome Leiner’s disease Omenn’s syndrome Phenylketonuria Prolidase deficiency Wiskott-Aldrich syndrome Phenylketonuria Job’s syndrome Letterer-Siwe disease Mycosis fungoides Secondary syphilis

irritating to the skin, hydrophobic lotions or creams (Cetaphil, Diprobase, and Unguentum Merck) may be used. Many emollients are available that are suitable for use on atopic dry skin. These are best administered over slightly moistened skin, which seals in the moisture, rehydrates, lubricates, and moisturizes the skin and decreases inherent dryness and itchiness that appear to trigger the eczematous eruptions. They also aid in improving skin barrier function.18 In general, ointments are better than creams and are more beneficial than lotions. Ointment-based emollients include Vaseline petroleum jelly, Aquaphor, and Elta. However, these can be too greasy for everyday use; cream-based alternatives include DML Forte, Moisturel, Aveeno, Curél, Purpose, Dermasil, Neutrogena, and Eucerin. Lotions are better tolerated but trap less water and are less effective than ointment. Lotions include many brands such as Nivea, Aveeno, Curél, Vaseline, Lubiderm, Neutrogena, Dermasil, Suave, Olay, Jergens, and Moisturel. The moisturizer should be applied two to three times daily and after steroid application, so as not to impede steroid absorption. Topical corticoisteroids are the mainstay of treatment for AD.19 In general, corticosteroids should be used intermittently to control exacerbations. Inflammation should be treated aggressively initially, with the aim of complete clearance. Topical steroids should be applied only in areas of acute exacerbation, while emollients should be used over the remainder of the skin. Topical steroid ointment preparations are preferable to creams as they penetrate more efficiently and produce less stinging. Ointments, however, tend to occlude eccrine pores and may induce sweat retention and pruritus, and are less tolerable during the summer months. Creams are more practical in warm, humid weather and for the scalp, although lotions and gels are more aesthetically acceptable; however, their alcohol content may produce burning and discomfort. For mild cases of AD, a low-potency (class VI or VII) topical steroid should be used (Table 124–3). A 1% hydro-

cortisone ointment is adequate for thin skin areas such as the face, neck, axilla, and groin, all areas prone to atrophy if more potent preparations are used. Potent steroids are not usually required, except for localized areas of long-standing dermatitis where significant lichenification has occurred. For moderate cases of AD, intermediate-potency (class III, IV, and V) topical steroids may be used for brief periods (12 yr: 4 mg PO q4–6h 2–4 mg/kg/day PO divided q4–6h (maximum dose 400 mg/day) 0.5–1 mg/kg IM q4–6h 6 mo–2 yr: 2.5 mg PO qd 2–5 yr: 2.5–5 mg PO qd ≥6 yr: 5–10 mg PO qd 2–6 yr: 5 mg PO qd >6 yr: 10 mg PO qd 6–11 yr: 30 mg PO bid ≥12 yr: 60 mg PO bid or 180 mg PO qd 6–11 mo: 1 mg PO qd 1–5 yr: 1.25 mg PO qd 6–11 yr: 2.5 mg PO qd >12 yr: 5 mg PO qd

Chlorpheniramine maleate

Hydroxyzine Cetirizine Loratadine Fexofenadine Desloratidine

FIGURE 124–8. Friction diaper dermatitis.

Abbreviations: IM, intramuscularly; IV, intravenously; PO, orally.

of skin cancer and lymphoma and use of these agents; therefore, they should be prescribed only if other therapies are ineffective or inappropriate and when patients have wellestablished follow-up care.43 Other agents tried for severe recalcitrant AD include cyclosporine, methotrexate, azathioprine, and phototherapy; however, their use is associated with significant adverse reactions such as renal damage, hypertension, infections, premature aging, and malignancy.44-48 High-dose intravenous immune globulins have been used successfully in recalcitrant atopic dermatitis.49 Diaper Dermatitis The term diaper dermatitis includes all inflammatory eruptions that occur in the area covered by the diaper. The etiology of irritant diaper dermatitis (IDD) is multifactorial and only partially understood, and includes recent antibiotic use, diarrhea, occlusion, overhydration of skin, maceration, prolonged contact with urine and feces, and the interaction of Candida and bacterial organisms.50-53 The critical step in the development of diaper dermatitis is the occlusion of the skin under the diaper.54 Infrequent diaper changes create overhydration and maceration of the stratum corneum, which makes the skin more sensitive to friction. Elevations in the pH of the diaper area from feces mixed with urine activate fecal lipases and proteases; this together with Candida albicans causes damage to the epidermis, resulting in loss of the barrier function and fostering increased susceptibility to irritation.55 The incidence of IDD is equal between the sexes and begins around 3 to 18 months of age, peaking at 6 to 9 months of age. The prevalence in infants is 7% to 35%.52,53,56 Clinical Presentation Friction dermatitis presents on areas where friction is most pronounced, such as the inner surfaces of thighs, genitalia,

FIGURE 124–9. Irritant contact diaper dermatitis.

buttocks, and abdomen. It appears as a confluent shiny erythema with occasional papules that spares the intertriginous folds of the skin (Fig. 124–8). Irritant contact dermatitis is generally asymptomatic and presents with erythema on the convex surface of the inner and upper thigh area, buttocks, and lower abdomen. The intertriginous creases are spared, as is the area over the mons pubis in boys. The eruption subsequently becomes deeply erythematous with a typical glistening or glazed appearance and with a wrinkled surface (Fig. 124–9). Papules, vesicles, and secondary erosions may occur in severe cases. Candida diaper dermatitis presents with a diffuse erythematous patch extending over the genitalia with a peripheral scale. At the periphery of the patch it characteristically displays satellite red pustules or papules54 (Fig. 124–10). The anterior perineal and perianal area are either both or separately involved, as are the intertriginous creases, which helps differentiate this from IDD. In cases in which diaper dermatitis has been present for 3 or more days, C. albicans has been isolated in up to 80% of infants.54 Children with oropharyngeal candidiasis often have candidal diaper dermatitis due to excretion of C. albicans in the feces.57 Candida growth is more common after taking antibiotics. The differential diagnosis of diaper dermatitis is extensive (Table 124–6).

Chapter 124 — Dermatitis

FIGURE 124–11. Id reaction from Candida.

FIGURE 124–10. Candida diaper dermatitis.

Table 124–6

Differential Diagnosis of Diaper Dermatitis

Irritant contact dermatitis Allergic contact dermatitis Bullous impetigo Seborrheic dermatitis Psoriasis Biotin deficiency Jacquet’s erosive diaper dermatitis Langerhans cell histiocytosis (Letterer-Siwe disease) Acrodermatitis enteropathica Granuloma gluteale infantum Congenital syphilis Scabies Urticaria Miliaria Herpes simplex virus Varicella Epidermolysis bullosa Dermatitis herpetiformis Chronic bullous dermatosis of childhood Child abuse Perianal cellulitis (streptococcal)

865

Table 124–7

Topical Antifungal Agents for Candida Diaper Dermatitis

Agents

Dosage

Nystatin (Mycostatin) cream, ointment, powder Clotrimazole (Lotrimin) 1% cream, lotion, solution Econazole (Spectazole) 1% cream Sertaconazole (Ertaczo) 2% cream Sulconazole (Exelderm) 1% cream, solution Ciclopirox (Loprox) 0.77% cream, gel, suspension Miconazole (Micatin, Monistat-Derm) 2% cream, lotion, spray

bid or tid bid bid bid bid bid bid

Table 124–8

Oral Antifungal Agents for Candida Diaper Dermatitis

Agents

Dosage

Nystatin

2 ml PO qid (1 ml in each side of mouth after feeding) 6 mg/kg PO once, then 3 mg/kg/day PO (maximum 200 mg/day)

Fluconazole Abbreviation: PO, orally.

Candidal dermatitis with psoriaform id reaction represents a candidal infection in the diaper area followed by an explosive erythematous papulosquamous eruption resembling psoriasis on the cheeks and body58 (Fig. 124–11). An id reaction occurs from generalized and symmetric response to severe local inflammation. Management Attempts should be made to prevent all inciting factors.59 Frequent diaper changing is one of the most important factors in curing and preventing diaper dermatitis.54,60 Using diapers made of sodium polyacrylate polymers that form a gel when hydrated to keep liquid away from the skin has been shown to decrease the incidence and severity of diaper dermatitis compared with the use of cloth diapers or other disposable diapers.61 The diaper area should be gently cleaned at each diaper change. This is best done by immersing the area in lukewarm water in a basin. Harsh rubbing should be avoided. The area should be gently but completely dried. Use of cornstarch was believed to increase growth of C. albicans,

but recent studies refute this, and its use does decrease moisture.62 Use of emollients, particularly zinc oxide preparations and petrolatum, will prevent overhydration of the skin and provides protection from urine and feces. Other topical barriers with proven efficacy include cod liver oil, dimethicone, and lanolin.63 A nonfluorinated corticosteroid (hydrocortisone 1%), covered by the emollient, may be applied three times a day if emollients are ineffective. Their use, however, should be stopped after 14 days since overuse of corticosteroids can lead to skin atrophy or striae.64 Candidal superinfection is treated with topical anticandidal therapy, such as nystatin or an imidazole, two to three times daily in order to produce resolution in under 2 weeks (Table 124–7). If Candida is resistant to topical therapy or if there is evidence of Candida in the mouth as well as the perineal area, topical therapy may be supplemented with oral nystatin or fluconazole (Table 124–8). Adding

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hydrocortisone 1% to these agents may provide an antiinflammatory effect and promote more rapid healing. The treatment of the id reaction involves a low-potency corticosteroid ointment on the face and a mid-potency corticosteroid ointment on the body (see Table 124–3). Seborrheic Dermatitis Seborrheic dermatitis refers to a chronic inflammatory disease with remissions and exacerbations, characterized by an erythematous, scaly, or crusting eruption that occurs primarily in the seborrheic areas, where the highest concentration of sebaceous glands exists. These areas include the scalp, face, and postauricular, presternal, axillary, and intertriginous folds. Seborrheic dermatitis is a disease of unknown etiology that affects infants from 3 weeks of age onward, is uncommon after 6 months of age, and usually clears by 12 months of age. It then can reoccur in adolescents. The organism Pityrosporum ovale (Malassezia furfur) has been implicated in the etiology of adult seborrheic dermatitis, but its role in the infantile form of the disease is yet to be proven.65-67 It has, however, been recovered more often in patients with seborrheic dermatitis than in controls.68 In addition, some patients improve with topical or systemic ketoconazole.69 Clinical Presentation

the hairline and eyebrow area, where the scale is yellow and greasy and the underlying skin becomes erythematous (Fig. 124–13). The intertriginous, flexural, axillary, and postauricular areas and neck are involved in more severe cases, with scaling and linear erythema. In the diaper area, well-demarcated erythematous plaques are topped by a thin white scale or covered with thick, yellowish brown, greasy crusts. The lesions may become macerated, crusted, and superinfected with C. albicans. Pruritus is usually absent in comparison to AD. Infants are usually asymptomatic, and it is the parents who are dismayed by the cosmetic appearance. However, in one study up to 33% were seemingly itchy.70 In children between middle school age and puberty, seborrheic dermatitis may appear on the scalp as a dry, fine, flaky desquamation known as pityriasis sicca or dandruff. Erythema and scaling may also involve the supraorbital region, nasolabial crease, lips, pinna, retroauricular area, aural canal, and chest (Fig. 124–14). Pruritus is common. The differential diagnosis of seborrheic dermatitis includes atopic dermatitis, contact dermatitis, tinea facialis, tinea capitis, psoriasis, Langerhans cell histiocytosis (Letterer-Siwe disease), and Leiner’s disease. Management

The first area of involvement is generally the scalp. Here the lesions consists of diffuse greasy, yellow or white scales, frequently called “cradle cap” (retention hyperkeratosis) (Fig. 124–12).69a Lesions may spread to involve the face, especially

These lesions respond quickly to treatment with bathing in soothing oatmeal baths once or twice a day and shampooing with a tar shampoo daily. Shampoos containing salicylic acid should be avoided as they may be irritating and absorption may cause problems with salicylism. The use of ketoconazole

FIGURE 124–12. Seborrheic dermatitis (“cradle cap”).

FIGURE 124–13. Yellow and greasy rash from seborrheic dermatitis.

Chapter 124 — Dermatitis

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FIGURE 124–14. Erythematous scaly patches in an adolescent with seborrheic dermatitis.

2% results in clinical cure in patients with seborrheic dermatitis and has been found safe in infants.71,72 Itraconazole has been shown to be effective in adults.73 If the scale is extremely thick and adherent, it can be loosened by warmed mineral oil massaged into the scalp and then removed with a comb. In stubborn cases, a topical corticosteroid lotion may be used on the scalp one to three times daily. Adolescents with seborrhea of the scalp may use antiseborrheic shampoos, which include zinc pyrithone (Head & Shoulders, DHS Zinc, Zincon, or XSeb), selenium sulfide (Exsel or Selsun), ketoconazole (Nizoral), corticosteroids (FS Shampoo), and tar (T/Gel). Recently, the immunomodulators pimecrolimus and tacrolimus have been shown to be effective in improving lesions of seborrheic dermatitis.74,75 However, these agents have been associated with the development of dermal cancer and lymphoma and should be considered only for resistant cases.43 Ciclopirox (Loprox) shampoo, which has anti-Malassezia activity, will improve lesions in seborrheic dermatitis. Topical lithium gluconate and topical metronidazole (MetroCream, MetroGel, MetroLotion, Noritate) have also been shown to be effective.76,77 Contact Dermatitis Contact dermatitis may be defined as an eczematous eruption produced either by local exposure to a primary irritating substance (irritant contact dermatitis) or by an acquired allergic response to a sensitizing substance (allergic contact dermatitis).78-80 Irritant contact dermatitis requires an irritant—any agent that is capable of producing cell damage in any individual if applied for sufficient time and in sufficient concentration. Common substances include harsh soaps, bleaches, detergents, acids, alkalis, solvents, fiberglass, bubble baths, certain foods, saliva, talcum, urine, feces, and intestinal secretions. Allergic contact dermatitis (ACD) is unusual in children less than 10 years of age. It is a type IV hypersensitivity reaction only affecting previously sensitized individuals. There are two phases, the induction or sensitization phase and the elicitation phase.78,80 During the induction phase, an allergen, or hapten, penetrates the epidermis, where a cascade of events causes T lymphocytes to become memory cells. The elicitation phase occurs when the sensitized individual is reexposed to the antigen. The antigen causes T lymphocytes to produce lymphokines that mediate the inflammatory response that is characteristic of an allergic contact dermatitis. The elicita-

FIGURE 124–15. Allergic contact dermatitis from poison ivy.

FIGURE 124–16. Köbner’s phenomenon from contact dermatitis.

tion phase requires several hours to develop, and as a result symptoms are delayed. In infants, the only ACD seen with any frequency is nickel dermatitis, while in children ACD may include poison ivy, nickel, preservative or fragrances used in cosmetics, topical medications, and rubber (Figs. 124–15, 124–16, and 124–17). Teenagers may react to cosmetics and to formaldehyde used to size clothing. Flowers and pollens may all cause allergic reactions, but rarely in children. Adhesive tape reactions may occur in all ages. Several dermatitis conditions in children have characteristic presentations (Table 124–9). The differential diagnosis of contact dermatitis is lengthy (Table 124–10). Management Once the diagnosis of contact dermatitis has been made and the causative agent elicited, elimination of the offending substance results in cure within 2 to 3 weeks, but during this time patients may be severely incapacitated. Symptomatic treatment should be initiated as soon as the diagnosis is made. For relief of pruritus, antihistamines (see Table 124–5) can be given, and calamine lotion and oatmeal baths are soothing for the skin, but systemic corticosteroid therapy is the treatment of choice. If there is widespread skin involvement, corticosteroids should be given orally and tapered over 2 to 3

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weeks to avoid a rebound flare. If the skin involvement is small, topical corticosteroids are used. As in other acute eczematous eruptions, wet dressings for 15 to 30 minutes three times a day (modified Burow’s solution 1 : 40, 1 packet of Domeboro [aluminum acetate topical] powder per 12 ounces of water) are a useful adjunct to topical steroids. The crusts can be gently loosened from affected sites, followed by the application of a thin layer of emollient or antibacterial ointment.

Table 124–10

FIGURE 124–17. Contact dermatitis caused by nickel.

Table 124–9

Differential Diagnosis of Contact Dermatitis

Angioedema Atopic dermatitis Burns Candidiasis Diaper dermatitis Dyshidrotic eczema Herpes simplex virus Impetigo Scabies Sunburns Tinea infections Pityriasis rosea Mycosis fungoides Psoriasis Systemic lupus erythematosus Varicella Zoster

Common Pediatric Dermatitis Conditions

Poison Ivy Dermatitis • Most common ACD in children • Caused by the plant of the Rhus or Toxicodendron genuses (poison ivy, oak, or sumac). Poison ivy occurs in all parts of the United States as a shrub or vine. Poison oak, an upright shrub, appears only on the West Coast. Poison sumac grows as a shrub or tree in Mississippi • Sensitizing agent is an oleoresin (urushiol). • Occurs in spring, summer, and autumn • Sensitization may take 5–25 days and may be followed by the development of an acute pruritic dermatitis. • Reexposure will always result in an eruption within 24–48 hours. Initial lesions consists of erythematous vesicular streaks mainly on the lower legs, but any area may be involved (see Fig. 124–15). • A few hours to days later, other erythematous patches, papules, and bullae may develop. • Linear distribution of papules or vesicles after minor epidermal trauma (Köbner's phenomenon) is highly characteristic of contact dermatitis (see Fig. 124–16). • Allergen may be washed off within 20 minutes without causing an eruption. • Oleoresin may remain in clothing for months to years, causing a typical dermatitis if contacted by a sensitized person. Nickel Allergy • Earrings with nickel result in bilateral dermatitis consisting of erythema, scaling, vesicles, and crusts on the back and less often on the front of the earlobe. • Also widely used in bracelets, necklaces, watches, and rings as a hardening agent for gold (see Fig. 124–17). • Area immediately below the umbilicus where the nickel snap on blue jeans comes in contact with the skin is commonly involved.81 • Areas of inflammation may become chronic with shiny lichenoid papules from constant rubbing. Shoe Dermatitis • Acute or subacute dermatitis along the dorsa of the toes and foot • Erythema, lichenification, and, in severe cases, weeping and crusting • Webs of the toes not involved • Ball and heel also involved when rubber is the causative agent • Most common cause is rubber, but other agents include chromates, adhesives, and dyes. • Commonly misdiagnosed as tinea pedis (usually involves toe web spaces and is rarely seen prior to puberty).

Chapter 124 — Dermatitis

REFERENCES 1. Laughter D, Istvan JA, Tofte SJ, Hanifi n JM: The prevalence of atopic dermatitis in Oregon school children. J Am Acad Dermatol 43:649– 655, 2000. 2. Mortz CG, Lauritsen JM, Bindslev-Jensen C, Andersen KE: Prevalence of atopic dermatitis, asthma, allergic rhinitis, hand and contact dermatitis in adolescents: The Odense Adolescent Cohort Study on Atopic Diseases and Dermatitis (TOACS). Br J Dermatol 144:523–532, 2001. *3. Beltrani VS, Boguneiwicz M: Atopic dermatitis. Dermatol Online J 9:1–24, 2003. 4. Foley P, Zuo Y, Plunkett A, Marks R: The frequency of common skin condition in preschool-age children in Australia: atopic dermatitis. Arch Dermatol 137:293–300, 2001. 5. William HC, Burney PG, Hay RJ, et al: The U.K. Working Party’s diagnostic criteria for atopic dermatitis. I. Derivation of a minimum set of discriminators for atopic dermatitis. Br J Dermatol 131:383–396, 1994. 6. Aoki T, Fukuzumi T, Adachi J, et al: Re-evaluation of skin lesion distribution in atopic dermatitis: analysis of cases 0 to 9 years of age. Acta Derm Venereol Suppl 176:19–23, 1992. 6a. Stone KD: Atopic disease of childhood. Curr Opin Pediatr 15:495– 511, 2003. 7. Uehara M, Hayashi S: Hyperlinear palm: association with ichthyosis and atopic dermatitis. Arch Dermatol 117:490–491, 1981. 8. Williams HC, Pembroke AC: Infraorbital crease, ethnic group, and atopic dermatitis. Arch Dermatol 132:51–54, 1996. 9. Gelmetti C: Extracutaneous manifestations of atopic dermatitis. Pediatr Dermatol 9:380–382, 1992. 10. Garrity JA, Liesegang TJ: Ocular complications of atopic dermatitis. Can J Ophthalmol 19:21–24, 1984. 11. Oshinskie L, Haine C: Atopic dermatitis and its ophthalmic complications. J Am Optom Assoc 53:889–894, 1982. 12. Takahashi M, Suzuma K, Inaba I, et al: Retinal detachment associated with atopic dermatitis. Br J Ophthalmol 80:54–57, 1996. 13. Goodyear HM, McLeish P, Randall S, et al: Immunological studies of herpes simplex virus infection in children with atopic eczema. Br J Dermatol 134:85–93, 1996. 14. Arslanagic N, Arslanagic R: Atopic dermatitis and Staphylococcus aureus. Med Arh 58:363–365, 2004. 15. Su JC, Kemp AS, Varigos GA, Nolan TM: Atopic eczema: its impact on the family and fi nancial cost. Arch Dis Child 76:159–162, 1997. 16. Stender IM, Blichmann C, Serup J: Effects of oil and water baths on the hydration state of the epidermis. Clin Exp Dermatol 15:206–209, 1990. 17. Hanifi n JM, Tofte SJ: Update on therapy for atopic dermatitis. J Allergy Clin Imunol 104:S123–S125, 1999. 18. Loden M, Andersson AC, Lindberg M: Improvement in skin barrier function in patients with atopic dermatitis after treatment with a moisturizing cream (Canoderm). Br J Dermatol 140:264–267, 1999. 19. Thomas KS, Armstrong S, Avery A, et al: Randomized controlled trial of short bursts of a potent topical corticosteroid versus prolonged use of a mild preparation for children with mild or moderate atopic dermatitis. BMJ 324:768, 2002. 20. Railian D, Wilson JK, Feldman SR, Fleischer AB: Pediatricians who prescribe clotrimazole-betamethasone dipropionate (Lotrisone) often utilize it in inappropriate settings regardless of their knowledge of the drug’s potency. Dermatol Online J 8:3, 2002. 21. Nilsson EJ, Henning CG, Magnusson J: Topical corticosteroids and Staphylococcus aureus in atopic dermatitis. J Am Acad Dermatol 27:29– 34, 1992. 22. Bass JW, Chan DS, Creamer KM, et al: Comparison of oral cephalexin, topical mupirocin and topical bacitracin for the treatment of impetigo. Pediatr Infect Dis J 16:708–710, 1997. 23. Klein PA, Clark RA: An evidence-based review of the efficacy of antihistamines in relieving pruritus in atopic dermatitis. Arch Dermatol 135:1522–1525, 1999. 24. Doherty V, Sylvester DG, Kennedy CT, et al: Treatment of itching in atopic eczema with antihistamines with a low sedative profi le. BMJ 298:96, 1989. 25. Simons FE, Simons KJ: The pharmacology and use of H1-receptorantagonist drugs. N Engl J Med 330:1663–1670, 1994.

*Selected readings.

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26. Roth T, Roehrs T, Kosnorek G, et al: Sedative effects of antihistamines. J Allergy Clin Immunol 80:94–98, 1987. 27. Nakagawa H, Etoh T, Ishibashi Y, et al: Tacrolimus ointment for atopic dermatitis. Lancet 344:883, 1994. 28. Pascual JC, Fleisher AB: Tacrolimus ointment (Protopic) for atopic dermatitis. Skin Ther Lett 9:1–5, 2004. 29. Kapp A, Allen BR, Reitamo S: Atopic dermatitis management with tacrolimus ointment (Protopic). J Dermatol Treat 14(Suppl 1):5–16, 2003. 30. Paller A, Eichenfield LF, Leung DY, et al: A 12-week study of tacrolimus ointment for the treatment of dermatitis in pediatric patients. J Am Acad Dermatol 44(Suppl 1):S47–S57, 2001. 31. Bekersky I, Fitzsimmons W, Tanase A, et al: Nonclinical and early clinical development of tacrolimus ointment for the treatment of atopic dermatitis. J Am Acad Dermatol 44(1 Suppl):S17–S27, 2001. 32. Drake L, Prendergast M, Maher R, et al: The impact of tacrolimus ointment on health-related quality of life of adult and pediatric patients with atopic dermatitis. J Am Acad Dermatol 44(1 Suppl):S65–S72, 2001. 33. Kang S, Lucky AW, Pariser D, et al: Long-term safety and efficacy of tacrolimus ointment for the treatment of atopic dermatitis in children. J Am Acad Dermatol 44(1 Suppl):S58–S64, 2001. 34. Reitamo S, Harper J, Bos JD, et al; European Tacrolimus Ointment Group: 0.03% Tacrolimus ointment applied once or twice daily is more efficacious than 1% hydrocortisone acetate in children with moderate to severe atopic dermatitis: results of a randomized double-blind controlled trial. Br J Dermatol 150:554–562, 2004. 35. Ruzicka T, Bieber T, Schopf E, et al: A short-term trial of tacrolimus ointment for atopic dermatitis. N Engl J Med 337:816–821, 1997. 36. Thestrup-Pedersen K: Tacrolimus treatment of atopic eczema/ dermatitis syndrome. Curr Opin Allergy Clin Immunol 3:359–362, 2003. 37. Eichenfield LF, Lucky AW, Boguniewicz M, et al: Safety and efficacy of pimecrolimus (ASM 981) cream 1% in the treatment of mild and moderate atopic dermatitis in children and adolescents. J Am Acad Dermatol 46:495–504, 2002. 38. Allen BR, Lakhanpaul M, Morris A, et al: Systemic exposure, tolerability, and efficacy of pimecrolimus cream 1% in atopic dermatitis patients. Arch Dis Child 88: 969-973, 2003. 39. Wolff K, Stuetz A: Pimecrolimus for the treatment of inflammatory skin disease. Expert Opin Pharmacother 5:643–655, 2004. 40. Torok HM, Mass-Irslinger R, Slayton RM: Clocortolone pivalate cream 0.1% used concomitantly with tacrolimus ointment 0.1% in atopic dermatitis. Cutis 72:161–166, 2003. 41. Nakahara T, Koga T, Fukagawa S, et al: Intermittent topical corticosteroid/tacrolimus sequential therapy improves lichenification and chronic papules more efficiently than intermittent topical corticosteroid/emollient sequential therapy in patients with atopic dermatitis. J Dermatol 31:524–528, 2003. 42. Fleischer AB Jr, Ling M, Eichenfield L, et al: Tacrolimus Ointment Study Group: Tacrolimus ointment for the treatment of atopic dermatitis is not associated with an increase in cutaneous infections. J Am Acad Dermatol 47:562–570, 2002. 43. Wooltorton E: Eczema drugs tacrolimus (Protopic) and pimecrolimus (Elidel): cancer concerns. CMAJ 172:1179–1180, 2005. 44. Jekler J, Larko O: Combined UVA-UVB versus UVB phototherapy for atopic dermatitis: a paired-comparison study. J Am Acad Dermatol 22:49–53, 1990. 45. Pasic A, Ceovic R, Lipozencic J, et al: Phototherapy in pediatric patients. Pediatr Dermatol 20:71–77, 2003. 46. de Prost Y, Bodemer C, Telliac D: Randomised double-blind placebocontrolled trial of local cyclosporin in atopic dermatitis. Acta Dermatol Venereol Suppl 144:136–138, 1989. 47. Buckley DA, Baldwin P, Rogers S: The use of azathioprine in severe adult atopic eczema. J Eur Acad Dermatol Venereol 11:137–140, 1998. 48. Lee SS, Tan AW, Giam YC: Cyclosporin in the treatment of severe atopic dermatitis: a retrospective study. Ann Acad Med Singapore 33:311–313, 2004. 49. Jolles S: A review of high-dose intravenous immunoglobulin treatment for atopic dermatitis. Clin Exp Dermatol 27:3–7, 2002. 50. Campbell RL, Barlett AV, Sarbaugh FC, Pickering LK: Effects of diaper types on diaper dermatitis associated with diarrhea and antibiotic use in children in day-care centers. Pediatr Dermatol 5:83–87, 1988.

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51. Seymour JL, Keswick BH, Milligan MC, et al: Clinical and microbial effects of cloth, cellulose core, and cellulose core/absorbent gel diapers in atopic dermatitis. Pediatrician 149(14 Suppl)1:39–43, 1987. 52. Ward DB, Fleischer AB Jr, Feldman SR, Krowchuk DP: Characterization of diaper dermatitis in the United States. Arch Pediatr Adolesc Med 154:943–946, 2000. 53. Visscher MO, Chatterjee R, Munson KA, et al: Development of diaper rash in the newborn. Pediatr Dermatol 17:52–57, 2000. 54. Hogan P: Irritant napkin dermatitis. Aust Fam Physician 28:385–386, 1999. 55. Berg RW: Etiology and pathophysiology of diaper dermatitis. Adv Dermatol 3:75–98, 1988. *56. Kazaks EL, Lane AT: Diaper dermatitis. Pediatr Clin North am 47:909–919, 2000. 57. Hoppe J: Treatment of oropharyngeal candidiasis and candidal diaper dermatitis in neonates and infants: review and reappraisal. Pediatr Infect Dis J 16:885–894, 1997. 58. Fergusson AG, Fraser NG, Grant PW: Napkin dermatitis with psoriasiform “ide”: a review of fi fty-two cases. Br J Dermatol 78: 289–296, 1966. 59. Boiko S: Treatment of diaper dermatitis. Dermatol Clin 17:235–240, 1999. 60. Leyden JJ: Diaper dermatitis. Dermatol Clin 4:23–28, 1986. 61. Odio M, Friedlander SF: Diaper dermatitis and advances in diaper technology. Dermatology 12:342–346, 2000. 62. Leyden JJ: Corn starch, Candida albicans, and diaper rash. Pediatr Dermatol 1:322–325, 1984. 63. Wolf R, Wolf D, Tüzün B, Tüzün Y: Diaper dermatitis. Clin Dermatol 18:657–660, 2001. 64. De Zeeuwa R, van Praag MC, Oranje AP: Granuloma gluteale infantum: a case report. Pediatr Dermatol 17:141–143, 2000. 65. McGinley KJ, Leyden JJ, Marples RR, Kligman AM: Quantitative microbiology of the scalp in non-dandruff, dandruff, and seborrheic dermatitis. J Invest Dermatol 64:401–405, 1975. 66. Meshkinpour A, Sun J, Weinstein G: An open pilot study using tacrolimus ointment in the treatment of seborrheic dermatitis. J Am Acad Dermatol 49:145–147, 2003. 67. Tollesson A, Frithz A, Stenlund K: Malssezia furfur in infantile seborrheic dermatitis. Pediatr Dermatol 14:423–425, 1997.

68. Perez Chavarria EL, Castanon LR, Tamayo L, et al: Pityrosporum ovale in seborrheic dermatitis in children and in other dermatoses in children. Med Cutan Ibero Lat Am 17:98–102, 1989. 69. Pierard-Franchimont C, Pierard GE, Arrese JE, De Donker P: Effect of ketoconazole 1% and 2% shampoos on severe dandruff and seborrheic dermatitis: clinical, squamometric and mycological assessments. Dermatology 202:171–176, 2001. 69a. Gupta AK, Madzia SE, Batra R: Etiology and management of seborrheic dermatitis. Dermatology 208:89–93, 2004. 70. Yates VM, Kerr RE, Frier K, et al: Early diagnosis of infantile seborrheic dermatitis and atopic dermatitis—total and specific IgE levels. Br J Dermatol 108:639–645, 1983. 71. Mozzanica N: Pathogenic aspects of allergic and irritant contact dermatitis. Clin Dermatol 10:115–121, 1992. 72. Brodell R, Patel S, Venglarick J, et al: The safety of ketoconazole shampoo for infantile seborrheic dermatitis. Pediatr Dermatol 15:406– 407, 1988. 73. Baysal V, Yildirim M, Ozcanli C, Ceyhan AM: Itraconazole in the treatment of seborrheic dermatitis: a new treatment modality. Int J Dermatol 43:63–66, 2004. 74. Rigopoulos D, Ioannides D, Kalogeromitros D, et al: Pimecrolimus cream 1% vs. betamethasone 17-valerate 0.1% cream in the treatment of seborrheic dermatitis: a randomized open-labeled clinical trial. Br J Dermatol 151:1071–1075, 2004. 75. Gupta AK, Bluhm R: Ciclopirox shampoo for treating seborrheic dermatitis. Skin Ther Lett 9:4–5, 2004. 76. Dreno B, Moyse D: Lithium gluconate in the treatment of seborrheic dermatitis: a multicenter, randomized, double-blind study versus placebo. Eur J Dermatol 12:549–552, 2002. 77. Parsad D, Pandhi R, Negi KS, Kumar B: Topical metronidazole in seborrheic dermatitis—double-blind study. Dermatology 202:35–37, 2001. *78. Bruckner A, Weston WL: Allergic contact dermatitis in children: a practical approach to management. Skin Ther Lett 7:3–5, 2002. 79. Mortz CG, Andersen KE: Allergic contact dermatitis in children and adolescents. Contact Dermatitis 41:121–130, 1999. 80. Gawkroger DJ, Lewis FM, Shah M: Contact sensitivity to nickel and other metals in jewelry. J Am Acad Dermatol 43:31–36, 2000. 81. Weston WL, Bruckner A: Allergic contact dermatitis. Pediatr Clin North Am 47:897–907, 2000.

Chapter 125 Infestations Antonio E. Muñiz, MD

Key Points

lead to infestation by contact with objects or clothing containing the mites.2

The hallmark symptom of scabies is intense pruritis.

Clinical Presentation

Failure to find mites on microscopic examination does not rule out scabies.

The earliest symptom is itching, especially at night. Primary lesions include burrows, papules, vesicles, and pustules (Fig. 125–1). Secondary lesions occur from scratching and include excoriated papules with honey-colored exudates and crusts (Figs. 125–2 and 125–3). Lesions are commonly located on the abdomen, dorsa of hands, flexural surfaces of the wrists and elbows, periaxillary skin, areolae, genitalia, ankles, feet, and interdigital web spaces of the hands.2a In infants, eczematous eruptions of the face and trunk are seen. In older children, adolescents, and adults, the head and neck regions are almost never involved. A few patients develop a nodular form of scabies, exhibiting firm, erythematous, pruritic, domeshaped lesions 5 to 6 mm in diameter. The genitalia, groin, buttocks, and axillary folds are the usual sites of involvement. Some patients present with urticaria as the initial manifestations of scabies.3 S-shaped burrows are diagnostic, but not commonly seen in children4 (Fig. 125–4). Occasionally the burrows are straight or curved, and they are usually 2 to 5 mm in length. A burrow is caused by the female mite when it tunnels into the skin, and appears as a white or gray threadlike, linear, wavy papule with a small vesicle at one end. It is most often found in the interdigital web spaces of the hand, flexural surfaces of the wrists and elbows, areolae in women, penis, scrotum, and belt line area.5 The term scabies crustosa (formerly known as Norwegian or crusted scabies) is used to describe heavy infections with severe cutaneous crusting and hundreds to thousands of adult mites on a patient’s body.6 Patients with this form of scabies are usually immunocompromised, debilitated, or developmentally disabled, but it has also been encountered among indigenous Australians with no known immune deficiency.7 It begins with poorly defined erythematous patches that quickly develop a prominent scale. Any area may be affected, but the scalp, hands, and feet are particularly susceptible. Untreated, it spreads rapidly and may eventually involve the entire integument. Scales become warty and crusts appear. Scabies may be confused with other pruritic conditions (Table 125–1). The most common complication is secondary bacterial infection with Staphylococcus aureus, which is clinically suspected when there is pustule formation, bullous impetigo,

Empirical treatment after a tick bite is not recommended. Rocky Mountain spotted fever occurs in many geographic areas and must be considered in a child with a tick exposure who presents with fever, headache, myalgias, and rash.

Selected Diagnoses Scabies Tick bites Lyme disease Rocky Mountain spotted fever Pediculoses (louse infestations)

Discussion of Individual Diagnoses Scabies Scabies is a highly contagious, papular, pustulovesicular and occasionally crusting, pruritic eruption of the skin caused by the release of toxic or antigenic secretions of the eight-legged human female arachnid mite Sarcoptes scabiei var hominis.1 The organism is an obligate parasite, requiring an appropriate host for survival. The life cycle begins with the mating of adult male and female mites, after which the adult male dies. The female mite tunnels into the stratum corneum and deposits up to 90 eggs during its life span of 30 to 40 days. The eggs reach maturity in 10 to 14 days, and a new cycle begins. The average patient is infected with about 10 to 15 live adult female mites.2 A delayed type IV hypersensitivity reaction to the mites, their eggs, or scybala (fecal pellets) that occurs approximately 30 days after infestation is responsible for the intense pruritus, the hallmark of the disease. Transmission of scabies requires prolonged human contact, although female mites can survive 2 to 3 days off the human body and theoretically

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FIGURE 125–3. Scales and excoriations from scabies.

FIGURE 125–1. Excoriations, pustules, and vesicles on the hand from scabies.

FIGURE 125–4. Burrows from scabies.

Table 125–1

FIGURE 125–2. Excoriations, pustules, and vesicles on the feet from scabies.

severe crusting, cellulitis, ecthyma, paronychia, or furunculosis.8 Another organism causing secondary skin infection is Streptococcus pyogenes. Poststreptococcal glomerulonephritis may follow if nephritogenic strains of streptococci are involved.9 Other complications may include lymphangitis, suppurative lymphadenitis, staphylococcal scalded skin syndrome, scarlet fever, rheumatic fever, osteomyelitis, septic arthritis, pneumonia, and sepsis. The diagnosis of scabies is confirmed by scraping an unscratched burrow that is covered with a drop of microscopic immersion oil and placing the scrapings on a glass slide with a cover slip. Placing a drop of oil on the lesion prior to scraping with a number 15 scalpel blade improves the chance of obtaining a good specimen. Using the 10× magnification objective of the microscope, the female mite and/or

Differential Diagnosis of Scabies

Atopic dermatitis Irritant or contact dermatitis Lichen planus Dermatitis herpetiformis Seborrheic dermatitis Urticaria Gianotti-Crosti syndrome Insect bites Papular urticaria Acropustulosis of infancy Dyshidrotic eczema Impetigo Letterer-Siwe disease (histiocytosis X)

its eggs or excreta (scybala) should be visible. Failure to find the mite does not rule out scabies, since it is difficult to obtain adequate scrapings from an uncooperative, crying and moving child or infant. Videodermatoscopy has been demonstrated to be an effective and sensitive diagnostic tool, allowing for noninvasive in vivo visualization of the skin at magnifications of up to 600 times to detect signs of infestations.10 Management Treatment of scabies involves the control of symptoms, prevention of secondary infection, and eradication of the mites. Antihistamines, oatmeal baths, and calamine lotion may be

Chapter 125 — Infestations

used to help alleviate pruritus. Persistent itching after appropriate therapy may respond to topical corticosteroids. Secondary bacterial infections are treated with antistaphylococcal antibiotics. Application of a scabicide (Table 125–2), such as 5% permethrin (Elimite) cream, is considered the treatment of choice.1,4 It is recommended for infants older than 2 months of age but has been reported to be safe in neonates.11 It can be used in pregnant patients and those who are breast-feeding. In children, the scabicide is applied to the entire body, including the scalp and face, and washed off in 8 to 14 hours. The treatment is repeated in 1 week to ensure complete eradication. In adults, the scabicide is applied to areas below the head, since scabies rarely involves the face; a 30-g tube is usually sufficient for an average adult. Permethrin produces a 98% cure rate.1,11,12 In the past, 1% gamma benzene hexachloride (lindane; Kwell) lotion has been used. Although equally effective in eradicating scabies, prolonged absorption or repetitive use of gamma benzene hexachloride, especially in infants less than 6 months of age, concentrates the compound in the central nervous system and may cause seizures and rarely death.13,14 Other adverse effects include headache, nausea, vomiting, dizziness, restlessness, tremors, disorientation, weakness, twitching of eyelids, and respiratory failure.15,16 In addition to the patient, all family members and close contacts should be treated with a scabicide.1,4 Normal laundering or dry cleaning of clothing is sufficient to prevent the potential reinfection with the mite. Potential fomites that cannot be laundered or dry cleaned should be sealed in plastic bags for 1 week, since the adult mite cannot survive more than 3 to 4 days when separated from humans. For crusted scabies, crust and scale removal is necessary for scabicide penetration. Permethrin is the topical medication of choice, but when used by itself, topical treatment requires weeks of repeated application, and the failure rate is high. Oral ivermectin is rapidly becoming the treatment of choice for scabies crustosa17 (see Table 125–2). Follow-up within 2 weeks should be arranged to ascertain success of therapy. Many patients experience persistent

Table 125–2

873

symptoms for up to 2 weeks after curative treatment. This is likely due to the ongoing immune response to mite antigens. However, if symptoms persist beyond this period, one must consider other possibilities, such as an incorrect diagnosis, incorrect application of the topical scabicide, poor penetration of the agent into scaly skin, reinfection from untreated contacts or contaminated fomites, contact dermatitis from the topical agent, or drug-resistant infection. Tick Bites Tick bites are usually painless and inconspicuous in children and not noted until several hours to days later when pruritus becomes prominent. Tick bites are acquired when children play in woods or when ticks are transferred from animals to children. The tick attaches itself to the skin by its head in an effort to suck blood. The tick cuts the skin surface with chelicerae, introduces its proboscis, and secretes saliva into the wound. The saliva contains a cement substance, anesthetic, anti-inflammatory agent, and anticoagulant, and may also include a neurotoxin responsible for tick paralysis or other infections, such as agents for relapsing fever, rickettsial infections (Rocky Mountain spotted fever, typhus, trench fever, Q fever, ehrlichiosis, boutonneuse fever), Lyme disease, Colorado tick fever, babesiosis, and tularemia. After a tick bite, a localized urticarial reaction occurs. The most common sites for tick attachment are the occiput, ear canal, axilla, groin, and vulva.18,19 On rare occasions a systemic reaction consisting of fever, nausea, abdominal pain, and headache may occur. A persistent pruritic nodule with surrounding alopecia may be the result of an incompletely removed tick in which mouth parts remain in the skin. Lyme Disease Ticks may carry the spirochete Borrelia burgdorferi, which is responsible for Lyme disease (see Chapter 71, Selected Infectious Diseases). The predominant tick in the northeastern and midwestern United States is the deer tick, Ixodes dammini (or Ixodes scapularis). In the northwestern United States, Ixodes pacificus is the vector, and Amblyomma americanum (Lone Star tick) is the vector in the southern United States.20

Medications for the Treatment of Scabies64-66

Agent

Application

Cautions

Permethrin 5% (Elimite) cream

Apply and wash off in 8–14 hr; repeat in 1 wk

1% gamma benzene hexachloride (lindane; Kwell) lotion

Apply and wash off in 8–12 hr; repeat in 1 wk

Precipitated sulfur (3–10%) in petrolatum ointment

Apply for 3 consecutive days; can be washed off after every 24 hr

Crotamiton 10% (Eurax) cream or lotion

Apply and repeat in 24 hr, then washed off in 48 hr. Better results occur if applied for 5 days Apply three times in a 24-hr period, then wash off 150–200 mcg/kg/day PO as a single dose; repeat 2 wk later

>2 mo old (reported safe in neonates), safe in pregnancy and breast-feeding Repeated use may cause seizures and death (131° F or 55° C). Potential fomites such as towels, pillow cases, hats, and children's stuffed animals may benefit from washing in hot water. Because adult lice cannot survive more than 6 to 10 days when separated from humans, sealing potential fomites in plastic bags for 12 to 14 days is effective when they cannot be laundered or dry cleaned. For treatment of body lice, the most important therapy is disinfection of all contaminated clothing and linens.62a The clothing may be dry cleaned, steam fumigated, or washed in hot water and dried on high heat. Furniture in the house should be sprayed with agents specifically approved for disinfecting lice, such as permethrin spray. The patient should be treated from head to toe with a pediculicide. Permethrin 5% topical cream is the safest agent and should be applied for 8 to 14 hours and repeated in 1 week to ensure appropriate cure. Treatment of pubic lice with permethrin or pyrethrin applied for 10 minutes and repeated in 1 week is sufficient. Sexual contacts should be treated, and laboratory tests for other sexually transmitted infections should be performed. The safest and most effective treatment for P. pubis of the eyelashes is petrolatum (Vaseline). The ointment is applied three to five times daily. Physostigmine 0.25% (Eserine) has been used successfully, but has the major drawback of miosis from an anticholinergic effect. For severe resistant cases, ivermectin has been successful.62,63 Human louse infection causes an annoying pruritic sensation. When treated with appropriate agents, the infection can easily be controlled.

Treatment of Head Lice67-72

Agents

Instructions for Use

Precautions

Permethrin (Elimite 5%, Nix 1%) cream

Apply to hair for 10 min and wash; repeat in 1 wk Apply to hair for 10 min and wash; repeat in 1 wk

Approved for > 2 mo old

Apply for no more than 4 min and wash; repeat in 1 wk

Not recommended due to neurotoxic adverse effects, such as seizures if used repeatedly; avoid if seizure disorder, pregnant, or breastfeeding Approved for > 6 yr old; high alcohol content makes it flammable, may cause respiratory depression if ingested Not FDA approved and safety in children unknown Not FDA approved; use in resistant cases and if > 15 kg Not FDA approved; increased effectiveness if given with permethrin Safe in pregnancy, breast-feeding, and infants < 2 mo of age; bad odor and messy; in hot or humid climate may lead to irritant dermatitis; less effective than permethrin

Piperonyl butoxide 4%/pyrethrins 0.33% (RID Mousse, RID shampoo, A-200 shampoo, R & C, Pronto, Clear lice system, End Lice) 1% gamma benzene hexachloride shampoo and cream (lindane; Kwell, G-well) Malathion 0.5% (Ovide) lotion

Apply and leave for 8–12 hr, then wash; repeat in 1 wk

Crotamiton 10% (Eurax) cream and lotion Ivermectin (Mectizan, Stromectal)

Apply and leave for 24 hr, then wash 200 mcg/kg PO; repeat in 1 wk

Sulfamethoxazole/trimethoprim (co-trimoxazole) Precipitated sulfur (3–10%) in petrolatum

8–10 mg/kg/day of trimethoprim q12h PO for 3 days; repeat in 1 wk Apply daily for several days

Abbreviations: FDA, Food and Drug Administration; PO, orally.

Approved for > 2 yr old; 80% cure rate

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29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41.

42. 43.

44. 45.

46. 47. 48. 49. 50.

51. 52. 53. 54. 55. 56. 57.

*Selected readings.

sequences by a highly sensitive PCR-ELISA. J Am Acad Dermatol 48:376–384, 2003. Steere AC, Dhar A, Hernandez J, et al: Systemic symptoms without erythema migans as the presenting picture of early Lyme disease. Am J Med 114:58–62, 2003. Steere AC: Lyme disease. N Engl J Med 345:115–125, 2001. Pinto DS: Cardiac manifestations of Lyme disease. Med Clin North Am 86:285–296, 2002. Peters AH: Tick-borne typhus (Rocky Mountain spotted fever): epidemiology trends with particular reference to Virginia. JAMA 216:1003– 1007, 1971. Walker DH, Lesesne HR, Varma VA, Thacker WC: Rocky Mountain spotted fever mimicking acute cholecystitis. Arch Intern Med 145:2194– 2196, 1985. Myers SA, Sexton DJ: Dermatology manifestations of arthropod-borne diseases. Infect Dis Clin North Am 8:689–712, 1994. Calhan EF, Adal KA, Tomecki KJ: Cutaneous (non-HIV) infections. Dermatol Clin 18:497–507, 2000. Kelsey DS: Rocky Mountain spotted fever. Pediatr Clin North Am 26:367–376, 1979. Kirkland KB, Marcom PK, Sexton DJ, et al: Rocky Mountain spotted fever complicated by gangrene: report of six cases and review. Clin Infect Dis 101:629–634, 1996. Conlon PJ, Procop GW, Fowler V, et al: Predictors of prognosis and risk of acute renal failure in patients with Rocky Mountain spotted fever. Am J Med 101:621–626, 1996. Needham GR: Evaluation of five popular methods for tick removal. Pediatrics 75:997–1002, 1985. Warshafsky S, Nowakowski J, Naldelman RB, et al: Efficacy of antibiotic prophylaxis for prevention of Lyme disease. J Gen Intern Med 11:329–333, 1996. Nadelman RB, Nowakowski J, Fish D, et al; Tick Bite Study Group: Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after Ixodes scapularis tick bite. N Engl J Med 345:79–84, 2001. Barsic B, Maretic T, Majerus L, Strugar J: Comparison of azithromycin and doxycycline in the treatment of erythema migrans. Infection 28:153–156, 2000. Arnez M, Radsel-Medvescek A, Pleterski-Rigler D, et al: Comparison of cefuroxime axetil and phenoxymethyl penicillin in the treatment of children with solitary migrans. Wien Klin Wochenschr 111:916–922, 1999. Kirkland KB, Wilkinson WE, Sexton DJ: Therapeutic delay and mortality in cases of Rocky Mountain spotted fever. Clin Infect Dis 20:1118–1121, 1995. Centers for Disease Control and Prevention: Consequences of delayed diagnosis of Rocky Mountain spotted fever in children—West Virginia, Michigan, Tennessee, and Oklahoma, May–July 2000. MMWR Morb Mortal Wkly Rep 49:885–888, 2000. Stallings SP: Rocky Mountain spotted fever and pregnancy: a case report and review of the literature. Obstet Gynecol Surv 56:37–42, 2001. Fradin MG: Mosquitoes and mosquito repellants: a clinician’s guide. Ann Intern Med 128:931–940, 1998. Archibald LK, Sexton DJ: Long-term sequelae of Rocky Mountain spotted fever. Clin Infect Dis 20:1122–1125, 1995. Chosidow O: Scabies and pediculosis. Lancet 355:819–826, 2000. Burkhart CN, Burkhart CG, Pchalef I, Arbogast J: The adherent cylindrical nit structure and its chemical denaturation in vitro: an assessment with therapeutic implications for head lice. Arch Pediatr Adolesc Med 152:711–712, 1998. Speare R, Buettner PG: Head lice in pupils of a primary school in Australia and implications for control. Int J Dermatol 38:285–290, 1999. Frankowski BL, Weiner LB: Head lice. Pediatrics 110:638–643, 2002. Spach DH, Kanter AS, Dougherty MJ, et al: Bartonella (Rochalimaea) quintane bacteremia in inner-city patients with chronic alcoholism. N Engl J Med 332:424–428, 1995. Sunders KO, Haimanot AT: Epidemic of louse-borne relapsing fever in Ethiopia. Lancet 432:1213–1215, 1993. Ko CJ, Elston DM: Pediculosis. J Am Acad Dermatol 50:1–12, 2004. Elston DM: What’s eating you? Pediculus humanus (head louse and body louse). Cutis 65:259–264, 1999. Pierzchalski JL, Bretl DA, Matson SC: Phthirus pubis as a predictor from Chlamydia infections in adloscents. Sex Transm Dis 29:331–334, 2002.

Chapter 125 — Infestations 58. Elgart ML: Pediculosis. Dermatol Clin 8:219–228, 1990. 59. Abramowicz M: Drugs for head lice. Med Lett Drugs Ther 39:3–7, 1997. 60. Burkhart CG, Burkhart CN, Burkhart KM: An assessment of topical and oral prescriptions and over-the-counter treatments for head lice. J Am Acad Dermatol 38:979–982, 1998. 61. Dawes M, Hicks NR, Fleminger M, et al: Evidence based case report: treatment for head lice. BMJ 318:385, 1999. 62. Schachner LA: Treatment resistant head lice: alternative therapeutic approaches. Pediatr Dermatol 14:409–410, 1997. 62a. Flinders DC, de Schweintz P: Pediculosis and scabies. Am Fam Physican 69:341–348, 2004. 63. Bukhart CN, Burkhart CG: Oral ivermectin therapy for phthiriasis palpebrum. Arch Ophthalmol 118:134–135, 2000. 64. Roos TC, Alam M, Roos S, et al: Pharmacotherapy of ectoparasitic infections. Drugs 61:1067–1088, 2001. 65. Meinking TL, Taplin D, Hermida JL, et al: The treatment of scabies with ivermectin. N Engl J Med 333:26–30, 1995.

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66. Barkwell R, Shields S: Deaths associated with ivermectin treatment of scabies. Lancet 349:1144–1445, 1997. 67. Carson DS, Tribble PW, Weart CW: Pyrethrins combined with piperonyl butoxide (RID) vs. 1 per cent permethrin (Nix) in the treatment of head lice. Am J Dis Child 142:768–769, 1988. 68. Rassmussen JE: Pediculosis and the pediatrician. Pediatr Dermatol 2:74–79, 1984. 69. Tenenbein M: Seizures after lindane therapy. J Am Geriatr Soc 39:394– 395, 1999. 70. Hipolito RB, Mallorca FG, Zuniga-Macaraig ZO, et al: Head lice infestation: single drug versus combination therapy with one percent permethrin and trimethoprim/sulfamethoxazole. Pediatrics 107:e30, 2001. 71. Glaziou P, Nguyen LN, Moulia-Pelat JP, et al: Efficacy of ivermectin for the treatment of head lice (pediculosis capitis). Trop Med Parasitol 45:253–254, 1994. 72. Burkhart CN, Burkhart CG: Another look at ivermectin in the treatment of cabbies and head lice [letter]. Int J Dermatol 38:235, 1999.

Chapter 126 Other Important Rashes Antonio E. Muñiz, MD

Key Points Scarlet fever is treated with penicillin to prevent local suppurative complications and the development of acute rheumatic fever. Staphylococcal scalded skin syndrome and toxic shock syndrome require antistaphylococcal antibiotics, fluid and electrolyte replacement, and meticulous skin care. Tinea capitis is the most common cause of hair loss in children and is usually treated with prolonged oral antifungal therapy. Tinea corporis is the most common fungal skin infection in children and is usually treated with topical antifungal therapy. Kawasaki disease is treated with aspirin and intravenous immune globulin to prevent formation of coronary artery aneurysms.

Selected Diagnoses Scarlet fever (scarlatina, second disease) Staphylococcal scalded skin syndrome Staphylococcal toxic shock syndrome Tinea capitis Tinea corporis Pityriasis versicolor Molluscum contagiosum Pityriasis rosea Kawasaki disease (mucocutaneous lymph node syndrome) Impetigo

Discussion of Individual Diagnoses Scarlet Fever (Scarlatina, Second Disease) Scarlet fever is a toxin-mediated disease characterized by fever, oral mucous membrane changes, and an exanthem. It occurs most often in children between 2 and 10 years of age.1 880

The disease is rare under 2 years of age presumably due to the presence of maternal antitoxin antibodies. Most cases of scarlet fever are due to group A β-hemolytic streptococcal pyrogenic exotoxin–producing strains.2 Occasionally cases are caused by strains of group C or G streptococci. Its highest incidence is in the late fall, winter, and early spring. Transmission occurs through person-to-person contact with infectious respiratory droplets. The incubation period prior to appearance of the rash is 2 to 5 days. The most common infection that leads to scarlet fever is tonsillopharyngitis, but the rash develops in less than 10% of cases.3 It can also occur after a streptococcal skin and soft tissue infection, or infection of surgical wounds (surgical scarlet fever) or the uterus (pubertal scarlet fever). Clinical Presentation The illness begins with nonspecific signs and symptoms: fever, headache, malaise, nausea, vomiting, abdominal pain, and myalgias. Exudative tonsillopharyngitis is characterized by an erythematous oral mucosa, petechiae, and punctate erythematous macules on the palate and uvula (Forschheimer spots). The tongue is covered initially by a yellowish white coat; protruding red papillae give it the appearance of a “white strawberry tongue.” Within 2 to 4 days, disappearance of the white coating reveals a beefy red tongue with enlarged papillae known as a “red strawberry tongue” (Fig. 126–1). The exanthem appears 24 to 48 hours afterward and consists of erythematous macules and papules, beginning on the neck, face, and upper trunk and spreading downward to the extremities over the next 1 to 2 days. Generalized erythroderma is punctuated by numerous pinpoint, erythematous, blanchable papules, imparting a sandpaper-like texture (Fig. 126–2). Occlusion of sweat glands produces the papular rash. In severe cases the exanthem may be petechial and worsened by the application of a tourniquet. Capillary fragility causes petechiae in a linear pattern along major skinfolds, such as the axilla, antecubital fossa, and inguinal fossa, known as Pastia’s lines. The palms and soles are generally spared, and there is a facial flush with circumoral pallor. Generalized adenopathy is common, but particularly inguinal nodes and splenomegaly may occur. The rash fades over 5 to 7 days, and is followed by fine superficial desquamation of the face, trunk, axilla, groin, and extremities. Desquamation may continue for weeks, especially in the hands and feet.

Chapter 126 — Other Important Rashes

Table 126–1

881

Differential Diagnosis for Scarlet Fever

Staphylococcal scarlet fever Viral hepatitis Infectious mononucleosis Kawasaki disease Toxic shock syndrome Measles Rubella Staphylococcal scalded skin syndrome Roseola infantum Erythema infectiosum Echovirus 14 Drug-associated eruptions Secondary syphilis Juvenile rheumatoid arthritis Streptobacillus moniliformis (rat bite fever) Arcanobacterium haemolyticum FIGURE 126–1. Red strawberry tongue in scarlet fever.

Table 126–2

Antimicrobial Agents Effective for Scarlet Fever

Antimicrobials

Doses

Penicillin V potassium Benzathine penicillin

25–50 mg/kg/day qid PO for 10 days Single daily dose: 8 mm in diameter) will have 50% stenosis and

obstruction, and two thirds will have evidence of myocardial ischemia.102 Other cardiac findings may include congestive heart failure, valvulitis (especially of the mitral valve), and pericardial effusion. The earliest cardiac changes occur within the first 10 days of onset and include endocarditis, myocarditis, and pericarditis. The formation of a coronary aneurysm may lead to turbulent flow and thrombus formation with coronary stenosis and subsequent myocardial ischemia, infarction, or sudden death.103 Aneurysm may occur in other extraparenchymal muscular arteries such as the celiac, mesenteric, femoral, iliac, renal, axillary, and brachial arteries.104 Laboratory findings are nonspecific: leukocytosis with left shift, eosinophilia, and elevated ESR, CRP, and α1-antitrypsin. Thrombocytosis, ranging from 500,000/mm3 to greater

Chapter 126 — Other Important Rashes

FIGURE 126–20. Desquamation seen in Kawasaki disease.

than 1,000,000/mm3, occurs on the second week of illness, and serum immunoglobulins may increase. A normochromic, normocytic anemia is frequent, and elevated hepatic transaminases and bilirubin may be seen. Urinalysis reveals sterile pyuria in a third of the patients. Arthrocentesis during the arthritis yields purulent-appearing fluid with a mean white blood cell count of 125,000/mm3 to 300,000/mm3, normal glucose level, and negative Gram stain and bacterial culture.105 Cerebrospinal fluid may show a mononuclear pleocytosis without hypoglycorrhachia or elevated protein. Abnormalities in serum lipids can occur, with increased triglycerides and low-density lipoproteins and decreased high-density lipoproteins.106 Elevation of serum cardiac troponin I has been reported.107 Electrocardiographic changes may include prolongation of the PR interval or QT interval and ST-segment and T-wave changes. The diagnosis of coronary artery aneurysm is accomplished by two-dimensional echocardiography. It is noninvasive and has a high sensitivity and specificity for detection of abnormalities in the coronary arteries. Other modalities used to diagnose coronary artery aneurysms have included magnetic resonance imaging, magnetic resonance angiography, and coronary angiography.108 The differential diagnosis for KD includes Stevens-Johnson syndrome, toxic shock syndrome, scarlet fever, measles, Yersinia pseudotuberculosis (Izumi fever), juvenile rheumatoid arthritis, drug eruption, serum sickness, Rocky Mountain spotted fever, infantile polyarteritis nodosa, acute adenovirus infection, measles, echovirus, leptospirosis, and mercury hypersensitivity reaction.109 Management Treatment of KD in the acute phase is directed at decreasing inflammation in the coronary artery wall and preventing coronary thrombosis, whereas long-term therapy in patients who develop coronary aneurysms is aimed at preventing myocardial ischemia or infarction. It is now clear that IVIG and aspirin combined therapy results in a more rapid anti-inflammatory effect and reduces coronary artery abnormalities more than aspirin alone. In the United States, it is recommended to give a single 2-g/kg infusion of IVIG over 8 to 12 hours and aspirin (80 to 100 mg/kg four times a day) within the first 10 days of onset, with the aspirin dose reduced (3 to 5 mg/kg) after defervescence.112,111 In Japan, the initial aspirin dose is 30 to 50 mg/kg. Aspirin is discontinued if no coronary artery abnormalities

893

have been detected by 6 weeks after onset. Aspirin has been used to decrease inflammation and to inhibit platelet aggregation, although it has no effect on the development of coronary artery aneurysms.112 Children who take salicylates while they are experiencing active infection with varicella or influenza are at risk of Reye’s syndrome, and it has been reported in patients taking high-dose aspirin for a prolonged period after KD.113 It is unclear whether the low-dose treatment increases the risk of Reye’s syndrome. Nevertheless, children who are taking salicylates long term should receive an annual influenza vaccine. Those who cannot take aspirin should be given dipyridamole or clopidogrel. About 10% to 15% of patients treated with aspirin and IVIG will have persistent fever and are at higher risk of developing coronary artery aneurysms.114,115 It is common practice to give a second dose of IVIG.103,116 If fever persists, other options used successfully include pulsed intravenous methylprednisolone (30 mg/kg once daily for 2 to 3 days), cyclophosphamide and prednisone, cyclosporine, plasmapheresis, and etanercept or infliximab (monoclonal antibodies to TNFα).103,112,117,118 In Japan, other agents used include ulinstatin (human trypsin inhibitor) and abciximab (platelet glycoprotein IIb/IIIa receptor inhibitor).119-121 Despite earlier reports that corticosteroids may worsen outcomes, a recent report shows that adding methylprednisolone to IVIG and aspirin had a faster resolution of fever, more rapid improvement in markers of inflammation, and shorter length of hospitalization.118 About 20% of patients who develop coronary artery aneurysms during the acute disease will develop coronary stenosis and might need treatment for myocardial ischemia, including percutaneous transluminal balloon angioplasty, coronary artery stenting, percutaneous transluminal coronary rotational ablation, coronary artery bypass grafting, and even cardiac transplantation.122-124 KD may be difficult to diagnosis when the classic features are not present. However, the diagnosis should be suspected in any child with fever greater than 5 days without a source. There should be follow-up with asymptomatic patients for repeat two-dimensional echocardiography in 2 weeks and at 6 to 8 weeks after onset of disease to detect dysrhythmias, heart failure, valvular insufficiency, or myocarditis. Impetigo Impetigo is a superficial vesiculopustular infection localized to the subcorneal epidermis and is the most common bacterial infection in children.125 The peak incidence is between the ages of 2 and 6 years. The most common pathogen found on children’s skin is S. aureus (70% to 80%), followed by S. pyogenes.125-127 Microscopic breaks in the epidermal barrier, such as trauma from scratching dermatitic skin, predispose to impetigo, as these organisms penetrate the skin and proliferate. A warm, humid climate favors the development of impetigo. Impetigo has a high attack rate, and its spread is enhanced by crowding, poor socioeconomic conditions, and poor personal hygiene. Impetigo can be subdivided into nonbullous (70%) and bullous forms. Bullous impetigo results from invasion by phage group II S. aureus onto the skin. The epidermolytic toxin disrupts epidermal cell attachment. An ulcerative form called ecthyma is due to group A β-hemolytic streptococcus. Group B streptococci can cause impetigo in neonates. Recent

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SECTION IV — Approach to the Acutely Ill Patient

data from hospitalized patients demonstrate that S. aureus, Enterococcus species, coagulase-negative staphylococci, Escherichia coli, and Pseudomonas aeruginosa are the most prevalent pathogens in skin and soft tissue infections.128 Clinical Presentation Erosions covered by moist, honey-colored crusts are suggestive of impetigo.129 Impetigo begins as small (1- to 2-mm) erythematous macules, which soon develop into vesicles or bullae with friable roofs surrounded by red borders that are quickly lost. The vesicles rupture easily, with release of a thin, cloudy, yellow fluid. The serous discharge subsequently dries, with formation of thick, soft, honey-colored crusts, the hallmark of impetigo (Fig. 126–21). They occur mostly on the face, nares, and extremities. The exudates spread easily by autoinoculation and produce satellite lesions adjacent to areas of impetigo or other parts of the body. Fever and regional lymphadenopathy may be present. The term bullous impetigo has been used to describe lesions with a central moist crust and an outer zone of blister formation. The blister is translucent, with a flaccid roof that is easily shed, such that bullous impetigo may be seen as shallow erosions, like a “scalded skin,” with an outer rim of desquamation (Fig. 126–22).126 The differential diagnosis is shown in Table 126–12. Poststreptococcal glomerulonephritis may follow impetigo if nephritogenic strains of streptococci are involved. This most commonly occurs in children 3 to 7 years of age, and is seen 18 to 21 days after the onset of impetigo. Other complications include cellulitis, lymphangitis, suppurative lymphadenitis, SSSS, scarlet fever, rheumatic fever, osteomyelitis, septic arthritis, pneumonia, and sepsis.

is as effective as oral therapy.130 For penicillin-allergic patients, choices of antibiotics include azithromycin, clarithromycin, and clindamycin. If Haemophilus influenzae is suspected, possible antibiotics include cefotaxime, ceftriaxone, and cefuroxime, and in those allergic to penicillin, clindamycin can be administered. Removal of the crust and scrubbing skin lesions with antibacterial soap has not been shown to be effective.126 Use antibiotics effective against MRSA if there is a high prevalence of this organism in the community.

Management Antibiotics effective against S. aureus are indicated in cases of impetigo. Choices include cephalexin, dicloxacillin, and amoxicillin-calvunalate (Table 126–13). Topical mupirocin can be used for impetigo involving a small surface area and

FIGURE 126–21. Erosions seen in impetigo.

FIGURE 126–22. Bullous impetigo.

Chapter 126 — Other Important Rashes

Table 126–12

Differential Diagnosis of Impetigo

Nummular dermatitis Herpes simplex virus infection Herpes zoster Second-degree burns Fixed drug eruptions Linear Immunoglobulin A dermatosis Bullous pemphigoid Pemphigus vulgaris Erythema multiforme Staphylococcal scalded skin syndrome Stevens-Johnson syndrome Cellulitis Lymphangitis Thermal burns Candidiasis Scabies

Table 126–13

Antibiotics Effective against Impetigo

Antimicrobials

Dose

Cephalexin Amoxicillin–calvulanic acid Dicloxacillin Azithromycin Clarithromycin Clindamycin Cefotaxime Ceftriaxone

25–100 mg/kg/day divided q6h PO 25–45 mg/kg/day divided q12h PO

Cefuroxime Mupirocin Trimethoprim [TMP]/ sulfamethoxazole

12.5–25 mg/kg/day divided q6h PO 5 mg/kg/day qd PO 15 mg/kg/day bid PO 25–40 mg/kg/day divided q6–8h PO/IV 100–200 mg/kg/day divided q6–8h IV/IM 50–75 mg/kg/day divided q24h or q12h IV/IM 75–150 mg/kg/day divided q8h IV/IM Apply qd-tid 8–12 mg/kg/day of TMP divided bid

Abbreviations: IM, intramuscularly; IV, intravenously; PO, orally.

Hand washing with surgical soap and simple measures of good hygiene may reduce the likelihood of spread. A child with recurrent impetigo should be evaluated for carriage of S. aureus, especially in the nares, as this is the site of colonization three fourths of the time.131 Nasal carriage of both methicillin-susceptible and methicillin-resistant strains of S. aureus has been eliminated in more than 90% of patients within 2 to 4 days through use of topical mupirocin three time daily.132 REFERENCES 1. Manders SM: Toxin-mediated streptococcal and staphylococcal disease. J Am Acad Dermatol 39:383–398, 1998. 2. Efstratiou A: Group A streptococci in the 1990s. J Antimicrob Chemother 45(Suppl):3S–12S, 2000. 3. Bialecji C, Feder HM Jr, Grant-Kels JM: The six classic childhood exanthems: a review and update. J Am Acad Dermatol 21:891–903, 1989. 4. Miller RA, Brancato F, Holmes KK: Corynebacterium haemolyticum as a cause of pharyngitis and scarlatiniform rash in young adults. Ann Intern Med 105:867–872, 1986. 5. Guven A: Hepatitis and hematuria in scarlet fever. Indian J Pediatr 69:985–986, 2002.

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6. Randolph MF, Gerber MA, DeMeo KK, Wright L: Effect of antibiotic therapy on the clinical course of streptococcal pharyngitis. J Pediatr 106:870–875, 1985. 7. Bass JW, Person DA, Chan DS: Twice-daily oral penicillin for treatment of streptococcal pharyngitis: less is best. Pediatrics 105:423– 424, 2000. 8. Pichichero ME: Cepahlosporins are superior to penicillin for treatment of streptococcal tonsillopharyngitis: is the difference worth it? Pediatr Infect Dis J 12:268–274, 1993. 9. Elias PM, Fritsch P, Epstein EH: Staphyloccocal scalded skin syndrome: clinical features, pathogenesis, and recent microbiological and biochemical developments. Arch Dermatol 113:207–219, 1977. 10. Sarai Y, Nakahara H, Ishikawa T, et al: A bacteriologic study on children with staphylococcal toxic epidermal necrolysis in Japan. Dermatologica 154:161–167, 1977. 11. Ridgway HB, Lowe NJ: Staphylococcal scalded skin syndrome in an adult with Hodgkin’s disease. Arch Dermatol 115:589–590, 1979. 12. Cribier B, Piemont Y, Grosshans E: Staphylococcal scalded skin syndrome in adults: a clinical review illustrated with a new case. J Am Acad Dermatol 30:319–324, 1984. *13. Patel GK, Finlay AY: Staphylococcal scalded skin syndrome: diagnosis and management. Am J Clin Dermatol 4:165–175, 2003. 14. Melish ME, Glasgow LA: Staphylococcal scalded skin syndrome: the expanded clinical syndrome. J Pediatr 78:958–967, 1971. 15. Ladhani S, Joannou CL, Lochrie DP, et al: Clinical, microbial, and biochemical aspects of exfoliative toxins causing staphylococcal scalded-skin syndrome. Clin Microbiol Rev 12:224–242, 1999. 16. Lina G, Gillet Y, Vandenesch F, et al: Toxin involvement in staphylococcal scalded skin syndrome. Clin Infect Dis 25:1369–1373, 1997. 17. Saiman L, Jakob K, Holmes KW, et al: Molecular epidemiology of staphylococcal scalded skin syndrome in premature infants. Pediatr Infect Dis J 17:329–334, 1998. 18. Ladhani S, Evans RW: Staphylococcal scalded skin syndrome. Arch Dis Child 78:85–88, 1998. 19. Loughead JL: Congenital staphylococcal scalded skin syndrome: report of a case. Pediatr Infect Dis J 11:413–414, 1992. 20. Schlievert PM, Kelly JA: Clindamycin-induced suppression of toxic-shock syndrome-associated exotoxins production. J Infect Dis 149:471, 1984. 21. Vergeront JM, Stolz SJ, Crass BA, et al: Prevalence of serum antibody to staphylococcal enterotoxin F among Wisconsin residents: implication for toxic shock syndrome. J Infect Dis 148:692–698, 1983. 22. Ejlertsen T, Jensen A, Lester A, Rosdahl VT: Epidemiology of toxic shock shock syndrome toxin-1 production in Staphylococcus aureus strains in Denmark 1959 and 1990. Scand J Infect Dis 26:599–604, 1994. 23. Kain KC, Schulzer M, Chow AW: Clinical spectrum of nonmenstrual toxic shock syndrome (TSS): comparison with menstrual TSS by multivariate discriminant analyses. Clin Infect Dis J 16:100–106, 1993. 24. Reingold AL: Nonmenstrual toxic shock syndrome: the growing picture. JAMA 249:932, 1983. 25. Chesney PJ, Davis JP, Purdy WK, et al: Clinical manifestations of toxic shock syndrome. JAMA 246:741–748, 1981. 26. Chesney PJ: Clinical aspects and spectrum of illness of toxic shock syndrome: overview. Rev Infect Dis 11(Suppl 1):S1–S7, 1989. 27. Rosene KA, Copass MK, Kasner LS, et al: Persistent neuropsychological sequelae of toxic shock syndrome. Ann Intern Med 96:865–870, 1982. 28. Hurwitz RM, Rivera HP, Gooch MH, et al: Toxic shock syndrome or toxic epidermal necrolysis? Case reports showing clinical similarity and histologic separation. J Am Acad Dermatol 7:246–254, 1982. 29. Bach MC: Dermatologic signs in toxic shock syndrome—clues to diagnosis. J Am Acad Dermatol 8:343–347, 1983. 30. Chesney PJ, Crass BA, Polyak MB, et al: Toxic shock syndrome: management and long-term sequelae. Ann Intern Med 96:847–851, 1982. 31. Reingold AL, Dan BB, Shands KN, Broome CV: Toxic-shock syndrome not associated with menstruation: a review of 54 cases. Lancet 1:1–4, 1982. 32. Annane D, Clair B, Salomon J: Managing toxic shock syndrome with antibiotics. Expert Opin Pharmacother 5:1701–1710, 2004. 33. Herold BC, Immergluck LC, Maranan MC, et al: Communityacquired methicillin-resistant Staphylococcal aureus in children. Pediatr Infect Dis J 279:593–598, 1998. *Selected readings.

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34. Tack DA, Fleishcer A Jr, McMichael A, Feldman S: The epidemic of tinea capitis disproportionately affects school-aged African Americans. Pediatr Dermatol 1:75, 1999. 35. Bonventre PF, Thompson MR, Adinolfi LE, et al: Neutralization of toxic shock syndrome toxin-1 by monoclonal antibodies in vitro and in vivo. Infect Immun 56:135–141, 1988. 36. Best GK, Scott DF, Kling JM, et al: Protection of rabbit in an infection model of toxic shock syndrome (TSS) by a TSS toxin-1-specific monoclonal antibody. Infect Immun 56:998–999, 1988. 37. Todd JK, Ressman M, Caston SA, et al: Corticosteroid therapy for patients with toxic shock syndrome. JAMA 252:399–402, 1984. 38. Aly R, Hay RJ, Del Palacio A, Galimberti R: Epidemiology of tinea capitis. Med Mycol 38(Suppl 1):S183–S188, 2000. 39. Frieden IJ: Tinea capitis: asymptomatic carriage of infection. Pediatr Infect Dis J 18:186–190, 1999. 40. Philpot C: Some aspects of the epidemiology of tinea. Mycopathologia 62:3–13, 1977. 41. Babel DE, Baugmans A: Evaluation of the adult carrier stage in juvenile tinea capitis caused by Trichophyton tonsurans. J Am Acad Dermatol 21:1209–1212, 1989. 42. Hubbard TW: The predictive value of symptoms in diagnosing childhood tinea capitis. Arch Pediatr Adolesc Med 153:1150–1153, 1999. 43. Pomeranz AJ, Sabnis SS: Tinea capitis: epidemiology, diagnosis, and management strategies. Paediatr Drugs 4:779–783, 2002. 44. Honig PJ, Caputo GL, Leyden JJ, et al: Treatment of kerions. Pediatr Dermatol 11:69–71, 1994. 44a. Fuller LC, Child FJ, Midgley G, Higgins EM: Diagnosis and management of scalp ringworm. BMJ 326:539–541, 2003. 45. Abdel-Rahman SM, Nahata MC, Powell DA: Response to initial griseofulvin therapy in pediatric patients with tinea capitis. Ann Pharmacother 31:406–410, 1997. 46. Gupta AK, Adam P, Dlova N, et al: Therapeutic options for the treatment of tinea capitis caused by Trichophyton species: griseofulvin versus the new oral antifungal agents, terbinafi ne, itraconazole, and fluconazole. Pediatr Dermatol 18:433–438, 2001. 47. Chan YC, Friedlander SF: New treatment for tinea capitis. Curr Opin Infect Dis 17:97–103, 2004. 47a. Gupta AK, Cooper EA, Ryder JE, Nicol KA: Optimal management of fungal infections of the skin, hair, and nails. Am J Clin Dermatol 5:225–237, 2004. 48. Allen H, Honig PJ, Leyden JJ, McGinley KJ: Selenium sulfide: adjunctive therapy for tinea capitis. Pediatrics 69:81–83, 1982. 49. Keipert JA: Beneficial effect of corticosteroid therapy in Microsporum canis kerion. Australas J Dermatol 25:127–130, 1984. 50. Hussain I, Muzaffar F, Rashid T, et al: A randomized, comparative trial of treatment of kerion celsi with griseofulvin plus oral prednisolone vs. griseofulvin alone. Med Mycol 37:97–99, 1999. 51. Laude TA, Shah BR, Lynfield Y: Tinea capitis in Brooklyn. Am J Dis Child 136:1047–1050, 1982. 52. Faergemann J, Mörk NJ, Hagland A, Ödegård A: A multicenter (double-blind) comparative study to assess the safety and efficacy of fluconazole and griseofulvin in the treatment of tinea corporis and tinea cruris. Br J Dermatol 136:575–577, 1997. 53. Bronson DM, Desai DR, Barsky S, Foley SM: An epidemic of infection with Trichophyton tonsurans revealed in a 20-year survey of fungal infections in Chicago. J Am Acad Dermatol 8:322–330, 1983. 54. Smith KJ, Neafie RC, Skelton HG 3rd, et al: Majocchi’s granuloma. J Cutan Dermatol 18:28–35, 1991. 55. Jones HE, Reinhardt JH, Rinaldi MG: Acquired immunity to dermatophytes. Arch Dermatol 109:840–848, 1974. 56. Raynolds RD, Boiko S, Lucky AW: Exacerbation of tinea corporis during treatment with 1% clotrimazole/0.05% betamethasone diproprionate (Lotrisone). Am J Dis Child 145:1224–1225, 1991. 57. Solomon BA, Lee WL, Green SC, et al: Modification of neutrophils function by naftifi ne. Br J Dermatol 128:393–398, 1993. 58. Terragni L, Lasagni A, Oriani A: Pityriasis versicolor of the face. Mycoses 34:345–347, 1991. 59. Faergemann J: Pityrosporum species as a cause of allergy and infection. Allergy 54:413–419, 1999. 59a. Gupta AK, Batra R, Bluhm R, Faergemann J: Pityriasis versicolor. Dermatol Clin 21:413–429, 2003. 60. Diven DG: An overview of poxviruses. J Am Acad Dermatol 44:1–16, 2001. 61. Mandel MJ, Lewis RJ: Molluscum contagiosum of the newborn. Br J Dermatol 84:370–372, 1970.

62. Kipping HF: Molluscum dermatitis. Arch Dermatol 103:106–107, 1971. 63. Thompson CH: Identification and typing of molluscum contagiosum virus in clinical specimens by polymerase chain reaction. J Med Virol 53:205–211, 1997. 64. Brown ST, Nalley JF, Kraus SJ: Molluscum contagiosum. Sex Transm Dis 8:227–234, 1981. 65. Weston WL, Lane AT: Should molluscum be treated? Pediatrics 65:865, 1980. 66. Moed L, Shwayder TA, Chang MW: Cantharidin revisited: a blistering defense of an ancient medicine. Arch Dermatol 137:1357–1360, 2001. 67. Niizeki K, Hashimoto K: Treatment of molluscum contagiosum with silver nitrate paste. Pediatr Dermatol 16:395–397, 1999. 68. Silverberg NB, Sidbury R, Mancini AJ: Childhood molluscum contagiosum: experience with cantharidin therapy in 300 patients. J Am Acad Dermatol 43:503–507, 2000. 68a. Bikowski JB Jr: Molluscum contagiosum: the need for physician intervention and new treatment options. Cutis 73:202–206, 2004. 69. Davies EG, Thrasher A, Lacey K, Harper J: Topical cidofovir for severe molluscum contagiosum. Lancet 353:2042, 1999. 70. Zabawski EJ Jr: A review of topical and intralesional cidofovir. Dermatol Online J 6:3, 2000. 71. Meadows KP, Tyring A, Pavia AT, Rallis TM: Resolution of recalcitrant molluscum contagiosum virus lesions in human immunodeficiency virus infected patients treated with cidofovir. Arch Dermatol 133:987–990, 1997. 72. Yashar SS, Shamiri B: Oral cimetidine treatment of molluscum contagiosum. Pediatr Dermatol 16:493, 1999. 73. Hicks CB, Myers SA, Giner J: Resolution of intractable molluscum contagiosum in a human immunodeficiency virus-infected patient after institution of antiretroviral therapy with ritonavir. Clin Infect Dis 24:1023–1025, 1997. 74. Hurni MA, Bohlen L, Furrer H, Braathen LR: Complete regression of giant molluscum contagiosum lesions in an HIV-infected patient following combined antiretroviral therapy with saquinavir, zidovudine and lamivudine. AIDS 11:1784–1785, 1997. 75. Betlloch I, Pinazo I, Mestre F, et al: Molluscum contagiosum in human immunodeficiency virus infection: response to zidovudine. Int J Dermatol 28:351–352, 1989. 76. Theos AU, Cummins R, Silverberg NB, Paller AS: Effectiveness of imiguimid cream 5% for treating childhood molluscum contagiosum in a double-blind, randomized pilot trial. Cutis 74:134–138, 2004. 77. Nelson MR, Chard S, Barton SE: Intralesional interferon for the treatment of recalcitrant molluscum contagiosum in HIV antibody– positive individuals—a preliminary report. Int J STD AIDS 6:351–352, 1995. 78. Janniger CK, Schwartz RA: Molluscum contagiosum in children. Cutis 52:194–196, 1993. 79. Yoshinaga IG, Conrado LA, Schainberg SC, Grinblat M: Recalcitrant molluscum contagiosum in a patient with AIDS: combined treatment with CO2 laser, trichloroacetic acid, and pulsed dye laser. Lasers Surg Med 27:291–294, 2000. 80. Scott PM: Curettage for molluscum contagiosum. JAAPA 15:53–54, 2002. 81. Ronnerfalt L, Fransson J, Wahlgren CF: EMLA cream provides rapid relief for the curettage of molluscum contagiosum in children with atopic dermatitis without causing serious application-site reactions. Pediatr Dermatol 15:309–312, 1998. 82. Parsons JM: Pityriasis rosea update: 1986. J Am Acad Dermatol 15: 159–167, 1986. 83. Drago F, Ranieri E, Malaguti F, et al: Human herpesvirus 7 in patients with pityriasis rosea: electron microscopy investigations and polymerase chain reaction in mononuclear cells, plasma and skin. Dermatology 195:374–378, 1997. 84. Miranda SB, Lupi O, Lucas E: Vesicular pityriasis rosea: response to erythromycin treatment. J Eur Acad Dermatol Venerol 18:622–625, 2004. 85. Friedman SJ: Pityriasis rosea with erythema-multiforme-like lesions. J Am Acad Dermatol 17:135–136, 1987. 86. Pireson JC, Dijkstra JW, Elston DM: Purpuric pityriasis rosea. J Am Acad Dermatol 28:1021, 1993. 87. Imamura S, Ozaki M, Oguchi M, et al: Atypical pityriasis rosea. Dermatologica 171:474–477, 1985.

Chapter 126 — Other Important Rashes 88. Ahmed I, Charles-Holmes R: Localized pityriasis rosea. Clin Exp Dermatol 25:624–626, 2000. 89. Vidimos AT, Camisa C: Tongue and cheek: oral lesions in pityriasis rosea. Cutis 50:276–280, 1992. 90. Sharma PK, Tadav TP, Gautam RK, et al: Erythromycin in pityriasis rosea: a double-blind placebo-controlled clinical trial. J Am Acad Dermatol 42:241–244, 2000. 91. Leenutaphong V, Jiamton S: UVB phototherapy for pityriasis rosea: a bilateral comparison study. J Am Acad Dermatol 33:996–999, 1995. 92. Kawasaki T: General review and problems in Kawasaki disease. Jpn Heart J 36:1–12, 1995. 93. Taubert KA, Rowley AH, Shulman ST: Nationwide survey of Kawasaki disease in children. Circulation 87:1776–1780, 1993. 94. Melish ME, Hicks RM, Larson EJ: Mucocutaneous lymph node syndrome in the United States. Am J Dis Child 130:599–607, 1976. 95. Chang LY, Chang IS, Lu CY, et al; Kawasaki Disease Research Group: Epidemiologic features of Kawasaki disease in Taiwan, 1996–2002. Pediatrics 114:e678–e682, 2004. 96. Rozo JC, Jefferies JL, Eidem BW, Cook PJ: Kawasaki disease in the adult: a case report and review of the literature. Tex Heart Inst J 31:160–164, 2004. 96a. Burns JC, Glodé MP: Kawasaki syndrome. Lancet 364:533–544, 2004. 97. Tomita S, Chung K, Mas M, et al: Peripheral gangrene associated with Kawasaki disease. Clinical Infect Dis 14:121–126, 1992. 98. Freeman AF, Crawford SE, Finn LS, et al: Inflammatory pulmonary nodules in Kawasaki disease. Pediatr Pulmonol 36:102–106, 2003. 99. Palazzi DL, McClain KL, Kaplan SL: Hemophagocytic syndrome after Kawasaki disease. Pediatr Infect Dis J 22:663–666, 2003. 100. Beiser AS, Takahashi M, Baker AL, et al: A predictive instrument for coronary artery aneurysms in Kawasaki disease. Am J Cardiol 81:1116–1120, 1998. 101. Nakamura Y, Yashiro M, Uehara R, et al: Use of laboratory data to identify risk factors of giant coronary aneurysms due to Kawasaki disease. Pediatr Int 46:33–38, 2004. 102. Hwong TM, Arifi AA, Wan IY, et al: Rupture of a giant coronary artery aneurysm due to Kawasaki disease. Ann Thorac Surg 78:693– 695, 2004. *103. Newburger JW, Takahashi M, Gerber MA, et al; Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association: Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Pediatrics 114:1708–1733, 2004. (Published erratum in: Pediatrics 115:1118, 2005) 104. Naoe S, Takahashi K, Masuda H, Tanaka N: Kawasaki disease: with particular emphasis on arterial lesions. Acta Pathol Jpn 41:785–797, 1991. 105. Hicks RV, Melish ME: Kawasaki syndrome: rheumatic complaints and analysis of salicylate therapy. Arthritis Rheum 22:621–622, 1979. 106. Newburger JW, Burns JC, Beiser AS, Loscalzo J: Altered lipid profi le after Kawasaki syndrome. Circulation 84:625–631, 1991. 107. Kim M, Kim K: Elevation of cardiac troponin I in the acute stage of Kawasaki disease. Pediatr Cardiol 20:184–188, 1999. 108. Danias PG, Stuber M, Botnar RM, et al: Coronary MR angiography clinical applications and potential for imaging coronary artery disease. Magn Reson Imaging Clin N Am 11:81–99, 2003. 109. Sato K, Ouchi K, Taki M: Yersinia pseudotuberculosis infection in children resembling Izumi fever and Kawasaki syndrome. Pediatr Infect Dis 2:123–126, 1983. 110. Newburger JW, Takahashi M, Beiser AS, et al: A single intravenous infusion of gamma globulin as compared with four infusions in the treatment of acute Kawasaki syndrome. N Engl J Med 324:1633–1639, 1991.

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111. Brogan PA, Bose A, Burgner D, et al: Kawasaki disease: an evidence based approach to diagnosis, treatment, and proposals for future research. Arch Dis Child 86:286–290, 2002. 112. Al-Mayouf SM: The use of corticosteroid therapy in refractory Kawasaki patients. Clin Rheumatol 23:11–13, 2004. 113. Lee JH, Hung HY, Huang FY: Kawasaki disease with Reye syndrome: report of one case. Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi 33:67–71, 1992. 114. Burns JC, Capparelli EV, Brown JA, et al: Intravenous gamma globulin treatment and retreatment in Kawasaki disease. US/Canadian Kawasaki Syndrome Study Group. Pediatr Infect Dis J 17:1144–1148, 1998. 115. Durongpisitkul K, Soongswang J, Laohaprasitiporn D, et al: Immunoglobulin failure and retreatment in Kawasaki disease. Pediatr Cardiol 24:145–148, 2003. 116. Miura M, Ohki H, Tsuchihashi T, et al: Coronary risk factors in Kawasaki disease treated with additional gammaglobulin. Arch Dis Child 89:776–780, 2004. 117. Wright DA, Newburger JW, Baker A, Sundel RP: Treatment of immune globulin-resistant Kawasaki disease with pulsed doses of corticosteroids. J Pediatr 123:146–149, 1996. 118. Weiss JE, Eberhard BA, Chowdhurry D, Gottlieb BS: Infl iximab as a novel therapy for refractory Kawasaki disease. J Rheumatol 31:808– 810, 2004. 119. Zaitsu M, Hamasaki Y, Tashiro K, et al: Ulinastatin, an elastase inhibitor, inhibits the increased mRNA expression of prostaglandin H 2 synthetase-type 2 in Kawasaki disease. J Infect Dis 181:1101–1109, 2000. 120. Williams RV, Wilke VM, Tani LY, Minich LL: Does abciximab enhance regression of coronary aneurysms resulting from Kawasaki disease? Pediatrics 109:e4, 2002. 121. Sundel RP, Baker AL, Fulton DR, Newburger JW: Corticosteroids in the initial treatment of Kawasaki disease: report of a randomized trial. J Pediatr 142:611–616, 2003. 122. Lee JY, Song JY, Kim SJ, et al: Coronary rotational ablation for calcific coronary artery stenosis in a young child. Int J Cardiol 99:349–350, 2005. 123. Tsuda E, Kitamura S; Cooperative Study of Japan: National survey of coronary artery bypass grafting for coronary stenosis caused by Kawasaki disease in Japan. Circulation 110:(11 Suppl 1):II61–II66, 2004. 124. Iliadis EA, Duvernoy CS: Stent placement for coronary stenosis in Kawasaki disease: case report and literature review. J Interv Cardiol 15:29–31, 2002. 125. Hayden GF: Skin diseases encountered in a pediatric clinic: a one-year prospective study. Am J Dis Child 139:36–38, 1985. 126. Brook I, Frazier EH, Yeager JK: Microbiology of nonbullous impetigo. Pediatr Dermatol 14:192–195, 1997. 127. Darmstadt GL: Oral antibiotic therapy for uncomplicated bacterial skin infections in children. Pediatr Infect Dis J 16:227–240, 1997. 128. Hogan P: Pediatric dermatology: impetigo. Aust Fam Physician 27: 735–736, 1998. 129. Jones ME, Karlowsky JA, Draghi DC, et al: Epidemiology and antibiotic susceptibility of bacteria causing skin and soft tissue infections in USA and Europe: a guide to appropriate antimicrobial therapy. Int J Antimicrob Agents 22:406–419, 2003. 130. Bass JW, Chan DS, Creamer KM, et al: Comparison of oral cephalexin, topical mupirocin and topical bacitracin for the treatment of impetigo. Pediatr Infect Dis J 16:708–710, 1997. 131. Dancer SJ, Noble WC: Nasal, axillary, and perineal carriage of Staphylococcus aureus among women: identification of strains producing epidermolytic toxin. J Clin Pathol 44:681–684, 1991. 132. Doebbeling BN, Breneman DL, Neu HC, et al: Elimination of Staphylococcus aureus nasal carriage in health care workers: analysis of six clinical trials with calcium mupirocin ointment. Clin Infect Dis 17:466–474, 1993. 133. Burns JC, Joffe L, Sergeant RA, Glode MP: Anterior uveitis associated with Kawasaki syndrome. Pediatr Infect Dis 4:258–261, 1985.

Chapter 127

Hematologic/Oncologic

Sickle Cell Disease Timothy G. Givens, MD

Key Points Children with sickle cell disease are at risk for a variety of potentially life-threatening complications, due to vaso-occlusive phenomena, profound anemia, and infection. Rapid identification of acute crises in sickle cell disease is essential to successful intervention and preservation of function. Prompt reversal of hypoxemia, restoration of perfusion and oxygen-carrying capacity, and administration of antibiotics targeted toward encapsulated organisms remain the cornerstones of emergency department management.

Recognition and Approach As the abnormal hemoglobin molecule is deoxygenated, it irreversibly forms a rigid polymer within the RBC, distorting its configuration. As a consequence, occlusion of small blood vessels, increased blood viscosity and concomitant stasis, and further tissue hypoxia follow. Sickle cell patients therefore develop symptoms related to impaired perfusion and ischemia, such as pain, impaired mental status, neurologic deficits, and tissue engorgement. The rate and extent of sickling is related to three factors: the degree of cellular hypoxia, the hemoglobin concentration within the erythrocyte, and the presence (or absence) of fetal hemoglobin (Hb F).5 Therapy for sickle cell disease is often directed at these three variables.

Clinical Presentations and Important Clinical Features Complications of sickle cell disease present in one of four general ways: vaso-occlusive crisis, acute splenic sequestration crisis, acute aplastic crisis, and infection/sepsis.

Introduction and Background

Vaso-occlusive Crisis

Sickle cell disease refers to a group of disorders resulting from mutations in the hemoglobin gene that can lead to deformation of the red blood cell (RBC) into a crescent, or sickle, shape. Hemoglobin S is formed when valine replaces glutamine at the sixth amino acid position of the beta chain of hemoglobin. Patients who inherit hemoglobin S in a homozygous autosomal recessive fashion (Hb SS) have sickle cell anemia, while those who are heterozygous have sickle trait (Hb AS).1 Sickle cell disease primarily affects persons of African, Mediterranean, Indian, and Middle Eastern descent. In the United States, African Americans are most affected, with approximately 0.15% having sickle cell anemia (Hb SS) and approximately 8% having sickle trait (Hb AS).1,2 There is also a high incidence of sickle cell disease in Hispanic Americans from the Caribbean, Central America, and South America.3,4 Children born in many hospitals in the United States are routinely screened in the neonatal period, and antenatal diagnosis is becoming more prevalent in at-risk populations. However, an index of suspicion is necessary when treating patients born outside U.S. hospitals or when results of the neonatal screen are unavailable.

Vaso-occlusive phenomena can occur in any tissue or organ system, as the microvasculature becomes clogged with sickled erythrocytes. Most commonly, this results in pain. As occlusion of small vessels occurs, tissue hypoxemia results, leading to further sickling in a cascade effect. Interruption of this vicious cycle with hydration, oxygen, and analgesia is the goal of therapy for vaso-occlusive pain crisis. Virtually all patients with sickle cell disease experience acute pain to some degree. Coping abilities vary between patients, yet epidemiologic studies indicate that patients who seek medical care for pain have lower levels of fetal hemoglobin (Hb F) and higher steady state hemoglobin levels.6 To expeditiously evaluate and manage a painful episode can be difficult. Painful crises may mimic a number of other disease states. A careful history and physical examination is key. The most frequently affected body regions are the lumbosacral spine, knee, shoulder, elbow, and femur. At times, pain episodes may be accompanied by localized tenderness, erythema, warmth, and swelling, raising a concern for osteomyelitis. Joint effusions are particularly common when the knees and elbows are involved. Often, however, there are no correlative physical findings, save for mild tachycardia

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and hypertension. The clinician must exercise caution not to dismiss all pain in patients with sickle cell disease as a vasoocclusive crisis, as in doing so, one may overlook serious underlying pathology. In light of the range of clinical findings of vaso-occlusive pain crises, it is best to proceed conservatively in the emergency setting, taking the patient’s pain at face value and yet maintaining an attitude of critical discernment for underlying disease. Hand-Foot Syndrome Often the first episode of vaso-occlusive pain occurs in infants and toddlers as acute swelling of the hands and feet (dactylitis).1 It may provide the first indication that a child has sickle cell disease in the event that he or she has escaped detection by neonatal screening.7 Hand-foot syndrome typically occurs symmetrically, involving the metacarpals and/or metatarsals. It may be unaccompanied by hematologic or radiographic abnormalities. When fever is present, osteomyelitis is difficult to exclude and may require a bone scan or MRI. Hand-foot syndrome should be treated as any other pain crisis, with regularly scheduled analgesia.

Table 127–1

Causes of Acute Chest Syndrome

Cause Infarction without known precipitant Viral Mycoplasma Fat embolism ± infection Chlamydia Mixed infections Bacteria Mycobacterium (tuberculosis & avium complex) Unknown*

0–9 years N = 329 patients (%)

10–19 years N = 188 patients (%)

50 (15.9%)

43 (22.9%)

36 (10.9%) 29 (8.8%) 24 (7.3%) 19 (5.8%) 16 (4.9%) 13 (4%) 3 (0.9%)

5 7 16 15 3 12 0

129 (41.3%)

(2.7%) (3.7%) (8.5%) (8%) (1.6%) (6.4%)

79 (42%)

*The cause of episodes for which some or all of the diagnostic data were incomplete and no etiologic agent was identified was considered to be unknown. From Vichinsky EP, Neumayr LD, Earles AN, et al; National Acute Chest Syndrome Study Group: Causes and outcomes of the acute chest syndrome in sickle cell disease. N Engl J Med 342:1855– 1865, 2000.

Acute Chest Syndrome When the microcirculation of certain organ systems is compromised, life-threatening complications may result. One of these is acute chest syndrome, a leading cause of morbidity and mortality among patients with sickle cell disease. Pulmonary sequestration of erythrocytes and sickling leads to infarction of lung tissue and may progress to a full-blown acute respiratory distress syndrome picture. As with pain crises, the risk of developing acute chest syndrome is higher in sickle cell patients who are younger, have a lower concentration of Hb F, have a higher steady state hemoglobin concentration, or have a higher steady state leukocyte count.8 Clinically, acute chest syndrome is a common manifestation of a variety of pathologic processes, which may be difficult to differentiate in a patient with Hb SS disease. Findings may include fever, cough, chest pain, dyspnea, productive cough or hemoptysis, hypoxia, leukocytosis, and new pulmonary infi ltrates on chest radiograph. Hence, admission diagnoses in those patients found ultimately to have acute chest syndrome include fever, anemia, infection, nonpulmonary vasoocclusive events, abdominal pain, asthma, heart failure, and orthopedic conditions.9,10 In children, infection is somewhat more likely as a cause of acute chest syndrome than it is in adults, though often no etiologic agent is identified. When a pathogen is identified, the leading three organisms implicated are Chlamydia, Mycoplasma, and respiratory syncytial virus10 (Table 127–1). While there are other minor differences in the presentation of acute chest syndrome between adults and children, these do not appreciably impact its management. Cerebrovascular Accident Cerebrovascular accidents (CVAs) are another serious complication of vaso-occlusive sickling. Strokes are more common in children with homozygous (Hb SS) disease, occurring in about 11% of patients by the age of 20 years.11,12 Three quarters of CVAs are infarcts, and less than 10% are preceded by transient ischemic attacks. An association between recent and frequent episodes of acute chest syndrome and risk of CVA exists in children, perhaps because recurrent damage to the endothelium of the pulmonary vascular bed predicts

damage to cerebral vasculature.11,13 The diagnosis of stroke in patients with sickle cell disease can be challenging. Clinical signs are nonspecific and often subtle. Less than 10% of patients present with classic CVA symptoms, and headaches are common in sickle cell patients regardless of central nervous system involvement. Any sickle cell patient with focal neurologic signs, including seizure or hemiparesis, requires an intracranial imaging study and emergent intervention to limit ischemic injury (see Chapter 44, Central Nervous System Vascular Disorders). Priapism Males with sickle cell disease are susceptible to priapism, the presence of a persistent and often painful penile erection. Priapism may occur as a sustained episode lasting hours to weeks or as a series of repetitive, reversible erections with intervening detumescence (“stuttering”). Acute attacks of priapism sometimes follow sexual activity, but generally have no known precipitating event. In addition to the immediate effects of pain, cumulative ischemic damage with either a prolonged erection or recurrent priapism episodes over time puts the patient who suffers these episodes at risk of sexual dysfunction and impotence. Pediatric patients with priapism are more likely to respond to conservative measures such as analgesia and hydration, while management in adult patients usually requires a more aggressive approach, including surgery (see Chapter 89, Penile and Testicular Disorders).3 Acute Abdominal Pain One of the most perplexing scenarios is the patient with sickle cell disease and acute abdominal pain. Intraabdominal sickling and vaso-occlusion may occur and be difficult to distinguish from other myriad causes of intraabdominal pathology. Analgesic therapy should not be withheld while pursuing a diagnosis in sickle cell patients with abdominal pain. Biliary colic and acute cholecystitis due to gallstones should always be considered. Sickled RBCs undergo chronic hemolysis, leading to hyperbilirubinemia and formation of bilirubin-containing gallstones. Patients

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are often asymptomatic, but the gallstones may cause abdominal pain due to obstruction or inflammation. The resultant right upper quadrant pain may be indistinguishable from intrahepatic sickling or pain due to lower lobe pneumonia. If gallstones are present, however, abdominal pain coupled with fever, nausea, and vomiting point to cholecystitis, and should be managed appropriately (see Chapter 85, Gallbladder Disorders). Acute Sequestration Crisis Young children with Hb SS disease whose spleens have not yet experienced recurrent infarctions and resultant fibrosis, as well as those with other hemoglobin S syndromes with spleens that remain enlarged into adult life, may undergo obstruction of splenic sinusoids with sickled cells. This may lead to sudden trapping of large amounts of blood and a massively enlarged spleen. The patient rapidly develops a precipitous drop in hemoglobin level and signs of circulatory collapse, requiring prompt intervention to reverse hypovolemic shock. While a specific causative agent is often hard to identify, infection is a frequent precipitant. Acute sequestration usually occurs in patients with Hb SS after 6 months of age (due to the protective effects of Hb F prior to this) and is rare after the age of 2 years.3,7 It is a leading cause of morbidity and mortality among sickle cell patients in this age group. Acute sequestration may also occur in the liver. Clinical signs include hepatomegaly and tenderness to palpation of the right upper quadrant, hyperbilirubinemia, anemia, and reticulocytosis. The liver is not as distensible as the spleen, however, so this presentation is seldom accompanied by cardiovascular collapse. Acute Aplastic Crisis The erythrocytes of patients with sickle cell disease have a shortened half-life (15 to 50 days) compared with normal erythrocytes (120 days). In the usual state, patients with Hb SS compensate for this by increasing marrow production of erythrocytes six- to eightfold.1 However, any agent that can cause marrow suppression places the patient with sickle cell disease at risk of developing a profound anemia, as the hemoglobin concentration steadily falls by 10% to 15% per day without a compensatory reticulocytosis. Typically this phenomenon follows infection with parvovirus B19, although toxins, folate deficiency, and other viral and bacterial infections have been associated with erythropoietic suppression. While pallor and tachycardia are common features of an aplastic crisis, bone pain and hemodynamic instability are not. Patients may present with vague, nonspecific symptoms such as fever, headache, nausea and vomiting, fatigue, and dyspnea. The diagnosis is confirmed by noting the correlative laboratory values of anemia and absent reticulocyte production (i.e., reticulocyte count < 3%). Infection/Sepsis By far the most common cause of death in children with sickle hemoglobinopathies is infection. This is primarily related to splenic dysfunction. Both of the spleen’s immunologic functions—removal of particulate matter from the intravascular space, and antibody synthesis—are impaired in sickle cell disease.1 Additionally, the serum of patients with sickle cell disease is lacking in heat-labile opsonizing activity

related to an abnormality of the properidin pathway, which is specific for phagocytosis of pneumococci.14,15 Hence, Hb SS patients are at increased risk of sepsis from encapsulated organisms, particularly pneumococci. Outcomes for patients with sickle cell disease have been enhanced through the use of active immunization against Streptococcus pneumoniae and Haemophilus influenzae and through the use of prophylactic penicillin. Prophylactic penicillin is efficacious in reducing the incidence of pneumococcal sepsis and meningitis in children less than 5 years of age. After this age, this therapy shows no clinically beneficial effect and it is often discontinued.16 Prophylactic penicillin should be continued indefinitely in children with prior pneumococcal sepsis, as they are at much higher risk of recurrent sepsis.17 In spite of prophylactic penicillin use, the risk of sepsis is still great (see Chapter 13, Sepsis).

Management Patients with sickle cell disease, like other emergency department patients, should first and foremost have their airway, breathing, and circulatory status addressed. Complications such as sequestration or sepsis can occur precipitously and become rapidly severe and even life-threatening. Frequent assessment of the patient is necessary to note subtle changes in physiologic status. Do not attribute tachycardia to baseline anemia in Hb SS patients and remember that, in the youngest patients, compensatory vasoconstriction can mask volume depletion and maintain blood pressure in the face of shock. In addition, ancillary tools for assessment of physiologic status may provide deceptive information. Pulse oximetry is not an accurate predictor of actual oxygen saturation in vasoocclusive crisis, with true oxygen saturation averaging 5% higher than values measured by pulse oximetry.18,19 Vaso-occlusive Crisis A complete history will catalog the frequency and nature of prior pain crises, medications required to control pain crises in the past and current medication use, and baseline laboratory values. Physical examination must be thorough and target the identification of acute infection or other precipitants of a vaso-occlusive crisis. The development of new neurologic signs or symptoms is of particular concern and mandates appropriate imaging studies. Laboratory tests beyond a baseline hemoglobin determination add little to management in patients who present with typical sickle crisis symptoms.20,21 For patients with unusual presentations (e.g., worsening anemia, signs of joint or bone infection, fever, increased jaundice, or chest or abdominal pain) additional testing is generally required. Some clinicians routinely obtain a chest radiograph to screen for infection, though this practice in low-risk patients (i.e., those without fever, chills, or pulmonary signs or symptoms) is not supported by data.22 The cornerstones of therapy for vaso-occlusive episodes are hydration and provision of analgesia. Initial intravenous fluid is usually isotonic saline, particularly in patients with evidence of impaired circulation. There are theoretical benefits to use of hypotonic fluids, in that hyponatremia is known to interfere with the polymerization of hemoglobin S. One study demonstrated that hyponatremia induced by using desmopressin (DDAVP) in combination with a lowsodium diet and a diuretic correlated with a decline in the

Chapter 127 — Sickle Cell Disease

frequency and duration of painful crises.23 However, there are no data to support the routine use of hypotonic fluids during acute vaso-occlusive crisis. Analgesia is the other arm of mainstream therapy. Achieving adequate pain control while avoiding the complications of analgesic agents, such as opioids, is a clinical challenge. This is particularly true in pediatric patients who may not have developed tolerance to such agents. Oral analgesics are adequate for most patients with mild to moderate pain. Ibuprofen or acetaminophen with or without codeine is often adequate to control pain in children who are not yet of school age. Massage and local heat may also provide ancillary relief. Parenteral medications are generally reserved for those who cannot tolerate oral therapy or who are in severe pain. Ultimately, this is the majority of patients who seek emergency care. The experience of pain is multifactorial and difficult to objectively measure. By the teen years, many patients with Hb SS disease have experienced numerous pain crises, developed a level of opioid tolerance, and require high doses of opioid agents to relieve their acute pain. Medical personnel are often concerned about the chance of furthering drug dependence in these individuals with repeated provision of higher doses of medication. Unfortunately, there is little beyond subjective self-report by patients to inform the clinician about the level of their pain. In an effort to control the patient’s pain adequately, analgesia must be titrated to patient need and not to artificially derived limits, while monitoring the patient appropriately for side effects. A fi xed administration schedule, with an interval that maintains adequate analgesia, will foster a steady state drug level, improved pain control, and decreased patient anxiety.3 When using parenteral narcotics, morphine is preferred to meperidine (Demerol), which has a metabolite (normeperidine) that is epileptogenic and poorly metabolized in patients with sickle cell disease.24 Also, morphine may be administered subcutaneously if venous access is problematic. A synergistic therapy is intravenous ketorolac (Toradol), which has a narcotic-sparing effect when administered for acute pain of various origins, including sickle cell disease.25,26 Patientcontrolled analgesia (PCA) is an effective method for administering narcotics to older children and adolescents. In addition to enabling titration of medication to pain severity, PCA provides patients with a sense of control and involvement in their own care (see Chapter 158, Approach to Pain Management). Acute Chest Syndrome Any patient with vaso-occlusive disease and demonstrated hypoxemia should receive supplemental oxygen therapy. While oxygen has been shown to reverse sickling in vitro, clinically it has not been shown to affect the incidence or course of vaso-occlusive episodes.27,28 Paradoxically, oxygen can suppress erythropoietin levels and reticulocytosis, interfering with a compensatory response and increasing the mass of sickled cells. Also, empirical oxygen therapy in the child who is not hypoxic can mask the evolution of acute chest syndrome and delay its diagnosis.1 At present, there are no conclusive data either supporting or contradicting the use of oxygen in this clinical setting, though it is traditionally provided to Hb SS patients in some centers. Splinting due to pain and resultant atelectasis can exacerbate or even cause acute chest syndrome. Pain control is

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therefore an important facet of chest pain management in Hb SS patients. Nonetheless, judicious care must be exercised with opioids due to the attendant risks of pulmonary edema and respiratory depression. Incentive spirometry has been shown to be of use in limiting progression of acute chest syndrome.29 These patients are also easily fluid overloaded and, once rehydrated, should receive fluid only at maintenance rates. Patients who have or are at risk of developing this complication often deteriorate quickly and require close monitoring, often in a pediatric intensive care unit. Hypoxemia is common and should be treated with supplemental oxygen. Because this disorder is difficult to distinguish from pneumonia, and because infection is a concomitant or antecedent factor in acute chest syndrome, empirical antibiotics are routinely given. Typically, a broad-spectrum cephalosporin such as cefuroxime and a macrolide to cover for atypical organisms are the recommended antimicrobial agents. Patients usually have hemoglobin levels 1 to 2 g/dl below their baseline and often respond well to simple transfusion of packed RBCs. In more severe cases, partial exchange transfusion should be considered. Guidelines for partial exchange transfusion include multilobar disease, rapidly progressive disease, marked respiratory distress, partial pressure of oxygen (Po2) less than 70 mm Hg in a child, or a fall of 25% in baseline Po2.30 This is best accomplished in the intensive care setting. Cerebrovascular Accident Cerebrovascular events are managed with expeditious exchange transfusion. The goal in treatment of acute stroke is to limit further sickling by acutely decreasing the proportion of hemoglobin S to less than 30%. While doing so, it is advisable to avoid hyperviscosity by keeping the hematocrit in the 35% range. Seizures should be controlled with anticonvulsants. Intensive care monitoring is usually necessary, as some patients develop increased intracranial pressure requiring assisted ventilation and pharmacologic therapy. Because the recurrence rate for stroke is high (greater than two thirds of patients who are not chronically transfused), regular transfusions of packed erythrocytes at monthly intervals are employed to keep the hemoglobin S level below 30%. This approach has been shown to be effective in limiting further strokes.11,12 Priapism Treatment of priapism is aimed at relieving pain, emptying the distended corpora cavernosa, and preventing impotence. The initial physical examination should include prostatic massage, which may cause detumescence. Minor repetitive episodes of priapism are often managed at home, with warm baths, exercise, and frequent bladder emptying. However, extremes of temperature should be avoided, as cold increases sickling and heat increases blood flow, compounding pain. If an individual episode persists for greater than 3 hours, patients should be encouraged to seek medical attention. Therapy of a more prolonged episode includes pain management with parenteral opioids, intravenous fluids, and, if needed, placement of a Foley catheter. As in stroke, reduction of the hemoglobin S level to less than 30% is the next immediate goal, via exchange transfusion. Complete detumescence may take weeks, but a response to exchange transfusion should see the onset of detumescence within a day or two.

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If a response is not realized within that time frame, surgical intervention may be required, and a urologic consultation should be sought. Surgical techniques are seldom necessary in prepubertal boys, who usually respond to simpler maneuvers. The usual surgical procedure is the Winter procedure or one of its modifications, which may be performed under local anesthesia.31 The Winter procedure is a corporospongiosum shunt performed by inserting a needle or scalpel through the glans into one of the corpora cavernosa and draining the viscous blood. The instrument is removed, the skin closed, and an ongoing drainage of cavernous blood into the systemic circulation occurs. Intermittently applied compression limits refi lling of the corpora cavernosa. The shunt usually closes spontaneously after several weeks, permitting normal subsequent erectile function. Without intervention, severe priapism results in impotence in greater than 80% of cases, while with transfusions and surgery the incidence falls to between 25% and 50%.3 Acute Abdominal Pain Management of patients with acute abdominal pain in sickle cell disease is like that of other patients with acute abdominal pain. Early involvement of a surgical consult is critical in the appropriate at-risk population, based upon history, physical examination, and laboratory and radiographic studies. If an Hb SS patient requires surgery, a simple or exchange transfusion should be performed prior to the operation if possible. Abdominal ultrasonography is an excellent imaging choice when considering gallstone disease in the differential diagnosis, as up to 50% of bilirubin stones are not radiopaque on plain radiographs. The clinician should be aware that the mere existence of gallstones in the presence of right upper quadrant pain and fever may not be indicative of acute cholecystitis. Often patients who have undergone cholecystectomy have been surprised to have their “cholecystitis” symptoms return. Acute Sequestration Crisis In the emergency setting, therapy for sequestration is directed at restoration of both intravascular volume and oxygencarrying capacity via immediate transfusion of packed RBCs. Once normal hemodynamics are restored, patients improve quickly. If there is a delay in obtaining blood for transfusion, a bolus of isotonic saline may temporize and possibly mobilize some red cells from the spleen. However, in this situation, transfusion is life saving. Other general supportive measures are appropriate. Splenic sequestration may recur, usually within a few months of the initial episode. On this basis, some hematologists have advocated elective splenectomy after the fi rst instance of sequestration. Because asplenic patients have increased susceptibility to invasive disease from encapsulated organisms (e.g., S. pneumoniae), which primarily affect children under 2 years of age, splenectomy is ideally delayed until after the patient’s second birthday. Acute Aplastic Crisis Most aplastic episodes are short lived and require no specific therapy beyond supportive measures. Transfusion of packed RBCs is primarily based on symptoms, though some recommend elective transfusion in patients whose hematocrit falls 20% to 25% below baseline values, or below an arbitrary

Table 127–2

Criteria for Outpatient Treatment of Fever in Sickle Cell Disease (6 mo–12 yr of Age)

Normal mental status Normal blood pressure/capillary refill Temperature ≤ 40° C (104° F) No prior pneumococcal sepsis Mild pain only No evidence of pneumonia WBC count 5000–30,000 cells/mm3 Hemoglobin ≥ 5 gm/dl Platelets > 100,000/mm3 Able to administer ceftriaxone 50 mg/kg IV/IM (no allergy) Reliable 24-hr follow-up Abbreviations: IM, intramuscularly; IV, intravenously; WBC, white blood cell. From Wilimas JA, Flynn PM, Harris SC, et al: A randomized study of outpatient treatment with ceftriaxone for selected febrile children with sickle cell disease. N Engl J Med 329:472–476, 1993.

value such as 18%. During the aplastic episode, the patient with sickle cell disease is contagious and should be isolated from vulnerable groups such as pregnant women and the immunocompromised. Infection/Sepsis Because of the heightened risk of serious infection in sickle cell patients, the diagnostic approach to a young child who has fever without apparent source is fairly dogmatic. A thorough history and physical examination notwithstanding, a complete blood count, urinalysis, chest radiograph, and cultures of the blood, urine, and throat are generally obtained on febrile patients. Children who appear toxic or who have signs of meningitis should additionally have a lumbar puncture performed. All children who appear ill and all infants ≤ 6 months old require empirical parenteral antibiotics (e.g., ceftriaxone), even before the return of laboratory results, and admission to the hospital.3 Well-appearing infants and children ≥ 6 months old who meet specific criteria (Table 127–2) may be treated as outpatients with closely coordinated followup.32-35 It is prudent to confer with the patient’s hematologist in making disposition decisions for sickle cell patients with fever. All patients with a new infi ltrate on chest radiograph, even if nontoxic appearing and with normal laboratory indices, require hospital admission due to the possibility of developing acute chest syndrome. Empirical antibiotics should be administered as previously described—a cephalosporin and a macrolide. Those with clinical findings suggestive of osteomyelitis require needle aspiration and culture of the offending lesion, and administration of empirical antibiotics directed against likely organisms (i.e., Staphylococcus aureus, S. pneumoniae, and Salmonella). Patients with urinary tract infections and pyelonephritis often develop papillary necrosis coincident with the infection, due to sickling in the renal papillae. The sloughing of the papillae may present clinically as hematuria. Urine cultures should guide antibiotic selection, and urologic consultation is recommended. Hydration should accompany intravenous antibiotic therapy in these instances, to ensure adequacy of renal perfusion.

Chapter 127 — Sickle Cell Disease

Future Directions Research continues into ways to cure sickle cell disease or prevent its complications. Some of these investigations are noted here. Hydroxyurea, an oral metabolite that promotes the synthesis of Hb F, has shown promise as a prophylactic agent to reduce the incidence of vaso-occlusive crises, acute chest syndrome, and stroke in pediatric patients with severe sickle cell disease.36 Recent data have shown it to be safe, effective, and well tolerated by children over prolonged periods.37 Bone marrow transplantation has been attempted and been curative in some cases of sickle cell disease. It is not without complications, however, and is expensive and not widely available. A substantial barrier to widespread use is the lack of human lymphocyte antigen–matched sibling donors.38 Stem cell transplantation using cells harvested from cord blood may avoid the problems encountered by bone marrow transplantation, and this is being actively investigated.39 Use of gene therapy is being explored as well. Angles of attack include attempts to inactivate the sickle gene, ways to increase expression of the Hb F gene, and introduction of genes whose protein products will block hemoglobin S polymerization.40

Summary Infants and children with sickle cell disease are at risk for a variety of potentially life-threatening complications due to vaso-occlusive phenomena, profound anemia, or infection. Evaluation to exclude these and other complications is mandatory. Rapid identification of acute crises in sickle cell disease is essential to successful intervention and preservation of function. Prompt reversal of hypoxemia, restoration of perfusion and oxygen-carrying capacity, and administration of antibiotics targeted toward encapsulated organisms remain the cornerstones of emergency department management. REFERENCES 1. Dover GJ, Platt OS: Sickle cell disease. In Nathan DG, Orkin SH (eds): Nathan and Oski’s Hematology of Infancy and Childhood. Philadelphia: WB Saunders, 1998, pp 762–809. *2. Minter KR, Gladwin MT: Pulmonary complications of sickle cell anemia: a need for increased recognition, treatment, and research. Am J Respir Crit Care Med 164:2016–2019, 2001. 3. National Heart, Lung and Blood Institute: The Management of Sickle Cell Disease (NIH Publication No. 02-2117). Bethsda, MD: National Institutes of Health, 2002. *4. Steinberg MH: Management of sickle cell disease. N Engl J Med 340:1021–1030, 1999. 5. Bunn HF: Pathogenesis and treatment of sickle cell disease. N Engl J Med 337:762–769, 1997. 6. Platt OS, Brambilla DJ, Rosse WF, et al: Mortality in sickle cell disease: life expectancy and risk factors for early death. N Engl J Med 330:1639– 1644, 1994. 7. Rodewald LE, Slovis CM, Palis J: Sickle cell syndromes: recognition and management of six crises. Emerg Med Rep 11:43–51, 1990. 8. Castro O, Brambilla DJ, Thorington B, et al: The acute chest syndrome in sickle cell disease: incidence and risk factors. Blood 84:643–649, 1994. 9. Quinn CT, Buchanan GR: The acute chest syndrome of sickle cell disease. J Pediatr 135:416–422, 1999. 10. Vichinsky EP, Neumayr LD, Earles AN, et al; National Acute Chest Syndrome Study Group: Causes and outcomes of the acute chest syndrome in sickle cell disease. N Engl J Med 342:1855–1865, 2000. *Selected readings.

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11. Adams RJ: Lessons from the Stroke Prevention Trial in Sickle Cell Anemia (STOP) study. J Child Neurol 15:344–349, 2000. 12. Adams RJ, McVie VC, Hsu L, et al: Prevention of a fi rst stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. N Engl J Med 339:5–11, 1998. 13. Frempong KO, Weiner SJ, Sleeper LA, et al: Cerebrovascular accidents in sickle cell disease: rates and risk factors. Blood 91:288–294, 1998. 14. Winkelstein JA, Drachman RH: Deficiency of pneumococcal serum opsonizing activity in sickle-cell disease. N Engl J Med 279:459, 1968. 15. Johnston RB Jr, Newman SL, Struth AG: An abnormality of the alternate pathway of complement activation in sickle-cell disease. N Engl J Med 288:803–808, 1973. 16. Falletta JM, Woods GM, Verter JI, et al: Discontinuing penicillin prophylaxis in children with sickle cell anemia. Prophylactic Penicillin Study II. J Pediatr 27:685–690, 1995. 17. Hongeng S, Wilimas JA, Harris S, et al: Recurrent Streptococcus pneumoniae sepsis in children with sickle cell disease. J Pediatr 130:814–816, 1997. 18. Comber JT, Lopez BL: Evaluation of pulse oximetry in sickle cell anemia patients presenting to the emergency department in acute vasoocclusive crisis. Am J Emerg Med 14:16–18, 1996. *19. Blaisdell CJ, Goodman S, Clark K, et al: Pulse oximetry is a poor predictor of hypoxemia in stable children with sickle cell disease. Arch Pediatr Adolesc Med 154:900–903, 2000. 20. Lopez BL, Griswold SK, Navek A, Urbanski L: The complete blood count and reticulocyte count—are they necessary in the evaluation of acute vasoocclusive sickle-cell crisis? Acad Emerg Med 3:751–757, 1996. 21. Chapman JI, El-Shammaa EN, Bonsu BK: The utility of screening laboratory studies in pediatric patients with sickle cell pain episodes. Am J Emerg Med 22:258–263, 2004. 22. Ander DS, Vallee PA: Diagnostic evaluation for infectious etiology of sickle cell pain crisis. Am J Emerg Med 15:290–292, 1997. 23. Rosa RM, Bierer BE, Thomas R, et al: A study of induced hyponatremia in the prevention and treatment of sickle cell crises. N Engl J Med 303:1138–1143, 1980. 24. Barsan W, Hedges J: Meperidine usage in patients with sickle cell crisis. Ann Emerg Med 15:1506–1508, 1986. 25. Beiter JL Jr, Simon HK, Chambliss R, et al: Intravenous ketorolac in the emergency department management of sickle cell pain and predictors of its effectiveness. Arch Pediatr Adolesc Med 155:496–500, 2001. 26. Hardwick WE Jr, Givens TG, Monroe KW, et al: Effect of ketorolac in pediatric sickle cell vaso-occlusive pain crisis. Pediatr Emerg Care 15:179–182, 1999. 27. Robieux IC, Kellner JD, Coppes MJ: Analgesia in children with sickle cell crisis: comparison of intermittent opioids vs. continuous infusion of morphine and placebo controlled study of oxygen inhalation. Pediatr Hematol Oncol 9:317–326, 1992. 28. Zipursky A, Robieux IC, Brown EJ, et al: Oxygen therapy in sickle cell disease. Am J Pediatr Hematol Oncol 14:222–228, 1992. 29. Bellet PS, Kalinyak KA, Shukla R, et al: Incentive spirometry to prevent acute pulmonary complications in sickle cell diseases. N Engl J Med 333:699–703, 1995. 30. Vichinsky E, Lubin BH: Suggested guidelines for the treatment of children with sickle cell anemia. Hematol Oncol Clin North Am 1:483– 501, 1987. 31. Winter CC, McDowell G: Experience with 105 patients with priapism: update review of all aspects. J Urol 140:980–983, 1988. 32. Rogers ZR, Morrison RA, Vedro DA, Buchanan GR: Outpatient management of febrile illness in infants and young children with sickle cell anemia. J Pediatr 117:736–739, 1990. *33. Wilimas JA, Flynn PM, Harris SC, et al: A randomized study of outpatient treatment with ceftriaxone for selected febrile children with sickle cell disease. N Engl J Med 329:472–476, 1993. 34. West TB, West DW, Ohene-Frempong K: The presentation, frequency, and outcome of bacteremia among children with sickle cell disease and fever. Pediatr Emerg Care 10:141–143, 1994. 35. Williams LL, Wilimas JA, Harris SC, et al: Outpatient therapy with ceftriaxone and oral cefi xime for selected febrile children with sickle cell disease. J Pediatr Hematol Oncol 18:257–261, 1996. 36. Scott JP, Hillery CA, Brown ER, et al: Hydroxyurea therapy in children severely affected with sickle cell disease. J Pediatr 128:820–828, 1996.

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37. Zimmerman SA, Schultz WH, Davis JS, et al: Sustained longterm hematologic efficacy of hydroxyurea at maximum tolerated dose in children with sickle cell disease. Blood 103:2039–2045, 2004. 38. Walters MC, Patience M, Leisenring W, et al: Bone marrow transplantation for sickle cell disease. N Engl J Med 335:369–376, 1996.

39. Brichard B, Vermylen C, Ninane J, Cornu G: Persistence of fetal hemoglobin production after successful transplantation of cord blood stem cells in a patient with sickle cell anemia. J Pediatr 128:241–243, 1996. 40. Wethers DL: Sickle cell disease in childhood: Part II. Diagnosis and treatment of major complications and recent advances in treatment. Am Fam Physician 62:1309–1314, 2000.

Chapter 128 Cancer and Cancer-Related Complications in Children Peter D. Sadowitz, MD and Abdul-Kader Souid, MD, PhD

Key Points Cancer remains a leading cause of death in children, accounting for approximately 10% of fatalities. Febrile-neutropenic events are common in children receiving chemotherapy. Often the first sign of sepsis is fever (>38.0° C). The standard care for these patients includes immediate triage and clinical assessment, appropriate central venous line and peripheral blood cultures, administration of broad-spectrum antibiotics, and hospitalization. Tumor lysis syndrome may produce hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcaemia, and renal failure. Patients with these complications require vigorous hydration, diuretics, and allopurinal or rasburicase. Potassium-containing solutions should be avoided. Tumors compressing the airway, superior vena cava, or spinal cord require immediate assessment and urgent interventions.

Selected Diagnoses Acute leukemias and lymphomas Abdominal tumors Neuroblastoma Wilms’ tumor Hepatoblastoma Bone and tissue sarcomas Osteosarcoma Ewing’s sarcoma (primitive neuroectodermal tumor) Rhabdomyosarcoma Other tumors Hodgkin’s lymphoma Retinoblastoma Germ cell tumors

Complications of chemotherapy Febrile neutropenia Acute tumor lysis syndrome Tumor-induced compression

Discussion of Individual Diagnoses Acute Leukemias and Lymphomas Acute leukemias and lymphomas account for approximately one third of childhood cancers. Children with immune deficiency (e.g., hypogammaglobulinemia, immunosuppressive therapy, human immunodeficiency virus infection) or constitutional chromosomal anomalies (e.g., trisomy 21) are particularly susceptible. Acute lymphoblastic leukemia (ALL) accounts for approximately 85% of childhood leukemias. The disease peaks in early childhood. Malignant lymphoblasts originate from immature B cells in 80% of cases (B-cell precursor ALL), mature B cells in 5% of cases (B-cell or Burkitt’s leukemia/ lymphoma) and immature T cells in 15% of cases (T-cell leukemia/lymphoma). The term lymphoma is used when lymphoblasts arise primarily within lymph nodes, and the percentage of malignant cells in the bone marrow is less than 25%. Certain chromosomal abnormalities in lymphoblasts produce poor outcome, such as t(9;22)(q34;q11) or Philadelphia chromosome.1 Acute myelogenous leukemia (AML) accounts for approximately 15% of childhood leukemias. Its incidence is steady from birth to 18 years of age. Myeloblasts may originate from myeloid (M1 through M4), monocytic (M4 and M5), erythroid (M6), or megakaryocytic (M7) precursors. Clinical Presentation Patients may be asymptomatic, with leukemia detected on routine examination of blood smear or complete blood counts (CBCs). Symptoms and signs of leukemia (Table 128–1) occur when blasts proliferate in the bone marrow cavity (producing anemia, neutropenia, and/or thrombocytopenia) and other organs (producing lymphadenopathy, hepatomegaly, and splenomegaly). Clinical manifestations may also include fever (due to infection or leukemia itself), pallor, fatigue (due to anemia), bacterial infections (due to neutropenia), petechiae, and bruises (due to thrombocytopenia). 905

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Table 128–1

Emergency Department Recognition, Workup and Management of Acute Lymphoblastic Leukemia (ALL) and Lymphoma B-Cell Precursor (Common) ALL

Presentation • Fever (1/2 of patients) • Petechiae/bruises (1/2 of patients) • Bone/joint pain (1/3 of patients), limp, refusal to walk • Lymphadenopathy (2/3 of patients) • Hepatomegaly (2/3 of patients) • Splenomegaly (2/3 of patients) • Pallor (1/2 of patients) Workup • CBC, type and screen, blood culture • Serum electrolytes, BUN, creatinine, calcium, phosphate, uric acid, LDH, PT, PTT, TT, fibrinogen, AST, ALT, bilirubin • Chest radiograph • Urinalysis Laboratory Findings • Anemia, thrombocytopenia, neutropenia, and circulating blasts are common. • White blood cell counts are ≤ 10 × 103/mm3 in 1/2 of the patients, 10–50 × 103/mm3 in 1/4 of the patients, and > 50 × 103/mm3 in 1/4 of the patients. • Hemoglobin concentrations are ≤ 7.5 g/dl in 1/2 of the patients, 7.5–10 g/dl in 1/4 of the patients, and > 10 g/dl in 1/4 of the patients. • Platelet counts are < 20 × 103/mm3 in 1/4 of the patients, 20–100 × 103/mm3 in 1/2 of the patients, and > 100 × 103/mm3 in 1/4 of the patients. • LDH and uric acid are frequently elevated. Management • IVF (5% dextrose, 0.45% NaCl or 5% dextrose, 0.2% NaCl + 30 mEq/L NaHCO3) at twice the maintenance rate • IV antibiotics for febrile neutropenia (see Table 128–3) • PRBC transfusion for hemoglobin concentration < 8.0 g/dl (see Chapter 132) • Platelet transfusion for platelet count < 20 × 103/mm3 (see Chapter 132) • Allopurinol (10 mg/kg/day in three divided doses) or rasburicase (single IV dose of 0.15–0.2 mg/kg/day, mixed in 50 ml of 0.9% NaCl, over 30 min)

T-Cell ALL/Lymphoma Presentation • Cough, wheezing, stridor • Massive cervical or mediastinal lymphadenopathy Workup • Same as for B-cell precursor ALL • CT scans of the neck and chest Laboratory Findings • Leukocytosis and circulating blasts are common. Hemoglobin concentration and platelet count are frequently normal. • LDH and uric acid are markedly elevated. Management • Consultations with pediatric oncology, intensive care, and anesthesia services • Careful airway management (e.g., may require steroid therapy and/or mediastinal radiation after pediatric oncology consultation to prevent life-threatening airway compromise) • Frequent monitoring of vital signs and urine output, preferably in a pediatric intensive care unit (since intubation to secure the airway may be necessary) • IVF and allopurinol or rasburicase as for B-cell precursor ALL

Burkitt’s (B-Cell) Lymphoma Presentation • Abdominal involvement is common as the lymphoma cells infiltrate the various abdominal organs (e.g., abdominal mass, ascites, ileocecal intussusception, small bowel obstruction, mesenteric/retroperitoneal lymphadenopathy, renal infiltration and hepatosplenomegaly). • Other sites of the disease include bone marrow and lymph nodes (including the tonsils). • Spinal cord compression by a tumor occurs in ~10% of patients, producing paresis, neurogenic bladder, and lower extremity motor and sensory defects. Workup • Same as for B-precursor and T-cell leukemias • Abdominal CT scan and spinal MRI (if neurologic findings are present) • Peritoneal fluid (ascites) aspiration may be needed to obtain cells for diagnosis. Laboratory Findings • CBC could be normal if there is no bone marrow involvement. • LDH and uric acid are markedly elevated. Management • Emergent consultations with pediatric oncology and surgery services are necessary. • IVF and allopurinol or rasburicase as for B-cell precursor ALL Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; CBC, complete blood count; CT, computed tomography; IV, intravenous(ly); IVF, intravenous fluids; LDH, lactate dehydrogenase; MRI, magnetic resonance imaging; PRBC, packed red blood cells; PT, prothrombin time; PTT, partial thromboplastin time; TT, thrombin time.

Chapter 128 — Cancer and Cancer-Related Complications in Children

Bone pain (due to expanding leukemic clumps in the marrow cavity and infi ltration into the subperiosteal space) is common, producing limp, refusal to walk, swollen joints, and arthralgias (mimicking juvenile rheumatoid arthritis). Respiratory compromise with cough, wheezing, and stridor may result from airway compression by massive cervical, thoracic, and/or mediastinal lymphadenopathy (see Table 128–1). Superior vena cava compression produces venous congestion, swelling, and cyanosis in the upper chest, neck, and face. Eye examination is necessary to evaluate orbital masses (more common in AML) and retinal infi ltration. Leukemic involvement of the testes should be carefully documented. Abdominal masses, ascites, and small bowel obstruction (e.g., ileocecal intussusception) can be seen in Burkitt’s (B-cell) lymphoma (see Table 128–1). The initial workup includes a CBC and examination of a blood smear (for blasts). Anemia, neutropenia, and thrombocytopenia are present in the majority of patients with B-cell precursor (common) ALL (see Table 128–1). The remaining workup includes a chest radiograph (a large thymus and mediastinal lymphadenopathy are common in T-cell leukemia/lymphoma); blood typing (for possible need of packed red blood cell and/or platelet transfusions); blood culture (in the presence of fever); prothrombin time, activated partial thromboplastin time, and thrombin time (all are prolonged in AML-induced disseminated intravascular coagulopathy [DIC]); fibrinogen (low in AML-induced DIC); serum electrolytes, creatinine, calcium, and phosphate (the initial value is often low due to phosphate uptake by the leukemia clone); lactate dehydrogenase and uric acid (both are usually elevated); and hepatic transaminases, bilirubin, and urinalysis. All patients with suspected leukemia/lymphoma require admission for definitive evaluation, which includes a spinal tap to evaluate central nervous system (CNS) infi ltration and a bone marrow examination to evaluate leukemic cell morphology, immunophenotyping, and cytogenetics. These procedures should be done after thrombocytopenia and coagulopathy are corrected. Cerebrospinal fluid (CSF) should be evaluated for cytology, cell count, protein, and glucose. CNS disease (present in approximately 5% of cases) is associated with an increased CSF white cell count (>5/mm3) and leukemic blasts on a cytospin slide prepared shortly after CSF collection. The differential diagnosis of acute leukemia includes juvenile rheumatoid arthritis, Epstein-Barr virus or cytomegalovirus infection, aplastic anemia, and bone marrow infi ltration by metabolic cells (e.g., Gaucher’s disease) or other neoplasms (blood smear frequently shows nucleated red blood cells and left shift). Management Intravenous antibiotics should be given for bacterial infections or febrile neutropenia. Packed red blood cell and platelet transfusions (using leukoreduced and irradiated products) may be necessary. The goals are to raise the hemoglobin concentration to greater than 8.0 g/dl and the platelet count to greater than 50 × 103/mm3, especially prior to invasive procedures (e.g., spinal tap, central venous catheter placement). Patients with wheezing, cough, and/or respiratory distress due to a massive mediastinal or cervical lymphadenopathy may require emergent airway control. These patients

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should be admitted to the intensive care unit for observation. Immediate interventions (e.g., steroid therapy, mediastinal radiation) may be necessary. Other complications include tumor lysis syndrome (see “Complications of Chemotherapy” section),2,3 renal failure (due to leukemic infi ltrations and/or uric acid nephropathy), seizures (due to CNS leukemia, intracranial bleeding, or metabolic derangements), pleural effusion (due to leukemic infiltration), and DIC (seen in AML) (see Chapter 40, Seizures; Chapter 42, Conditions Causing Increased Intracranial Pressure; and Chapter 88, Renal Disorders). Abdominal Tumors Neuroblastoma Neuroblastomas arise in the adrenal glands (~40% of cases) and abdominal (~25% of cases) or thoracic (~20% of cases) sympathetic ganglia. These tumors occur in children less than 5 years of age. Over 90% of tumors produce catecholamines (e.g., homovanillic acid [HVA], vanillylmandelic acid [VMA]).8 These biochemical markers aid in establishing the diagnosis and in documenting a response to therapy. Patients may present with a large abdominal mass (potentially causing respiratory distress) or metastatic lesions to the orbits, bones, bone marrow, or lymph nodes. Tumors in the posterior mediastinum may be asymptomatic (discovered on a chest radiograph) or result in airway obstruction. Dumbbellshaped tumors involving the intervertebral foramina may compress the spinal cord, causing paraplegia. Tumors involving the cervical sympathetic chain may produce Horner’s syndrome (miosis, ptosis, enophthalmos, and anhydrosis). About 5% of the tumors produce cerebellar dysfunction, causing opsoclonus-polymyoclonus syndrome (ataxia and dancing eyes). Periorbital metastases produce “raccoon eyes.” Hypertension due to excess catecholamines may require antihypertensives. The workup includes a CBC; urine HVA/ VMA; CT scans of the chest, abdomen, and pelvis; bone marrow examination; and technetium-99m (99mTc) bone scan. Spine MRI should be obtained if paraspinal tumors are suspected. Spinal cord compression requires immediate neurosurgical evaluation, radiation therapy, dexamethasone, or chemotherapy. Wilms’ Tumor Wilms’ tumors account for approximately 5% of the childhood cancer. Most children are less than 8 years old. Aniridia, hemihypertrophy, and Beckwith-Wiedemann syndrome (neonatal hypoglycemia, omphalocele, macroglossia, and visceromegaly) are highly associated with Wilms’ tumors. Patients with any of these anomalies require regular abdominal ultrasounds for the first several years of life to detect tumor at an early stage. Urinary tract malformations (e.g., hypospadia, cryptorchidism, horseshoe kidney, ureteral duplication, polycystic kidney) are also associated with Wilms’ tumors. Patients may present with a large abdominal mass, acute abdominal pain (due to tumor necrosis or hemorrhage), constipation, hypertension, microscopic hematuria, anemia, and rarely polycythemia. The workup includes abdominal and chest CT scans to evaluate the renal vein, inferior vena cava, right atrium (for tumor thrombus), regional lymph nodes (iliac, periaortic, and celiac), liver, opposite kidney, and lungs (lung metastasis occurs in

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SECTION IV — Approach to the Acutely Ill Patient

approximately 15% of the cases). Nephrectomy is necessary for all tumors. More than 90% of children are cured with surgery plus chemotherapy (with or without radiation).9 Hepatoblastoma Hepatoblastomas affect children in the first 2 years of life. They may occur in association with Beckwith-Wiedemann syndrome, hemihypertrophy, or extreme prematurity. Familial forms also occur in association with CNS anomalies, glycogen storage disease, and familial adenomatous polyposis.10 Children usually present with a large abdominal mass. Lungs are a common metastatic site. Most tumors produce αfetoprotein, which confirms the diagnosis and guides the treatment. The workup includes CBC, blood type (for possible need of packed red blood cell transfusion), serum αfetoprotein and β-human choriogonadotrophin (βhCG), abdominal CT scan (shows large hepatic tumor), chest radiograph, and chest CT scan. The diagnosis is confirmed by tumor biopsy. The risk of tumor bleeding is high due to extensive tumor vascularity. As a consequence, tumor rupture can be produced by overzealous abdominal examination. The differential diagnosis includes hepatocellular carcinoma and hemangioma. The majority of patients are cured with chemotherapy followed by tumor resection.

share common abnormalities involving chromosome 22 [t(11:22)(q24:q12) or t(21:22)(q 22:q 12)]. Successful treatment requires surgery and chemotherapy (with or without radiation).13 Rhabdomyosarcoma Rhabdomyosarcomas arise from mesenchymal cells that normally differentiate to striated muscles. This tumor is the most common soft tissue sarcoma in children, accounting for approximately 50% of all sarcomas.14 The disease may occur at any age. Tumors originate in the head and neck region (e.g., orbit, nasopharynx, sinuses, middle ear) in 40% of cases, genitourinary area (e.g., bladder, prostate, paratesticular, perineal, vaginal) in 20% of cases, extremities and trunk in 20% of cases, and retroperitoneum in 10% of cases. Parameningeal tumors may invade the CNS, causing cranial nerve palsies, increased intracranial pressure, and meningeal involvement. Lungs, lymph nodes, bones, bone marrow, and liver are common metastatic sites. The workup includes CBC, CT scan of involved sites, bone marrow examination, and 99mTc bone scan. Parameningeal tumors require brain or spine MRI and CSF cytology. The standard treatment involves chemotherapy, surgery, and radiation.

Bone and Tissue Sarcomas

Other Tumors

Osteosarcoma

Hodgkin’s Lymphoma

Osteosarcoma (spindle cell tumor of the metaphysis) is the most common bone cancer.11 The disease peaks between approximately 10 and 18 years of age (coinciding with the growth spurt). More than 80% of these tumors occur in the knee region (lower femur or upper tibia) and approximately 15% in the humerus. Lungs and bones are the most common metastatic sites. Typical presentations include localized pain with or without physical findings (e.g., firm, tender mass fi xed to underlying bone) and pathologic fractures. A plain radiograph of involved bone shows poorly defined tumor margins, bone destruction, periosteal reaction, and calcification (reflecting new bone formation). In approximately 10% of cases, the lesion is purely osteolytic. In contrast, benign tumors are round, smooth, and well circumscribed, without cortical destruction or periosteal reaction. The workup includes MRI of the entire extremity (to detect skip lesions), 99m Tc bone scan (to detect bone metastasis), chest radiography, and chest CT scan (to detect lung metastasis). The diagnosis is confirmed by open biopsy. The treatment involves preoperative chemotherapy followed by surgery (e.g., “en bloc” tumor resection with endprosthesis).12

Hodgkin’s lymphoma is a neoplasm arising in the lymphatic system. Despite their undetermined origin, Reed-Sternberg cells are responsible for the disease.15,16 Tumors spread from one nodal area to an adjacent nodal region. Extranodal spread (bone marrow, lungs, and bones) is rare. The disease is more common in adolescents. A typical presentation includes painless cervical, supraclavicular, or mediastinal lymphadenopathy, which progresses over several months. Symptoms such as fatigue, anorexia, weight loss, and night sweats may be present. The workup includes chest radiograph; CT scans of neck, chest, abdomen, and pelvis; and 99m Tc and gallium bone scans. Lymph node biopsy is necessary to confirm the diagnosis. Treatment involves chemotherapy with or without radiation.17 The cure rate is over 80%.

Ewing’s Sarcoma (Primitive Neuroectodermal Tumor) Ewing’s sarcomas are small round cell tumors of neuronal origin. The tumor arises in the diaphyses of long or flat bones and in soft tissues. Pelvic and femoral tumors account for approximately 50% of cases. Undifferentiated tumors are termed Ewing’s sarcoma, and tumors exhibiting primitive neural characteristics are termed peripheral primitive neuroectodermal tumors (PNET). Ewing’s sarcoma typically occurs after 10 years of age, with lungs, lymph nodes, bones, and bone marrow being the most common metastatic sites. The clinical presentation is similar to osteosarcoma. The tumors

Retinoblastoma Retinoblastomas are the most common primary eye tumor.18 They arise from the outer layer of the retina. The mean age at diagnosis is approximately 17 months, with few cases occurring after 5 years of age. The most common presentations are leukocoria (white reflex within the eye), strabismus, and poor vision. The workup includes orbit MRI/CT scan, CSF cytology, bone marrow examination, and bone scan. Photocoagulation or cryotherapy is used for tumors less than 4 disk diameters in size, while larger tumors are treated with surgery or radiation. Chemotherapy is used for extensive local disease or distant metastasis. Enucleation is reserved for advanced unilateral disease. The current approach cures greater than 90% of patients. Children with a known family history of the disease need retinal examinations at regular intervals. Patients with the inherited form of retinoblastoma have increased risk of developing second malignancy (e.g., osteosarcoma).

Chapter 128 — Cancer and Cancer-Related Complications in Children

Germ Cell Tumors Germ cell tumors (germinoma, dysgerminoma, teratoma, endodermal sinus or yolk sac tumor, embryonal carcinoma, and choriocarcinoma) involve the gonads (testes and ovaries) and extragonadal regions (pineal gland, suprasellar area, anterior mediastinum, and sacrococcygeum).19,20 Serum αfetoprotein and βhCG are usually elevated, which confirms the diagnosis and guides the treatment. Clinical presentations vary depending on tumor location. Pineal/suprasellar tumors produce headache, upward paralysis, and poor coordination. Anterior mediastinal lesions produce cough and wheezing. Sacrococcygeal tumors occur in infants, who may present with constipation and a mass in the buttock or presacral region. Ovarian tumors occur in young girls and present with an abdominal or pelvic mass. Testicular tumors produce painless testicular swelling or torsion of the testis. Optimal therapy includes chemotherapy and, in some cases, radiation. Complications of Chemotherapy Febrile Neutropenia Fever and neutropenia (febrile neutropenia) are common in children receiving chemotherapy (Table 128–2). In this setting, neutropenia is defined as an absolute neutrophil count (ANC) of less than 500/mm3, and determined as the total white blood cell count multiplied by the percentage of neutrophils plus bands. Fever is defi ned as temperature greater than 38.0° C (100.4° F). The risk of bacterial infection correlates with the severity of neutropenia and its duration. For example, life-threatening sepsis is more common when the ANC is less than 200/mm3 for more than 7 days. Other predictive parameters for invasive bacterial infections include

Table 128–2

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high-dose chemotherapy (e.g., myeloablative therapy), young age, delayed capillary fi lling time (>3 seconds), tachycardia, hypotension, high temperature (>39° C), pneumonia (cough, short of breath, decreased hemoglobin-oxygen saturation, or abnormal chest radiograph), and compromised physical barriers due to oral mucositis or enterocolitis.21-24 Fever may the first and only sign of a life-threatening infection. Other clinical presentations may include headache, fatigue, chills, gastrointestinal symptoms (abdominal pain, nausea, vomiting, diarrhea, and perianal or perirectal cellulitis), mucositis or pain at central venous catheter or rectal region. All patients with fever and neutropenia require immediate clinical evaluation, appropriate cultures (blood cultures from central and peripheral venous catheter, and cultures of infected mucosal or skin lesions), prompt administration of broad-spectrum intravenous antibiotics, and hospitalization. The choice of empirical antibiotics (which should be administered as soon as intravenous access and cultures are obtained) is based on commonly isolated pathogens.25 Grampositive organisms include the low-virulence coagulasenegative Staphylococcus species and viridans streptococci (common contaminants of central venous catheters), and high-virulence α-hemolytic streptococci, enterococci, and Streptococcus pneumoniae (producing disseminated infections, such as meningitis). These organisms respond to vancomycin (15 mg/kg per dose intravenously every 8 hours). Common gram-negative organisms include Escherichia coli, Pseudomonas species, and Klebsiella species. These organisms respond to antipseudomonal cephalosporins (ceftazidime, cefoperazone, or cefepime) or aminoglycosides (e.g., amikacin, 5 mg/kg per dose every 8 hours) (see Table 128–2).

Febrile Neutropenia

Definitions • Neutropenia is defined as an absolute neutrophil count of < 500/mm3. • Fever is defined as a temperature of ≥ 38.0° C (100.4° F). Presentation • Fever may be the only sign of a life-threatening infection. • Other symptoms may include headache, lethargy, abdominal pain, nausea, vomiting, diarrhea, oral mucositis, perianal pain, and pain at central venous catheter site. Workup • CBC, type and screen, and blood cultures from the central venous catheter • Peripheral blood cultures • Cultures from infected mucosal or skin lesions Monitoring • All patients require immediate clinical evaluation, including frequent vital signs. Tachycardia and hypotension may reflect sepsis. • Physical examination includes careful assessment of the cardiopulmonary-neurologic status, tissue perfusion, perianal region, oral mucosa, and central line site. • Continuous patient monitoring is necessary for several hours following antibiotic administration, since endotoxin release may produce septic shock. Management • All patients with febrile neutropenia should be admitted and receive parenteral antibiotics. • Hemodynamically unstable patients should be admitted to a pediatric intensive care unit. • Vancomycin (15 mg/kg IV q8h) plus antipseudomonal cephalosporins (ceftazidime, cefoperazone or cefepime) or aminoglycosides (e.g., amikacin, 5 mg/kg q8h) • Tachycardia, hypotension, and poor tissue perfusion require emergent fluid resuscitation (e.g., 0.9% NaCl or Ringer's lactate at 20–60 ml/kg). Dopamine may be required if fluid resuscitation does not improve perfusion and blood pressure. • Packed red blood cell (if hemoglobin concentration < 8.0 g/dl) and platelet (if platelet count < 20 × 103/mm3) transfusions are necessary. The products should be leukoreduced and irradiated (see Chapter 132). Abbreviations: CBC, complete blood count; IV, intravenously.

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Antifungal treatment is given for prolonged fever and neutropenia while on broad-spectrum antibiotics. Aspergillus species respond to voriconazole and Candida species respond to fluconazole.26 All patients require admission. Hemodynamically unstable patients (tachycardia, hypotension, and poor tissue perfusion) require emergent intravenous fluid resuscitation (with 20 to 60 ml/kg of 0.9% NaCl or Ringer’s lactate); vasoactive pressors (e.g., dopamine) may also be necessary. Stress-dose steroids may be required, especially in patients on steroid therapy. Careful physical evaluation, including overall appearance, vital signs (tachycardia and hypotension reflect sepsis), tissue perfusion, and perirectal, oral, and central catheter sites, is essential. Digital rectal examination and rectal temperatures should be avoided. Tachycardia and hypotension may reflect sepsis. Continuous monitoring is necessary, since septic shock may follow antibiotic administration. Packed red blood cell transfusion (~15 ml/kg over ~2 hours) improves tissue perfusion and may help correct tachycardia and hypotension in anemic patients. Platelet transfusion (1 apheresis unit, or ~15 ml/kg for infants, over 1 hour) may also be necessary in thrombocytopenic patients. Blood products should be leukoreduced and irradiated (see Chapter 132, Utilizing Blood Bank Resources/Transfusion Reactions and Complications). Patients with a history of a prior transfusion reaction (e.g., urticaria, chills, and fever) require premedication with acetaminophen (15 mg/kg orally), diphenhydramine (0.5 mg/kg orally or intravenously), methylprednisolone (1 mg/kg intravenously), and/or cimetidine (1 mg/kg; 25 mg maximum, intravenously) to decrease transfusion reactions. Granulocyte colonystimulating factor decreases the incidence of febrile neutropenia and may be useful in severely neutropenic patients when documented bacterial infections cannot be controlled.27 Acute Tumor Lysis Syndrome Acute tumor lysis syndrome may complicate the course of induction chemotherapy2 (Table 128–3). The metabolic derangements include hyperuricemia (due to increased purine metabolism), hyperkalemia, and hyperphosphatemia.

Table 128–3

Hyperphosphatemia can produce hypocalcemia (cramps, tetany, and seizures). Phosphate and uric acid may precipitate in renal tubules, producing renal failure. Vigorous hydration to ensure production of dilute urine (specific gravity < 1.010) and adequate elimination of cellular debris (e.g., 5% dextrose + 0.45% NaCl [D51/2NS] or 5% dextrose + 0.2% NaCl [D51/4NS] plus 30 mEq/L NaHCO3 at twice the maintenance rate) is necessary. If urine output is inadequate, diuretics (furosemide, 0.5 to 1.0 mg/kg) can be used. Potassiumcontaining solutions must absolutely be avoided. Urine alkalization (with intravenous NaHCO3 or acetozolamide) is necessary in the presence of marked hyperuricemia. Allopurinol (300 mg/m2/day or 10 mg/kg/day in three divided doses orally) or rasburicase3 (a single dose of 0.15 to 0.2 mg/kg/day, mixed in 50 ml of 0.9% NaCl and infused intravenously over 30 minutes) should be administered to prevent uric acid formation. Rasburicase, a recombinant uricolytic agent (urate oxidase) derived from Aspergillus, converts uric acid to allatoin, which is easily excreted in the urine. By preventing uric acid nephropathy, phosphate and potassium excretion are also improved.3 Hyperkalemia and symptomatic hypocalcemia require urgent corrections; patients with these complications require continuous cardiac monitoring. Dialysis is required for severe hyperkalemia and renal failure (see Chapter 114, Hyperkalemia; and Chapter 115, Hypocalcemia). Tumor-Induced Compression Tumor-induced airway compression produces cough, wheezing, stridor, dyspnea, and cyanosis. Superior vena cava compression produces face and neck swelling, dyspnea, cyanosis, and prominent chest wall veins. All patients will require admission, imaging (chest radiograph and CT), and a tissue diagnosis for confirmation. Management includes administration of oxygen, elevating the head of the bed, and observing the patient for airway compromise. Clinicians should be aware that sedation may further compromise the airway. Thus early involvement of pediatric intensive care, pediatric oncology, and anesthesia teams should be considered. Emer-

Acute Tumor Lysis Syndrome

Definition • The metabolic derangements (hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia) that occur during induction chemotherapy from the destruction of tumor cells. Complications • Phosphate and uric acid may precipitate in renal tubules and can produce renal insufficiency or failure. • Hyperphosphatemia may produce hypocalcemia, which may become symptomatic. Management • Hydration with 5% dextrose + 0.45% NaCl (D51/2NS) or 5% dextrose + 0.2% NaCl (D51/4NS) plus 30 mEq/L of NaHCO3 at twice the maintenance rate. Intravenous boluses with 0.9% NaCl (20 ml/kg each) may be necessary in severely dehydrated patients. Potassiumcontaining solutions must be avoided. • If urine output remains low (e.g., < 2 ml/kg/hr) after ~8 hr of adequate hydration, furosemide IV at 1 mg/kg IV should be administered. • Allopurinol (300 mg/m2/day or 10 mg/kg/day orally in three divided doses) or rasburicase (single IV dose of 0.15–0.2 mg/kg/day, mixed in 50 ml of 0.9% NaCl, given over 30 min) • Dialysis is required for severe hyperkalemia and renal failure. Monitoring • Close monitoring of urine output and urine parameters is essential. • Serum electrolytes, BUN, creatinine, phosphate, calcium, and uric acid should be repeated every 4–24 hr depending on the severity of tumor lysis. Abbreviations: BUN, blood urea nitrogen; D, dextrose; IV, intravenously; NS, normal saline.

Chapter 128 — Cancer and Cancer-Related Complications in Children

gent use of steroids or radiation may be necessary (although these modalities may obscure the diagnosis). Spinal cord compression is most frequently caused by tumor extension through the neural foramina and may occur at any level of the cervical, thoracic, or lumbar spine. Most of these tumors distribute evenly throughout the cervical, thoracic, and lumbar spine. The mass can be intramedullary (e.g., astrocytoma, ependymoma, lipoma), intradural extramedullary (e.g., dermoid, neuroblastoma, neurofibroma, schwannoma, meningoma, PNET, hemangioepithelioma), or epidural (e.g., Ewing’s sarcoma, neuroblastoma, ganglioneuroma, rhabdomyosarcoma, osteosarcoma, germ cell tumor, teratoma, lymphoma). Signs and symptoms of spinal cord compression include back pain, weakness, reflex changes, sensory deficit, atrophy, extremity pain, and incontinence. MRI (with and without gadolinium) of the involved region should be obtained. Consultations with neurosurgery, radiation therapy, and pediatric oncology are necessary. Dexamethasone (1 to 2 mg/kg intravenously) may decrease localized edema and swelling. In the absence of severe spinal cord compression, most tumors can be treated with chemotherapy or radiation. However, sarcomas usually require immediate surgical decompression. REFERENCES *1. Holleman A, Cheok MH, den Boer ML, et al: Gene expression in drug resistant acute lymphoblastic leukemia cells and response to treatment. N Engl J Med 351:533–542, 2004. 2. Davidson MB, Thakkar S, Hix JK, et al: Pathophysiology, clinical consequences and treatment of tumor lysis syndrome. Am J Med 116:546– 554, 2004. 3. Lee AC, Li CH, So KT, et al: Treatment of impending tumor lysis with single-dose rasburicase. Ann Pharmacother 37:1614–1617, 2003. 4. Fang Z, Kulldorff M, Gregorio DI: Brain cancer mortality in the United States, 1986 to 1995: a geographic analysis. Neurooncology 6:179–187, 2004. 5. Baldwin RT, Preston-Martin S: Epidemiology of brain tumors in childhood—a review. Toxicol Appl Pharmacol 199:118–131, 2004. 6. Bucci MK, Maity A, Janss AJ, et al: Near complete surgical resection predicts a favorable outcome in pediatric patients with non-brainstem, malignant gliomas: results from a single center in the magnetic resonance imaging era. Cancer 101:817–824, 2004. *7. The epidemiology of headache among children with brain tumor. Headache in children with brain tumors. The Childhood Brain Tumor Consortium. J Neurooncol 10:31–46, 1991.

*Selected readings.

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*8. Riley RD, Heney D, Jones DR: A systematic review of molecular and biological tumor markers in neuroblastoma. Clin Cancer Res 10:4–12, 2004. *9. Green DM: The treatment of stages I-IV favorable histology Wilms’ tumor. J Clin Oncol 22:1366–1372, 2004. 10. Reynolds P, Urayama KY, Von Behren J, et al: Birth characteristics and hepatoblastoma risk in young children. Cancer 100:1070–1076, 2004. 11. Gorlick R, Anderson P, Andrulis I, et al: Biology of childhood osteogenic sarcoma and potential targets for therapeutic development: meeting summary. Clin Cancer Res 9:5442–5453, 2003. 12. Rao BN, Rodriguez-Galindo C: Local control in childhood extremity sarcomas: salvaging limbs and sparing function. Med Pediatr Oncol 41:584–587, 2003. 13. Krasin MJ, Rodriguez-Galindo C, Davidoff AM, et al: Efficacy of combined surgery and irradiation for localized Ewings sarcoma family of tumors. Pediatric Blood Cancer 43:229–236, 2004. *14. Meyer WH, Spunt SL: Soft tissue sarcomas of childhood. Cancer Treat Rev 30:269–280, 2004. 15. Thorley-Lawson DA, Gross A: Persistence of the Epstein-Barr virus and the origins of associated lymphomas. N Engl J Med 350:1328–1337, 2004. 16. Thomas RK, Re D, Wolf J, et al: Part I: Hodgkin’s lymphoma—molecular biology of Hodgkin and Reed-Sternberg cells. Lancet Oncol 5:11– 18, 2004. 17. Diehl V, Thomas RK, Re D: Part II: Hodgkin’s lymphoma—diagnosis and treatment. Lancet Oncol 5:19–26, 2004. 18. Castillo BV Jr, Kaufman L: Pediatric tumors of the eye and orbit. Pediatr Clin North Am 50:149–172, 2003. 19. Ueno T, Tanaka YO, Nagata M, et al: Spectrum of germ cell tumors: from head to toe. Radiographics 24:387–404, 2004. 20. Holzik MF, Rapley EA, Hoekstra HJ, et al: Genetic predisposition to testicular germ-cell tumors. Lancet Oncol 5:363–371, 2004. 21. Crawford J, Dale DC, Lyman GH: Chemotherapy-induced neutropenia: risks, consequences and new directions for its management. Cancer 100:228–237, 2004. 22. West DC, Marcin JP, Mawis R, et al: Children with cancer, fever and treatment-induced neutropenia: risk factors associated with illness requiring the administration of critical care therapies. Pediatr Emerg Care 20:79–84, 2004. *23. Mullen CA: Ciprofloxacin in treatment of fever and neutropenia in pediatric cancer patients. Pediatr Infect Dis J 22:1138–1142, 2003. 24. Offidani M, Corvatta L, Malerba L, et al: Risk assessment of patients with hematologic malignancies who develop fever accompanied by pulmonary infi ltrates: a historical cohort study. Cancer 101:567–577, 2004. 25. Vidal L, Paul M, Ben dor I, et al: Oral versus intravenous antibiotic treatment for febrile neutropenia in cancer patients: a systematic review and meta-analysis of randomized trials. J Antimicrob Chemother 54:29–37, 2004. 26. Neth O, Klein N: Febrile neutropenia: past, present and future. Adv Exp Med Biol 549:119–124, 2004. 27. Sung L, Nathan PC, Lange B, et al: Prophylactic granulocyte colonystimulating factor and granulocyte-macrophage colony-stimulating factor decrease febrile neutropenia after chemotherapy in children with cancer: a meta-analysis of randomized controlled trials. J Clin Oncol 22:3350–3356, 2004.

Chapter 129 Acute Childhood Immune Thrombocytopenic Purpura and Related Platelet Disorders Peter D. Sadowitz, MD and Abdul-Kader Souid, MD, PhD

Key Points Acute childhood immune thrombocytopenic purpura is a common pediatric disease. Children with profound thrombocytopenia (platelet counts < 20 × 103/mm3) and severe mucosal or cutaneous bleeding have significant risk of developing a life-threatening hemorrhage (intracranial, pulmonary, or upper airway). Patients with these findings should be admitted, and promptly treated with high-dose corticosteroids and anti-D antibody or immunoglobulin concentrates. Aspirin and nonsteroidal anti-inflammatory drugs are absolutely contraindicated in children with thrombocytopenia.

Introduction and Background Acute childhood immune thrombocytopenic purpura (ITP) is characterized by the sudden onset of profound thrombocytopenia in an otherwise healthy child.1 The disease results from production of antiplatelet antibodies, which promote Fc/γ receptor–mediated platelet destruction in the spleen. Anti-D antibodies and immunoglobulins block these receptors.2-4

Recognition and Approach Bruising and mild bleeding from minor trauma is common in active, healthy children and must be differentiated from serious or life-threatening disorders. To accurately diagnose ITP, clinicians must consider its diagnosis in all children with mucocutaneous bleeding that is either prolonged, profuse, in an unusual location, or inconsistent with the level of trauma. 912

In children with significant bleeding, the history, physical examination, and radiologic and laboratory screening are focused on discriminating between trauma (nonaccidental or accidental), blood vessel disorders, and hematologic disorders. Accidental trauma occurs in typical exposed areas with a history that is consistent with findings on physical examination. Children with nonaccidental trauma have bleeding or bruising that is inconsistent with the history given, while typical bony and soft tissues injuries are usually present (see Chapter 119, Physical Abuse and Child Neglect). Defects in coagulation are often associated with muscle, joint, or intracranial bleeding (see Chapter 130, Disorders of Coagulation). In contrast, platelet and vessel diseases (vasculitis) typically cause mucousal bleeding (e.g., epistaxis; gastrointestinal, gynecologic, or genitourinary) or purpura or petechiae. Importantly, other signs of systemic illness are often present in other serious causes of bleeding, while children with ITP are usually well appearing unless intracranial bleeding or significant blood loss is present. In contrast to adults with ITP, males and females are affected with equal frequency. The median age of childhood ITP is 3 to 5 years, with most cases less than 10 years old. Childhood ITP is more likely to resolve spontaneously and to respond to treatment compared to adult cases.

Clinical Presentation The typical clinical presentation of acute childhood ITP includes the sudden onset of bruises and petechiae in an otherwise healthy child. Often there is an antecedent viral illness. In a few patients, the thrombocytopenia follows infection with varicella virus, mumps, Epstein-Barr virus, cytomegalovirus, human immunodeficiency virus (HIV), viral hepatitis (A, B, or C), or vaccination (usually approximately 2 to 3 weeks following attenuated live virus immunization). The physical examination reveals a healthy-appearing child (unless there is significant blood loss or intracranial bleeding) with widespread bruises, petechiae, and purpuric lesions involving the skin (especially dependent areas). Mucous membrane bleeding (e.g., gingival or gastrointesti-

Chapter 129 — Acute Childhood Immune Thrombocytopenic Purpura and Related Platelet Disorders

nal bleed, epistaxis, menorrhagia) is also common with ITP. Intracranial bleeding, the most feared complication, occurs in less than 1% of cases. Lymphadenopathy, hepatomegaly, splenomegaly, bone or joint pain, fever, neutropenia, and anemia are characteristically absent; their presence suggests bone marrow infi ltration by leukemia or solid tumor. The complete blood count (including peripheral blood smear examination) demonstrates an isolated thrombocytopenia. The diagnosis of ITP should be considered if the platelet count is less than 150 × 103/mm3 ; most patients have a platelet count of less than 20 × 103/mm3. The platelets are typically large, reflecting production of fresh platelets. The hemoglobin concentration, white blood cell count, and differential are normal. Neutropenia, anemia, or circulating nucleated red blood cells, promyelocytes, metamyelocytes, or blasts are not found in ITP. Bone marrow examination shows normal trilineage hematopoietic cells with increased megakaryocytes. This procedure (usually performed by a pediatric hematologist) is sometimes necessary to confirm the diagnosis of ITP (e.g., to exclude acute leukemia, which can be partially treated with corticosteroids). The majority of children recover without recurrence. The platelet count usually becomes normal in 1 to 6 months. Recurrent thrombocytopenia occurs in approximately 10% of patients. Chronic ITP occurs in approximately 10% of children, and is defined as thrombocytopenia that persists more than 6 months. Patients with common variable immunodeficiency frequently develop ITP (alone or in combination with autoimmune hemolytic anemia, or Evans’ syndrome). Thus it is recommended to measure immunoglobulin levels in patients with chronic ITP.5 In some patients, eradicating Helicobacter pylori infection cures chronic ITP.6,7 Thus it is also recommended to search for and treat H. pylori in patients with chronic ITP. Chronic ITP is more common in adolescents.8 In these patients, other autoantibodies (e.g., antinuclear and anti-DNA antibodies) or autoimmune diseases (e.g., systemic lupus erythematosus) may be present or develop in the future.8

Important Clinical Features and Considerations ITP should be distinguished from other causes of thrombocytopenia (Tables 129–1 and 129–2).9 The most common entities are discussed in this section. Acute leukemia often produces bone or joint pain, pallor, fever, and fatigue (in addition to bruising and petechiae). The physical examination usually reveals lymphadenopathy and hepatosplenomegaly. The blood smear may show circulating blasts. The complete blood count often shows abnormalities involving the leukocyte and erythroid lineages in addition to thrombocytopenia (e.g., anemia, reticulocytopenia, neutropenia, abnormal leukocyte differential) (see Chapter 128, Cancer and Cancer-Related Complications in Children). Vasculitis (endothelial cell injury) produces microangiopathic intravascular hemolytic anemia (thrombocytopenia, circulating red blood cell fragments, hemoglobinemia, and hemoglobinuria). This process occurs in hemolytic-uremic syndrome (see Chapter 131, Hemolytic-Uremic Syndrome), thrombotic thrombocytopenic purpura, disseminated intravascular coagulation, and autoimmune vasculitis.

Table 129–1

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Causes of Thrombocytopenia

Increased Platelet Destruction Immune Mediated • Immune thrombocytopenic purpura (ITP) • Collagen vascular diseases (e.g., systemic lupus erythematosus) • Post–viral infections (e.g., human immunodeficiency virus) • Drug-induced thrombocytopenia • Neonatal alloimmune thrombocytopenia (due to incompatibility between fetus and mother)19 • Neonatal thrombocytopenia due to maternal chronic ITP19 Non–Immune Mediated • Hemolytic-uremic syndrome • Thrombotic thrombocytopenic purpura • Disseminated intravascular coagulation • Prosthetic heart valve Platelet Sequestration • Hemangiomas (e.g., Kasabach-Merritt syndrome) • Venous malformation • Splenomegaly with hypersplenism Decreased Platelet Production Congenital • Fanconi's aplastic anemia • Thrombocytopenia and absent radii • Amegakaryocytic thrombocytopenia • Wiskott-Aldrich syndrome (X-linked, characterized by thrombocytopenia, severe eczema, and recurrent bacterial infections) • Paroxysmal nocturnal hemoglobinuria Acquired • Bone marrow infiltration (e.g., leukemia, metastatic tumors, metabolic disorders) • Drug induced • Acquired aplastic anemia Bruises with Normal Platelet Counts • Child abuse • Henoch-Schönlein purpura • Increased vascular leak Pseudothrombocytopenia

Bone marrow failure is associated with various severities of neutropenia, anemia, and thrombocytopenia (with smallsize platelets) and a reduced number of megakaryocytes in the bone marrow. Many medications (e.g., heparin, penicillin, cephalothin, sulfisoxazole, rifampin, phenytoin, valproic acid) produce destructive thrombocytopenia or decreased platelet production. On rare occasions, platelets can be trapped and destroyed in capillary hemangiomas, producing thrombocytopenia (Kasabach-Merritt syndrome). HIV infection is often associated with immune-mediated thrombocytopenia. The clinical presentation can be similar to that of acute ITP. Thus, HIV infection should be considered in high-risk patients (see Chapter 69, Human Immunodeficiency Virus Infection and Other Immunosuppressive Conditions). Thrombocytopenia is common in infants with congenital viral infections. These infants usually have microcephaly, low birth weight, hepatosplenomegaly, and intracranial calcifications. Henoch-Schönlein purpura is a systemic vasculitis associated with the development of painful symmetric, palpable purpura involving proximal regions of the extremities, particularly the legs and buttocks. There may be renal involvement with associated hematuria and proteinuria. Vasculitis

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Table 129–2

Discriminating Features of Patients with Thrombocytopenia

Disorder

Clinical Findings

Laboratory Findings

ITP

Well-appearing child Generalized bruises and petechiae Absence of lymphadenopathy and hepatosplenomegaly Often appears ill Bone and/or joint pain, fever, etc. Lymphadenopathy and hepatosplenomegaly

Isolated thrombocytopenia

Acute leukemia

Bone marrow failure Hemolytic-uremic syndrome

DIC

Child abuse Henoch-Schönlein purpura Hypersplenism

Pallor, bruising, and fever Absence of hepatomegaly and lymphadenopathy Pallor Petechiae and bruising Diarrhea Oliguria and hematuria Ill-appearing child Pallor with petechiae and purpura Bruises of earlobes, back, buttocks, genitalia, etc. Painful purpura involving the buttocks and lower extremities Splenomegaly

Anemia Thrombocytopenia Neutropenia Circulating blasts Pancytopenia of varying severity Thrombocytopenia Microangiopathic anemia Hemoglobinuria Elevated creatinine Thrombocytopenia Microangiopathic anemia Prolonged PT, PTT, and TT Hypofibrinogenemia Normal CBC, PT, PTT, and TT Normal CBC Occasionally hematuria and proteinuria Pancytopenia (cells are trapped in the spleen)

Abbreviations: CBC, complete blood count; DIC, disseminated intravascular coagulation; ITP, immune thrombocytopenic purpura; PT, prothrombin time; PTT, partial thromboplastin time; TT, thrombin time.

involving the intestinal tract can lead to intussusception. The platelet count is normal (see Chapter 122, Henoch-Schönlein Purpura). Petechiae can result from increased vascular leak/pressure due to vomiting, coughing, or application of a tourniquet. The resulting petechiae mostly involve the upper chest and extremities. The platelet count is normal. Child abuse should be considered in the presence of petechiae and bruises in certain locations (e.g., earlobes, back, buttocks) if the platelet count and coagulation studies are normal. The bruises are typically limited to contact sites (see Chapter 119, Physical Abuse and Child Neglect). Rarely, platelets may agglutinate in blood tubes containing ethylenediaminetetraacetate (the anticoagulant used for blood counts), producing pseudothrombocytopenia. This possibility should be considered if the patient has no signs of thrombocytopenia. An estimation of the platelet count can be obtained by placing the patient’s blood directly on a slide. Alternatively, the blood sample can be collected in a citratecontaining blood tube.

Management Corticosteroids remain the best treatment option (Table 129–3).10 Steroids increase vascular stability, decrease antiplatelet antibody production, and reduce clearance of the antibody-platelet complexes. Clinical improvement (e.g., decreased tendency to bruise) usually occurs before a rise in the platelet count. Conventional treatment is prednisone at 2 mg/kg/day (in three divided doses) for 14 days, followed by tapering and discontinuation by day 21. The efficacy of highdose corticosteroids for 1 to 4 days (e.g., intravenous methylprednisolone at 6 mg/kg per dose over 30 minutes every 8 hours for approximately 2 days; pulsed dexamethasone

Table 129–3

Management of Childhood Acute ITP

Corticosteroids Conventional Dose Options • Prednisone, 2 mg/kg/day (in three divided doses) for 14 days, followed by tapering and discontinuation by day 21 • Prednisone, 4 mg/kg/day (in three divided doses) for 14 days, followed by tapering and discontinuation by day 21 • Prednisolone, 60 mg/m2 (in three divided doses) for 14 days, followed by tapering and discontinuation by day 21 High-Dose Options (Active bleeding—platelet count < 20 × 103/mm3) • Pulsed methylprednisolone, 30 mg/kg (maximum dose, 1 g) IV over 30 min q24h for two or three doses20 • Methylprednisolone, 6 mg/kg IV over 30 min q8h for 2–4 days • Pulsed dexamethasone, 40 mg/day (maximum dose) orally for 4 days11 Immunoglobulins Intravenous Anti-D Antibody (for patients who are Rh+): • Rh0 (D) immune globulin, 50–75 mcg/kg IV over 5 min (one dose) (see text for appropriate precautions) Intravenous IgG Concentrate Options (for patients who are Rh–): • Conventional schedule: 0.4 g/kg/day IV over ~4 hr for 5 consecutive days • Two-day schedule: 0.8–1 g/kg/day IV over ~4 hr for 2 consecutive days • One-day schedule: 1 g/kg/day IV over ~4 hr for one dose (the most commonly used regimen) Combined Corticosteroids and Immunoglobulins (for Severe ITP) Conventional or high-dose steroid plus IV anti-D antibody or IgG concentrate Abbreviations: IgG, immunoglobulin G; ITP, immune thrombocytopenic purpura; IV, intravenous(ly).

Chapter 129 — Acute Childhood Immune Thrombocytopenic Purpura and Related Platelet Disorders

at 40 mg/day [maximum dose] orally for 4 days11; or dexamethasone 0.25 mg/kg every 6 hours orally for approximately 2 days) in severe acute ITP is well documented. This approach increases the platelet count to greater than 20 × 103/mm3 by approximately 48 hours in the majority of patients. Intravenous anti-D antibody, or human Rh0 (D) immune globulin, is an effective treatment for patients who are Rh positive.12 The dose is 50 to 75 mcg/kg intravenously over 5 minutes. In most patients, the platelet count rises to greater than 20 × 103/mm3 within approximately 48 hours. Anti-D antibodies bind to red cells, promoting their destruction in the spleen. This process temporarily spares platelet destruction. Intravenous anti-D antibody is contraindicated in immunoglobulin A (IgA) deficiency and in patients with hemoglobin concentrations less than 8 g/dl. The immediate side effects include headache, chills (due to hemolysis of Rh0 (D) antigen–positive red cells), nausea, vomiting, fever, hemolysis, and reduction in hemoglobin concentration. The hemoglobin concentration typically drops by 1 to 3 g/dl in approximately 24 hours. Marked drops in hemoglobin (requiring blood transfusion) and renal insufficiency (due to hemolysis) have been reported; however, their occurrence is very rare. Administration of methylprednisolone (1 mg/kg), acetaminophen, and ondansetron prior to anti-D antibody treatment may prevent fever, nausea, vomiting, and headache. Intravenous polyvalent immunoglobulin G (IgG) concentrates (e.g., 1 g/kg intravenously over approximately 4 hours daily twice) represent an alternative treatment to anti-D antibody for patients who are Rh negative. IgG molecules block splenic Fc/γ receptors on macrophages (sites of platelet destruction). Disadvantages of IgG infusion include high cost and inconvenience (given over 4 hours). Adverse effects include headache (migraine like, lasting for 1 to 2 days), positive Coombs' tests, hemolytic anemia (due to high isoagglutinins), anaphylaxis (occurs in patients with IgA deficiency; IgA-depleted preparations are available), and viral transmission (e.g., hepatitis C). Life-threatening hemorrhage (intracranial, pulmonary, and upper airway) may occur in children with platelet counts less than 20 × 103/mm3.13,14 The presence of severe mucosal, retinal, and cutaneous bleeding identifies patients at greatest risk for serious bleeding. These patients should be admitted and promptly treated with high-dose corticosteroids and anti-D antibody or immunoglobulin concentrates (see Table 129–3). Danazol, mycophenolate mofetil, and rituximab (recombinant antibodies to the lymphocyte membrane antigen CD20) are used in refractory ITP.15-17 Emergency splenectomy is considered for life-threatening, refractory bleeding. Platelets should be administered in active, life-threatening bleeding. Platelet survival is improved if they are transfused soon after immunoglobulin infusion. Aspirin, aspirin-containing compounds, nonsteroidal anti-inflammatory drugs, and anticoagulants are absolutely contraindicated. Intramuscular injections should be avoided. For venous access, the dorsa of the hands and feet are the most suitable sites. Antecubital fossa, jugular, and femoral veins should be avoided to prevent neurovascular compromise if excessive bleeding occurs. After a venipuncture, pressure should be applied to the site for 5 to 10 minutes. Arterial punctures are absolutely contraindicated.

915

The risk for significant bleeding should be carefully assessed. Patients with potential complications related to thrombocytopenia require prompt treatment (see Table 129– 3) and admission for observation. For example, patients with significant head injury require combined therapy (see Table 129–3) and hospitalization (even if a head computed tomography scan is normal). Similarly, patients with significant trauma (e.g., blunt trauma from a car accident) should also receive combined therapy and be admitted for observation. In patients with suspected meningitis, antibiotics should be administered and the spinal tap deferred until the platelet count is approximately 50 × 103/mm3. Major trauma with the need for emergent surgery (e.g., chest, abdominal, central nervous system, orthopedic) requires aggressive combined therapy (see Table 129–3) and immediate consultations with a hematologist and surgeon. A hematology consultation should be considered for assistance in confirming the diagnosis or, in the patient with known stable ITP, arranging disposition and follow-up care, if appropriate. Children should be kept away from sports and playground activities until the platelet count is approximately 50 × 103/ mm3. Protective equipment should be used during activities to prevent trauma, especially head injury (e.g., wearing a helmet).

Summary Acute childhood ITP is a self-limited disease in the majority of children. The diagnosis requires a careful medical history, a thorough physical examination, and complete blood counts (including a careful review of the blood smear) to exclude other etiologies of thrombocytopenia. Physicians outside tertiary care centers can diagnose and treat children with acute ITP based on clinical and laboratory evaluations. Consultation and referral to a tertiary care center are necessary for children who deviate from the “typical” features of this entity.18 REFERENCES 1. Blanchette VS, Carcao M: Childhood acute immune thrombocytopenic purpura: 20 years later. Semin Thromb Hemost 29:605–617, 2003. 2. Beardsley DJ, Tang C, Chen BG, et al: The disulfide-rich region of platelet glycoprotein (GP) IIIa contains hydrophilic peptide sequences that bind anti-GPIIIa autoantibodies from patients with immune thrombocytopenic purpura (ITP). Biophys Chem 105:503–515, 2003. 3. Cooper N, Heddle NM, Haas M, et al: Intravenous (IV) anti-D and IV immunoglobulin achieve acute platelet increases by different mechanisms: modulation of cytokine and platelet responses to IV anti-D by FcγRIIa and FcγRIIIa polymorphisms. Br J Haematol 124:511–518, 2004. 4. Hansen RJ, Balthasar JP: Mechanisms of IVIG action in immune thrombocytopenic purpura. Clin Lab 50:133–140, 2004. 5. Michel M, Chanet V, Galicier L, et al: Autoimmune thrombocytopenic purpura and common variable immunodeficiency: analysis of 21 cases and review of the literature. Medicine (Baltimore) 83:254–263, 2004. 6. Kurtoglu E, Kayacetin E, Ugur A: Helicobacter pylori infection in patients with autoimmune thrombocytopenic purpura. World J Gastroenterol 10:2113–2115, 2004. 7. Michel M, Cooper N, Jean C, et al: Does Helicobater pylori initiate or perpetuate immune thrombocytopenic purpura? Blood 103:890–896, 2004. 8. Buchanan GR, Journeycake JM, Adix L: Severe chronic idiopathic thrombocytopenic purpura during childhood: defi nition, management and prognosis. Semin Thromb Hemost 29:595–603, 2003.

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*9. Kaplan RN, Bussel JB: Differential diagnosis and management of thrombocytopenia in childhood. Pediatr Clin North Am 51:1109–1140, 2004. 10. Bolton-Maggs P, Tarantino MD, Buchanan GR, et al: The child with immune thrombocytopenic purpura: is pharmacotherapy or watchful waiting the best initial management? A panel discussion from the 2002 meeting of the American Society of Pediatric Hematology/Oncology. J Pediatr Hematol Oncol 26:146–151, 2004. 11. Cheng Y, Wong RS, Soo YO, et al: Initial treatment of immune thrombocytopenic purpura with high-dose dexamethasone. N Engl J Med 349:831–836, 2003. 12. Moser AM, Shalev H, Kapelushnik J: Anti-D exerts a very early response in childhood acute idiopathic thrombocytopenic purpura. Pediatr Hematol Oncol 19:407–411, 2002. 13. Butros L, Bussel JB: Intracranial hemorrhage in immune thrombocytopenic purpura: a retrospective analysis. J Pediatr Hematol Oncol 25:660–664, 2003.

*Selected readings.

*14. Thomas K, Buchanan GR, Zimmerman S: A prospective comparative study of 2540 infants and children with newly diagnosed idiopathic thrombocytopenic purpura (ITP) from the Intercontinental Childhood ITP Study Group. J Pediatr 143:605–608, 2003. 15. Maloisel F, Andres E, Zimmer J, et al: Danazol therapy in patients with chronic idiopathic thrombocytopenic purpura: long-term results. Am J Med 116:590–594, 2004. 16. Narang M, Penner JA, Williams D: Refractory autoimmune thrombocytopenic purpura: responses to treatment with a recombinant antibody to lymphocyte membrane antigen CD20 (rituximab). Am J Hematol 74:263–267, 2003. 17. Imbach P, Kuhne T, Zimmerman S: New developments in idiopathic thrombocytopenic purpura (ITP): cooperative, prospective studies by the Intercontinental Childhood ITP Study Group. J Pediatr Hematol Oncol 25:S74–S76, 2003. *18. Modak SI, Bussel JB: Treatment of children with immune thrombocytopenic purpura: are we closer to resolving the dilemma? J Pediatr 133:313–314, 1998. 19. Bussel JB: Fetal and neonatal cytopenias: what have we learned? Am J Perinatol 20:425–431, 2003. 20. Kelton JG: Management of the pregnant patient with idiopathic thrombocytopenic purpura. Ann Intern Med 99:796–800, 1983.

Chapter 130 Disorders of Coagulation Abdul-Kader Souid, MD, PhD

Key Points Regarding the need for a product replacement, the clinician should remember: when in doubt, infuse. The product of choice for patients with factor VIII deficiency is recombinant factor VIII, and for patients with factor IX deficiency, recombinant factor IX. For factor VIII deficiency, 20 to 30 units/kg are infused for mild to moderate bleeding, and 50 to 75 units/kg for moderate to severe bleeding. Follow-up infusions may be necessary. For factor IX deficiency, 40 to 60 units/kg are infused for mild to moderate bleeding, and 80 to 100 units/kg for moderate to severe bleeding. Inherited thrombophilia underlies a large percentage of venous thromboembolic events in children. Other risk factors include estrogen therapy, central venous catheters, congenital heart disease, and nephrotic syndrome.

Selected Diagnoses Factor VIII deficiency (hemophilia A or classic hemophilia) Factor IX deficiency (hemophilia B or Christmas disease) Factors VIII and IX inhibitors von Willebrand’s disease Venous thromboembolism

Discussion of Individual Diagnoses Factor VIII Deficiency (Hemophilia A or Classic Hemophilia) Factor VIII deficiency is the most common inherited (Xlinked recessive) disorder involving secondary hemostasis (affecting approximately 1 in 5000 to 10,000 males). Normal plasma levels of factor VIII are 50 to 150 units/dl. Male patients and female carries who have factor VIII levels greater than 30 units/dl generally have normal hemostasis. Patients with levels less than 1 unit/dl have severe disease (60% of

total patients), those with levels of 1 to 5 units/dl have moderate disease, and those with levels greater than 5 units/dl have mild disease (mild and moderate disease comprise 40% of all patients). Patients with severe disease have frequent bleeding episodes (spontaneously or following trauma), particularly into the joints and muscles. Patients with moderate disease experience bleeding after minor trauma. Patients with mild disease experience bleeding after significant trauma or surgery. Some female carriers have factor levels less than 30 units/dl, and may exhibit symptoms of mild hemophilia (symptomatic carriers). The half-life of endogenous factor VIII is approximately 8 to 12 hours. The half-life of infused factor VIII should be measured in each patient at the time of starting a new product. For repetitive infusions, factor VIII is usually given every 8 to 12 hours. Some patients receive prophylactic infusions (e.g., two to three times per week). Most patients, however, receive on-demand treatment (e.g., following trauma or symptoms related to bleeding). The average cost of factor VIII concentrates is about $1.00 per unit. Most patients with moderate and severe disease have a supply of factor at home. Young children with severe hemophilia usually have an intravenous access device to facilitate infusions (see Chapter 170, Access of Ports and Catheters and Management of Obstruction). Self-infusion education usually begins after about 10 years of age. Clinical Presentation Patients with hemophilia A are typically males. Their symptoms may begin at the time of crawling and walking. Almost all severely affected patients are diagnosed by about 1 year of age. It should be noted that normal screening coagulation tests—prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin time (TT)—exclude a clinically significant coagulation factor deficiency (including hemophilias). The diagnosis of hemophilia A should be suspected in children with a family history of the disease or a bleeding event (e.g., prolonged bleeding from circumcision, medical procedure, surgery, dental extraction, hemarthrosis, or hematoma) associated with a prolonged PTT. A positive family history for the disease is present in only two thirds of patients; the remaining cases have de novo mutations. Infants with hemophilia may tolerate circumcision without excessive bleeding. Thus a history of uneventful circumcision does not exclude the presence of a severe bleeding disorder. 917

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The hallmarks of factor VIII deficiency are joint and muscle hemorrhages.1 The initial symptoms of hemarthrosis are warmth and a tingling sensation (these complaints require immediate factor infusion). As blood fi lls the joint space, swelling, pain, and limitation of movement occur. Bleeding into a target joint (a joint that the patient bleeds into repetitively due to synovitis; defined as 4 bleeding episodes in 6 months, 8 bleeding episodes in 12 months or 20 total bleeding episodes) produces progressive synovitis, hemophilic arthropathy, and chronic arthritis. The latter complication is progressive and irreversible. Thus joint bleeding should be treated at the onset of the earliest symptoms and prior to the development of physical findings. The joint should be immobilized with no weight bearing by using crutches for weightbearing joints or splinting for joint support. Management includes elevating the limb, applying ice packs, and wrapping the joint.1 Joint bleeding is common in severe and less common in mild hemophilia. Thus some patients with severe hemophilia receive prophylactic factor infusion to prevent chronic arthritis. Patients with hematomas present with pain and limited mobility. Iliopsoas bleeding causes pain in the right lower quadrant, resembling appendicitis or hip disease. Muscle bleeding at this site (after heavy weight lifting or strenuous exercise) causes leg flexion, pain in the anterior surface of the thigh due to femoral nerve compression, and inability to extend the leg. Abdominal cavity bleeding (into the liver, spleen, pancreas, or retroperitoneum) produces falling hemoglobin and abdominal or back pain. Buttock, thigh, deltoid, and forearm bleeding may produce neurovascular compression and compartment syndrome. Neck or oral hematoma may cause dyspnea and dysphagia and compromise the airway. Gastrointestinal (GI) bleeding causes melena and bloody vomiting. Each of these scenarios requires immediate (major-dose) factor infusion, rest, close observation, and consultation with a hematologist. Bleeding in the gum, tooth, frenulum, tongue, throat, or pharynx may last a few days. It responds to factor infusions, antifibrinolytic therapy (aminocaproic acid), and diet instructions (using soft/cool diet, such as jello, soft drinks, baby foods, and spaghetti; avoiding hard foods, such as chips, popcorn, and tacos). Painless hematuria is treated by increased fluid intake and bed rest for several days. Factor infusions (for 2 to 4 days) are necessary for persistent painless hematuria. Painless hematuria should be distinguished from hematuria with flank pain. Painful hematuria (e.g., abdominal or flank pain) requires renal ultrasound to assess renal parenchymal bleed and to rule out clots obstructing the ureter, bed rest, and factor infusions for a few days, depending on severity of the bleeding. Antifibrinolytic agents should be avoided due to their ability to cause clots that may obstruct the ureter. Intracranial bleeding is the leading cause of death. Central nervous system (CNS) bleeding may be spontaneous. Head trauma or any signs or symptoms of intracranial hemorrhage (e.g., headache, irritability, vomiting, seizure, ocular or visual problems, focal deficits, stiff neck, change of consciousness) require immediate treatment with a major-dose factor infusion prior to any diagnostic imaging or lengthy clinical evaluation. The onset of neurologic signs or symptoms following head trauma may be delayed due to the slowly oozing nature of hemophiliac bleeding.

Hemophilia A is diagnosed by prolonged aPTT and low factor VIII activity (20 × 103/mm3), central nervous system involvement (e.g., stroke, seizure), and prolonged anuria (>7 days) or oliguria (>14 days). Relapses lead to hypertension and end-stage renal disease. Laboratory Evaluation A complete blood count often shows normocytic anemia and thrombocytopenia (Table 131–1). The plasma is pink-red, reflecting hemoglobinemia. The blood smear shows red cell fragments and thrombocytopenia. Blood typing is necessary because of a potential need for packed red blood cell transfusion. Serum electrolytes, blood urea nitrogen (BUN), creatinine, phosphate, and uric acid levels may show disturbances produced by diarrhea (hyperchloremic metabolic acidosis with normal anion gap) or acute renal failure (increase serum Table 131–1

creatinine, hyperkalemia, hyperphosphatemia, elevated uric acid, and metabolic acidosis). Lactate dehydrogenase is markedly elevated due to red cell hemolysis and microangiopathy. Indirect bilirubin is mildly elevated due to the hemolysis. Urinalysis shows hemoglobinuria (without red blood cells) and, sometimes, granular casts. A centrifuged urine sample remains pink-red, containing free hemoglobin molecules. In contrast, hematuria due to the presence of red blood cells produces clear urine supernatant. Normal tests in HUS include direct and indirect antiglobulin (Coombs’) tests, partial thromboplastin time, prothrombin time, thrombin time, and fibrinogen. Antinuclear antibodies, anti-DNA antibodies, and C3 and C4 are negative (as evidence against the presence of systemic lupus erythematosus and membranoproliferative glomerulonephritis). Other frequently abnormal but nonspecific laboratory tests include serum albumin, amylase, lipase, glucose, triglyceride, and liver transaminases. Stool culture may identify the infectious agent (important for reporting outbreaks). However, routine stool cultures may not identify E. coli. A rapid screening test for E. coli (based on failure to ferment on sorbitol) has been developed; a positive reaction should be confirmed by commercially available agglutination tests. Positive results are more common within 7 days of the onset of diarrhea. Verotoxin can be identified in stool samples by polymerase chain reaction or other readily available laboratory techniques. Differential Diagnosis Thrombotic thrombocytopenic purpura (TTP) has a presentation similar to HUS (Table 131–2). TTP usually develops in adolescents and adults. It produces more prominent neurologic deterioration than renal involvement. Prompt recognition is essential, since this entity requires immediate plasmapheresis. Autoimmune hemolytic anemia may produce intravascular hemolysis (more commonly seen in cold agglutinin disease and paroxysmal cold hemoglobinuria). In these entities, platelet count and renal function are normal. In cold agglutinin disease, immunoglobulin M–coated red blood cells activate the hemolytic complement cascade, causing intravascular hemolysis (red blood cell fragments, hemoglobinemia, and hemoglobinuria). Acrocyanosis and hemolysis follow exposure to cold. A direct antiglobulin test is positive with the reagent containing anticomplement antibodies. Par-

Interpretation of Laboratory Results in Hemolytic-Uremic Syndrome

Laboratory Tests

Interpretation/Purpose

CBC Peripheral blood smear Urinalysis Serum electrolytes, BUN, creatinine, phosphate, and uric acid Lactate dehydrogenase and bilirubin Stool culture and other stool studies Antiglobulin (Coombs’) tests aPTT, PT, TT, and fibrinogen Antinuclear antibodies, anti-DNA antibodies, C3 and C4

Anemia and thrombocytopenia. Red blood cell fragments. Hemoglobinuria. Metabolic derangements (e.g., hyperkalemia, metabolic acidosis) are common. Elevated levels reflect hemolysis. Used to detect E. coli, verotoxin, or other causative pathogens. Normal, positive results suggest autoimmune hemolytic anemia and not HUS as cause of symptoms. Normal, prolonged results suggest DIC and not HUS as cause of symptoms. Normal, positive results suggest systemic lupus erythematosus or membranoproliferative glomerulonephritis and not HUS as cause of symptoms.

Abbreviations: aPTT, activated partial thromboplastin time; BUN, blood urea nitrogen; CBC, complete blood count; DIC, disseminated intravascular coagulation; HUS, hemolytic-uremic syndrome; PT, prothrombin time; TT, thrombin time.

Chapter 131 — Hemolytic-Uremic Syndrome

Table 131–2

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Differential Diagnosis of Hemolytic-Uremic Syndrome

Disorder

Clinical Features

HUS

Prodrome manifestations include diarrhea, abdominal pain, and bloody or heme-positive stools. Simultaneous occurrence of acute anemia with circulating red cell fragments, hemoglobinemia, hemoglobinuria, thrombocytopenia, and increased serum creatinine. Clinical presentation similar to HUS. More prominent neurologic deterioration than renal involvement. Immediate plasmapheresis is necessary. Normal renal function; absence of hematuria; normal hemoglobin (see Chapter 129). Acute hemolytic anemia with positive Coombs’ tests. Platelet count and renal function are normal. Normal platelet count and absence of microangiopathic hemolytic anemia. Prolonged PT, aPTT, and TT; hypofibrinogenemia. Painful symmetric, palpable purpura involving proximal regions of the extremities, particularly legs and buttocks. Petechiae/purpura with normal platelet count.

TTP ITP Autoimmune hemolytic anemia Renal disease DIC Henoch-Schönlein purpura

Abbreviations: aPTT, activated partial thromboplastin time; DIC, disseminated intravascular coagulation; HUS, hemolytic-uremic syndrome; ITP, immune thrombocytopenic purpura; PT, prothrombin time; TT, thrombin time; TTP, thrombotic thrombocytopenic purpura.

oxysmal cold hemoglobinuria is produced by immunoglobulin G antibodies (Donath-Landsteiner cold autoantibodies), having biphasic thermal activities. These antibodies fi x to red blood cell membranes in the cold (4° C) and activate the hemolytic complement cascade at 37° C. Thrombocytopenia (see Chapter 129, Acute Childhood Immune Thrombocytopenic Purpura and Related Platelet Disorders) may occur as a result of immune-mediated destruction (acute childhood immune thrombocytopenic purpura), after a viral infection (human immunodeficiency virus, chicken pox, and postimmunization), drugs, vasculitis (systemic lupus erythematosus), intravascular destruction (disseminated intravascular coagulation and prosthetic heart valve), platelet trapping (venous malformation, hemangiomas, and hypersplenism), and decreased platelet production (aplastic anemia, thrombocytopenia–absent radius syndrome, amegakaryocytic thrombocytopenia, and WiscottAldrich syndrome). In disseminated intravascular coagulation, fibrinogen is low. Renal parenchymal disease is usually associated with a normal platelet count and absence of microangiopathic hemolytic anemia.

Important Clinical Features and Considerations Clinicians should be aware that HUS might reoccur. While debate exists as to causation or worsening of disease with antibiotic administration,11,12 clinicians should avoid their use unless absolutely necessary (e.g., proven bacterial infection, bowel perforation). Renal manifestations including hematuria, oliguria, and hypertension many herald the onset of renal failure. Neurologic findings include altered mental status, seizures, and coma. The skin features include pallor (due to anemia), petechiae, and purpura.

Management All patients require hospitalization for observation and appropriate interventions. Treatment is mainly supportive2 (Table 131–3). Dehydration due to diarrhea and decreased intake must be corrected while avoiding volume overload. Acute hypertension is treated with short-acting oral agents if asymptomatic or intravenous agents for encephalopathy or other hypertensive emergencies (see Chapter 65, Hyper-

Table 131–3

Management of Hemolytic-Uremic Syndrome

1. Correct dehydration due to diarrhea while avoiding fluid overload 2. Adequately treat hypertension using intravenous agents (e.g., nicardipine, sodium nitroprusside) for hypertensive emergencies. 3. Avoid platelet transfusions. 4. Use antibiotics only for proven infections or suspected bowel perforation. 5. Dialysis is indicated if patient develops anuria, severe oliguria, hyperkalemia unresponsive to conventional therapy, severe azotemia (e.g., encephalopathy), fluid overload, or pulmonary edema. 6. Administer packed red blood cells to keep hemoglobin ~8.0 g/dl. 7. Plasma infusion (10 ml/kg over 2–4 hr) or plasmapheresis is indicated in patients with central nervous system involvement or severe renal disease. 8. Patients with seizures require emergent imaging to exclude intracranial pressure or bleeding. Promptly treat seizures with standard agents (e.g., lorazepam followed by fosphenytoin). 9. Early consultations with nephrology, hematology, and plasmapheresis teams to assist with clinical care and to expedite interventions (e.g., dialysis, plasmapheresis). 10. Admit patients to a floor that can adequately monitor vital signs and fluid intake/output, and observe for acute deterioration (e.g., seizures).

tensive Emergencies). Packed red blood cells should be administered to maintain hemoglobin concentrations above approximately 8.0 g/dl. Seizures should be investigated with computed tomography or magnetic resonance imaging of the brain and treated appropriately (see Chapter 40, Seizures). Platelet transfusion should be avoided and antibiotics reserved for suspected bowel perforation or documented bacterial infection. Dialysis is indicated in the presence of anuria (>24 hours), severe oliguria, uncontrollable hyperkalemia, severe azotemia (e.g., encephalopathy, BUN >100 mg/dl), or fluid overload with pulmonary edema. Once fluid deficit is corrected, total fluid intake should be limited to replacing insensible water loss (pure water at ~50% of estimated maintenance fluid therapy), measured urine output, and measured ongoing fluid loss from the diarrhea. Plasma infusion or plasmapheresis is indicated in patients with central nervous system involvement or severe renal disease (e.g., oliguria, hypertension, hyperkalemia, hypervolemia, pulmonary edema). Treatment frequency varies

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from daily to twice weekly.2 Consultations include those to nephrology, hematology, and plasmapheresis teams. Controversial therapies include tissue-type plasminogen activator (Alteplase) and aspirin (platelet inhibitor).

Summary Children with mild to moderate HUS can be treated with supportive care only. Children with moderate to severe HUS are more likely to need plasmapheresis and dialysis (especially if neurologic and severe renal involvements are present). TTP has a presentation similar to HUS; it occurs in adolescents and requires aggressive treatment, particularly with plasmapheresis. Antibiotics may increase the release of verotoxin and should be avoided unless they are absolutely indicated. Platelet transfusion may lead to thrombosis, and should be avoided in the absence of a life-threatening hemorrhage. REFERENCES 1. Siegler RL: Management of hemolytic uremic syndrome. J Pediatr 112:1014–1020, 1988. *2. Chandler WL, Lelacic S, Boster DR, et al: Prothrombotic coagulation abnormalities preceding the hemolytic-uremic syndrome. N Engl J Med 345:23–32, 2002.

*Selected readings.

*3. Bergstein JM, Riley M, Bang NU: Role of plasminogen-activator inhibitor type 1 in the pathogenesis and outcome of the hemolytic uremic syndrome. N Engl J Med 327:755–759, 1992. 4. Nevard CH, Blann AD, Jurd KM, et al: Markers of endothelial cell activation and injury in childhood hemolytic uremic syndrome. Pediatr Nephrol 13:487–492, 1999. 5. Moake JL, Rudy CK, Troll JH, et al: Unusually large plasma factor VIII:von Willebrand factor multimers in chronic relapsing thrombotic thrombocytopenic purpura. N Engl J Med 307:1432–1435, 1982. 6. Moake JL, Byrnes JJ, Troll JH, et al: Abnormal VIII:von Willebrand factor patterns in the plasma of patients with the hemolytic uremic syndrome. Blood 64:592–598, 1984. 7. Furlan M, Robles R, Galbusera M, et al: Von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura. N Engl J Med 339:1578–1584, 1998. 8. Veyradier A, Obert B, Houllier A, et al: Specific von Willebrand factorcleaving protease in thrombotic microangiopathies: a study of 111 cases. Blood 98:765–772, 2001. 9. Karpman D, Papadopoulou D, Nilsson K, et al: Platelet activation by Shiga toxin and circulatory factors as a pathogenic mechanism in the hemolytic uremic syndrome. Blood 97:3100–3108, 2001. 10. Tsai H, Chandler WL, Sarode R, et al: Von Willebrand factor and von Willebrand factor-cleaving metalloprotease activity in Escherichia coli O157:H7-associated hemolytic uremic syndrome. Pediatr Res 49:653– 659, 2001. 11. Wong CS, Jelacic S, Habeeb RL, et al: The risk of the hemolytic-uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 infections. N Engl J Med 342:1930–1936, 2000. 12. Safdar N, Said A, Gangnon RE, et al: Risk of hemolytic uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 enteritis: a meta-analysis. JAMA 288:996–1001, 2002.

Chapter 132 Utilizing Blood Bank Resources/ Transfusion Reactions and Complications Abdul-Kader Souid, MD, PhD, Lazaro G. Rosales, MD, and Boura’a Bou Aram, MD

Key Points A transfusion should be recommended only after the risks and benefits are carefully considered. Most transfusion fatalities occur as a result of ABO incompatibility due to an error in identifying the patient or a unit of blood. Leukocyte-depleted blood components are recommended for patients requiring chronic transfusion. Irradiated blood components are recommended for immune-compromised patients. Permission with informed consent to transfuse should be obtained for each patient.

Blood Bank Resources Collecting Donated Blood and Testing Blood Components Prior to Use Blood products obtained for medical use are donated by healthy volunteers under federal and state regulations.1,2 Donated blood is tested for infectious disease markers, such as syphilis, hepatitis B surface and human immunodeficiency virus type 1 (HIV-1) p24 antigens, and hepatitis B core, human T-cell lymphotropic virus types I and II (HTLV-I and HTLV-II), hepatitis C, HIV-1, and HIV type 2 (HIV-2) antibodies. Polymerase chain reaction is performed for HIV and hepatitis C virus. Risk of missing the detection of infectious agents occurs in the “window period” between exposure and positive testing. A high risk especially involves hepatitis B

virus due to its long window period; vaccination for hepatitis B virus reduces this risk. Other rare viruses and diseases include West Nile virus, herpesviruses, parvovirus B19, variant Creutzfeldt-Jakob disease, and severe acute respiratory syndrome. Current standard testing does not detect these infections; nevertheless, viral transmission via blood components is very rare.3,4 The blood groups routinely tested for donors and recipients are the ABO and Rh systems. The ABO blood group is determined because anti-A and/or anti-B immunoglobulin M (IgM) alloantibodies in the recipient’s serum produce rapid hemolysis of donor red cells. Commercially available anti-A and anti-B antibodies are used to determine ABO blood type. These IgM molecules bind to A group and B group red cell antigens, respectively, producing direct (macroscopic) agglutination. Moreover, incubating the recipient’s serum with commercially available group A and group B red cells demonstrates the presence of specific alloantibodies, confirming the ABO blood type. For example, blood type A shows the recipient’s red cell agglutination with commercial anti-A antibodies and commercial group A red cell agglutination with the recipient’s serum. Commercially available (modified) anti-Rh immunoglobulin G (IgG) can directly agglutinate (macroscopically visible) D-positive (or Rh0) red blood cells. The Rh blood group is determined because D antigen, the major determinant of the Rh system, is a strong immunogen, producing anti-D antibodies in Rh-negative recipients. An Rh-negative woman who is immunized to D antigen by transfusion or pregnancy is at risk of delivering a newborn with severe hemolysis. Thus individuals who are Rhnegative, especially females of childbearing age, require Rhnegative blood and platelets to prevent Rh sensitization. For Rh-negative recipients, the decision to stay with Rhnegative blood versus switching to Rh-positive components is based on the anticipated need for future red blood cell (RBC) transfusion, availability of Rh-negative components, and urgency of transfusing other Rh-negative patients. As soon as it becomes apparent that the Rh-negative patient will 931

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receive massive transfusion (more than the patient’s blood volume in 24 hours; blood volume is estimated as 100 ml/kg for preterm neonates, 85 ml/kg for term neonates, and 75 ml/kg for children >1 month of age) that will exceed the Rh-negative blood inventory, the patient should be switched to Rh-positive components. The problem with giving Opositive red cells immediately without antibody screening in an emergency is the potential for developing hemolytic transfusion in patients who have anti-D antibodies. Detecting blood group antibodies (isoagglutinins) directed against non-ABO blood group antigens is also performed prior to blood transfusion. This antibody screening test is performed using recipient serum against a panel of “group O” RBCs of known antigenic composition. The term antibody screening test is sometimes used synonymously with the term indirect antiglobulin (Coombs) test (IAT). If the test is positive (hemolysis or agglutination), further tests to determine specific antibodies will be performed. The IAT is performed by incubating the recipient’s serum (at 37° C) with commercially available red blood cells of known antigen type. Unbound antibodies are removed by washing RBCs with 0.9% NaCl. An antiglobulin reagent (rabbit anti-human IgG or IgG plus complement) is then added. A positive test shows red cell agglutination, reflecting the presence of allo- or autoantibodies. Allo- versus autoantibodies are determined by a commercially available panel of red cells, varying with antigen phenotype. Agglutination of all red cell panels indicates autoantibodies (e.g., patients with autoimmune hemolytic anemia). By contrast, specific reactivity indicates alloantibodies (e.g., patients with alloimmunization). The direct antiglobulin (Coombs') test detects antibodies or complement on the surface of red cells. Washed recipient's red cells are incubated with antiglobulin reagent (rabbit anti-human IgG or IgG plus complement) as in the IAT. Agglutination is observed if antibodies or complement are present on the surface of red cells. A crossmatch with an ABO- and Rh-compatible unit of blood determines whether the recipient's serum contains unexpected antibodies to the donor's red cell antigens. Whenever red cell products are requested, ABO and Rh typing, antibody screening, and a full crossmatch are routinely performed. If the antibody screen is negative, the patient may be transfused the appropriate ABO/Rh type. An immediate spin crossmatch (mixing the patient's serum with RBCs from a unit selected for transfusion and observing for hemolysis or agglutination) provides added safety. If the antibody screen is positive, the specificity of the antibody is identified; if clinically significant, only red cells negative for the relevant antigen will be transfused. A full crossmatch is also performed. Additional time is required to identify the antibodies, find antigen-negative red cells, and perform full crossmatch tests. This may take hours or days if multiple antibodies are present (Table 132–1). In an emergency situation, blood may need to be transfused before standard testing is completed. In these circumstances, physicians are asked to sign an “emergency release form” to document the reason for the urgent need and to acknowledge that the blood is not fully crossmatched at the time of transfusion. O-negative red cells are available for immediate transfusion to any patient, but should be used only when the patient’s blood type is not known and there is no time to determine it. This situation sometimes occurs in

Table 132–1

Estimated Times for Blood Bank to Release Units of Red Blood Cells

Test/Product −

O ABO and Rh typing Type and screen Type and crossmatch Leukocyte-reduced PRBCs Irradiated PRBCs

Time to Completion Immediate 10 min 15 min 45 min Typically performed at the time of blood collection or at the bedside using a filter 10 min

Abbreviation: PRBCs, packed red blood cells.

the setting of trauma and should apply to the first few units transfused. Packed Red Blood Cell (Red Cell Concentrate) Transfusion Packed red blood cell (PRBCs) transfusions are used to improve blood oxygen-carrying capacity and restore blood volume. Units are prepared from whole blood by removing most of the plasma (producing an average hematocrit value of 70%). This procedure reduces the transfusion volume and the isoagglutinin load. Each unit usually contains approximately 200 ml of RBCs, 70 ml of plasma, and 100 ml of additive nutrient solution (e.g., citrate [as an anticoagulant], phosphate, dextrose, and ATP). Clinical citrate toxicity (hypocalcemia due to calcium chelation) is rare, occurring only with massive transfusions (e.g., exchange transfusion), and responds to calcium supplements. Prolonged storage produces a leakage of potassium into the plasma, which is usually clinically insignificant. Blood should be infused through a fi lter (170 to 260 µm) to remove debris caused by storage.1,2 Transfusion is usually given if the symptoms of anemia or blood loss are severe and further delay might result in significant disability or death. Selected indications for transfusion include acute bleeding, high-dose chemotherapy, severe prematurity, sickle cell disease (e.g., splenic sequestration, severe acute chest syndrome), thalassemia major, aplastic anemia, pure red cell aplasia, and severe autoimmune hemolytic anemia (using the most compatible unit).2 Transfusing 10 to 15 ml/kg of PRBCs in a child raises the hemoglobin concentration by 2 to 3 g/dl and the hematocrit by 6% to 9% (Table 132–2).1,5 Transfusion is usually given at 15 ml/kg over 2 to 4 hours. Faster transfusion may be necessary to replace acute blood loss. If the intention is to transfuse small amounts (e.g., in infants), a unit can be divided into several aliquots. Leukocyte-reduced PRBCs are prepared by passing the unit through a fi lter that removes 85% to 90% of the white blood cells; the procedure is frequently performed at the time of blood collection. This type of product produces fewer nonhemolytic febrile reactions, which are mediated by antibodies against the donor’s white cell antigens as well as by cytokines produced during component storage. This product also produces less alloimmunization and viral (e.g., cytomegalovirus) transmission. It is indicated for patients who need chronic transfusion (e.g., children on chemotherapy or with hemoglobinopathy) or who have prior exposure to blood antigens (e.g., multiparous females).1

Chapter 132 — Utilizing Blood Bank Resources/Transfusion Reactions and Complications

Table 132–2

933

Blood Component Transfusion*

Product

Indication

Crossmatch

Dose

Expected Rise

PRBCs Leukocyte-reduced PRBCs Irradiated PRBCs Washed PRBCs

Improving blood oxygen-carrying capacity and restoring blood volume Chronic PRBC transfusions Immune-compromised patients Persistent allergic reactions Thrombocytopenia

Complete

10–15 ml/kg

Hemoglobin concentration increases by 2–3 g/dl†

ABO

Platelet count increases by 25–50 × 103/mm3

Chronic platelet transfusions

ABO

Acquired coagulopathy, reversal of warfarin, clotting factor (II, X, XI and XIII) deficiency, TTP and HUS Rich in fibrinogen, von Willebrand’s factor, and factor VIII

ABO

1 unit/10 kg; 4–6 units for adults‡ 10 ml/kg; 1 unit for adults § 10–25 ml/kg

Platelets (whole blood derived) Platelets (apheresis) FFP Cryoprecipitate

ABO

1–4 units/10 kg; 8–12 units for adults**

Each coagulation factor increases by 10% –20%¶ Plasma fibrinogen increases by 60–100 mg/dl

*Modified from Pisciotto P (ed): Pediatric Hemotherapy Data Card. Bethesda, MD: American Association of Blood Banks, 2002. † Increments depend on anticoagulant-preservative solution. ‡ Each unit contains 5.5 × 1010 platelets in 50 ml of plasma. § Each unit contains 3.0 × 1011 platelets in 250 ml of plasma. ¶ Different recovery for each factor (depending on circulatory half-lives). **Each unit contains approximately 250 mg of fibrinogen. Abbreviations: FFP, fresh frozen plasma; HUS, hemolytic-uremic syndrome; PRBC(s), packed red blood cell(s); TTP, thrombotic thrombocytopenic purpura.

Irradiated PRBCs are prepared by exposing the unit to 2500 cGy of radiation. This treatment inactivates the donor’s T cells, which reduces the risk of a graft-versus-host reaction in the recipient. This type of product is recommended for immune-compromised patients (e.g., children on chemotherapy).1 Washed PRBCs are prepared by washing red cells with 0.9% NaCl, which removes most of the plasma. This type of product is used for patients who have severe allergic reactions (e.g., cough, wheezing, swollen lips, and urticaria) to transfusion despite antihistamine administration. Immunoglobulin E antibodies against the donor’s plasma proteins mediate this adverse reaction. This product is also used for patients with immunoglobulin A (IgA) deficiency who have developed IgA antibodies.2 Platelet Transfusion Platelets are the principal mediator of hemostasis and are constantly required to support endothelial functions. Bleeding (e.g., petechiae, epistaxis, melena, hematemesis, menorrhagia, hematuria) is common when the platelet count is 10,000/mm3 or less. Moreover, life-threatening hemorrhage (e.g., into the airway, lungs, central nervous system, and gastrointestinal tract) becomes more likely when the platelet count is 5000/mm3 or less. Thus profound thrombocytopenia (defined as a platelet count < 20,000/mm3) due to decreased production (e.g., patients on chemotherapy or with aplastic anemia) should be promptly treated with platelet transfusion. A prophylactic transfusion is recommended when the platelet count is less than 20,000/mm3. A therapeutic transfusion, in contrast, is given to treat any significant bleeding even if the platelet count is greater than 20,000/mm3.2 Platelet concentrates are prepared from routinely donated whole blood by centrifugation, producing platelet-rich plasma that, on further centrifugation and separation of

the supernatant plasma, yields a platelet concentrate (unit) of 50 ml. A single unit (prepared from 1 unit of whole blood) should contain greater than 5.5 × 1010 platelets, which raises the platelet count by 6 to 10 × 103/mm3 in adults. Transfusing 4 to 6 pooled random-donor units of platelets for adults and children greater than 20 kg (1 unit/10 kg for children < 20 kg) raises the platelet count by 25 to 50 × 103/mm3 (see Table 132–2), which is usually adequate for supporting hemostasis (see Table 132–2).5 Platelets are also prepared from blood from a single donor with the use of blood cell separator machines, yielding a platelet product (apheresis) equivalent to that of 5 random units. For adults and children greater than 20 kg, a platelet transfusion requires 1 single-donor apheresis unit (10 ml/kg for children < 20 kg) (see Table 132–2).1,5 This type of product (apheresis unit of platelets) aims to minimize donor exposure and is recommended for patients requiring chronic transfusion.5 If the intention is to transfuse a small volume (e.g., in infants), an apheresis unit of platelets can be divided into two aliquots. Platelet survival (normal, 9.6 ± 0.6 days) is shorter in patients with profound thrombocytopenia (platelets are normally consumed in the spleen and blood vessels), alloimmunization, fever, infection, and splenomegaly. ABOcompatible, single-donor apheresis, leukocyte-depleted and irradiated platelets are less likely to produce alloimmunization, and are therefore recommended for patients requiring chronic transfusion. Other indications for leukocyte-depleted and irradiated products are as discussed for PRBC transfusion. Platelet transfusion is not recommended in patients with hemolytic-uremic syndrome, thrombotic thrombocytopenic purpura, heparin-induced thrombocytopenia, and idiopathic thrombocytopenic purpura. Any medication that could inhibit platelet function (e.g., salicylates and nonsteroidal anti-inflammatory drugs) should be avoided in thrombocytopenic patients.

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Fresh Frozen Plasma and Cryoprecipitate Transfusion Fresh frozen plasma (FFP) is prepared from whole blood; it should be frozen at less than 18° C within 6 hours of collection. This procedure preserves the activities of labile proteins, such as factors V and VII. It is a nonconcentrated source of clotting factors and is used for acquired coagulopathy (e.g., liver disease and disseminated intravascular coagulation), rapid reversal of warfarin, congenital coagulation factor deficiency (e.g., factors II, X, XI, XIII), thrombotic thrombocytopenic purpura, and hemolytic-uremic syndrome (see Chapter 129, Acute Childhood Immune Thrombocytopenic Purpura and Related Platelet Disorders; and Chapter 131, Hemolytic-Uremic Syndrome). The dose ranges from 10 to 25 ml/kg, repeated as necessary (see Table 132–2).5 The product should be ABO compatible. Potential complications include viral transmission (e.g., HIV, hepatitis), anaphylactic reaction, urticaria, and alloimmunization. Because of the risk of viral transmission, FFP should be used only if absolutely necessary. Cryoprecipitate is prepared from FFP by thawing at 4° C. The precipitate is then suspended in 15 ml plasma and refrozen at less than 18° C. It is rich in fibrinogen (each unit contains approximately 250 mg), factor VIII, and von Willebrand's factor. It is used to treat bleeding due to fibrinogen deficiency, such as severe liver disease, disseminated intravascular coagulation, and afibrinogenemia (rare). The recommended dose is 1 to 4 units (bags) per 10 kg (8 to 12 units for adults), which raises plasma fibrinogen to by 60 to 100 mg/dl (see Table 132–2).5 Due to the risk of viral transmission and availability of safer products, cryoprecipitate should not be used to treat patients with hemophilia A or von Willebrand’s disease.

Transfusion Reactions Hemolytic Transfusion Reactions ABO incompatibility produces severe immune-mediated hemolytic reactions. The anti-A and/or anti-B IgM alloantibodies in the recipient’s plasma produce intravascular hemolysis (circulating RBC fragments, hemoglobinemia, and hemoglobinuria) of the donor’s RBCs. The symptoms include rigors, headache, fever, chest tightness, flank pain, red/black urine, hypotension, nausea, and vomiting. Serious progression may be fatal due to shock and organ failure. Management includes immediately stopping the transfusion and administering isotonic fluid (0.9% NaCl) and mannitol (0.25 g/kg intravenously) to induce diuresis. Careful monitoring (respiratory and circulatory status, urine output, and urine color), supportive care (intravenous fluid, diuretics, and oxygen) and appropriate consultations (blood bank, nephrology, and hematology) are necessary. The blood bag and blood sample from the recipient should be returned to the blood bank for retyping. Nonimmune hemolytic reaction occurs when RBCs are damaged prior to transfusion (e.g., exposed to improper temperature during shipping or storage, mishandling during transfusion). Hemoglobinemia and hemoglobinuria are present in the recipient without symptoms. This complication requires no treatment.

Nonhemolytic Transfusion Reactions Febrile reactions are caused by cytokines (produced by the donor’s leukocytes) accumulated in stored blood. These molecules produce fever, rigors, tachycardia, and dyspnea. Management consists of stopping the transfusion and excluding a hemolytic transfusion reaction (repeat crossmatching of the unit of blood and performing Coombs’ tests). The symptoms usually subside within 30 minutes of stopping the transfusion. Premedication with acetaminophen is usually helpful. Allergic symptoms (rash and urticaria, pruritus, flushing, and, rarely, angioedema) follow the recipient’s exposure to the donor’s plasma proteins or other substances (e.g., medications taken by the donor). This reaction can be ameliorated by premedicating with diphenhydramine (0.5 to 1 mg/kg) and methylprednisolone (0.5 to 1 mg/kg). A severe form of allergic reaction (anaphylactic) can occur in recipients who are IgA deficient. Management of urticaria consists of discontinuing the transfusion and administering diphenhydramine and methylprednisolone. Anaphylaxis requires intravenous fluids, steroids, and subcutaneous or intravenous epinephrine administration depending upon the severity. Transfusion-related acute lung injury is a noncardiogenic pulmonary edema associated with passive transfusion of donor granulocyte antibodies. The reaction occurs when the donor’s antileukocyte antibodies (e.g., in multiparous or previously transfused donors) react with the recipient’s leukocytes, which are then aggregated and activated in the lung microvasculature, producing altered vascular permeability and pulmonary capillary leak syndrome, resembling acute respiratory distress syndrome (ARDS). It should be managed similarly to ARDS. Circulatory overload (cough, precordial pain, tachycardia, tachypnea, dyspnea, and hypoxia) may follow rapid transfusion. This complication is more common in patients with cardiac or renal disease, hypertension, or profound anemia (hemoglobin concentration < 5.0 g/dl). Treatment includes stopping the transfusion, oxygen supplementation, and administration of furosemide (0.5 to 1 mg/kg intravenously). Volume overload can be avoided by transfusing half of the desired transfusion over 4 hours, followed by administration of intravenous furosemide (0.5 to 1 mg/kg), followed by the second half of the transfusion over 4 hours. Rare acute complications include bacterial contamination (most notably from platelet transfusion), citrate-induced hypocalcemia, and hyperkalemia (due to ruptured red cells). Delayed Transfusion Reactions Viral contamination with cytomegalovirus, HIV, and hepatitis A, B, and C virus remains a serious complication. Posttransfusion hepatitis is of particular concern because donors are usually asymptomatic. The risk of HIV transmission is almost negligible (probably 1 in 8 million transfusions). Alloimmunization (developing alloantibodies against red cell, platelet, and leukocyte antigens) results from multiple exposures to donor antigens. Every transfusion has the potential to induce alloimmunization. Posttransfusion graft-versus-host reaction occurs in patients on chemotherapy or with immunodeficiency. It also occurs

Chapter 132 — Utilizing Blood Bank Resources/Transfusion Reactions and Complications

in newborns and young infants who receive transfusion from blood relatives. Donor T cells attack recipient tissues, producing skin rash, increased transaminases, and diarrhea. Gamma irradiation of blood components eliminates this risk. Iron overload results from repeated PRBC transfusions. Long-term complications of hemochromatosis include cirrhosis, fibrosis of the pancreas, and cardiomyopathy. Chelation therapy with deferoxamine mesylate (Desferol) is necessary for patients receiving long-term transfusions.

Summary Viral transmission through transfusion occurs very rarely, and the risk of developing acquired immunodeficiency syndrome from a blood transfusion is almost negligible. Nevertheless, the risk of not receiving a transfusion should always outweigh the potential adverse effects. Serious transfusion reactions can be avoided by verifying each patient’s identification and the blood groups of recipients and donors. Blood

935

components should be transfused slowly in the first 15 minutes, with the patient being closely monitored. Diphenhydramine (0.5 to 1 mg/kg), methylprednisolone (1 mg/kg), and acetaminophen can be given for minor allergic and/or febrile reactions. These medications also can be used as prophylaxis for patients with prior adverse reactions to transfusion. Leukocyte-reduced and irradiated blood components produce less adverse reactions. REFERENCES 1. Gorlin JB (ed): Standards for Blood Banks and Transfusion Services, 21st ed. Bethesda, MD: American Association of Blood Banks, 2002. 2. Roseff AD, Luban NLC, Manno CS: Guidelines for assessing appropriateness of pediatric transfusion. Transfusion 42:1398–1413, 2002. 3. Ceccherini-Nelli L, Filipponi F, Mosca F, Campa M: The risk of contracting an infectious disease from blood transfusion. Transplant Proc 36:680–682, 2004. 4. Pealer LN, Marfi n AA, Petersen LR, et al: Transmission of West Nile virus through blood transfusion in the United States in 2002. N Engl J Med 349:1236–1245, 2003. 5. Pisciotto P (ed): Pediatric Hemotherapy Data Card. Bethesda, MD: American Association of Blood Banks, 2002.

Toxicologic

Chapter 133

Common Pediatric Overdoses Deborah J. Mann, MD and Richard M. Cantor, MD

Key Points Specific medications are harmful to children, even in small amounts. Cyanosis unresponsive to supplemental oxygen may be a sign of methemoglobinemia. Exposure to long-acting oral hypoglycemics often necessitates overnight admission for glucose monitoring. Serum acetaminophen and aspirin levels are mandatory in all intentional overdose cases. Acetaminophen levels drawn before 4 hours postingestion do not reflect or predict potential toxicity or the need for N-acetylcysteine therapy.

Introduction and Background Epidemiology of Pediatric Poisonings Exposure to toxins represents a large subset of pediatric emergencies, both within the home and in emergency departments. Poisoning is ranked as the third leading cause of mortality following motor vehicle accidents and farm injuries. Poisoning was the underlying cause of death for 18,549 people in the United States in 1998.1,2 Analysis of Poison Control Center national data reveals that 75% of exposures occur within the home. In the pediatric subgroup, 85% to 90% of exposures are unintentional. There is a peak age under 5 years with parallel rises at ages 12, 13 to 19, the 20s, and the 30s. As children enter adolescence, accidental exposures become rare and intentional exposures more common. Seventy-five percent of exposures are ingestions, followed by dermal, inhalation, and ocular exposures. Commonly involved agents and reported fatalities are listed in Tables 133–1 and 133–2.3,4 Parents often underestimate the motor skills of children. Children are curious about their environment. They explore using hand-to-mouth behavior. Children’s higher respiratory rates impart greater susceptibility to toxic gases and aspira936

tion. Enhanced skin permeability of children is a factor in absorption as well. The average 2-year-old places nonfood items in his or her mouth at a rate that approximates three events per hour; however, most pediatric ingestions are benign in nature. A small percentage of pediatric patients (12%) will develop signs and symptoms following ingestion.3,4 Current annual estimates suggest that 2000 patients less than 6 years of age will develop life-threatening events as a result of intoxication. Approximately 20 fatal cases are reported from toxic exposure each year.1-4 Ingestion involves a complex interplay of variables that include the child, the substance, and the environment. The typical child is unable to discriminate safe from unsafe, and is observant of the ritual of self-medication in other family members. The child often mistakes the substance for an edible ingredient, when in fact it is a medication (as in “looka-like medications”) (Table 133–3). The environment may be unsafe for children, with poor storage techniques of toxicants within the household (Table 133–4). A common pitfall is storage of a harmful substance within a recognizable container (i.e., kerosene or gasoline in a soda bottle). Many poisonings are a result of poor parental supervision. The Individual Encounter An ingestion should be suspected when a preverbal child is found with an open container, when a classic toxidrome is present, or in cases of unexplained multiorgan system abnormality. Liquids or pelleted materials are more likely to be ingested in larger amounts than aerosols or powders. Flavoring or irritant additives have little to do with determining whether the product was actually ingested. The volume of the swallow is a function of body mass. The volume of a swallow is 0.27 ml/kg, or roughly 1 teaspoon, for a 2-year-old, 1 tablespoon for an adult female, and 1 to 2 tablespoons for an adult male. The situation of an unwitnessed disappearance of the contents of a container of a toxic substance often presents poison centers with difficult management decisions. When the amount of toxicant ingested is difficult to estimate, the physician must default to the assumption that the child may have consumed the full container of the toxicant involved. When two children are involved in an ingestion, it must be assumed that each took the entire amount. The classic concept of sharing may not apply.

Chapter 133 — Common Pediatric Overdoses

Table 133–1

Nationally Reported Ingestions Children £ 6 Yr Old

All Calls to the Poison Center Substance

Percent

Analgesics Cleaning products Cosmetics Foreign bodies Plants Cold and cough medicines Bites and envenomations Sedatives and hypnotics Topical agents Pesticides

Table 133–2

937

10.5 9.5 9.4 5.0 4.9 4.5 4.2 4.1 4.1 4.0

Substance

Percent

Cosmetics Cleaning products Analgesics Foreign bodies Plants Topical agents Cold and cough medicines Pesticides Vitamins GI preparations

13.3 10.5 7.2 6.8 6.6 6.3 5.3 4.1 3.6 3.2

Nationally Reported Fatalities Children £ 6 Yr Old

All Calls Groups Substance

Percent

Analgesics Antidepressants Sedatives and hypnotics Stimulants and street drugs Cardiovascular drugs Toxic alcohols

44 26 24 20 12 11

While most pediatric exposures are benign in nature, there are some toxins that are dangerous even when presented in the form of a small taste, lick, or swallow (Table 133–5).

Selected Pediatric Overdoses Nonsteroidal anti-inflammatory drugs Oral hypoglycemics Agents causing methemoglobinemia Iron poisoning Acetaminophen Aspirin (salicylate) Selected comments on other pharmaceuticals

Discussion of Individual Pediatric Overdoses Nonsteroidal Anti-Inflammatory Drugs The nonsteroidal anti-inflammatory drugs (NSAIDs) are a group of medications that have antipyretic, antiinflammatory, and analgesic properties. With their widespread availability and increasing use in the United States, NSAIDs represent some of the most common medications involved in the overdose setting. Fortunately, most NSAID exposures cause minimal morbidity and mortality. The most prevalent complications are therapeutic side effects, specifically gastrointestinal (GI) bleeding. NSAIDs exert their pharmacologic effect by inhibiting cyclooxygenases, which are involved in prostaglandin synthesis.5,6 NSAIDs are rapidly and almost completely absorbed. They are weak acids, highly protein bound, and metabolized by the cytochrome P-450 system. More than half of the drug is excreted unchanged in the urine.

Substance Carbon monoxide Iron Analgesics Cleaning substances Cardiovascular agents Antidepressants Insecticides/pesticides

Percent 15 7 7 6 6 6 5

NSAIDs seldom cause serious toxicity, even in large doses. At this time, there are inadequate data defining the minimum toxic or lethal dose.7 Following acute overdose, most children are asymptomatic or develop only mild GI symptoms. Specific signs and symptoms are summarized in Table 133–6. Generally, full recovery can be expected within 6 to 24 hours. In contrast, phenylbutazone and its active metabolite oxyphenbutazone can cause coma, seizures, shock, respiratory alkalosis, and metabolic acidosis. Within 24 hours, hepatic necrosis may develop. Urine discoloration due to a metabolite may result in a red hue. The emergency department evaluation consists of standard supportive care and GI decontamination. Gastrointestinal bleeding should be treated by standard measures for hemodynamic support. Activated charcoal remains the preferred method of GI decontamination.7 Oral Hypoglycemics Diabetes mellitus is the most common endocrine disorder in our country today and is frequently managed with oral agents. Oral medications including sulfonylureas, meglitinides, biguanides, and thiazolidinediones. Of all these drug classes, only the sulfonylureas and meglitinides are truly hypoglycemic agents (Table 133–7). Most poisonings from oral hypoglycemic agents involve sulfonylureas, with most of the fatalities involving biguanides.8-10 Their primary mechanism of action is the release of endogenous insulin. Glyburide has the highest incidence of hypoglycemia and is the most widely utilized of these agents. Most hospitalizations are due to overdose of long-acting agents. In the overdose setting, hypoglycemia typically occurs within the first several hours after ingestion. Delayed hypoglycemia has also been reported in some cases. In a retrospective pediatric study, 96% of children exposed to oral

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Table 133–3

Pharmaceuticals Toxic to Children

Analgesics Acetaminophen Nonsteroidal anti-inflammatory drugs Salicylates Anesthetics Benzocaine Lidocaine Anticholinergics Cyproheptadine Diphenhydramine Dimenhydrinate Hydroxyzine Hyoscyamine Orphenadrine Scopolamine Anticonvulsants Barbiturates Carbamazepine Phenytoin Antidepressants/Antipsychotics Chlorpromazine Clozapine Cyclic antidepressants Lithium Monoamine oxidase inhibitors Sertraline Thioridazine Antihypertensives/Antidysrhythmics Captopril Clonidine Digoxin Nifedipine Verapamil Antimalarials Chloroquine Quinines Antituberculosis Drugs Isoniazid Bronchodilators Albuterol Caffeine Ephedrine Theophylline Fluoride Ammonium fluoride, befluoride Hypoglycemics Sulfonylureas Iron Prenatal hematinics Methylxanthines Caffeine Theophylline Opioids Codeine Diphenoxylate Hydrocodone Methadone Pentazocine Propoxyphene Sedatives Triazolam Sympathomimetics Amphetamine Cocaine Nasal/ocular imidazoline Phencyclidine Phenylpropanolamine Pseudoephedrine

Table 133–4

Household Products and Plants Toxic to Children

Acid/Alkali Products Boric acid Bowl cleansers Clinitest tablet Disc battery Alcohols Ethanol Ethylene glycol Isopropyl alcohol Methanol Antiseptics Camphor Cantharidin Hydrogen peroxide Phenol Pine oil Cyanide Hydrocarbons Industrial Chemicals Butyrolactone (solvent for acrylate polymers) Methylene chloride (paint thinner) Selenious acid (gun blueing) Zinc chloride (soldering flux) Mothballs Naphthalene Nail Products Acetone (polish remover) Acetonitrile (sculptured nail remover) Methacrylic acid (artificial nail primer) Nitromethane (artificial nail remover) Organophosphates Carbamate Plants Aconite Castor bean Clove oil Comfrey Foxglove Ma huang Mushrooms (specific) Nutmeg Oleander Pennyroyal oil Rodenticides Arsenic Hydroxycoumarin Indanediones Strychnine Weed/Bug Killers Lindane Nicotine Paraquat

hypoglycemics had a drop in their blood sugar within 8 hours.11 The biguanide class includes metformin and phenformin. Phenformin was removed from U.S. distribution as a result of fatal lactic acidosis. Metformin is the only biguanide in common use today. It increases insulin sensitivity, decreases hepatic gluconeogenesis, and diminishes intestinal glucose absorption. Insulin secretion remains unaffected. Therefore, metformin will correct hypoglycemia in diabetics but will

Chapter 133 — Common Pediatric Overdoses

Table 133–5

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Medicinal Preparations Fatal to a 10-kg Toddler Minimal Potential Fatal Dose (per kg weight)

Drug Camphor Chloroquine Hydroxychloroquine Imipramine Desipramine Quinine Methyl salicylate Theophylline Thioridazine Chlorpromazine

100 20 20 15 15 80 200 8.4 15 25

mg mg mg mg mg mg mg mg mg mg

Maximal Unit Dose Available

Amount Causing Fatality

1 g/5 ml 500 mg 200 mg 150 mg 75–150 mg 650 mg 1.4 g/ml 500 mg 200 mg 200 mg

1 10 µg/mL AST/ALT increased

Yes: Continue NAC

If pH < 7.3 INR > 6.5 Cr > 3.3 AMS

Refer for possible liver transplant

If the patient presents within 4 hours of the acetaminophen ingestion or there is a history of a co-ingestant, oral activated charcoal can be given. There is no evidence that administering activated charcoal will interfere with oral NAC therapy.26 In patients who present greater than 8 hours postingestion with serum acetaminophen levels that plot above the treatment line, liver function tests (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) should be ordered before and after NAC therapy27 (see Fig. 133–1). ACUTE ACETAMINOPHEN INGESTION WITH UNKNOWN TIME OR GREATER THAN 24 HOURS POSTINGESTION

It may be challenging to obtain the exact time of acetaminophen ingestion, but with a careful history obtained from the patient, family, and others, a time window can often be established. If the time of ingestion cannot be determined or it has been greater than 24 hours, a serum acetaminophen level and liver function tests (AST and ALT) should be drawn immediately. The acetaminophen nomogram cannot be used. Potential toxicity must be assumed and NAC therapy started (see Fig. 133–1). EXTENDED RELEASE ACETAMINOPHEN INGESTION

For patients presenting after an overdose of an extendedrelease acetaminophen, a serum acetaminophen level is drawn 4 hours postingestion and repeated again in 4 hours.

No: Supportive care FIGURE 133–1. Treatment guidelines for acetaminophen ingestion. All times noted are postingestion. Abbreviations: ALT, alanine aminotransferase; AMS, altered mental status; APAP, acetaminophen; AST, aspartate aminotransferase; Cr, creatinine; GI, gastrointestinal; INR, international normalized ratio; LFTs, liver function tests; NAC, Nacetylcysteine; PT, prothrombin time; Rx, treatment.

The acetaminophen levels are plotted on the acetaminophen nomogram.24,28 If either of the acetaminophen levels drawn falls above the treatment line, NAC therapy is started (see Fig. 133–1). REPEATED SUPRATHERAPEUTIC ACETAMINOPHEN DOSING

Although death has rarely been reported in children less than 6 years old with a single overdose of acetaminophen, there have been multiple reports of hepatotoxicity and death associated with repeated supratherapeutic doses of acetaminophen in children.29 Many studies have investigated what factors may put children at increased risk of hepatoxicity with repeated supratherapeutic dosing, such as febrile illness, starvation states, total dose given, duration of acetaminophen therapy, and use of P-450–inducing medications. Although there have been more cases of hepatoxicity and death in children with febrile illness who received supratherapeutic doses of acetaminophen than in nonfebrile children, it is not clear what role fever plays. Prevention of future overdoses may be accomplished with adequate therapy instructions or education during well-child visits. All recommendations for acetaminophen therapy should include the dose, frequency, duration of therapy, and specific strength and formulation for the individual child. Chronic acetaminophen toxicity should be considered in any child with a history of acetaminophen doses of

Acetaminophen plasma concentration

Chapter 133 — Common Pediatric Overdoses µg mL

µmoL

300

2,000

200

1,300

150

1,000 900 800 700 600 500 400

100 90 80 70 60 50 40 30

Potential for toxicity 300 250 200

20

10 9 8 7 5 4

Toxicity unlikely (treatment line)

100 90 80 70 60 50 40 30

Recommend treatment if level is above broken line

20 2 Take level at least 4 hours postingestion

10

4

8

12 14 18 Hours post-ingestion

24

28

FIGURE 133–2. Acetaminophen nomogram: serum acetaminophen concentration versus time after ingestion. (From Management of Acetaminophen Overdose. Raritan, NJ: McNeil Consumer Products, 1986.)

150 mg/kg/day for more than 2 days or in an adult with a history of acetaminophen doses of 4 g/day for more than 2 days, as well as in a patient who presents with signs of hepatic dysfunction. In patients with signs or symptoms of hepatic injury, acetaminophen levels should be drawn immediately. Additional laboratory workup should include liver function tests (AST and ALT), international normalized ratio (INR) for prothrombin time, bilirubin, glucose, blood urea nitrogen, creatinine, lactate, phosphate, electrolytes, and arterial blood gases. With repeated doses, the physician should assume the ingestion to begin from the time of the first dose, and use this to plot the level on the acetaminophen nomogram. Laboratory tests should be repeated every 12 to 24 hours.30 NAC therapy should be started if the acetaminophen level is greater than 10 µg/ml or if the acetaminophen level is not detectable but the liver function test results are elevated (see Fig. 133–1). Treatment of Acetaminophen Toxicity The treatment of acetaminophen toxicity consists of GI decontamination with activated charcoal, supportive care, and the timely administration of the antidote, NAC.31 Activated charcoal may be given orally or by nasogastric tube (1 g/kg) if the patient presents within 4 hours or if co-ingestants are suspected. More aggressive GI decontamination, with orogastric lavage and whole bowel irrigation, is not recommended for isolated acetaminophen toxicity because of acetaminophen’s rapid absorption and the effectiveness of NAC as an antidote. Aggressive forms of GI decontamination

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should be reserved for potentially life-threatening polydrug overdoses. NAC is the mainstay of therapy for acetaminophen toxicity, although its mechanisms of action are not fully understood. One of several ways that NAC prevents hepatoxicity is through its conversion to cysteine, which repletes glutathione stores. Secondly, NAC binds directly to NAPQI, creating a nontoxic metabolite. Thirdly, it provides a substrate for sulfonation and thus promotes nontoxic metabolism of acetaminophen. These mechanisms of action promote the early administration of NAC (within 24 hours of acetaminophen overdose) to prevent hepatoxicity, but there is evidence that IV NAC is also effective in late acetaminophen overdose (>24 hours postingestion) and in fulminant hepatic failure.32 Proposed mechanisms for this benefit in late toxicity include an antioxidant effect, decreased neutrophil accumulation, improved oxygen delivery to tissues, and improved microcirculatory changes in the liver. Both the oral and IV treatment protocols are nearly 100% effective in preventing hepatoxicity when given within 8 hours of ingestion, and lessen the risk of hepatoxicity when given within the first 24 hours. The 72-hour oral NAC regimen had been the standard of care for acetaminophen toxicity in the United States, but the Food and Drug Administration approved IV NAC in January of 2004. The standard 72-hour oral NAC regimen is a loading dose of 140 mg/kg followed by maintenance doses of 70 mg/kg every 4 hours for 17 additional doses. Few side effects are associated with oral NAC except for nausea and vomiting, which are aggravated by oral NAC’s foul rotten egg odor. In order to mask its unpleasant odor, the standard 10% to 20% NAC solution may diluted to a 5% concentration in a chilled beverage, and served from a covered cup with a straw. Beverages that may mask the odor are soft drinks and fruit juice. If this is not enough to prevent nausea and vomiting, then an antiemetic such as metaclopromide or ondansetron can be given. In cases in which the nausea and vomiting cannot be controlled or oral NAC is contraindicated because of a caustic ingestion, IV NAC should be considered. The IV solution is well tolerated by most patients and considered safe when administered properly. The most common complication of IV NAC is an anaphylactoid reaction producing flushing, urticaria, angioedema, and bronchospasm. Most of these reactions are mild and related to the infusion rate. Symptoms can be controlled by slowing down the rate of infusion, or by treatment with an antihistamine or epinephrine if needed.33 There is the potential for severe hyponatremia in small children when following the manufacturer’s guidelines, since the amount of NAC received is weight based but the amount of fluid is constant for all patients: 1700 ml of free water over 20 hours. When using the 20-hour IV NAC protocol, a concentration of 40 mg/ml should be used in children less than 40 kg in order to avoid hyponatremia34 (Table 133–9). Fulminant Hepatic Failure Unfortunately, a small percentage of acetaminophen overdose patients do develop fulminant hepatic failure. The mortality rate without NAC therapy is greater than 50%. NAC increases a patient’s chances for survival even in the setting of fulminant hepatic failure. Predictors of poor outcome, including death and the need for a liver transplant, are as follows: serum pH less than 7.3 after fluid resuscitation, INR

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Table 133–9

Intravenous NAC (Acetadote) Pediatric Dosing (weight < 40 kg)/ Fluid Restrictions

Prepare 4% Concentration in D5W • Mix 50 ml of NAC (20% solution) with 200 ml of D5W (remove 50 ml from a 250-ml bag of D5W) to obtain 40 mg/ml (4% concentration) Loading Dose • 150 mg/kg infused over NOT LESS THAN 15 min • Infuse 3.75 ml/kg over NOT LESS THAN 15 min First Maintenance Infusion • 50 mg/kg infused over 4 hr • Infuse 1.25 ml/kg over 4 hr (0.31 ml/kg/hr) Second Maintenance Infusion • 100 mg/kg infused over 16 hr • Infuse 2.5 ml/kg over 16 hr (0.16 ml/kg/hr) Abbreviations: D5W, dextrose 5% in water; NAC, N-acetylcysteine. Adapted from package insert for Acetadote (2004) and Sung et al.34

greater than 6.5, grade III or IV encephalopathy; creatinine greater than 3.3 mg/dL (275 micromol/L), lactate greater than 25 mg/dl (3.0 mmol/L) after fluid resuscitation, and phosphorus greater than 3.8 mg/dl (1.2 mmol/L) after fluid resuscitation.30 Patients with acetaminophen-induced fulminant hepatic failure should receive early referral to a liver transplant center. The treatment of patients with fulminant hepatic failure includes correction of metabolic acidosis, correction of coagulopathy, and close monitoring and aggressive treatment of cerebral edema. In addition, IV NAC therapy is preferable to oral NAC therapy and should be continued until the patient improves, receives a liver transplant, or dies. Aspirin (Salicylate) The use of childproof containers, aspirin alternatives such as acetaminophen, and education to avoid the use of aspirin in children because of Reye’s syndrome have reduced the incidence of unintentional salicylate poisoning in the United States. The American Association of Poison Control Centers’ Toxic Exposure Surveillance System reported approximately 20,000 salicylate exposures and 60 salicylate-related deaths in the United States in 2003. Approximately half of these exposures occurred in people less than 19 years old. Serious intoxications continue to occur because people are often unaware that over-the-counter medications such as Pepto-Bismol contain salicylate (1 ml contains 8.77 mg of aspirin), or that topical ointments or liniments used in hot vaporizers contain methyl salicylate (oil of wintergreen). Topical ointments may cause toxicity with extensive application. Even more dangerous is the consumption of oil of wintergreen. It contains 1440 mg/ml of salicylate, and even a small ingestion of 1 to 2 ml may be fatal for a young child.35 Aspirin continues to be readily available, and serious salicylate toxicity may result from suicide attempts in adolescents and adults. Clinical Presentation The toxic effect of salicylates is complex. Salicylates stimulate the respiratory center of the brainstem, causing early hyper-

ventilation and respiratory alkalosis. In children, the initial respiratory alkalosis may be missed at the time of presentation, whereas metabolic acidosis may be quite pronounced.36 Salicylates uncouple oxidative phosphorylation, leading to increased heat production, heavy sweating, and dehydration. In addition, salicylates interfere with glucose metabolism and may cause hypoglycemia or hyperglycemia. In acute large ingestions, salicylates may produce nausea and vomiting resulting from gastric irritation and direct stimulation of chemoreceptor zones. Vomiting, if severe, may result in dehydration, which impairs renal salicylate elimination and contributes to acid-base and electrolyte disturbances. These physiologic abnormalities are progressive and more severe with larger ingestions and at extremes of age. ACUTE ASPIRIN OVERDOSE

Potential aspirin toxicity occurs at doses of 150 mg/kg and should be suspected with any ingestion of methyl salicylate. The symptoms vary with the amount ingested, but usually begin 3 to 8 hours postingestion and may progress more rapidly in children. The earliest signs and symptoms of salicylate poisoning include nausea, vomiting, diaphoresis, and tinnitus. As the CNS salicylate levels rise, tinnitus may progress to deafness. Other CNS effects include tachypnea, disorientation, agitation, delirium, convulsions, and lethargy. Coma is rare and usually occurs with massive or mixed overdoses. Children usually present with an unintentional ingestion, and symptoms occur within a few hours of ingestion. Children less than 4 years of age typically present with metabolic acidosis, whereas older children and adults typically present with a mixed disturbance of respiratory alkalosis and increased anion gap metabolic acidosis. Sweating, dehydration, tachypnea, and fever are often attributed to the underlying illness for which the patient is taking aspirin or aspirin-containing products, and not correctly attributed to salicylate toxicity. The clinical presentation of salicylate toxicity may be indistinguishable from septic shock with multiple organ failure, encephalopathy, and acute respiratory distress syndrome. Adult and adolescent salicylate toxicity typically occurs after an intentional overdose and often mixed with substances such as CNS depressants, which impair hyperpneic response. This produces a respiratory acidosis rather than the expected respiratory alkalosis. Salicylate and acetaminophen levels must be obtained for all intentional overdoses. CHRONIC ASPIRIN TOXICITY

Chronic toxicity occurs most commonly in the elderly, with symptoms that overlap with those of acute ingestion. However, symptoms of chronic toxicity are typically milder at the time of presentation and have a more gradual onset. These patients are more difficult to diagnose and often have a worse prognosis.37 Diagnosis and Treatment of Salicylate Toxicity The differential diagnosis of salicylate toxicity in all age groups includes infection, sepsis, diabetic ketoacidosis, and other causes of increased anion gap metabolic acidosis. If potential salicylate toxicity is suspected in an asymptomatic patient, a urine ferric chloride test should be obtained. Do not rely on a serum salicylate level unless it is obtained

Chapter 133 — Common Pediatric Overdoses

at least 6 hours post-ingestion. Chronic toxicity and sustained release tablets may cause problems in interpreting serum levels. The salicylate level is repeated in 1 hour to obtain a trend, and at intervals of every 2 to 4 hours based on the patient’s clinical condition until the serum salicylate level is ≤ 15 mg/dL. If the patient is symptomatic, vital signs and mental status should be monitored and the following laboratory studies obtained: serum salicylate level, electrolytes, and arterial blood gases. The serum salicylate level should be repeated in 1 hour and every 2 to 4 hours thereafter as clinically indicated. If the patient requires intubation, the same degree of hyperventilation needed prior to intubation should be maintained, since failure to do so may cause rapid deterioration of the patient.38 Failure to hyperventilate the patient causes respiratory acidosis and the rapid shift of salicylate into the CNS. Supportive care includes hydration at 1.5 to 2 times maintenance to compensate for dehydration and fluid losses brought on by salicylates. Glucose must be monitored closely and should be administered in all cases of altered mental status, even if there is peripheral euglycemia. CNS hypoglycemia can occur despite peripheral euglycemia.39 Gastric decontamination with multiple doses of activated charcoal should be used to prevent further salicylate absorption in doses of 1 to 2 g/kg without sorbitol. Although there is no true antidote for salicylate toxicity, alkalinization therapy is crucial. Alkalinizing the blood and urine traps salicylate (a weak acid) in the blood, preventing CNS toxicity. Alkalinization also increases urinary excretion of the salicylate ion. The recommended dosage of NaHCO3 is 1 to 2 mEq/kg as an IV bolus followed by an infusion of 3 ampules of NaCHO3 (containing 44 mEq NaHCO3 each) in 1 L of dextrose 5% in water at 1.5 to 2 times maintenance. (The bolus of NaHCO3 can be omitted if blood pH is > 7.45.) This fluid may replace the hydration fluid discussed previously. Alkalinization is successful when the blood pH is 7.45 to 7.55 and the urine pH is greater than 7. Potassium should be monitored and supplemented prophylactically since the increasing pH causes intracellular shifting of potassium and may cause hypokalemia, which will limit urinary alkalinization.36,40 Acetazolamide and other carbonic anhydrase inhibitors are dangerous and should not be used since they achieve urinary alkalinization at the expense of blood acidification, which promotes salicylate movement into the CNS.41,42 Hemodialysis is indicated in acute overdoses when the salicylate level is 100 mg/dl or rapidly approaching such levels. It is also indicated if acidosis is refractory to alkalinization, CNS symptoms are already present, there is progressive deterioration despite appropriate treatment, there are signs of pulmonary edema, or the patient has severe cardiac disease or renal failure. In chronic overdoses, hemodialysis should be considered if the salicylate level is greater than 30 mg/dl and the patient is symptomatic. Selected Comments on Other Pharmaceuticals Chloroquine and quinine are antimalarial medications. Toxic symptoms include immediate epigastric discomfort, nausea, vomiting, and diarrhea followed by CNS stimulation or seizures. Imidazoline products are sympathetic amines present in ocular drops and nasal sprays. Toxicity occurs rapidly with

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CNS stimulation and/or depression and either hypertension and tachycardia or hypotension and bradycardia. Naloxone is indicated for altered sensorium, atropine or isoproterenol for bradycardia, and dopamine for hypotension refractory to fluid administration. Theophylline, once a mainstay of asthma therapy, is a xanthine producing GI manifestations, generalized major motor seizures, tachydysrhythmias, hypotension, hypokalemia, hyperglycemia, and acidosis. Whole bowel irrigation alone or whole bowel irrigation combined with activated charcoal will greatly enhance elimination. Seizures may occur and should be managed with standard protocols. Acetonitrile is an artificial nail removing compound that causes cyanide toxicity. Gastrointestinal manifestations herald the onset of CNS alterations and the cardiac manifestations of cyanide. Utilization of the cyanide antidote kit is indicated. Camphor is contained in over-the-counter liniments. Patients present with GI disturbances followed by CNS excitation and seizures. Hydrocarbons are common ingredients in household cleaning products, solvents, and gasoline. Emesis and lavage are contraindicated. Patients may present with transient CNS or GI disturbances followed by bronchospasm, seizures, or dysrhythmias.

Summary The details of individual toxic ingestions can vary considerably, and the guidelines and therapies may change over time. Therefore, calling a regional Poison Control Center (1-800222-1222) for consultation should always be considered. REFERENCES *1. Watson WA, Lovitz TL, Rodgers GC Jr, et al: 2002 Annual Report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med 21:353–421, 2003. *2. Litovitz TL, Klein-Schwartz W, Rodgers GC Jr, et al: 2001 Annual Report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med 20:391–452, 2002. *3. Koren G: Medications which can kill a toddler with a tablet or teaspoonful. J Toxicol Clin Toxicol 31:407–412, 1993. 4. Emery D: Highly toxic ingestions for toddlers: when a pill can kill. Pediatr Emerg Med Rep 3:111–122, 1998. 5. Brater DC: Clinical pharmacology of NSAIDs. J Clin Pharmacol 28:518–523, 1988. 6. Hawkey CJ: COX-2 inhibitors. Lancet 353:307–314, 1999. 7. Vale JA, Meredith TJ: Acute poisoning due to non-steroidal antiinflammatory drugs: clinical features and management. Med Toxicol 1:12–31, 1986. 8. Harrigan RA, Nathan MS, Beattie P: Oral agents for the treatment of type 2 diabetes mellitus: pharmacology, toxicity, and treatment. Ann Emerg Med 38:68–78, 2001. *9. Quadrani DA, Spiller HA, Widder P: Five year retrospective evaluations of sulfonylurea ingestion in children. J Toxicol Clin Toxicol 34:267–270, 1996. 10. Spiller HA, Villalobos D, Krenzelok EP, et al: Prospective multicenter study of sulfonylurea ingestion in children. J Pediatr 131:141–146, 1997. 11. Burkhart KK: When does hypoglycemia develop after sulfonyurea ingestion? Ann Emerg Med 31:771–772, 1998. 12. Bailey CJ, Turner RC: Metformin. N Engl J Med 334:574–579, 1996. 13. McLaughlin SA, Crandall CS, McKinney PE: Octreotide: an antidote for sulfonylurea-induced hypoglycemia. Ann Emerg Med 36:133–138, 2000. *Suggested readings.

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14. Curry S: Methemoglobinemia. Ann Emerg Med 11:214–221, 1982. 15. Kulick RM: Pulse oximetry. Pediatr Emerg Care 3:127–130, 1987. 16. Yano SS, Danish EH, Hsia YE: Transient methemoglobinemia with acidosis in infants. J Pediatrics 100:415–418, 1982. 17. Mills KC, Curry SC: Acute iron poisoning. Emerg Med Clin North Am 12:397–413, 1994. 18. Penna A, Buchanan N: Paracetamol poisoning in children and hepatotoxicity. Br J Clin Pharmacol 32:143–149, 1991. *19. Sztajnkrycer M, Bond G: Chronic acetaminophen overdosing in children: risk assessment and management. Curr Opin Pediatr 13:177–182, 2001. 20. Brackett C, Bloch J: Phenytoin as a possible cause of acetaminophen hepatotoxicity: case report and review of the literature. Pharmacotherapy 20:229, 2000. 21. Bray G, Harrison P, O’Grady J, et al: Long-term anticonvulsant therapy worsens outcome in paracetamol-induced fulminant hepatic failure. Hum Exp Toxicol 11:265, 1992. *22. American Academy of Pediatrics, Committee on Drugs: Acetaminophen toxicity in children. Pediatrics 108:1020–1024, 2001. 23. Ashbourne J, Olson K, Khayam-Bashi H: Value of rapid screening for acetaminophen in all patients with intentional overdose. Ann Emerg Med 18:1035, 1989. 24. Bizovi K, Smilkstein M: Acetaminophen. In Goldfrank L, Flomenbaum N, Lewin N, et al (eds): Goldfrank’s Toxicologic Emergencies, 7th ed. New York: McGraw-Hill, 2002, pp 480–501. 25. Roth B, Woo O, Blanc P: Early metabolic acidosis and coma after acetaminophen ingestion. Ann Emerg Med 33:452–456, 1999. 26. Spiller H, Krenzelok E, Grande G, et al: A prospective evaluation of the effect of activated charcoal before the oral N-acetylcysteine in acetaminophen overdose. Ann Emerg Med 23:519, 1994. 27. Smilkstein M, Knapp G, Kulig K, Rumack B: Efficacy of oral Nacetylcysteine in the treatment of acetaminophen overdose. N Engl J Med 319:1557–1562, 1988. 28. Bizovi K, Aks S, Paloucek F, et al: Late increase in acetaminophen concentration after overdose of Tylenol Extended Relief. Ann Emerg Med 28:549–551, 1996.

29. Sztajnkrycer M, Bond G: Chronic acetaminophen overdosing in children: risk assessment and management. Curr Opin Pediatr 13:177–182, 2001. 30. O’Grady J, Alexander G, Hayllar K, Williams R: Early indicators of prognosis in fulminant hepatic failure. Gastroenterology 97:439–445, 1989. 31. Linden C, Rumack B: Acetaminophen overdose. Emerg Clin North Am 2:103–119, 1984. 32. Tucker JR: Late-presenting acute acetaminophen toxicity and the role of N-acetylcysteine. Pediatr Emerg Care 14:424–426, 1998. 33. Bailey B, McGuigan M: Management of anaphylactoid reactions to intravenous N-acetylcysteine. Ann Emerg Med 31:710–715, 1998. 34. Sung L, Simons J, Dayneka N: Dilution of intravenous N-acetylcysteine as a cause of hyponatremia. Pediatrics 100:389–391, 1997. 35. Chan TY: Medicated oils and severe salicylate poisoning: quantifying the risk based on methyl salicylate content and bottle size. Vet Hum Toxicol 38:133–134, 1996. 36. Flomenbaum N: Salicylates. In Goldfrank L, Flomenbaum N, Lewin N, et al (eds): Goldfrank’s Toxicologic Emergencies, 7th ed. New York: McGraw-Hill, 2002, pp 507–518. 37. Anderson R, Potts D, Gabow P, et al: Unrecognized adult salicylate intoxication. Ann Intern Med 85:745–748, 1976. 38. Gabow P, Anderson R, Potts D, Schrier R: Acid-base disturbances in the salicylate-intoxicated adult. Arch Intern Med 138:1481–1484, 1978. 39. Thurston J, Pollock P, Warren S, Jones E: Reduced brain glucose with normal plasma glucose in salicylate poisoning. J Clin Invest 49:2139– 2145, 1970. 40. Goldberg M, Barlow C, Roth L: The effects of carbon dioxide on the entry and accumulation of drugs in the central nervous system. J Pharmacol Exp Ther 131:308–318, 1961. 41. Hill JB: Experimental salicylate poisoning: observations on the effects of altering blood pH on tissue and plasma salicylate concentrations. Pediatrics 47:658–665, 1971. 42. Kaplan S, del Carmen F: Experimental salicylate poisoning: observations on the effects of carbonic anhydrase inhibitor and bicarbonate. Pediatrics 21:762–770, 1958.

Chapter 134 Toxic Alcohols Kevin C. Osterhoudt, MD, MSCE

Key Points Ethanol intoxication may cause hypoglycemia in young children. Isopropyl alcohol poisoning does not typically cause acidosis, but may cause profound central nervous system depression. Methanol poisoning causes metabolic acidosis and may lead to blindness, encephalopathy, and/or multisystem organ failure. Ethylene glycol poisoning causes metabolic acidosis and may lead to renal failure and/or multisystem organ failure. Ethanol or fomepizole, both of which inhibit alcohol dehydrogenase, are important emergency antidotes for methanol or ethylene glycol poisoning.

Selected Diagnoses Ethanol intoxication Isopropanol poisoning Methanol poisoning Ethylene glycol poisoning

Discussion of Individual Diagnoses Ethanol Intoxication Ethanol is nearly ubiquitous in American homes as a constituent of beverages, mouthwashes, and cleaning products. In 2003, over 19,000 pediatric ethanol exposure cases were reported to the American Association of Poison Control Centers (AAPCC).1 Of note, these statistics do not represent the formidable health hazards associated with driving while intoxicated, or other risk behaviors associated with inebriation and impaired decision making. An ethanol dose of 0.7 g/kg produces a blood alcohol concentration of approximately 0.1 g/dl (100 mg/dl). This equates to ingestion of 17.5 ml (slightly more than one tablespoon) of 80-proof vodka by a 10-kg toddler. Ethanol is a central

nervous system (CNS) depressant. Intoxication initially manifests through loss of inhibition, incoordination, slurred speech, and stupor. The examiner may note flushing of the face, dysarthria, and/or nystagmus. As blood ethanol levels approach 0.3 g/dl, coma, inhibition of airwayprotective reflexes, and respiratory depression ensue. Aspiration pneumonia is a frequent complication, as is gastritis. Hepatic alcohol dehydrogenase is the primary metabolic pathway for ethanol; dependent upon differences in individual enzyme phenotypes and ethanol tolerance, ethanol may be metabolized at a rate of 10 to 30 mg/dl/hr.2 The enzymatic activity of alcohol dehydrogenase requires the cofactor nicotinamide adenine dinucleotide, oxidized (NAD +), and the consumption of this cofactor inhibits gluconeogenesis. As a result, young children, with reduced glycogen stores, are at risk for profound hypoglycemia.3 This most often presents with CNS depression in the morning hours after the overnight fast. Ethanol intoxication may be suspected based upon clinical history, physical examination findings, hypoglycemia, or an elevated osmolal gap (Table 134–1). It can be confirmed by measurement of the blood alcohol concentration. Careful attention to the patient’s airway, breathing, and circulation will be sufficient treatment for most cases of ethanol intoxication. There is no evidence to support a correlation between the Glasgow Coma Scale score and a need for endotracheal intubation after alcohol poisoning, so individual risks and benefits should be considered. Rapid bedside blood glucose concentration should be performed on any obtunded patient, and hypoglycemia should be treated as indicated (see Chapter 106, Hypoglycemia). Due to the diuretic nature of ethanol, hypovolemia may warrant intravenous fluid administration. Hemodialysis effectively eliminates ethanol from the bloodstream, and may be considered in severe cases of ethanol-induced coma and respiratory depression, but is rarely indicated. The possibility of concomitant traumatic injury, or co-ingestion, should be considered in any intoxicated adolescent. Alcohol withdrawal seizures and delirium tremens are rare among pediatric patients, but may complicate hospitalization of chronic highlevel alcohol-abusing teens. A pattern of chronic alcohol abuse would warrant activation of social services. Isopropanol Poisoning Isopropyl alcohol, also known as “rubbing alcohol,” is a widely used solvent and is commonly found within the home 947

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Table 134–1

Estimation of Alcohol and Glycol Levels from the Osmolal Gap*

Toxic Alcohol

Conversion Factor

Methanol Ethanol Isopropanol Ethylene glycol

3.2 4.6 6.0 6.2

*[Osmolal gap (mOsm/L) × conversion factor] estimates alcohol concentration (mg/dl). Osmolal gap = measured − calculated osmolality. Calculated osmolality = 2[Na (mEq/L)] + [glucose (mg/dl)]/18 + [BUN (mg/dl)]/2.8.

Magnitude of gap

Anion gap acidosis

Osmolal gap

Time FIGURE 134–1. Relationship of osmolal gap to anion gap acidosis.

as the cooling ingredient among topical liniments. Over 12,000 isopropanol exposures among children up to 19 years of age were reported to the AAPCC in 2003.1 Isopropyl alcohol toxicity may occur via the dermal and inhalation routes, such as may result during misguided sponge baths for fever. Isopropanol is twice as potent as ethanol in terms of CNS depression. Altered mental status, when it occurs, typically manifests within 2 hours of ingestion.4 Hypotension may occur due to diuresis, peripheral vasodilation, and myocardial depression. In addition to an osmolal gap (see Table 134–1), ketonemia or ketonuria may occur. Isopropyl alcohol is metabolized to acetone by alcohol dehydrogenase without the production of significant metabolic acidosis but may lead to hypoglycemia in young children, as was described for ethanol. Gastritis is common after ingestion. Patient care is supportive. The risks and benefits of hemodialysis may be considered for comatose patients with blood isopropanol levels exceeding 500 mg/dl. Methanol Poisoning Methanol poisoning may result from the ingestion of windshield washer fluid, gasoline additives, duplicating fluids, canned cooking fuels, and a variety of other products found in the home and workplace. Over 1000 pediatric exposures were reported to the AAPCC in 2003.1 Ingestion of greater than 100 mg/kg of methanol should be deemed potentially toxic. Therefore, even a single swallow of windshield washer fluid, with 40% methanol, is to be considered dangerous. Methanol is less inebriating than ethanol or ethylene glycol, so patients may appear well shortly after ingestion. As methanol is osmotically active, an increased osmolal gap is sometimes evident on initial laboratory testing (see Table 134–1), but disappears as methanol is

Table 134–2

Antidotal Therapy for Methanol Poisoning

Alcohol Dehydrogenase Inhibition Ethanol (10% ethanol in D5W IV or 40% ethanol by NG) • 600 mg/kg load, then • 100 mg/kg/hr infusion* Or Fomepizole • 15 mg/kg IV load, then • 10 mg/kg IV q12h × 4 doses, then 15 mg/kg q12h† Folate • 1 mg/kg (max: 50mg) IV q4h *Titrate ethanol infusion to achieve blood ethanol concentration of 100 mg/dl. During hemodialysis, the infusion rate may need to be doubled (or ethanol may be added to dialysate). † During hemodialysis, fomepizole should be dosed every 4 hours. Abbreviations: D5W, dextrose 5% in water; IV, intravenously; NG, nasogastric tube.

metabolized (Fig. 134–1). The presence of an increased osmolal gap has good positive predictive value, but the absence of an osmolal gap is not sensitive enough to screen for methanol poisoning.5 Blood methanol levels greater than 50 mg/dl, obtained soon after ingestion, should be regarded with concern.6 Unfortunately, blood methanol levels are not available on an immediate basis in many emergency departments, mandating that clinical decisions be based on a combination of history, examination, and laboratory factors. Gastritis and/or pancreatitis sometimes occur after acute ingestion of methanol. Methanol is slowly metabolized by alcohol dehydrogenase into formaldehyde, which is further metabolized to formic acid. Hypoglycemia may occur as was described for ethanol. After several hours, profound metabolic acidosis, with a wide anion gap (see Chapter 111, Metabolic Acidosis), is common. Clinical evidence of toxicity may be further delayed if ethanol has also been ingested. Formic acid is directly toxic to the retina, and may lead to blindness.7 Patients may describe the initial visual disturbance as being akin to “standing in a snowfield.” Funduscopic examination may reveal a hyperemic optic disc and venous engorgement. Severe poisoning may progress to seizures, coma, and possibly persistent encephalopathy. Emergency management of methanol poisoning should first focus upon support of airway patency, breathing, circulation, and glycemic control. Endotracheal intubation, if performed, should be accompanied by mechanical ventilation to match the patient’s physiologic hyperventilation to prevent worsening acidemia. Intravenous fluids should be administered to reverse hypovolemia, and sodium bicarbonate is a useful adjunct in the face of metabolic acidosis6 (and may reduce the penetration of formic acid through the bloodbrain barrier). Specific antidotal therapies for methanol poisoning are summarized in Table 134–2. Fomepizole, as an alcohol dehydrogenase inhibitor, may be easier to use than ethanol therapy as it is not inebriating, does not cause hypoglycemia, and does not require a continuous infusion.8 However, fomepizole is more expensive than ethanol, and its use in pediatrics is off-label. Alcohol dehydrogenase inhibition should be continued until all metabolic acidosis is corrected and the blood methanol level falls below 20 mg/dl. The

Chapter 134 — Toxic Alcohols

Table 134–3

Relative Indications for Hemodialysis after Methanol or Ethylene Glycol Poisoning

Methanol or ethylene glycol level >50 mg/dl PLUS one or more of the following: • Visual disturbance or renal failure • Acidemia not corrected with bicarbonate therapy • Coma • Difficulty maintaining adequate alcohol dehydrogenase inhibition • Long elimination half-life, which portends prolonged, intensive hospitalization

relative indications for hemodialysis are listed in Table 134–3. Ethylene Glycol Poisoning Ethylene glycol is a sweet-tasting common constituent of automobile antifreeze, and the similarly toxic diethylene glycol is commonly used as a glycerin substitute in commercial products. Sporadic epidemics of diethylene glycol–tainted medications and beverages still occur. Over 1400 pediatric ethylene glycol exposures were reported to poison control centers in 2003.1 Ethylene glycol is inebriating, and ingestion may first manifest with vomiting, somnolence, nystagmus, and/or incoordination. As described for methanol, ethylene glycol in the bloodstream may produce an osmolal gap (see Table 134–1), but metabolism to glycolic and oxalic acids by alcohol dehydrogenase leads to metabolic acidosis as the osmolal gap recedes (see Fig. 134–1). Calcium oxalate crystals in the urine and urine fluorescence under Wood’s lamp illumination (due to fluoroscein added to some commercial antifreezes) have been advocated as screens for ethylene glycol poisoning; but neither is sensitive or specific enough to be recommended clinically.9,10 Hypocalcemia may be noted after severe poisoning due to calcium and oxalic acid complex formation. Hypoglycemia, dehydration, and pancreatitis are common complications. However, metabolic acidosis, encephalopathy, and especially renal failure are complications of ethylene glycol poisoning. Blood ethylene glycol levels greater than 50 mg/dl should warrant concern. The principles of management of ethylene glycol poisoning are similar to those presented for methanol. Appropriate ventilation must be maintained to compensate for metabolic acidosis, intravenous fluid hydration is commonly warranted,

Table 134–4

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Antidotal Therapy for Ethylene Glycol Poisoning

Alcohol Dehydrogenase Inhibition • As described in Table 134–2 for methanol Thiamine • 50 mg IV/IM q6h Pyridoxine • 50 mg IV/IM q6h Abbreviations: IM, intramuscularly; IV, intravenously.

and blood glucose, renal function, and clinical manifestations of hypocalcemia must be closely monitored. Sodium bicarbonate can be useful to alleviate metabolic acidosis. Specific antidotal therapy for ethylene glycol poisoning is presented in Table 134–4, and alcohol dehydrogenase inhibition should be continued until the blood ethylene glycol concentration is below 20 mg/dl and acidosis is resolved. The indications for hemodialysis are presented in Table 134–3. REFERENCES *1. Watson WA, Litovitz TL, Klein-Schwartz W, et al: 2003 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med 22:335–404, 2004. *2. Brennan DF, Betzelos S, Reed R, Falk JL: Ethanol elimination rates in an ED population. Am J Emerg Med 13:276–280, 1995. 3. Marks V, Teale JD: Drug-induced hypoglycemia. Endocrinol Metab Clin North Am 28:555–577, 1999. 4. Stremski E, Hennes H: Accidental isopropanol ingestion in children. Pediatr Emerg Care 16:238–240, 2000. 5. Hoffman RS, Smilkstein MJ, Howland MA, Golfrank LR: Osmol gaps revisited: normal values and limitations. J Toxicol Clin Toxicol 31:81– 93, 1993. *6. Barceloux DG, Bond GR, Krenzelok EP, et al: American Academy of Clinical Toxicology practice guidelines on the treatment of methanol poisoning. J Toxicol Clin Toxicol 40:415–446, 2002. 7. Treichel JL, Murray TG, Lewandowski MF, et al: Retinal toxicity in methanol poisoning. Retina 24:309–312, 2004. 8. Brent J, McMartin K, Phillips S, et al: Fomepizole for the treatment of methanol poisoning. N Engl J Med 344:424–429, 2001. 9. Jacobsen D, Akesson I, Shefter E: Urinary calcium oxalate monohydrate crystals in ethylene glycol poisoning. Scand J Clin Lab Invest 42:231–234, 1982. 10. Casavant MJ, Shah MN, Battels R: Does fluorescent urine indicate antifreeze ingestion by children? Pediatrics 107:113–114, 2001.

*Suggested readings.

Chapter 135 Drugs of Abuse John A. Tilelli, MD

Key Points One should always treat the patient, not the poison. Supportive care is the first priority in the setting of drug abuse. Drug abuse histories are unreliable and laboratory testing is only minimally helpful. Polydrug ingestion is common in the setting of drug abuse. Drug diluents and vehicles may be more toxic than the ingested drug.

Introduction and General Principles Patterns of Abuse Drug abuse is largely a phenomenon of the young. Drug experimentation and use achieves significant proportions by adolescence and peaks in the early 20s.1 By age 30, the rate of use of and addiction to all substances of abuse declines, and continues to do so throughout adulthood. It is clear that specific socioeconomic status correlates exist among all drugs of abuse, and that certain drugs are more prevalent in one age population as opposed to another.2 Inhalant abuse, for example, begins to appear at age 10, peaks by age 14, and declines thereafter. Tobacco use appears at age 10 and increases throughout adolescence. Alcohol, marijuana, amphetamine, cocaine, and hallucinogen use follow a similar pattern. Age-related incidences of each class of drug may reflect drug availability, perception of safety, financial independence, peer interactions, or parental control of children and permissiveness. General Approach to the Intoxicated Patient The intoxicated patient generally presents with acute symptoms that may at first suggest an illness unrelated to intoxication. The agitated, hyperthermic patient might be considered to have encephalitis or meningitis. Focal neurologic symptoms secondary to stroke might be suggestive of a clotting disorder or embolic event. Similarly, seizures, loss of consciousness, ataxia, peripheral neuropathy, tremor, weakness, 950

acute psychosis, chest pain, palpitations, and respiratory distress have extensive differential diagnoses of diseases unrelated to poisoning. Similarly, many common complaints have toxic diagnoses. A brief, and by no means comprehensive, list of drugs of abuse associated with common complaints is provided in Table 135–1. Finally, the patient experiencing withdrawal from a substance of abuse may present with a confusing array of symptoms that may mimic another intoxication. Withdrawal toxidromes are discussed later. Detection of Drugs of Abuse All laboratory tests have intrinsic sensitivity and specificity, as well as timeliness and cost-effectiveness constraints. Testing for drugs of abuse is no exception. Compared to the number of potential intoxicants comprising the drugs of abuse, few analytic techniques of value are available. Definitive assays are often time consuming and unavailable on an emergency basis. Screening techniques are often insensitive to intoxicants at clinically significant concentrations, and may be masked by or detected as a cross-reacting substance present in the sample. Commonly tested substrates for substances of abuse include blood, urine, and gastric aspirate. The latter should be inspected, as gastric contents may contain pill fragments suggestive of a particular intoxicant. Although medical management issues should take priority, it should be recalled that a crime might have been committed. Specimen collection should be done, if appropriate, in a manner that will make the laboratory assays useful in subsequent legal proceedings, by preservation of the chain of custody, retention of the specimen, and processing. Frequently, forensic specimens, when obtained, are separated from those destined for clinical use, and are handled by law enforcement officers present. The emergency department should have policies in place for the collection of specimens compliant with the National Institute on Drug Abuse Guidelines.3,4 The commonly available drug assays rely upon either immunologic or chromatographic techniques to determine the presence of a drug or its metabolite. Other techniques rely upon specific physical-chemical properties of the compound, such as atomic absorption spectra. The sensitivity and specificity of both techniques are method specific.5 Serum testing is available for barbiturates and ethanol, but most of the commonly tested substances are assayed in urine. Table 135–2 summarizes the tests commonly provided by

Chapter 135 — Drugs of Abuse

hospital laboratory services on site. Notably absent from this list, or missed by assay techniques, are lysergic acid diethylamide (LSD) and the other hallucinogens, methylenedioxymethamphetamine (MDMA) and other substituted amphetamines, toxic inhalants, nitrates and nitrites, γhydroxybutyrate (GHB), anabolic steroids, and the botanical agents (except Ma Huang). Laboratory techniques, then, can be incorrect, misleading, or irrelevant. Not uncommonly, the intoxicated patient may have another substance present more toxic than the compound detected in testing. The caveat is, therefore, that one should always treat the patient, not the poison. A positive laboratory test should not deter the clinician from considering an alternative etiology to the substance detected in screening, nor persuade the clinician that another cannot be present. In the emergency setting, managing the patient in accordance with the symptoms is less fraught with risk than an approach reliant upon analytic techniques. Withdrawal Many of the drugs of abuse are associated with some form of tolerance and dependence. Irrespective of the agent, tolerance is caused by pharmacologic or pharmacodynamic alterations Table 135–1

Drugs of Abuse Associated with Common Complaints

If the Patient Demonstrates

Consider

Depressed LOC, somnolence

Narcotics, sedative-hypnotics, toxic inhalants, GHB, ketamine, nitrous oxide, amphetamine withdrawal Phencyclidine, amphetamines, MDMA, cocaine Cocaine, phencyclidine, amphetamine, MDMA Cocaine, phencyclidine, amphetamine, LSD, anticholinergics, narcotic and sedative withdrawal LSD, MDMA, other organic hallucinogens Nitrates

Delirium, agitation Hypertension, stroke, chest pain Hyperpyrexia

Hallucinations Cyanosis/priapism

Abbreviations: GHB, γ-hydroxybutyrate; LOC, level of consciousness; LSD, lysergic acid diethylamide; MDMA, methylenedioxymethamphetamine.

Table 135–2

951

necessitating increasing the dose of a drug to achieve an equivalent desired effect. Withdrawal is a constellation of symptoms that appear after a period of drug abstinence and represent a displacement of homeostasis that occurs when a drug is administered. The two processes are linked, and, generally speaking, one occurs in the context of the other. Both stimulant and depressant drugs are associated with symptomatic withdrawal. Like drugs tend to produce similar symptoms in abstinence. Withdrawal from both narcotics and sedative-hypnotic drugs is associated with restlessness, hypertension, and tachycardia (see Table 135–3 for their similarities and differences). Considerable overlap exists between the two presentations, but the presence of seizures, hyperpyrexia, and agitated delirium strongly suggest sedative withdrawal. Sedative-hypnotic withdrawal and alcohol withdrawal seem to be similarly mediated, by down-regulation of the central nervous system inhibitory transmitter γ-aminobutyric acid (GABA). Alcohol withdrawal presents also with tremor, diaphoresis, irritability, restlessness, nausea, vomiting, hallucinations, insomnia, and agitation, but hyperpyrexia and hypertension are uncommon.6 Hallucinations associated with alcohol withdrawal may be the consequence of depleted thiamine stores.7 Symptoms of alcohol withdrawal seem to be related to the intensity of drinking and duration, and the age of onset of problem drinking behavior. Alcoholics who began drinking before age 20 were more likely to experience symptomatic withdrawal upon cessation than older drinkers, notwithstanding a substantial difference in duration of the behavior.8 Delirium tremens has been reported in a child who was 10 years old and had a history of alcohol consumption for 3 years.9 There is a strong similarity between the alcohol abstinence syndrome and that of benzodiazepines, barbiturates, hydrocarbon inhalants, and GABA. It is strongly suggested that therapeutic effects as well as symptoms of withdrawal are mediated by GABA.10 A strategy for therapy, then, would include, in addition to basic stabilization measures, augmentation of GABA with either a benzodiazepine or barbiturate. There are no studies comparing one approach to the other; both have been reported effective.11 A recent double-blind, controlled study comparing the use of the benzodiazepine antagonist flumazenil to oxazepam in the treatment of symptomatic withdrawal found that flumazenil does not precipitate withdrawal in tolerant subjects, and is effective at modulating symptoms.12

Commonly Used Screening Tests for Drugs of Abuse

Drug or Class

Sensitivity

Cross-Reacting Substance

Cannabinoids Opioids Phencyclidine Cocaine Benzodiazepines Barbiturates Amphetamine

Good Fair Fair Good Fair Good Poor

None Dextromethorphan* Dextromethorphan None None None Pseudoephedrine, ephedrine‡

Misses Dextromethorphan,* all synthetic narcotics, notably fentanyl PCP congeners Many congeners unrelated to oxazepam† (especially flunitrazepam) None MDMA and congeners

*Dextromethorphan may (when detected) be from a cough suppressant and confused for an abused drug. On the other hand, many assays are of insufficient sensitivity to detect dextromethorphan, which also may confound PCP assays. † Benzodiazepines detected by urinary screens include chlordiazepoxide, oxazepam, diazepam, temazepam. ‡ Over-the-counter decongestants are most commonly confused with abused amphetamines. Abbreviations: MDMA, methylenedioxymethamphetamine; PCP, phencyclidine.

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Table 135–3

Manifestations of Narcotic versus Sedative-Hypnotic Withdrawal Narcotics

Sedative-Hypnotics

Blood pressure Pulse Respiratory rate Temperature Mental status

Hypertension Tachycardia Elevated NORMAL Normal (or restless)

Miscellaneous

Piloerection Nausea Diarrhea Myalgias

Hypertension Tachycardia Elevated ELEVATED Restless, irritable, DISORIENTED Tremor SEIZURES

Adapted from Hamilton RJ: Substance withdrawal. In Goldfrank LR, Flomenbum NE, Lewin NA, et al (ed): Goldfrank’s Toxicologic Emergencies, 7th ed. New York: McGraw-Hill, 2002, pp 1059–1074.

Opiate withdrawal differs from sedative-hypnotic withdrawal, as it is not commonly associated with seizures or hyperpyrexia, and psychosis is rarely seen. Opiate effects and withdrawal symptoms are mediated by specific receptor proteins in the brain and spinal cord that are down-regulated with the administration of an agonist drug. These receptors are closely linked central α2 receptors that may be stimulated by the centrally acting agent clonidine. Symptoms of withdrawal, while uncomfortable, are rarely life threatening. A strategy of symptomatic relief from opiate withdrawal would consist of basic stabilization and the administration of a pure narcotic agonist or clonidine to modulate symptoms.13-15 Rapid opiate withdrawal techniques use general anesthesia to subdue symptoms and accelerate the course of withdrawal.16 It has been used successfully in a child.17 Experience is too limited to make a general recommendation on the utility of this technique. A syndrome of excessive somnolence, craving, depression, and lethargy has been identified with the discontinuation of amphetamines and hallucinogens. It has been identified in children after discontinuation of stimulant medications and in neonates exposed to amphetamines in utero.18,19 While symptoms are not life threatening, drug craving may precipitate a relapse or exploration of the use of another drug. Recently bupropion has been used successfully to modulate the symptoms of amphetamine withdrawal.20

Selected Drugs of Abuse Marijuana Opioids Sedative-hypnotics Barbiturates Benzodiazepines Cocaine Amphetamines Lysergic acid diethylamide “Club drugs” Ketamine and phencyclidine Flunitrazepam γ-Hydroxybutyrate Inhalants Volatile nitrogen oxides

FIGURE 135–1. Drug paraphernalia. Pipes commonly used in the smoking of crack cocaine and hashish. Nitrous oxide whippet.

Miscellaneous agents Over-the-counter drugs Botanicals and natural products Anabolic steroids

Discussion of Individual Agents Marijuana Marijuana is the most commonly encountered drug of abuse among children and adolescents after tobacco and alcohol. As many as 20 million Americans may use this drug on a regular basis. Marijuana is the popular term for the substances obtained from the plant Cannabis sativa that grows wild and is cultivated, both domestically and abroad, for recreational purposes. The principles of Cannabis horticulture are easily available on the Internet. As a consequence, availability is widespread and difficult to eradicate. All parts of the plant, including leaves and flowers, contain the active alkaloids known as cannabinoids. The most important of these is ∆9tetrahydrocannabinol (THC), which is present in its highest concentration in the buds. The leaves are dried and ground into a mass resembling oregano or tobacco. The buds may be compressed into a fine powder or resin (“hashish” or “hash”), prized for its potency. Marijuana is conventionally smoked, but is effective orally. Hashish is smoked in small pipes resembling those used for crack cocaine abuse, while marijuana is rolled into cigarettes (Fig. 135–1). Occasionally, its use may be ritualized, inhaling the drug through an elaborate water pipe or “bong.” The subjective sense attendant to marijuana use is dose dependent, but also varies among individuals. The widespread belief is that naive users do not appreciate its effect as much as those who have prior extensive drug experience. The user generally describes a state of dreamy intoxication, in which sensory perception, especially to color and sound, seems enhanced. Increased appetite is commonly expressed. Conjunctival injection is commonly present. Judgment, especially that which is required for complex or subtle activities such as driving, is significantly impaired, a finding that may persist as long as 24 hours after use.21 The concurrent use of ethanol with marijuana appears to impair judgment

Chapter 135 — Drugs of Abuse

more than either drug alone. Acute psychosis and panic attacks are infrequent, but have been described. Pneumomediastinum and pneumothorax may occur as a consequence of the widespread practice of taking the drug by deep inhalation and retaining the breath to encourage absorption of the drug. Chronic effects of marijuana include chronic lung disease and gynecomastia, caused by diminished testosterone levels associated with its use.22 It may appear after relatively brief use.23 There is debate over a relationship to psychiatric disease, cognitive impairment, or a chronic amotivational state attributed to its use, but unequivocal data are lacking.24 Neuropsychiatric effects attributed to the chronic use of marijuana may be attendant to preexistent psychopathology. Marijuana is advocated for a variety of medical indications, including cachexia, glaucoma, and chemotherapy-induced nausea, none of which has been rigorously investigated.25-29 Its legalization in various states has been the subject of great public debate.30 The precise clinical role, if any, for marijuana in the medical center has not yet been well defined. Some analgesic potential for marijuana may exist, but its role in pain management is uncertain. Severe intoxication due to marijuana use is rare. The patient who presents to the emergency department with complaints directly related to its use can be often managed by removal to a nonthreatening environment and emotional support. Occasionally an especially anxious or agitated patient may benefit from the administration of a benzodiazepine. Marijuana is frequently adulterated with other compounds of greater potency. The user may be unaware of the presence of excipients, added to alter or increase the effect of the drug. Among these are phencyclidine, LSD, amphetamines, anticholinergics, narcotics, and benzodiazepines. The presence of severe hypertension and tachycardia, mydriasis, miosis, frank hallucinations, hyperthermia, depressed level of consciousness, or respiratory depression should alert the caregiver to the possibility of an occult co-intoxicant. Opioids In the simplest terms, opioids (narcotics) are a class of drugs characterized by the production of analgesia, miosis, sedation, and respiratory depression; in overdose they are treated with supportive care. The term narcotic, however, is misleading, as these drugs produce analgesia better than sleep. The generic term narcotic is used to connote a group of drugs that alter the perception of pain, notwithstanding that many of these drugs bear no structural similarity. The drugs most commonly identified with the narcotics are the natural and semisynthetic alkaloids of the poppy that have been used throughout the ages for recreational and religious purposes. The natural poppy alkaloids are morphine, thebane, and papaverine. Alteration of the chemical structure was undertaken in an attempt to modulate the undesirable properties of the drug without altering analgesic strength. Heroin (diacetyl morphine) was the first such semisynthetic derivative. Codeine, dihydromorphone (Dilaudid), and oxycodone (OxyContin) are the three other semisynthetic derivatives of poppy alkaloids, the latter being a thujone derivative. Other commonly used narcotic analgesics, such as dextromethorphan, pentazocine, meperidine, fentanyl, methadone, and propoxyphene, are synthetic.

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Opioids are absorbed by the oral, parenteral, and inhalational routes. Intravenous abuse of narcotics in the 1950s has given way to abuse by smoking or intranasal insufflation. Effects are noted shortly after administration, and peak 10 minutes after an intravenous dose and 30 minutes after administration by another route. Some addicts may introduce the drug by the subclavian vessels (a so-called “pocket shot”) to increase the effect, a technique associated with air embolism, subclavian vessel thrombosis, and pulmonary thromboembolism.31 Generally, however, an intravenous abuser will self-administer the drug until a subjective effect is perceived (the “flash”), and then stop. This practice may lead to fatal overdose if the drug is of unanticipated potency.32,33 Abused opioids are inevitably adulterated with extraneous substances, some of which have pharmacologic activity. Heroin is often diluted with quinine, manitol, lactose, talc, bicarbonate, acetaminophen, lidocaine, phenobarbital, methaqualone, caffeine, antihistamines, or phencyclidine.34 The specific pattern of adulterants may be of forensic value in determining the source of the drug.35 As a consequence, the original bag of drug, and any paraphernalia with the patient, should be saved with the protection of the chain of custody for later use by law enforcement. As these are nonsterile, they are often contaminated by biologic agents, including Clostridium species, Bacillus, and others.36 Intravenous users typically prepare heroin for consumption by dissolving the drug in a spoon and heating it with a flame. It is then aspirated through a cotton ball into a syringe. The cotton is subsequently reused, causing “cotton fever,”37 the etiology of which is obscure. Inhalation of heroin fumes is called “chasing the dragon.” Tolerance develops to all effects of narcotics except miosis. The central nervous system effects include tolerance to pain, suppression of anxiety, sedation, suppression of the cough reflex, and euphoria. The therapeutic index of narcotic agonists varies considerably depending on the relative potency of the drug and the experience of the user. Cross-tolerance is the rule, and resistance to one narcotic generally implies resistance to all others. In overdose, therapeutic symptoms are exaggerated. Pupils may become dilated in the presence of hypoxia or with overdose of meperidine, pentazocine, diphyenoxylate/atropine (Lomotil), propoxyphene or nonnarcotic coingestants. Respiratory depression and hypoxia are generally the mechanism for death. Orthostatic hypotension and syncope may occur as a consequence of histamine release observed uniquely with morphine. Noncardiogenic pulmonary edema may occur, although rarely at therapeutic doses. Seizures rarely occur except uniquely after the abuse of pentazocine or propoxyphene. Similarly, meperidine has an active metabolite that is capable of causing seizures. The naturally occurring and semisynthetic opioids may be detected in the urine by a commonly available and rapid urinary immunofluorescent assay. Morphine, heroin, oxycodone, and codeine are all detected, but many assays are not of sufficient sensitivity to detect agents such as dextromethorphan, and drugs with unrelated structures, such as meperidine and fentanyl, are not detected at all.38 Definitive drug testing and confirmation of positive drug screens may be accomplished by chromatographic techniques such as gas chromatography–mass spectrometry. Basic stabilization is the mainstay of therapy. The presence of an adequate airway should be assured in all patients with

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a depressed level of consciousness and/or lack of airwayprotective reflexes. Noncardiogenic pulmonary edema should be managed by the administration of oxygen and positive airway pressure. The use of narcotic antagonists is controversial, as they may precipitate withdrawal symptoms. They may have a role in the diagnostic assessment of the patient. Partial response may indicate the presence of another drug, such as a sedative-hypnotic, or hypoxia. Naloxone, a pure opioid antagonist, reverses all effects of opiates, including analgesia, miosis, respiratory depression, and sedation. It is unknown if it protects against seizures encountered with some opiates such as propoxyphene, but appears to do so in animal models. It does not appear to reverse pulmonary edema. It has a half-life of 20 to 30 minutes. The initial dose is 0.01 mg/kg IV or SQ. Give a subsequent dose of 0.1 mg/kg if there is an inadequate response. Higher doses may be required for the reversal of some drugs such as propoxyphene and dextromethorphan. If the use of naloxone is undertaken, it should be remembered that the half-life of the abused substance may exceed that of the antagonist, and that continued observation of the patient, and possibly repeated or continuous administration, is indicated. Recently, a shortage of naloxone has been reported, mitigating against its prolonged use except in unusual circumstances. Nalmefene, a newer agent, has a halflife of 10.3 to 12.9 hours, and appears to be safe and potent. Bowel decontamination of ingested drugs may be occasionally indicated. Polyethylene glycol catharsis may be useful for the removal of packets of drugs from body packers or body stuffers when bowel obstruction is not present. Gastrointestinal hypomotility may prolong the gastric retention of the ingested substance. Some of the acute and chronic complications of narcotic abuse are listed in Table 135–4. Infectious complications are especially common among intravenous drug abusers. Infective endocarditis, hepatitis, human immunodeficiency virus (HIV) infection, and abscess formation are commonplace among them.36-38 Patients may present with a complication attendant to their habit and symptoms only peripherally suggestive of an acute complication of narcotic abuse, with chronic illness acquired as the result of a high-risk behavior, or both. Malnutrition and accessory diseases unrelated to the intoxication, but related to the lifestyle of a drug-addicted individual (e.g., tuberculosis, sexually transmitted disease) are also common. The general belief is that some tolerance occurs after both the therapeutic and nontherapeutic use of all narcotic agonists, usually after the administration of successively higher doses over several weeks. However, some tolerance begins after the first dose, especially with the more potent drugs, such as fentanyl. The course is similar for all opiates, with the time course compressed for the more potent and shorter acting drugs. The initial stage of withdrawal begins with drug craving and anxiety. Later, yawning, mydriasis, lacrimation, rhinorrhea, piloerection (from which is derived the term “cold turkey”), twitching, nausea, vomiting, diarrhea, and abdominal pain are observed. Dehydration, fever, hyperglycemia, and spontaneous erections may occur. Symptom intensity seems to correlate with the duration and dose of the abused drug. The administration of opioid agonists is effective in modulating the symptoms of withdrawal, and may be required in significant doses. Fear of enhancing the patient’s

Table 135–4

Complications of Narcotic Abuse

Infection HIV Hepatitis B, C, and D Soft tissue infection Bacterial sepsis Cardiovascular Bacterial endocarditis Thrombophlebitis Pulmonary Pneumonia Aspiration Nontuberculous granulomas Dermatologic Abscess formation Cellulitis Neurologic Cerebral edema Transverse myelitis Seizures Polyneuritis Brain abscess Hepatic Cirrhosis Liver abscess Renal Nephritis Hematologic Thrombocytopenia Leukopenia Musculoskeletal Myositis ossificans Osteomyelitis Miscellaneous False-positive VDRL Abbreviations: HIV, human immunodeficiency virus; VDRL, Venereal Disease Research Laboratory (test).

addiction to a narcotic should not prevent the clinician from administering them to the individual with symptomatic withdrawal. Recently, centrally acting α2 agonist drugs such as clonidine have been reported effective as well. The effects of clonidine and opiates, including respiratory depression and sedation, are additive. Sedative agents, such as the benzodiazepines, may assist in relieving the agitation and anxiety that accompany narcotic withdrawal, but do not reverse the autonomic effects.14 Sedative-Hypnotics The first of the sedative-hypnotic drugs, the barbiturates, appeared in the early 20th century. The barbiturates, and associated drugs such as the benzodiazepines, whose principal manifestations are anxiolysis and sedation, have been widely used in medicine and as targets for illicit abuse. Between 1950 and 1970, they were the most common cause of drug-induced death. The replacement of barbiturates with drugs of wider therapeutic index, and a general trend of decline in illicit drug use of sedative-hypnotics, have significantly reduced mortality associated with these agents. Numerous agents unrelated to the barbiturates and benzodiazepines are used for their sedative properties. The clinical

Chapter 135 — Drugs of Abuse

effects and unique toxicities of some of these agents are summarized here. The barbiturates and benzodiazepines are used, often in combination with other drugs, to treat anxiety, pain, and sleep disorders. They also have important use in the acute and chronic treatment of seizure disorders, and are used as anesthetic agents.39 Barbiturates all share a common nucleus, the modification of which alters its pharmacologic properties but not its effects, which are common to all drugs of this class. All barbiturates are absorbed well by the intestine. The rate of elimination among them varies considerably. The half-life of these agents depends on their lipophilicity, and thus volume of distribution. More lipophilic agents, such as thiopental, are classified as ultra-short acting, while longer acting drugs such as phenobarbital are more water soluble. Shorter acting agents are eliminated by hepatic metabolism. Only the longer acting barbiturates have substantial renal clearance. Toxic doses are generally seen at five times the therapeutic dose, and toxicity is an extension of the therapeutic effects. Benzodiazepines are among the most commonly prescribed drugs. Over 3000 have been synthesized and over 50 are marketed worldwide. As a group, they account for the majority of toxic exposures to sedative-hypnotic agents. Like barbiturates, all drugs of this class share a common chemical nucleus, but unlike the barbiturates, each varies slightly in effects. Some, such as flunitrazepam and midazolam, are more commonly associated with amnesia and hallucinations than other benzodiazepines. They are metabolized in the liver. Many have active metabolites, the notable exception being lorazepam, which is metabolized to solely inactive compounds. Both the barbiturates and benzodiazepines have sedative, hypnotic, amnestic, anxiolytic, and anticonvulsant properties.40 Additionally, the benzodiazepines are muscle relaxants, and are often prescribed for that purpose. Although specific benzodiazepine and barbiturate receptors probably exist, both appear to exert their sedative and anticonvulsant effects by exerting an effect on the inhibitory neurotransmitter GABA. The effects of sedative-hypnotic drugs are related to dose and prior drug experience. The onset and duration of symptoms depend on the type and amount of drug ingested.39 While short-acting agents have an onset of symptoms 15 to 20 minutes after ingestion, the effects of longer acting agents may be delayed as much as 18 hours. The early stage of intoxication may resemble the effects of alcohol, a substance commonly co-ingested with sedative agents. Patients with mild intoxication may appear stuporous but responsive. More impaired patients become unresponsive, and eventually anemic, arreflexic, and hypotensive. Pupils generally demonstrate miosis in early coma, but are dilated later. Respiratory depression is common in symptomatic ingestion. Hypoglycemia and hypothermia are occasionally observed. Cardiovascular instability with hypotension and shock is more characteristic of barbiturate than benzodiazepine overdose, but the effects of both drugs are similar in type if not degree.41 Tolerance and dependence on sedative-hypnotics are well recognized.42 An abstinence syndrome of restlessness, insomnia, irritability, agitation, seizures, tremors, tachycardia, and hypertension may be seen, its intensity and duration being dependent on the type and amount of the substance

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abused. Hyperpyrexia, uncommon in narcotic withdrawal, is observed in the sedative-hypnotic abstinence syndrome.43 The treatment of sedative-hypnotic overdose relies heavily on supportive measures. Protection of the airway and the support of respiration with adequate oxygenation is the cornerstone of management of the seriously intoxicated patient. Hypotension is mediated by vasodilation, and may be managed with the administration of volume expansion and vasopressor drugs such as dopamine and norepinephrine. Pure inotropic agents such as dobutamine and milrinone are rarely necessary except in the most severe circumstances, as many sedatives do not lend themselves to enhanced elimination. Phenobarbital, which has a smaller volume of distribution than many of the other agents, is the exception, and has been reported as being successfully treated with dialysis.44 The effects of the benzodiazepines may be reversed by the specific antagonist flumazenil. It may provoke seizures and withdrawal symptoms in the patient who chronically uses a benzodiazepine either therapeutically or as a recreational drug,45 or in the patient who has an underlying seizure diathesis.46 A recent study concluded that flumazenil was not cost effective compared to supportive therapy, nor did it improve outcome.47 It does not reverse the sedative effects of other drugs with similar manifestations such as the barbiturates. Its use in the acutely intoxicated patient may be of diagnostic benefit. Failure to respond may imply the presence of another substance, hypoxic encephalopathy, or the postictal state. Its half-life is shorter than that of many benzodiazepines, and repeated administration may be necessary. Flumazenil should not be considered a replacement for supportive therapy. Barbiturates Massive oral overdose of barbiturates is associated with bezoar formation, which may be observable on plain fi lm or demonstrable by endoscopy. Drug removal may be hastened by lavage or endoscopic removal. The detection of barbiturates may be accomplished by either serum or urine screens. The presence of a therapeutically administered drug such as phenobarbital may obfuscate the presence of another barbiturate. The management of barbiturate overdose may necessitate prolonged mechanical ventilation for a long-acting drug. Drug elimination may be hastened by the administration of multiple doses of activated charcoal.48 Barbiturate intoxication may precipitate noncardiogenic pulmonary edema, necessitating the administration of positive pressure ventilation.49 The unique manifestation of cutaneous bulla formation is occasionally seen with massive barbiturate poisoning.50 Benzodiazepines Generally speaking, the manifestations of benzodiazepine intoxication are less severe than barbiturate overdose. Death after the sole oral ingestion of a benzodiazepine is rare. Benzodiazepines are, however, additive to the effects of other depressant medications, such as narcotics and alcohol.51 Death is more commonly the result of a multiple drug ingestion. The exception may be flunitrazepam. A series of deaths were reported over a 2-year period in which flunitrazepam appeared to be the sole or principal precipitating agent.52 The most commonly abused agents at the time of this writing are diazepam and lorazepam. Both of these drugs are easily

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obtainable from offshore sources, and are frequently sought from legitimate sources in drug-seeking behavior. Most benzodiazepines are detectable by urinary screening assay, but some, such as flunitrazepam, may be present in a sufficiently small quantity to render screening techniques ineffective. This latter drug deserves special mention as it has achieved a reputation for producing amnesia, sexual arousal, and euphoria, making it a target drug for date rape (see the “Club Drugs” section later). The treatment of patients intoxicated with a benzodiazepine is supportive, as outlined previously. The usefulness of the benzodiazepine antagonist flumazenil in the management of benzodiazepine intoxication is at best limited. Recovery without sequelae is the rule in the absence of hypoxic encephalopathy acquired antecedent to the initiation of supportive management. Cocaine Cocaine is the alkaloid of the Erythroxylon coca, which grows wild in many South American countries. It has been advocated as an aid to psychotherapy, an analeptic, and an anesthetic agent. It has been considered a controlled substance in the United States since the passage of the Harrison Narcotic Act of 1914. Legal cocaine manufacture is strictly controlled. Illicit use in the United States, after a long period of relative quiescence, has increased dramatically over the past 20 years. As many as 11% of Americans over 11 years of age report having used cocaine at least once in their lifetime; 0.7% of children 12 to 17 years of age admitted using it at least twice per week.53 Cocaine intended for abuse is smuggled into the country by a variety of routes, the most important of which medically is the practice of “body packing,” in which condoms fi lled with drug are ingested orally with the intention of later passage through the gastrointestinal tract54 (Fig. 135–2). Children have been used as “mules” to assist in the illicit transport of cocaine. One such child was reported to have ingested 53 packets of cocaine, recovering after rupture of a packet.55 Bowel obstruction of ingested packets may occur, and accidental rupture of a packet may prove fatal. Oral polyethylene glycol administration has been advocated as a relatively safe method to expedite the passage of ingested packets. Bowel obstruction may necessitate surgical removal.56 Cocaine is absorbed by all routes—by ingestion, inhalation, intranasal absorption, or the intravenous route. Orally, its potency is about one tenth that of the intranasal route. A high vaporization temperature renders the hydrochloride salt unacceptable for smoking.57 The typical intranasal dose is between 30 and 45 mg. Cocaine is frequently adulterated with lidocaine, ephedrine, and caffeine,58 which are included to mimic the anticipated effects and suggest a higher potency drug to the user. The diagnosis of cocaine intoxication may be suggested in the appropriate clinical context by the finding of drug paraphernalia at the scene or a white residue on the nose. “Freebase” and “crack,” extractions of free cocaine from the hydrochloride salt, have a lower temperature of vaporization and are therefore better suited for smoking. The latter acquires its name from the popping sound when smoked. It is supplied as brown crystalline pebble wrapped in tin foil, which is ignited over a screen placed in the bottom of a pipe.

FIGURE 135–2. Computed tomographic scan of a body packer. Arrows indicate air trapped within, and outlining packets. (From Traub SJ, Hoffman RS, Nelson LS: Body packing—the internal concealment of illicit drugs. N Engl J Med 349:2519, 2003.)

The usual dose is 5 to 10 mg. Inhalation of the smoked vapors provides a more direct route for the drug to the circulation compared to the intranasal route, thereby amplifying its effect; both provide levels approximately two-thirds that of intravenously administered drug.59 Accidental fatal ingestion of crack cocaine by a child has been reported.60 Cocaine is the benzoic acid ester of ecgonine, with anesthetic and central stimulatory properties. Conventional detection techniques utilize enzyme-amplified immunofluo-

Chapter 135 — Drugs of Abuse

Table 135–5

Symptoms of Cocaine Intoxication

Phase 1: Early • Euphoria, elation, garrulousness, emotional lability, pseudohallucinations, sense of impending doom • Tics • Hypertension • Cold sweats • Mydriasis • Hyperpyrexia • Premature ventricular contractions • Increased respiratory rate Phase II: Advanced • Unresponsiveness to voice • Hyperreflexia, convulsions, status epilepticus • Incontinence • Severe hypertension giving way to hypotension • Cyanosis • Central nervous system hemorrhage • Congestive heart failure • Irregular respirations Phase III: Depressive • Flaccid paralysis • Coma • Fixed pupils • Arreflexia • Ventricular tachycardia and fibrillation, cardiac arrest • Apnea • Pulmonary edema Adapted from Comerci GD, Schwebel R: Substance abuse: an overview. Adolesc Med 11:79–101, 2000.

rescent techniques to detect one or another metabolite in urine. Cocaine is a potent central nervous system stimulant and anesthetic. It exerts its principal effects by blocking the reuptake of norepinephrine, serotonin, and other neurotransmitters at nerve endings. Administration is accompanied shortly by a sense of euphoria, elation, garrulousness, and restlessness. Intranasal use is attended by local anesthesia, termed “the freeze”. The pulse is usually elevated, but may be transiently depressed by reflex vagal effects. The blood pressure is usually elevated. Mydriasis and myoclonic twitching can be noted. The patient can experience auditory or visual hallucinations, or tactile hallucinations known as “cocaine bugs.” Toxic psychosis may occur. In more advanced intoxication, the patient becomes unresponsive and hyperreflexic. Seizures may occur. Hypertension or hypotension may be present, and arrhythmias, especially atrial and ventricular tachycardia, could occur. Irregular respirations may give way to apnea. Greater toxicity is accompanied by flaccid paralysis, coma, fi xed pupils, ventricular fibrillation, and death. Symptoms are summarized in Table 135–5.57 Cardiac complications of cocaine use include myocardial ischemia, infarction, accelerated atherosclerosis, and cardiomyopathy.61,62 Rhabdomyolysis and renal failure may occur as a consequence of hyperpyrexia.63 Cocaine-associated chest pain may mimic a myocardial infarction and merits monitored observation.64 Neurologic complications include central nervous system hemorrhage, ischemic infarction, and seizures. Headache in the patient who presents after cocaine exposure may be the result of sympathetic stimulation, migraine, impending stroke, or hemorrhage, and may occur during cocaine withdrawal. Concern for cerebrovascular injury

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should strongly suggest appropriate neuroimaging studies for all patients with altered mental status, focal neurologic signs, or severe headache. Smoking crack cocaine has been associated with pneumothorax.65 Chronic use has been associated with renal insufficiency and hypertension,66 chronic cognitive defects,67 nasal septal perforation, sinusitis, and a necrotizing vasculitis.68,69 Cocaine is likely a teratogen, with cardiac, urogenital, central nervous system, and gastrointestinal anomalies in 7% to 26% of exposed infants.70 Cocaine metabolites may be detected in meconium and infants’ hair. Treatment of cocaine intoxication is largely supportive. Elimination techniques are generally of no benefit, although activated charcoal absorbs cocaine and may have some role in the management of the body packer. There is no antidote of proven value. Airway control should be undertaken in patients with compromised mental status. Hyperthermia should be aggressively treated (see Chapter 139, Hyperthermia). The risk of rhabdomyolysis probably contraindicates the use of depolarizing muscle relaxants in rapid sequence intubation.71 Sedation with benzodiazepines has been demonstrated beneficial for the management of fever, seizures, hypertension, and agitation.72 Butyrophenones and other major tranquilizers may be associated with worse outcome.73 Rhabdomyolysis should be managed by the administration of intravenous fluids, and maintaining urine flow at 3 ml/kg/ hr. Hypertension is usually responsive to the administration of sedatives. Occasionally, antihypertensive agents are indicated. Nitroprusside, nitroglycerine, or other vasodilators are effective.74 Beta-blocking agents such as labetalol may worsen hypertension by failing to reverse α-mediated vasoconstriction, and do not reverse coronary vasoconstriction.75,76 They should be avoided in the management of cocaine intoxication. Anticoagulation for cocaine-induced thrombosis is not well studied. Most cocaine-associated arrhythmias respond to sedation. Ventricular tachycardia occurring shortly after exposure may result from the local anesthetic property of cocaine and should be managed similarly to intoxication with class IA or IC agents, with the administration of bicarbonate.77 Lidocaine in this circumstance may exacerbate seizures and arryhthmias and therefore is contraindicated.72,73 Conversely, ventricular arrhythmias occurring several hours after exposure are likely the result of ischemia, and may be managed safely with lidocaine.78 Pulmonary edema may be of cardiac or noncardiogenic origin and is managed with positive pressure ventilation. There is no consensus for the management of cocaine-associated congestive heart failure. Postmortem examination suggests a direct toxic effect of cocaine on the heart,79 correlating clinically with the development of a dilated cardiomyopathy.80 Management of the low cardiac output state would be directed at inotropic support and afterload reduction. Amphetamines The amphetamines are a group of substituted noncatecholamine phenylamines with diverse central nervous system stimulant and hallucinatory properties (Fig. 135–3). They were first synthesized in the late 19th century and were quickly recognized for their biologic effects. Amphetamines are still used in the management of attention deficit/hyperactivity disorder and narcolepsy and in weight control, and for these indications they are widely prescribed. Use migrated to the recreational market in the 1960s, when “speed freaks”

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2 3

1 6

4

N α

5

FIGURE 135–3. Amphetamine ring.

would engage in serial use, often consuming thousands of milligrams over days (“the rush”), to be terminated by a period of lethargy and somnolence during withdrawal (“the crash”). The introduction of substituted amphetamines as drugs of abuse began in 1968 with MDMA, known first as “Adam” and later as “Ecstasy,” which was, for a brief time, legally sold without prescription. What followed was a series of drugs, each replacing the one before, as the sale of prior agents was restricted or discredited by the community of users. The substituted amphetamines, then, became the first “designer” drugs. This process was interrupted in 1986 with the passage of the Controlled Substances Act.81 Notwithstanding their proscription, their popularity has not waned and they remain popular in the club culture as one of the so-called rave drugs (see later). It has been estimated that as many as 6.8 million individuals have used Ecstasy.82 Amphetamine is often abused orally, but may be used intravenously. In this form it may be used with heroin, known as a “speedball.” Tolerance develops to the drug, and users may take hundreds of milligrams at a time. The hydrochloride salt of amphetamine is smokable, and is known as “ice.” It is occasionally mixed with lidocaine to mimic the “freeze” of cocaine, and sold as that drug. Amphetamine is well absorbed orally and by inhalation, and has a large volume of distribution. It undergoes some hepatic metabolism, but substantial amounts are excreted in the urine. The half-life of amphetamine is dependent on urine pH, and is between 12 and 34 hours, an alkaline urine prolonging its retention.83 The clinical effects of amphetamine are caused by the release of norepinephrine, dopamine, and serotonin at nerve endings. A wide variety of signs and symptoms may be present.84 The intoxicated patient appears restless, hypervigilant, and agitated. Anxiety, paranoia, and delusions are common. Hallucinations, frequently visual, are also common. The seriously intoxicated patient may exhibit toxic psychosis, suicidal ideation, or aggressive behavior. Mydriasis may be present. Seizures, cerebral edema, intraventricular hemorrhage, and cerebral infarction occur. The patient may experience tightness in the chest, or chest pain, and a sense of impending doom. Hypertension is common and may be severe. A dilated cardiomyopathy may be present, to which sudden death in amphetamine abuse has been attributed.85 Renal failure, hyperpyrexia, rhabdomyolysis, and vasculitis are also reported. The intravenous user is subject to all the complications of the abuse of drugs by that route, including HIV and hepatitis. Additionally, pulmonary granulomas may occur as a consequence of the intravenous administration of dissolved pills containing talc.86,87 MDMA (Ecstasy) use has increased more rapidly than any other drug.88 It has acquired a place among the “club drugs,” used to enhance social experiences, along with flunitrazepam, ketamine, and GHB. Increasing use has been reported among 8th, 10th, and 12th graders.89 It has a reputation as a harmless drug and is easily synthesized in clandestine laboratories. Tablets typically contain 50 to 150 mg of the drug,

and are often imprinted in different colors with a popular icon. Common adulterants include aspirin, other amphetamines, ketamine, LSD, and dextromethorphan.90 Drug paraphernalia includes a pacifier, used to control bruxism common with MDMA use, and Vicks Vapo-Rub, inhaled through a surgical mask, which has a reputation for enhancing the effect of the drug. MDMA has both stimulant and hallucinogenic properties. Effects begin 30 minutes after ingestion, and include euphoria, increased libido, altered visual perception, and a distorted sense of time. Tachycardia is observed, and peaks 1 to 2 hours after administration.91 Ecstasy did not reliably increase the body temperature of volunteers,92 but life-threatening hyperpyrexia has been reported.93 Elevations in body temperature may be attendant to activities undertaken during its use that produce dehydration, but a relationship to the serotonin syndrome has also been proposed.94 Persistent cognitive defects have been reported after prolonged use.95 Side effects of Ecstasy are similar to those of other amphetamines. MDMA decreases thirst, and concurrent activity may cause dehydration. Hyponatremic dehydration has been reported.96 Cerebral infarction97 and myocardial infarction98 have been reported as a cause of death. In a recently reported series of Ecstasy-related deaths with a review of the literature, two thirds were attributable to aortic dissection, disseminated intravascular coagulation, rhabdomyolysis, myocardial infarction, hyperpyrexia, or sudden collapse, presumably due to arrhythmia.99 One third of deaths were due to blunt trauma or gunshot wounds. A relationship between inhibition of hepatic cytochromes by antiretroviral drugs and sudden death attendant to simultaneous use of Ecstasy has been proposed.100 Detection of the amphetamine-intoxicated patient is based on history and symptoms. Immunofluorescent screening of the urine may be of assistance. False-positive screens may be caused by ephedrine-containing over-the-counter medications. MDMA is detected by high-sensitivity urinary assays.101,102 Evaluation of the patient should include a search for commonly present co-intoxicants, such as fentanyl, GHB, and flunitrazepam. A diagnostic survey for occult injury should be performed. Diagnostic tests may include serum electrolytes, an electrocardiogram, and cardiac enzymes. Management of the patient who is intoxicated with an amphetamine congener is largely supportive. As symptoms usually are noted more than 1 hour after ingestion, there is little role for the use of activated charcoal or gastric lavage. The comatose patient should be intubated. Neuroimaging should be performed on patients with altered mental status or severe headache. There is no antidote, but most symptoms can be controlled with the aggressive administration of benzodiazepines. Dehydration and electrolyte abnormalities, especially hyponatremia, should be corrected. Hyperthermia should be aggressively controlled, and neuromuscular blockade may be required to control shivering that may contribute to heat production. Dantrolene may be helpful.103 A relationship between MDMA and the serotonin syndrome has been proposed, prompting the suggestion that cyproheptidine may also be of use.94,104 No clinical trials of either therapy have been conducted. Rhabdomyolysis with myoglobinuria mandates alkaline diuresis, to maintain a urine flow greater than 3 ml/kg/hr.88 Concern over prolongation of the excretion time of MDMA should not deter one from urinary

Chapter 135 — Drugs of Abuse

alkalinization. Hypertension may be severe, but is frequently controlled with satisfactory sedation. A vasodilator, such as nitroprusside, should be considered in those patients with refractory hypertensive urgency. Seizures are also usually responsive to benzodiazepines, but may be caused by hyponatremia, which, once again, should be corrected.105 Lysergic Acid Diethylamide LSD is one of a class of drugs abused for their perceptionaltering qualities. It is an indole derivative and was fi rst synthesized by Hoffman in 1946 from a rye fungus (ergot). Several other compounds share the neuropsychiatric characteristics of LSD and are similarly abused, or misrepresented as LSD. Among them are psilocybin, dimethyltryptamine, and dimethyoxy methylamphetamine (known as DOM or STP). The latter is a hallucinogenic amphetamine congener (see previous section). The piperidine derivatives ketamine and phencyclidine are also hallucinogens. Use of LSD peaked in the 1960s and then waned, with reemergence in the 1990s among high school students.106 It is sold in thin gelatin squares, on colored paper, or as tablets that may be crushed. LSD is commonly taken orally. Symptoms begin 30 to 90 minutes after ingestion, and persist for 2 to 4 hours. There is no clinically useful laboratory test for detection. There is a wide variation in clinical effect, but the most common experience is altered visual perception, including the unusual description of crossed sensory experience, or synesthesia, in which the subject believes he or she can smell a color or see a sound.107 Sympathomimetic effects such as mydriasis, flushing, tremor, hyperthermia, tachycardia, hypertension, and piloerection are seen, and a syndrome resembling neuroleptic malignant syndrome has been described.108 Depression, mood swings, and altered body perception may occur. Persistent or recurrent perceptual alterations, or “flashbacks,” are reported, and LSD may exacerbate preexisting psychosis.109 Panic attacks or “bad trips” are the most common reason for presentation to the emergency department. Most patients who present after LSD ingestion may be managed conservatively. There is no antidote, and elimination techniques are not of assistance. Vital signs should be monitored and the presence of other intoxicants ruled out. Patients with psychotic reactions frequently may be managed by removal to quiet surroundings and verbal reassurance. Benzodiazepines may occasionally be of use, but phenothiazines may potentiate seizures and has been associated with cardiovascular collapse.110,111 Clonazepam may be of assistance in the management of persistent hallucinations.112 “Club Drugs” A group of drugs has become popular at all-night dance parties called “raves.” The so-called club drugs are used recreationally in social settings, frequently among young people.113 Among them are MDMA (see earlier), phencyclidine, ketamine, GHB, and flunitrazepam. They are considered safe by the population of individuals who use them, and consumption, especially of Ecstasy, is increasing among adolescents, as reported by the Drug Awareness Warning Network and the Monitoring the Future studies.114 Ketamine and Phencyclidine Phencyclidine and ketamine are related piperidine derivatives with analgesic, amnestic, and dissociative properties.

959

Both have been used as anesthetic agents, and ketamine is still widely used for procedural sedation. They are termed dissociative, in that the patient may remain semiconscious but indifferent to surroundings.115 Phencyclidine was first synthesized in the 1950s and appeared as a substance of abuse in the 1970s. It is commonly sold as a powder or pill that is ingested, or laced in marijuana and smoked. Impurities such as benzocaine, ephedrine, caffeine, and other piperidine derivatives are common.116 Ketamine may be smoked or taken orally or intravenously. It is formulated for legal use as an intravenous drug, and entry to the illicit market is by diversion from legitimate sources. Pediatric intoxication after accidental ingestion has been reported.117 Phencyclidine and ketamine may be detected by a urinary immunofluorescent assay that is both sensitive and relatively specific. Phencyclidine and ketamine are agonists of N-methyl-daspartate, an excitatory neurotransmitter. A typical dose of phencyclidine is 0.01 mg/kg, which causes distorted body image and a sense of depersonalization; 10 mg causes total disorientation and catatonic stupor. Ketamine is given in doses typically of 1 mg/kg, which causes stupor and depersonalization. Higher doses are associated with progressive unconsciousness and respiratory arrest. Patients present with a combination of central nervous system stimulation and depression, as well as cholinergic and anticholinergic effects. Nystagmus, often rotatory, and hypertension are the most commonly noted findings.118 Miosis, an unusual finding in association with an excitatory drug, may be observed. Patients present with confusion, disorientation, agitation, or violence and behavior indistinguishable from acute schizophrenia.119,120 The level of consciousness may vary from alert to comatose. Hypertension, hyperthermia, and rigidity with opisthotonus may occur but are rarely severe. Rhabdomyolysis may attend violent behavior in both ketamine and phencyclidine abuse.121,122 Death in phencyclidine intoxication is commonly due to behavioral mishap, such as violent trauma, suicide, or bizarre behavior.123 Asphyxial death attendant to the restraint of a violent or uncooperative patient has been reported.124 A prior history of psychiatric disease is common among fatal cases.113 The management of phencyclidine and ketamine intoxication is supportive. There is no antidote, and elimination techniques are of little value. Accidental therapeutic administration of ketamine in as much as 100 times the intended dose has been associated with a favorable outcome.125 Comatose patients, or those with depressed respirations, should undergo intubation. The avoidance of depolarizing muscle relaxants that may transiently raise vagal tone or exacerbate hyperthermia seems prudent. Physical restraint of the severely agitated or combative patient should be avoided; a nonthreatening environment and chemical restraint would be better utilized, a benzodiazepine being the drug of choice. Rhabdomyolysis should be managed with intravenous fluids and attention to electrolyte balance. Patients should be observed for several hours until the return of normal mental status. Rhabdomyolysis, seizures, persistent psychosis, or injuries are indications for hospitalization. In a series of 20 patients presenting to the emergency department after ketamine abuse, 18 were discharged from the emergency department without admission.122

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SECTION IV — Approach to the Acutely Ill Patient

Flunitrazepam Flunitrazepam, marketed as Rohypnol, is a potent benzodiazepine that is marketed legally in South America, although its sale in the United States and Canada has been restricted. It is 10 times as potent as diazepam, and shares amnestic properties with other benzodiazepines.126 Its potency and ability to produce amnesia has led to its misuse in facilitating sexual assault, giving it the reputation of being a “date rape drug.”127,128 It is available under a variety of street names including “rookie,” “circle,” “rope,” and “forget-me,” as a 1or 2-mg scored pill that may be colored to obscure its identity. The pills are inexpensive, and thus thought of as a “cheap high.” They are imported illegally through the mail, and are acquired over the Internet from offshore sources. Although benzodiazepines may be detected by urine screen, flunitrazepam is generally taken at a dose below the detection limits of most assays.129 At low doses, flunitrazepam is an anxiolytic, muscle relaxant, and sedative-hypnotic. At higher doses, behavioral inhibition, amnesia, and unconsciousness occur, as may respiratory depression. Its effects are potentiated by the concurrent use of alcohol. Disinhibition may lead to motor vehicle accidents, other trauma, violent behavior, or sexual assault,130 and flunitrazepam has been implicated in the occurrence of violent crime.131 Fatal intoxication has been reported with the concurrent use of alcohol; rarely, death associated solely with the ingestion of flunitrazepam may occur.52 Management of flunitrazepam intoxication is largely supportive. Neurologic impairment, amnesia, and respiratory depression, which may begin as early as 30 minutes after ingestion, generally last for 8 to 12 hours and are dose related.132 Support of the patient with a jeopardized airway is indicated. Gastric lavage and activated charcoal are likely to be of little benefit, unless the patient presents shortly after the ingestion. The benzodiazepine antagonist flumazenil may reverse respiratory depression, but should be used with caution as it may precipitate benzodiazepine withdrawal, manifested as tremor, irritability, and seizures.133 Supportive care with airway protection and mechanical ventilation until the patient is fully awake is the safest approach. g-Hydroxybutyrate GHB was introduced to the mass market as a dietary supplement that could enhance muscle growth. Reports of intoxication and death appeared soon thereafter.134,135 Sale as a dietary supplement was restricted, but reports began appearing in 1997 of its use as a rave drug. Of 72 patients in a reported cohort, 20 were admitted to intensive care with coma or apnea; there was one death.136 Its reputation for increasing libido and producing amnesia increased its popularity. The prior restriction of its sale resulted in the appearance of two congeners, γ-butyrolactone (GBL) and 1,4-butanediol (1,4BD) with similar properties. It is easily manufactured, and instructions for production can be obtained on the Internet.137 In addition to increasing reports of acute toxicity, it has been recognized, along with flunitrazepam, as a date or acquaintance rape drug.128 GHB is a naturally occurring analogue of GABA, an inhibitory neurotransmitter. It is supplied as a white powder that has a soapy taste when dissolved. It is rapidly absorbed after

oral administration, and effects are observed within 15 to 30 minutes. There is no clinically useful laboratory assay detection or confirmation of the poisoning. Central nervous system effects include euphoria, headache, dizziness, ataxia, miosis, and hallucinations. The effect is dose dependent, and at higher doses euphoria gives way to somnolence and coma. Apnea is rare, but vomiting and salivation are common.138 Seizures have occasionally been noted. A withdrawal syndrome consisting of toxic psychosis, severe agitation, and seizures has been reported139 after compulsive repeated use.140 There is no antidote for GHB intoxication. Most patients may be treated supportively. Induced emesis is contraindicated because of the possibility of rapidly occurring loss of consciousness or seizures. There are no data on the use of activated charcoal or gastric lavage, but neither is likely to be effective in a symptomatic intoxication. Comatose patients should have their airway protected. Evacuation of the stomach by nasogastric suction may offer some protection against aspiration. Seizures may be treated with benzodiazepines. Most patients recover within 8 hours. There is no consensus on the treatment of GHB withdrawal syndrome, but high-dose benzodiazepines and barbiturates have been advocated. Inhalants The abuse of volatile substances is appealing to the drugseeking adolescent. Inhalation is associated with rapid onset and predictable euphoria, quickly dissipating, which allows the child to engage in the practice while unobserved. They are often legally obtained, readily available, and inexpensive. A national annual survey of drug abuse trends among schoolchildren has reported that the lifetime prevalence of inhalant abuse among 8th graders is 20%. The only more commonly abused substances are nicotine and alcohol.141 A wide variety of inhalant substances and sources are reported (Table 135–6).

Table 135–6

Commonly Abused Volatile Substances

Family

Substance

Source

Aliphatic hydrocarbons

Propane Butane Gasoline n-Hexane

Alkyl halides

1,1,1-Trochloroethane

Bottled fuel Cigarette lighter fluid Automotive fuel Model glue, rubber cement Correction fluid, degreaser Dry cleaning fluid Freon refrigerant Paint stripper Resins, varnishes Spray paint, glues Paint thinner, glue Mothballs Solvent Nail polish remover Adhesives Paint Spray paint Room air freshener Coronary vasodilator Whipped cream

Aromatic hydrocarbons Ethers Ketones

Nitrogen oxides

Trichloroethylene Trichorofluromethane Dichlormethane Benzene Toluene Xylene Naphthalene Diethyl ether Actone Butanone Methyl n-butyl ketone Methyl isobutyl ketone Butyl/isobutyl nitrite Amyl nitrate Nitrous oxide

Chapter 135 — Drugs of Abuse

Inhalants are often abused by a group, but may be engaged in as a solitary activity. Typically, the agent is sprayed into a bag, which is placed over the face and inhaled (so-called “bagging”), or sprayed into a rag, which is then placed over the face (“huffi ng”). Some agents are supplied in characteristic dispensers such as whippets or glass beads (see below). Intoxicated individuals frequently present with altered mental status, rendering history difficult, but the identification of an offending substance may be facilitated by inquiring among others present, or an inspection of the surroundings. Emergency medical services personnel should be instructed to retrieve items such as paint cans, rags, or other paraphernalia. These items, along with the patient’s clothing, should be brought in an airtight container along with the patient. Examination of the patient may be of assistance: the child may have a suggestive odor, or the presence of residue such as paint or correction fluid on the face. Mucous membrane irritation, especially perioral (termed a “huffer’s rash”), and swelling may be present. Cyanosis unresponsive to oxygen therapy suggests methemoglobinemia secondary to nitrite abuse. Inhalant abuse is a hazardous activity. Death, although uncommon, may result from cardiac arrhythmia or asphyxia.142 Severe burns have been reported after ignition of a volatile substance concurrent with cigarette smoking.143 Sudden death is associated with the abuse of butane, propane, and halogenated hydrocarbons. It has been attributed to the sensitization of myocardium to circulating catecholamines,144 and is suggested by the history of cardiac arrest following vigorous physical activity after inhalant abuse. Most recently, it has been described with the abuse of typewriter correction fluid, which contains 1,1,1-trichloroethylene, and spray containers using Freon propellants.145,146 Solvent inhalation generally produces central nervous system depression, which may impair ventilation and airway reflexes. Subjective effects and symptoms are dose dependent and are subject to considerable individual variation. Patients may be lethargic, disinhibited, ataxic, dysarthric, or comatose.147 Hallucinations may occur. Seizures have been reported.148 The duration of symptoms is dependent on the individual agent. Most solvents produce euphoria after 15 to 20 inhalations. Rebreathing the substance by bagging may produce hypoxia that enhances its effects.149 Duration of symptoms depends on the lipid solubility of the substance. Gasoline sniffing will produce sedation for as long as 8 hours. Patients may wake with headache, dizziness, palpitations, vomiting, and weakness. These symptoms, although unpleasant, are rarely life threatening. Tolerance to the acute effects of hydrocarbon inhalants, especially with toluene and 1,1,1trichloroethylene abuse, has been described after as little as 3 months’ regular use.150-152 An acute withdrawal syndrome characterized by tremor, agitation, insomnia, and delirium tremens has also been described.153 Acute methylene chloride exposure may produce the unique problem of carboxyhemoglobinemia, developing hours after exposure, as a consequence of carbon monoxide generated in its metabolism.154 Chronic solvent inhalant abuse produces a wide range of organ system injuries, summarized in Table 135–7. The most common neurologic sequelae are polyneuropathy and dementia.155-158 Gasoline sniffing presents unique problems. The chronic multifocal polyneuropathy associated with its chronic abuse may worsen after cessation of the practice.159

Table 135–7

Chronic Effects of Inhalant Abuse

Organ System

Manifestation

Associated with:

Neurologic

Cerebellar ataxia Electroencephalographic slowing Peripheral neuropathy Trigeminal neuralgia Parkinsonism Dementia, memory loss Renal tubular acidosis Myocarditis Chemical pneumonitis Emphysema Chemical hepatitis

Toluene n-Hexane

Psychiatric Renal Cardiovascular Pulmonary Hepatotoxicity Hematologic

961

Carboxyhemoglobinemia Leukemia, aplastic anemia

n-Hexane 1,1,1-Trichloroethylene Gasoline additive Multiple Toluene Gasoline Multiple Gasoline Chlorinated hydrocarbons Methylene chloride Benzene

Adapted from Brouette T, Anton R: Clinical review of inhalants. Am J Addict 10:79–94, 2001.

Additionally, acute and chronic lead encephalopathy has been reported.160 Volatile Nitrogen Oxides Nitrous oxide, still used as an anesthetic gas, has been increasingly reported as a drug of abuse. As many as 10% of adolescent youths in some populations may use nitrous oxide regularly; one third of adolescents surveyed at a correctional institution reported use, beginning at a median age of 13 years.161 It is readily available in health care facilities and restaurants, but in the pediatric population it has been obtained in the form of “whippets,” which are sold for the production of whipped cream. They can be obtained at grocery stores and at specialty shops specializing in drug paraphernalia, often sold with a device to puncture and evacuate the canister. The gas is expended into a balloon, which may be passed around in a group setting. Many first-time users experience nausea, chest tightness, or no effect; however, some report a sense of dreamlike anesthesia shortly after inhalation. Nitrous oxide, like other inhaled drugs of abuse, readily crosses the alveolus to the bloodstream and thereafter penetrates the blood-brain barrier. After termination of exposure, nitrous oxide in the bloodstream is rapidly excreted by the lungs. Its lifetime in the central nervous system is longer than its circulatory half-life. It has the reputation of being a clean and safe drug, but deaths, principally in the workplace, have been reported,162 attendant to asphyxia during the inhalation of high concentrations. Death has not been reported with the use of nitrous oxide whippets; however, impaired driving skills were observed after brief recreational exposure.163 Chronic intermittent inhalation has been associated with a diffuse polyneuropathy, commonly more sensory than motor, which is caused by inactivation of vitamin B12. Ataxia and lower extremity weakness are often noted.164,165 Megaloblastic anemia, leukopenia, and thrombocytopenia are also occasionally observed.166 Organic nitrites have been abused by inhalation since the 1970s, when they acquired the reputation of being a sexual stimulant, particularly among homosexuals. Popularity

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SECTION IV — Approach to the Acutely Ill Patient

waned with their unproven association with the acquisition of acquired immunodeficiency syndrome. Similarly, an alleged association of nitrite abuse with Kaposi’s sarcoma is unproven, and is more likely the result of promiscuous unprotected sex.167 Abuse of amyl nitrate and butyl nitrite, although less common than in the past, continues to be occasionally seen. Amyl, butyl, and isobutyl nitrite are potent vasodilators and have narcotic effects similar to nitrous oxide. Alkyl nitrites are also found as the propellant in a variety of cleaning products and sold as a “locker room deodorant,” to be bagged or huffed. Amyl nitrite is distributed in glass beads called “poppers,” which are broken and the contents inhaled. Inhalation is accompanied by sexual arousal and a dreamy, euphoric state. Onset is within seconds, but the effect last only minutes. The pattern of abuse is repeated inhalation, often dozens of times. Patients may present with flushing reactions that can be attributed to nitrite-induced vasodilation or allergy. The principal severe toxicities associated with volatile nitrite abuse, however, are consequent to oxidative stress, as nitriteinduced methemoglobin formation may overwhelm NADHand NADPH-dependent reduction pathways. Hemolytic anemia, often associated with congenital glucose-6phosphate dehydrogenase (G6PD) deficiency, has been reported.168 Methemoglobinemia is rare but may be life threatening. The diagnosis is suggested by the presentation of cyanosis unresponsive to 100% oxygen, and is confirmed by co-oximetry. Pulse oximeters do not detect methemoglobin and may falsely report satisfactory oxygen saturation in the presence of severe disease. Manifestations are those of acute anemia. Symptomatic tachycardia develops with a methemoglobin level over 30%. Neurologic symptoms, including headache, lethargy, and coma, are noted at a level over 55%. Arrhythmias and cardiovascular collapse occur at this level, and a concentration over 70% is frequently fatal. Symptomatic patients should be treated with methylene blue, 1 to 2 g of 1% solution.169 Unresponsiveness to therapy may indicate G6PD deficiency. Occasionally, exchange transfusion may be required. Miscellaneous Agents Over-the-Counter Drugs Over-the-counter medications are frequently abused by children and adolescents. A recent report from the Utah poison control system identified 2214 contacts over a 10-year period, asserting the inappropriate use of medications by children 6 to 19 years old.170 Most common among them were the anticholinergic decongestants, caffeine, dextromethorphan, and stimulants.38 Two thirds of the children were brought to a health care facility. There were no deaths. Caffeine is a methylxanthine, chemically related to theophylline and a ubiquitous substance in the Western diet. Caffeine is a stimulant that elevates blood pressure, pulse, and respiratory rate. It is used clinically in the management of neonatal apnea. At doses near therapeutic, it may produce palpitations, sweating, and a sense of anxiety. In overdose, tremors, fasciculations, and seizures are observed. Fatal caffeine poisoning has been reported.171 Caffeine dependence in childhood has been described, and a withdrawal syndrome consisting of somnolence and a decline in motor perfor-

mance 24 hours after the discontinuation of caffeinated beverages has been recognized.172 The acutely poisoned patient should be observed for the abrupt onset of seizures. Peritoneal dialysis was reported to be effective in accelerating the removal of caffeine from one seriously poisoned child.173 Ephedrine and pseudoephedrine are noncatecholamine stimulants chemically related to amphetamines, with biologic effects similar to that group of compounds. Ephedrine is a naturally occurring alkaloid and has been sold in herbal form (see later). It was sold as an over-the-counter stimulant, anorectic, and bronchodilator. Its sale was prohibited in 2004 after a series of deaths were reported,174 but it is still available by mail order from offshore sources. Pseudoephedrine is present in many decongestants, frequently with diphenhydramine or dextromethorphan, and is still widely sold. Both are abused by adolescents for their stimulant properties and as anorectic agents. Like caffeine, they are sold under the misrepresentation of being other illicit substances. At therapeutic doses, both ephedrine and pseudoephedrine produce tachycardia, hypertension, increased respirations, sweating, salivation, mydriasis, nausea, and palpitations. Tolerance develops rapidly, and increasing doses are required for the user to achieve the desired effect. The urine drug screen for amphetamines may be positive, rendering the distinction from methamphetamine or MDMA intoxication difficult. In acute overdose, arrhythmias, myocardial infarction, hypertension, hyperpyrexia, seizures, and death have been reported.175 A chronic dilated cardiomyopathy has been reported in adolescents using ephedrine as an anorectic.176-178 An acute toxic psychosis has been reported in children ingesting the combination of pseudoephedrine and dextromethorphan.179,180 An abstinence syndrome consisting of excessive somnolence and lethargy has been recognized.181 Dextromethorphan is a semisynthetic opioid with poor analgesic properties used commonly as a cough suppressant (e.g., Coricidin Cough and Cold whose street name is triple C’s). It is commonly sold in combination with acetaminophen, diphenhydramine, or pseudoephedrine. Sedation and relaxation are noted at recommended doses, but increasing amounts are associated with hallucinations and psychosis.182 The serotonin syndrome, consisting of confusion, ataxia, hyperthermia, and rigidity, has been associated with the use of dextromethorphan.183 The abuse potential of dextromethorphan has been long recognized.184 Dependence and death have been also associated with abuse.185 Recently, reports have appeared suggesting the increased abuse of Coricidin HBP, apparently because of its high dextromethorphan content.186 In 92 reported patients, the most common symptoms were tachycardia, hypertension, lethargy, mydriasis, agitation, ataxia, and dizziness. Most patients were treated in the emergency department and released. All patients recovered. Diphenhydramine, an antihistamine, is a common constituent of cough and cold remedies and is also sold as a sleep aid. Literally hundreds of over-the-counter formulations exist. Much of its therapeutic potential is obtained from its anticholinergic potential. Dry mouth, tachycardia, sedation, and mydriasis are observed. Its abuse potential has been long recognized,185,187 and unintentional intoxication in the therapeutic setting has been reported.188 Diphenhydramine has been used in intentional poisoning of children.189 A syndrome of diphenhydramine dependence has been recently recognized,190 and chronic abuse may manifest as adolescent

Chapter 135 — Drugs of Abuse

depression.68 Diphenhydramine is commonly taken orally, but it may occasionally be used intravenously or smoked with marijuana.191 In overdose, diphenhydramine produces symptoms of acute anticholinergic poisoning: fever, seizures, coma, agitation, toxic psychosis, and tachyarrythmias. A wide-complex tachycardia resembling torsades de pointes may be observed.192 There is no clinically useful laboratory assay, and the diagnosis must be made by history and physical examination with a high index of suspicion. Most patients recover with conservative management. Benzodiazepines may be used for agitation and seizures. Bicarbonate has been reported to be therapeutic in the treatment of wide-complex tachycardia. The use of physostigmine as an antidote for anticholinergic poisoning is controversial but has been reported effective.193,194 Its use is contraindicated if tricyclic antidepressant poisoning is considered in the differential diagnosis of the intoxicated child.

963

FIGURE 135–4. Wild ginseng.

Botanicals and Natural Products A wide variety of naturally occurring products are used as alternative medical therapies and substances of abuse. Many herbal remedies are available as dietary aids at health food stores and sold as stimulants, appetite suppressants, antidepressants, and dietary aids. They are subject to limited regulation, and neither purity nor safety nor consistent formulation can be assured. Common contaminants of herbal products include pesticides, metals, orthodox drugs such as phenylbutazone or salicylate, and microbial substances and toxins.195 Some substances of abuse are harvested as wild or locally grown plants. It is beyond the scope of this chapter to comprehensively review the botanical substances of abuse, but those of importance to the pediatric emergency physician are presented herein. Ephedrine, a precursor of methamphetamine, is the active alkaloid of the plant Ephedra vulgaris, which has been used in China for centuries as the herb Ma Huang. Ma Huang was extensively marketed as a stimulant and weight loss product, and is popular among adolescents. In this formulation, it was subject to the variations in purity and potency of other herbal products. Its sale, and that of other ephedrine-containing products, has recently been restricted by the Food and Drug Administration after the appearance of reports of adverse cardiovascular events, including stroke, myocardial infarction, and sudden death.175,196 The acute toxicity of ephedracontaining compounds is similar to that of other stimulants. Patients are restless, agitated, diaphoretic, tachycardic, and often hypertensive. Mydriasis is common. Seizures and unresponsiveness have been reported.197 A toxic psychosis has been reported.198 Chronic effects including vasculitis, myocarditis, hepatotoxicity, and a fi xed drug eruption have been reported with the use of Ma Huang, possibly the result of unidentified additives to the preparation.199-201 Ginseng is prepared from the root of Panax quinquefolium, and is advocated as a stimulant and general aid to well-being (Fig. 135–4). The active ingredients are poorly characterized saponins. It is widely popular and supplied as herbal tea, chewing gum, and dietary supplements. Few medical problems have been described specifically; however, a syndrome of hypertension, restlessness, and diarrhea has been attributed to heavy use.202 Many decorative and wild plants are sought as drugs of abuse. Two such common agents are angel’s trumpet and

FIGURE 135–5. Angel’s trumpet.

jimsonweed. They are related Datura species, and both are cultivated as a decorative plant and grow as weeds. Synonyms are “devil’s weed,” and “thorn apple,” and they contain solanine alkaloids that are potent anticholinergic substances. They appear as graceful, trumpet-shaped yellow or white flowers becoming thorny seedpods in the autumn (Figs. 135– 5 and 135–6). All parts of the plant are toxic. It is commonly harvested, dried, and either smoked or ingested as a soup or tea. Intoxicated patients present with agitation, delirium, hyperthermia, dry mouth, tachycardia, and mydriasis.203 In a reported series of 35 patients, all had mydriasis, 88% had delirium, and 33% had tachycardia. Symptoms were prolonged (18 to 29 hours). No patient had seizures or arrhythmias, and none died.204 Conservative management, with sedation and occasionally airway protection, is indicated. In

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FIGURE 135–6. Jimsonweed.

A

B FIGURE 135–8. A and B, Psilocybe mushrooms. FIGURE 135–7. Morning glory.

one reported case of severe anticholinergic syndrome secondary to angel’s trumpet abuse, physostigmine was of benefit.205 Several botanical agents are used for their hallucinogenic properties. Among these are the morning glory, mimosa, and peyote cactus. The seeds of the morning glory, of the Convolvulaceae family, produce an alkaloid similar to LSD that causes altered perception and hallucinations when ingested (Fig. 135–7). The seeds are first obtained from the mature plant or in garden supply stores. They are ground, soaked, and fi ltered before consumption. Synesthesia, visual hallucinations, and mydriasis are common signs and symptoms. The effect lasts about 60 minutes.206 Medical complications are rare, and death has not been reported.207 Dimethyltryptamine is a serotonin agonist contained in snuff manufactured from the seeds and bark of Justia pectoralis, Mimosa hostilis, and other plants. They are collected wild and are available by mail order. Abuse is by inhalation of the ground powder or by smoking. Intoxication closely resembles LSD. The treatment is supportive. Pharmacologic management of agitation may be undertaken with benzodiazepines. A powder ground from the seeds of the spice nutmeg is used as a hal-

lucinogen similar to LSD. Myristicin, the active alkaloid, is present in a concentration of 0.2 mg/g of spice. Ingestion of 5 g of ground nutmeg induces hallucinations and arousal.208 Symptoms are said to resemble acute anticholinergic poisoning, with mydriasis, tachycardia, palpitations, and a feeling of impending doom.209 Uncomplicated recovery with supportive care is the rule, but death, presumably secondary to tachyarrythmia, has been reported.210 The use of mushrooms and cactus as hallucinogenic agents dates back to antiquity. Psilocybe cubensis is found in moist southeastern climates and produces the alkaloids psilocybin and psilocin, which closely resemble dimethyl tryptamine, a serotonin analogue (Fig. 135–8). The active agent is stable and retains potency when boiled. It is foraged by amateur mushroom hunters and is sold as a street drug frequently misrepresented as LSD. It is commonly ingested as a soup or tea, but occasionally has been abused intravenously.211 Ingestion is accompanied by symptoms closely resembling those of other hallucinogens, with hallucinations, altered color perception, tachycardia, hypertension, and mydriasis. Patients may present with an agitated delirium or paranoid delusions. Symptoms begins shortly after ingestion and last

Chapter 135 — Drugs of Abuse

3 to 4 hours. Medical complications are rare, but convulsions and myocardial infarction have been reported.212,213 A principal danger is the misidentification of a more toxic species, such as Amanita species.214 Treatment is supportive. An attempt should be made to formally identify the mushroom if it is available. Peyote is the common name of the cactus Lophophora williamsii, from which the active alkaloid, mescaline, is extracted. It grows wild in the Southwest and is still used legally in religious ceremonies. As a drug of abuse, it is produced from buttons of the dried cactus, which are consumed as a tea. It is often misrepresented as LSD or phencyclidine. Effects begin 30 minutes after ingestion. A gastrointestinal phase is accompanied by nausea, vomiting, diaphoresis, and mydriasis, to be followed by a psychoactive phase closely resembling that of LSD. Prolonged psychosis and fatal intoxication have been reported.215,216 Treatment is once again supportive. Pharmacologic management of agitation is better accomplished with benzodiazepines rather than phenothiazines, which may contribute to hyperpyrexia.217 Anabolic Steroids Not all drugs are abused for their mind-altering properties. Androgenic steroids are frequently used by athletes to increase muscle mass and improve performance. They are structurally related to testosterone, and, in addition to masculinization, increase muscle mass (anabolism). Their use has increased among adolescents seeking to improve athletic performance. Two recent surveys of high-school children reported prevalence of anabolic steroid use in all students as 2.8% and 5.8%. One third of those who admitted use indicated that they abused these drugs parenterally.218 The use of anabolic agents, along with stimulants, hormones such as erythropoietin and growth hormone, and blood doping, is officially proscribed. In 1990, Congress enacted the Anabolic Steroid Control Act, which placed them on Schedule III of controlled substances, but acquisition is easily accomplished through illicit sources. Surreptitious use is accomplished by taking them in cycles to avoid detection. Athletes tend to use more than one agent and cycle their use to modulate drug tolerance. Numerous complications of anabolic steroid use have been reported and include toxic hepatitis, overuse injuries, gynecomastia, cerebral hemorrhage, and pulmonary embolism.219-223 Anabolic steroids lower high-density lipoprotein and increase platelet adhesiveness. Cardiac effects include myocardial infarction and sudden death.224 Athletes who parenterally abuse anabolic steroids are subject to the infectious and noninfectious complications of nonsterile administration, including hepatitis, HIV, and abscesses, but at a rate that may be lower than that of intravenous drug users.225 REFERENCES *1. Comerci GD, Schwebel R: Substance abuse: an overview. Adolesc Med 11:79–101, 2000. 2. Newcomb MD: Identifying high-risk youth: prevalence and patterns of adolescent drug abuse. NIDA Res Monogr 156:7–38, 1995. 3. Du Mont J, Parnis D: The doctor’s dilemma: caregiving and medicolegal evidence collection. Med Law 23:515–529, 2004. 4. Hoyt CA: Evidence recognition and collection in the clinical setting. Crit Care Nurs Q 22:19–26, 1999. *Selected readings.

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153. Henretig F: Inhalant abuse in children and adolescents. Pediatr Ann 25:47–52, 1996. 154. Horowitz BZ: Carboxyhemoglobinemia caused by inhalation of methylene chloride. Am J Emerg Med 4:48–51, 1986. 155. Ashton CH: Solvent abuse. BMJ 300:135–136, 1990. 156. Filley CM, Halliday W, Kleinschmidt-DeMasters BK: The effects of toluene on the central nervous system. J Neuropathol Exp Neurol 63:1–12, 2004. 157. Fornazzari L, Pollanen MS, Myers V, Wolf A: Solvent abuse-related toluene leukoencephalopathy. J Clin Forensic Med 10:93–95, 2003. 158. Hormes JT, Filley CM, Rosenberg NL: Neurologic sequelae of chronic solvent vapor abuse. Neurology 36:698–702, 1986. 159. Burns TM, Shneker BF, Juel VC: Gasoline sniffi ng multifocal neuropathy. Pediatr Neurol 25:419–421, 2001. 160. Fortenberry JD: Gasoline sniffi ng. Am J Med 79:740–744, 1985. 161. McGarvey EL, Clavet GJ, Mason W, Waite D: Adolescent inhalant abuse: environments of use. Am J Drug Alcohol Abuse 25:731–741, 1999. 162. Suruda AJ, McGlothlin JD: Fatal abuse of nitrous oxide in the workplace. J Occup Med 32:682–684, 1990. 163. Moyes D, Cleaton-Jones P, Lelliot J: Evaluation of driving skills after brief exposure to nitrous oxide. S Afr Med J 56:1000–1002, 1979. 164. Diamond AL, Diamond R, Freedman SM, Thomas FP: “Whippets”induced cobalamin deficiency manifesting as cervical myelopathy. J Neuroimaging 14:277–280, 2004. 165. Miller MA, Martinez V, McCarthy R, Patel MM: Nitrous oxide “whippit” abuse presenting as clinical B12 deficiency and ataxia. Am J Emerg Med 22:124, 2004. 166. Temple WA, Beasley DM, Baker DJ: Nitrous oxide abuse from whipped cream dispenser chargers. N Z Med J 110:322–323, 1997. 167. Romanelli F, Smith KM, Thornton AC, Pomeroy C: Poppers: epidemiology and clinical management of inhaled nitrite abuse. Pharmacotherapy 24:69–78, 2004. 168. Neuberger A, Fishman S, Golik A: Hemolytic anemia in a G6PDdeficient man after inhalation of amyl nitrite (“poppers”). Isr Med Assoc J 4:1085–1086, 2002. 169. Coleman MD, Coleman NA: Drug-induced methaemoglobinaemia: treatment issues. Drug Saf 14:394–405, 1996. 170. Crouch BI, Caravati EM, Booth J: Trends in child and teen nonprescription drug abuse reported to a regional poison control center. Am J Health Syst Pharm 61:1252–1257, 2004. 171. Shum S, Seale C, Hathaway D, et al: Acute caffeine ingestion fatalities: management issues. Vet Hum Toxicol 39:228–230, 1997. 172. Bernstein GA, Carroll ME, Dean NW, et al: Caffeine withdrawal in normal school-age children. J Am Acad Child Adolesc Psychiatry 37:858–865, 1998. 173. Walsh I, Wasserman GS, Mestad P, Lanman RC: Near-fatal caffeine intoxication treated with peritoneal dialysis. Pediatr Emerg Care 3:244–249, 1987. 174. Centers for Disease Control and Prevention: Adverse events associated with ephedrine-containing products—Texas, December 1993– September 1995. MMWR Morb Mortal Wkly Rep 45:689–693, 1996. 175. Haller CA, Benowitz NL: Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 343:1833–1838, 2000. 176. Naik SD, Freudenberger RS: Ephedra-associated cardiomyopathy. Ann Pharmacother 38:400–403, 2004. 177. To LB, Sangster JF, Rampling D, Cammens I: Ephedrine-induced cardiomyopathy. Med J Aust 2:35–36, 1980. 178. Roberge RJ, Hirani KH, Rowland PL 3rd, et al: Dextromethorphanand pseudoephedrine-induced agitated psychosis and ataxia: case report. J Emerg Med 17:285–288, 1999. 179. Hall RC, Beresford TP, Stickney SK, et al: Psychiatric reactions produced by respiratory drugs. Psychosomatics 26:605–608, 615–616, 1985. 180. Sauder KL, Brady WJ Jr, Hennes H: Visual hallucinations in a toddler: accidental ingestion of a sympathomimetic over-the-counter nasal decongestant. Am J Emerg Med 15:521–526, 1997. 181. Loosmore S, Armstrong D: Do-Do abuse. Br J Psychiatry 157:278–281, 1990. 182. Price LH, Lebel J: Dextromethorphan-induced psychosis. Am J Psychiatry 157:304, 2000. 183. Bodner RA, Lynch T, Lewis L, Kahn D: Serotonin syndrome. Neurology 45:219–223, 1995.

184. Craig DF: Psychosis with Vicks Formula 44-D abuse. CMAJ 146:1199– 1200, 1992. 185. Murray S, Brewerton T: Abuse of over-the-counter dextromethorphan by teenagers. South Med J 86:1151–1153, 1993. 186. Banerji S, Anderson IB: Abuse of Coricidin HBP cough & cold tablets: episodes recorded by a poison center. Am J Health Syst Pharm 58:1811–1814, 2001. 187. Brown JH, Sigmundson HK: Delirium from misuse of dimenhydrinate. Can Med Assoc J 101:49–50, 1969. 188. McGann KP, Pribanich S, Graham JA, Browning DG: Diphenhydramine toxicity in a child with varicella: a case report. J Fam Pract 35:210, 213–214, 1992. 189. Arnold SM, Arnholz D, Garyfallou GT, Heard K: Two siblings poisoned with diphenhydramine: a case of factitious disorder by proxy. Ann Emerg Med 32:256–259, 1998. 190. Cox D, Ahmed Z, McBride AJ: Diphenhydramine dependence. Addiction 96:516–517, 2001. 191. Brower KJ: Smoking of prescription anticholinergic drugs. Am J Psychiatry 144:383, 1987. 192. Farrell M, Heinrichs M, Tilelli JA: Response of life threatening dimenhydrinate intoxication to sodium bicarbonate administration. J Toxicol Clin Toxicol 29:527–535, 1991. 193. Padilla RB, Pollack ML: The use of physostigmine in diphenhydramine overdose. Am J Emerg Med 20:569–570, 2002. 194. Rinder CS, D’Amato SL, Rinder HM, Cox PM: Survival in complicated diphenhydramine overdose. Crit Care Med 16:1161–1162, 1988. 195. Chan K: Some aspects of toxic contaminants in herbal medicines. Chemosphere 52:1361–1371, 2003. 196. Samenuk D, Link MS, Homoud MK, et al: Adverse cardiovascular events temporally associated with ma huang, an herbal source of ephedrine. Mayo Clin Proc 77:12–16, 2002. 197. Kockler DR, McCarthy MW, Lawson CL: Seizure activity and unresponsiveness after hydroxycut ingestion. Pharmacotherapy 21:647– 651, 2001. 198. Walton R, Manos GH: Psychosis related to ephedra-containing herbal supplement use. South Med J 96:718–720, 2003. 199. Zaacks SM, Klein L, Tan CD, et al: Hypersensitivity myocarditis associated with ephedra use. J Toxicol Clin Toxicol 37:485–489, 1999. 200. Matsumoto K, Mikoshiba H, Saida T: Nonpigmenting solitary fi xed drug eruption caused by a Chinese traditional herbal medicine, ma huang (Ephedra hebra), mainly containing pseudoephedrine and ephedrine. J Am Acad Dermatol 48:628–630, 2003. 201. Nadir A, Agrawal S, King PD, Marshall JB: Acute hepatitis associated with the use of a Chinese herbal product, ma-huang. Am J Gastroenterol 91:1436–1438, 1996. 202. Siegel RK: Ginseng abuse syndrome: problems with the panacea. JAMA 241:1614–1615, 1979. 203. Greene GS, Patterson SG, Warner E: Ingestion of angel’s trumpet: an increasingly common source of toxicity. South Med J 89:365–369, 1996. 204. Isbister GK, Oakley P, Dawson AH, Whyte IM: Presumed Angel’s trumpet (Brugmansia) poisoning: clinical effects and epidemiology. Emerg Med (Fremantle) 15:376–382, 2003. 205. Hall RC, Popkin MK, McHenry LE: Angel’s trumpet psychosis: a central nervous system anticholinergic syndrome. Am J Psychiatry 134:312–314, 1977. 206. Brady ET Jr: A note on morning glory seed intoxication. Am J Hosp Pharm 25:88–89, 1968. 207. Whelan FJ, Bennett FW, Moeller WS: Morning glory seed intoxication: a case report. J Iowa Med Soc 58:946–948, 1968. 208. Hallstrom H, Thuvander A: Toxicological evaluation of myristicin. Nat Toxins 5:186–192, 1997. 209. Abernethy MK, Becker LB: Acute nutmeg intoxication. Am J Emerg Med 10:429–430, 1992. 210. Stein U, Greyer H, Hentschel H: Nutmeg (myristicin) poisoning— report on a fatal case and a series of cases recorded by a poison information centre. Forensic Sci Int 118:87–90, 2001. 211. Curry SC, Rose MC: Intravenous mushroom poisoning. Ann Emerg Med 14:900–902, 1985. 212. Borowiak KS, Ciechanowski K, Waloszczyk P: Psilocybin mushroom (Psilocybe semilanceata) intoxication with myocardial infarction. J Toxicol Clin Toxicol 36:47–49, 1998. 213. McCawley EL, Brummett RE, Dana GW: Convulsions from psilocybe mushroom poisoning. Proc West Pharmacol Soc 5:27–33, 1962.

Chapter 135 — Drugs of Abuse 214. O’Brien BL, Khuu: A fatal Sunday brunch: amanita mushroom poisoning in a Gulf Coast family. Am J Gastroenterol 91:581–583, 1996. 215. Brown RT, Braden NJ: Hallucinogens. Pediatr Clin North Am 34:341– 347, 1987. 216. Reynolds PC, Jindrich EJ: A mescaline associated fatality. J Anal Toxicol 9:183–184, 1985. 217. Haddad LM: Management of hallucinogen abuse. Am Fam Physician 14:82–87, 1976. 218. Melia P, Pipe A, Greenberg L: The use of anabolic-androgenic steroids by Canadian students. Clin J Sport Med 6:9–14, 1996. 219. Liow RY, Tavares S: Bilateral rupture of the quadriceps tendon associated with anabolic steroids. Br J Sports Med 29:77–79, 1995.

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220. de Luis DA, Aller R, Cuellar LA, et al: [Anabolic steroids and gynecomastia: review of the literature]. An Med Interna 18:489–491, 2001. 221. Stimac D, Milic S, Dintinjana RD, et al: Androgenic/anabolic steroidinduced toxic hepatitis. J Clin Gastroenterol 35:350–352, 2002. 222. Kennedy C: Myocardial infarction in association with misuse of anabolic steroids. Ulster Med J 62:174–176, 1993. 223. Robinson RJ, White S: Misuse of anabolic drugs. BMJ 306:61, 1993. 224. Dickerman RD, McConathy WJ, Schaller F, Zachariah NY: Cardiovascular complications and anabolic steroids. Eur Heart J 17:1912, 1996. 225. Rich JD, Dickinson BP, Feller A, et al: The infectious complications of anabolic-androgenic steroid injection. Int J Sports Med 20:563– 566, 1999.

Chapter 136 Adverse Effects of Anticonvulsants and Psychotropic Agents Paul Kolecki, MD and Richard D. Shih, MD

Key Points The side effects of anticonvulsant medications are categorized as acute or long-term adverse effects. The treatment of anticonvulsant adverse events is mainly supportive. Phenothiazine’s mechanism of action is through central and peripheral dopaminergic blockade. The management of antipsychotic adverse effects is mainly supportive.

Introduction and Background Seizures and status epilepticus (SE) are common pediatric emergencies. Approximately 60,000 patients suffer from SE annually.1 Prompt pharmacologic treatment of pediatric seizures and SE is necessary to terminate the seizures and avoid permanent and potentially fatal neurologic damage. Antipsychotics are medications used to reduce and potentially terminate hallucinations, delusions, and other mental and behavioral disturbances. Many child and adolescent psychiatrists prescribe antipsychotics on both an inpatient and outpatient basis.2 In addition, many antipsychotics may cause significant adverse effects, including death. Typical pediatric anticonvulsant agents (Table 136–1) and typical pediatric antipsychotic agents (Table 136–2) are discussed.

Selected Pediatric Overdoses Anticonvulsant agents Antipsychotic agents Phenothiazines Butyrophenones Atypical antipsychotics 970

Discussion of Individual Overdoses Anticonvulsant Agents Phenytoin (Dilantin) Phenytoin is a first-line anticonvulsant used for most seizure disorders, except for absence seizures. Phenytoin’s anticonvulsant activity stems from its ability to block neural sodium channels. Unlike the benzodiazepines and other anticonvulsants, phenytoin does not cause sedation in therapeutic doses. Phenytoin can be given orally and intravenously. Therapeutic levels are 10 to 20 mg/L. Adverse effects associated with phenytoin use can be subdivided based on acute use versus chronic use. Idiosyncratic adverse effects can also occur. Adverse effects associated with acute use include nystagmus, ataxia, dizziness, diplopia, and dyskinesia-like movements. Rapid intravenous (IV) phenytoin administration can cause significant hypotension, bradycardia, atrioventricular conduction delays, ventricular tachycardia, ventricular fibrillation, and asystole. Extravasation of IV phenytoin can produce local skin irritation, skin and soft tissue necrosis, compartment syndrome, gangrene, and amputation. A delayed bluish discoloration of the effected extremity (purple glove syndrome) followed by erythema, edema, vesicles, bullae, and local tissue ischemia, can also occur. These cardiovascular and soft tissue side effects from IV administration occur secondary to phenytoin’s diluent (propylene glycol). Adverse effects associated with long-term phenytoin use include gingival hyperplasia, facial coarsening, peripheral neuropathy, collagen disturbances, bone diseases, hypovitaminosis D, and megaloblastic anemia (secondary to folic acid deficiency). Idiosyncratic reactions include leukopenia, thrombocytopenia, aplastic anemia, agranulocytosis, and a hypersensitivity syndrome.3 The treatment of the adverse effects with both acute and chronic phenytoin use is mainly supportive. No specific antidote exists for phenytoin poisoning. Serial phenytoin levels are necessary when treating overdose patients. Activated charcoal binds phenytoin well, and multiple doses of activated charcoal should be considered for patients with rising phenytoin levels. Oral overdoses of phenytoin rarely produce

Chapter 136 — Adverse Effects of Anticonvulsants and Psychotropic Agents

Table 136–1

Pediatric Anticonvulsant Agents

Benzodiazepines (Ativan, Valium) Carbamazepine (Tegretol) Clonazepam (Klonopin) Ethosuximide (Zarontin) Felbamate (Felbatol) Fosphenytoin (Cerebyx) Gabapentin (Neurontin) Lamotrigine (Lamictal) Levetiracetam (Keppra) Oxcarbazepine (Trileptal) Phenobarbital (Luminal) Phenytoin (Dilantin) Primidone (Mysoline) Tiagabine (Gabitril) Topiramide (Topamax) Valproate (Depakote) Vigabatrin (Sabril) Zonisamide (Zonegran)

Table 136–2

Pediatric Anticonvulsant Agents

Phenothiazines Aripiprazole (Abilify) Chlorpromazine (Thorazine) Fluphenazine (Prolixin) Loxapine (Loxitane) Mesoridazine (Serentil) Molindone (Moban) Perphenazine (Trilafon) Pimozide (Orap) Thioridazine (Mellaril) Thiothixene (Navane) Trifluoperazine (Stelazine) Butyrophenones Droperidol (Inapsine) Haloperidol (Haldol) Atypicals Clozapine (Clozaril) Olanzapine (Zyprexa) Quetiapine (Seroquel) Risperidone (Risperdal) Ziprasidone (Geodon)

cardiovascular complications, thus cardiac monitoring is not routinely recommended. Admission should be considered for patients suffering severe ataxia or dizziness. Patients with mild and moderate symptoms can be discharged and observed closely by responsible individuals. Discharged patients need timely follow-up with their primary care physician and/or neurologist. Intravenous phenytoin–induced hypotension is best avoided with slow infusions ( 1000 mg/L). Patients with mild and moderate symptoms can be discharged and observed closely by responsible individuals. Discharged patients need timely follow-up with their primary care physician and/or neurologist. Gabapentin (Neurontin) Gabapentin is a derivative of the inhibitory neurotransmitter GABA and is used mainly for the treatment of partial seizures. Gabapentin levels are not readily available in most hospital laboratories. The recommended therapeutic level for seizure control is 2 to 15 mg/L. Sedation, ataxia, and slurred speech can occur after an overdose of gabapentin. Adverse effects associated with gabapentin use include somnolence, dizziness, ataxia, fatigue, nystagmus, weight gain, headache, and rhinitis.9 Compare to many other anticonvulsants, the adverse effects associated with gabapentin use are relatively benign. The treatment of gabapentin overdose is mainly supportive. No specific antidote exists. Felbamate (Felbatol) Felbamate is a sodium channel–blocking anticonvulsant. Felbamate levels are not readily available in most hospital laboratories. Overdoses may cause mild CNS depression and mild gastrointestinal irritation, and treatment is supportive. Chronic felbamate use is associated with significant hepatic toxicity and aplastic anemia.4 Lamotrigine (Lamictal) Lamotrigine is an anticonvulsant used for the treatment of partial seizures. Lamotrigine is also a sodium channel–blocking anticonvulsant. Lamotrigine levels are not readily available in most hospital laboratories. Acute poisoning with lamotrigine may cause lethargy, ataxia, nystagmus, slurred speech, and QRS prolongation. Acute pediatric lamotrigine poisoning may cause seizures.10 Chronic lamotrigine use can cause rashes, Stevens-Johnson syndrome, elevations in the hepatic aminotransferases, and elevations in creatine phosphokinase.4 The treatment of lamotrigine poisoning is supportive. Cardiac monitoring is recommended, and sodium bicarbonate may resolve QRS durations greater than 100 msec. Sei-

zures secondary to lamotrigine poisoning can be treated with benzodiazepines. Admission to a monitored unit is recommended for poisoned patients with moderate or severe neurologic and/or cardiovascular toxicity. Patients with mild symptoms can be discharged and observed closely by responsible individuals. Discharged patients need timely follow-up with their primary care physician and/or neurologist. Topiramate (Topamax) Topiramate is an anticonvulsant used mainly for adults with partial seizures. Topiramate’s precise mechanism of action is unclear. Topiramate levels are not readily available in most hospital laboratories. Large overdoses are presumed to cause neurologic impairment, cardiac conduction abnormalities, metabolic acidosis, electrolyte disturbances, ataxia, slurred speech, hallucinations, and possibly seizures.11,12 Adverse effects associated with the chronic use of topiramate include lethargy, confusion, somnolence, dizziness, ataxia, diplopia, paresthesias, weight loss, and the formation of kidney stones.4,9 The treatment of a topiramate overdose is mainly supportive. Cardiac and electrolyte monitoring are recommended. Admission to a monitored unit is recommended for poisoned patients with moderate or severe neurologic, metabolic, and/ or cardiovascular toxicity. Patients with mild symptoms can be discharged and observed closely by responsible individuals. Discharged patients need timely follow-up with their primary care physician and/or neurologist. Tiagabine (Gabitril) Tiagabine, a new anticonvulsant, blocks the uptake of GABA. Tiagabine levels are not readily available in most hospital laboratories. Large tiagabine ingestions may cause seizures.13 Other adverse effects include dizziness, tremor, and difficulty concentrating.4 Admission is recommended for poisoned patients with moderate or severe neurologic toxicity. Discharged patients need timely follow-up with their primary care physician and/or neurologist. Levetiracetam (Keppra) Levetiracetam, a new anticonvulsant, is generally well tolerated. The mechanism of action is unknown. Levetiracetam levels are not readily available in most hospital laboratories. Reported adverse effects include dizziness, asthenia, flulike syndrome, headache, rhinitis, and somnolence.4,14,15 Treatment of overdose is supportive care. Oxcarbazepine (Trileptal) Oxcarbazepine, a sodium channel–blocking anticonvulsant, is structurally related to carbamazepine.15 Oxcarbazepine levels are not readily available in most hospital laboratories. Reported adverse effects include vomiting, somnolence, fatigue, dizziness, nausea, rash (Stevens-Johnson syndrome), and hyponatremia.4,9,16 Treatment of overdose is supportive care. Zonisamide (Zonegran) Zonisamide, a sodium channel– and calcium channel–blocking anticonvulsant, is a sulfonamide derivative. Zonisamide levels are not readily available in most hospital laboratories Reported adverse effects include ataxia, somnolence, agitation, anorexia, psychosis, nephrolithiasis, oligohydrosis, rash (Stevens-Johnson syndrome), and hyperthermia.4,17-19

Chapter 136 — Adverse Effects of Anticonvulsants and Psychotropic Agents

Treatment of overdose is supportive care. Zonisamide is contraindicated in patients allergic to sulfonamides.9 Vigabatrin (Sabril) Vigabatrin is a new anticonvulsant that decreases the metabolism of the neurotransmitter GABA. Vigabatrin levels are not readily available in most hospital laboratories. The major adverse effects are depression, psychosis, and visual field deficits.4 Antipsychotic Agents Phenothiazines Phenothiazines are used to treat a variety of psychiatric conditions. The mechanism of action is central and peripheral dopaminergic blockade. Many of the phenothiazines have anticholinergic, α receptor–blocking, sodium channel– blocking, and potassium channel–blocking properties. These properties cause the clinical manifestations listed in the following paragraph. Phenothiazine levels are not readily available in most hospital laboratories. These medications are given orally, IM, or IV. Numerous adverse effects are associated with phenothiazine use. The first is orthostatic hypotension. QRS and QT interval prolongation can occur along with tachycardia, conduction abnormalities, and anticholinergic toxicity.20,21 Movement disorders (acute dystonia, parkinsonism, akathisia, and tardive dyskinesia) frequently are seen with phenothiazine use. Acute dystonic reactions (oculogyric crisis, torticollis, retrocollis, and opisthotonos) typically occur within 24 to 72 hours of phenothiazine use. Akathisia, the sensation of restlessness and the inability to sit still, also occurs rapidly. Phenothizine-induced parkinsonism and tardive dyskinesia are delayed, typically 1 month to years after initiating therapy. The treatment for phenothiazine toxicity is predominantly supportive. Activated charcoal and/or gastric lavage should be considered for an acute symptomatic overdose, as long as the airway is protected. No specific antidote exists for phenothiazine poisoning. Hypotensive patients should receive IV fluids and vasopressors if necessary. Cardiac monitoring is recommended, and IV sodium bicarbonate should be considered for QRS widening of greater than 100 msec. Admission to an intensive care unit is recommended for poisoned patients with severe neurologic and/or cardiovascular toxicity. Discharged patients need timely follow-up with their primary care physician and/or psychiatrist. Acute dystonic reactions rapidly resolve with anticholinergic agents (diphenhydramine 1 mg/kg IM or IV; benztropine 1 to 2 mg IV or IM) and typically do not require hospital admission. To prevent a recurrence of the dystonic reactions, all treated patients should receive several days of anticholinergic therapy. Akathisia also resolves with anticholinergic therapy. Phenothiazine-induced parkinsonism and tardive dyskinesia are more difficult to treat, often necessitating a reduction in phenothiazine dosage. Butyrophenones Butyrophenones, like the phenothiazines, block central and peripheral dopaminergic receptors. These medications typically are given orally, IM, or IV. Butyrophenone levels are not readily available in most hospital laboratories.

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Severe cardiac toxicity may occur with high-dose butyrophenone use, mainly cardiac dysrhythmias including prolonged QT-associated torsades de pointes.20,21 Dystonic reactions can also occur following butyrophenone use. The treatment for butyrophenone overdose is mainly supportive. Activated charcoal and/or gastric lavage should be considered for an acute symptomatic overdose, as long as the airway is protected. No specific antidote exists for butyrophenone poisoning. Cardiac monitoring is recommended. Treatment options for torsades de pointes include magnesium (25 to 50 mg/kg IV or IM), isoproterenol (0.05 to 2 mcg/kg/min IV), and overdrive pacing. Admission to an intensive care unit is recommended for poisoned patients with cardiovascular toxicity. Discharged patients need timely follow-up with their primary care physician and/or psychiatrist. Dystonic reactions rapidly resolve with anticholinergic agents (diphenhydramine or benztropine) and typically do not require hospital admission. To prevent a recurrence of the dystonic reactions, all treated patients should receive several days of anticholinergic therapy. Atypical Antipsychotics The atypical antipsychotics have effects mainly at the dopaminergic and serotonergic receptors. Clozapine and olanzapine have strong anticholinergic properties. All of these agents can be given orally, IM, or IV. Several adverse acute effects are associated with the atypical antipsychotics. Clozapine and olanzapine, when taken as an overdose, can cause CNS depression and seizures mainly from their anticholinergic properties. Interestingly, olanzapine poisoning has been reported to cause miosis and not mydriasis.22 Acute risperidone, quetiapine, and ziprasidone poisoning may cause obtundation, respiratory depression, and cardiac conduction abnormalities. Acute dystonic reactions may also occur.23,24 Chronic clozapine use has been reported to cause agranulocytosis. The treatment for an atypical antipsychotic adverse effect is mainly supportive. Airway and cardiac monitoring are recommended. REFERENCES 1. Bebin M: The acute management of seizures. Pediatr Ann 28:225–229, 1999. 2. Findling RL, Schultz SC, Reed MD, Blumer JL: The antipsychotics: a pediatric perspective. Pediatr Clin North Am 45:1205–1232, 1998. 3. Doyon S: Anticonvulsants. In Goldfrank LR, Flomenbum NE, Lewin NA, et al (eds): Goldfrank’s Toxicologic Emergencies, 7th ed. New York: McGraw-Hill, 2002, pp 614–630. 4. Begin AM, Connolly M: New antiepileptic drug therapies. Neurol Clin 20:1163–1182, 2002. 5. Spiller HA: Management of carbamazepine overdose. Pediatr Emerg Care 17:452–456, 2001. 6. Schmidt S, Schmitz-Buhl M: Signs and symptoms of carbamazepine overdose. J Neurol 242:169–173, 1995. 7. Seymour JF: Carbamazepine overdose: features in 33 cases. Drug Saf 8:81–88, 1993. 8. Stremski ES, Brady WB, Prasad K, et al: Pediatric carbamazepine intoxication. Ann Emerg Med 25:624–630, 1995. 9. Kopec K: New anticonvulsants for use in pediatric patients. J Pediatr Health Care 15:81–86, 2001. 10. Thundiyil J, Stuart P, Anderson IB, Olson KR: Lamotrigine-induced seizures in a pediatric patient [Abstract]. J Toxicol Clin Toxicol 42:716– 717, 2004. 11. Marquardt KA, Alsop JA, Albertson TE: Unreported symptoms seen in a series of topiramate overdose [Abstract]. J Toxicol Clin Toxicol 42:726–727, 2004.

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12. Lin G, Lawrence R: Topamax toxicity in the pediatric population [Abstract]. J Toxicol Clin Toxicol 42:718–719, 2004. 13. Kazzi Z, Jones C, Hamilton E, Morgan B: Tiagabine overdose in a toddler resulting in seizure activity [Abstract]. J Toxicol Clin Toxicol 42:721, 2004. 14. Cereghino JJ, Biton V, Abou-Khalil B, et al: Levetiracetam for partial seizures: results of a double-blind, randomized clinical trial. Neurology 55:236–242, 2000. 15. McAuley JW, Biederman TS, Smith JC, Moore JL: Newer therapies in the drug treatment of epilepsy. Ann Pharmacother 36:119–129, 2002. 16. Barcs G, Walker EB, Elger CE, et al: Oxcarbazepine placebo-controlled, dose ranging trial in refractory period epilepsy. Epilepsia 41:1597–1607, 2000. 17. Chadwick DW, Marson AG: Zonisamide for drug-resistant partial epilepsy. Cochrane Database Syst Rev (2):CD001416, 2000.

18. Kubota M, Nishi-Nagase M, Sakakihara Y, et al: Zonisamide-induced urinary lithiasis in patients with intractable epilepsy. Brain Dev 22:230–233, 2000. 19. Prescribing information: Zonegran (zonisamide). San Francisco, CA: Elan Pharmaceuticals, 2000. 20. Wolbrette DL: Drugs that cause torsades de pointes and increase the risk of sudden cardiac death. Curr Cardiol Reps 6:379–384, 2004. 21. LoVecchio F, Lewin NA: Antipsychotics. In Goldfrank LR, Flomenbum NE, Lewin NA, et al (eds): Goldfrank’s Toxicologic Emergencies, 7th ed. New York: McGraw-Hill, 2002, pp 875–884. 22. Stewart SK, Doyon S: One-dose dangers in pediatric patients. Crit Decisions Emerg Med 18(11):15–21, 2004. 23. Adamou M, Hale AS: Extrapyramidal syndrome and long-acting injectable risperadone. Am J Psychiatry 161:756–757, 2004. 24. Remington G, Kapur S: Atypical antipsychotics: are some more atypical than others? Psychopharmacology 148:3–15, 2000.

Chapter 137 Cardiovascular Agents John A. Tilelli, MD

Key Points Most antihypertensive and antiarrhythmic poisoning is treated with supportive measures (i.e., fluid replacement, correction of electrolyte abnormalities, and inotropic support). Intoxicated patients may present with an array of symptoms not related to the heart, such as vomiting, lethargy, ataxia, weakness, tinnitus, and visual disturbance. Digoxin Fab antidote is indicated for unstable arrhythmias and hyperkalemia. It may be given for acute and chronic intoxications. Specific therapies, when available, should not substitute for stabilization with supportive care. Children may present with either intoxication with their own medication, or, more commonly from ingestion of a caregiver’s pills. Ingestion of medications, such as quinidine and digoxin, can have a high morbidity and mortality even with a single pill.

present with the ingestion of a medication intended for an adult. Accidental antihypertensive ingestion is among the most common of pediatric intoxications. More than 20,000 exposures to cardiovascular medications were reported to poison control centers in 2003.1 The therapeutic index of these drugs may be sufficiently narrow such that the ingestion of 1 pill may provoke toxicity in a child. The emergency physician also commonly uses these drugs in clinical practice. A general understanding of the acute toxicity of these agents is essential to their safe use in the emergency department (ED). A broad overview of cardiac drugs leads one to approach them in two distinct classes: antihypertensives and antiarrhythmics. While this approach may provide some cognitive separation, it is of less practical use, as many drugs serve in both roles. The calcium channel blockers and β-blockers, for example, serve both roles. Some drugs, such as the nitrate vasodilators, bipyridine inotropes, amrinone, and milrinone, are rarely encountered in the outpatient setting but deserve individual mention. Digoxin, the most commonly prescribed cardiac glycoside, is important because of its widespread use as an inotrope and antiarrythmic. In this overview of the cardiac medications, emphasis is placed on toxicity rather than therapeutic utility.

Selected Pediatric Overdoses Introduction and Background The emergency physician frequently encounters children with toxicity from cardiovascular medications. Antiarryhthmic, inotropic, and antihypertensive medications are commonly prescribed for children with congenital and acquired cardiac and renal diseases, and are often used in a context of multiple therapies. Altered drug clearance, a change in the underlying disease, or the addition or alteration of another therapy may provoke drug toxicity. The symptoms of intoxication may be difficult to distinguish from an acceleration of the underlying condition or intercurrent illness, leading to uncertainty as to whether or not a symptom is the consequence of the disease or of the therapy. The pitfall for the emergency physician is the failure to consider that new symptoms, such as vomiting or mental status change, might represent drug toxicity. Children may also

Antiarryhthmics Antihypertensives Clonidine Angiotensin-converting enzyme inhibitors Vasodilators Diuretics Digoxin Miscellaneous agents Amrinone and milrinone Adenosine

Discussion of Individual Overdoses Antiarrhythmics Antiarrhythmic drugs affect cardiac automaticity by altering the flux of sodium, potassium, and calcium as they cross the myocardial cell membrane during an action potential. These agents are classified by the component of the action potential altered. Class IA agents, for example, decrease sodium 975

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conductance during depolarization, thereby decreasing automaticity, additionally slowing calcium flux, and thereby impairing contractility. Class IB agents decrease sodium and potassium flux. A basic understanding of the mechanism of each class of agent is helpful in predicting an agent’s toxicity and planning for the therapeutic interventions. Class IA Drugs: Quinidine, Procainamide, and Disopyramide Quinidine, procainamide, and disopyramide comprise the drugs in class IA. Their low therapeutic index and idiosyncratic pharmacokinetics limit their usefulness. They are still widely prescribed, however, and are used in both adult and pediatric patients for the control of atrial arrhythmias. All class 1A agents inhibit fast sodium channels and decrease the rate of rise of the action potential, inhibiting automaticity of the heart. QRS and QT prolongation may be observed at therapeutic doses.2 All drugs of this class, but most importantly disopyramide, have negative inotropic effects and may exacerbate heart failure. Side effects of these drugs, especially quinidine, are significant and may limit their utility. “Quinidine syncope” and hypersensitivity are potentially life threatening. Procainamide is associated with drug-induced lupus.3 Quinidine is well absorbed orally and widely distributed. Its metabolism is by hepatic hydroxylation. Both its therapeutic effect and toxicity are related to the concentration, but therapeutic drug monitoring is not usually performed. Quinidine’s potential for toxicity increases when additional medications that inhibit hepatic oxidation are used. Such drugs include ketoconazole, cimetidine, and drugs that affect sodium influx, such as macrolide antibiotics, neuroleptics, and tricyclic antidepressants.4 Similarly, procainamide is well absorbed orally and distributed widely. Its plasma half-life is approximately 3 hours. It is both excreted unchanged in the urine and metabolized by hepatic acylation; the metabolite is excreted at a lower rate than the parent compound. The rate of acylation is genetically determined. Both the plasma concentration of procainamide and that of of its acylated metabolite are commonly available for therapeutic drug monitoring. Disopyramide is well absorbed orally and has a small volume of distribution. It is also metabolized by renal excretion and hepatic metabolism. Manifestations of toxicity due to class IA antiarrhythmic drugs are numerous and frequently life threatening. Most characteristic is a polymorphic ventricular tachyarrhythmia termed torsades de pointes, in which the QRS complexes appear to twist about an isoelectric line (Fig. 137–1). Polymorphic ventricular tachycardia appears to be the cause of quinidine syncope. It may occur at therapeutic levels.5 Its etiology is not completely understood, but it is likely due to transient arrhythmias that spontaneously resolve. Patients who experience syncope should be considered toxic. Prolongation of the QRS complex is common with quinidine therapy, but an increase of 25% over baseline may be considered evidence of toxicity.6 Depression of myocardial function is dose related. Severe overdose is accompanied by hypotension and shock. The acylated metabolite of procainamide is capable of causing torsades in the absence of accumulation of the parent compound. Disopyramide has more negative inotropic potential than either quinidine or procainamide.

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

II

FIGURE 137–1. Torsades de pointes.

Overdoses of all three agents are accompanied by cardiovascular collapse and ventricular arrhythmias. Extracardiac manifestations of quinidine toxicity include cinchonism, a syndrome consisting of tinnitus, vertigo, blurry vision with altered color perception, and confusion.7 Procainamide at therapeutic doses may cause hallucinations and anticholinergic side effects. Gastrointestinal side effects are common. Hypersensitivity reactions and blood dyscrasias, most commonly agranulocytosis, are commonly associated with quinidine. Fever may appear shortly after the initiation of a class IA medication, and may be accompanied by rash and eosinophilia. Both quinidine and procainamide are associated with the development of antinuclear antibodies and drug-induced systemic lupus erythematosus. Rarely, antiphospholipid antibodies may be associated with thrombosis.8 Because of the narrow therapeutic index of these agents, intoxication in a child may accompany the accidental ingestion of 1 pill. Therefore, decontamination with activated charcoal is indicated in all patients suspected of exposure, irrespective of symptoms. All patients should be admitted for observation.9 Hypokalemia and hypomagnesemia may provoke the development of torsades, and should be corrected. Intoxication with any of the class IA agents may present with dramatic, life-threatening torsades de pointes. Magnesium sulfate and sodium bicarbonate are the first-line treatment of drug-induced torsades.10 Their efficacy is multifactorial, altering intracellular potassium concentration and increasing protein binding of the drug. Treatment should be undertaken in patients with ventricular tachyarrhythmias. Magnesium may assist in preventing the early afterdepolarizations that are thought to initiate torsades.11 Lidocaine has been recommended for the treatment of torsades, but should be undertaken, if at all, with caution, as it may be proarrhythmic (see the next section). Overdrive pacing has also been used successfully.12 Class 1B Drugs: Lidocaine, Tocainide, and Mexiletine Lidocaine is the most commonly used drug among the class IB antiarrhythmic drugs, both as an antiarrhythmic and an analgesic. Intoxication, however, is relatively uncommon. Life-threatening events (LTEs) have been observed after the accidental administration of an intravenous overdose. More commonly, they are observed during the administration of

Chapter 137 — Cardiovascular Agents

therapeutic doses in the context of impaired clearance, as in the case of congestive heart failure, or intravenous injection of a local anesthetic. LTEs are occasionally observed after the topical administration of analgesic jelly to a mucous membrane. Although oral lidocaine is poorly bioavailable, oral intoxication has been reported.13 Mexiletine and tocainide are both well absorbed. All undergo extensive hepatic metabolism. The half-life of lidocaine is between 1.5 and 2 hours, but may be altered in the face of hepatic disease, circulatory disturbances, or heart failure.14 Therapeutic drug monitoring of lidocaine is widely available. Central nervous system manifestations of lidocaine toxicity include dysarthria, tremors, seizures, respiratory depression, and coma.15 Similar toxicity has been reported with mexiletine and tocainide. Cardiovascular toxicity of class IB agents includes sinus bradycardia, conduction disturbances, heart block, and asystole.16 Arrhythmias may occur at therapeutic doses in patients with underlying rhythm disturbances. Ventricular tachycardia, ventricular fibrillation, and torsades de pointes have been observed. None of the class IB agents alters the QT interval or affects the QRS duration. Management of class IB intoxication consists of discontinuation of the drug, and, in the case of ingestion of tocainide or mexiletine, decontamination of the bowel with activated charcoal. Stabilization of the comatose patient should be undertaken with endotracheal intubation and mechanical ventilation. Seizures may be treated with benzodiazepines or barbiturates. Symptomatic bradyarrhythmias necessitate cardiac pacing. Hypotension may be due both to cardiac depression and vasodilation, and should be treated with fluid administration and vasopressor agents, such as dopamine and epinephrine. Extracorporeal support may be considered in severe cases.17 Class IC Drugs: Flecainide, Encainide, and Propafenone Poisoning with the class IC antiarrhythmic drugs, flecainide and encainide, has rarely been reported in childhood. An infant who ingested 1 pill of encainide was reported to have ventricular tachycardia.18 Seizures have been reported with flecainide toxicity.19 Decontamination of the potentially exposed child with activated charcoal is standard. Supportive management and therapy for arrhythmias and hypotension is the same as with class IA and IB agents. Extracorporeal membrane removal of the class 1C drugs has been suggested for the seriously intoxicated patient.20 Class II Drugs: b-Blockers β-Blocking agents are widely used in children and adults to control hypertension and arrhythmias. Additionally, they are used in the management of congestive heart failure, cardiomyopathies, and (in adults) angina. Their common mechanism is the blockade of membrane β receptors, modulating calcium-mediated excitation-contraction. Clinical effects are expressed by the location of the receptor, and the affinity of the drug for it. Classically, two receptors exist; β1-receptors are located in the myocardium, kidney, and eye, while β2receptors are found in smooth and skeletal muscle, pancreas, liver, and adipose tissue. Stimulation of the former receptors increases cardiac chronotropy and inotropy, while stimulation of the latter receptors relaxes smooth muscle in the

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bronchial tree, uterus, and blood vessels. β-blockers may also have centrally mediated effects as well as membranestabilizing ability, which is apparent in overdose. Some have intrinsic sympathomimetic activity.21 β-Blocker toxicity manifests as decreased cardiac contractility and conduction delay. Sinus bradycardia is common in most ingestions, but may be absent in overdose of agents with partial agonist activity. QRS prolongation and conduction abnormalities may be present, especially in poisoning with propranolol. Hypotension, often profound, is secondary to negative inotropy. Paradoxical hypertension secondary to partial agonist activity may occur. Depressed level of consciousness and seizures may occur, especially with propranolol overdose.22 Respiratory depression may be centrally mediated. Bronchospasm is common, especially in agents that are not β1 selective. Patients with underlying reversible obstructive airway disease may experience worsening symptoms at therapeutic doses.23 Hypoglycemia may occur in toxicity with nonselective agents such as atenolol and propranolol.24 Overdose in children is relatively common. Despite its frequency, serious intoxication is rare. No case of fatal β-blocker intoxication in a child has been documented in the literature.25 In a review of self-poisonings, all patients who developed toxicity did so within 6 hours of ingestion.26 The seriously intoxicated patient may present a significant therapeutic challenge. Basic measures for the treatment of overdose should be undertaken, including decontamination with activated charcoal. Enhanced elimination techniques such as dialysis may be feasible for selected agents with a small volume of distribution and little protein binding. Seizures may be treated with conventional agents such as benzodiazepines and barbiturates. Hypoglycemia, if present, should be corrected. Respiratory failure may be treated with conventional supportive therapy, including mechanical ventilation and inhaled bronchodilators. Catecholamines have been a mainstay of therapy for β-blocker overdose, with variable results.27 Isoproterenol, a pure β-agonist, is rational therapy but is not uniformly successful at restoring blood pressure. Epinephrine has been used in high doses, beginning at 1 mg/kg/min.28 Optimal dosing should be determined by blood pressure and tissue perfusion. Dobutamine has not been well studied. Glucagon has been reported useful as a noncatecholamine inotrope with a mechanism unrelated to catecholamines, but has not been subjected to clinical trials. A review of the case literature reports a total of seven adult patients given between 1 and 80 mg of glucagon, all of whom survived.29 If used, experts recommend a starting dose of 50 mcg/kg diluted and infused over 1–2 minutes × 1–2 doses, then begin an infusion of 50 mcg/kg/min. The impact of glucagon on survival, however, has been questioned.30 Atropine is safe, but rarely effective at improving the heart rate. The experience with amrinone in augmenting cardiac output is limited. Transvenous pacing may be attempted, but capture may not be possible.31 Class III Drugs: Sotalol and Amiodarone Amiodarone and sotalol, class III antiarrhythmic drugs, are being used with increasing frequency in the pediatric setting. Amiodarone, in particular, has become more prominent in the management of arrhythmias refractory to other agents. All class III agents prolong the action potential without

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SECTION IV — Approach to the Acutely Ill Patient

affecting depolarization. These drugs may be proarrhythmic and should be used in the context of defined indications.32,33 Amiodarone acts by inhibiting the slow outward current of potassium, delaying intraventricular conduction and reducing cardiac automaticity. Significant childhood poisoning has been rarely reported. Overdose of both class III drugs has generally been accompanied by an exaggeration of the primary effects. Massive overdose has been accompanied by bradycardia, hypotension, and cardiovascular collapse.34 The level of consciousness may be unimpaired in the absence of symptomatic bradycardia. The electrocardiogram generally shows bradycardia and, rarely, heart block or QT interval prolongation. Prolongation of the PR interval is considered a therapeutic and not a toxic effect. Symptoms are related to the plasma level and generally disappear within 12 hours. Torsades de pointes has been described as occurring with both drugs,35,36 and has been successfully treated with lidocaine. Hypotension is associated with amiodarone administration and is generally the result of rapid intravenous administration. The hypotension is attributed to the benzyl alcohol additive. Oral amiodarone has no hypotensive effect. Chronic amiodarone administration is associated with multiple problems. In children followed during amiodarone therapy for an average of 1.5 years, toxicity was reported in 29%. Complaints included cataracts, thyroid abnormalities, pulmonary fibrosis, hypertension, rash, peripheral neuropathy, and vomiting. Skeletal dysplasia has been reported, but its significance may have been overestimated.37 These problems resolved with reduction of the dose or cessation of the drug. Emergency physicians should be aware of the possible relationship of these complaints to the administration of amiodarone. Acute intoxication with a class III antiarrhythmic agent rarely presents with life-threatening problems. Activated charcoal significantly reduces the bioavailability of both amiodarone and sotalol. Cholestyramine may shorten the half-life of amiodarone by interrupting its enterohepatic circulation.34 An unstable rhythm such as profound bradycardia, attributed to amiodarone, may be treated with the cautious administration of magnesium or potassium. Lidocaine may be helpful in the therapy of torsades de pointes. The treatment of hypotension during intravenous administration of amiodarone is supportive. Class IA agents are contraindicated. Class IV Drugs: Calcium Channel Blockers Calcium channel–blocking agents are a chemically diverse group of drugs used in the treatment of hypertension and arrhythmias. Verapamil, diltiazem, and nifedipine are three of the most commonly prescribed and have different structures. They act by inhibiting calcium flux through low-voltage channels in cardiac and smooth muscle, as well as pacemaker cells in the sinoatrial and atrioventricular nodes. Therefore, all share the properties of vasodilation, myocardial depression, and slowed atrioventricular nodal conduction. Each, however, has characteristics that render one effect more prominent than others. None of the currently available agents has a demonstrated effect on skeletal muscle. They are poorly bioavailable and undergo principally hepatic metabolism, and drugs that inhibit hepatic cytochromes may increase calcium channel blocker bioavailability and potentiate toxicity.38 Many are marketed in sustained-release preparations.

In childhood, they are used in the management of hypertension and the control of supraventriular tachycardia. In adults, they are used additionally in the management of angina. Poisoning in childhood is relatively common. In 2003, the American Association of Poison Control Centers reported 9650 exposures, 57 of which resulted in death.1 Little agreement exists on the toxic dose or time to onset of symptoms. As these drugs are intended to lower blood pressure, it would be expected that symptoms might occur at or near the therapeutic dose. In a recent review of calcium channel blocker poisoning in children, the majority of symptomatic children ingested doses at or near what might be considered the therapeutic range.39 Symptoms generally develop within 5 hours of ingestion, but may be delayed as long as 15 hours in the event of the ingestion of a sustained-release product. Their effects are additive with other antihypertensive agents, and may be aggravated by hypovolemia, as may occur with concurrent diuretic administration, or a concurrent disease such as gastroenteritis. Symptoms of intoxication consist of an exaggeration of the effects of the drug. Cardiovascular collapse with hypotension, which may be profound, and bradycardia resistant to conventional therapy may occur. Noncardiogenic pulmonary edema has been reported.40 Lethargy, nausea, and vomiting have been observed, but severe central nervous system depression is usually present only in the context of cardiovascular collapse. Electrolyte abnormalities are not generally present. Metabolic acidosis is observed as a consequence of low cardiac output, and, if severe or unremitting, carries a poor prognosis. Therapy for the child who has ingested a calcium channel blocker is largely supportive. One study suggests that children who ingest less than 12 mg/kg of verapamil or 2.7 mg/kg of nifedipine may be monitored at home.39 The same study indicates that children who are asymptomatic 3 hours after ingestion of a regular-release product or 14 hours after ingestion of a sustained-release product may be discharged. Activated charcoal has been advocated for all patients, but gastric lavage and emesis should be undertaken with caution, if at all, as the resulting vagal maneuver may worsen preexisting bradycardia. Multiple doses of activated charcoal should be considered in the patient who has ingested a sustained-release preparation. Correction of hypovolemia should be a priority. Calcium salts have been advocated as specific therapy, although reports of benefit are conflicting.41 Administration of calcium salts to maintain at least normal calcium is reasonable. Alternately, administer calcium gluconate at 20–40 mg/kg (0.2–0.4 ml/kg of 10% solution) IV over 5 minutes, with an infusion of 20–40 mg/kg/hr if there is a favorable response. Care should be undertaken to avoid extravasations of peripherally administered calcium, and monitor carefully its serum concentration, especially in the context of concurrent digoxin administration. Insulin and glucagon have both been recommended for calcium channel blocker overdose. The latter is thought to directly affect myocardial contractility. If used, administer a regular insulin bolus of 1.0 U/kg, followed by an infusion of 1.0 U/kg/hr for the first hour, then 0.5 U/kg/hr until toxicity resolves. At the same time a 0.5 g/kg bolus of glucose is administered with an additional 0.5 g/kg/hr until insulin is discontinued. Frequent monitoring of glucose (hourly during treatment and hourly until 6 hours after treatment) and potassium is required with this regimen.

Chapter 137 — Cardiovascular Agents

Supportive care of the child with a calcium channel blocker intoxication is challenging. Many strategies have been advocated with varying success. Fluid replacement should be undertaken with caution to avoid pulmonary edema. Inotropic support with dopamine, epinephrine, or norepinephrine may be required; however, myocardium and vascular smooth muscle may be resistant to conventional doses. No consensus exists regarding the superiority of one drug over another. Amrinone in conjunction with glucagon was reported successful in treating one patient with refractory hypertension secondary to verapamil overdose.42 No controlled studies have been published to date suggesting their routine use. Atropine may be administered for appropriate arrhythmias, although its benefit is unproven. Cardiac pacing may be undertaken for bradyarrhythmias resistant to therapy.43 Both intra-aortic balloon counterpulsation and cardiopulmonary bypass have been reported as successful in restoring hemodynamic stability.44 A retrospective study of patients with symptomatic calcium channel blocker overdose reported that both calcium and dopamine were effective in restoring blood pressure and cardiac rhythm to all patients who received them.45 Antihypertensives Clonidine Clonidine is a centrally acting antihypertensive agent. Its mechanism of action is the stimulation of central α receptors. It has no peripheral α receptor activity. It is widely used in the treatment of hypertension, and is useful in the management of narcotic withdrawal. Its widespread use makes it a frequent source of pediatric poisonings. α-Methyldopa, another clinically useful centrally acting antihypertensive, is far more infrequently prescribed and is therefore uncommonly accidentally ingested. Clonidine therapy in adults is commonly initiated at a dose of 0.1 mg, and 1 tablet may be sufficient to cause symptoms in a small child. Overdose may occur when a small child has access to the pills of a parent or caregiver, or as the result of an intentional overdose in an older child. Symptomatic clonidine overdose presents as bradycardia, hypotension, lethargy, coma, and miosis. Respiratory depression sufficient to require mechanical ventilation is common in severely intoxicated patients. Hypotension may be modest or absent, but may occasionally require therapy. A large review of 10,060 clonidine exposures reported to the American Association of Poison Control Centers revealed that 60% of the patients were symptomatic, lethargy being the most common symptom (80%).46 Bradycardia, hypotension, and respiratory depression were each observed, in decreasing frequency. Basic management of clonidine poisoning includes decontamination with activated charcoal. Airway protection and mechanical ventilation are needed in the unconscious or severely lethargic patient. Hypothermia may be corrected with surface warming. Hypotension is usually responsive to fluid administration. Occasionally, vasopressor agents may be indicated. As the mechanism of clonidine resembles that of opioid (narcotic) agonists, naloxone has occasionally been recommended.47 It may be diagnostically useful, but supportive measures will frequently be satisfactory until the drug is eliminated. Tolazoline, an α-adrenergic antagonist,

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has been considered as theoretically useful48 but has also failed to be of benefit in individual case reports.49 The outcome of conservatively managed clonidine overdose is generally good, and death is rare. Angiotensin-Converting Enzyme Inhibitors Angiotensin-converting enzyme (ACE) inhibitors are among the most commonly prescribed drugs in the management of hypertension and congestive heart failure in adults, and are frequently used in combination with other agents such as βblockers and centrally acting agents. Captopril and enalapril are commonly used in children for these indications. Symptomatic hypotension is rare, but acute overdose may be accompanied by profound and prolonged hypotension.50 ACE inhibitors reduce systemic vascular resistance, but may induce renal insufficiency.51 Hyperkalemia has been observed at therapeutic doses, and renal insufficiency may occur as a consequence of ACE inhibition.52 The emergency physician should be mindful of the possibility that preexisting disease and concurrent therapy in the patient prescribed an ACE inhibitor may compound the risk for renal insufficiency and hyperkalemia.53 Hypotension in the patient who has acutely ingested an ACE inhibitor is frequently responsive to fluid administration. Vasopressors are occasionally required.54 Hypotension encountered in the patient who is using an ACE inhibitor for therapeutic purposes is similarly managed, keeping in mind that symptoms of congestive heart failure may be worsened in doing so. Hyperkalemia and renal insufficiency should be addressed with the appropriate laboratory studies and acute interventions. There is no accepted antidotal therapy. Vasodilators Oral vasodilators are less commonly prescribed in the management of hypertension in children and adults, and, therefore, infrequently seen as causes of pediatric poisonings. Hydralazine overdose has only been reported in the adult literature. Hypotension is the predominant symptom, but electrocardiographic changes suggestive of ischemia are also described.55 There is no consensus on therapy, but the aforementioned patient, who was additionally ethanol intoxicated, responded to conservative management. Hydralazine has been implicated in drug-induced lupus, which is characterized by arthralgia, myalgia, pleurisy, rashes, fever, and a positive antinuclear antibody screen. Procainamide, and to a lesser extent β-blockers, methyldopa, quinidine, and numerous other drugs, have also been implicated.56 Recognition by the emergency physician is important, as resolution of the syndrome occurs within a few weeks of discontinuation of the drug. Nitrates are used in the management of angina, congestive heart failure, and hypertension in adults. Children who have ingested an oral nitrate preparation may present with flushing, headache, tachycardia, and hypotension resulting in syncope. As the effect is short lived, the symptomatic patient may improve prior to arrival in the ED. Management is similar to that of other vasodilators. In addition to inadvertent overdose, the nitrates are also drugs of abuse (see Chapter 135, Drugs of Abuse). Methemoglobinemia and hemolytic anemia have been reported.57,58 The intoxicated patient presents with cyanosis and acidosis, but normal external oxygen

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tension. Diagnosis is confirmed by the demonstration of an elevated methemoglobin concentration by co-oximetry. Hereditary deficiency in the enzyme glucose-6-phosphate dehydrogenase may predispose the individual to this occurrence. Limited experience with nitrite-induced methemoglobinemia suggests that it responds to the administration of methylene blue in a manner similar to other etiologies59 (see Chapter 133, Common Pediatric Overdoses). Nitroprusside is widely used in the management of a hypertensive emergency. Chronic complications include methemoglobinemia and hemolytic anemia, which are not encountered in the acute overdose, and are unlikely to be seen in the emergency management of children. The degradation of nitroprusside releases cyanide, which is once again rarely problematic in the ED. Thiocyanate is formed with the degradation of nitroprusside after administration. Levels are of no use in predicting nitroprusside toxicity. Hypotension is treated by decreasing or discontinuing the medication, which has a half-life of minutes.60 Minoxidil is a potent vasodilator prescribed for the treatment of severe hypertension. It is rarely used in childhood. Hirsuitism is a side effect that accompanies its chronic use and, it has been marketed as an over-the-counter drug intended for topical use. Overdose in childhood has rarely been observed, but intentional ingestion of the hair treatment by an adult produced severe hypotension and tachycardia that required massive fluid administration, vasopressor support, and mechanical ventilation.61 Diuretics Diuretics are widely used in both children and adults in the management of hypertension and congestive heart failure. Their availability makes them frequently seen in accidental overdose. Additionally, the emergency physician may be called upon to evaluate a child with a preexisting illness for which diuretic therapy has been undertaken. Diuretics are commonly classified as either potassium wasting or potassium sparing. The former consist of the potent loop diuretics, including furosemide and ethacrynic acid, and the thiazide diuretics. Potassium wasting is commonplace, and secondary metabolic alkalosis is frequently seen as a consequence of attendant urinary hydrogen ion excretion. Calciuria also occurs with the loop agents, but hypocalcemia is rarely a problem in the acute setting. Potassium-sparing agents include the aldosterone antagonist spironolactone, and acetazolamide, a carbonic anhydrase inhibitor. As their classification implies, therapeutic use of these drugs is not accompanied by hypokalemia. The child with acute overdose is rarely a therapeutic challenge. Ingestion of loop diuretics and thiazides present more acute problems than do the potassium-sparing agents. Dehydration may occasionally be seen, as well as electrolyte disturbances. Hyponatremia is generally mild. Hypokalemia may be present after an acute ingestion, but is more common with chronic therapeutic use. Appropriate fluid and electrolyte replacement should be undertaken.62 Chronic complications of diuretic use include hypokalemia, severe metabolic alkalosis, and, with loop diuretic use, hypocalcemia. Occasionally tetany may be seen, requiring the cautious administration of intravenous calcium (see Chapter 115, Hypocalcemia). Seizures and hypocalcemic prolongation of the QT interval are rarely seen.63 Chronic use

of loop diuretics is associated with pancreatitis.64 Renal insufficiency may be worsened by diuretic therapy when administered concurrently with an ACE inhibitor.65 Caution should be undertaken in the fluid replacement of a child who presents with diuretic-induced dehydration, renal insufficiency, and the concurrent use of a loop diuretic and potassium-sparing agent. Acetazolamide is infrequently used as a diuretic, but more commonly prescribed in the control of intraocular pressure and pseudotumor cerebri. Acetazolamide toxicity may present with significant metabolic acidosis, manifesting as lethargy and Kussmaul’s respirations. A toddler reported to have ingested 10 g of acetazolamide recovered completely with the administration of sodium bicarbonate.66 Digoxin Digoxin is a member of a group of glycosides derived from the foxglove plant and increases cardiac contractility and automaticity. Digoxin and digitoxin are the sole agents currently in use. Therefore, they are still widely used in the management of congestive heart failure and arrhythmias in both children and adults. They have a narrow therapeutic index, and poisoning is common both in the setting of clinical use and in accidental ingestion. Cardiac glycosides are found in many common decorative plants such as yellow oleander, and accidental ingestion presents with symptoms similar to digitalis poisoning. Because of its prolonged kinetics, digoxin therapy is frequently initiated by a loading dose, commonly 35 to 50 mcg/kg, given in divided doses over several days, followed by maintenance therapy of 7 to 10 mcg/kg/dose every 12 hours. The dose is adjusted in the face of renal insufficiency. Digoxin has a large volume of distribution, being concentrated in the muscle mass. Bioavailability after oral ingestion is variable, depending substantially on the manufacturer. For that reason Lanoxin is the most widely prescribed agent, in which nearly 90% of an oral dose is absorbed. Onset of effect is between 1.5 and 6 hours. It is slowly excreted intact by the kidneys. A decrease in renal function or significant dehydration may provoke digoxin intoxication in the patient who has previously been safely taking a given dose. In this setting, peritoneal dialysis may be useful in addition to the other measures undertaken to treat digitalis intoxication.67 Digoxin impairs the Na+/K+ membrane pump, increasing intracellular sodium and impairing Na+ -Ca2+ dependent egress of calcium from the cell, thereby enhancing contractility. The transmembrane potential is raised, increasing automaticity. Digoxin also increases cardiac vagal tone, slowing the heart rate and delaying atrioventricular nodal conduction. As digoxin’s effect is dependent on its membrane-bound fraction, serum digoxin levels, although widely available, are poor prognostic indicators for the development of digitoxicity.68 Intracellular electrolytes, although not widely available, may be a sensitive indicator of the risk for digitoxicity.69 Therapeutic drug monitoring may be more useful in specific settings, such as the management of congestive heart failure in a patient with renal impairment. Elevated digoxin levels in the correct clinical setting may be of assistance in establishing the diagnosis of digitoxicity, but too great an overlap exists between therapeutic and toxic levels to use the digoxin level as a sole index of toxicity.70

Chapter 137 — Cardiovascular Agents

Lead I

aVR

V1

V4

Lead II

aVL

V2

V5

Lead III

aVF V3

V6

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FIGURE 137–2. Bidirectional ventricular tachycardia.

Acute digoxin poisoning presents with vomiting, bradycardia, and arrhythmias, frequently heart block and bradycardia, although virtually any cardiac rhythm disturbance may be attributed to digitalis poisoning. Hyperkalemia is frequently observed and may be life threatening. Chronic digoxin poisoning may present with an array of bizarre complaints, including vomiting, anorexia, weakness, altered mental status, and visual disturbances such as altered color perception. Cardiac manifestations of poisoning include ventricular arrhythmias, heart block, and nodal escape rhythms. Rhythm disturbances commonly manifest some form of myocardial irritability with delayed conduction. Bidirectional ventricular tachycardia is thought to be particularly characteristic of digitalis poisoning71 (Fig. 137–2). Emesis is not recommended in digoxin poisoning, as it may increase vagal tone, exacerbating bradycardia. Activated charcoal binds digoxin well, and should be given. Multipledose activated charcoal is not clearly beneficial.72 There are no data on the efficacy of catharsis. Dialysis is of no benefit. The development of digoxin-specific antibody fragments (Fab) has significantly altered the management of digoxin poisoning. Administration rapidly reverses bradycardia, arrhythmias, and hyperkalemia associated with digoxin poisoning and related, naturally occurring, cardiac glycosides.73,74 It is effective in the treatment of poisoning due to digoxin, digitoxin, and congeners, as well as the naturally occurring glycosides.75 Fab should be given to patients with any dysrrhythmia causing hemodynamic compromise or with a serum potassium level greater than 10 mEq/L.76 It should be given after ingestion of more than 4 mg in a child without underlying disease, and may be given intravenously or by the intraosseous route. The amount administered may be determined by the following formula if the dose taken is known77:

Number of Fab vials (38 mg/vial) = amount ingested (mg) × 0.48 (mg neutralized/vial) If the dose is unknown, the amount given may be determined by the steady state serum digoxin concentration 6 hours after the ingestion: Number of Fab vials = serum digoxin level (ng/ml) × body weight (kg)/100 Fab is also useful in the treatment of chronic digoxin intoxication. The previous equation may be used, obtaining the steady state concentration. If the dose ingested is unknown, 5 vials may be given to a child, 10 to 20 vials to an acutely intoxicated adult, or 10 vials to an adult with chronic toxicity. Atropine is useful as an antidote and is indicated for severe bradycardia. Phenytoin and lidocaine were both previously considered primary therapy for the treatment of ventricular dysrrhythmias, and may still be useful in the absence of Fab, or as adjunctive therapy.78 Amiodarone has been reported to be of assistance in the conversion of ventricular fibrillation.79 Magnesium has occasionally been reported to be of assistance in the conversion of ventricular arrhythmias attendant to chronic digitalis poisoning. Miscellaneous Agents Amrinone and Milrinone Amrinone and milrinone are bipyridine derivatives useful in the management of congestive heart failure, and have both inotropic and vasodilator properties. Although commonly used in inpatient settings for the management of shock and low cardiac output postoperative states, they are also used in the outpatient setting and may rarely present as an overdose. Oral overdose is usually well tolerated. Amrinone is associated with thrombocytopenia. Milrinone, which is not associated with this adverse effect, is more commonly prescribed.

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SECTION IV — Approach to the Acutely Ill Patient

Administration of milrinone has been rarely associated with hypotension. Vasopressor support and fluid administration may rarely be required. One fatality was reported after a massive intravenous overdose,80 manifesting as hypotension unresponsive to fluid administration and vasopressors. Peritoneal dialysis was ineffective. An adult who had tachycardia attributed to milrinone was successfully treated with β-blockers.81 Adenosine Adenosine is useful in the conversion of supraventricular tachyarrhythmias sustained by atrioventricular reentry by prolonging atrioventricular nodal conduction time. In a large series of cardioversions, 72% of patients with presumed supraventricular tachycardia were successfully converted.82 The half-life of adenosine is short, limited to a single pass through the circulation. It is therefore administered by rapid intravenous injection. The usual dose is 0.1 mg/kg. Repeated administration may be undertaken, with incremental increases of 0.05 mg/kg, to a dose of 0.2 mg/kg or until an effect is observed. In another study, 96% of children were successfully converted, but recurrent tachycardia and other significant complications, including atrial fibrillation, accelerated ventricular tachycardia, apnea, and asystole, occurred.83 Continuous monitoring and equipment should be available in this event. Prolonged heart block and ventricular fibrillation may be encountered in the setting of administration of adenosine with digoxin, calcium channel blockers, or class IA antiarrhythmics.84,85 Adenosine can cause cardiac arrest in de-inervated hearts (post-transplant), high degree heart block in patients who already have second degree heart block or who are on carbemazepine, and bronchospasm in asthmatics (especially if they are taking theophylline preparations).

Summary Complications of cardiac drugs are fortunately infrequent. When they do occur, they are frequently managed in the ED. The principles of management revolve around attention to basic hemodynamic stabilization, followed by specific therapy based on knowledge of the drug. Correction of hypotension, restoration of a stable rhythm, attention to fluid and electrolyte balance, and support of ventilation will optimize therapy directed toward an individual agent. REFERENCES *1. Watson WA, Litovitz TL, Klein-Schwartz W, et al: 2003 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med 22:335–404, 2004. *2. Roden DM: Drug Therapy: Drug-induced prolongation of the QT interval. N Engl J Med 350:1013–1022, 2004. 3. Lin JC, Quasny HA: QT prolongation and development of torsades de pointes with the concomitant administration of oral erythromycin base and quinidine. Pharmacotherapy 17:626–630, 1997. *4. Trujillo TC, Nolan PE: Antiarrhythmic agents: drug interactions of clinical significance. Drug Saf 23:509–532, 2000. 5. Jenzer HR, Hagemeijer F: Quinidine syncope: torsades de pointes with low quinidine plasma concentrations. Eur J Cardiol 4:447–451, 1976. 6. Kim SY, Benowitz NL: Poisoning due to class IA antiarrhythmic drugs—quinidine, procainamide and disopyramide. Drug Saf 5:393– 420, 1990.

*Suggested readings.

7. Wolf LR, Otten EJ, Spadafora MP: Cinchonism: two case reports and review of acute quinine toxicity and treatment. J Emerg Med 10:295– 301, 1992. 8. Bateman DN, Dyson EH: Quinine toxicity. Adverse Drug React Acute Poisoning Rev 5:215–233, 1986. 9. Hruby K, Missliwetz J: Poisoning with oral antiarrhythmic drugs. Int J Clin Pharmacol Ther Toxicol 23:253–257, 1985. 10. Gowda RM, Khan IA, Wilbur SL, et al: Torsade de pointes: the clinical considerations. Int J Cardiol 96:1–6, 2004. 11. Bailie DS, Inoue H, Kaseda S, et al: Magnesium suppression of early afterdepolarizations and ventricular tachyarrhythmias induced by cesium in dogs. Circulation 77:1395–1402, 1988. 12. Pinski SL, Eguia LE, Trohman RG: What is the minimal pacing rate that prevents torsades de pointes? Insights from patients with permanent pacemakers. Pacing Clin Electrophysiol 25:1612–1615, 2002. 13. Hess GP, Walson PD: Seizures secondary to oral viscous lidocaine. Ann Emerg Med 17:725–727, 1988. 14. Denaro CP, Benowitz NL: Poisoning due to class 1B antiarrhythmic drugs: lignocaine, mexiletine and tocainide. Med Toxicol Adverse Drug Exp 4:412–428, 1989. 15. Ryan CA, Robertson M, Coe JY: Seizures due to lidocaine toxicity in a child during cardiac catheterization. Pediatr Cardiol 14:116–118, 1993. 16. Edgren B, Tilelli J, Gehrz R: Intravenous lidocaine overdosage in a child. J Toxicol Clin Toxicol 24:51–58, 1986. 17. Freedman MD, Gal J, Freed CR: Extracorporeal pump assistance— novel treatment for licocaine poisoning. Eur J Clin Pharmacol 22:129– 135, 1982. 18. Mortensen ME, Bolon CE, Kelley MT, et al: Encainide overdose in an infant. Ann Emerg Med 21:998–1001, 1992. 19. Kennerdy A, Thomas P, Sheridan DJ: Generalized seizures as the presentation of flecainide toxicity. Eur Heart J 10:950–954, 1989. 20. Pond SM: Extracorporeal techniques in the treatment of poisoned patients. Med J Aust 154:617–622, 1991. 21. Frishman W, Jacob H, Eisemberg E, et al: Clinical pharmacology of the new beta-adrenergic blocking drugs. Am Heart J 98:798–811, 1979. 22. Lifshitz M, Zucker N, Zalzstein E: Acute dilated cardiomyopathy and central nervous sytem toxicity following propranolol intoxication. Pediatr Emerg Care 15:262–263, 1999. 23. Boskabady MH, Snashall PD: Bronchial responsiveness to betaadrenergic stimulation and enhanced beta-blockade in asthma. Respirology 5:111–118, 2000. 24. Hesse B, Pederson JT: Hypoglycaemia after propranolol in children. Acta Med Scand 193:551–552, 1973. 25. Love JN, Silka N: Are 1-2 tablets dangerous? Beta-blocker exposure in toddlers. J Emerg Med 26:309–314, 2004. 26. Reith DM, Dawson AH, Epid D, et al: Relative toxicity of beta blockers in overdose. J Toxicol Clin Toxicol 34:273–278, 1996. 27. Langemeijer JJ, de Wildt DJ, de Groot G, Sangster B: Intoxication with beta-sympathicolytics. Neth J Med 40:308–315, 1992. 28. Kerns W, Kline J, Ford MD: Beta-blocker and calcium channel blocker toxicity. Emerg Med Clin North Am 12:365–390, 1994. 29. Boyd R, Gosh A: Glucagon for the treatment of symptomatic β blocker overdose. Emerg Med J 20:266–267, 2003. 30. Bailey B: Glucagon in beta-blocker and calcium channel blocker overdoses: a systematic review. J Toxicol Clin Toxicol 41:595–602, 2003. 31. Lane AS, Woodward AC, Goldman MR: Massive propranolol overdose poorly responsive to pharmacologic therapy: use of the intra-aortic balloon pump. Ann Emerg Med 16:1381–1383, 1987. 32. Hohnloser SH: Proarrhythmia with class III antiarrhythmic drugs: types, risks, and management. Am J Cardiol 80:82G–89G, 1997. 33. Hohnloser SH, Woosley RL: Sotalol. N Engl J Med 331:31–38, 1994. *34. Leatham EW, Holt DW, McKenna WJ: Class III antiarrhythmics in overdose: presenting features and management principles. Drug Saf 9:450–462, 1993. 35. Assimes TL, Malcolm I: Torsade de pointes with sotalol overdose treated successfully with lidocaine. Can J Cardiol 14:753–756, 1998. 36. Hohnloser SH, Klingenheben T, Singh BN: Amiodarone-associated proarrhythmic effects: a review with special reference to torsade de pointes tachycardia. Ann Intern Med 121:529–535, 1994. 37. Guccione P, Paul T, Garson A Jr: Long-term follow-up of amiodarone therapy in the young: continued efficacy, unimpaired growth, moderate side effects. J Am Coll Cardiol 15:1118–1124, 1990. 38. Abernathy DR, Schwartz JB: Calcium-antagonist drugs. N Engl J Med 341:1447–1457, 1999.

Chapter 137 — Cardiovascular Agents 39. Belson MG, Gorman SE, Sullivan K, Geller RJ: Calcium channel blocker ingestions in children. Am J Emerg Med 18:581–586, 2000. 40. Brass BJ, Winchester-Penny S, Lipper BL: Massive verapamil overdose complicated by noncardiogenic pulmonary edema. Am J Emerg Med 14:459–461, 1996. 41. Salhanick SD, Shannon MW: Management of calcium channel antagonist overdosage. Drug Saf 26:65–79, 2003. 42. Wolf LR, Spadafora MP, Otten EJ: Use of amrinone and glucagons in a case of calcium channel blocker overdose. Ann Emerg Med 22:1225– 1228, 1993. 43. Proano L, Chiang WK, Wang RY: Calcium channel blocker overdose. Am J Emerg Med 13:444–450, 1995. 44. Durward A, Guerguerian AM, Lefebvre M, Shemie SD: Massive diltiazem overdose treated with extracorporeal membrane oxygenation. Pediatr Crit Care Med 4:372–376, 2003. 45. Ramoska EA, Spiller HA, Winter M, Borys D: A one-year evaluation of calcium channel blocker overdoses: toxicity and treatment. Ann Emerg Med 22:196–200, 1993. 46. Klein Schwartz W: Trends and toxic effects from pediatric clonidine exposures. Arch Pediatr Adolesc Med 156:392–396, 2002. 47. Kappagoda C, Schell DN, Hanson RM, Hutchins P: Clonidine overdose in childhood: implications of increased prescribing. J Paediatr Child Health 34:508–512, 1998. 48. Anderson RJ, Hart GR, Crumpler CP, Lerman MJ: Clonidine overdose: report of six cases and review of the literature. Ann Emerg Med 10:107– 112, 1981. 49. Olsson JM, Priutt AW: Management of clonidine ingestion in children. J Pediatr 103:646–650, 1983. 50. Barr CS, Payne R, Newton RW: Profound prolonged hypotension following captopril overdose. Postgrad Med J 67:953–954, 1991. 51. Navis G, Faber HJ, de Zeeuw D, de Jong PE: ACE inhibitors and the kidney: a risk-benefit assessment. Drug Saf 15:200–211, 1996. 52. Warner NJ, Rush JE: Safety profi les of the angiotensin-converting enzyme inhibitors. Drugs 35(Suppl 5):89–97, 1988. 53. Rimmer JM, Horn JF, Gennari FJ: Hyperkalemia as a complication of drug therapy. Arch Intern Med 147:867–869, 1987. 54. Lip GY, Ferner RE: Poisoning with antihypertensive drugs: angiotensin converting enzyme inhibitors. J Hum Hypertens 9:711–715, 1995. 55. Smith BA, Ferguson DB: Acute hydralazine overdose: marked ECG abnormalities in a young adult. Ann Emerg Med 21:326–330, 1992. 56. Price EJ, Venables PJ: Drug-induced lupus. Drug Saf 12:283–290, 1995. 57. Stainikowicz R, Amitai Y, Bentur Y: Aphrodisiac drug-induced hemolysis. J Toxicol Clin Toxicol 42:313–316, 2004. 58. Romanelli F, Smith KM, Thornton AC, Pomeroy C: Poppers: epidemiology and clinical management of inhaled nitrite. Pharmacotherapy 24:69–78, 2004. 59. Modarai B, Kapadia YK, Kerins M, Terris J: Methylene blue: a treatment for severe methaemoglobinaemia secondary to misuse of amyl nitrite. Emerg Med J 19:271–272, 2002. 60. Curry SC, Arnold-Capell P: Toxic effects of drugs used in the ICU: nitroprusside, nitroglycerin, and angiotensin-converting enzyme inhibitors. Crit Care Clin 7:555–581, 1991. 61. Farrell, SE, Epstein SK: Overdose of Rogaine Extra Strength for Men topical minoxidil. J Toxicol Clin Toxicol 37:781–783, 1999. 62. Lip GYH, Ferner RE: Poisoning with antihypertensive drugs: diuretics and potassium supplements. J Hum Hypertens 9:295–301, 1995. 63. Chvilicek JP, Hurlbert BJ, Hill GE: Diuretic-induced hypokalaemia inducing torsades de pointes. Can J Anaesth 42:1137–1139, 1995.

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64. Lankisch PG, Droge M, Gottesleben F: Drug induced acute pancreatitis: incidence and severity. Gut 37:565–567, 1995. *65. Loboz KK, Shenfield GM: Drug combinations and impaired renal function—the ‘triple whammy.’ Br J Clin Pharmacol 59:239–243, 2005. 66. Baer E, Reith DM: Acetazolamide poisoning in a toddler. J Paediatr Child Health 37:411–412, 2001. 67. Berkovitch M, Akilesh MR, Gerace R, et al: Acute digoxin overdose in a newborn with renal failure: use of digoxin immune Fab and peritoneal dialysis. Ther Drug Monit 16:531–533, 1994. 68. McCormick W, Ingelfi nger JA, Isakson G, Goldman P: Errors in measuring drug concentrations. N Engl J Med 299:1118–1121, 1978. 69. Loes MW, Singh S, Lock JE, Mirkin BL: Relation between plasma and red-cell electrolyte concentrations and digoxin levels in children. N Engl J Med 299:501–504, 1978. 70. Biddle TL, Weintraub M, Lasagna L: Relationship of seruim and myocardial digoxin concentration to electrocardiographic estimation of digoxin intoxication. J Clin Pharmacol 18:10–15, 1978. 71. Ma G, Brady WJ, Pollack M, Chan TC: Electrocardiographic manifestations: digitalis toxicity. J Emerg Med 20:145–152, 2001. 72. Position statement and practice guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning. American Academy of Clinical Toxicology; European Association of Poison Control Centres and Clinical Toxicologists. J Toxicol Clin Toxicol 37:731–751, 1999. 73. Antman EM, Wenger TL, Butler VP, et al: Treatment of 150 cases of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments: fi nal report of a multicenter study. Circulation 81:1774–1752, 1990. 74. Cheung K, Urech R, Taylor L, et al: Plant cardiac glycosides and digoxin Fab antibody. J Paediatr Child Health 27:312–313, 1991. 75. Flanagan RJ, Jones AL: Fab antibody fragments: some applications in clinical toxicology. Drug Saf 27:1115–1133, 2004. 76. Marchlinski FE, Hook BG, Callans DJ: Which cardiac disturbances should be treated with digoxin immune Fab (ovine) antibody? Am J Emerg Med 9(2 Suppl 1):24–28, 1991. 77. Heard K: Digoxin and therapeutic cardiac glycosides. In Dart R, Caravati EM, et al (eds): Medical Toxicology, 3rd ed. Philadelphia: JB Lippincott, 2004, pp 700–706. 78. Rumack BH, Wolfe RR, Gilfrich H: Phenytoin treatment of massive digoxin overdose. Br Heart J 36:405–408, 1974. 79. Nicholls DP, Murtagh JG, Holt DW: Use of amiodarone and digoxin specific Fab antibodies in digoxin overdosage. Br Heart J 53:462–464, 1985. 80. Lebovitz DJ, Lawless ST, Weise KL: Fatal amrinone overdose in a pediatric patient. Crit Care Med 23:977–980, 1995. 81. Alhashemi JA, Hooper J: Treatment of milrinone-associated tachycardia with beta-blockers. Can J Anaesth 45:67–70, 1998. 82. Losek JD, Endom E, Dietrich A, et al: Adenosine and pediatric supraventricular tachycardia in the emergency department: multicenter study. Ann Emerg Med 33:185–191, 1999. 83. Crosson JE: Therapeutic and diagnostic utility of adenosine during tachycardia evaluation in children. Am J Cardiol 74:155–160, 1994. 84. Mulla N, Karpawich PP: Ventricular fibrillation following adenosine therapy for supraventricular tachycardia in a neonate with concealed Wolff-Parkinson-White syndrome treated with digoxin. Pediatr Emerg Care 11:238–239, 1995. 85. Lowenstein SR, Laperin BD, Reiter MJ: Paroxysmal supraventricular tachycardias. J Emerg Med 14:39–51, 1996.

Chapter 138 Near Drowning and Submersion Injuries T. Kent Denmark, MD and Steven C. Rogers, MD

Key Points The literature predicting outcome of submersion injury is contradictory. Rare, evidence-based, guideline-defying recoveries occur. Technological advances have not affected outcomes. Patients who remain asymptomatic for 4 to 6 hours may be discharged home.

Introduction and Background While more common in temperate climates, submersion injuries and drowning will be encountered and managed by every emergency physician at some point during his or her career. Drowning deaths occur throughout the United States, in decreasing order, from the South, West, Midwest, and Mid-Atlantic to New England.1 Drowning is the second leading cause of injurious deaths in children 1 to 14 years of age. The Centers for Disease Control estimates that over 2000 children less than 4 years of age seek medical attention for near drowning per year. In addition, 1000 children ages 5 to 14 years, and approximately 900 adolescents, will also be treated for near drowning.2 The most dangerous water exposures occur with children less than 4 years of age in either pools or bathtubs.3-5 In contrast to the exploratory behavior of children, adolescents who have submersion injuries or drown are usually intoxicated and swimming at lakes or rivers.6 Adolescent incidents tend to occur while swimming or boating and are usually witnessed.3 There is an additional sense of tragedy when these cases are encountered in the emergency department (ED) because drowning is one of the most preventable causes of morbidity and mortality. Drowning and submersion injuries continue to occur in large part due to lack of recognition of the danger on the part of parents and caregivers. A study of parental beliefs and practices regarding home safety showed that the potential

injury severity and extent of effort required to implement the safety practices determined which precautions were undertaken.7 Parents simply do not believe their particular child is at risk, and their assumptions about the inherent safety of an above-ground pool are inaccurate.7 Partial preventative efforts may not be enough to prevent submersion or drowning from occurring. For example, two thirds of 4-year-olds can scale a smooth 48-inch barrier in less than 2 minutes.8 Appreciation of this information may enable emergency physicians to serve as an important resource for home safety education.9 One of the most distressing decisions in managing a patient who has drowned is the decision to discontinue the resuscitation. While clinical guidelines exist, several cases have been reported in the medical literature and in the popular media that defy these guidelines. First documented by Kvittingen in 1963, there are several reports of “near drownings” in patients who fully recovered from significant submersion events of up to 66 minutes.10,11 Therefore, family members’ expectations of resuscitation outcome may be inaccurate and overly optimistic. The media have contributed to these beliefs by focusing on the dichotomous outcomes from arrest while completely ignoring the severe neurologic impairment that may result from a significant cardiopulmonary arrest.12 The reality is that hospitalized near-drowning victims in the United States have a high case fatality rate (~25%) and high rate of subsequent sequelae (10%).4 This is consistent with a comprehensive study in the British Isles that found that greater than one third of admitted patients either expired or had residual neurologic deficits following a near-drowning incident.13 Therefore, the treating physician should be mindful of these faulty beliefs when informing the family about management decisions. In spite of an increase in understanding of the pathophysiology of submersion injuries and advances in therapy, the mortality has not significantly decreased, but the number of neurologically impaired children who survive may be increasing.4,14,15

Recognition and Approach The physiologic response to submersion has been studied extensively. The initial response to a cold water submersion is tachypnea, tachycardia, and hypertension for 1 to 2 minutes 987

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followed by apnea 3 minutes after submersion and finally hypotension and asystole between 6 and 8 minutes postsubmersion.16-18 Either electroencephalographic silence or seizure activity occurs with hypotension prior to asystole.18 The rapidity of significant physiologic changes in submersion victims underscores the necessity of supervisory vigilance and prevention. Some children survive prolonged submersions, and a number of explanations for this phenomenon have been offered. The diving reflex, defined as apnea, generalized marked peripheral vasoconstriction, and bradycardia, is well described in marine mammals and has been generally accepted as the mechanism for survival.19 However, given that breath-holding duration is decreased by 25% upon rapid exposure to water colder than 15° C, the theory of the diving reflex as an explanation for remarkable recoveries is questionable.17,20 In addition, it has been proven that, even with the greater body surface area of infants, surface cooling does not occur quickly enough to be cerebroprotective.21-23 Hypothermia is only protective if the central nervous system (CNS) temperature drops by greater than 7° C in 10 minutes.24 Aspiration of cold water causes rapid cooling when compared to submersion.16 Dog studies have shown that rapid, involuntary respirations occur following submersion for a little more than a minute.25 Extremely rapid core cooling can occur within 2 minutes of submersion when cold water is aspirated, leading to rapid core cooling to protective levels, which occurs about 1 minute before cardiac arrest.16,18 Microaspiration with initial tachypnea will cause rapid cooling of circulation, which is preferentially shunted to the CNS.19 Animals resuscitated with cold solutions following 20 minutes of arrest have good functional recovery compared those resuscitated with room-temperature fluids.26 Pulmonary vasoconstriction and pulmonary hypertension following aspiration are attenuated when cold fluid is aspirated.27 This may help explain the miraculous cases of full recovery from extended submersions. Studies of military and competitive swimmers show that even body-only immersion increases cardiac preload and pulmonary arterial pressure from peripheral vasoconstriction.28 Subsequently, ventilation-perfusion (V/Q) mismatch, hypoxemia, and pulmonary vasoconstriction will lead to a decrease in functional residual capacity.28 This clinically manifests itself as tachypnea to compensate for inefficient gas exchange. Swimming-induced pulmonary edema occurs in about 2% of healthy competitive swimmers and presents with dyspnea, cough, and hemoptysis.29 The effects may still be detected on pulmonary function tests for up to a week.29 Patients who are actually submerged have more extensive sequelae. Surfactant loss or inactivation decreases pulmonary compliance, and there may be significant V/Q mismatch, with 75% of blood flow to nonventilated areas.30,31

Clinical Presentation In most cases, the history of submersion is known or apparent as relayed by rescue personnel, parents, or bystanders. History can be especially helpful in a witnessed event when trying to differentiate between primary submersion injury and an event secondary to another process such as seizure or arrhythmia. While seizures can occur from anoxia, seizure

activity prior to submersion or in a patient with a history of epilepsy should raise concern for a primary neurologic process.18 Patients with a history of seizures or epilepsy have a 10-fold increased risk for drowning.32 Typical epileptic submersion victims are older than 5 years of age and in the bathtub, although children and adolescents with epilepsy are also at increased risk of drowning in pools.32 Patients with a known seizure disorder should never be left unattended near water. In particular, patients with a history of febrile seizures should not be left unattended while receiving “cooling measures” in the bathtub. Complaints of palpitations prior to submersion or a history of arrhythmia should prompt a more thorough cardiac investigation. In teenagers, a significant percentage of submersion injuries involve alcohol or other drugs.6,15 This potentially complicates mental status assessment and evaluation for associated trauma. A serum alcohol level and urine drug screen should be obtained in all adolescents with submersion injury to aid in management decisions. Cervical spine injuries in adolescents do not occur without a significant mechanism; the routine activation of the trauma team without a suspicious mechanism (such as diving or submersion in ocean surf) is not useful, nor are routine cervical spine radiographs in nontraumatic submersions.33 A subpopulation at high risk for associated traumatic injuries are those patients who are submersed in bathtubs. In a landmark study, two thirds of bathtub drownings seen at one facility over a 10-year period had historical fi ndings consistent with neglect and one third had physical findings of child abuse.34 In this population, 49% either expired or had significant neurologic sequelae.34 It is therefore prudent to have concern for abuse and/or neglect in these patients. Chest radiographs do not predict disposition or clinical course.35,36 Specifically, the presence or absence of radiographic findings does not correlate with clinical findings, pulse oximetry, or length of oxygen requirement and is not useful. Although electrolyte disturbances do occur, the presence of an abnormality does not automatically necessitate hospitalization, and should not alter initial fluid resuscitation. Similarly, the initial pH is not prognostic in predicting morbidity or mortality, so that routinely obtaining blood gases in submersion patients is not beneficial.35,36 However, patients who have been intubated should be monitored appropriately, including regular evaluation of arterial blood gases and electrolytes.

Management Immediate airway management and initiation of CPR are unequivocally the most effective interventions for the submersion victim (Table 138–1). Bystander cardiopulmonary resuscitation (CPR) has been shown to significantly affect patient survival, and even rescue breathing or cardiac compressions alone are superior to no intervention.37-39 All patients should be transported to the hospital for evaluation. Basic life support protocols and standard trauma protocols must be followed, including cervical spine immobilization when there is a history suggestive of an injury or suspicion of a traumatic mechanism.33 Wet clothing should be removed to minimize heat loss. Airway protection must be a high priority due to the high frequency of vomiting (up to 86%) with chest compressions.40 Early placement of a

Chapter 138 — Near Drowning and Submersion Injuries

Table 138–1

Clinical Pearls and Pitfalls

Pearls • “Just do something”: chest compressions and assisted ventilation improve outcome in asphyxial arrest.37 • Cardiopulmonary resuscitation prior to Emergency Medical Services arrival is associated with significantly better neurologic outcome.38,39,69 Pitfalls • Ending a resuscitation too soon risks an inadequate chance for return of spontaneous circulation in very cold water submersions.55-57 • Continuing resuscitation too long creates neurologically devastated survivors.4 • Decrease in core temperature during rewarming is not necessarily a sign of inadequate therapy.45 • Pulse oximetry does not always correlate with hypoxemia in severe hypothermia.44

nasogastric tube to decompress the stomach will decrease the risk of vomiting in patients who have received rescue breaths. Early tracheal intubation is recommended for airway protection, to ensure removal of any foreign material from the airway, and to institute continuous positive airway pressure or positive end-expiratory pressure as needed for respiratory failure.40 Once the airway is controlled, hypoxia and acidosis are better tolerated than hypoxia and hypotension. Permissive hypercapnia is preferable to avoid hypotension secondary to high mean airway pressures, which impede preload.41 No literature specifically addresses the use of bronchodilators for wheezing in a submersion victim. A reasonable approach is a one-time trial of bronchodilator therapy, with repeated treatments for the patients who improve clinically. In patients with a history of reactive airways disease or asthma, bronchodilators should be considered beneficial despite a dearth of evidence to support this recommendation. Pediatric submersion victims are frequently hypothermic upon arrival to the ED. Due to significant peripheral vasoconstriction, rectal temperature lags behind true core temperature.16,18 Jugular bulb temperature reflects body temperature, not true CNS temperature, but determining true CNS temperature is impossible without invasive monitoring.42 An exaggerated response to warming occurs, making hyperthermia after resuscitation common.43 When monitoring the hypothermic patient, the clinician should remember that pulse oximetry is not reliable under 27° C.44 “Afterdrop” is a phenomenon that occurs during rewarming when a patient experiences a drop in core temperature secondary to mobilization of cold blood from the peripheral circulation. Afterdrop has been associated with sudden death in otherwise intact hypothermia survivors.45 Care must be taken not to be overly aggressive during the rewarming process. Rewarming with forced air (Bair Hugger) can increase temperature at a safe rate of 1.7° C/hr.46 This method requires circulation to be effective. In cases of severe hypothermia or cardiac arrest, extracorporeal rewarming may be beneficial.11 This technique has been available outside the surgical suite since 1993.47 Extracorporeal rewarming has a 50% intact survival rate for adults with severe accidental nonsubmersion hypothermia but presents obvious logistic difficulties for ED care.48 Alternatively, therapeutic hypothermia is potentially beneficial and neuroprotective for submersion victims.49,50 The

Table 138–2

989

Complications of Submersion Injury

Acute respiratory distress syndrome Arrhythmias Aspiration Cerebral edema Chronic pulmonary dysfunction Disseminated intravascular coagulopathy Hyperthermia Hypotension Neurologic impairment Renal impairment Sepsis

stipulation is that the hypothermia must occur within 7 minutes of hypoxemia to be beneficial.24 However, hypothermia can also decrease peripheral circulation and may inhibit adequate distribution of rescue medications. Caution must be exercised to not overmedicate based on lack of effect at time of administration in patients with compromised circulation or peripheral vasoconstriction. Multiple secondary therapeutic interventions have been investigated. High-dose barbiturate therapy has been shown to help control intracranial pressure (ICP), but neither barbiturate therapy nor ICP monitoring appears to improve neurologic outcome.40,51 Prophylactic steroids and antibiotics have been studied extensively and do not increase the odds of survival52 (see Chapter 9, Cerebral Resuscitation). Patients who are initially hypothermic must be continually monitored to gauge the success of intervention and to guard against hyperthermia. An initial decrease in temperature as a result of afterdrop is not uncommon and should not be equated with inadequate rewarming.45 During rewarming from profound hypothermia, care must be taken so that rewarming does not occur too quickly and precipitate arrhythmias. Overly rapid rewarming also leads to hypotension from peripheral vasodilation, hypoxemia, and sinus bradycardia.53 Aspiration, whether of gastric contents or from the body of water, is a risk in any patient with an altered level of consciousness (Table 138–2). Tachypnea secondary to the pulmonary effects of submersion and the possibility that some rescuers will perform the Heimlich maneuver increases the odds of an aspiration. Awake, alert patients who are asymptomatic after 4 to 6 hours of observation may be safely discharged home.35,36 Historically, there have been reports of “secondary drowning” in otherwise normal-appearing patients, but similar cases have not been seen in subsequent research. Upon review, such cases were not clinically subtle or suitable for discharge.54 Patients who are clinically symptomatic after 6 hours require inpatient care in a monitored bed. The emergency physician should communicate early with pediatric intensivists and/or referral centers for children with persistent symptoms or severe initial condition to arrange for admission or transport to a capable facility. Bathtub drownings or other cases suspicious for nonaccidental injury or neglect should be evaluated in conjunction with social work and law enforcement in accordance with local protocols. As noted earlier, maintaining high concern for abuse and/or neglect is the key to identifying these cases.

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When a patient has a clear traumatic mechanism of injury associated with submersion, surgical consultants should be involved in evaluation and management. Other subspecialty services should be consulted as needed for patients with identifiable predisposing factors such as seizures or arrhythmias. If possible, the emergency physician should contact the patients’ primary care physician to identify any unknown history and to arrange for adequate follow-up or ongoing care of more severe patients. The primary care physician may also be helpful in assisting the family in making important decisions about termination of life support when neurologic devastation is apparent. Consensus exists for poor prognostic signs and symptoms, yet it is important to acknowledge that there will be outlying cases that defy all predictions of survival despite meeting all poor prognostic criteria.55-57 These cases occur very rarely and must be weighed against the more frequent occurrence of survival with neurologic devastation. There are no absolutely reliable indicators of intact survival with cold water submersions.58 Positive prognostic indicators include submersion time less than 10 minutes, no evidence of aspiration, and body core temperature less than 35° C.58 Younger age of the victim as a positive prognosticator is supported in some studies but not others.58-60 Hypothermia that is delayed 15 minutes does not have the same protective effect (only moderate disability) as immediate hypothermia.61 Severe acidosis, with a pH as low as 6.33, has been reported with full recovery, reinforcing the poor prognostic value of this particular test.62 Mean time to return of spontaneous circulation for hypothermic submersion patients requiring CPR upon arrival at the ED is 58 minutes.63 It seems prudent to continue resuscitation of the hypothermic patient from a cold water submersion for a total of at least 1 hour. In the ED, outcome of patients who have spontaneous circulation without spontaneous respirations cannot be reliably predicted. Children may experience an unexpected full recovery following a prolonged vegetative state.64 Dilated pupils 6 hours after injury and seizures 24 hours after admission have been associate with poor outcome, but again, case reports with exceptions have been published.13,55,57,65 The Pediatric Risk of Mortality (PRISM) score is somewhat helpful, but often does not differentiate neurologically intact survival among patients with median scores.14,66,67 There is universally poor neurologic outcome for patients who were normothermic, pulseless, and apneic upon arrival in the ED, although some still recommend continued support for 24 hours.63 The prognosis for children requiring CPR regardless of etiology is poor, and patients requiring more than two doses of epinephrine or resuscitation longer than 20 minutes also have a very poor prognosis.39,68 All patients with spontaneous respirations on presentation to the ED recover, and reactive pupils support a good prognosis.13

Summary Submersion injuries in children are common and are likely to be seen in geographically diverse practice settings. Patients who are asymptomatic 4 to 6 hours after submersion may be discharged home, while all others require admission to a monitored bed. Since near-drowning patients may be difficult to ventilate, it is prudent to expeditiously transfer symptomatic patients to a tertiary care facility.

In spite of advances in knowledge and technology, the prognosis of near-drowning patients has not changed. While there is a possible role for therapeutic hypothermia, the most effective strategy in minimizing morbidity and mortality from drowning is obviously prevention. Once a near drowning has occurred, immediate bystander CPR is the most effective intervention. REFERENCES 1. Brenner RA, Trumble AC, Smith GS, et al: Where children drown, United States, 1995. Pediatrics 108:85–89, 2001. 2. Gilchrist J, Gotsch K, Ryan G: Nonfatal and fatal drownings in recreational water settings—United States, 2001–2002. MMWR Morb Mortal Wkly Rep 53:447–452, 2004. 3. Quan L, Cummings P: Characteristics of drowning by different age groups. Inj Prev 9:163–168, 2003. 4. Joseph MM, King WD: Epidemiology of hospitalization for neardrowning. South Med J 91:253–255, 1998. 5. O’Carroll PW, Akron E, Weiss B: Drowning mortality in Los Angeles County, 1976–1984. JAMA 260:380–383, 1988. 6. Quan L, Gore EJ, Wentz K, et al: Ten-year study of pediatric drownings and near-drownings in King County, Washington: lessons in injury prevention. Pediatrics 83:1035–1040, 1989. 7. Morrongiello BA, Kiriakou S: Mothers’ home-safety practices for preventing six types of childhood injuries: what do they do, and why? J Pediatr Psychol 29:285–297, 2004. 8. Ridenour MV: Climbing performance of children: is the above-ground pool wall a climbing barrier? Percept Mot Skills 92:1255–1262, 2001. 9. Posner JC, Hawkins LA, Garcia-Espana F, et al: A randomized, clinical trial of a home safety intervention based in an emergency department setting. Pediatrics 113:1603–1608, 2004. 10. Kvittingen TD, Naess A: Recovery from drowning in fresh water. Br Med J 1:1315–1317, 1963. 11. Bolte RG, Black PG, Bowers RS, et al: The use of extracorporeal rewarming in a child submerged for 66 minutes. JAMA 260:377–379, 1988. 12. Diem SJ, Lantos JD, Tulsky JA: Cardiopulmonary resuscitation on television—miracles and misinformation. N Engl J Med 334:1578–1582, 1996. 13. Kemp AM, Sibert JR: Outcome in children who nearly drown: a British Isles study. BMJ 302:931–933, 1991. 14. Spack L, Gedeit R, Splaingard M, et al: Failure of aggressive therapy to alter outcome in pediatric near-drowning. Pediatr Emerg Care 13:98– 102, 1997. 15. Cummings P, Quan L: Trends in unintentional drowning: The role of alcohol and medical care. JAMA 281:2198–2202, 1999. 16. Conn AW, Miyasaka K, Katayama M, et al: A canine study of cold water drowning in fresh versus salt water. Crit Care Med 23:2029–2037, 1995. 17. Hayward JS, Eckerson JD: Physiological responses and survival time prediction for humans in ice water. Aviat Space Environ Med 55:206– 211, 1984. 18. Gilbertson L, Safar P, Stezowski X, et al: Pattern of dying during cold water drowning in dogs. Crit Care Med 4:216, 1982. 19. Golden F: Mechanisms of body cooling in submersed victims. Resuscitation 35:107–109, 1997. 20. Gooden BA: Why some people do not drown: hypothermia versus the diving response. Med J Aust 157:629–632, 1992. 21. Xu X, Tikuisis P, Giesbrecht G: A mathematical model for human brain cooling during cold-water near-drowning. J Appl Physiol 86:265–272, 1999. 22. Mohri H, Dillard DH, Crawford EW, et al: Method of surface induced deep hypothermia for open-heart surgery in infants. J Thorac Cardiovasc Surg 58:262–270, 1969. 23. Zeiner A, Holzer M, Sterz F, et al: Mild resuscitative hypothermia to improve neurological outcome after cardiac arrest. Stroke 31:86–94, 2000. 24. Stern WE, Good RG: Studies of the effects of hypothermia upon cerebrospinal fluid oxygen tension and carotid blood flow. Surgery 48:13– 30, 1960. 25. Fainer DC, Martin CG, Ivy AC: Resuscitation of dogs from fresh water drowning. J Appl Physiol 3:417–426, 1951.

Chapter 138 — Near Drowning and Submersion Injuries 26. Behringer W, Prueckner S, Safar P, et al: Rapid induction of mild cerebral hypothermia by cold aortic flush achieves normal recovery in a dog outcome model with 20-minute exsanguinations cardiac arrest. Acad Emerg Med 7:1341–1348, 2000. 27. Colebatch HJH, Halmagyi DJF: Effect of vagotomy and vagal stimulation on lung mechanics and circulation. J Appl Physiol 18:881–887, 1963. 28. Lund KL, Mahon RT, Tanen DA, Bakhda S: Swimming-induced pulmonary edema. Ann Emerg Med 41:251–256, 2003. 29. Adir R, Shupak A, Gil A, et al: Swimming-induced pulmonary edema: clinical presentation and serial lung function. Chest 126:394–399, 2004. 30. Halmagyi DFJ, Colebatch HJH: Ventilation and circulation after fluid aspiration. J Appl Physiol 16:35–40, 1961. 31. Bergquist RE, Vogelhut MM, Modell JH, et al: Comparison of ventilatory patterns in the treatment of freshwater near-drowning in dogs. Anaesthesiology 52:142–148, 1980. 32. Diekema DS, Quan L, Holt VL: Epilepsy as a risk factor for submersion injury in children. Pediatrics 91:612–616, 1993. 33. Hwang V, Shofer FS, Durbin DR, et al: Prevalence of traumatic injuries in drowning and near drowning in children and adolescents. Arch Pediatr Adolesc Med 157:50–53, 2003. *34. Lavelle JM, Shaw KN, Seidl T: Ten-year review of pediatric bathtub near-drownings: evaluation for child abuse and neglect. Ann Emerg Med 25:344–348, 1995. *35. Causey AL, Tilelli JA, Swanson ME: Predicting discharge in uncomplicated near-drowning. Am J Emerg Med 18:9–11, 2000. 36. Noonan L, Howrey R, Ginsburg CM: Freshwater submersion injuries in children: a retrospective review of seventy-five hospitalized patients. Pediatrics 98:368–371, 1996. 37. Berg RA, Hilwig RW, Kern KB, et al: “Bystander” chest compressions and assisted ventilation independently improve outcome from piglet asphyxial pulseless “cardiac arrest.” Circulation 101:1743–1748, 2000. 38. Kyriacou DN, Arcinue EL, Peek C, et al: Effect of immediate resuscitation on children with submersion injury. Pediatrics 94(2 Pt 1):137–142, 1994. 39. Sirbaugh PE, Pepe PE, Shook JE, et al: A prospective, population-based study of the demographics, epidemiology, management, and outcome of out-of-hospital pediatric cardiopulmonary arrest. Ann Emerg Med 33:174–184, 1999. 40. Kloeck W, Cummins R, Chamberlain D, et al: Special resuscitation situations: an advisory statement from the International Liaison Committee on Resuscitation. Circulation 95:2196–2210, 1997. 41. Bender TM, Johnston JA, Manepalli AN, et al: Correlation of brain tissue pH with histopathology in a piglet model of perinatal asphyxia. Pediatrics 100:494, 1997. 42. Rumana CS, Gopinath SP, Rzura M, et al: Brain temperature exceeds systemic temperature in head-injured patients. Crit Care Med 26:562– 567, 1998. 43. Hickey RW, Kochanek PM, Ferimer H, et al: Hypothermia and hyperthermia in children after resuscitation from cardiac arrest. Pediatrics 106:118–122, 2000. 44. Iyer P, McDougall P, Loughnan P, et al: Accuracy of pulse oximetry in hypothermic neonates and infants undergoing cardiac surgery. Crit Care Med 24:507–511, 1996. 45. Nuckton TJ, Claman DM, Goldreich D, et al: Hypothermia and afterdrop following open water swimming: the Alcatraz/San Francisco swim study. Am J Emerg Med 18:703–707, 2000. 46. Kornberger E, Schwarz B, Lindner KH, et al: Forced air surface rewarming in patients with severe accidental hypothermia. Resuscitation 41:105–111, 1999. *Selected readings.

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47. Waters DJ, Belz M, Lawse D, et al: Portable cardiopulmonary bypass: resuscitation from prolonged ice-water submersion and asystole. Ann Thorac Surg 57:1018–1019, 1994. 48. Walpoth BH, Walpoth-Aslan BN, Mattle HP, et al: Outcome of survivors of accidental deep hypothermia and circulatory arrest treated with extracorporeal blood warming. N Engl J Med 337:1500–1505, 1997. 49. Holzer M, Behringer W, Schörkhuber W, et al: Mild hypothermia and outcome after CPR. Acta Anesthesiol Scand 111(Suppl):55–58, 1997. 50. Thoresen M, Bagenholm R, Loberg EM, et al: Posthypoxic cooling of neonatal rats provides protection against brain injury. Arch Dis Child 74:F3–F9, 1996. 51. Bohn DJ, Biggar WD, Smith CR, et al: Influence of hypothermia, barbiturate therapy, and intracranial pressure monitoring on morbidity and mortality after near-drowning. Crit Care Med 14:529–534, 1986. 52. Modell JH, Graves SA, Ketover A: Clinical course of 91 consecutive near-drowning victims. Chest 70:231–238, 1976. 53. Thoresen M, Whitelaw A: Cardiovascular changes during mild therapeutic hypothermia and rewarming in infants with hypoxic-ischemic encephalopathy. Pediatrics 106:92–99, 2000. 54. Pearn JH: Secondary drowning in children. BMJ 281:1103–1105, 1980. 55. Modell JH, Idris AH, Pineda JA, et al: Survival after prolonged submersion in freshwater in Florida. Chest 125:1948–1951, 2004. 56. Associated Press: “Dead” boy survived drowning. Boise, ID: May 28, 2004. 57. Yi D, Mena J: Near drowning: toddler resuscitated 40 minutes after being declared dead. LA Times, Nov 8, 2003. 58. Bierens JJ, van der Velde EA, van Berkel M, et al: Submersion in the Netherlands: prognostic indicators and results of resuscitation. Ann Emerg Med 19:1390–1395, 1990. 59. Suominen PK, Korpela RE, Silfvast TGO, et al: Does water temperature affect outcome of nearly drowned children? Resuscitation 35:111–115, 1997. 60. Suominen P, Baillie C, Korpela R, et al: Impact of age, submersion time and water temperature on outcome in near-drowning. Resuscitation 52:247–254, 2002. 61. Kuboyama K, Safar P, Radovshy A, et al: Delay in cooling negates the beneficial effect of mild resuscitative cerebral hypothermia after cardiac arrest in dogs: a prospective, randomized study. Crit Care Med 21:1348–1358, 1993. 62. Opdahl H: Survival put to the acid test: Extreme arterial blood acidosis (pH 6.33) after near drowning. Crit Care Med 25:1431–1436, 1997. 63. Biggart MJ, Bohn DJ: Effect of hypothermia and cardiac arrest on outcome of near-drowning accidents in children. J Pediatr 117(2 Pt 1):179–183, 1990. 64. Quan L, Wentz KR, Gore EJ, et al: Outcome and predictors of outcome in pediatric submersion victims receiving prehospital care in King County, Washington. Pediatrics 86:586–593, 1990. 65. Christensen DW, Janesen P, Perkin RM: Outcome and acute care hospital costs after warm water near drowning in children. Pediatrics 99:715–721, 1997. 66. Gonzales-Luis G, Pons M, Cambra FJ: Use of the Pediatric Risk of Mortality score as predictor of death and serious neurologic damage in children after submersion. Pediatr Emerg Care 17:405–409, 2001. 67. Zuckerman GB, Gregory PM, Santos-Diamiani SM: Predictors of death and neurologic impairment in pediatric submersion injuries. Arch Pediatr Adolesc Med 152:134–140, 1998. 68. Young KD, Seidel JS: Pediatric cardiopulmonary resuscitation: A collective review. Ann Emerg Med 33:195–205, 1999. 69. Schindler MB, Bohn D, Cox PN, et al: Outcome out-of-hospital cardiac or respiratory arrest in children. N Engl J Med 335:1473–1479, 1996.

Chapter 139 Hyperthermia Paul Ishimine, MD

Key Points The hallmark of heatstroke is central nervous system dysfunction, but children with heatstroke may only have subtle neurologic findings and may be sweating profusely. Cooling measures should be initiated immediately in patients with heatstroke even in the prehospital environment. Heatstroke should be considered in children who collapse while exercising, even if their temperature is minimally elevated upon emergency department presentation.

Introduction and Background Heat-related illness results from excessive heat stress. This may occur from an increased environmental burden or from an inability of the body to dissipate endogenous heat. The spectrum of heat illness ranges from minor to life threatening. Heat-related morbidity and mortality increase significantly during periods of high environmental temperature1-3 Heat-related morbidity and mortality also increases in the presence of comorbid disease and increasing age; the highest rate of death is in the elderly population.4,5 However, children are also susceptible to heat-related morbidity and mortality because of unique anatomic and physiologic characteristics.

Recognition and Approach The human body is remarkably homeostatic and constantly regulates body temperature through a balance of heat production, absorption, and dissipation. Heat transfer occurs by four mechanisms: evaporation, convection, radiation, and conduction. Evaporation is the conversion of a liquid into a gas. The evaporation of sweat is the primary means of heat loss as ambient temperature rises, but this mechanism of heat transfer becomes less effective as ambient humidity increases. Additionally, dehydration results in decreased skin blood 992

flow and increased rate of sweating, which in turn results in a decrease in evaporative cooling. Convection is the transfer of heat from skin to circulating air and water vapor molecules. Convective heat loss directly varies with wind velocity, and once the air temperature exceeds the skin temperature, convection results in heat gain. Radiation refers to the transfer of heat between the body and its surroundings by electromagnetic waves, and this represents a substantial source of heat gain in hot environments. Conduction is the transfer of heat from warmer to cooler objects via direct physical contact. This generally represents a minimal source of heat transfer, unless the skin is in contact with water. Heat regulation is mediated by thermosensors, a central integrative area, and thermoregulatory effectors. Thermosensors are located peripherally in the skin and centrally in the preoptic area of the anterior hypothalamus, brainstem and spinal cord, and abdominal viscera. The central integrative area interprets information from the thermosensors and regulates thermoregulatory effectors. The thermoregulatory effectors stimulate sweating, vasodilation, and cold-seeking behavior, which are the main means by which heat loss is accelerated. Several key anatomic and physiologic differences exist between children and adults. Children have a higher surface area–to-mass ratio, resulting in a greater rate of heat loss by convection than adults. In extreme conditions this results in a higher rate of heat absorption in hot environments. Children have both a smaller absolute blood volume and a smaller blood volume relative to body mass and surface area, which limits potential heat transfer from the body core to the body surface, where it can be dissipated.6 Children have a lower rate of sweating than adults as a result of a lower sweat rate per gland,7 and they take longer than adults to acclimatize to hot environments.8 Children have higher energy expenditure and heat production compared with adults. Exercising children, who are dehydrated, have a greater rise in rectal temperature than adults who are exercising in the heat even when corrected for body weight.9 They inadequately replenish fluid losses during exercise.10 Children are also susceptible to heatrelated illness because of an inability to escape from hot environments. Young children are at high risk for morbidity and mortality when left unattended in vehicles, as intravehicular temperatures rapidly rise to dangerous levels.11,12 Heavily bundled young children have also died from hyperthermia while in bed.13 Teenage athletes are another group that is at high risk for exertional heat-related illness.

Chapter 139 — Hyperthermia

Clinical Presentation The degree to which children develop signs and symptoms from heat stress depends on a number of factors. Much of the risk for heat illness is attributable to the environment, such as the ambient temperature and humidity level. However, individual variables also place the child at risk for heat-related disease. Children with special health care needs are especially vulnerable to heat-related illness (Table 139–1). Miliaria (“prickly heat” or “heat rash”) is an inflammatory rash resulting from blockage and subsequent rupture of sweat glands. Miliaria crystallina occurs typically in neonates and in sunburned areas. This rash is characterized by clear, small, sweat-fi lled vesicles. Miliaria rubra is an erythematous papular rash typically seen in intertriginous areas or in truncal areas covered by clothing. The sweat glands enlarge and rupture within the lower epidermis, resulting in an erythematous rash. Heat cramps are muscle cramps that usually occur several hours after exertion and commonly involve the large muscle groups of the legs. These are thought to occur because of dilutional hyponatremia from rehydration with free water but not salt, but the exact etiology is unclear.14 While these can be quite uncomfortable, heat cramps do not lead to significant morbidity. Heat cramps are often confused with heat tetany, which is caused by hyperventilation associated with heat stress, resulting in respiratory alkalosis, circumoral and extremity paresthesias, and carpopedal spasm. Heat edema and heat syncope are heat-related conditions found more commonly in the elderly than in children. Heat edema, which causes swelling of the hands and feet, results from vasodilation and pooling of increased interstitial fluid in dependent extremities, as well as an increase in aldosterone and antidiuretic hormone secretion. Heat syncope results from volume depletion, peripheral vasodilation, and decreased vasomotor tone. Table 139–1

Risk Factors for Heat Illness31

Excessive Fluid Loss Febrile illness Gastrointestinal illness Dehydration Diabetes Burns Sweating Dysfunction Cystic fibrosis32-34 Spina bifida Sweating insufficiency syndrome Ectodermal dysplasia Diminished Fluid Intake Developmental delay Young children Thermoregulatory Dysfunction Anorexia nervosa Previous heat-related illness Multifactorial Obesity Medications (e.g., anticholinergic agents, pseudoephedrine, amphetamines, cocaine,35 alcohol) Prepubescent age Lack of fitness or acclimatization Sickle cell disease36-38

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Heat exhaustion is characterized by volume depletion, and is usually (but not always) associated with a slightly elevated body temperature. Heat exhaustion can be further subclassified as water-depletion heat exhaustion (characterized by inadequate water replacement) or salt-depletion heat exhaustion (characterized by salt loss and replacement by hypotonic solution), but most patients have combined water-salt depletion. Symptoms are nonspecific and include thirst, weakness, fatigue, dizziness, irritability, headache, nausea, and vomiting. Patients with water-depletion heat exhaustion typically have elevated sodium and chloride levels, while those patients with salt-depletion heat exhaustion have hyponatremia and hypochloremia. Heatstroke is typically defined as a core temperature ≥ 40° C and central nervous system (CNS) dysfunction. This must be continuously monitored with a rectal probe thermometer that is accurate to high temperatures. While anhidrosis is commonly present, this is not an absolute criterion for making this diagnosis.15 Signs of heatstroke may occur abruptly. Classic heatstroke arises from environmental exposure to heat and is more common in younger children who are unable to escape from hot environments. Exertional heatstroke results from strenuous exercise and is more common in older children and adolescents. The differential diagnosis for heatstroke is presented in Table 139–2. Heatstroke is associated with a systemic inflammatory response, with a predominance of CNS symptoms. While CNS symptoms may be subtle and manifest as impaired judgment or inappropriate behavior, children commonly present with more significant neurologic symptoms such as seizures, delirium, hallucinations, ataxia, or coma. Anhidrosis results from severe dehydration and sweat gland dysfunction, but profuse sweating may precede anhidrosis. Patients are tachycardic and tachypneic. Vomiting, diarrhea, and gastrointestinal bleeding are thought to be consequences of impaired perfusion to the mesentery. Patients may be incontinent and have hematuria, oliguria, or anuria. Coagulopathies may result in purpura, subconjunctival hemorrhage, and other signs of bleeding. Table 139–2

Differential Diagnosis of Heat Stroke

Infectious Central nervous system infections Sepsis Neurologic Status epilepticus Intracranial hemorrhage Hypothalamic dysfunction Drug Related Anticholinergic medications Stimulants (e.g., amphetamines, cocaine) Salicylates Drug withdrawal (e.g., ethanol) Serotonin syndrome Neuroleptic malignant syndrome Malignant hyperthermia Endocrine Thyroid storm Miscellaneous Hemorrhagic shock and encephalopathy syndrome39-42

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SECTION V — Approach to Environmental Illness and Injury

Patients with heatstroke have abnormal laboratory tests, reflecting the systemic inflammatory response and end-organ damage as a result of heat stress. Hematologic findings include hemoconcentration and elevated white blood cell count. Thrombocytopenia and disseminated intravascular coagulation are seen frequently in heatstroke, although these findings are seen 18 to 36 hours after the initial heat stress.16,17 Electrolytes disturbances are frequent. Patients are usually hypokalemic but may be hyperkalemic. While hypernatremia may be present, normal sodium levels are common as well. Serum calcium levels can be either high or low. Elevated blood urea nitrogen and creatinine levels indicate acute renal failure, which occurs from a combination of factors, including dehydration and direct renal injury. Rhabdomyolysis, with an accompanying rise in creatine kinase, contributes to renal failure. Patients can be hyper-, normo-, or hypoglycemic. Metabolic acidosis is the most commonly observed acid-base disturbance and is associated with the degree of hyperthermia; respiratory alkalosis is seen frequently as well.18 Elevation of liver enzymes is common in heatstroke,19 but liver failure is much less common. The presence of hepatic injury has been suggested as a criterion to distinguish between heat exhaustion and heatstroke. A computed tomography scan of the head should be obtained if a child has persistently altered mental status despite cooling, or if a neurologic cause of hyperthermia (e.g., intracranial hemorrhage) is suspected.

Important Clincial Features and Considerations The diagnosis of heat illness is usually straightforward with the acute onset of symptoms in the setting of heat stress, but may be more difficult in other circumstances. In the presence of elevated body temperature and nonspecific symptoms, these patients are sometimes misdiagnosed as having infectious illnesses. The diagnosis may be difficult or missed when children undergo cooling interventions in the prehospital setting, as they may arrive in the emergency department with near-normal body temperature. There is some overlap of symptoms between heat exhaustion and heatstroke. While the distinction between heat exhaustion and heatstroke is sometimes unclear, the hallmark of heatstroke is CNS dysfunction. Children with elevated body temperature and CNS abnormalities should always be treated as having heatstroke, given the significant morbidity and mortality associated with this condition. Heat stroke must be distinguished from malignant hyperthermia and neuroleptic malignant syndrome which are induced by medications (phenothiazines, anesthetics, succinylcholine) and cause fever and muscle rigidity. While complications with minor heat illness are uncommon, patients with heatstroke are prone to many significant complications. Heatstroke patients have hyperdynamic cardiovascular systems with low peripheral vascular resistance. This low peripheral resistance persists even after cooling, leading to speculation that this is similar to a postshock or sepsis state, and this can lead to high-output cardiac failure. Heatstroke patients frequently have pulmonary edema, which is likely due to a combination of capillary leak and overaggressive fluid resuscitation, and this may progress to acute respiratory distress syndrome. Rhabdomyolysis and oliguric renal failure are common findings in heatstroke as well. The

gastrointestinal system plays a key role in the pathogenesis of heat injury. Intestinal mucosal injury from heat stress, with subsequent release of toxic substances into the circulation, is thought to contribute to the systemic response to heat injury.20 For patients with heatstroke-associated liver failure, hepatic transplantation has been performed, but experience in children and young adults is limited. Two case reports described unsuccessful liver transplantation in teenagers.21-23 Both liver dysfunction and coagulation abnormalities are seen in a delayed fashion after the initial heat injury.

Management Most patients with minor heat illness can be treated and discharged home. Treatment for miliaria entails allowing the skin to dry, use of lightweight clothing, and avoidance of further sweating. Superinfection of miliaria occasionally occurs and should be treated with antistaphylococcal antibiotics. Heat cramps are usually treated sufficiently with oral salt solutions, although some patients may need intravenous normal saline. The treatment for heat tetany is removal from the heat, which allows the patient to cease hyperventilation. Treatment for heat edema entails elevation and compressive stockings as well as removal from the heat source. Heat syncope is usually treated with either oral or intravenous fluids depending on the degree of symptoms. Heat exhaustion should be treated with cooling measures and hydration. Correction of fluid and electrolyte abnormalities with replacement of free water deficit and electrolyte losses is the therapeutic goal. Children with heatstroke need to be treated aggressively since the extent of CNS damage is related to the duration of hyperthermia. After the usual resuscitative maneuvers addressing airway, breathing, and circulation, heatstroke patients need aggressive cooling measures. The most commonly utilized modalities for rapid cooling are evaporative cooling and cold water immersion. The goal of therapeutic cooling is to bring the core temperature down to 40° C as quickly as possible. Treatment should always be initiated in the prehospital setting if possible. Immediate therapeutic interventions include removal of the patient from the heat source and removal of all clothing. Evaporative cooling is quickly accomplished by spraying tepid water (to minimize shivering) over patients and then using high-flow fans to circulate air to facilitate evaporation. Both spray bottles and fans are usually available from hospital housekeeping services. Cold water immersion of the trunk and extremities is an effective cooling mechanism as well.24 Children can be immersed in wading pools that are commonly found in supplies used for chemical decontamination. Logistically, however, monitoring and performing interventions on submerged patients is challenging. Additional methods of cooling include covering patients in ice, and selective application of ice packs to the neck, axillae, and groin. The latter technique can be used in conjunction with evaporative cooling techniques.25 Theoretically, the most effective method of lowering the core body temperature quickly is the use of cardiopulmonary bypass. Cold water gastric26,27 and peritoneal28 lavage have been proposed as additional means of invasive cooling, but these techniques have not been well studied in humans. Consider dantrolene administration (2–3 mg/kg IV to maximum

Chapter 139 — Hyperthermia

of 10 mg) if malignant hyperthermia or neuroleptic malignant syndrome are a consideration.29 There is no role for isopropyl alcohol sponge baths or antipyretic medications in the heatstroke patient. Anticipate and treat rhabdomyolysis as needed (see Chapter 99, Rhabdomyolysis). Care must be taken to prevent shivering, since this physiologic response will increase endogenous heat production. Shivering is best treated with benzodiazepines. Another complication associated with cooling measures is overshoot hypothermia. A decrease in measured body temperatures generally lags behind the actual drop in core temperature, and for this reason, cooling measures are generally stopped once the core temperature reaches 40° C. While heatstroke patients are generally dehydrated, they also have low peripheral resistance because of cutaneous vasodilation and may be hypotensive. Consequently, these patients often receive large amounts of fluids, which may lead to pulmonary edema if these fluids are not administered judiciously. Simple preventive measures may forestall significant complications associated with excessive heat. Children become dehydrated when exercising in hot environments, even when allowed to drink water freely.9,10 Flavoring water and adding both carbohydrates and sodium chloride may eliminate hypohydration.30 Restricting physical activity during hot times of the day and wearing loose-fitting, light-colored clothing reduces the risk of heat-related illness. Children should be encouraged to drink approximately 10 ml/kg prior to engaging in a period of intense exercise in hot ambient temperatures and to maintain hydration at 5 ml/kg/hr throughout the duration of the exercise.

Summary Most patients with heat-related illness have minor symptoms that are correctable in the emergency department and can thus be discharged home. Some patients with heat exhaustion may need to be admitted to the hospital if they have significant electrolyte abnormalities or if there is a concern about recurrence. All children with heatstroke must be admitted to the hospital. Patients with heatstroke generally have dysfunction of multiple organ systems and therefore need to be monitored closely. Specifically, these patients need close hemodynamic and neurologic monitoring. Because of these monitoring requirements and the potential for delayed complications (e.g., coagulopathies, hepatic dysfunction), these patients may require transfer to a pediatric critical care facility. The prognosis in patients with heatstroke is directly related to the duration of hyperthermia, and for this reason, heatstroke must be treated aggressively. Poor prognostic indicators include persistent CNS dysfunction despite cooling and persistent hypotension despite adequate fluid resuscitation. REFERENCES 1. Dematte JE, O’Mara K, Buescher J, et al: Near-fatal heat stroke during the 1995 heat wave in Chicago. Ann Intern Med 129:173–181, 1998. 2. Kaiser R, Rubin CH, Henderson AK, et al: Heat-related death and mental illness during the 1999 Cincinnati heat wave. Am J Forensic Med Pathol 22:303–307, 2001. 3. Naughton MP, Henderson A, Mirabelli MC, et al: Heat-related mortality during a 1999 heat wave in Chicago. Am J Prev Med 22:221–227, 2002.

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4. Centers for Disease Control and Prevention: Heat-related deaths—four states, July–August 2001, and United States, 1979–1999. MMWR Morb Mortal Wkly Rep 51:567–570, 2002. 5. Centers for Disease Control and Prevention: Heat-related deaths— Chicago, Illinois, 1996–2001, and United States, 1979–1999. MMWR Morb Mortal Wkly Rep 52:610–613, 2003. *6. Falk B, Bar-Or O, Calvert R, et al: Effects of thermal stress during rest and exercise in the paediatric population. Sports Med 25:221–240, 1998. 7. Falk B, Bar-Or O, Calvert R, et al: Sweat gland response to exercise in the heat among pre-, mid-, and late-pubertal boys. Med Sci Sports Exerc 24:313–319, 1992. *8. Wagner JA, Robinson S, Tzankoff SP, et al: Heat tolerance and acclimatization to work in the heat in relation to age. J Appl Physiol 33:616– 622, 1972. 9. Bar-Or O, Dotan R, Inbar O, et al: Voluntary hypohydration in 10- to 12-year-old boys. J Appl Physiol 48:104–108, 1980. *10. Bar-Or O, Wilk B: Water and electrolyte replenishment in the exercising child. Int J Sport Nutr 6:93–99, 1996. 11. King K, Negus K, Vance JC: Heat stress in motor vehicles: a problem in infancy. Pediatrics 68:579–582, 1981. 12. Roberts KB, Roberts EC: The automobile and heat stress. Pediatrics 58:101–104, 1976. 13. Krous HF, Nadeau JM, Fukumoto RI, et al: Environmental hyperthermic infant and early childhood death: circumstances, pathologic changes, and manner of death. Am J Forensic Med Pathol 22:374–382, 2001. *14. Noakes TD: Fluid and electrolyte disturbances in heat illness. Int J Sports Med 19:S146–S149, 1998. *15. Bouchama A, Knochel JP: Heat stroke. N Engl J Med 346:1978–1988, 2002. 16. Bouchama A, Hammami MM, Haq A, et al: Evidence for endothelial cell activation/injury in heatstroke. Crit Care Med 24:1173–1178, 1996. 17. Bouchama A, Bridey F, Hammami MM, et al: Activation of coagulation and fibrinolysis in heatstroke. Thromb Haemost 76:909–915, 1996. 18. Bouchama A, De Vol EB: Acid-base alterations in heatstroke. Intensive Care Med 27:680–685, 2001. 19. Hassanein T, Razack A, Gavaler JS, et al: Heatstroke: its clinical and pathological presentation, with particular attention to the liver. Am J Gastroenterol 87:1382–1389, 1992. 20. Eshel GM, Safar P, Stezoski W: The role of the gut in the pathogenesis of death due to hyperthermia. Am J Forensic Med Pathol 22:100–104, 2001. 21. Hadad E, Ben-Ari Z, Heled Y, et al: Liver transplantation in exertional heat stroke: a medical dilemma. Intensive Care Med 30:1474–1478, 2004. 22. Berger J, Hart J, Millis M, et al: Fulminant hepatic failure from heat stroke requiring liver transplantation. J Clin Gastroenterol 30:429– 431, 2000. 23. Pastor MA, Perez-Aguilar F, Ortiz V, et al: [Acute hepatitis due to heatstroke]. Gastroenterol Hepatol 22:398–399, 1999. 24. Gaffi n SL, Gardner JW, Flinn SD: Cooling methods for heatstroke victims. Ann Intern Med 132:678–679, 2000. 25. Eshel GM, Safar P, Stezoski W: Evaporative cooling as an adjunct to ice bag use after resuscitation from heat-induced arrest in a primate model. Pediatr Res 27:264–267, 1990. 26. White JD, Riccobene E, Nucci R, et al: Evaporation versus iced gastric lavage treatment of heatstroke: comparative efficacy in a canine model. Crit Care Med 15:748–750, 1987. 27. Syverud SA, Barker WJ, Amsterdam JT, et al: Iced gastric lavage for treatment of heatstroke: efficacy in a canine model. Ann Emerg Med 14:424–432, 1985. 28. White JD, Kamath R, Nucci R, et al: Evaporation versus iced peritoneal lavage treatment of heatstroke: comparative efficacy in a canine model. Am J Emerg Med 11:1–3, 1993. 29. Bouchama A, Cafege A, Devol EB, et al: Ineffectiveness of dantrolene sodium in the treatment of heatstroke. Crit Care Med 19:176–180, 1991. 30. Wilk B, Bar-Or O: Effect of drink flavor and NaCl on voluntary drinking and hydration in boys exercising in the heat. J Appl Physiol 80:1112–1117, 1996. *31. Climatic heat stress and the exercising child and adolescent. American Academy of Pediatrics, Committee on Sports Medicine and Fitness. Pediatrics 106:158–159, 2000. *Selected readings.

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32. Orenstein DM, Henke KG, Costill DL, et al: Exercise and heat stress in cystic fibrosis patients. Pediatr Res 17:267–269, 1983. 33. Bar-Or O, Blimkie CJ, Hay JA, et al: Voluntary dehydration and heat intolerance in cystic fibrosis. Lancet 339:696–699, 1992. 34. Kriemler S, Wilk B, Schurer W, et al: Preventing dehydration in children with cystic fibrosis who exercise in the heat. Med Sci Sports Exerc 31:774–779, 1999. 35. Martinez M, Devenport L, Saussy J, et al: Drug-associated heat stroke. South Med J 95:799–802, 2002. 36. Kerle KK, Nishimura KD: Exertional collapse and sudden death associated with sickle cell trait. Mil Med 161:766–767, 1996. 37. Kark JA, Posey DM, Schumacher HR, et al: Sickle-cell trait as a risk factor for sudden death in physical training. N Engl J Med 317:781–787, 1987.

38. Wirthwein DP, Spotswood SD, Barnard JJ, et al: Death due to microvascular occlusion in sickle-cell trait following physical exertion. J Forensic Sci 46:399–401, 2001. 39. Levin M, Hjelm M, Kay JD, et al: Haemorrhagic shock and encephalopathy: a new syndrome with a high mortality in young children. Lancet 2:64–67, 1983. 40. Chaves-Carballo E, Montes JE, Nelson WB, et al: Hemorrhagic shock and encephalopathy: clinical defi nition of a catastrophic syndrome in infants. Am J Dis Child 144:1079–1082, 1990. 41. Ince E, Kuloglu Z, Akinci Z: Hemorrhagic shock and encephalopathy syndrome: neurologic features. Pediatr Emerg Care 16:260–264, 2000. 42. Bacon CJ, Bell SA, Gaventa JM, et al: Case control study of thermal environment preceding haemorrhagic shock encephalopathy syndrome. Arch Dis Child 81:155–158, 1999.

Chapter 140 Hypothermia Paul Ishimine, MD

Key Points Hypothermia can occur in any climate during any season. While environmental exposure is the predominant cause of hypothermia in older children, other causes, especially sepsis, should be considered in the hypothermic neonate. Severely hypothermic children without signs of life have been successfully resuscitated, but severe primary hypothermia resulting from cold exposure must be differentiated from secondary hypothermia resulting from prolonged cardiac arrest; the latter rarely responds to resuscitative efforts.

Introduction and Background Hypothermia is defined as a core temperature of less than 35° C (95° F).1 Primary (“accidental”) hypothermia is a result of environmental exposure, while secondary hypothermia is a result of underlying disease. Hypothermia is more frequently seen in cold environments and in winter months,2,3 but children may become hypothermic in any location or climate. While the role of therapeutically induced hypothermia is an area of ongoing investigation for a number of different medical conditions,4-12 this discussion focuses on accidental hypothermia.

Recognition and Approach Hypothermia is further categorized as mild (32.2° C to 35° C), moderate (28° C to 32.1° C), and severe ( fat > tendon > skin > muscle > blood vessels > nerves. Skin resistance, however, is extremely variable depending on moisture, thickness, and age. Wet skin can decrease resistance by over 100-fold,5 and a neonate’s skin provides relatively lower resistance due to its thinness and high water content. Resistance will also determine the pathway of current, with the most dangerous circuit being 1011

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from hand to hand with heart involvement, or head to toe with brain and respiratory drive involvement. The type of current, AC or DC, also plays a major factor in determining injury severity. AC current is generally more dangerous due to the “locked-on” phenomenon. This results from simultaneous tetanic contractions of both hand flexors and extensors. Since the flexors are stronger, the hand cannot be opened and gets “locked on” the electricity source. This phenomenon is associated with standard 60-Hz household current and increases duration of contact. Lightning has an extremely short duration of contact ( 1 ml/kg/hr Consider antidotal therapy as indicated

Management When burned children with inhalation injuries receive mechanical ventilation, permissive hypercapnia may minimize barotrauma.14 Continuous positive airway pressure or positive end-expiratory pressure (5 to 15 cm H2O) is recommended for refractory hypoxemia.8,9 Inhaled β2-agonist bronchodilators are useful for acute bronchospasm. There is no documented benefit from steroids or prophylactic antibiotics.8,12 All symptomatic children should be admitted to the hospital. Clinical experience suggests observing asymptomatic children for a minimum of 4 to 6 hours and admitting them to the hospital if signs or symptoms of inhalation injury develop during this observation period. Family members who survive house fires should be encouraged to develop an emergency plan and use smoke and CO detectors in their homes. Carbon Monoxide CO is a colorless, odorless, tasteless, and nonirritating gas formed as a by-product of incomplete combustion of fossil fuels or materials such as wood or charcoal. CO poisoning is most commonly due to smoke inhalation, but also occurs from exposure to malfunctioning or improperly vented heating and cooking appliances, automobile exhaust fumes, and methylene chloride (found in paint strippers). CO exerts its potentially lethal effects via several different mechanisms. CO binds to hemoglobin 250 times as tenaciously as oxygen; therefore, it greatly reduces the ability of hemoglobin to carry oxygen. CO also shifts the oxyhemoglobin dissociation curve to the left, making it more difficult for oxygen to be released from hemoglobin to the cells. As a result of binding to myoglobin, there is impaired diffusion of oxygen to cardiac and

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skeletal muscles, resulting in the victim’s reduced ability to move and escape.7 Analysis of data from the National Center for Health Statistics for the years 1994 to 1998 identified an average of 516 annual deaths from unintentional non–fire-related CO poisoning in the United States.15 These fatality figures do not include intentional poisoning and deaths from fire and smoke inhalation, some of which were undoubtedly the result of CO toxicity. Unintentional CO toxicity and deaths are more common in northern climates and during the winter months. The mortality rate among patients with severe CO poisoning is about 30%. Most patients who die do so at the scene of exposure. Up to 11% of survivors develop persistent gross neurologic or psychiatric deficits. A larger number may develop more subtle pathology such as personality changes or memory impairment. Up to 25% of treated patients will experience delayed neurologic deterioration following a period of apparent recovery. Although most delayed sequelae will resolve, the course may span years.16 Clinical Presentation Clinical signs and symptoms of CO poisoning are relatively nonspecific and correlate only roughly with the COHb level. The longer the interval between exposure and evaluation in the emergency department, the more likely that the symptoms and COHb level will be discordant. Many patients with relatively mild CO intoxication complain of flulike symptoms with headache, nausea, and fatigue. More severe symptoms include unexplained alterations of mental status, neurologic abnormalities, syncope, and metabolic acidosis. In infants, the only suggestion of toxicity may be irritability or feeding difficulties. COHb levels do not correlate with clinical signs and symptoms in children.17 COHb levels are measured using co-oximetry. COHb levels are adequately reflected in both arterial and venous samples. Chest radiography is not indicated unless there is clinical evidence of pulmonary edema or a concern about related smoke inhalation injury. A urinalysis and serum creatine kinase are indicated for patients with prolonged unconsciousness or those otherwise at risk for rhabdomyolysis (see Chapter 99, Rhabdomyolysis). Computed tomography may be performed for other indications (see Chapter 9, Cerebral Resuscitation), but is not specifically indicated in the acute management of suspected CO poisoning.16,18 Management The cornerstone of treatment is high-flow supplemental oxygen. The short-term administration of high concentrations of oxygen is indicated as soon as the diagnosis of CO poisoning is suspected as this treatment offers little, if any, risk to most patients. In the awake patient, a fraction of inspired oxygen (FiO2) of nearly 100% can be achieved using a tight-fitting non-rebreathing mask with a reservoir. The half-life of COHb is approximately 3 to 4 hours while breathing room air, 60 minutes while breathing 100% oxygen, and 20 minutes breathing hyperbaric oxygen (HBO) at 2.5 atmospheres of pressure. HBO treatment of CO poisoning is controversial. Traditional recommendations for HBO treatment were based on COHb levels. This approach is no longer advocated.19-21 It is not currently clear that HBO treatment is beneficial for patients for CO poisoning.19-21 Until these treatment issues

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are resolved, a hyperbaric specialist or poison control center it is reasonable to consult for cases of severe CO toxicity. U.S. emergency physicians can find the location of the nearest hyperbaric chamber by calling the Divers Alert Network (DAN), Duke University, Durham, NC, at 1-919-684-8111 (see Chapter 144, Dysbarism). An absolute contraindication to HBO treatment is an untreated pneumothorax. Complications of HBO treatment include rare seizures, vascular gas emboli, and barotrauma to the ears, sinuses, and lungs. The use of HBO typically involves transport to another facility with the inherent risks incurred during transport. Clinical experience suggests that CO-exposed patients who are asymptomatic or manifest mild, flulike symptoms may be discharged if a repeat CO level is less than 5 mg/dl after 4 hours receiving 100% FiO2. All other patients with CO exposures should be admitted. Severely ill children should be transferred to a pediatric tertiary care center. Summary CO poisoning is common, but the diagnosis is not always obvious. It should be suspected when multiple victims or family members present with headache and vague flulike symptoms. Accurate testing requires co-oximetry, which can accurately be performed on arterial or venous blood. A hyperbaric specialist or poison control center should be consulted for severe cases. Cyanide Cyanide is a cellular asphyxiant. Cyanide binds with the ferric ion of mitochondrial cytochrome oxidase enzymes and halts aerobic cellular respiration. This shift to anaerobic metabolism results in a severe lactic acidosis. Cyanide also shifts the oxygen-hemoglobin dissociation curve to the left, further impairing oxygen delivery to the tissues. HCN gas is formed when wool, silk, synthetic fabrics, and some building materials catch fire. It is estimated that up to 35% of all house fire victims may have been exposed to cyanide.22 Cyanide also is used in the mining and photographic chemical recycling industries. Industrial firms in the United States manufacture over 300,000 tons of cyanide each year. As a terrorist weapon, cyanide gas could be generated in an enclosed space via the addition of an acid to a solid cyanide salt, but is highly volatile and rapidly disperses in air. In the 10-year period between 1993 and 2002, the Toxic Exposure Surveillance System compiled by the American Association of Poison Control Centers recorded 3165 human exposures to cyanide.23 Eighty (2.5%) of these exposures resulted in death and 413 (13%) resulted in serious morbidity. In the Union Carbide pesticide plant disaster in Bhopal, India, there were an estimated 1800 to 5000 deaths and almost 200,000 injuries.24

Table 143–2

Clinical Presentation The onset of symptoms following inhalation exposure to HCN gas is immediate. Low concentrations (e.g., < 50 parts per million) cause restlessness, anxiety, palpitations, dyspnea, and headache. Very high concentrations result in marked tachypnea, immediately followed by severe respiratory depression, convulsions, respiratory arrest, and death.7 Patients who are alert may hyperventilate and complain of breathlessness. Since cyanide prevents tissue extraction of oxygen from the blood, the oxygen content of venous blood approaches that of arterial blood, resulting in the brightening of venous blood. The typical seriously poisoned patient is hyperventilating, hypotensive, and bradycardic without cyanosis. There is no rapid or readily available diagnostic test for cyanide exposure. In the absence of a known cyanide exposure, the diagnosis must be made empirically (e.g., smoke inhalation with high lactate, enclosed space, or mass casualty). A high anion gap metabolic acidosis and plasma lactate levels greater than 10 mmol/L (90 mg/dl) are consistent with cyanide toxicity.25 Comparing arterial and venous blood gases may demonstrate a diminished arterial-venous O2 difference. Management The mainstay of therapy for cyanide poisoning is aggressive supportive care (see Table 143–1) and prompt administration of the cyanide antidote kit (Table 143–2). The antidotal action of the cyanide antidote kit is at least in part due to nitrites causing methemoglobinemia. Caution must be used in the administration of the cyanide antidote kit to fire victims with possible simultaneous CO and cyanide poisoning. Since COHb does not carry oxygen, the creation of methemoglobin can further decrease oxygen delivery. In this situation, sodium thiosulfate should be used alone.26 The reported death of a child from methemoglobinemia following aggressive treatment of a nonlethal ingestion has led to the recommendation of adjusting the pediatric dose of sodium nitrite according to the patient’s hemoglobin level (Table 143–3). Side effects of nitrite administration include headache, blurred vision, nausea, vomiting, and hypotension. Methemoglobin levels of 20% to 30% are associated with symptoms of headache and nausea. Weakness, dyspnea, and tachycardia occur at levels of 30% to 50%. Dysrhythmias, central nervous system depression, and seizures occur at levels of 50% to 70%. Death typically occurs at methemoglobin levels above 70%. In contrast to the nitrites, thiosulfate has few if any side effects other than burning at the injection site, localized muscle cramping, and occasional nausea and vomiting.27 There are limited data on hydroxocobalamin use in children.

Cyanide Antidote Kit: Contents and General Instructions for Usage

Antidote

Quantity/Form Supplied

Pediatric Dose

Amyl nitrite

12 perles (0.3 ml/perle)

Sodium nitrite

2 ampules of 3% solution (300 mg/10 ml)

Sodium thiosulfate

2 ampules of 25% solution (12.5 g/50 ml)

Crush 1–2 perles in gauze and hold under patient’s nose or over ET tube for 15–30 sec every minute until sodium nitrite is infusing 0.3 ml/kg (9 mg/kg), not to exceed 10 ml (300 mg), IV at 2.5 ml/min, or over 30 min, in smoke inhalation victims with CO poisoning 1.6 ml/kg (400 mg/kg), up to 50 ml (12.5 g), at rate of 3–5 ml/min

Abbreviations: CO, carbon monoxide; ET, endotracheal; IV, intravenously.

Chapter 143 — Inhalation Exposures

Table 142–3

Hemoglobin Level (g/dl) 7 8 9 10 11 12 13 14

Dose Adjustment Recommendations for Sodium Nitrite Based on Hemoglobin Level 3% Sodium Nitrate (NaNO2) (ml/kg)

25% Sodium Thiosulfate (Na2S2O3) (ml/kg)*

0.19 0.22 0.25 0.27 0.30 0.33 0.36 0.39

1.65 1.65 1.65 1.65 1.65 1.65 1.65 1.65

*There is a uniform dose for sodium thiosulfate for all hemoglobin levels.

Chlorine Gas Chlorine gas is a pulmonary irritant. Pulmonary irritants are among the most common toxic inhalants. Chlorine is a yellow-green gas that is slightly water soluble and has a pungent, irritating odor. With a density almost twice that of air, it descends and remains near ground level. Chlorine gas is 20 times more potent and irritating than HCl. When chlorine gas and mucosal water react, HCl and hypochlorous acid (HOCl) are produced and are responsible for the caustic effects. As particle size and water solubility decrease, progressively lower regions of the airways are affected, and resultant symptoms are more insidious and severe. The potential sources of exposure to chlorine are multiple and include industrial operations, inappropriate mixing of household cleaning agents, emissions during transport, school chemistry experiments, and mishaps in the chlorinating of swimming pools. Chlorine is shipped widely by truck, train, and barge, making transportation and storage accidents everpresent dangers. Chlorine exposures are most frequently due to industrial (pulp mills), household cleaner, and swimming pool exposures.28 Children and adolescents younger than 18 years constitute the majority and most severely affected of patients.29,30 The medical literature is replete with household exposures involving cleaning agents. Household ammonia and bleach are two of the most common cleaning agents. Combining them releases chloramine gas. When inhaled, chloramine gas reacts with the moisture of the respiratory tract to release ammonia, HCl, and oxygen free radicals. Typically, exposures to low concentrations of chloramines produce only mild respiratory tract irritation. In higher concentrations, the combination of HCl, ammonia, and oxygen free radicals may cause corrosive effects and cellular injury, resulting in pneumonitis and edema.31,32 Aside from the initial cough and irritation, serious morbidity is rare and no deaths have been reported from household cleaning agents.31,32 Toxic manifestations of chlorine gas may be significant, and occur within seconds or minutes of exposure, depending on the concentration. Upper airway symptoms include irritation of the eyes, nose, and throat. Stridor and upper airway swelling leading to obstruction may occur. Lower airway manifestations include cough, shortness of breath, chest pain, and wheezing. Pulmonary edema and death may occur with significant exposure. Burns and corneal abrasions have

1019

resulted from skin and eye exposures. Various nonspecific symptoms, such as headache and nausea, may be present.30,31 Clinical manifestations are predictable and typically resolve within 6 hours after mild exposures. Blood gases are generally normal. Mild hypoxemia and hypercarbia or respiratory alkalosis may be seen.30,32,33 Chest radiographs are generally normal.33 Standard treatment of acute chlorine gas exposure includes removal of the patient from the source and respiratory support measures as needed. Eye and skin exposure requires copious irrigation with water or saline. Bronchospasm usually responds to standard β2-agonists (e.g., albuterol). Corticosteroids and nebulized sodium bicarbonate have no clear efficacy and are not recommended.30,33 Long-term effects after acute and chronic exposures to chlorine do not appear to be clinically significant, and the risk of reactive airways disease is undefined.28,33 Exposures to chlorine gas and other pulmonary irritants are relatively common. Symptoms are usually acute and short lived. Humidified oxygen and β-agonist applications are the best supportive therapy for chlorine gas exposure. Acute household cleaning agent exposures are generally benign. More severe injuries are possible with industrial exposures to more highly concentrated chemicals. REFERENCES *1. Marshall SW, Runyan CW, Bangdiwala SI, et al: Fatal residential fi res: who dies and who survives? JAMA 279:1633–1637, 1998. 2. Feck GA, Baptise MS, Tate CLJ: Burn injuries: epidemiology and prevention. Accid Anal Prev 11:129–136, 1983. *3. Sheridan RL, Remensnyder JP, Schnitzer JJ, et al: Current expectations for survival in pediatric burns. Arch Pediatr Adolesc Med 154:245–249, 2000. 4. Karter MJ: 1996 U.S. fi re loss. NFPA J Sep/Oct:77–83, 1997. *5. Barrow RE, Spies M, Barrow LN, et al: Influence of demographics and inhalation injury on burn mortality in children. Burns 30:72–77, 2004. 6. Wolf SE, Rose JK, Desai MH, et al: Mortality determinants in massive pediatric burns: an analysis of 103 children with ≥ 80% TBSA burns (≥ 70% full-thickness). Ann Surg 225:554–569, 1997. 7. Alarie Y: Toxicity of fi re smoke. Crit Rev Toxicol 32:259–289, 2002. 8. Herndon DN, Langner F, Thompson P, et al: Pulmonary injury in burned patients. Surg Clin North Am 67:31–46, 1987. 9. Heimbach DM, Waeckerle JF: Inhalation injuries. Ann Emerg Med 17:1316–1320, 1988. 10. Shirani KZ, Pruitt BA, Mason AD. The influence of inhalation injury and pneumonia on burn mortality. Ann Surg 205:82–87, 1987. *11. Bozeman WP, Myers RA, Barish RA: Confi rmation of the pulse oximetry gap in carbon monoxide poisoning. Ann Emerg Med 30:608– 611, 1997. 12. Parish RA: Smoke inhalation and carbon monoxide poisoning in children. Pediatr Emerg Care 2:36–39, 1986. 13. Wittram C, Kenny JB: The admission chest radiograph after acute inhalation injury and burns. Br J Radiol 67:751–754, 1994. 14. Sheridan RL, Kacmarek RM, McEttrick MM, et al: Permissive hypercapnia as a ventilatory strategy in burned children: effect of barotrauma, pneumonia, and mortality. J Trauma 39:854–859, 1995. 15. Mah JC: Non-Fire Carbon Monoxide Deaths Associated with the Use of Consumer Products: 1998 Estimates. Bethesda, MD: Consumer Products Safety Commission, 1998. 16. Parkinson RB, Hopkins RO, Cleavinger HB, et al: White matter hyperintensities and neuropsychological outcome following carbon monoxide poisoning. Neurology 58:1525–1532, 2002. 17. Crocker PJ, Walker JS: Pediatric carbon monoxide toxicity. J Emerg Med 3:443–448, 1985. 18. Gale SD, Hopkins RO: Effects of hypoxia on the brain: neuroimaging and neuropsychological fi ndings following carbon monoxide poi*Selected readings.

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soning and obstructive sleep apnea. J Int Neuropsychol Soc 10:60–71, 2004. *19. Gilmer B, Kilkenny J, Tomaszewski C, et al: Hyperbaric oxygen does not prevent neurologic sequelae after carbon monoxide poisoning. Acad Emerg Med 9:1–8, 2002. 20. Juurlink D, Buckley N, Stanbrook M, et al: Hyperbaric oxygen for carbon monoxide poisoning. Cochrane Database Syst Rev (4): CD002041, 2005. 21. Weaver LK, Hopkins RO, Chan KJ, et al: Hyperbaric oxygen for acute carbon monoxide poisoning. N Engl J Med 347:1057–1067, 2002. 22. Sauer SW, Keim ME: Hydroxocobalamin: improved public health readiness for cyanide disasters. Ann Emerg Med 37:635–641, 2001. 23. American Association of Poison Control Centers: Toxic Exposure Surveillance System. Annual Reports 1993–2002. Available at http://www. aapcc.org/poison.htm. 24. Mehta PS, Mehta AS, Mehta SJ, et al: Bhopal tragedy’s health effects: a review of methyl isocyanate toxicity. JAMA 264:2781–2187, 1990. 25. Baud FJ, Barriot P, Toffis V, et al: Elevated blood cyanide concentrations in victims of smoke inhalation. N Engl J Med 325:1761–1766, 1991.

26. Kulig K: Cyanide antidotes and fi re toxicology. N Engl J Med 325: 1801–1802, 1991. 27. Forsyth JC, Mueller PD, Becker CE, et al: Hydroxocobalamin as a cyanide antidote: safety, efficacy and pharmacokinetics in heavily smoking normal volunteers. J Toxicol Clin Toxicol 31:277–294, 1993. 28. Vohra R, Clark RF: Chlorine-related inhalation injury from a swimming pool disinfectant in a 9-year-old girl. Pediatr Emerg Care 22: 254–257, 2006. 29. Agabiti N, Ancona C, Forastiere F, et al: Short term respiratory effects of acute exposure to chlorine due to a swimming pool accident. Occup Environ Med 58:399–404, 2001. 30. Fleta J, Calvo C, Zuniga J, et al: Intoxication of 76 children by chlorine gas. Hum Toxicol 5:99–100, 1986. 31. Tanen DA, Graeme KA, Raschke R: Severe lung injury after exposure to chloramines gas from household cleaners. N Engl J Med 341: 848–849, 1999. 32. Mrvos R, Dean BS, Krenzelok EP: Home exposures to chlorine/chloramines gas: review of 216 cases. South Med J 86:654–657, 1993. 33. Sexton JD, Pronchik DJ: Chlorine inhalation: the big picture. J Toxicol Clin Toxicol 36:87–93, 1998.

Chapter 144 Dysbarism John P. Santamaria, MD

Key Points Pediatric divers are at special risk for serious diving injuries due to emotional immaturity. Patients tend to minimize the importance of vague symptoms and may fail to associate them with diving. Patients with dysbarism may present days after a dive with relatively vague complaints. Recompression treatment should begin as soon as decompression illness is suspected.

Introduction and Background Dysbarism is a term for any clinical syndrome caused by a difference between the atmospheric pressure and the total gas pressure in a body tissue, fluid, or cavity.1 Although the term could be applied to changes in atmospheric pressure such as occurs during a space walk,2 the most common situations in which emergency physicians will encounter children and adolescents with dysbarism is either at high altitudes in mountainous regions (see Chapter 145, High Altitude– Associated Illnesses) or after scuba diving. Given that the symptoms of diving-related illnesses can arise several hours after a dive and that patients may present days after diving, emergency physicians working several hours’ travel from the coast may occasionally see patients with diving-related illnesses. Although many interesting and serious conditions can arise from spending time in the ocean3 (see Chapter 140, Hypothermia), this discussion focuses on those conditions related to changes in atmospheric pressure associated with scuba diving.

Recognition and Approach The vast majority of scuba divers are middle-aged adults.4-8 Not surprisingly, most dive-related injuries and fatalities occur in middle-aged adults.4-8 However, increasingly younger children have been accepted into scuba certification courses and encouraged to dive. In 2000, diving certification organizations lowered the minimum training age from 12 to 8

years.9,10 Although still relatively rare, serious pediatric diving injuries and fatalities occur. Of 423 diving-related fatalities reported to the Divers Alert Network from 1999 through 2003, 7 (2%) occurred in children ≤ 19 years4-8 (Table 144–1). From data on citizens of the United States and Canada, the age of the youngest child to sustain a diving injury is 11 years and the age of the youngest child to suffer a diving fatality is 14 years.3 Emotional maturity, appropriate training, and tight supervision appear to be key components to successful pediatric diving. Many children and adolescents are intellectually capable of completing and excelling in the cognitive portions of scuba diving classes. The concern is that a child or adolescent will react badly to unexpected, uniquely stressful experiences under water or take unnecessary, dangerous risks. Poor decision making, lack of proper training, ignoring proper procedures for safe diving, and panicking at a critical moment are recurrent themes in fatal adolescent dives (see Table 144–1). The pathophysiology of dysbarism falls into two general categories. The first category involves pressure changes in relatively fi xed body spaces. These disorders are generally referred to as “barotrauma.” These types of injuries are reasonably straightforward and based on a well-described physical principle, Boyle’s law.11,12 Boyle’s law states that, at a constant temperature, volume and pressure are inversely proportional. Every 10 meters of sea water in depth adds 1 additional atmosphere of pressure. So, if an air-fi lled ball is taken down 10 m in the ocean, the volume of the ball would be half of its volume at the surface because the air in the ball would be exposed to twice the atmospheric pressure. The same principles apply to body cavities such as sinuses. Unfortunately, the bony walls of a sinus cannot easily accommodate large changes in volume. The signs and symptoms will reflect the body cavity involved. The second category in the pathophysiology of dysbarism involves gases dissolved in liquids. Affecting one or more body regions, the constellation of problems arising from nitrogen dissolving in body tissues is typically referred to as “decompression illness.”4,11 The relevant physical law in this instance is Henry’s law.13 Henry’s law states that the amount of gas dissolved in a liquid is proportional to the partial pressure of that gas in contact with the liquid.13 The higher the pressure, the more gas dissolved in that liquid. When diving, the higher atmospheric pressure drives nitrogen into the body tissues. Since nitrogen is not metabolized by the body, 1021

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Table 144–1 Year

Age (yr)

2003

Deaths Associated with Scuba Diving by Children and Adolescents ≤ 19 Years, 1999–2003 Gender

Prior Diving Experience

Circumstances

18

Male

Certified for 18 mo; 130 dives completed

2001

19

Male

Completed open water certification the morning of the day he died

2001

17

Male

No formal dive training or experience

2001

17

Female

No formal dive training or experience

2001

19

Female

Completed certification course; participating in her first dive after certification and first dive in cold water

2000

16

Male

Certified by an organization with no national affiliation 1 year prior

1999

19

Male

Open-water certified for 2 wk

Shore-entry night dive using nitrox. Third dive of the day. Depth to 93 feet of sea water (28 m) for 25 min. Rapid ascent after running out of breathing gas. Unconscious upon surfacing. Without prior planning, separated from an instructor and entered an underwater cave with 35-yr-old diving buddy. Ran out of air after becoming lost in the cave. Did not dive with a buddy. Did not use a buoy or any other mark for his location. When his body was found 2 days later, his tank was empty. Collecting sand dollars at a depth of 10 feet. Did not wear fins. Began with a partially empty tank. Was holding hands with another equally inexperienced diver during the dive, but let go at the surface. Her body was found 8 hr later. Strong current and poor visibility. Planned a dive to 50 feet of sea water (15 m), but descended to 200 feet of sea water (60 m). She lost consciousness after appearing to panic and have difficulty with her buoyancy compensator. She was too heavy for the dive buddy to lift. Her body was never recovered. Second dive of the day that went past 200 feet of sea water (60 m). Shot an extremely large fish and attached it to his buoyancy compensation device. Struggle with the fish resulted in him being hit in the face and neck. Unconscious when his dive buddy reached him. Went beyond maximum for depth and time based on buddy’s dive computer. Made a dive to 227 feet of sea water (69 m) with two other divers. Ascended to 190 feet of sea water (57.8 m). He ran out of air and began to buddy breath with one of the other divers. Then made a rapid ascent to the surface from 170 feet of sea water. Pronounced dead at a local hospital.

Data source: Divers Alert Network: Report on Decompression Illness, Diving Fatalities and Project Dive Exploration (2001 through 2005 editions). Available at http://www.DiversAlertNetwork.org.

if ascent is too rapid, the nitrogen may be released rapidly from tissues and bubbles may form. These bubbles can obstruct arteries, veins, and lymphatics or distort local tissue architecture. The signs, symptoms, and clinical syndrome relate to the body parts involved.

Clinical Presentation The feature most strongly affecting the clinical presentation and severity of dysbarism is the body part affected. The degree to which the dysbarism is life threatening can be deduced directly from the body part involved. Overall, the most common symptoms reported by divers are pain and paresthesias.4 The most immediately life-threatening conditions involve loss of consciousness or loss of motor function while underwater. Brain The most serious manifestations of dysbarism in the brain are acute stroke, altered mental status, and loss of consciousness.14 An acute stroke arises when a bubble of gas (i.e., a gas embolism) occludes a critical artery supplying the brain. The symptoms will reflect the area of brain injured (see Chapter 44, Central Nervous System Vascular Disorders). Unconsciousness may be the dominant sign and is often fatal if this occurs while the diver is underwater (see Table 144–1). Patients with a patent foramen ovale are at increased risk for strokes from arterial gas emboli.15-17 Arterial gas emboli occur during ascent. Another condition affecting the brain is nitrogen narcosis. At depths of 30 m or greater, dissolved nitrogen

alters the ionic conductance through neuronal membranes.11 This leads to a clinical condition similar to alcohol intoxication. Impaired judgment, clumsiness, light-headedness, euphoria, and disorientation are common symptoms. Divers may misuse their equipment, fail to acknowledge low air in their tanks, become trapped, or go deeper and lose consciousness. Nitrogen narcosis occurs during the deepest portions of a dive. Spinal Cord The spinal cord is particularly vulnerable to decompression sickness.18 Symptoms can range from limb paresthesias to paraplegia. Spinal cord injuries occur during ascent. Inner Ear Vertigo, nausea, vomiting, unsteadiness, tinnitus, and hearing loss are common symptoms of inner ear decompression sickness.19 In adults, the onset of symptoms is usually within the first hour or two after a dive, but symptoms may arise after more than 5 hours.19 Inner ear decompression sickness occurs during ascent. Middle Ear and Ear Canal If a diver’s eustachian tubes are partially or completely occluded, spontaneous equalization of the pressure in the middle ear with the environmental pressure encountered during a dive will be impaired. This condition is the most common form of dysbarism, affecting 30% of new divers on their first dive and 10% of experienced divers.20 This condition is commonly referred to as “barotitis media” or “middle

Chapter 144 — Dysbarism

ear squeeze.” Signs and symptoms of barotitis media include ear pain, tympanic membrane injury or rupture, and blood in the ear canal. If the tympanic membrane ruptures, cold water may enter the middle ear and lead to life-threatening severe vertigo and disorientation during a dive. A similar phenomenon may occur if ear plugs or a wax plug completely occlude the external ear canal, creating a pocket of air.21 Middle ear and canal injuries more frequently occur during descent, but may occur during ascent. Sinuses If the sinus ostia are occluded, spontaneous equalization of the pressure in a sinus with the environmental pressure encountered during a dive will be impaired. The maxillary sinus is the most frequently affected. The most common symptoms are facial pain and epistaxis. Decreased facial sensation in the area innervated by the infraorbital nerve may also occur.22 Sinus barotrauma is also known as “sinus squeeze.”13 Sinus barotrauma occurs twice as frequently during descent as ascent. Teeth Air pockets may be present in teeth due to recent dental work or from pathology such as cavities. Pressure changes during a dive may cause pain with or without tooth fracture.23 This condition is referred to as “barodontalgia” or “tooth squeeze.” Barodontalgia typically occurs during descent. Tongue An arterial gas embolism may leave a well-circumscribed area of pallor on the tongue. This physical finding is also called Liebermeister’s sign.24 Lungs Pulmonary barotrauma is the most life-threatening form of barotrauma. The classic example of pulmonary barotrauma occurs when a diver takes a breath at depth and then rapidly ascends while holding his or her breath. As the diver ascends, the pressure and volume of gas in the lungs will progressively increase due to the continually decreasing environmental pressure as the diver approaches the surface. Resulting injuries include simple pneumothorax, tension pneumothorax, pneumomediastinum, alveolar rupture, and the release of gas emboli into the central circulation. Signs and symptoms include chest pain, dyspnea, cardiovascular collapse, stroke, hemoptysis, and unconsciousness.11 Divers with uncontrolled asthma or wheeze precipitated by exercise, cold, or emotion are at increased risk for pulmonary barotrauma.25 Pulmonary barotrauma occurs during ascent. Gastrointestinal Tract The gastrointestinal tract is a distensible tube containing air and liquid. As the environmental pressure changes during a dive, the air in the gastrointestinal tract will contract or expand. Although serious conditions such as rupture of the stomach have been reported,26 most cases of gastrointestinal dysbarism result in crampy abdominal pains or dyspepsia. Gastrointestinal dysbarism occurs during ascent. Skin Cutaneous manifestations of decompression illness most commonly occur on the torso. Itching is the most common

1023

symptom.12 Examination of the skin may reveal an erythematous, macular rash or patchy mottling.12 Localized lymphedema may be present.11 The onset of cutaneous manifestations of decompression illness is variable, but may occur after a dive has concluded. Extremities Deep, aching pains in the extremities due to decompression illness may occur up to an hour after surfacing from a dive.11 The severity is variable, but the pain may be severe. A common name for this syndrome is “the bends.” The bends occurs after resurfacing. Face When a mask is tightly adhered to a diver’s face at the surface, this air-fi lled space is vulnerable to dysbarism. If a diver does not properly ventilate his or her mask by exhaling through the nose during descent, a “mask squeeze” may occur.27,28 Signs and symptoms of a mask squeeze include periorbital pain, conjunctival and periorbital edema, subconjunctival hemorrhages, periorbital ecchymoses, and petechial hemorrhages in the distribution of the mask on the face.28 Mask squeeze occurs during descent.

Important Clinical Features and Considerations When a diver presents to the emergency department after a dive, reviewing his or her dive table may have some utility. The risk for dysbarism is directly related to the duration and depth of a dive. Dive tables offer a rough estimate of safe dive plans based on duration and depth.29 Identifying a diver who has substantially deviated from a published dive table helps risk-stratify that patient. However, divers are notorious for underestimating and underreporting depth and “bottom times.” There are significant differences among various decompression tables that are used by different dive agencies and in different parts of the world. Dive computers used during a dive to estimate the duration and depth of a dive extrapolate values from various dive tables. This, in turn, results in more bottom time and a greater risk of dysbarism.

Management The management of dysbarism is based on the clinical syndrome. In general, serious signs and symptoms warrant the immediate application of high-flow oxygen and transfer to the care of a dive specialist at a facility capable of recompression therapy in a hyperbaric chamber.30 In anticipation of transfer, the only test indicated is a chest radiograph to identify a pneumothorax. If a patient with a small, unrecognized pneumothorax undergoes recompression therapy, the patient may develop a tension pneumothorax in the hyperbaric chamber. Identifying a pneumothorax and placing a thoracostomy tube (see Chapter 168, Thoracostomy) allows the patient to undergo recompression therapy more safely. The performance of other tests that do not clearly meet other indications (e.g., a glucose check in a known diabetic diver) only delays recompression therapy without offering the patient additional benefit. Unconsciousness after a rapid ascent or acute stroke symptoms are obvious indication for recompression therapy. Other indications for consultation

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SECTION V — Approach to Environmental Illness and Injury

with a dive specialist regarding recompression therapy that are less obvious to emergency physicians who do not dive are numbness and tingling in the extremities, dizziness and vertigo, crampy extremity pains, joint pains, Liebermeister’s sign, and skin mottling. Inexperienced divers may not associate their symptoms with dysbarism. Experienced divers may minimize their symptoms. A dive specialist should be consulted if these or other vague symptoms arise within days of a dive. Untreated dysbarism can lead to permanent injuries, particularly to the central nervous system. Recommendations regarding returning to diving should be deferred to a dive specialist. Relatively minor diving injuries, including the “squeezes,” rarely require emergent treatment. Barotitis media should be treated symptomatically, and follow-up arranged with a primary care doctor. Tympanic membrane rupture may be an indication for follow-up with an otolaryngologist. Barodontalgia, including most dental fractures, should also be treated symptomatically. The patient can follow up with a dentist at his or her convenience. Mask squeeze and sinus squeeze should be treated symptomatically.

Summary An increase in the number of children and adolescents experiencing dysbarism is expected given the recent lowering of the minimum scuba training age. Emotional maturity, appropriate training, and tight supervision appear to be key components to successful pediatric diving. Poor decision making, lack of proper training, ignoring proper procedures for safe diving, and panicking at a critical moment are recurrent themes in fatal adolescent dives. Signs and symptoms of dysbarism, although often dramatic and unmistakable, may also be subtle. Children and adolescents with dysbarism may present to emergency departments far from the coast days after diving. REFERENCES 1. Anderson DM, Novak PD, Keith J, et al: Dorland’s Illustrated Medical Dictionary, 30th ed. Philadelphia: WB Saunders, 2003, p 573. 2. Conkin J, Powell MR, Gernhardt ML: Age affects severity of venous gas emboli on decompression from 14.7 to 4.3 psia. Aviat Space Environ Med 74:1142–1150, 2003. 3. Armoni M, Ohali M, Hay E, et al: Severe dyspnea due to jellyfish envenomation. Pediatr Emerg Care 19:84–86, 2003. 4. Divers Alert Network: Report on Decompression Illness, Diving Fatalities and Project Dive Exploration. 2005. Available at http://www. DiversAlertNetwork.org (accessed May 8, 2006). 5. Divers Alert Network: Report on Decompression Illness, Diving Fatalities and Project Dive Exploration. 2004. Available at http://www. DiversAlertNetwork.org (accessed May 8, 2006). 6. Divers Alert Network: Report on Decompression Illness, Diving Fatalities and Project Dive Exploration. 2003. Available at http://www. DiversAlertNetwork.org (accessed May 8, 2006).

7. Divers Alert Network: Report on Decompression Illness, Diving Fatalities and Project Dive Exploration. 2002. Available at http://www. DiversAlertNetwork.org (accessed May 8, 2006). 8. Divers Alert Network: Report on Decompression Illness, Diving Fatalities and Project Dive Exploration. 2001. Available at http://www. DiversAlertNetwork.org (accessed May 8, 2006). 9. Tsung JW, Chou KJ, Martinez C, et al: An adolescent scuba diver with 2 episodes of diving-related injuries requiring hyperbaric oxygen recompression therapy: a case report with medical considerations for child and adolescent scuba divers. Pediatr Emerg Care 21:681–686, 2005. 10. Table of programs offering scuba diving training courses for children aged 8 to 15 years. Available at http://dive.scubadiving.com/html/ 200110Childcert_chart.html (accessed May 8, 2006). 11. DeGorordo A, Vallejo-Manzur F, Chanin K, et al: Diving emergencies. Resuscitation 59:171–180, 2003. 12. Smith DJ: Diagnosis and management of diving accidents. Med Sci Sports Exerc 28:587–590, 1996. 13. Clenney TL, Lassen LF: Recreational scuba diving injuries. Am Fam Physician 53:1761–1774, 1996. 14. Carstairs S: Arterial gas embolism in a diver using a closed-circuit oxygen rebreathing diving apparatus. Undersea Hyperb Med 28: 229–231, 2001. 15. Torti SR, Billinger M, Schwerzmann M, et al: Risk of decompression illness among 230 divers in relation to the presence and size of patent foramen ovale. Eur Heart J 25:1014–1020, 2004. 16. Schwerzmann M, Seiler C, Lipp E, et al: Relation between directly detected patent foramen ovale and ischemic brain lesions in sport divers. Ann Intern Med 134:21–24, 2001. 17. Bove AA: Risk of decompression sickness with patent foramen ovale. Undersea Hyperb Med 25:175–178, 1998. 18. Chesire WP Jr, Ott MC: Headache in divers. Headache 41:235–247, 2001. 19. Hills BA: Spinal decompression sickness: hydrophobic protein and lamellar bodies in spinal tissue. Undersea Hyperb Med 20:3–16, 1993. 20. Nachum Z, Shupak A, Spitzer O, et al: Inner ear decompression sickness in sport compressed-air diving. Laryngoscope 111:851–856, 2001. 21. Brown M, Jones J, Krohmer J: Pseudoephedrine for the prevention of barotitis media: a controlled clinical trial in underwater divers. Ann Emerg Med 21:849–852, 1992. 22. Butler FK, Bove AA: Infraorbital hypesthesia after maxillary sinus barotrauma. Undersea Hyperb Med 26:257–259, 1999. 23. Robichaud , McNally ME: Barodontalgia as a differential diagosis: symptoms and fi ndings. J Can Dent Assoc 71:39–42, 2005. 24. Decompression Sickness. Available at http://www.ukdivers.net/ physiology/dcs.htm (accessed May 10, 2006). 25. British Thoracic Society Fitness to Dive Group, Subgroup of the British Thoracic Society Standards of Care Committee: British Thoracic Society guidelines on respiratory aspects of fitness for diving. Thorax 58:3–13, 2003. 26. Yeung P, Crowe P, Bennett M: Barogenic rupture of the stomach: a case for non-operative management. Aust N Z J Surg 68:76–77, 1998. 27. Butler FK, Gurney N: Orbital hemorrhage following face-mask barotrauma. Undersea Hyperb Med 28:31–34, 2001. 28. Rudge FW: Ocular barotrauma caused by mask squeeze during a scuba dive. South Med J 87:749–750, 1994. 29. Van Liew HD, Flynn ET: Decompression tables and dive-outcome data: graphical analysis. Undersea Hyperb Med 32:187–198, 2005. 30. Brubakk A: Hyperbaric oxygen therapy: oxygen and bubbles. Undersea Hyperb Med 31:73–79, 2004.

Chapter 145 High Altitude–Associated Illnesses William M. McDonnell, MD, JD and Mark G. Roback, MD

Key Points A history of rapid onset of nonspecific symptoms shortly after ascent to high altitude suggests acute mountain sickness. It is important to rapidly recognize acute mountain sickness, because it may progress to the life-threatening conditions of high-altitude pulmonary edema and high-altitude cerebral edema. Preventative strategies are available for acute mountain sickness. Severe complications of acute mountain sickness can be treated effectively with transport to lower elevation, and less effectively with supportive care and pharmacotherapy.

Selected Diagnoses Acute mountain sickness High-altitude pulmonary edema High-altitude cerebral edema

Discussion of Individual Diagnoses Acute Mountain Sickness Altitude illness historically affected explorers and a few extreme sport adventurers, with little impact on the broader population. However, with increasing access to high-altitude recreation and tourism destinations, there is increasing potential for altitude-related illness in the general population, including children. Substantial research has been done regarding the incidence, etiology, treatment, and prevention of altitude-related illness in adults. However, little has been reported in these areas with respect to children. Therefore, pediatric health care providers, in many cases, must care for their pediatric patients based on elements of adult practice. Although quite variable,1 the incidence of altitude illness is approximately 25% in travelers to altitudes above 6500 feet (2000 m),2 and up to 60% above 14,000 feet (4200 m).3 Both

hypoxia and the lower atmospheric pressure contribute to acute mountain sickness (AMS).4 A history of travel to altitude is the most important factor in recognizing altitude illness. The most common of the acute altitude illnesses, AMS includes the nonspecific symptoms of headache, anorexia, nausea, dyspnea, sleep disturbance, low-grade fever, and malaise. In young children, AMS may manifest as tachypnea,5 increased fussiness, sleep disturbance, decreased playfulness, and decreased appetite.6 Symptoms in both adults and children typically develop within 1 to 2 days of exposure to altitude, with the majority of those affected first experiencing symptoms within 12 hours of arrival at altitude.2,6 The primary risk factors for developing AMS are rapid rate of ascent to high altitude, lack of acclimatization at moderate altitude, and previous altitude illness.7 Strenuous exercise at altitude may result in increased incidence and severity of AMS.8 Dehydration also increases the risk of AMS and worsens its symptoms. Dehydration stimulates increased renal sodium and bicarbonate reabsorption, and the resulting relative metabolic alkalosis reduces the patient’s ability to compensate for the hypoxia of altitude with an appropriately increased ventilatory response.9 Although obesity has been associated with a greater risk for the development of AMS,10 physical fitness does not appear to be protective.7 It is uncertain whether children are at greater risk of developing AMS than adults. One study observed a higher rate of AMS symptoms among children ages 6 to 48 months than among adolescents and adults.11 This study also noted more pronounced hypoxemia among the children with AMS than among the adults and adolescents with the same condition. However, other studies have found no significant difference in the incidence of AMS between preverbal children and adults.6,12 Nevertheless, it is clear that children can and do develop AMS. Clinical Presentation A history of rapid onset of headache and other symptoms such as anorexia, nausea, dyspnea, sleep disturbance, lowgrade fever, and malaise shortly after travel to high altitude strongly suggests AMS, which may progress to the more severe acute altitude illnesses, high-altitude pulmonary edema (HAPE) and high-altitude cerebral edema (HACE). Evaluation of the patient should include a careful assessment of vital signs, and a physical examination with particular scrutiny of respiratory, cardiovascular, and neurologic status. 1025

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Physical examination findings common in AMS include mild temperature elevation, tachypnea, tachycardia, and mild hypoxia. Chest auscultation may reveal diminished aeration, diffuse crackles, or both. AMS may mimic conditions commonly encountered in lower altitude settings, including pneumonitis of viral, bacterial, fungal, or chemical etiologies; dehydration; intracranial hemorrhage or infarction; cerebral edema; and migraine headache. Many of these diagnoses remain in the differential diagnosis, and may be systematically distinguished from altitude illness. An extensive laboratory and radiologic evaluation is rarely warranted. A chest radiograph may help identify the progression of AMS to HAPE, but the findings of AMS or HAPE may be difficult to distinguish from pneumonia. Pulse oximetry helps in assessing the degree of respiratory compromise. Management For all patients with AMS, further ascent is contraindicated, and patients should promptly descend to lower altitude if symptoms worsen. Indications for immediate descent to lower altitude include hypoxia unresponsive to supplemental oxygen, worsening dyspnea, ataxia, and mental status changes. Children’s AMS symptoms resolve quickly after return to lower elevation.6 Moreover, brief AMS from highaltitude exposure produces no lasting neuropsychological impairment or anatomic changes of the brain.13 Patients with mild AMS symptoms may be treated at altitude. Therapy consists of supportive care. Rest and oral hydration are frequently sufficient treatment for mild AMS. As dehydration has been noted to worsen AMS, rehydration with intravenous normal saline may be indicated. However, progression to pulmonary edema is a risk of AMS, and it is prudent to avoid excessive fluid administration. Analgesics such as acetaminophen and ibuprofen typically provide effective relief from the headaches and nausea generally associated with AMS.14,15 However, common migraine headache therapies such as sumatriptan are not effective in treating high-altitude headaches.15 Prevention of AMS is more effective than treatment. The best preventative strategy for AMS is gradual ascent, allowing time for acclimatization. A few days’ acclimatization at altitude generally allows resolution of mild AMS symptoms and may prevent progression of symptoms. An overnight stay at an intermediate altitude has been shown to reduce the incidence of subsequent AMS symptoms.2 The acclimatization effect is generally attributed to increased ventilation and diuresis.16 Similar acclimatization effects have been observed in subjects exposed to brief simulated intermittent altitude exposures in a hypobaric chamber over a period of 3 weeks.17 Acetazolamide has been demonstrated to be useful in preventing AMS, with treated adult subjects showing a decrease in symptoms and greater oxygen saturation levels at altitude.18-20 However, no specific data regarding efficacy or dosing recommendations exist for children. Low-dose glucocorticoids hold promise for prophylaxis against AMS,21 and one adult study has shown that prophylactic acetazolamide in combination with low-dose dexamethasone is more effective in preventing AMS than is acetazolamide alone.22 Another adult study investigating the use of prophylactic nifedipine to prevent HAPE also found a significant reduction in AMS symptoms.23

Although there is some evidence that the use of the herbal supplement ginkgo biloba before and during ascent may reduce the severity of AMS symptoms in healthy adults,24 this finding is not conclusive. A recent large, prospective, randomized controlled study concluded that ginkgo is not effective in reducing either the incidence or severity of AMS, and there are some indications that ginkgo may worsen AMS symptoms.20 Summary Generalized, nonspecific symptoms following ascent to high altitude suggest AMS. The primary risk factors for AMS are rapid ascent to high altitude and a prior history of AMS. Although AMS is generally self-limited, and responds well to acclimatization, as many as 5% to 10% of patients with AMS may develop the more serious altitude illnesses of HAPE or HACE if they do not promptly return to lower altitude.1 High-Altitude Pulmonary Edema With extended exposure to high altitude, a patient with AMS may develop HAPE, with progression to severe hypoxemia. HAPE is a form of rapidly progressive hydrostatic pulmonary edema.25,26 HAPE is characterized by the marked elevation of pulmonary artery and capillary pressures, and changes in left ventricular diastolic function.26-28 Insufficient hypoxic ventilatory response at high altitude, combined with impaired gas exchange resulting from pulmonary edema, produces the severe hypoxemia seen with HAPE.16 Untreated, HAPE may rapidly progress to respiratory failure and death. Although the reported incidence of HAPE is somewhat variable, most individuals will probably experience HAPE if the rate of ascent, maximum elevation attained, and physical exertion are great enough.29 People who exhibit an increased pulmonary artery pressure response to exercise are more likely also to have an increased pulmonary artery pressure response to altitude-related hypoxia, and thus are more prone to develop HAPE.30 It may be possible to identify these individuals at increased risk of developing HAPE by Doppler echocardiography during strenuous exercise.30 For children, the risk of developing HAPE is exacerbated by a concomitant upper respiratory viral infection, while adults seem to face no such increased risk.31 Clinical Presentation The usual progression to HAPE includes the typical nonspecific signs and symptoms of AMS, and the development of a cough that may be productive of blood-tinged mucus, increasing tachypnea, dyspnea at rest, and marked hypoxia.28 Crackles and wheezes are often detected on chest auscultation. Some patients with HAPE have described a “gurgling” sensation in their chests.32 When HAPE is suspected, the patient’s respiratory, hemodynamic, and neurologic status are the focus of the evaluation. Preparations for transport to lower elevation are indicated. As with AMS, only limited laboratory and imaging studies are needed. Chest radiographs show dilation of the central pulmonary arteries, and patchy, peripheral, bilateral or unilateral infi ltrates that are often asymmetric.33 Electrocardiography may show evidence of right ventricular strain, with extensive T-wave negativity in precordial leads,34 which is consistent with autopsy studies that have demonstrated right ventricular dilation.35

Chapter 145 — High Altitude–Associated Illnesses

Management With the progression of AMS to HAPE, further ascent is absolutely contraindicated. Appropriate treatment includes supplemental oxygen at the maximum available concentration, stabilization of hemodynamic status, and prompt descent to lower elevation. Although some patients with mild HAPE may be treated at moderate altitudes (below 10,000 feet/3000 m) with bed rest and supplemental oxygen, any significant deterioration requires immediate transport to lower elevation.36 Portable fabric hyperbaric chambers can be used to provide increased atmospheric pressure while awaiting transport or en route to a lower altitude. With the progression of substantial pulmonary edema, some patients may develop inadequate ventiation and severe hypoxia despite supplemental oxygen, requiring endotracheal intubation and positive pressure ventilation. High pulmonary artery pressure is key to the development of HAPE.26,28 In adults with HAPE, nifedipine reduces pulmonary vascular resistance and pulmonary artery pressures, and thereby reduces symptoms such as dyspnea and chest pain, as well as improving oxygen saturation.37 Although transport to lower elevation remains the definitive treatment for HAPE, nifedipine is generally accepted as an appropriate temporizing therapy in adults when transport is unavoidably delayed. The benefits of nifedipine therapy in children with HAPE have not been established. The signs and symptoms of HAPE typically reverse completely after patients are transferred to low altitude.26 However, patients who have experienced HAPE are at an increased risk of recurrence on return to high altitude.23 Prophylactic inhalation of a β-adrenergic agonist (e.g., albuterol) may reduce the risk of recurrence of HAPE.38 The prophylactic use of nifedipine has also been shown to be effective in preventing HAPE in adults.23 Some victims of HAPE may slowly reascend after a few days at lower altitude and after complete resolution of their symptoms, without recurrence.39 However, such patients should immediately descend at the first sign of recurrence. In summary, patients with AMS who remain at high altitude may develop the worsening pulmonary symptoms of HAPE. Although unrecognized HAPE may be fatal, prompt recognition and transport to lower elevation typically results in complete resolution of symptoms. High-Altitude Cerebral Edema Patients with AMS who remain at high altitude or who continue to climb may progress to HACE. HACE is generally considered to be the end-stage progression of AMS, and is characterized by reversible brain white matter edema, particularly in the corpus callosum.32,40 The mechanism appears to be vasogenic, with movement of fluid and proteins out of the vascular compartment.40 There is some evidence that patients with early AMS are already experiencing minor cerebral edema, which can be demonstrated by subtle cognitive changes on psychomotor testing.41 HACE is usually preceded by the generalized, nonspecific symptoms of AMS. Signs and symptoms of HACE include severe headache, cognitive-behavioral changes, and ataxia, which may quickly progress to obtundation and coma.32 Patients may experience vivid hallucinations.32 The time period for progression from mild neurologic symptoms to

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deep coma is variable, from hours to days.33 HACE is often comorbid with HAPE.32,35 Management As with AMS and HAPE, the initial approach to a patient with HACE includes careful evaluation and stabilization of respiratory and circulatory functions, including securing the patient’s airway in the case of significant depression of mental status. Supplemental oxygen is indicated, and preparations for immediate medical evacuation to lower altitude should be started. Pulse oximetry and arterial blood gases may be useful in evaluating respiratory function. As in any setting of altered mental status, evaluating serum glucose levels is appropriate. Brain imaging studies of HACE patients reveal a picture of cerebral edema. Computed tomography shows diffuse edema, with a paucity or absence of sulci, small ventricles, and diffuse low density of white matter.32,42 Brain magnetic resonance imaging shows increased T2 signal in the white matter, with a characteristic marked increased signal in the corpus callosum.32,40 HACE can usually be diagnosed based on a history of ascent to high elevation and the progression of signs and symptoms, making brain imaging studies unnecessary. HACE is a potentially fatal, but easily reversible, illness. The optimal and definitive management includes immediate transport to lower elevation. After prompt return to low altitude, HACE patients typically have no appreciable residual central nervous system impairment on brain magnetic resonance imaging and neuropsychological testing.13 However, when transport to lower elevation is delayed, HACE may progress to brain herniation and death. Accordingly, transport should not be delayed by any therapy other than assuring adequate respiratory and circulatory function. In the event that transport is unavoidably delayed, oral or parenteral dexamethasone may be of benefit.32,40,41 As with HAPE, portable hyperbaric chambers may be used to simulate lower elevation while awaiting transport. In summary, the development of neurologic signs in a patient with AMS signals the onset of HACE. Although unrecognized and untreated HACE can be fatal, patients who are promptly transported to lower elevation typically have complete resolution of their HACE without sequelae. Immediate transport to lower elevation is universally indicated in cases of HACE. REFERENCES 1. Hackett PH, Rennie D, Levine HD: The incidence, importance, and prophylaxis of acute mountain sickness. Lancet 308:1149–1155, 1976. 2. Honigman B, Theis MK, Koziol-McLain J, et al: Acute mountain sickness in a general tourist population at moderate altitudes. Ann Intern Med 118:587–592, 1993. 3. Ziaee V, Yunesian M, Ahmadinejad Z, et al: Acute mountain sickness in Iranian trekkers around Mount Damavand in Iran. Wilderness Environ Med 14:214–219, 2003. 4. Roach RC, Loeppky JA, Icenogle MV, et al: Acute mountain sickness: increased severity during simulated altitude compared with normobaric hypoxia. J Appl Physiol 81:1908–1910, 1996. *5. Yaron M, Niermeyer S, Lindgren KN, et al: Physiologic response to moderate altitude exposure among infants and young children. High Alt Med Biol 4:53–59, 2003.

*Selected readings.

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*6. Yaron M, Waldman N, Niermeyer S, et al: The diagnosis of acute mountain sickness in preverbal children. Arch Pediatr Adolesc Med 152:683–687, 1998. 7. Schneider M, Bernasch D, Weymann J, et al: Acute mountain sickness: influence of susceptibility, preexposure, and ascent rate. Med Sci Sports Exerc 34:1886–1891, 2002. 8. Roach RC, Maes D, Sandoval D, et al: Exercise exacerbates acute mountain sickness at simulated high altitude. J Appl Physiol 88:581–585, 2000. 9. Cumbo TA, Basnyat B, Graham J, et al: Acute mountain sickness, dehydration, and bicarbonate clearance: preliminary field data from the Nepal Himalaya. Aviat Space Environ Med 73:898–901, 2002. 10. Ri-Li G, Chase PJ, Witkowski S, et al: Obesity: associations with acute mountain sickness. Ann Intern Med 139:253–258, 2003. *11. Moraga FA, Osorio JD, Vargas ME: Acute mountain sickness in tourists with children at Lake Chungara (4400 m) in northern Chile. Wilderness Environ Med 13:31–35, 2002. *12. Yaron M, Niermeyer S, Lindgren KN, et al: Evaluation of diagnostic criteria and incidence of acute mountain sickness in preverbal children. Wilderness Environ Med 13:21–26, 2002. 13. Anooshiravani M, Dumont L, Mardirosoff C, et al: Brain magnetic resonance imaging (MRI) and neurological changes after a single high altitude climb. Med Sci Sports Exerc 31:969–972, 1999. 14. Harris NS, Wenzel RP, Thomas SH: High altitude headache: efficacy of acetaminophen vs. ibuprofen in a randomized, controlled trial. J Emerg Med 24:383–387, 2003. 15. Burtscher M, Likar R, Nachbauer W, et al: Ibuprofen versus sumatriptan for high-altitude headache. Lancet 346:254–255, 1995. 16. Bartsch P, Swenson ER, Paul A, et al: Hypoxic ventilatory response, ventilation, gas exchange, and fluid balance in acute mountain sickness. High Alt Med Biol 3:361–376, 2002. 17. Beidleman BA, Muza SR, Fulco CS, et al: Intermittent altitude exposures reduce acute mountain sickness at 4300 m. Clin Sci 106:321–328, 2004. *18. Basnyat B, Gertsch JH, Johnson EW, et al: Efficacy of low-dose acetazolamide (125 mg BID) for the prophylaxis of acute mountain sickness: a prospective, double-blind, randomized, placebo-controlled trial. High Alt Med Biol 4:45–52, 2003. 19. Carlsten C, Swenson ER, Ruoss S: A dose-response study of acetazolamide for acute mountain sickness prophylaxis in vacationing tourists at 12,000 feet (3630 m). High Alt Med Biol 5:33–39, 2004. 20. Gertsch JH, Basnyat B, Johnson EW, et al: Randomised, double blind, placebo controlled comparison of ginkgo biloba and acetazolamide for prevention of acute mountain sickness among Himalayan trekkers: the Prevention of High Altitude Illness Trial (PHAIT). BMJ 328:797, 2004. 21. Basu M, Sawhney RC, Kumar S, et al: Glucocorticoids as prophylaxis against acute mountain sickness. Clin Endocrinol 57:761–767, 2002. 22. Bernhard WN, Schalick LM, Delaney PA, et al: Acetazolamide plus low-dose dexamethasone is better than acetazolamide alone to ameliorate symptoms of acute mountain sickness. Aviat Space Environ Med 69:883–886, 1998. 23. Bartsch P, Maggiorini M, Ritter M, et al: Prevention of high-altitude pulmonary edema by nifedipine. N Engl J Med 325:1284–1289, 1991.

24. Gertsch JH, Seto TB, Mor J, et al: Ginkgo biloba for the prevention of severe acute mountain sickness (AMS) starting one day before rapid ascent. High Alt Med Biol 3:29–37, 2002. *25. Swenson ER, Maggiorini M, Mongovin S, et al: Pathogenesis of highaltitude pulmonary edema: inflammation is not an etiologic factor. JAMA 287:2228–2235, 2002. 26. Maggiorini M: Cardio-pulmonary interactions at high altitude: pulmonary hypertension as a common denominator. Adv Exp Med Biol 543:177–189, 2003. 27. Allemann Y, Rotter M, Hutter D, et al: Impact of acute hypoxic pulmonary hypertension on LV diastolic function in healthy mountaineers at high altitude. Am J Physiol Heart Circ Physiol 286:H856–H862, 2004. 28. Maggiorini M, Melot C, Pierre S, et al: High-altitude pulmonary edema is initially caused by an increase in capillary pressure. Circulation 103:2078–2083, 2001. 29. Cremona G, Asnaghi R, Baderna P: Pulmonary extravascular fluid accumulation in recreational climbers: a prospective study. Lancet 359:303–309, 2002. 30. Grunig E, Mereles D, Hildebrandt W, et al: Stress Doppler echocardiography for identification of susceptibility to high altitude pulmonary edema. J Am Coll Cardiol 35:980–987, 2000. 31. Durmowicz AG, Noordeweir E, Nicholas R, et al: Inflammatory processes may predispose children to high-altitude pulmonary edema. J Pediatr 130:838–840, 1997. 32. Yarnell PR, Heit J, Hackett PH: High-altitude cerebral edema (HACE): The Denver/Front Range experience. Semin Neurol 20:209– 217, 2000. 33. Vock P, Fretz C, Franciolli M, et al: High-altitude pulmonary edema: fi ndings at high-altitude chest radiography and physical examination. Radiology 170:661–666, 1989. 34. Fiorenzano G, Papalia MA, Parravicini M, et al: Prolonged ECG abnormalities in a subject with high altitude pulmonary edema (HAPE). J Sports Med Phys Fitness 37:292–296, 1997. 35. Hultgren HN, Wilson R, Kosek JC: Lung pathology in high-altitude pulmonary edema. Wilderness Environ Med 8:218–220, 1997. 36. Zafren K, Reeves JT, Schoene R: Treatment of high-altitude pulmonary edema by bed rest and supplemental oxygen. Wilderness Environ Med 7:127–132, 1996. 37. Oelz O, Ritter M, Jenni R, et al: Nifedipine for high altitude pulmonary oedema. Lancet 334:1241–1244, 1989. 38. Sartori C, Allemann Y, Duplain H, et al: Salmeterol for the prevention of high-altitude pulmonary edema. N Engl J Med 346:1631–1636, 2002. 39. Litch JA, Bishop RA: Reascent following resolution of high altitude pulmonary edema (HAPE). High Alt Med Biol 2:53–55, 2001. *40. Hackett PH, Yarnell PR, Hill R: High-altitude cerebral edema evaluated with magnetic resonance imaging: clinical correlation and pathophysiology. JAMA 280:1920–1925, 1998. 41. Lafleur J, Giron M, Demarco M: Cognitive effects of dexamethasone at high altitude. Wilderness Environ Med 14:20–23, 2003. 42. Kobayashi T, Koyoma S, Kubo K, et al: Clinical features of patients with high-altitude pulmonary edema in Japan. Chest 92:814–821, 1987.

Chapter 146 The Sick or Injured Child in a Community Hospital Emergency Department Alfred Sacchetti, MD, John A. Brennan, MD, and Neil Schamban, MD

Key Points Tertiary children’s hospitals and community hospitals have different available resources. Different diagnostic and therapeutic strategies exist in a children’s hospital emergency department versus a community hospital’s emergency department. The lack of tertiary pediatric services in a community hospital is countered by increased capabilities within the community emergency department. Appropriate interactions with consultants from a children’s hospital will favorably impact the care of a critically injured or ill child. Pediatric emergency medicine leadership is very important in a community-based emergency department.

Introduction and Background There are over 31 million pediatric emergency department (ED) visits per year, most of which are treated in facilities that may be described as community hospitals.1 Many of these visits will be for relatively minor ambulatory complaints, although an important minority will be critically ill or injured children. The principles of resuscitation and stabilization do not vary between a tertiary children’s hospital and a community ED, although the manner in which these fundamentals are accomplished can differ dramatically.

Issues and Solutions Institutional Differences Tertiary children’s hospitals and community hospitals are intrinsically different.2 One of the hallmarks of a children’s

hospital is immediate access to subspecialists from almost every discipline. More importantly, pediatric anesthesiologists, intensivists, and surgeons maintain a continuous presence in the hospital for assistance with resuscitation attempts. By contrast, the community ED frequently has limited subspecialty resources available, and resuscitation attempts are the exclusive domain of ED personnel.3,4 Ironically, this clinical situation mandates a greater degree of individual competence in the community ED than is required at the tertiary care center. Stated more simply, the ED capabilities of any hospital are an inverse function of the hospital’s inpatient capabilities. This rule of ED functional capacity is applicable to any area of medicine and is summarized in Figure 146–1. The ability of the community ED to deliver care equivalent to that of a tertiary care hospital requires motivated clinicians with access to appropriate equipment, medications, diagnostic studies, and timely transfers. The qualifications and roles of ED personnel needed to optimize pediatric care are contained in the joint American Academy of Pediatrics–American College of Emergency Physicians publication “Care of Children in the Emergency Department: Guidelines for Preparedness.”5 To provide appropriate care with good outcomes, though, any group of clinicians will require appropriate institutional support. It is important to recognize the need for specialized pediatric equipment in the emergency department, even in facilities with no inpatient pediatric capabilities (see Chapter 154, The Child Friendly Emergency Department: Practices, Policies, and Procedures). These same considerations need to be given to medications not typically contained in the formulary of a nonpediatric hospital. Because of its responsibility in the extended stabilizations of critical children, the ED requires access to a wider assortment of procedural sedation and resuscitation medications. The best example of such a need might be the use of prostaglandin E to reopen the ductus arteriosus in a cyanotic neonate. Unless specifically requested by the ED, no hospital without obstetric services is likely to stock this medication. Procedural sedation medications must be given special consideration in EDs with expanded pediatric responsibilities. 1031

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SECTION VI — The Practice Environment ED capabilities = f (1/Hospital capabilities)

FIGURE 146–1. Law of emergency department (ED) functional capacity. To optimize patient outcomes, the capabilities of the ED vary inversely with the capabilities of the hospital.

Table 146–1

Essential Procedural Sedation Medications

Propofol or methohexital Etomidate Ketamine Fentanyl Rocuronium Vecuronium

Simple sedation for diagnostic imaging, analgesia for painful conditions, procedural sedation for invasive procedures, or extended sedation for ventilator cooperation all require unrestricted access to an extended formulary to optimize patient outcomes. At the very least, emergency physicians should be granted privileges for and unrestricted access to the medications listed in Table 146–1.6,7 Diagnostic studies unique to the ED must also be available to accommodate unusual pediatric presentations. In particular, the ability to handle microsized specimens for blood counts, electrolytes, and basic metabolic analysis must be assured. The introduction of single-drop blood analyzers can resolve this issue for institutions hesitant to purchase expensive pediatric-specific laboratory equipment.8 Radiology departments may also be required to provide pediatricspecific imaging studies applicable only to ED pediatric patients. Although it is unreasonable to expect a hospital to purchase expensive equipment simply for a potential ED need, it is appropriate to request basic pediatric imaging capabilities. In some institutions the problem may not be with the technical component of an imaging study, but with the staff radiologist, who may be uncomfortable interpreting certain pediatric studies. This problem may be solved through the use of teleradiology to a remote pediatric center.9-11 For some EDs, access to appropriate diagnostic studies may just not be possible. In these instances, the emergency physician may be required to transfer a child to a pediatric center for a simple diagnostic study to exclude a potential disease condition. The expanded responsibilities of the ED or emergency personnel may require modifications of hospital policies. If patient outcomes are to be optimized, then the ED must be equipped and the emergency physicians must be credentialed to perform all of the initial stabilization activities not provided by the remainder of the hospital. This credentialing of emergency physicians for procedures reserved only for hospital subspecialists may be the only way to assure that a critical child receives all of the necessary support in a timely manner. Credentialing for deep sedation, ultrasonography, fluoroscopy, and fiberoptic evaluations must be provided for the emergency physicians or be immediately available from other members of the medical staff. Finally, emergency physicians may find themselves in the role of children’s advocate at hospitals that lack any in-patient pediatric services. As the sole providers for this “orphaned” subset of patients, they will need to compete for hospital resources that may not be shared by other departments or

medical staff. In these institutions a representative emergency physician will need to assume a leadership position in the acute management of the sick or injured child. Fortunately, this is a role that emergency physicians are uniquely qualified to assume. Clinical Skills Maintenance of clinical capabilities is a problem in all aspects of medicine. In certain surgical specialties, evidence exists that a minimum number of procedures must be performed annually to assure successful outcomes.12-17 The ED is unique in that emergency physicians do not have the ability to arrange elective patient encounters to maintain certain skills. However, unlike studies involving surgeons or other interventionalists, there are no data to indicate any outcome differences in children managed in EDs with limited pediatric encounters. The clinical skills of any practitioner are a function of his or her past experiences and ongoing patient encounters. General emergency physicians may draw on their ability to perform resuscitative procedures on adults to assist them in performing the same procedures in children. Arguments about children not being small adults aside, procedural differences between adults and children are relatively minor and easily incorporated into clinical practice. Recognition of the subtle signs of diseases can be difficult for clinicians with limited pediatric exposures. Ongoing contact with ambulatory children remains the best means to improve recognition of a sick child. However, in critically ill children, the degree of distress will generally be obvious and unlikely to be missed. Unique Clinical Aspects of Community ED Stabilization The principles of pediatric stabilization do not change, although the manner in which the care is delivered can vary greatly between institutions. For a number of reasons, treatment in a community ED trends towards more aggressive management of critical children. For facilities without an onsite pediatric intensive care unit (PICU), extended observation is not an option. Immediate access to tertiary care support provides an opportunity to initially provide more conservative care in a critical care setting and withhold interventions until they are unavoidable. In contrast, the need for an actual physical transfer requires immediate reversal of any downward physiologic trends in order to minimize the risk of decompensation once the child leaves the sending hospital. The concept of waiting to see if a child turns around on his or her own is unrealistic for anyone anticipating an extended ground or air transport. The actual performance of a resuscitative procedure is also more easily accomplished in a hospital setting than in a moving transport vehicle. An in-house PICU also provides another set of hands to assure expedient management of the child regardless of the point at which the child decompensates. In contrast, in an ED with only one physician, and no in-house critical care backup, watchful waiting can jeopardize the care of the child if a sudden change occurs and multiple procedures are immediately required, or if a second emergent patient presents to the ED. An underappreciated aspect of the single-coverage community ED, which directly affects the timing of procedures,

Chapter 146 — The Sick or Injured Child in a Community Hospital Emergency Department

Oxygen saturation/pH

100 90

Early ETI attempt Early ETI completed

80 Late ETI attempt

70 60 Late ETI completed

50 0

3

6

9

12

15

18

21

24

27

30

Time (minutes) FIGURE 146–2. Loss of reserves in a child with progressive respiratory failure. Initiation of endotracheal intubation (ETI) attempt early will permit completion of even a very difficult procedure while the child still has acceptable physiologic parameters. A late intubation attempt may lead to exhaustion of any reserves and cardiac arrest prior to completion.

is the continuing responsibility for all patients within the department. Early completion of potential procedures permits a lone emergency physician to manage a critically ill child from a distance. For example, a ventilated child with secure vascular access and proper electronic monitoring may be managed by a bedside nurse who can relay information back and forth to a physician elsewhere in the department. The same child, with less aggressive care, will require a near-continuous bedside presence from that single attending physician regardless of what other patient responsibilities may arise. Earlier procedure attempts also increase the odds of successful outcomes, particularly in children with rapidly evolving findings. As a child’s condition deteriorates so, too, do his or her reserves. Figure 146–2 presents the physiologic decline of a child progressing from respiratory failure toward respiratory arrest. If endotracheal intubation is begun before the child’s pH and oxygen saturation have begun to drop, even a time-consuming, difficult intubation will be completed before premorbid physiologic conditions develop. However, if airway attempts are delayed until the child is severely hypoxic and acidotic, then that same timeconsuming intubation may not be completed until the child has progressed on to a cardiac arrest. Aggressive medical management will also help define further treatment options when care is relinquished to the tertiary care facility. Defining what has been attempted and what has not worked places an accepting physician much further along a treatment algorithm than if only first-line therapies were applied. Determining that benzodiazepines and barbiturates failed to control a child’s seizures moves the consultant immediately to more advanced interventions without having to recommend each of the earlier treatments and waiting to see an effect. Managing Patient Transfers and Consultation Like every other aspect of patient care in a community ED, the transfer of a patient must be coordinated with other ongoing activities in the department. The extent to which the transfer process can be streamlined will impact greatly the amount of time nurses and physicians will be diverted from direct patient care. Ideally, clinicians should be involved only in conversations related to patient management while support

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personnel address administrative and logistic issues. Development of transfer agreements with specific institutions and internal policies governing individual ED staff responsibilities during patient transfers decreases medical errors and improves patient outcomes. The degree of interaction between the sending and receiving medical staffs will be determined by the nature of the transfer. In some instances the management of a child is straightforward and the transfer is strictly for services unavailable at the community hospital. A stable child with an isolated femur fracture being moved to a hospital with inpatient pediatric facilities exemplifies such a transfer. The communication between the emergency physician and receiving physician will likely be minimal and focus primarily on the logistics of the transfer. In other instances the emergency physician may require management consultations as well as transfer arrangements. In these instances the emergency physician and consultant interactions may become as important as the management of the patient. All tertiary care institutions have protocols in place to assist facilities transferring patients. Depending on the receiving facility, a call to initiate a transfer is coordinated by a nurse, a transfer center, a resident or fellow in training, or a subspecialty attending physician. If immediate management advice is required, it is important for the emergency physician to gain access to the necessary consultant as efficiently as possible. Valuable time can be wasted with extended delays on telephone hold or working up through a resident hierarchy to reach the consultant needed. Transfer agreements or policies to assist unit secretaries in locating the appropriate personnel at the receiving hospital can help to resolve these types of problems. When discussing the specifics of the clinical scenario with a consultant, it is imperative for the sending emergency physician to direct the conversation. In presenting the case, the sending emergency physician should begin with the suspected diagnosis and a very succinct summary of care to that point. This can be followed by any questions or solicitations for recommendations. The more focused the sending emergency physician can keep the conversation, the quicker patient care issues can be addressed. An example of a concise presentation might be: “We have a 9-month-old male with septic shock, diffuse purpura, intubated, fluid resuscitated with 60 ml/kg of NSS, on a 10-mcg/kg dopamine infusion, with a blood pressure of 60/20, who has received 100 mg/kg of ceftriaxone. We are preparing to begin a neosynephrine infusion; do you wish to change this?” This presentation sets the tone for a very efficient conversation. In addition, the description of the interventions and management of the case cues the consultant as to the capabilities of the clinicians in the sending ED. This is useful in helping the consultant determine the sophistication of the advice to be given. In contrast, a less effective conversation may begin “We have a 9-month-old who’s been less active for 2 days and then developed a slight fever yesterday.” Such an introduction takes far too long to move the consultant to the current point in the child’s treatment and will provide extraneous information not needed for the immediate care. A consultant can always ask for additional information or clarification as the conversation progresses. Once a consultant has been contacted, determination of a child’s ongoing treatment is by mutual agreement. It is

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SECTION VI — The Practice Environment

perfectly reasonable for a sending physician to ask for justification for unusual recommendations, just as it is appropriate for a consultant to request specific procedures be accomplished prior to transfer. The logistics of the actual transfer will vary with the complexity of the case, the arrangements between the sending and receiving facilities, and the degree of stabilization accomplished at the community hospital.

Summary Community hospital EDs manage the majority of critically sick or injured children presenting for acute care. The community hospital ED must be appropriately equipped with physicians and nurses capable of caring for these children. Community EDs provide the key management link between their community and a tertiary children’s hospital care. REFERENCES *1. Gausche-Hill M, Fuchs S, Yamamoto L (eds): APLS: The Pediatric Emergency Medicine Resource, 4th ed. Sudbury, MA: Jones & Bartlett, 2004. 2. Goldfrank L, Henneman PL, Ling LJ, et al: Emergency center categorization standards. Acad Emerg Med 6:638–655, 1999. 3. Sacchetti AD, Brennan J, Kelly-Goodstein N, et al: Should pediatric emergency care be decentralized? An out of hospital destination model for critically ill children. Acad Emerg Med 7:787–791, 2000. 4. Sacchetti AD, Warden T, Moakes ME, et al: Can sick children tell time? Emergency department presentation patterns of critically ill children. Acad Emerg Med 6:906–910, 1999.

*Selected readings.

*5. American College of Emergency Physicians: Emergency care guidelines. Ann Emerg Med 29:564–571, 1997. *6. EMSC Grant Panel Writing Committee; Mace SE, et al: Clinical Policy: Evidence-based approach to pharmacologic agents used in pediatric sedation and analgesia in the emergency department. Ann Emerg Med 44:342–377, 2004. 7. Gerardi MJ, Sacchetti AD, Cantor RM, et al: Rapid-sequence intubation in the pediatric patient. Ann Emerg Med 28:55–74, 1996. 8. Rossi AF, Khan D: Point of care testing: improving pediatric outcomes. Clin Biochem 37:456–461, 2004. 9. Randolph GR, Hagler DJ, Khandheria BK, et al: Remote telemedical interpretation of neonatal echocardiograms: impact on clinical management in a primary care setting. J Am Coll Cardiol 34:241–245, 1999. 10. Yamamoto LG, Inaba AS, DiMauro R: Personal computer teleradiology interhospital image transmission to facilitate tertiary pediatric telephone consultation and patient transfer: soft-tissue lateral neck and elbow radiographs. Pediatr Emerg Care 10:273–277, 1994. 11. Krupinski E, Nypaver M, Poropatich R, et al: Telemedicine/telehealth: an international perspective. Clinical applications in telemedicine/ telehealth. Telemed J E Health 8:13–34, 2002. 12. Birkmeyer JD, Stukel TA, Siewers AE, et al: Surgeon volume and operative mortality in the United States. N Engl J Med 349:2117–2127, 2003. 13. Jollis JG, Peterson ED, DeLong ER, et al: The relation between the volume of coronary angioplasty procedures at hospitals treating Medicare beneficiaries and short-term mortality. N Engl J Med 331:1625– 1629, 1994. 14. Birkmeyer JD, Dimick JB: Potential benefits of the new Leapfrog standards: effect of process and outcomes measures. Surgery 135:569–575, 2004. 15. National Center of Healthcare Leadership (NCHL) web site. Available at http://www.nchl.org/ns/about/aboutnchl.asp *16. Gausche-Hill M, Johnson RW, Warden CR, et al: The role of the emergency physician in emergency medical services for children. Ann Emerg Med 42:206–215, 2003. 17. The Institute of Family Centered Care web site. Available at http:// www.familycenteredcare.org/about-us-frame.html

Chapter 147 Emergency Medical Services and Transport Michael G. Tunik, MD and George L. Foltin, MD

Key Points Physicians, nurses, and other practitioners should understand the components and capabilities of their Emergency Medical Services (EMS) system, which plays a critical role in caring for acutely ill or injured children. Improving the EMS system will improve the care of ill or injured children. Appropriate EMS equipment and protocols and a quality program are essential components of a successful EMS program. Effective communications with and transfer of care from the out-of-hospital setting to the emergency department are essential components of a successful EMS program.

Introduction and Background Definitions Emergency Medical Services (EMS) System Emergency Medical Services (EMS) systems are groups of organizations responsible for delivering emergency care in the out-of-hospital setting. The collaboration of these organizations delivers appropriate out-of-hospital care, triage, and transport of children who are acutely ill or injured.

tion is usually by radio or telephone. Medical personnel are typically based in the receiving hospital, or a centralized EMS system communications facility. Protocols for Out-of-Hospital Care Out-of-hospital protocols are written guidelines that are the standing medical orders directing the interventions, triage, and transport of acutely ill or injured children. These protocols are written by physicians participating in off-line or indirect medical control. Emergency Medical Services for Children (EMSC) Emergency Medical Services for Children (EMSC) is not a separate EMS system, but is the integration of the special needs of children into existing EMS system. The components of an EMS system that may need specific modifications for children1 are listed in Table 147–1. Trauma System A trauma system is a system of care involving out-of-hospital stabilization, care, triage (based on trauma severity scores), and transport to trauma centers capable of addressing the unique needs of traumatized patients, including emergency care, surgical care, anesthesia care, critical care, and rehabilitation. Transport Primary transport is the movement of a patient from the out-of-hospital location of an injury or illness to a hospital emergency department (ED). Secondary transport occurs when the patient is moved from the ED or hospital ward to a specialty center (e.g., trauma center, burn center) or defi nitive care center.

Medical Control Off-line, or indirect, medical control includes the development and modification of equipment lists, treatment protocols, criteria for dispatch, the system’s quality and safety programs, and triage. On-line, or direct, medical control is the real-time communication between EMS care providers and authorized medical personnel who assist out-of-hospital providers with interventions, triage, and transport decisions. Communica-

Issues History of EMS The need for systemized EMS was first identified in the 1960s.2,3 Surgeons returning from Korea and Vietnam observed the inadequate care that victims of vehicular trauma were receiving in comparison to the care of injured military personnel. This resulted in the publication of a milestone 1035

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SECTION VI — The Practice Environment

Table 147–1

Components of an EMS System

Personnel Training Communications Medical control Transportation Transfer of patients Facilities Critical care units Public safety agencies Disaster linkage Mutual aid agreements Consumer participation Consumer education Access to care Medical record keeping Independent review (continuous quality improvement)

paper, “Accidental Death and Disability: The Neglected Disease of Modern Society” which explicitly delineated the inadequate level of EMS.4 This publication stimulated the development of a systems approach to EMS. Pioneering work in EMS systems development was taking place in the late 1960s and early 1970s funded by the Department of Transportation and the Robert Wood Johnson Foundation, among others. The federal government provided funding for the development of EMS systems with the Emergency Medical Services Act of 1973 (PL 93-154). The program specified patient populations that would benefit from specialized care at regional hospitals within an integrated EMS system. This included seven populations: patients with trauma, cardiac disease, burns, spinal cord injuries, poisonings, and behavioral emergencies, and those requiring neonatal care.5 Neonatal care patients were the fi rst nonmilitary population in which the process of regionalization, specialty transport, and secondary transport was successfully utilized. The EMS system components developed included manpower, training, communications, transportation, facilities, critical care units, public safety agencies, consumer participation, access to care, patient transfer, coordinated patient record keeping, public information and education, review and evaluation, and disaster planning. These components were to be found in a spectrum of independent organizations, and the success of a given EMS system was a result of these organizations’ ability to work interdependently.6 Ill and injured children were not initially included as a target population for regionalized care, nor did developing EMS systems recognize their special needs. No pediatric specialists other than neonatologists became involved at that time.7 Studies of children’s needs and outcome after EMS care were not available; children were simply overlooked. To effectively provide care for children, their needs must be identified and methods to provide for those special needs integrated into already existing EMS systems. Adult needs that have been demonstrated to improve outcome include rapid defibrillation of ventricular dysrhythmias, and immobilization and rapid transport of multisystem trauma patients to definitive care. Recent studies have also demonstrated that adults benefit from advanced life support (ALS) for complaints of chest pain and respiratory difficulty.8,9

Table 147–2

Personnel Providing EMS for Children

Parents (medical home) Public Primary care physician “911” operators/medical dispatch Out-of-hospital personnel (first responder, EMT, paramedic) Medical control physicians (direct and indirect) Emergency department physicians, nurses Hospital inpatient physicians, nurses, respiratory therapists, and other health care providers Secondary transportation team Pediatric critical care/trauma center Rehabilitation team

A goal for EMS for children is to identify the etiologies of morbidity and mortality and to incorporate interventions into the already existing EMS system that will improve outcome. Models of Care The trauma model of out-of-hospital care is to provide a patent airway and adequate ventilation, to control hemorrhage, and to transport the patient to an appropriate trauma center, which provides definitive care. Out-of-hospital interventions should not prolong transport time, as this may be deleterious to patient outcome.7 In the medical (cardiac) model of care, the priority in adults includes rapid delivery of defibrillation to treat ventricular dysrhythmias and reverse sudden cardiac death. Emergency Medical Services for Children Historical Perspective The needs of children in EMS systems were not initially addressed. In 1985 the federal government recognized the need for improved EMSC and passed legislation that funded the EMSC program. Senator Daniel Inoue (D–Hawaii), his aide Patrick DeLeon, and Calvin Sia, MD, provided the impetus for EMS. Senators Orrin Hatch (R–Utah) and Lowell Weicker (R–Connecticut) joined Senator Inouye in writing the EMSC legislation (PL 98-555), which established a national EMSC program. Other organizations have also targeted resources and personnel toward improved EMSC; these include but are not limited to the American Academy of Pediatrics (Committee on Pediatric Emergency Medicine), the American College of Emergency Physicians (Section on Pediatric Emergency Medicine), the Ambulatory Pediatric Association (Special Interest Group on Pediatric Emergency Medicine), the National Association of EMS Physicians (Pediatric Committee), and the National Association of Emergency Medical Technicians. To be effective in integrating EMSC into EMS, individuals and members of organizations must be involved in improving EMSC care based on their area of expertise (Table 147–2). The process of education about the special needs of children and the provision of formal education are critical steps to ensure that all these individuals deliver the best care possible.

Chapter 147 — Emergency Medical Services and Transport

Pediatric Model of Care Respiratory distress, failure, and arrests are relatively infrequent events in the out-of-hospital care of children. However, recent studies demonstrate a high rate of respiratory arrest in children, compared to cardiac arrest, with the rate and absolute numbers of survivors from respiratory arrest far surpassing the rate and absolute numbers of survivors from pediatric cardiac arrests.10-12 Airway management skills are critical for out-of-hospital providers caring for children. The pediatric out-of-hospital care model should be conservative (providing basic life support [BLS] care, focusing on airway and ventilation, and on transport to pediatric-capable hospital EDs) yet permissive (providing ALS) when the life-saving benefits are clearly present (e.g., treating ventricular dysrhythmias with defibrillation, reactive airways disease with bronchodilators, and anaphylaxis with epinephrine).7

Solutions: EMSC System Development Epidemiology The epidemiology of pediatric illness and injury encountered by the EMS system dictates the training, equipment, and protocols for treatment, triage, and transfer, as well as the capabilities of the transport system. Studies of the epidemiology of illness and injury in the out-of-hospital setting have demonstrated similar patterns. Children are frequently transported by their caregivers for emergency evaluation, which accounts for approximately one third of all ED visits nationally. In the out-of-hospital setting, children account for approximately 6% to 10% of all ambulance runs.13-15 The acuity level for pediatrics in the out-ofhospital setting is lower than for adults. Approximately 0.3% to 0.5% of transported children require tertiary care, and 5% of these cases involve life- or limb-threatening problems. Most children are transported between 12 noon and 12 midnight.13 Children present in a bimodal age distribution, with the most frequent transports for ages less than 2 years and greater than 10 years. Younger children frequently present with medical problems; above age 2 years, trauma predominates. Most pediatric patients are managed by first responders and emergency medical technicians (EMTs) providing BLS, and about one third are managed by paramedics and receive ALS. Children transported to emergency departments by EMS personnel are three to four times more likely to require admission than are those who arrive by other methods.16 Injury mechanisms include motor vehicle accidents (including vehicle occupant, pedestrian struck, or bicyclist struck), burns, and falls. Medical complaints include seizures, respiratory difficulty (choking, stridor, lower airway disease, apnea), submersion injuries, and poisonings. Other problems include pregnancy-related problems, out-of-hospital births, and abdominal pain. These patterns of illness and injury are different than adult patterns, requiring education and treatment protocols that meet the needs of children.13,17 Early EMSC System Development In 1978, Los Angeles County EMS developed guidelines for out-of-hospital care of pediatric emergencies, a pediatric equipment list for out-of-hospital care providers, a curricu-

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lum for the education of paramedics in pediatric emergencies, and a plan for integration of EMSC into the existing EMS system. Through their work, guidelines for a two-tiered system developed with facilities designated as Emergency Departments Approved for Pediatrics (EDAPs) or Pediatric Critical Care Centers (PCCCs). EDAPs are emergency facilities that provide basic emergency services and also voluntarily meet minimum standards for staffing, education, equipment, supplies, and protocols appropriate for the initial care and stabilization of critically ill and injured children. PCCCs must meet EDAP criteria and, in addition, have specialized pediatric services, including a pediatric intensive care unit and dedicated pediatric medical and surgical specialists.18 Others cities were also involved in improving EMSC (Mobile, Alabama; New York City; and Milwaukee, Wisconsin) through cooperative efforts initiated by and involving pediatricians, emergency physicians, and EMS physicians in the area.7,10,19 The Maryland Institute for Emergency Medical Service Systems (MIEMSS) also became a model for a successful and fully integrated EMS/trauma system and was one of the first to incorporate pediatric trauma receiving hospitals. EMS System Stages of Care There are seven stages of care for children in EMS systems: entry (recognition and activation), response, treatment and triage, transport, hospital, rehabilitation, and prevention. Entry (Recognition and Activation) Phase A parent, teacher, sibling, or bystander must recognize the urgency of signs and symptoms in ill or injured children that begin the entry stage of care. Advice on when to activate the EMS system is readily available.20 In many regions, a “911” or a “911”-enhanced telephone system exists and provides direct access to the EMS system. Parents, caregivers, and schools should be familiar with this number and its correct use.21 Physicians should provide information for parents regarding when to contact the physicians’ office versus “911”20 (Table 147–3), as well as which EDs are most appropriate for children. A call to “911” for a minor ailment can cause potentially life-threatening delays in the EMS response to a serious injury requiring emergent care.

Table 147–3

Example Situations Requiring Activation of the EMSC System

Acting strangely, less alert Less and less of a response when you talk to your child Unconsciousness or lack of response Rhythmic jerking and loss of consciousness (a seizure) Increasing trouble with breathing Skin or lips that look blue, purple, or gray Neck stiffness or rash with fever Increasing or severe persistent pain A cut or burn that is large or deep, or involves the head, chest, or abdomen Bleeding that does not stop after applying pressure for 5 minutes A burn that is large or involves the hands, groin, or face Any loss of consciousness, confusion, headache, or vomiting after a head injury

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Response Phase The response phase includes activation of the “911” system to elicit an ambulance dispatch, which should be medically directed and coordinated. EMS systems may be one, two, or three tiered, composed of first responders, BLS, and/or ALS units. The type of unit dispatched, and the priority of the dispatch (high, medium, or low priority, response with lights and sirens, etc.) should be based on predetermined guidelines developed by a regional medical control physician.22,23 Standardized dispatch protocols include standard prearrival instructions, allowing the dispatcher to assist the on-scene parent, caregiver, or bystander to deliver optimal care. Adultoriented ambulance dispatching may not adequately triage pediatric calls in determining which patient requires an ALS unit versus a BLS unit.16 More research is needed to determine the optimal dispatch protocols for children as these should be part of every EMS-EMSC integrated system. There are five levels of EMS providers with regard to training and care. First responders can clear and maintain the airway, perform assisted ventilations and cardiopulmonary resuscitation (CPR), and establish hemorrhage control. Emergency Medical Technicians–Basic (EMT-Bs) provide these skills and, in addition, perform patient assessment, administer oxygen, assist ventilation using a bag-mask device, immobilize the spine, and transport patients. In some EMS systems, EMTs are trained to assist in administering autoinjected epinephrine to treat anaphylaxis, and to administer inhaled bronchodilators. EMT-Ds (providers of BLS) possesses all the skills of EMT-Bs, and are also trained to use an automated external defibrillator and defibrillate. EMTIntermediates (EMT-Is) are trained to an intermediate level between EMT-Ds and paramedics. The level of training varies with the state and EMS system. EMT-Is may perform endotracheal intubation and obtain vascular access. Paramedics (EMT-Ps) are trained to obtain vascular access and deliver medications via inhaled, intraosseous, intravenous, intramuscular, and endotracheal routes. Paramedics perform endotracheal intubation, and in some EMS systems are trained to perform intubation using sedative and paralytic medications. Care by EMS providers (first responder, EMT, paramedic) includes a scene assessment and assessment of the child (standard assessment approach now includes the Pediatric Assessment Triangle; see Chapter 2, Respiratory Distress and Respiratory Failure). Initial interventions include maintenance of the airway, adequate ventilation, and circulation. Other interventions depend on the particular medical illness or traumatic injury. Treatments are determined by the training of EMS providers (assessment skills, technical skills), as well as protocols for allowable interventions, appropriate equipment on the ambulance, and on-line medical control communication to guide therapy and transportation decisions.

Table 147–4

Model Pediatric Protocols

General patient care Trauma Burns Foreign body obstruction Respiratory distress, failure, or arrest Bronchospasm Neonatal resuscitation Bradycardia Tachycardia Nontraumatic cardiac arrest Ventricular fibrillation or pulseless ventricular tachycardia Asystole Pulseless electrical activity Altered mental status Seizures Nontraumatic hypoperfusion (shock) Anaphylactic shock/allergic reaction Toxic exposure Near drowning Pain management Sudden infant death syndrome

147–5). Other priorities include maintenance of temperature, triage decisions (based on severity of illness or injury), and primary transport to a hospital ED or pediatric critical care or trauma center. The scope of training necessary for EMS personnel to appropriately care for children has been developed through a national consensus process. Recommended curriculum content for paramedics26 can be found in Table 147–6. Paramedic skills necessary for caring for children26 are listed in Table 147–7. Treatment priorities include airway maintenance, providing oxygen, assisting ventilation, spinal immobilization, prevention of hypothermia, and transport to definitive care. Triage includes the identification of an appropriate hospital destination and method of transport and is based on the patient’s age and medical problem or type of trauma, an objective measure of the acuity of the condition, and the distance from an ED. Triage decisions can be made by protocol or with direct (on-line) medical control. An important aspect of an EMSC system is having trained physicians, nurses, and EMTs to provide direct medical control for the unique issues that arise in the care of children in the field. These include pediatric treatment protocols, medication dosing, and triage protocols. Validated pediatric trauma scores exist (e.g., Pediatric Trauma Score), though currently no triage score for medical illness has been developed or validated for children in the out-of-hospital setting. Very few systems currently triage children for medical problems based on severity. Preliminary studies suggest that, whether their problems are medical or traumatic, children have improved outcomes when triaged and transported to tertiary care facilities.14

Treatment and Triage Phase

Transport Phase

The National Association of EMS Physicians (NAEMSP) has developed model protocols for out-of-hospital care of children. The conditions covered are listed in Table 147–4. Protocols and policies are available from NAEMSP at http://www. naemsp.org and from the American College of Emergency Physicians (ACEP) at http://www.acep.org. Recommended pediatric equipment lists have also been published24,25 (Table

Transport to a hospital involves triage decisions to determine the type of facility the child should be transported to, and the type of transportation used (ground ambulance vs. helicopter vs. fi xed-wing aircraft). Most pediatric EMS transports are by ground ambulance. When severity of the child’s condition dictates transport in a short period of time, the use of a helicopter may be required. For greater distances, fi xed-

Chapter 147 — Emergency Medical Services and Transport

Table 147–5

Basic Life Support (BLS) and Advanced Life Support (ALS) Ambulance Equipment for Children

BLS Equipment and Supplies Essential Oropharyngeal airways: infant, child, adult (sizes 00–5) Self-inflating resuscitation bag-valve devices: child and adult sizes Masks for bag-valve resuscitation devices: infant, child, and adult sizes Oxygen masks: infant, child, and adult sizes Non-rebreathing masks: pediatric and adult sizes Stethoscope Backboard Cervical immobilization devices: infant, child, and adult sizes Blood pressure cuffs: infant, child, and adult sizes Portable suction unit with regulator Suction catheters: tonsil-tip and 6F–14F Extremity splints: pediatric sizes Bulb syringe Obstetric pack Thermal blanket Water-soluble lubricant Desirable Infant car seat Nasopharyngeal airways: sizes 18F–34F, or 4.5 mm–8.5 mm Glasgow Coma Scale reference Pediatric Trauma Score reference Small stuffed toy Computer w/CD ROM capability and EMSC training CDs at base station for pediatric continuing medical education ALS Equipment and Supplies ALS ambulance equipment includes everything on the BLS list, plus the following items: Essential Transport monitor Defibrillator with adult and pediatric paddles Monitoring electrodes: pediatric sizes Laryngoscope with straight blades (0–2) and curved blades (2–4) Endotracheal tube stylets: pediatric and adult sizes Endotracheal tubes: uncuffed sizes 2.5–6.0, cuffed sizes 6.0–8.0 Magill forceps: pediatric and adult sizes Nasogastric tubes: 8F–16F Nebulizer Intravenous catheters: 16–24 gauge Intraosseous needles Length/weight-based drug dose chart or tape (e.g., Broselow tape) Needles: 20–25 gauge Resuscitation drugs and intravenous fluids that meet local standards of practice Desirable Blood glucose analysis system Disposable CO2 detection device

wing aircraft are needed. Paramedics providing ALS should be available in such circumstances. Additional treatments, including vascular access and fluid resuscitation for shock, are frequently provided en route or if there is unavoidable transport delay due to an extrication problem. Occasionally, when prolonged transport times are anticipated, endotracheal intubation or vascular access may be performed prior to transport as these procedures are more difficult to perform in a moving vehicle. Ambulance transportation of children has risks. Principles of transport should include a balance between the risk of transportation and the benefit of rapid arrival. High speeds and the use of lights and sirens, which potentially results in ambulance crashes that may injure or cause the death of patients, providers, pedestrians, or other motor vehicle occupants, are con-

Table 147–6

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Out-of-Hospital Pediatric Curriculum Content

Patient Assessment Growth and Development Emergency Medical Services for Children Illness and Injury Prevention Respiratory Emergencies (Airway and Breathing Problems) Respiratory distress, respiratory failure, respiratory arrest Possible causes of respiratory emergencies: Airway obstruction (upper airway and lower airway obstruction) Fluid in the lungs Cardiovascular/Circulatory Emergencies Shock (compensated and decompensated shock) Rate and rhythm disturbances, cardiopulmonary arrest Altered Mental Status Possible causes: airway/breathing problems, shock, seizures, poisoning, metabolic, occult trauma, serious infection Trauma Burns Child Abuse and Neglect Behavioral Emergencies Suicide, aggressive behavior Child-Family Communications Critical Incident Stress Management Fever Medicolegal Issues Do Not Resuscitate (DNR) order, consent, guardianship, refusal of care Newborn Emergencies Near Drowning Pain Management Poisoning SIDS and Death in the Field Transport Considerations Destination issues, methods for transport (safety seats and parental transport) Infants and Children with Special Needs Technically Assisted Children (TAC): tracheostomy care, apnea monitors, central lines, chronic illness, gastrostomy tubes, home artificial ventilators and shunts

cerns. To make ambulance transport safer, guidelines are currently being developed. A list of recomendations is available from the EMSC program27 and includes the following: 1. Drive cautiously at safe speeds, observing traffic laws. 2. Tightly secure all monitoring devices and other equipment. 3. Ensure that available restraint systems are used by EMTs and other occupants, including the patient. 4. Transport children who are not patients, properly restrained, in an alternate passenger vehicle whenever possible. 5. Encourage utilization of the Department of Transportation National Highway Traffic Safety Administration Emergency Vehicle Operating Course (EVOC), National Standard Curriculum. Ongoing therapy and reassessment are performed during transport. Radio or telephone communication with a medical control physician or the receiving facility is not standardized, but communication with direct medical control may be optimal in certain circumstances. Contact with poison control centers for instructions on correct management of a pediatric poisoning during transport is a good example. Once at the receiving hospital, EMS providers report the child’s current status, detailed information from the scene, treatments performed en route, and changes in the child’s

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Table 147–7

Out-of-Hospital Pediatric Skills for Paramedics

Assessment of infants and children Use of a length-based resuscitation tape Airway management Mouth-to-mouth barrier devices Oropharyngeal airway Nasopharyngeal airway Oxygen delivery system Bag-mask ventilation Endotracheal intubation Endotracheal placement confirmation devices (CO2 detection) Optional: rapid sequence induction Foreign body removal with Magill forceps Needle thoracostomy Nasogastric or orogastric tubes Suctioning Tracheostomy management Monitoring Cardiorespiratory monitoring Pulse oximetry End-tidal CO2 monitoring and/or CO2 detection Vascular access Intravenous line placement Intraosseous line placement Fluid/medication administration Endotracheal Intramuscular Intravenous Nasogastric Nebulized Oral Rectal Subcutaneous Cardioversion Defibrillation Drug dosing in infants and children Immobilization/extrication Car seat extrication Spinal immobilization

status during transport. Patient care is then transferred to hospital personnel, which begins the next stage of care. Hospital Phase The hospital phase includes stabilization in a hospital ED and, if needed, transfer (secondary transport) to a pediatriccapable trauma center or critical care center. Hospital care also includes defi nitive therapy, which may be in an operating room, an intensive care unit, or an inpatient hospital ward. Hospitals capable of caring for critically ill or severely injured children are pre-identified. Preferential transport to these hospitals should be part of written triage protocols and/or included in on-line medical control communications and triage. EMS systems contain hospitals with varying levels of pediatric capability and resources. Improvements in the care of children within EMS systems have been achieved through regionalization of pediatric care. Other approaches include improving the pediatric capability of all EDs in the EMS system. ED guidelines to improve pediatric preparedness exist.28-31 Unfortunately, there is evidence that not all hospitals follow available guidelines.32-34 Rehabilitation Phase Appropriate physical or mental rehabilitation is needed to allow patient to continue receiving care for illness or injury in a family-centered care environment whenever possible.

Table 147–8

Prevention of Critical Injury in EMSC

Child restraints in motor vehicles Infant seats, booster seats, seat belts Safe driving for teens Driver’s education Education regarding dangers of alcohol and driving Burn prevention Smoke detectors Limitation of hot water temperature Bicycle safety Bicycle helmets Educational programs Drowning Mandatory pool fencing Boating safety Poisoning Education Safety caps on containers Falls Mandatory window guards

Prevention Phase Emergency and intensive care to treat critically ill and injured children is expensive in terms of both personal anguish and societal cost.35 Prevention is the least expensive intervention possible and has the best outcome. A functioning EMS system should be involved in identifying, developing, improving, and supporting successful prevention aactivities. The key to prevention is education. Parents, children, the lay public, pediatricians, family physicians, and emergency physicians, nurses, and EMS providers can all be involved in this phase by delivering anticipatory information concerning prevention in many areas (Table 147–8). Parents can be taught CPR, how to recognize significant illness and injury, what to do for particular medical emergencies, when to call for help (“911”), and what to do until help arrives. The EMSC Program and Improvements in EMSC The EMSC program has facilitated significant changes in EMS systems and EMS organizations in the United States. Some of these include educational programs for out-ofhospital providers in pediatrics. The EMSC Program’s National Education of Out-of-Hospital Providers Task Force makes recommendations for EMS educational curricula.26 Pediatric out-of-hospital education programs developed based on this model include the following: 1. Teaching Resource for Instructors in Prehospital Pediatrics (TRIPP) and Paramedic TRIPP from the Center for Pediatric Emergency Medicine (http://www. cpem.org)36,37 2. Pediatric Education for Prehospital Professionals (PEPP) course (http://www.PEPPsite.com) from the American Academy of Pediatrics (http://www.aap.org)38 3. Pediatric Prehospital Care (PPC) course from the National Association of EMTs (http://www.naemt.org)39 The Institute of Medicine’s report on EMSC published in 1993 recognized these improvements and recommended further changes in access to care, equipment, educational programs, and research.34 The National Association of EMS Physicians, supported by the EMSC program, developed model protocols for out-of-hospital care of children (see

Chapter 147 — Emergency Medical Services and Transport

Table 147–4). Ambulance equipment was recommended by a multidisciplinary committee for out-of-hospital care of children24 (see Table 147–5). Guidelines for EDs to prepare for pediatric patients have been developed by several national organizations.28-31 The EMSC program has also supported a landmark study, one of the few randomized controlled trials in out-of-hospital care for children. This study examined the outcomes of children who had out-of-hospital endotracheal intubation versus bag-mask ventilation performed by paramedics in California and showed that there were no outcome differences in patients who were intubated versus those who had appropriate bag-valve-mask ventilation performed.9 Despite these accomplishments, not all EMS systems or EDs are prepared to care for children.32,33 Emergency physicians and pediatricians must continue to provide leadership for local EMS systems and receiving hospitals so that the resources, guidelines, and products designed for children are used and incorporated into all EMS systems and EDs in the United States.

Summary The development of resources, products, system changes, and research networks has improved the care children receive in our nation’s EMS systems. More research is needed to demonstrate the positive impact that many EMSC programs and initiatives have already produced. Maintaining the collaboration of national, public, and government organizations and programs that have concentrated on improving children’s out-of-hospital and emergency care will ensure continued improvements in the outcome of children cared for in our EMS system. REFERENCES 1. History of emergency medical services for children. In Seidel JS, Henderson DP (eds): Emergency Medical Services for Children: A Report to the Nation. Washington, DC: National Center for Education in Maternal and Child Health, 1991. 2. Pantridge JF, Geddes JS: Cardiac arrest after myocardial infarction. Lancet 1:807–808, 1966. 3. Mustalish A: Emergency medical services: twenty years of growth and development. N Y State J Med 86:414–420, 1986. *4. National Research Council: Accidental Death and Disability: The Neglected Disease of Modern Society. Washington, DC: National Academy of Sciences, 1966. *5. Seidel JS: EMS-C in urban and rural areas: The California experience. In Haller JA Jr (ed): Emergency Medical Services for Children: Report of the Ninety-Seventh Ross Conference on Pediatric Research. Columbus, OH: Ross Laboratories, 1989, pp 22–30. 6. Luten RC: Educational overview. In Luten RC, Foltin G (eds): Pediatric Resources for Prehospital Care, 2nd ed. Elk Grove Village, IL: American Academy of Pediatrics, 1990, pp 16–24. *7. Foltin G, Salomon M, Tunik M, et al: Developing prehospital advanced life support for children: the New York City experience. Pediatr Emerg Car 6:141–144, 1990. *8. Stiell I, Wells G, Spaite D, et al for the OPALS Study Group: Multicenter controlled clinical trial to evaluate the impact of advanced life support on out-of-hospital respiratory distress patients. Acad Emerg Med 9:357, 2002. 9. Stiell IG, Nesbitt L, Wells GA, et al for the OPALS Study Group: Multicenter controlled clinical trial to evaluate the impact of advanced life support on out-of-hospital chest pain patients. Acad Emerg Med 10:501–502, 2003. *Selected readings.

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*10. Gausche M, Lewis RJ, Stratton SJ, et al: Effect of out-of-hospital pediatric endotracheal intubation on survival and neurological outcome: a controlled clinical trial. JAMA 283:783–790, 2000. 11. Foltin G, Galea S, Treiber M, et al: Pediatric Pre Hospital Evaluation of New York Cardiorespiratory Survival (PHENYCS): a large, prospective population based study of cardiac and respiratory arrest. Analysis of cardiac arrests. Acad Emerg Med 12(5 Suppl 1):107–108, 2005 12. Tunik M, Richmond N, Treiber M, et al: Pediatric Pre Hospital Evaluation of New York Cardiorespiratory Survival (PHENYCS): a large, prospective population based study of cardiac and respiratory arrest. Analysis of respiratory arrests. Acad Emerg Med 12(5 Suppl 1):107–108, 2005. 13. Tsai A, Kallsen G: Epidemiology of pediatric prehospital care. Ann Emerg Med 16:284–292, 1987. 14. Seidel JS, Hornbein M, Yoshiyama K, et al: Emergency medical services and the pediatric patient: Are the needs being met? Pediatrics 73:769– 772, 1984. 15. Babl FE, Vinci RJ, Bauchner H, Mottley L: Pediatric pre-hospital advanced life support care in an urban setting. Pediatr Emerg Care 17:5–9, 2001. *16. Foltin G, Pon S, Tunik M, et al: Pediatric ambulance utilization in a large American city: a systems analysis approach. Pediatr Emerg Care 14:254–258, 1998. *17. Systems approach to care of ill and injured children. In Seidel JS, Henderson DP (eds): Emergency Medical Services for Children: A Report to the Nation. Washington, DC: National Center for Education in Maternal and Child Health, 1991. 18. Seidel JS, Henderson DP (eds): Prehospital Care of Pediatric Emergencies. Los Angeles: Los Angeles Pediatric Society, 1987, pp 102– 106. 19. Ramenofsky ML, Luterman A, Curreri PW, et al: EMS for pediatrics: optimum treatment or unnecessary delay? J Pediatr Surg 18:498–504, 1983. 20. American Academy of Pediatrics: Injury prevention program TIPP. http://www.aap.org/family/tipp-ems.htm 21. Luten RC, Foltin G, Pons P: Access to optimal care. In Luten RC, Foltin G (eds): Pediatric Resources for Prehospital Care, 2nd ed. Elk Grove Village, IL: American Academy of Pediatrics, 1990, pp 1–15. 22. Clawson JJ: Emergency medical dispatching. In Roush WR (ed): Principles of EMS Systems. Dallas: American College of Emergency Physicians Press, 1989, pp 127–128. 23. Foltin GL, Schneiderman WJ, Dieckmann RA: 911 and ambulance dispatch. In Dieckmann RA (ed): Pediatric Emergency Care and Systems: Planning and Management. Baltimore: Williams & Wilkins, 1992, pp 109–116. 24. Seidel JS, Glaeser P, Zimmerman L, et al: Guidelines for pediatric equipment and supplies for basic and advanced life support ambulances. Ann Emerg Med 28:699–701, 1996. 25. Seidel JS, Tittle S, Henderson DP, et al: Guidelines for pediatric equipment and supplies for emergency departments. Ann Emerg Med 31:54– 57, 1998. 26. Gausche M, Henderson DP, Brownstein D, Foltin G: The education of out of-hospital medical personnel in pediatrics: report of a national task force. Ann Emerg Med 31:58–63, 1998; and Prehosp Emerg Care 2:56–61, 1998. *27. EMS for Children National Resource Center: The Do’s and Don’ts of Transporting Children in an Ambulance. Available at http://www. ems-c.org/products/frameproducts.htm 28. American Medical Association, Commission on Emergency Medical Services: Pediatric emergencies: an excerpt from “Guidelines for Categorization of Hospital Emergency Capabilities.” Pediatrics 85:879– 887, 1990. 29. American College of Emergency Physicians: Emergency care guidelines. Ann Emerg Med 29:564–571, 1997. *30. American Academy of Pediatrics, Committee on Pediatric Emergency Medicine: Guidelines for pediatric emergency care facilities. Pediatrics 96:526–537, 1995. *31. American Academy of Pediatrics, Committee on Pediatric Emergency Medicine; American College of Emergency Physicians, Pediatric Committee: Care of children in the emergency department: guidelines for preparedness. Pediatrics 107:777–781, 2001; and Ann Emerg Med 37:423–427, 2001. 32. Athey J, Dean JM, Ball J, et al: Ability of hospitals to care for pediatric emergency patients. Pediatr Emerg Care 17:170–174, 2001.

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33. McGillivray D, Nijssen-Jordan C, Kramer MS, et al: Critical pediatric equipment availability in Canadian hospital emergency departments. Ann Emerg Med 37:371–376, 2001. 34. Durch JS, Lohr KN (eds): Emergency Medical Services for Children. Washington, DC: National Academy Press, 1993. 35. Division of Injury Control, Centers for Disease Control: Childhood injuries in the United States. Am J Dis Child 144:627–644, 1990. 36. Foltin GL, Tunik MG, Cooper A, et al (eds): Teaching Resource for Instructors in Prehospital Pediatrics (EMT-Basic). New York: Maternal and Child Health Bureau, 1998.

37. Foltin GL, Tunik MG, Cooper A, et al (eds): Paramedic Teaching Resource for Instructors in Prehospital Pediatrics. New York: Center for Pediatric Emergency Medicine, 2002. *38. Dieckmann RA, Brownstein D, Gausche-Hill M (eds): Pediatric Education for Prehospital Professionals. Sudbury, MA: Jones and Bartlett, 2000. 39. Markenson D (ed): Pediatric Prehospital Care. Upper Saddle River, NJ: Prentice-Hall, 2002.

Chapter 148 End-of-Life Issues Jill M. Baren, MD, MBE

Key Points It is the responsibility of the emergency physician to develop prognostic information and to convey it, accurately and comprehensively, to children and families so that the most well-informed decisions can be made at the end of life. Physicians should never delegate the task of death notification to another emergency department (ED) staff member. Implementing palliative care in the ED can alleviate the feeling that “there is nothing we can do” for dying children.

Introduction and Background Each year in the United States, approximately 53,000 children die.1 Pediatric deaths can be delineated into three categories: the deaths of infants (babies born prematurely through 1 year of age), deaths from illness, and traumatic deaths. Of these, the most likely to occur in emergency departments (EDs) are traumatic deaths. Almost 17,000 children die each year from traumatic injuries.1 Sudden infant death syndrome continues to be the leading cause of postneonatal infant death, accounting for about 25% of all deaths between 1 month and 1 year of age, and many of these infants are pronounced dead in the ED.2 The epidemiology of pediatric death from medical illness in the ED is not well studied. Decision making about the goals of care immediately following traumatic injury is rarely complicated. For a previously healthy child who sustains injuries in a motor vehicle crash or from a gunshot wound, a fall, blunt force trauma, or any other cause, all efforts to cure are made under most circumstances. Decisions about whether cure is possible may arise, but generally occur after the patient is admitted to the hospital. The same principles apply in the case of cardiopulmonary arrest or critical illness such as meningitis or sepsis. When a child is dying from a chronic illness in the ED, such as cancer, muscular dystrophy, cystic fibrosis, or another previously diagnosed condition, as opposed to an acute infectious process, the clinical picture—especially whether cure

is possible—is often not clear upon presentation. The difficult question confronting the ED staff is, “What is the appropriate goal for this child at this time?” For children with life-threatening conditions in the ED, several factors must be considered in decision making: • What were the goals of treatment or care, if any, before the child came to the ED? • Who is aware of these goals? • Are these goals appropriate given the child's pathophysiology at this time? • How do these goals fit with this child's current visit to the ED? • Who is appropriate and available for decision making? • What can and should the ED staff do to facilitate these goals? A framework for answering these questions is provided in this chapter.

Issues Death occurs more frequently in the ED compared with many other health care environments, even in the pediatric population. Many barriers make the provision of empathic and timely end-of-life care more difficult to provide in the ED. Care in the ED is characterized by rapid turnover of patients and complex interactions both within and outside of the ED. ED patients frequently experience acute changes in their condition, and there may be little available information and little time for gathering additional information before decision making. The impact of this incomplete physiologic database may be further complicated by medical conditions that render ED patients incapable of participating in the process of decision making. Furthermore, appropriate surrogate decision makers may be unknown, unprepared, or unavailable, which, in the case of children, is the major issue. The lack of a prior physician-patient-family relationship contributes to the complexity of the emotionally and medically difficult situations of dying children. The unpredictability of conditions in the ED at any given time leads to great difficulty in establishing relationships between clinicians and patients and among clinicians with different areas of expertise and different clinical end points. This may be the greatest barrier in establishing effective care for dying patients as it these relationships that provide the necessary foundation of trust. 1043

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Despite these limitations, it remains the responsibility of emergency physicians to provide high-quality and compassionate care and support to terminally ill and acutely dying patients and their families. Professional organizations have strongly endorsed this concept by creating codes of ethics and professional statements. The Code of Ethics for Emergency Physicians, established by the American College of Emergency Physicians in 1997, acknowledges that the fundamental moral responsibility of emergency physicians includes embracing patient welfare as the primary professional responsibility; respecting the rights and best interests of patients, particularly those most vulnerable and those unable to make treatment choices due to diminished decision-making capacity; and communicating truthfully with patients.3 This code establishes the obligation that emergency physicians have to be “patient and family focused” in situations in which there is the greatest need for this level of commitment.4

Solutions To arrive at the best possible solutions for the difficult issues raised in the care of dying patients in the pediatric ED, an informed, structured, and empathetic approach is needed in the clinical practice of pediatric emergency medicine. Three particularly important aspects of this approach are communication, palliation, and education. Excellence in these three areas is likely to lead to a high degree of professional and family satisfaction regardless of clinical outcome. Communication Most adults have never confronted the death or dying of a child. This applies not only to families, but also to health care providers. Physicians, nurses, social workers, chaplains, and others may lack the skills to engage in conversations about such deaths. A belief that children do not/should not die often results in an extremely aggressive pursuit of an extremely improbable or even impossible cure. As with adults, the burdens to the child must be weighed against the likelihood of benefit. Clinicians should engage in this calculation before bringing the discussion to the family and the child if appropriate. While this suggestion is often met with protestations—“That’s the family’s decision, not ours!”— part of the decision does lie with clinicians. Any clinical decision exists only in the context of physiologic parameters. It is the responsibility of providers, even in the ED, to develop this information and to convey it accurately and comprehensively to children and families, so that the most well-informed decisions can be made. Adults faced with critical illness or injury may have established advance directives as a mechanism to formulate and communicate health care preferences. Advance directives have two components: (1) naming a surrogate decision maker, and (2) conveying information to guide health care decision making if the patient is unable to, or chooses not to, participate. Living wills, durable powers of attorney for health care, Do Not Resuscitate (DNR) or Do Not Attempt Resuscitation (DNAR) orders, and informal documents are all widely accepted types of advance directives. Certain advance directives apply to more than end-of-life situations. Most, however, are prepared with considerations of what one wants or does not want when dying. In clinical practice, advance directives are often not helpful for a number

of reasons. Many advance directives (especially living wills) are written with categorical statements (I ____ do/do not want ____ . . .) that are difficult to apply to a specific clinical situation. Similarly, advance directives are also likely to contain well-meaning but murky phrases such as “no heroic measures” or “no extraordinary means.” While the author may have had some notion of what was intended, in reality these statements cannot be construed as a comprehensible conveyal of the patient’s preferences for health care. More importantly for this discussion, advance directives are not intended to be written by, or used for children, at least from a legal perspective. A return to the intent of advance directives, however, reveals a way that advance directives can be wisely and appropriately used with and for children. For most children who come to the ED, the goal is to save lives. However, there will be children for whom all the best curative efforts are not enough to restore or prolong life.1 These children either will die, or will live with sequelae (physical, psychological, and/or cognitive) of the illness or injury. Second, for certain children, the goals of care, and of medical interventions, must shift from cure to comfort. From a clinical perspective, children may have the wherewithal to make informed decisions about their care at the end of life. It has been demonstrated that dying children, even of preschool age, know they are dying.5 Often, the adults involved in dying children’s lives are slower to recognize the inevitability of the death. The responsibility of health care providers is to be honest about prognosis, with ourselves, and with our patients and their families. Often this is not the case. Not only are prognoses calculated inaccurately, but there is a tendency to convey more optimistic data about prognosis than is truly believed.6 If objective criteria lead to the conclusion that a patient has a poor prognosis, clinicians should not attempt to find a reason why that poor prognosis does not apply, nor should they allow that to dominate the conversation. Before a parent, guardian, and even a child is engaged in a discussion about end of life, the providers must be clear about the prognosis. In the ED, a team approach often makes this difficult activity more feasible. When an infant or child presents to the ED in cardiopulmonary arrest, parents should receive information in a stepwise fashion, hearing first that the situation is grave but that everything possible is being done. This information can be delivered by a social worker, nurse, or caring and trained administrative person prior to the clinician meeting with the family. When it becomes inevitable that death is the outcome, the physician involved in the child’s care should deliver that message. Physicians should never delegate this task to another ED staff member. In the unusual case of a dying child or adolescent who is capable of speaking with the clinician, it is often helpful to pose the following question, “What do you think is going on with your disease?” When given the opportunity, children will often speak at length about their feelings and what they know. If a child does wish to discontinue life-prolonging therapies, the child’s experienced-based knowledge allows one to consider him/her an informed and appropriate decision maker. What must be assessed is whether the child understands the decision about which he/she is being asked; if the child understands the burdens/costs and benefits of the treatment being offered, or of refusing the treatment; and whether the child responds consistently in conveying the

Chapter 148 — End-of-Life Issues

decision. Many children who have lived with life-threatening illnesses or the sequelae of injuries do have this expertise, perhaps with a stronger base in reality than the adults around them. Palliation Understanding of palliative care has evolved markedly over the past decade. Palliative care is now understood as distinct from hospice, though many of the same concepts apply. Palliative care, like hospice, focuses on the patient’s life being lived as well as is possible. What distinguishes them is that hospice care is provided with and for patients whose expected life span is limited. Prognosis is often difficult to develop and even more difficult to convey. Calculating life expectancy is more difficult still in the case of children.1 Palliative care refers to aggressive symptom management across the trajectory of disease. Palliative care can and should be pursued concurrently with curative therapies. Palliative care for children in the ED includes aggressive symptom management while pursuing whatever goals of treatment are physiologically indicated. Dying children often have a high symptom burden.7 When children come to the ED, palliative care must be considered. Fear and lack of knowledge often result in children’s pain being grossly undertreated.8,9 The claim that one cannot manage pain and other symptoms because of a need to assess and diagnose is frequently misapplied and results in undue burden of suffering. In most cases, optimal pain management will not interfere with an assessment of level of consciousness. The American Academy of Pediatrics, in conjuction with the Canadian Pediatric Society and the American Pain Society, have developed guidelines for the management of pain and stress in neonates, children, and adolescents.8,9 In the most difficult cases when a child is dying, parents are often told, “We’ve done everything we can. There is nothing else we can do.” To the contrary, there is always something else that can be done. Understanding palliative care as a mandate for broad-based, aggressive symptom management shapes interventions with dying children. Whether the death of a child is from a progressive neurodegenerative disease, advanced cancer, or trauma, a focus on relieving pain, dyspnea, anxiety, and other symptoms benefits both the child and the family. Most providers are not trained in these skills in the context of dying. Developing a paradigm shift toward implementing palliative care in the ED can alleviate the feeling that “there is nothing we can do.” Emergency physicians have a duty to preserve life, but must recognize that there are key differences between withholding and withdrawing treatment in the pediatric emergency setting that may differ from the moral equivalence that has been afforded to these actions in other medical settings.10 From a societal viewpoint, there is an expectation that emergency physicians will act to preserve life in the absence of a few well-established conditions (rigor mortis, decapitation, failed cardiopulmonary resuscitation [CPR]). The withholding of treatment often feels like a public event and has been described as the most traumatic of all decisions in the practice of emergency medicine.10 From a practical standpoint, the lack of information about a child presenting to an ED is a frequent characteristic in life-threatening situations. Clinicians have little insight regarding patient identity, wishes, and prognosis, and there-

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fore aggressive therapy aimed at preserving life should be immediately instituted with one exception—the intervention is unequivocally judged to be nonbeneficial or futile. If and when surrogate decision makers or additional information become available, treatment options can be discussed and modified. Terminally ill children who are actively dying, who do not possess advance directives or other clearly articulated wishes for their care, who are not accompanied to the ED by surrogate decisions makers, or who have multiple surrogate decision makers in conflict about withholding specific interventions should have life-saving care initiated until additional information is available and conflict can be mediated. This does not imply that such care will always be successful in reversing the life-threatening condition. Withdrawal of life support in the ED is a viable option depending on the subsequent information and circumstances. Treatments should be chosen and implemented within the context of what is physiologically indicated. A vast array of ethical issues surrounds the process of CPR in children. Fortunately, pediatric cardiopulmonary arrest is rare. Outcomes from pediatric cardiac arrest are well documented in the literature and are dismal.11,12 The underlying medical condition of the patient, the presenting cardiac rhythm, and response to prehospital advanced life support measures are important factors affecting both the outcome of CPR and medical decisions surrounding CPR.13 Approximately one to two traumatic or medical pediatric cardiopulmonary arrests occur in busy EDs per month, thus the skills involved are not easily practiced let alone perfected. In the early stages of resuscitation, when few to no data are available, the emergency physician must be primarily concerned with the restoration of circulation and life of the patient. As additional data are gathered, medical decision making can be broadened to include new information such as the underlying condition of the patient and the likelihood of survival. An important but often overlooked part of the resuscitation process is the need for lessening the guilt of survivors and providing a sense of closure. This involves developing important skills for incorporation into resuscitation protocols: recognition of futility, procedures for stopping the resuscitation, and ability to communicate with families. Numerous studies in the emergency medicine literature indicate that patients, families, and health care providers believe that a supported, structured environment for the presence of family members during resuscitation and other medical encounter is both feasible and desirable.14,15 Although this concept has been fraught with controversy and resisted in many health care environments, there appears to be a general trend in many institutions toward the development of protocols to allow families to be present, albeit with assistance (see Chapter 153, Family Presence). Mishandling the events surrounding a pediatric death can set the stage for an abnormal bereavement for survivors. To facilitate a family’s recovery, various postmortem activities have been suggested for ED staff. Surveys of families whose children were either pronounced dead on arrival or underwent unsuccessful resuscitation showed the following activities to be highly desired and helpful16 : strong preference that the news of a patient’s death be delivered by a physician, viewing the body, having the child’s clothing be returned to them even after it was used as part of the investigation of the

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SECTION VI — The Practice Environment

cause of death, having a physical memento such as a lock of hair or a mold or print of the baby’s hand, and a follow-up phone call from the ED after the death.16 These are not things that parents are capable of thinking about during the acute event, so there should be processes in place to make sure they are offered. These activities can be time consuming but could be accomplished by a few dedicated individuals. Although the impact of such practices on bereavement and long-term coping by survivors has not been studied, they may at the very least contribute significantly to the perception that the ED, the hospital, and its health care providers are caring entities. Request for Autopsy and Organ/Tissue Donation Request for autopsy and organ/tissue donation is often viewed by physicians as one of the more difficult tasks in the death of a patient in the ED. Some of the barriers inherent in asking for an autopsy, when it is not required by law, are fear of offending the family, fear of legal retribution for care that resulted in death, and avoidance of contact with the family after the death notification has occurred. Autopsies are mandated by law whenever an unexpected death has occurred or when there are suspicious circumstances surrounding the death (suicide, homicide, child abuse). Emergency physicians must be aware of the specific cases that need to be referred to their local medical examiner’s office. Learning the results of an autopsy can be extremely helpful for grieving families, providing them with closure or some explanation for a terribly tragic and seemingly inexplicable event. In addition, there are some myths regarding autopsy that should be dispelled. The autopsy is not disfiguring and will not interfere with funeral arrangements as it is typically performed within 24 to 48 hours. Autopsy is not disallowed by most major religions; families should be encouraged to consult with hospital chaplains or their own religious advisors to confirm this. Finally, the performance of an autopsy does not result in additional cost to the family. The cost is absorbed by either the hospital or the medical examiner. The emergency physician can offer to meet with the family to go over the results; alternatively, the results can be forwarded to the pediatrician or family physician for discussion. Physicians should not discount how valuable autopsy results are for their own closure and continued medical knowledge. Request for organ/tissue donation has a different set of associated issues. Many states have laws mandating the request for organ/tissue donation. In the case of a beating heart potential donor, and in some cases a non–beating heart donor, trained specialists from organ procurement agencies can be dispatched to the ED to make the request in person. These individuals have expertise in the language necessary to obtain permission for donation and the knowledge to answer difficult questions when they arise. In addition, having the request come from someone distinct from the patient care team can provide valuable separation of the death and the events that must occur for organ harvest. The initial idea, however, must be introduced by the emergency physician. Many families view organ donation as a way to bring about some good from a bad situation, and may be waiting for the opportunity to be asked; therefore, both organ/tissue donation and autopsy requests should be a standard part of the death encounter.

Education There is much evidence to support the fact that physicians in training and in practice still feel relatively uneducated and largely unsupported on issues of death and dying. In 1993, the American Medical Association reported that only 26% of primary care residencies offered training in the care of dying patients.17 Yet studies have indicated that exposure to dying patients is high, with pediatric residents caring for an average of 35 dying children during the first 2.5 years of residency training. The specific exposure of emergency physicians to dying patients is not known. However, neither high nor low exposure rates will necessarily be associated with a greater level of comfort in dealing with death and dying for any given physician. Training must not only address knowledge and skills to improve interactions with families, but examine personal reactions as well. Programs such as Education for Physicians on End-of-Life Care (EPEC), End of Life Nursing Education Consortium (ELNEC), and Toolkit for Nursing Excellence at End of Life Transition (TNEEL) are formal, albeit relatively brief mechanisms for education. If knowledge and skills are lacking, both children and families will suffer, physically and otherwise. Education, however, is not enough in that it does not always translate into practice. Optimal end-of-life care must be integrative. There must be an expectation of excellence within institutions, at the levels of attending physicians, clinical directors, and chief medical and nursing officers. There must be integration into practice at the levels of staff nurses, house officers, and beginning providers. Real excellence will require a change in culture within disciplines and health care systems. Death should not be viewed as a failure, and excellence in the provision of end-of-life care is the responsibility of all providers in an ED.

Summary The death of a child is not a common event, but there remain variations across populations, geography, and socioeconomic status. For most people, however, the death of a child is almost unheard of and leaves the family at risk for complicated bereavement.18 While the provision of excellent end-oflife care for children is not likely to alter families’ grief significantly, the absence of excellence will leave families with memories and impressions of their child’s suffering. The knowledge and skills exist to provide excellent end-of-life care to children even, and perhaps especially, in the ED. REFERENCES 1. Children’s International Project on Palliative/Hospice Services (ChIPPS) Administrative/Policy Workgroup of the National Hospice and Palliative Care Organization: A Call for Change: Recommendations to Improve the Care of Children Living with Life-Threatening Conditions. National Hospice and Palliative Care Organization. Available at www.nhpco.org (accessed May 3, 2002). 2. Mathews TJ, Menacker F, MacDorman MF; U.S. Centers for Disease Control and Prevention, National Center for Health Statistics: Infant mortality statistics from the 2002 period: linked birth/infant death data set. Natl Vital Stat Rep 53:1–29, 2004. *3. Code of ethics for emergency physicians. American College of Emergency Physicians. Ann Emerg Med 30:365–372, 1997.

*Selected readings.

Chapter 148 — End-of-Life Issues 4. Iserson KV: Principles of biomedical ethics. Emerg Med Clin North Am 17:283–306, 1999. 5. Bluebond-Langner M: The Private Worlds of Dying Children. Princeton, NJ: Princeton University Press, 1978. 6. Christakis NA: Death Foretold: Prophecy and Prognosis in Medical Care. Chicago: University of Chicago Press, 1999. 7. Wolfe J, Grier HE, Klar N, et al: Symptoms and suffering at the end of life in children with cancer. N Engl J Med 342:326–333, 2000. 8. American Academy of Pediatrics & Canadian Paediatric Society: Prevention and management of pain and stress in the neonate. Pediatrics 105:454–461, 2000. *9. American Academy of Pediatrics & American Pain Society: The assessment and management of acute pain in infants, children, and adolescents. Pediatrics 108:793–797, 2001. 10. Iserson KV: Withholding and withdrawing medical treatment: an emergency medicine perspective. Ann Emerg Med 28:51–54, 1996. 11. Young KD, Seidel JS: Pediatric cardiopulmonary resuscitation: a collective review. Ann Emerg Med 33:195–205, 1999.

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12. Young KD, Gausche-Hill M, McClung CD, Lewis RJ: A prospective, population-based study of the epidemiology and outcome of out-ofhospital pediatric cardiopulmonary arrest. Pediatrics 114:157–164, 2004. *13. Marco CA: Ethical issues of resuscitation. Emerg Med Clin North Am 17:527–538, 1999. 14. Meyers T, Eichhorn DJ, Guzzetta CE: Do families want to be present during CPR? A retrospective survey. J Emerg Nurs 24:400–405, 1998. 15. Boudreaux ED, Francis JL, Loyacano T: Family presence during invasive procedures and resuscitations in the emergency department: a critical review and suggestions for future research. Ann Emerg Med 40:193–205, 2002. 16. Aherns WR, Hart RG: Emergency physicians’ experience with pediatric death. Am J Emerg Med 15:642–643, 1997. 17. Hill TP: Treating the dying patient: the challenge for medical education. Arch Intern Med 155:1265–1269, 1995. 18. Rando T: Treatment of complicated mourning. Champaign, IL: Research Press, 1993.

Chapter 149 Patient Safety, Medical Errors, and Quality of Care David P. John, MD, John A. Brennan, MD, Nancy E. Holecek, RN, and Patricia Sweeney-McMahon, RN, MS

Key Points The “culture of blame” has done little to improve quality and patient safety. Malpractice litigation, morbidity and mortality rounds, and physician profi ling drive errors underground. A “just culture” error reporting system with data tracking must be in place in order to understand, categorize, and decrease system failures. Individual institutions should use data to understand the problems within their health care system. Hospitals’ administration, physician, and nursing leadership should be directly involved and drive these changes. However, true culture change occurs with staff involvement. Quality and safety initiatives should focus on system re-evaluation that ensures safe, effective, patientcentered, efficient, timely, and equitable health care for all patients. Pediatric patients are particularly prone to medication errors secondary to miscalculations.

Introduction and Background Quality and safety in medicine have not evolved to anywhere near the standards of other industries. Medicine has always been viewed as a “calling” or “art” rather than a business. As such, it has not been subject to the scrutiny of the business model (productivity, efficiency, and quality) . . . until now.1 An Institute of Medicine (IOM) report2 and pay-forperformance initiatives have suddenly made quality and patient safety top priorities in medicine. The IOM report To Err is Human: Building a Safer Health System3 brought to light what most health care workers already know: errors occur and patients are harmed, and occasionally die. 1048

• Between 44,000 and 98,000 Americans die from medical errors annually.3-5 • Medication-related errors for hospitalized patients cost roughly $2 billion annually.3,6 • The lag between the discovery of more effective forms of treatment and their incorporation into routine patient care averages 17 years.7,8 Now, however, the public, health care regulatory agencies, and the federal government are aware of the shortcomings in quality and safety in medicine. Additionally, the Agency for Healthcare Research and Quality, the Institute of Healthcare Improvement, and Six Sigma have also been instrumental in addressing the patient safety and quality process change and developing best practices (Table 149–1). Joseph M. Juran and W. Edwards Deming pioneered quality improvement in industry. In post–World War II Japan, “Made in Japan” was synonymous with inexpensive, mass-produced, poor-quality goods. Under the guidance of Deming and Juran, Japan redesigned systems and developed a culture of quality in their businesses. Companies such as Sony and Toyota equaled, and perhaps surpassed, some of their American counterparts. In the 1960s, 1 in 1000 airline takeoffs had some form of system flaw. Many of these resulted in crashes, causing loss of human life, loss of million-dollar aircraft, and countless dollar losses in profit to the industry.9,10 “Aviation safety was not built on evidence that certain practices reduced the frequency of crashes. Instead it relied on the widespread implementation of hundreds of small changes in procedures, equipment, training, and organization that aggregated to establish an incredibly strong safety culture and amazingly effective practices.”3 Over the last 20 years, the specialty of anesthesia has reduced its death rate from 1 in 20,000 to 1 in 200,000. Anesthesiologists developed processes that helped them better understand and measure the effectiveness of their systems.11-13 With this basic knowledge, they standardized procedures, orders, monitoring capabilities, competencies, and recovery room criteria. Their systems became simpler, with multiple checks and balances to help avoid adverse events. Standardizing anesthesiology carts and making it mechanically impossible to hook up the wrong gas to the

Chapter 149 — Patient Safety, Medical Errors, and Quality of Care

Table 149–1

Emergency Medicine Best Practice Resources

Organization Name

Web Site

Agency for Healthcare Research and Quality (AHRQ) American Academy of Pediatrics (AAP) American College of Emergency Physicians (ACEP)–Clinical Policies American College of Quality American College of Surgeons American Society for Healthcare Risk Management Hospital Quality Incentive Demonstration Project (Premier and CMS) Institute for Safe Medication Practices (ISMP) Voluntary Reporting of Medication Errors Institute of Healthcare Improvement (IHI) Joint Commission on Accreditation of Healthcare Organizations (JCAHO) Leapfrog Group National Committee on Quality Assurance (NCQA) National Guideline Clearinghouse (NGC) National Hospital Voluntary Reporting Initiative Consensus Standards for Hospital Care National Patient Safety Foundation National Quality Forum (NQF) Physician Consortium for Performance Improvement (AMA)

www.ahrq.gov www.aap.org www.acep.org www.asq.org www.acs.org www.ashrm.org www.cms.gov www.ismp.org www.ihi.org www.jcaho.org www.leapfroggroup.org www.ncqa.org www.ngc.org www.cms.gov www.npsf.org www.qualityforum.org www.ama-assn.org

wrong tube are just two examples of how system changes can prevent adverse events. In emergency medicine, the development of the colorcoded tape is one of the first pediatric safety initiatives. Medication dosing and equipment size are based on the weight and length of the child. Calculations are difficult, cumbersome, and not readily available during an emergency, and errors can result in patient harm. To help prevent this, a color scheme based on the length of the child was developed to aid in accessing the proper-sized equipment and medication doses for the child. These length-based, color-coded systems have been placed in many emergency departments (EDs) in the country because14 • The system is easy to use. • It is not prohibitively expensive. • It improves patient outcomes.

Issues Since the IOM report To Err is Human, quality and patient safety issues have come to light in the media, in hospital boardrooms, and among consumers. This report, as well the IOM’s report Crossing the Quality Chasm: A New Health System for the 21st Century,2 has refocused the government, regulatory agencies, and private payers on health care reform. The Joint Commission on Accreditation of Healthcare Organizations, along with state and federal governments, has recently implemented a mandatory reporting system for medical errors. This initiative, like the current medical liability system, seems intuitively to drive disclosure underground. Why would a health care provider openly report a medical

Table 149–2

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Impact of Overcrowding on Quality and Safety Outcomes

Medication errors Inability to provide standard level of care for high-acuity patients Continuity of care threatened Inability to meet quality core measure best practices Miscommunication Delay in diagnostics Patient and staff dissatisfaction

error in this system? The individual reporting the error could be sued, lose his or her ability to practice medicine, and be publicly reported. The airline industry has a “just culture” with mandatory error reporting and they study “near misses” and malfunctions in an effort to improve quality and safety. No medical practitioner intends to harm patients. Providers of emergency care work in a chaotic environment. They are overworked, understaffed, and overcrowded. They handle numerous sound bytes of information from every direction and, not unusually, the unexpected occurs.15 These events occur in every ED across the country every day. To prevent adverse events, one needs to understand what went wrong, categorize it, collect data on it, and then, most importantly, put systems in place to prevent or minimize harm to patients.16 Some of the chief impediments to reporting errors include the fear of punishment by state licensing boards and regulatory agencies, embarrassment, and being branded as a troublemaker. In order to analyze and decrease errors, a just culture environment must be created. Evidence-based clinical guidelines and pathways have been shown to improve quality and patient safety.17,18 Like the Emergency Medical Treatment Act and Labor Act, quality and patient safety are largely unfunded mandates. In a time of decreasing reimbursement, who is going to pay for the infrastructure changes needed to implement sweeping reforms and new technology? Despite the financial implications, emergency medicine needs to embrace this concept in all aspects of patient care. As Karl Albrecht noted, “You seldom improve quality by cutting costs, but you can often cut costs by improving quality.” EDs are frequently in an overcapacity state. This was referred to initially as ED overcrowding when it was actually a systems issue within the individual hospital. The unintended consequence of overcapacity is ambulance diversion. Ambulances are asked to take sick patients to other hospitals, often a distance away. The quality and safety issues inherent in this situation are numerous (Table 149–2). Diversion is a symptom of, not a solution to, overcrowding. Numerous problems have an impact on crowding, but one of the most critical is access of care (Table 149–3). Emergency departments are the last safe harbor for economically challenged parents with children, the frail elderly, and patients with urgent needs whose doctors cannot see them. When the ED/hospital is over capacity, waiting times increase, the number of patients who have “Left Without Being Seen” increases, and the fi xed staff cannot provide the type of care that they have been trained to give. In an overcapacity situation, the criteria for a disaster or mass casualty incident are often met but not matched with a prescribed action plan. Additionally, hours and even days go by without

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SECTION VI — The Practice Environment

Table 149–3

Reasons for Lack of Access to Health Care

Doctor’s offices are full. Doctor’s offices are closed. Offices are not accepting new Medicare patients. Patient cannot afford outpatient care or prescription drugs. The “clinic system” has failed.

Table 149–4

Selected Hospital-Related Opportunities to Decrease Overcrowding

• Measure each step of the admission process to identify the opportunities for improvement. • Include key members of the multidisciplinary team in all process improvement discussions. • Create units that can expand to accept greater number of patients and avoid adding nonclinical ancillary personnel. • Improve the accuracy of forecasting beds for elective surgery and the resources to support it. • Expand the elective surgery schedule for nonpeak hours; negotiate with the surgical staff to comply. • Assign accountability for timely discharges, efficient room turnover, and adequate resources for timely transportation. • Assign executive leadership to adopt or “own” a project or process. • Analyze operational data as they relate to quality and safety outcomes and report regularly.

any relief, giving the impression that overcrowding is “status quo” for the ED. As a result, quality and safety are compromised, and hospital-related opportunities to decrease overcrowding should be strategically discussed and accountability assigned (Table 149–4). EDs/hospitals must have an overcapacity or surge plan that includes the ability to increase resources and obtain additional staff. The senior management of the ED/hospital must streamline and reallocate resources throughout the hospital, including the canceling of elective surgeries, to focus on the overcapacity. They must establish the importance and priority of the ED, prior to overcapacity, as part of a strategic plan. Additional areas of the hospital must be opened up for patient care, including the creation of transition areas for admitted and discharged patients. Preparation for overcapacity and the prevention of the errors resulting from overcapacity includes education planning and the hospital’s commitment to patient safety and quality. This preparation is mandatory, and the operational effort required to implement an overcapacity plan must be simple and administratively supported. At the very least, there should be an “ED dashboard” or mechanism in place to communicate the real-time current condition of the ED to all members of the management team responsible for patient throughput (Table 149–5).

Solutions Benchmarking quality indicators, measuring them, and making system changes to improve compliance are fundamental components of an ED quality improvement program. It is necessary to understand best practices and share successes to improve the way care is delivered. The department must do away with the “culture of blame,” and develop an

Table 149–5

Emergency Department (ED) “Real-Time” Dashboard: Reflects the Current Condition in the ED

Patients Currently in the ED Capture Time at Seen by a provider Door Triaged and waiting for screening examination Waiting to be triaged Current Resources Physicians Assigned to Mid-level practitioners Patient Care Registered nurses Ancillary staff: clerks, technicians, registrars etc. Total Turnaround Time Average chemistry TAT: order to result (TAT) Average microbiology TAT: order to result Average radiology plain film TAT: order to film Average radiology CT TAT: order to result Patients Holding in the ED Patient

Admitting Physician

Acuity (CC, Tele, Regular, OB)

Bed Assigned

Comments

Patient 1 Patient 2 Patient 3 Etc. Abbreviations: CC, critical care; CT, computed tomography; OB, obstetric; Tele, telephone.

environment in which “near misses” are reviewed in a just culture reporting system and systems are put into place to prevent harm. In order to implement national best practices, there must be a complete facility buy-in to achieve the desired quality and/or safety outcomes. The Institute for Healthcare Improvement describes one such example as the “Plan-DoStudy-Act” cycle. This process tests a quality/safety change in the real work setting—by planning it, trying it, observing the results, and acting on what is learned. This is the scientific method used for action-oriented learning. The department focuses on a desired outcome that is presently challenging and maps the process to help define critical steps that are captured and measured for analysis. A multidisciplinary team is selected that best represents key stakeholders, and changes for improvement are defined. A trial is implemented and the results are used to support a permanent change in process or policy. All successful quality programs must have the support of their hospital’s leadership. As stated by L. L. Leape, “Management must ‘manage’ for patient safety and quality just as they manage for efficiency and profit maximization. Safety must become part of what a hospital or healthcare organization prides itself on.”19 Successful organizations have implemented the following practices and created a culture of quality and safety: Collaborative Environment: Create an environment in which every member of the patient care team is empowered to provide information, ask questions, and question orders or a patient disposition. Just Culture Error Reporting Systems: Incident reports must be simple to complete. Root-cause analysis must be

Chapter 149 — Patient Safety, Medical Errors, and Quality of Care

completed to understand system errors. An anonymous reporting system provides practitioners with a “safe harbor” reporting environment. Staff education will raise the level of awareness about medication errors and near misses. Dashboard: An ED dashboard should reflect the current/ real-time condition of the ED and be accessible to all appropriate leadership via a shared computer hard drive or Intranet. This report should help facilitate the appropriate actions to decompress the ED and allocate the appropriate resources to meet patient care demands (see Table 149–4). Report card: The ED report card must include fi nancial, operational, quality, and satisfaction data, with the appropriate benchmarks to provide leadership with the insight to identify opportunities for improvement and processes that are successful. The data points selected to create the measurement should adequately reflect the processes of the department and the results should be validated (Table 149–6). Clinical Information System: Electronic information systems should facilitate easy documentation of assessments, care, and treatment of ED patients and access to that information in an organized and retrievable format. Additionally, they should provide tools to prevent error, improve the staff’s ability to communicate, and provide up-to-date clinical best practices to drive quality outcomes. Quality Program: The most successful quality programs include executive leadership with multidisciplinary representation, evidence-based care paths, the appropriate tools to assure successful implementation, and a process to measure outcomes and communicate them to all departments involved in the care path.

Table 149–6

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Safety Program: A successful safety program is one that promotes a collaborative and patient-centric culture throughout the entire organization. Patient Callbacks: Radiology discrepancies, positive cultures, and patients who left without being seen all provide useful quality and follow-up data. Clinical Guidelines and Pathways: Best practices should be developed for frequent and high-risk/complex patient presentations. Asthma, fever, and dehydration are examples for which specific evidence-based medicine protocols should be tracked and linked to outcomes. Sign Out/Change of Shift: Every patient must have a physician and nurse who understand his or her problem and treatment plan. A policy on how a patient’s care is transitioned from one health care provider to another is critical to prevent errors. Improvement of All Communications: Improving written and verbal exchange of imformation applies to how one communicates to other medical personnel as well as to the patients and their families. • Written: Utilize electronic ordering systems where possible. Safety protocols implemented at the institution should include: Discontinuing the use of all error prone abbreviations. Never using a trailing “0” (1.00 mg/kg). Always using a leading “0” (0.1 mg/kg). Do not write or accept poorly written orders or charts. Always customize discharge instructions to include a simple but explicit follow-up plan regarding outpatient care and medication. To enhance understanding, choose the appropriate language and grade level for all people involved in the care.

Selected Emergency Department (ED) Report Card Measurements: Monitoring of the ED Over Time

Financial

Quality & Safety

Operational

Satisfaction

Volume • Month to date (MTD) • Year to date (YTD) • Include % increase and decrease • Expected vs. actual • Track specialty service utilization • Fast track • Orthopedics

Core Measure Outcomes Driven by Care in the ED • AMI • Pneumonia • Infectious disease Monitor changes to the course of treatment implemented in the ED vs. inpatient and link to outcomes Safety Culture Measurement (CUSP)

Turnaround Times • Admitted • Discharged • ED area • Fast track • Pediatrics • Laboratory • Radiology

Patient Satisfaction • By question • By time of day • By staff member

Quality-Linked Operations • Door to ECG • Door to PCI • Door to thrombolytics Admission Process • Process map each step • Analyze by service • Analyze by destination

Employee Satisfaction • By discipline within the department • By shift Medical Staff Satisfaction • Monitor formally with a survey that reflects the distinction between ED and hospital process • Allow for ongoing monitoring

Resource Utilization • Patients per physician hour • Patients per provider hour Charge Capture: Assure adequate resources are available to maintain quality: • Adequate central line kits to support recommendations to decrease central line–associated primary bloodstream infections • Foley kits with urimeter attached to catheter to prevent UTIs associated with breaking the sterile field

Physician- and Nurse-toPatient Ratios • Measure by acuity • In real time, by time of day Map to outcomes

Abbreviations: AMI, acute myocardial infarction; ECG, electrocardiogram; PCI, patient controlled infusion; UTIs, urinary tract infections.

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• Verbal: Use appropriate time-out policy during procedures. Minimize use of verbal orders. Always do a read back of a verbal order. Introduce yourself and know your coworkers. Create a collaborative, not hierarchical, working environment. Identify high-risk or very unstable patients. When speaking to a patient, always follow verbal instructions with a written version. Emergency Medicine–Specific Quality Guidelines: Develop indicators based on chief complaint or clinical presentations versus the diagnosis. Patient-Centered Care: Historically, the environment of care was based on staff convenience (nursing stations, lack of test availability at night, etc.). The focus needs to change to “what is best for the patient.” Telephone and Verbal Orders: Limit these wherever possible and have them repeated and confirmed. ED Medications: Institute measures to prevent medication errors: • Reduce the number of medications with similar indications. • Consider having a pharmacist in the ED to mix all medications, similar to the intensive care unit. • Place concentrated electrolyte solutions from the ED in secured areas. • Clearly label medications and do not store look-alike/ sound-alike medications near each other. • Limit interruptions, if possible, during medication preparation and administration. On-Call Specialist and Follow-up Care: The hospital administration and physician leadership must ensure that there is adequate subspecialty care and follow-up. Table 149–1 is a resource for finding EM best practices. Systems must be in place to minimize human factors. As stated by W. A. Foster, “Quality is never an accident. It is always the result of high intention, sincere effort, intelligent direction, and skilled execution.”

Summary Individual EDs need to use the evidence, information, and technology that have already been demonstrated to improve patient outcomes. If the hospital administration is not visibly advocating for quality and patient safety, they must be motivated to become involved. Joseph Juran stated that “every successful quality revolution has included the participation of upper management. We know of no exception.” This is a cultural change and requires hospital-wide participation. Health care providers need to be patient advocates and provide patient-centered care. As with patient satisfaction, it is not enough to be good clinicians; they must make the

system work for their patients. As Aristotle noted several centuries ago, “We are what we repeatedly do. Excellence, then, is not an act but a habit.” Continuous improvement in patient care must be embraced by the entire health care industry.20 REFERENCES 1. Laffe G, Blumenthal D: The case for using industrial quality management science in health care organizations. JAMA 262:2869–2873, 1989. *2. Institute of Medicine: Crossing the Quality Chasm: A New Health System for the 21st Century. Washington, DC: National Academy Press, 2001. *3. Institute of Medicine; Kohn LT, Corrigan JM, Donaldson MS (eds): To Eerr is Human: Building a Safer Health System. Washington, DC: National Academy Press, 2000. 4. Thomas EJ, Studdert DM, Burstin HR, et al: Incidence and types of adverse events and negligent care in Utah and Colorado [Comment]. Med Care 38:261–271, 2000. 5. Thomas EJ, Studdert DM, Newhouse JP, et al: Costs of medical injuries in Utah and Colorado. Inquiry 36:255–264, 1999. 6. Bates DW, Spell N, Cullen DJ, et al: The costs of adverse drug events in hospitalized patients. Adverse Drug Events Prevention Study Group. JAMA 277:307–311, 1997. 7. Balas EA: Information systems can prevent errors and improve quality [Comment]. J Am Med Inform Assoc 8:398–399, 2001. *8. Greiner AC, Knebel E (eds): Health Professions Education: A Bridge to Quality. Washington, DC: National Academy Press, 2003. 9. Layton C, Smith PJ, McCoy CE: Design of a cooperative problemsolving system for en-route fl ight planning: an empirical evaluation. Hum Factors 36:94–119, 1994. 10. Weick KE, Roberts KH: Collective mind and organizational reliability: the case of fl ight operations on an aircraft carrier deck. Adm Sci Q 38:357–381, 1993. 11. Gaba DM, Maxwell MS, DeAnda A: Anesthetic mishaps: breaking the chain of accident evolution. Anesthesiology 66:670–676, 1987. 12. Gaba DM, Howard SK, Jump B: Production pressure in the work environment: California anesthesiologists’ attitudes and experiences. Anesthesiology 81:488–500, 1994. 13. Howard SK, Gaba DM, Fish KJ, et al: Anesthesia crisis resource management training: teaching anesthesiologists to handle critical incidents. Aviat Space Environ Med 63:763–770, 1992. *14. Broselow JB: Color coding kids . . . a patient safety initiative. Quality Improvement and Patient Safety Section News, Vol 4, July 2003. *15. Chisolm CD, Collison EK, Nelson DR, Cordell WH: Emergency department workplace interruptions: are emergency physicians “interrupt driven” and “multitasking”? Acad Emerg Med 7:1239–1243, 2000. 16. Grabowski M, Roberts KH: Risk mitigation in large-scale systems: lessons from high reliability organizations. Calif Manage Rev 39(4), Summer 1997. 17. Hauck LD, Adler LM, Mulla ZD: Clinical pathway care improves outcomes among patients hospitalized for community-acquired pneumonia. Ann Epidemiol 14:669–675, 2004. 18. Benenson R, Magalski A, Cavanaugh S, Williams E: Effects of a pneumonia clinical pathway on time to antibiotic treatment, length of stay, and mortality. Acad Emerg Med 6:1243–1248, 1999. *19. Leape LL, Berwick DM: Safe health care: are we up to it? BMJ 320:725– 726, 2000. *20. Berwick DM: Continuous improvement as an ideal in health care. N Engl J Med 320:53–56, 1989. *Suggested readings.

Chapter 150 Emergency Medical Treatment and Labor Act (EMTALA) Todd B. Taylor, MD

Key Points1 The original intent of the Emergency Medical Treatment and Labor Act (EMTALA) is consistent with standards of medical care. The EMTALA obligation is voluntarily accepted by hospitals as part of the Medicare Conditions of Participation Agreement. Physicians are duty-bound by EMTALA, by virtue of their voluntary agreement with the hospital, to serve on call and/or by agreement or contract with the hospital to provide emergency services. EMTALA requires Medicare-participating hospitals with emergency departments to provide screening for and treatment of emergency medical conditions in a nondiscriminatory manner to any individual regardless of ability to pay, insurance status, national origin, race, creed, color, and the like. EMTALA requires individuals with similar medical complaints or conditions to be treated similarly. It applies to all individuals at Medicare-participating hospitals, not just those covered by Medicare. As a federal statute, EMTALA supersedes state and local laws, including peer-review protections, certain tort reform limitations, and statutes of limitations. It grants every individual a federal right to emergency care and creates additional rights when hospitals or physicians fail to comply. EMTALA violations can result in significant penalties for hospitals and physicians, including civil monetary penalties of up to $50,000 per violation and/or Medicare participation termination. EMTALA is an unfunded mandate and does not require health insurance companies, governments, or individuals to pay for mandated emergency services.

Emergency physicians on average provide $138,300 of uncompensated EMTALA-related medical care each year, and one third of emergency physicians provide more than 30 hours of EMTALA-related care each week.2

Introduction and Background EMTALA’s Original Intent A hospital is charged only with the responsibility of providing an adequate first response to a medical crisis [which] means the patient must be evaluated and, at a minimum, provided with whatever medical support services and/or transfer arrangements that are consistent with the capability of the institution and the well-being of the patient.3 The Emergency Medical Treatment and Labor Act (EMTALA) was enacted by Congress in 1986 as part of the Consolidated Omnibus Budget Reconciliation Act of 1985 (42USC§1395dd). Often referred to as the patient “anti-dumping” law, it was originally designed to prevent hospitals from transferring uninsured or Medicaid patients to public hospitals without, at a minimum, providing a medical screening examination (MSE) and treatment to assure that such transfers could be done safely. The concern for patient safety at that time was not unwarranted. Studies showed that, in the early 1980s, of transfers to public or Veterans Administration hospitals, 87% were for economic reasons. Only 6% of patients gave informed consent, 24% of patients were unstable at the time of transfer, mortality was three times that of other patients, and 250,000 such transfers were occurring annually.4-7 Congress has amended and expanded the scope of EMTALA five times. For example, until 1989, EMTALA did not require hospitals or physicians to provide on-call services, nor did it require hospitals with specialized services to accept patients in transfer. Over the years, additional amendments enhanced the ability to impose fines, increased penalties, provided whistle-blower protections, and expanded the reach of the law and the mandated duties of providers. 1053

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Despite passage in 1986, there was little enforcement of EMTALA for the first 10 years.8,9 Enforcement increased significantly after the Centers for Medicare & Medicaid Services (CMS; formerly the Health Care Financing Administration) published rules for the enforcement of EMTALA in the Code of Federal Regulations (CFR) in 1994 [42CFR§489.xx]. (The full statute and definitions of terms are available at http:// www.gpoaccess.gov/cfr/index.html.) By 1999, there had been more than 2000 EMTALA investigations and more than 1000 confirmed violations.10 In June 1996, a diverse national EMTALA Task Force was formed to clarify the regulations with new Interpretive Guidelines published in July 1998. The Interpretive Guidelines did not carry the force of law and, while well intentioned, left many issues vague. As a result, federal and state civil courts continued to have a significant influence on EMTALA interpretation. Consequently, EMTALA now has little resemblance to its original intent of regulating economically motivated transfers.11 On November 10, 2003, CMS published a final rule revising the 1994 EMTALA CFR. In large part, these revised rules simply codified interim CMS guidance, but in addition they revised the definition of an “emergency department,” clarified what is considered “hospital property,” recognized certain limitations of on-call specialists and on-call panels, added a “prudent layperson” standard with regard to the request for services, and clarified applicability to hospitalowned ambulances. In addition, although EMTALA has never applied to inpatients, the new rules drew a “bright line” at admission for when the EMTALA obligation ends [42CFR§489.24(d)(2)]. Once a patient is admitted, other Medicare Conditions of Participation requirements apply, making EMTALA superfluous for hospital inpatients [42CFR§482.55]. While EMTALA is a complex law with many ambiguities, one would need to read no further if only one principle were adopted for EMTALA compliance: “Take care of the patient.” EMTALA is a “medical anti-discrimination” law. Anytime one considers treating any patient differently for other than a good medical reason, EMTALA is in jeopardy of being violated. The difficulty comes in properly documenting such reasoning and in achieving technical compliance. EMTALA is of special concern to hospitals with limited, focused, and special capabilities, such as pediatriconly hospitals and general hospitals that provide “specialized” pediatric services (e.g., a pediatric emergency department [ED]). This chapter presents the basics of EMTALA, drawing heavily upon the actual statutory language. It has been written primarily for physicians, and additional references and CRF and United States Code (USC) citations are provided for more detailed reading and study.

Issues: Implications of EMTALA for American Health Care According to Rep. Pete Stark (D-CA), co-sponsor of EMTALA: Patient dumping is but a symptom of a much larger problem. Thirty-seven million Americans [47 million in 2005] are without health insurance. Low income sick people are finding it increasingly difficult to get needed

health care, and the burden of caring for them is falling on fewer and fewer hospitals.12 Access should be the government’s responsibility at the federal, state, and local levels. We cannot and should not expect hospitals to be this nation’s National Health Service.13 From a legal perspective, EMTALA’s original purpose was simply to create a duty to provide an MSE to assure that either no emergency medical condition (EMC) exists or, if an EMC is present, it is “stabilized” prior to the patient’s transfer to a public hospital. With significant changes in payment mechanisms in the early 1980s (e.g., “diagnosis-related groups”), the onslaught of managed care, and increasing numbers of uninsured patients, private hospitals felt compelled to limit their exposure to revenue losses from uninsured and Medicaid patients. This led to a “wallet biopsy” being performed prior to offering even emergency care. Ultimately, this mistreatment of patients prompted the creation of a clever “voluntary” governmental solution we now know as EMTALA. EMTALA was the first time Congress had used the Medicare statute to create public policy extending beyond Medicare recipients. As a result, it became a national standard of care for emergency services and a federal right to emergency care.11 While noble in its intent, and representing what most would find to be ethical and a standard of medical care obligation, in the ensuing years the EMTALA statute and regulations resulted in many unintended and even untoward consequences. EMTALA now regulates virtually every aspect of care provided on hospital property, but by design has no bearing on payment. It allowed local and state governments to abdicate responsibility for charity care, thereby shifting this public responsibility to the private sector. Subsequently, many public “free” clinics were closed due to budgetary concerns, and public hospitals use EMTALA as a shield against accepting indigent patients. In essence, EMTALA made every Medicare-participating hospital a “public” hospital. EMTALA has become the de facto national health care policy for emergency care and for the uninsured. It also forced America’s EDs to become the safety net of the health care system.14-17 Until recently, the federal government had never accepted any direct financial responsibility for EMTALA. The Medicare Modernization Act of 200318 for the first time provides financial relief to hospitals burdened with undocumented aliens due to EMTALA. Nevertheless, the financial strain of EMTALA continues to plague hospitals and their associated physicians with over $25 billion in uncompensated care annually,19 and “55 percent of emergency services go[ing] uncompensated.”20 Furthermore, the traditional costshifting mechanism to compensate for this burden has largely been eliminated by managed care, and many managed care practices are irreconcilable with the requirements of EMTALA. The direct and indirect impact of EMTALA continues to mount. Specialists are fleeing hospital medical staffs to avoid ED on-call duties, hospitals are limiting the scope of services or creating “specialty” hospitals to carve out a niche with less EMTALA exposure, efforts are made to “manage” the financial risk with ED “triage-out” procedures for “nonurgent” conditions, and medical repatriation programs have been devised for foreign nationals; these are but a few examples.

Chapter 150 — Emergency Medical Treatment and Labor Act (EMTALA)

After more than two decades of EMTALA, two fundamental principles are clear: 1. How health care is funded (and litigated) drives health care availability and delivery. 2. America cannot solve the EMTALA conundrum until it addresses the reason EMTALA exits—a failure to appropriately fund and provide for indigent and uncompensated emergency medical care. General EMTALA Duty EMTALA creates a duty that otherwise would not exist for hospitals. Ethical duty aside, prior to enactment of EMTALA, there was no legal duty for a hospital to provide medical care (even emergency care) to anyone not already accepted as a patient. EMTALA was specifically design to create such a duty for any “individual” that arrived on hospital property and requested treatment for a “medical condition.” It should be noted that the statute does not say “emergency medical condition.” Whether the medical condition is an “emergency” must be determined by an MSE, and, if an EMC is present, additional EMTALA obligations are imposed. Under EMTALA, hospitals voluntarily accept this duty by virtue of their “contract” with Medicare, called the Medicare Conditions of Participation. In doing so, they agree to be investigated, sanctioned, and fined for noncompliance without due process. Physicians do not have a similar Medicare requirement; therefore, EMTALA is the sole burden of Medicare-participating hospitals. Nonparticipating hospitals, such as the Veterans Administration, certain military hospitals, non–hospital owned urgent care centers, and the like, are not obligated under EMTALA. Since EMTALA applies only to hospitals, administration must make arrangements to provide physician services as part of this duty. Ironically, EMTALA provides no formal

Table 150–1

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mechanism or requirement for this to be accomplished. So, while the law mandates that hospitals provide on-call physicians, it does not require physicians to provide on-call services. As a result, most hospitals do so via contract (e.g., with emergency physicians or employed physicians) or by imposing duties by voluntary participation in the medical staff and the ED on-call roster. Because EMTALA is “voluntary” (i.e., hospitals can choose not to participate in Medicare and physicians can choose not to be on the medical staff or choose not to take ED call), it avoids the U.S. Constitution’s XIIIth Amendment prohibition against involuntary servitude and slavery. Voluntary or not, EMTALA often creates opportunities for discord between hospitals, between a hospital and its medical staff, and among the medical staff itself, particularly between the ED and on-call physicians. This discord is often exacerbated by the threat of fines and sanctions, which are equally onerous for physicians as for hospitals. Statutory Definitions Increasingly, EMTALA is now controlled by statutory definitions that often have little basis in medical science [42CFR§489.24(b)]. Table 150–1 lists the potential sanctions and fines. Table 150–2 lists the regulatory agencies overseeing EMTALA.

EMTALA-Mandated Responsibilities for Hospitals and Physicians As a federal statute, EMTALA supersedes conflicting and contradictory state and local laws [42USC§1395dd(f)], including peer-review protections, certain tort reform limitations, and statutes of limitations. It grants every individual a federal right to emergency care and creates additional rights when hospitals or physicians fail to comply.

Potential EMTALA Sanctions and Fines (42CFR§1003.102)

Action

Amount/Duration

Comment

Regulation

Medicare & Medicaid program termination Civil monetary penalties

Up to 2 yr

This can be a financial “death sentence” for any hospital or physician. A malpractice insurance carrier may cover defense of the action, but fines are almost never covered without an EMTALA rider.

42CFR§489.24(g) & 42CFR§1003.105 42CFR§1003.103(e) & 42CFR§1003.106

Hospital vs. hospital Private cause of action

Up to $50,000 for each violation (not each patient) A hospital “dumped on” can recover all costs for the patient’s care. Depends on proven damages

Injunctions

Hill-Burton Act funds

Varies

Civil rights

Fines and/or incarceration

42USC§1395dd(d)(2)(B) Allows a civil case to be brought in federal court under “strict compliance with the law.” Strict liability is less open to “expert” defense and easier to prove. The court may impose an injunction requiring certain remedies to correct future violations or public notice of nondiscrimination policies. EMTALA violations may result in government action to recover loans and grants made to the facility. EMTALA violation based on discrimination may result in referral to the Civil Rights Division of DHHS, resulting in criminal prosecution under the Civil Rights Act.

Abbreviation: DHHS, Department of Health and Human Services.

42USC§1395dd(d)(2)(A)

State Operations Manual: Appendix V—Interpretive Guidelines25

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SECTION VI — The Practice Environment

Table 150–2

EMTALA Regulating Entities

Centers for Medicare & Medicaid Services (CMS) Office of the Inspector General (OIG) The courts Federal Administrative Courts Civil state or federal courts

Duty to Provide an “Appropriate” Medical Screening Examination [42CFR§489.24(a)(1) & (a)(1)(i)] The sole purpose of the MSE is to determine if an EMC exists. If the ED has the ability to rule out an EMC and documents this in the medical record, then EMTALA no longer applies. At that point the patient may be dispositioned in accordance with community standards of medical care, hospital policy, and local regulations. It is important to recognize that, even if EMTALA no longer applies, other regulations may, and many states have passed similar and even more stringent regulations regarding emergency care. The MSE is all encompassing and includes all the available hospital resources necessary to make a determination of an EMC, including on-call specialists. However, hospitals are not required to provide all services 24 hours a day, if these services are not routinely provided after hours. Application of the EMTALA MSE requirement now depends upon “where” the individual presents on hospital property. If they present to the “dedicated emergency department” and request examination or treatment for a “medical condition,” this duty applies. If they present anywhere else, the duty only applies if the request is for what may be an EMC. In actual practice, this differentiation is only important for legal defense purposes, but documentation to that effect may assist in such defense. Although not necessarily required by EMTALA, the safest course of action may be to take any individual who presents with anything remotely resembling a request for medical care to the appropriate area in the hospital (i.e., ED, pediatric ED, obstetrics triage, psychiatry, etc.) for a formal MSE. Perhaps the easiest way to train staff in this regard is to instruct them to ask such individuals, “Do you want to see a doctor?” If the answer is “yes,” then the individual should be taken to the ED or other appropriate department. If the answer is “no,” then staff should inquire further as to what the individual wants or needs. If there is any uncertainty, the safest course of action is to let the ED sort it out. Pediatric EDs, particularly those that are part of a pediatric hospital, must understand their obligation to medically screen and stabilize any “individual” (regardless of age) that “comes to the emergency department” and requests evaluation for a medical condition. While such a facility is only required to provide such screening and stabilization that is within their capacity and capability, it is assumed that any hospital ED can and will do as much as they can while making arrangements for transfer to a more appropriate facility. If an EMC cannot be ruled out, then the patient should be considered “unstable” for the purposes of transfer and an “appropriate” formal EMTALA transfer accomplished.

Special Circumstances Related to the MSE NO DELAY IN PROVIDING A MEDICAL SCREENING EXAMINATION OR TREATMENT [42CFR§489.24(d)(4)]

The “no delay” provision is often a misconstrued requirement. Some hospitals have taken the approach that, to be completely “safe,” no insurance information may be obtained until the MSE has been initiated. Clearly this is not a requirement and may itself delay treatment since managed care often utilizes certain specialty consultants that may be unknown until insurance information is available. Nevertheless, whatever information is obtained cannot alter the usual course of examination and treatment. This provision clearly prohibits prior authorization for at least the initial MSE and treatment. Also, the determination as to whether a patient has an EMC or is stable remains the purview of the on-site examining physician. Therefore, it is not appropriate for an off-site managed care gatekeeper to make such a determination. Once the MSE has determined that there is no EMC or the EMC has been stabilized, then authorization (e.g., for admission or nonemergent testing) may be obtained if necessary. However, this may become a very delicate situation when authorization for admission is denied and an “economic transfer” is requested by the health plan. For truly “stable” patients this should not be an EMTALA issue, but “stability” is often reviewed retrospectively if anything adverse occurs during or even after the transfer. Under strict EMTALA statute interpretation, an “economic transfer” is allowable, but the physician must always be correct about “stability.” In the current EMTALA and medical-legal climate, such transfers should be severely limited (i.e., to the absolutely most stable patients) or initiated after admission once stability is assured and EMTALA clearly no longer applies. If such “economic transfers” are to be contemplated, it is prudent to identify additional legitimate reasons for the transfer, such as “continuity of care,” and to assess the patient’s desire to be transferred to an in-network facility by his or her formal request to be transferred. Emergency physicians compelled by the hospital to initiate economic transfers for the hospital’s benefit may wish to seek indemnification by the hospital for any untoward EMTALA or other legal action. Regardless, it is always prudent to clearly document that the patient is “stable” and that he or she is aware of the reasons for transfer along with the risks and benefits. The following acknowledgment statement has been recommended: The physician has determined that my condition is stable and that there is no significant risk to my being transferred. I want the cost of further treatment to be covered by my health plan. My health plan has agreed to cover the cost of treatment at the receiving facility, but denied payment for services at this facility. AVAILABILITY OF ON- CALL PHYSICIANS [42CFR§489.24(j)]

On-call specialty coverage for EDs and hospital inpatients has emerged as a major health care issue21,22 but is beyond the scope of this chapter. While EMTALA is neither the cause nor the solution, along with other stresses in the health care system it continues to have a significant impact on ED specialty coverage.23 Increasingly, hospitals are finding it neces-

Chapter 150 — Emergency Medical Treatment and Labor Act (EMTALA)

sary to compensate or employ physician specialists in order to comply with the EMTALA mandate. Under EMTALA, the hospital and not its medical staff or individual physicians is responsible for maintaining an on-call roster for the ED [42 USC§1395cc(a)(1)(I)(i) & (iii)]. EMTALA case law requires hospitals to cajole, force, or otherwise negotiate and procure physician services to operate their EDs and provide on-call specialty care.24 USE OF DEDICATED EMERGENCY DEPARTMENT FOR NONEMERGENCY SERVICES [42CFR§489.24(c)]

If an individual comes to a hospital’s dedicated ED and a request is made on his or her behalf for examination or treatment for a medical condition, but the nature of the request makes it clear that the medical condition is not of an emergency nature, the hospital is required only to perform such screening as would be appropriate for any individual presenting in that manner, to determine that the individual does not have an EMC. This clarifies that hospitals are not required to provide EMTALA-related services for “nonemergencies.” However, this is a “chicken and egg” conundrum and in no way alleviates hospitals from performing an appropriate MSE for what may seem at triage to be the most trivial complaint yet later turns out to be an EMC. QUALIFIED MEDICAL PERSON PERFORMING THE MSE [42CFR§489.24(a)(1)(i)]

A hospital must formally determine who is qualified to perform the initial MSE, that is, a “qualified medical person” (see also “Duty to Transfer” section). While it is permissible for a hospital to designate a nonphysician practitioner as the qualified medical person, the designated nonphysician practitioners must be set forth in a document that is approved by the governing body of the hospital. Following governing body approval, those health practitioners designated to perform MSEs are to be identified in the hospital bylaws or in the rules and regulations governing the medical staff. It is not acceptable for the hospital to allow the medical director of the ED to make what may be informal personnel appointments that could frequently change. Duty to Stabilize [42CFR§489.24(a)(1)(ii) & 489.24(d)] If the MSE determines that an EMC exists, then additional EMTALA duties apply. However, it should be noted that the statutory definition of “emergency” medical condition is quite restrictive, in that it requires that the “absence of immediate medical attention” will result in bad things happening. This fact is useful from a legal defense perspective, but from a practical standpoint almost any acute medical condition should be treated to an appropriate conclusion in the ED prior to discharge. While not required by EMTALA, this approach is prudent in light of aggressive CMS EMTALA enforcement, the impact of an EMTALA investigation, the potential severity of penalties, and the current medial-legal climate. It should also be noted that other Medicare Conditions of Participation, state regulations, and general medical liability may apply even if EMTALA does not. Furthermore, a failure to follow hospital policy is often considered a per se EMTALA violation, even if the policy in question is not otherwise required by the EMTALA statute. Therefore, hospitals should construct their policies and procedures with extraordinary care to assure universal compli-

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ance. For example, an ED triage policy that requires every patient to be triaged within 5 minutes of arrival may be unrealistic in the current overcrowded ED environment. A requirement for on-call physicians to arrive within 30 minutes is unrealistic for most communities. Nevertheless, under EMTALA, 6 minutes to triage or 31 minutes for the specialist to arrive could both be potential violations for failing to comply with hospital policy. As with the MSE requirement, the duty to stabilize is all encompassing, including necessary on-call specialists. If the EMC can be resolved in the ED and is documented as such, then EMTALA no longer applies. If the EMC cannot be resolved in the ED and the hospital has inpatient services appropriate to resolve it, then the patient must be admitted. At the point of admission, the EMTALA obligation ends and is superseded by other Medicare Conditions of Participation requirements [42CFR§489.24(a)(1)(ii) & (d)(2)]. If the hospital does not have inpatient or emergency services (i.e., capacity and/or capability) necessary to stabilize the EMC, then an appropriate formal EMTALA transfer must be accomplished unless refused by the patient. Duty to Transfer [42CFR§489.24(e)] There are only three circumstances under which a patient may be transferred. 1. The patient is “stable” under the statutory EMTALA definition, in which case theoretically EMTALA does not apply. This is theoretical because transferring a “stable” patient for admission or for further ED workup begs the question as to why the patient is being transferred instead of simply being discharged home. Again, this makes for an excellent legal argument when a transfer “goes bad,” but in practice can be risky. While not required by EMTALA, it is prudent to document a legal “appropriate” transfer on all patients not otherwise being routinely discharged from the ED. While in many instances transferred patients will be declared “stable,” if in retrospect the patient deteriorates, the transfer documentation will help protect the transferring hospital. In addition, some states require similar documentation on all transfers regardless of stability. In an ill-conceived ploy, some have tried to circumvent EMTALA by “discharging” a patient with instructions to “go to the ‘county’ hospital.” For EMTALA purposes, a “discharge” is a transfer, and such behavior invariably raises suspicion and results in an investigation. 2. The individual (or legal representative) requests to be transferred and accepts, in writing, the documented risks. EMTALA does not empower hospitals to force involuntary treatment, admission, or transfer. However, it does require specific documentation and informed risk should a patient request to be transferred or refuse transfer, examination, or treatment. While this may seem relatively straightforward, an EMTALA conundrum can be created when a patient requests to be transferred to a hospital that then refuses to accept him or her based on the premise that the sending facility has the ability to treat. If the patient cannot be dissuaded, the best course of action is to have him or her sign out “against medical advice”; complete as much of the transfer documentation as is possible, including sending medical records; and notify the receiving facility of the situation.

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3. The transfer is medically indicated (i.e., the risk of transfer is outweighed by the benefits) as certified by a physician (or qualified medical person in consultation with an off-site physician). If the ED does not have the ability (capacity or capability) to determine if an EMC exists or to stabilize an identified EMC, then the patient should be considered unstable and an “appropriate” formal EMTALA transfer to a hospital with ability should occur unless refused by the patient.

and informs the individual (or a person acting on his or her behalf) of the risks and benefits of the transfer, but the individual does not consent to the transfer. The hospital must take all reasonable steps to secure the individual’s written informed refusal.

“Appropriate” Formal EMTALA Transfer [42CFR§489.24(e)(2)]

A participating hospital that has specialized capabilities or facilities—including, but not limited to, facilities such as burn units, shock-trauma units, neonatal intensive care units, or (with respect to rural areas) regional referral centers—may not refuse to accept from a referring hospital within the boundaries of the United States an appropriate transfer of an individual who requires such specialized capabilities or facilities if the receiving hospital has the capacity to treat the individual. The “duty to accept” is an often misunderstood and perhaps poorly defi ned requirement. The operative words are “including, but not limited to” and “if the receiving hospital has the capacity.” Pediatric hospitals, hospitals with pediatric EDs, and community hospitals that provide inpatient pediatric services should all be considered “hospitals with specialized services.” With increasing hospital ED and inpatient capacity issues, it is not uncommon for hospitals with “specialized services” to lack “capacity.” The issue becomes how to document such transfer refusals for individuals who never become patients. Another issue is who does this documentation if private on-call specialists screen these calls. There is no accepted standard and, in fact, most hospitals rely upon the good will of the calling facility to do this documentation for them. Nevertheless, some facilities have established “transfer coordinators” who document these calls and fi le a nonaccepted patient form by date of call for retrieval if necessary.

This section of the EMTALA statute lists the four required elements of an “appropriate transfer”: 1. Ongoing medical treatment until transfer 2. Confirmation of capability, capacity, and acceptance at the receiving facility 3. Sending of all available pertinent medical records 4. Assurance that the transfer is effected through qualified personnel and equipment Once the decision to transfer has been made, ongoing treatment and monitoring are required within the ability of the transferring facility until the transfer can be effected. This includes all available services, including on-call specialists even if they will not ultimately admit the patient. If the on-site physician requests the presence of an on-call specialist to help care for a patient while waiting for transfer, the specialist is required by EMTALA to come in within a “reasonable” time. There is a requirement to provide the name of any on-call physician that failed to appear whether or not that is the inciting reason for the transfer. Documentation that the receiving facility has the ability and has acknowledged acceptance of the transfer is required. While it is perhaps good medical practice under many circumstances, there is no specific requirement that a physician be contacted or accept the patient in transfer at the receiving facility. Anyone authorized at the receiving facility to accept the patient may do so, even a clerk in the admitting office. As with all medical encounters, documentation is important. For example, failure to document that medical records were sent is a per se EMTALA violation whether they were actually sent or not. The method of transport will depend upon the situation, but in most cases an ambulance is required. If for some reason an “unstabilized” patient is not being sent by ambulance (such as an eye injury sent with family to an ophthalmologist’s office with better equipment), careful documentation as to the reason for and safety of such method of transfer should be done. Documenting the required elements of an “appropriate transfer” in the medical record is sufficient, but difficult to consistently accomplish. While an EMTALA “Transfer Form” is not required, it is perhaps the best method to ensure technical compliance in documenting the three elements of a transfer: (1) request for transfer, (2) consent to transfer, and (3) certification of stability and/or risk/benefits of transfer. Special Circumstances Related to Transfers REFUSAL TO CONSENT TO TRANSFER [42CFR§489.24(d)(5)]

A hospital meets the EMTALA requirements if the hospital offers to transfer the individual to another medical facility

Duty to Accept Transfers Recipient Hospital Responsibilities [42CFR§489.24(f)]

Transfers Between the Same Hospital’s Departments or Facilities25 The movement of the individual between hospital departments is not considered an EMTALA transfer since the individual is simply being moved from one department of a hospital to another department or facility of the same hospital. Transfer Agreements Although transfer agreements are not required by EMTALA, they are mentioned in the State Operations Manual Interpretive Guidelines. They have been suggested as a way for specialized hospitals, such as pediatric hospitals, to expedite appropriate transfers of adults when necessary. They are useful because they allow for an established, well thought-out process before it is needed in the “heat of the moment.” However, transfer agreements are not the panacea that some may hope. First, there may be little incentive, and perhaps a disincentive, for a receiving hospital to cooperate without payment issues being addressed. Second, having a transfer agreement does not guarantee acceptance of a patient, because EMTALA requires services (i.e., inpatient beds) to be granted on a “first come, first served basis.” It is fundamentally dis-

Chapter 150 — Emergency Medical Treatment and Labor Act (EMTALA)

criminatory to give preference to one hospital over another in accepting transfers, and “holding beds” for this purpose will likely be construed as a violation of the section on “recipient hospital responsibilities” [42CFR§489.24(f)]. For these and other reasons, transfer agreements are rarely executed. Other EMTALA Duties for MedicareParticipating Hospitals Duty to Report [42CFR§489.20(m)] A hospital must report to CMS or the state survey agency any time it has reason to believe it may have received an individual who has been transferred in an unstable EMC from another hospital in violation of EMTALA. Whistle-Blower Protection [42CFR§489.24(e)(3)] A participating hospital may not penalize or take adverse action against a physician or a qualified medical person because he or she refuses to authorize the transfer of an individual with an EMC who has not been stabilized, or against any hospital employee because the employee reports an EMTALA violation. Only hospitals have the duty to report suspect violations, and then only for patients transferred to them (i.e., not for a refusal to accept an outgoing transfer). Although permitted to do so, physicians and hospital employees do not have a duty to report under EMTALA. However, they may have an obligation to report to hospital administration under hospital policy. Regardless, a hospital cannot take an adverse action against a physician or employee for complying with EMTALA or voluntarily reporting. Signage Requirement [42CFR§489.20(q)(1)] Hospitals must post conspicuously in any ED or in a place or places likely to be noticed by all individuals entering the ED, as well as those individuals waiting for examination and treatment in areas other than traditional EDs (i.e., entrance, admitting area, waiting room, treatment area), a sign specifying rights of individuals under EMTALA with respect to examination and treatment for EMCs and women in labor. Also, they must post conspicuously information indicating whether or not the hospital or rural primary care hospital participates in the Medicaid program under a state plan approved under Title XIX. Maintenance of Information [42CFR§489.20(r)(1)] Medical records related to individuals transferred to or from the hospital must be maintained for a period of 5 years from the date of the transfer. Also, a list of physicians who are on call for duty after the initial examination to provide treatment necessary to stabilize an individual with an EMC must be maintained, as well as a central log on each individual who comes to the ED seeking assistance and whether he or she refused treatment, was refused treatment, or was transferred, admitted and treated, stabilized and transferred, or discharged. Although perhaps not intuitively obvious, the “list of physicians on-call” must identify specific physicians’ names (i.e., not the group name and not a mid-level provider taking “first call”). Although most hospitals keep medical records indefinitely, the statute of limitations for an EMTALA violation is 2

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years [42USC§1395dd(d)(2)(C)], although penalties may be assessed up to 6 years [42USC§1320a-7(a)(c)(l)] after the incident. State Operations Manual Interpretive Guidelines The interpretive guidelines serve to interpret and clarify the responsibilities of Medicare participating hospitals in emergency cases. They contain authoritative interpretations and clarifications of statutory and regulatory requirements and are to be used to assist in making consistent determinations about a provider’s compliance with the requirements. These interpretive guidelines merely define or explain the relevant statutes and regulations and do not impose any requirements that are not otherwise set forth in the statutes or regulations. The revised guidelines clarify and provide detailed interpretation of the EMTALA provisions located at 42CFR§489.24 and parts 489.20 (l), (m), (q), and (r).26 The Interpretative Guidelines assist state surveyors (those who investigate potential EMTALA violations) and providers to better understand how CMS will enforce EMTALA and conduct investigations. The Guidelines do not carry the force of law and are ignored by the courts. Nevertheless, they are an important resource in avoiding an EMTALA citation. There are a few areas in which the Guidelines appear to overreach the EMTALA statutes. EMTALA Enforcement An EMTALA investigation, and the resulting citation process, can be quite complicated and is beyond the scope of this chapter. However, it should be noted that defending oneself in an EMTALA action can be expensive, often exceeding the amount of the potential civil monetary penalty. Furthermore, Medicare participation termination is a reality for both hospitals and physicians and a potential financial “death sentence.” EMTALA enforcement is fundamentally a complaintdriven process, so the principle objective in managing EMTALA risk should be to avoid being investigated. This requires that hospitals take an aggressive, yet very conservative approach to EMTALA compliance and at times implement policies more restrictive than technically required by the statute. Also, because of its complexity, the challenge for EMTALA is to achieve fail-safe compliance, but not interrupt the usual and reasonable ED process (Tables 150–3 and 150–4).

Summary: Ten Strategies for Successful EMTALA Compliance EMTALA continues to represent an ever-changing paradigm shift in how hospitals and physicians deliver emergency care and requires new ways of thinking, planning, and documentation.11 Regardless of its complexities, solutions are relatively straightforward: 1. Hospitals and physicians must acknowledge EMTALA’s existence and pervasiveness. 2. Area hospitals and medical staffs must act cooperatively because EMTALA compliance is impossible without cooperation from the medical staff leadership and hospital administration.

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Table 150–3

EMTALA Principles for Hospital Staff and Emergency Physicians

Inquiries about Any Medical Condition on Hospital Property • Ask, "Do you want to see a doctor?" • If "Yes," take individual to the ED. In the ED • Log ALL patients. • Provide MSE for ALL patients by a physician or a "qualified medical person." • If not, document why (i.e., left without treatment, refused MSE and/or treatment). • Treat ALL patients to a reasonable disposition in the ED. Transfers • Obtain acceptance from the receiving facility and complete a transfer form on ALL patients not otherwise being routinely discharged. • Accept ALL transfers if the hospital has the capacity (bed available and ever done it before) to treat the presenting problem. If not, document why. Reporting • Set up a system for reporting suspicious transfers. • Report ALL suspicious transfers to you. • Document ALL incoming and outgoing transfers.

Table 150–4

EMTALA Principles for Medical Staff Physicians*

If you are called, you are chosen. • Respond appropriately. • The emergency physician dictates appropriateness unless or until you assume care of the patient. Transfers • Accept ALL incoming transfers if the hospital has the capacity (bed available and ever done it before) to treat the presenting problem. If not, document why. ED Patient Outpatient Follow-Up • Do what you agreed to do in your office or risk being required to always come to the ED. • Do not demand payment up front or refer back to the ED if the patient is unable to pay or is a member of a noncontracted health plan. Do what the patient needs that day and make definitive arrangements for further care if necessary. • The best response to any inquiry from a hospital emergency department is, “How can I help you with this patient?” *These principles only apply when the physician is on call for the hospital emergency department.

3. Hospital EMTALA compliance policies and procedures, including forms, medical staff on-call responsibilities, and acceptance of patients in transfer, must be developed with extreme care. 4. Hospitals should require EMTALA education for anyone who may come into contact with individuals seeking medical care, including all hospital employees (nursing, ancillary, security, cafeteria, and administrative) and all medical staff. 5. Hospitals and physicians must document using the EMTALA paradigm, including appropriate legal terminology, new definitions of medical terms, and required norms and practices.

6. Hospital capabilities, including on-call services, must be defined and reviewed on a regular basis. 7. An in-house EMTALA compliance program should be created as part of the regular quality improvement process, and an EMTALA “hot line” should be established. 8. EMTALA issues must be addressed aggressively as they occur. It is not if, but when, so staff should prepare for an EMTALA investigation BEFORE it occurs by identifying resources. Preparing a model “corrective plan of action” may be worthwhile. 9. The emergency physicians are the hospital’s first, best, and final defense against an EMTALA violation. They must be empowered to do whatever is necessary to mitigate a developing EMTALA situation at the time it occurs. 10. Hospitals and physicians should always “take care of the patient” first. REFERENCES 1. American College of Emergency Physicians: EMTALA Fact Sheet. Dallas: American College of Emergency Physicians, 2005. 2. Kane CK: The impact of EMTALA on physician practices. AMA PCPS Report from 2001. Chicago: American Medical Association, 2003. 3. Testimony of Sen. Bob Dole (R–KS), co-sponsor of EMTALA. Congressional Record 28569, October 23, 1985. 4. Schiff RL, Ansell DA, Schlosser JE, et al: Transfers to a public hospital: a prospective study of 467 patients. N Engl J Med 314:552–557, 1986. 5. Himmelstein DU, Woolhandler S, Harnly M, et al: Patient transfers: medical practice as social triage. Am J Public Health 74:494–497, 1984. 6. Kerr HD, Byrd JC: Community hospital transfers to a VA Medical Center. JAMA 262:70–73, 1989. 7. Ansell DA, Schiff RL: Patient dumping: status, implications, and policy recommendations. JAMA 257:1500–1502, 1987. 8. Levine RJ, Guisto JA, Meislin HW, Spaite DW: Analysis of federally imposed penalties for violations of the Consolidated Omnibus Reconciliation Act. Ann Emerg Med 28:45–50, 1996. 9. Schiff RL, Ansell D: Federal anti-patient-dumping provisions: the first decade [Editorial]. Ann Emerg Med 28:77–78, 1996. 10. Centers for Medicare & Medicaid Services: Central Office Investigation Logs, June 2001. Washington, DC: Centers for Medicare & Medicaid Services, 2001. *11. Bitterman RA: Providing Emergency Care Under Federal Law: EMTALA. Dallas: American College of Emergency Physicians, 2000. 12. Testimony of Rep. Pete Stark (D–CA), co-sponsor of EMTALA. Congressional Record 13903, October 23, 1985. 13. Testimony of Sen. David Durenberger (R–MN). Congressional Record 13903, October 23, 1985. 14. Nolan L, Vaquerano L, Regenstein M, Jones K: An assessment of the safety net in Phoenix, Arizona. In Walking a Tightrope: The State of the Safety Net in 10 U.S. Communities. Washington, DC: George Washington University School of Public Health and Health Services, Urgent Matters Program, 2004. 15. Richardson LD, Hwang U: America’s health care safety net: intact or unraveling? Acad Emerg Med 8:1056–1063, 2001. 16. Fields W (ed): Defending America’s Safety Net: 1998–99 Safety Net Task Force Report. Dallas: American College of Emergency Physicians, 1999. 17. Shactman D, Altman SH: Utilization & overcrowding of hospital emergency departments. Paper presented at the Council on the Economic Impact of Heath System Change, January 2002, Waltham, MA. 18. Medicare Modernization Act of 2003, PL 108-173, Sec. 1011: Payment for EMTALA services for undocumented aliens. 19. American Hospital Association: Annual Survey of Hospitals, 2003. Chicago: American Hospital Association, 2003.

*Selected readings.

Chapter 150 — Emergency Medical Treatment and Labor Act (EMTALA) 20. American College of Emergency Physicians: Fact Sheet: Costs of Emergency Care. Dallas: American College of Emergency Physicians, 2003. 21. Vanlandingham B: On-Call Specialist Coverage in U.S. Emergency Departments—ED Director Survey. Dallas: American College of Emergency Physicians, 2004. 22. Johnson LA, Taylor TB, Lev R: The emergency department on-call backup crisis: fi nding remedies for serious public health problems. Ann Emerg Med 37:495–499, 1999. 23. Bitterman RA: Explaining the EMTALA paradox. Ann Emerg Med 40:470–475, 2002.

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24. Burditt v U.S. Department of Health and Human Services, 934 F2d 1362 (5th Cir 1991). 25. Centers for Medicare & Medicaid Services: Appendix V. Interpretive Guidelines. In State Operations Manual. Washington, DC: Centers for Medicare & Medicaid Services, 2004. 26. Centers for Medicare & Medicaid Services: Revised Appendix V. Interpretive Guidelines: Responsibilities of Medicare Participating Hospitals in Emergency Cases—Introductory Letter, May 13, 2004. In State Operations Manual. Washington, DC: Centers for Medicare & Medicaid Services, 2004.

Chapter 151 Issues of Consent, Confidentiality and Minor Status Cynthia R. Jacobstein, MD, MSCE

Key Points Consent for medical care of minors may be waived in four general situations: emergency need for care, emancipated minor status, conditions covered by minor treatment statutes, and cases involving mature minor doctrines. Minor treatment statutes and definitions of emancipation vary from state to state. The emergency physician should be familiar with the specific regulations of his or her state(s) of practice. Minors are more likely to seek health care when they are assured of confidentiality. The provision of confidential care, when appropriate, should be practiced in the emergency department treatment of minors. Psychosocial assessment is a key portion of the emergency department evaluation of most minors.

Introduction and Background Minors commonly present to the emergency department (ED) for medical care. While adult guardians frequently accompany them, minors may also seek care in the ED on their own or without legal guardians. A 1991 study looking at ED visits by minors to pediatric and general EDs found that approximately 3% of the visits by minors were unaccompanied.1 More recently, it has been estimated that this number may be even higher.2 In addition, the reasons for which minors seek care in the ED often involve complex psychosocial issues, such as sexually transmitted infection (STI) or undiagnosed pregnancy. Thus, it is imperative that the emergency physician is knowledgeable about the issues related to consent in the treatment of minors. A minor is defined as an individual who is younger than the age of consent. This age is 18 years in all but four states.3 It is generally expected that informed consent by a parent or 1062

legal guardian will be obtained prior to medical treatment of minors. This requirement is not always easily or readily accomplished in the ED setting as minor patients may present alone or with adults other than their parents, such as teachers or day care providers. Consent for medical care of minors may be waived for multiple reasons. Minors may be treated without the consent of a parent or guardian if they present with an emergency medical condition.2-8 Emergency medical conditions include those with potential threat to life or limb, as well as conditions in which extreme pain is present or in which the potential for a harmful outcome exists if the condition is not immediately treated. Furthermore, there are a number of presenting complaints or conditions for which minors may seek and be granted health care without parental consent. These categories include mental health care; testing and treatment for STIs, including human immunodeficiency virus; contraceptive services; and drug and alcohol dependency treatment.2-5,9 It is important to note that there are state-by-state variations with respect to the provision of confidential care for these treatment categories. The ED physician should be familiar with the laws of his or her state of practice regarding the treatment of such conditions. The GovSpot web site (Table 151–1) or individual state government web sites may serve as resources for this information. The Guttmacher Institute web site includes a table that lists the specific consent regulations for all 50 states.3 A subset of minors who may give their own consent for medical care are emancipated minors. Emancipated minors have living situations that suggest some degree of independence.2-6,8-10 Examples of reasons for emancipation include marriage, military service, legal ruling, financial independence and residence apart from parents, and parenthood. As with the specific medical conditions for which minors may seek care without parental consent, the definition of emancipation varies from state to state. The GovSpot web site (see Table 151–1) or individual state government web sites may serve as resources for this information. A further category of minors who may be allowed to consent to medical care is that of the mature minor.2-7,9,10 A mature minor is generally 14 years of age or older and deemed mature enough to understand the risks, benefits, and treatment options of a given medical condition. Other factors

Chapter 151 — Issues of Consent, Confidentiality and Minor Status

Table 151–1

Web Sites/Links to Guidelines, Policies, and Laws on Minor Consent Issues

Web Site

Organization

www.ama-assn.org

American Medical Association (click on Policy Finder) American Academy of Pediatrics Society of Academic Emergency Medicine The Guttmacher Institute: “The Alan Guttmacher Institute (AGI) is a nonprofit organization focused on sexual and reproductive health research, policy analysis and public education.” “GovSpot.com is a non-partisan government information portal designed to simplify the search for the best and most relevant government information online.”

www.aap.org www.saem.org www.guttmacher.org

www.govspot.com

Note: The Guttmacher Institute site is included as a source of factual reference material only and does not represent the opinions of the authors and editors of this text.

that should be considered when deciding if a patient qualifies as a mature minor include the seriousness of the illness and the risks and benefits of potential therapies. The provision of confidentiality in the treatment of minors in the ED is of utmost importance. The American Medical Association published a guideline for confidential health services for adolescents that outlines many of the important issues and recommendations regarding this topic.11 In addition, a number of medical societies, including the American College of Obstetricians and Gynecologists, the American Academy of Pediatrics, and the American Academy of Family Physicians, support the provision of confidentiality to adolescents seeking health care.12 The American College of Emergency Physicians also recognizes the importance of confidentiality in patient care but refers to confidentiality and the care of minors as a “problem area.”13,14 Adolescents are more likely to seek medical care and provide a complete and true history if their confidentiality is respected.11,15 Parents or guardians should be asked to leave the adolescent patient’s room when sensitive areas of the history are being obtained. A discussion of the availability and limits of confidentiality should be held with all minors and their guardians prior to asking potentially personal information as part of the medical history. Reasons that confidentiality may be breeched include cases of potential injury to self (suicidality) or others (homicidality) or abuse. These exceptions should be included in discussions of confidentiality.

Issues While the provision of confidentiality is of utmost importance to minors seeking care in the emergency department, situations often arise in which inclusion of a parent or guardian is essential to ensuring the best care for the minor. One example of such a scenario is the new diagnosis of pregnancy in a young adolescent. The treating physician may believe that it is in the minor’s best interest to involve a mature adult

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in the ongoing evaluation and care of such an issue. In cases such as this, the emergency physician should try to work with the teen to find a way to discuss the diagnosis with a parent or guardian. Possible solutions include having the physician tell the parent about the diagnosis with the adolescent’s permission, involving another mature relative (e.g., older sister or aunt) who may help the minor with the issues at hand, or involving a social worker to help with the discussion and follow-up. Other situations in which confidentiality may be inadvertently breached involve events that occur after the minor has been discharged from the ED. When there are pending test results at the time of discharge (e.g., STI results), it is important to discuss a follow-up plan with the adolescent. This may involve obtaining a mobile phone or pager number or some other way to reach the teen directly to discuss test results. Adolescent patients who are using the family insurance card should also be informed that their parents or guardians might receive an itemized bill that may contain specific information about the care provided, such as pregnancy or STI testing. One difficult situation that may arise in the care of minors in the ED is the request by a parent or guardian to have their child tested for drug use. There are some situations in which ED testing for drug use is appropriate. It is reasonable to test for substance use when the goal to be achieved is the diagnosis of and subsequent referral for treatment for substance abuse. In such cases, it is expected that the adolescent would give informed consent regarding the testing to be performed. In general, involuntary testing in an adolescent who is thought to be capable of making informed judgments is not approved or recommended by the American Academy of Pediatrics.16 Involuntary testing may be considered in cases in which the minor “lacks decision-making capacity” or in which “there are strong medical indications or legal requirements to do so.”16 Medical need for involuntary drug testing implies that identification of a particular substance would potentially avoid harm to the affected individual.

Solutions The psychosocial assessment of minors in the ED is an extremely important part of their medical care. A thorough psychosocial interview often uncovers significant stressors or problems that might not otherwise be brought up by the adolescent patient, including but not limited to depression and suicidality. The mnemonics HEADSS (home, education, activities, drug use and abuse, sexual behavior, and suicidality and depression) and SHADSSS (school, home, activities, depression/self-esteem, substance abuse, sexuality, and safety) are helpful reminders of the important issues to be considered and discussed when providing medical care to minors in the emergency department.17,18 The emergency physician must decide how much of the psychosocial assessment is necessary for any given patient care episode. At a minimum, it is important to consider the topics of safety, depression, and suicidality.

Summary Treatment of minors in the ED often requires the emergency physician to consider and apply a number of legal and ethical

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principles that are unique to this patient population. The emergency physician needs to be familiar with consent and confidentiality issues with respect to the treatment of minors. These issues take on even greater importance with a number of more sensitive patient complaints, such as STIs, pregnancy, and mental health issues. It is vital that the physician be aware of the specific exceptions to standard consent issues when a minor presents for emergency care so that these may be incorporated into practice. Likewise, the importance of confidential care for adolescent minors, when appropriate, cannot be overemphasized. However, this should not preclude involving a parent or responsible adult in the care of minors when it is important to ensure the best possible outcome for the given problem. The emergency physician may need to work with the teen and other support personnel to find the best way to involve an adult in the care when it is deemed necessary. REFERENCES 1. Treloar DJ, Peterson E, Randall J, et al: Use of emergency services by unaccompanied minors. Ann Emerg Med 20:297–301, 1991. *2. American Academy of Pediatrics, Committee on Pediatric Emergency Medicine: Consent for emergency medical services for children and adolescents. Pediatrics 111:703–706, 2003. 3. Boonstra H, Nash E: Minors and the right to consent to health care. Guttmacher Rep Public Policy 3:4–8, 2000.

*Selected readings.

*4. Kassutto Z, Vaught W: Informed decision making and refusal of treatment. Clin Ped Emerg Med 4:285–291, 2003. 5. Jacobstein CR, Baren JM: Emergency department treatment of minors. Emerg Med Clin North Am 17:341–352, 1999. 6. Guertler AT: The clinical practice of emergency medicine. Emerg Med Clin North Am 15:303–313, 1997. 7. Sullivan DJ: Minors and emergency medicine. Emerg Med Clin North Am 11:841–851, 1993. 8. Tsai AK, Schafermeyer RW, Kalifon D, et al: Evaluation and treatment of minors: reference on consent. Ann Emerg Med 22:1211–1217, 1993. 9. Kuther TL: Medical decision-making and minors: issues of consent and assent. Adolescence 38:343–358, 2003. 10. English A: Treating adolescents: legal and ethical considerations. Med Clin North Am 74:1097–1112, 1990. *11. American Medical Association, Council on Scientific Affairs: Confidential health services for adolescents. JAMA 269:1420–1424, 1993. 12. American College of Obstetricians and Gynecologists: ACOG Statement of Policy: Confidentiality in Adolescent Health Care. Washington, DC: American College of Obstetricians and Gynecologists, 1988. 13. American College of Emergency Physicians: Patient confidentiality. Ann Emerg Med 24:1209, 1994. 14. Larkin GL, Moskop J, Sanders A, et al: The emergency physician and patient confidentiality: a review. Ann Emerg Med 24:1161–1167, 1994. 15. Proimos J: Confidentiality issues in the adolescent population. Curr Opin Pediatr 9:325–328, 1997. 16. American Academy of Pediatrics, Committee on Substance Abuse: Testing for drugs of abuse in children and adolescents. Pediatrics 98:305–307, 1996. 17. Cohen E, Mackenzie RG, Yates GL: HEADSS, a psychosocial risk assessment instrument: implications for designing effective intervention programs for runaway youth. J Adolesc Health 12:539–544, 1991. 18. Clark LR, Ginsburg KR: How to talk to your teenage patients. Contemp Adolesc Gynecol Winter:23–27, 1995.

Chapter 152 Disaster Preparedness for Children Stuart B. Weiss, MD and Ryan S. McCormick, BS, EMT-P

Key Points Physicians caring for children during a mass casualty event will face challenges due to the unique anatomic, physiologic, cognitive, and behavioral characteristics of children. The needs for pediatric mass casualty care are often inadequately addressed in hospital and community disaster plans. All hospitals must adopt an incident management system that seamlessly integrates with community response agencies. All facilities are equally at risk to receive large influxes of children during a disaster, so all emergency department staff must receive adequate education and training in mass casualty pediatric care.

carry a weapon (knife, gun, or club) to school and 5% carried a gun to school in the past month.13 With large numbers of children involved in natural disasters and increasing risk to children from terrorist events or school violence, it is imperative that emergency physicians play an active role in developing hospital and community plans that include policies and procedures for delivering care to large numbers of affected children Emergency Medical Services (EMS) field triage may not distribute children to the correct receiving facility. Inadequate or incorrect triage of children may result in a mismatch of injuries to health care assets. In the Avianca Airline crash of 1990, for example, pediatric survivors were neither adequately triaged nor transported to appropriate facilities that could have optimized their care.14

Issues Unique Characteristics of Children in Disasters Children are uniquely susceptible to terrorist events and disasters due to a combination of anatomic, physiologic, developmental, and psychological characteristics.2,15,16 Additional factors that complicate pediatric care include caregiver issues and facility issues.

Introduction and Background

Anatomic and Physiologic Differences

Children are commonly involved as victims of both natural and man-made disasters. However, in many instances, hospital and community planners have not considered disasters that generate large numbers of sick or injured children.1 Hospitals run exercises utilizing adult patient scenarios and rarely exercise with scenarios that include a pediatric patient surge. Government plans often lack specific sections that deal with the unique characteristics of mass casualty care for children.2 As children constitute approximately 29% of the population in the United States, we can expect significant pediatric casualties in natural disasters.3-11 The growing problem with school violence has led to an increase in pediatric mass casualty events as well. In Columbine High School in Littleton, Colorado, on April 20, 1999, two students utilizing a combination of guns and homemade improvised explosive devices killed 14 students, seriously injured 23 others, and terrorized an entire community.12 Since then, concern about school violence and incidents involving weapons being brought into schools has been increasing. It is reported that 17% of high school students

Children are shorter and therefore are closer to the ground, resulting in high doses of some chemicals and radiation. Many chemical agents (including some that are commonly listed as potential terrorist agents, such as Sarin, mustard, chlorine, and phosgene) are heavier than air16 and would have a higher concentration closer to ground level. In addition, radiologic fallout material settles on the ground, emitting more radiation to children whose vital organs are closer to the particles. With certain types of cancer (e.g., thyroid cancer), children are especially more susceptible than adults.17 In both of these cases, children would receive a higher dose of the agent than adults. Children also have a proportionately larger body surface area–to-mass ratio than adults. For those agents that are absorbed through the skin, this results in a higher concentration per kilogram in an exposed child. Additionally, due to the larger surface area, children have a much higher risk for rapid body cooling and hypothermia if cold water is used during decontamination or if rapid drying and sheltering do not occur when decontamination is performed in cold environments. 1065

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Children’s skin is less keratinized than adults’ skin, resulting in potentially greater injury from vesicants and corrosives. In addition, children have an increased respiratory rate as compared with adults. This increased minute ventilation results in more rapid uptake and higher accumulated doses of a chemical, biologic, or radiologic agent by the lungs as well as a more rapid onset of effects. Developmental and Psychological Differences Due to physical developmental limitations, infants, toddlers, and young children may lack the motor skills to escape from the site of the disaster. For example, in the 2004 disaster in India and East Africa caused by tsunamis, young children were unable to grab onto stationary objects to prevent themselves from being swept underwater. Older children who may possess the motor skills to walk or evade the disaster may lack the cognitive ability to understand the events around them or appreciate the need to flee. Older children may also be frightened by the circumstances around them and refuse to cooperate with rescuers or will not take necessary protective actions, such as wearing a mask. Finally, curious children may actually migrate toward an event to better see a pretty colored gas, or to investigate noise or other chaos. Caregiver Issues Efforts are often made to keep children with their caregivers. This may result in pediatric emergency departments caring for adult patients or adult emergency departments caring for pediatric patients. In addition, most children older than 4 to 5 years spend most of their days away from their parents or caregivers in school or day care. In the devastating daytime earthquake in Armenia in December 1988, approximately 32,000 children were temporarily evacuated and had to be reunited with their parents at a later time.18 Tremendous logistical challenges are involved with reuniting displaced children with their parents. Young children may not know their last name or address and may not have any identifying items on them. Finally, issues related to treating minors without parental consent must be addressed in advance. Operational Issues In a large-scale disaster, especially one with a multiagency response, an incident management system or incident command system (ICS) must be utilized to manage the many problems that arise and the varied resources that come into play. Several incident management systems have been developed and utilized. The system that has been most widely adopted for health care facilities has been the Hospital Incident Command System (HICS). It is vital that hospital systems adopt some type of formal incident management system so that they seamlessly integrate into the community ICS structure. NIMS and ICS The National Incident Management System (NIMS) is a federally mandated structure designed to assist responders with coordination and resource management during a disaster. One component of NIMS is the ICS, a standardized framework for organizing resources during an event. ICS was developed for the fire service in the 1970s based on sound, tested business practices adapted for the changing needs of emergency services. This version of ICS (fire ICS) has been

widely adopted by fire departments and other public agencies across the country. To meet the needs of hospitals, in 1993 the HICS was developed.19 Fire ICS and HICS are based on many of the same principles; however, HICS applies only to hospitals and was not widely adopted by other response agencies. Under a federal mandate issued in 2003, all response agencies must adopt the NIMS.20 The HICS system is currently being adapted to meet NIMS requirements.21 ICS in Hospitals During a public health emergency or disaster, hospitals may find themselves inundated with patients, medical professionals, and resources. If each is not managed effectively, chaos, misuse of resources, or poor patient care may result. Management practices and systems in place during daily operations may not be adequate to manage a disaster, which often requires higher levels of coordination, control, and communication. It also may be necessary for hospital leadership to work with and direct the actions of personnel and agencies they do not typically oversee. In order to effectively manage incidents, hospital leadership must utilize a standardized management and organizational system such as NIMS or HICS. The use of such a system will allow for easier integration of outside resources and leadership into the hospital organizational structure. Several regulatory bodies require the adoption of an ICS. The Joint Commission on Accreditation of Healthcare Organizations requires that facilities adopt a command structure that links with that of the community.22 Also, while the 2003 federal NIMS mandate does not specifically require hospitals to adopt NIMS, it does link future federal funding to NIMS compliance. Use of an ICS by hospital personnel assures that the hospital will better interface with local, state, and federal agencies during a crisis. Training in NIMS and the ICS is available in many formats, including self-study and on-line courses from the Federal Emergency Management Agency at http://www.fema.gov/nims. Benefits of Adopting Standardized ICS There are several advantages to adopting a standard ICS. First, an ICS utilizes a common vocabulary and terminology across all responding agencies. This eliminates any confusion about job titles and responsibilities. Similar positions in fire, police, EMS, or the hospital have the same job title and similar responsibilities. Secondly, the ICS creates a uniform reporting hierarchy and employs a standardized set of job action sheets. HICS, for example, manages hospital responsibilities through predefined jobs with clearly written job action sheets. Job action sheets clearly outline the roles and responsibilities of each position in the HICS structure. When disasters occur, designated responders can quickly read an assigned job action sheet and immediately understand what is required of them. Finally, the ICS provides a method for expanding and contracting the command staff based on the requirements of the crisis. Facility Issues While children make up 29% of the U.S. population,7 they are essentially healthy and do not utilize a similar proportion of health care resources. In addition, while pediatric cases

Chapter 152 — Disaster Preparedness for Children

make up approximately 20% of emergency department volume,23 few facilities have excess pediatric capacity to cover a pediatric patient surge. This results in fewer pediatric beds, fewer pediatric specialists, and less overall experience in pediatric critical care. Thus, in many regions of this country, a true pediatric disaster would result in a critical shortage of pediatric resources.1 Patient Care Issues

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Can patient walk? Priority 3/ refer patient to CCP move on to next patient

Yes

No

Is patient breathing?

Check respirations >30 or 51

1 2 3

0.08–0.13 0.08–0.13 0.11 or less

24–46 24–46 35 or less

• Atropine: 0.05 mg/kg IV, IM (min. 0.1 mg, max. 5 mg), repeat q2–5min prn for marked secretions, bronchospasm • Pralidoxime: 25 mg/kg IV, IM* (max. 1 g IV; 2 g IM), may repeat within 30–60 min prn, then again q1h for 1 or 2 doses; 0.2 mg/kg prn for persistent weakness, high atropine requirement • Diazepam: 0.3 mg/kg (max. 10 mg) IV • Lorazepam: 0.1 mg/kg IV, IM (max. 4 mg) • Midazolam: 0.2 mg/kg (max. 10 mg) IM prn for seizures or severe exposure *Pralidoxime is reconstituted to 50 mg/ml (1 g in 20 ml water) for IV administration, and the total dose is infused over 30 minutes, or may be given by continuous infusion (loading dose 25 mg/kg over 30 minutes, then 10 mg/kg/hr). For IM use, it might be diluted to a concentration of 300 mg/ml (1 g added to 3 ml water—by analogy to the U.S. Army’s MARK I autoinjector concentration), to effect a reasonable volume for injection. Adapted from Henretig FM, Cieslak TJ, Eitzen EM: Biological and chemical terrorism. J Pediatr 141:311–326, 2002.

this person is removed from the source of radiation, they are no longer subject to irradiation. A good example of this would be patients who have had a chest radiograph taken. While they are exposed to x-ray radiation, they are not contaminated, are not radioactive, and do not pose a threat to health care workers. These patients do not require decontamination as they do not have any radioactive material on them. Contaminated victims, in contrast, actually have radioactive material on them and continue to be exposed to radiation even when removed from the event site. They may contaminate other surfaces or health care workers and must be decontaminated to reduce the risk to themselves and others. As with adults, the first step in decontamination of children is removing clothing. In many cases, this will eliminate up to 90% of contaminated particles. Contaminated clothing must be moved as far away from health care workers and victims as possible so as not to further expose individuals to radiation. It is important to remember that putting this clothing in a plastic bag is not an adequate shield from the radiation. In addition, it is important not to create a large pile of contaminated clothing as this will create a large irradiating source. The initial care of the radiologically injured patient involves treating any associated trauma or medical problems. Caring for his or her radiation injuries is secondary to the other medical needs. One caveat to remember is that all necessary surgery must be completed within 48 hours of a large exposure before immunosuppression and wound healing impairment prevents surgical intervention for up to 3 months.41 Table 152–5 lists commonly used treatments for radiation injuries. Consultation in the care of radiologically injured patients can be obtained at any time from the Radiation Emergency Assistance Center/Training Site at the Oak Ridge Institute for Science and Education at 1-865-576-1005.

Table 152–5

Radionuclide Treatment Options

Radionuclide

Radioprotectant

Americium (241Am)

Diethylenetriamine pentaacetic acid (DTPA) DTPA Prussian blue, sodium polystyrene sulfonate Laxatives* DTPA Potassium iodide (KI) Unknown DTPA Common antacids, barium sulfate Common antacids, barium sulfate DTPA Prussian blue Common antacids Filgrastim, amifostine, antiemetics, Neumune, 5-AED Laxatives, sodium polystyrene sulfonate

Californium (252Cf) Cesium (137Cs) Cobalt ( 60Co) Curium (244Cm) Iodine (131I) Iridium (192Ir) Plutonium (238Pu; 239Pu) Radium (226Ra) Strontium (90Sr) Technetium (99mTc) Thallium (201Tl) Uranium (235U; 238U) High radiation dose Gastrointestinal uptake of radionuclides

*Little information is available on treatment options. One should also consider EDTA, N-acetyl-L-cysteine, or penicillamine. From New Jersey Center for Public Health Preparedness: Radiological Countermeasures: Candidates for Inclusion in a State Stockpile. White paper, 2005.

There are some additional issues concerning potassium iodide (KI). Many people are under the misconception that KI is indicated as a general radiation antidote. There has been much press about this medication in the past few years. The only indication for this medication is in the prevention of thyroid cancer in releases of radioactive iodine (131I). Radioactive iodine is most likely to be released from a nuclear reactor accident. For this reason, the Nuclear Regulatory Commission has directed that KI be included in the

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emergency planning for the residents in areas 10 miles around a nuclear plant.42 This is in order to facilitate the rapid administration of KI to affected residents. It is unlikely that radiologic dispersal devices or “dirty bombs” will contain 131I due to the difficulty in obtaining large quantities of radioactive iodine and the short half-life of the material. Therefore, in these exposures, KI is not indicated. KI blocks the uptake of radioactive iodine by saturating the thyroid with nonradioactive iodine. In order for KI to be effective, the correct dose must be taken quickly, preferably within 2 hours of exposure. The protective effect of KI lasts approximately 24 hours, so additional doses may be required if continuing exposure to radioactive iodine is expected. Current recommendations for the safe and effective use of KI to prevent the uptake of radioiodine by the thyroid are based on a review of data from the Chernobyl nuclear accident in 1986 where large amounts of 131I were released into the atmosphere. Following the event, thyroid cancers in Belarus, Ukraine, and the Russian Federation skyrocketed. In neighboring Poland, where KI was used in 10.5 million children less than 16 years old and in 7 million adults, there was a significant decrease in cancer rates. As the risk of thyroid cancer is inversely proportional to age, it is essential to make KI available to children.43 Table 152–6 lists the current FDA recommendations for the use of KI during an emergency. The following caveats should be kept in mind: 1. Neonates who receive KI must be monitored for hypothyroidism by measuring thyroid-stimulating hormone

Table 152–6

and free thyroxine. Thyroid hormone replacement must be initiated in cases in which hypothyroidism develops to protect critical neurologic development. 2. Pregnant females should be given KI for their own protection and for that of the fetus, as iodine readily crosses the placenta. However, because of the risk of blocking fetal thyroid function with excess stable iodine, repeat dosing with KI should be avoided. Lactating females should be given KI for their own protection and potentially to reduce the concentration of radioiodine in their breast milk, but not as a means to deliver KI to infants, who should get their KI directly. Iodine as a component of breast milk may also pose a risk of hypothyroidism in nursing neonates. Therefore, repeat dosing of KI should be avoided in lactating mothers, except during continuing severe contamination. If repeat dosing of the mother is necessary, the nursing neonate should be monitored for hypothyroidism as noted above. Tables 152–7 and 152–8 outline methods for preparing KI solutions for children using the 130-mg tablets and the 65-mg tablets, respectively.44 During an emergency, high accuracy in dosing is less important than rapidly administering KI to affected populations.

Solutions Caring for children during a mass casualty event or disaster poses many challenges. Whether childhood casualities are the result of an accident, a natural phenomenon, or an inten-

Threshold Thyroid Radioactive Exposures and Recommended Doses of KI for Different Risk Groups—U.S. Food and Drug Administration (FDA)

Adults >40 yr Adults >18–40 yr Pregnant or lactating women Adolescents >12–18 yr* Children >3–12 yr Over 1 mo–3 yr Birth–1 mo

Predicted Thyroid Exposure(cGy)

KI Dose (mg)

# of 130-mg Tablets

# of 65-mg Tablets

≥500 ≥10 ≥5 ≥5 ≥5 ≥5 ≥5

130 130 130 65 65 32 16

1 1 1 1 /2 1 /2 1 /4 1 /8

2 2 2 1 1 /4 1 /2 1 /4

*Adolescents approaching adult size (≥ 70 kg) should receive the full adult dose (130 mg). The protective effect of KI lasts approximately 24 hours. For optimal prophylaxis, KI should therefore be dosed daily, until a risk of significant exposure to radioiodines by either inhalation or ingestion no longer exists. Individuals intolerant of KI at protective doses, and neonates and pregnant and lactating women (in whom repeat administration of KI raises particular safety issues; see below) should be given priority with regard to other protective measures (i.e., sheltering, evacuation, and control of the food supply). Note that adults over 40 need to take KI only in the case of a projected large internal radiation dose to the thyroid (>500 cGy) to prevent hypothyroidism. These recommendations are meant to provide states and local authorities as well as other agencies with the best current guidance on safe and effective use of KI to reduce thyroidal radioiodine exposure and thus the risk of thyroid cancer. FDA recognizes that, in the event of an emergency, some or all of the specific dosing recommendations may be very difficult to carry out given their complexity and the logistics of implementation of a program of KI distribution. The recommendations should therefore be interpreted with flexibility as necessary to allow optimally effective and safe dosing given the exigencies of any particular emergency situation. In this context, we offer the following critical general guidance: across populations at risk for radioiodine exposure, the overall benefits of KI far exceed the risks of overdosing, especially in children, though we continue to emphasize particular attention to dose in infants. These FDA recommendations differ from those put forward in the World Health Organization (WHO) 1999 guidelines† for iodine prophylaxis in two ways. WHO recommends a 130-mg dose of KI for adults and adolescents (over 12 years). For the sake of logistical simplicity in the dispensing and administration of KI to children, FDA recommends a 65-mg dose as standard for all school-age children while allowing for the adult dose (130 mg, 2 × 65-mg tablets) in adolescents approaching adult size. The other difference lies in the threshold for predicted exposure of those up to 18 years of age and of pregnant or lactating women that should trigger KI prophylaxis. WHO recommends a threshold of 1 cGy for these two groups. As stated earlier, FDA has concluded from the Chernobyl data that the most reliable evidence supports a significant increase in the risk of childhood thyroid cancer at exposures of 5 cGy or greater. † World Health Organization: Guidelines for Prophylaxis Following Nuclear Accidents: Update. Geneva: World Health Organization, 1999. Modified from Food and Drug Administration, Center for Drug Evaluation and Research: Guidance: Potassium Iodide as a Thyroid Blocking Agent in Radiation Emergencies. Washington, DC: Food and Drug Administration, 2001.

Chapter 152 — Disaster Preparedness for Children

Table 152–7

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Preparation of Potassium Iodide Solution for Children

Preparation Using 130-mg Potassium Iodide Tablet 1. Put one 130-mg potassium iodide tablet into a small bowl and grind it into a fine powder using the back of the metal teaspoon against the inside of the bowl. The powder should not have any large pieces. 2. Add four teaspoonfuls (20 ml) of water to the potassium iodide powder in the small bowl. Use a spoon to mix them together until the potassium iodide powder is dissolved in the water. 3. Add four teaspoonfuls of raspberry syrup, low-fat chocolate milk, juice, or flat soda* to the potassium iodide powder and water mixture described in Step 2. The amount of potassium iodide in the drink is 16.25 mg per teaspoon (5 ml). Dosing Guidelines (This is the amount for one dose. Repeat daily doses may be indicated.) Newborn–1 mo of age: Give 1 teaspoon (5 ml) 2 mo–3 yr of age: Give 2 teaspoons (10 ml) 4–17 yr of age: Give 4 teaspoons (20 ml) Children over 70 kg (154 pounds) should receive one 130-mg tablet or 8 teaspoons. Notes *To see what worked best to disguise the taste of potassium iodide, FDA asked adults to taste the following six mixtures of potassium iodide and drinks: water, low-fat white milk, low-fat chocolate milk, orange juice, flat soda (e.g., cola), and raspberry syrup. The mixture of potassium iodide with raspberry syrup disguised the taste of potassium iodide best. The mixtures of potassium iodide with low-fat chocolate milk, orange juice, and flat soda generally had an acceptable taste. Low-fat white milk and water did not hide the salty taste of potassium iodide. Potassium iodide in any of the six drinks listed above and in infant formulas will keep for up to 7 days in the refrigerator. FDA recommends that the potassium iodide drink mixtures be prepared weekly; unused portions should be discarded.

Table 152–8

Preparation of Potassium Iodide Solution for Children

Preparation Using 65-mg Potassium Iodide Tablet 1. Put one 65-mg potassium iodide tablet into a small bowl and grind it into a fine powder using the back of the metal teaspoon against the inside of the bowl. The powder should not have any large pieces. 2. Add four teaspoonfuls (20 ml) of water to the potassium iodide powder in the small bowl. Use a spoon to mix them together until the potassium iodide powder is dissolved in the water. 3. Add four teaspoonfuls of raspberry syrup, low-fat chocolate milk, juice, or flat soda* to the potassium iodide powder and water mixture described in Step 2. The amount of potassium iodide in the drink is 8.125 mg per teaspoon (5 ml). Dosing Guidelines (This is the amount for one dose. Repeat daily doses may be indicated.) Newborn–1 mo of age: Give 2 teaspoons (10 ml) 2 mo–3 yr of age: Give 4 teaspoons (20 ml) 4–17 yr of age: Give 8 teaspoons (40 ml) or one 65-mg tablet Children over 70 kg (154 pounds) should receive two 65-mg tablet or 16 teaspoons. Notes *To see what worked best to disguise the taste of potassium iodide, FDA asked adults to taste the following six mixtures of potassium iodide and drinks: water, low-fat white milk, low-fat chocolate milk, orange juice, flat soda (e.g., cola), and raspberry syrup. The mixture of potassium iodide with raspberry syrup disguised the taste of potassium iodide best. The mixtures of potassium iodide with low-fat chocolate milk, orange juice, and flat soda generally had an acceptable taste. Low-fat white milk and water did not hide the salty taste of potassium iodide. Potassium iodide in any of the six drinks listed above and in infant formulas will keep for up to 7 days in the refrigerator. FDA recommends that the potassium iodide drink mixtures be prepared weekly; unused portions should be discarded.

tional attack, there are several general planning principles that must be addressed when preparing for pediatric mass casualties: 1. Understand how the facility fits into the overall emergency management plan for the community. Most communities in this country have a Local Emergency Planning Committee. This committee is responsible for developing the emergency management plans for the community. Assess whether there is adequate representation of medical professionals on this committee and, more specifically, medical professionals with pediatric expertise. In addition, have planning discussions with local industry. It is important to determine what community medical risks are posed by industry and what emergency plans exist. There have been occasions when

local hospitals have been included in industry emergency response plans without their knowing it. Finally, review the hospital disaster command structure to guarantee that it utilizes an ICS that is NIMS compliant, to seamlessly interface with local response agencies. 2. Review community plans to ensure that the needs of pediatric patients will be met. Unfortunately, for a variety of reasons, pediatric needs are often overlooked in government and community planning. It is vital that emergency physicians bring their expertise in caring for children to the planning table. In addition, children spend the majority of their days in school. It is vital that adequate plans are in place to address the care of children when they are not with their parents.

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3. Review hospital plans to ensure that they address the needs of pediatric patients. Apply the plan to a fictitious influx of children during an exercise to assess how it functions. Train the staff so they are comfortable in mass casualty care of children. If the emergency department is segregated into adult and pediatrics sections, ensure that all staff are cross-trained to care for all patients. Finally, educate and drill the adult and pediatric emergency department staff in pediatric disaster triage. 4. Review antidotes for the most likely agents and plan how to administer them to pediatric patients. If premade kits are not available for children, develop plans to obtain necessary medications and devise ways to formulate them for administration to children. This may involve having the pharmacy mix antidotes into cherry syrup, and crush pills. Determine the hazards in the community and plan for any needed medications to treat victims of these hazards. 5. Develop community-wide transfer agreements and procedures to distribute injured or sick children across a region. Consider matching needed pediatric resources with the nature and severity of a child’s injuries. 6. Work with day care centers and schools to ensure that they have adequate disaster management plans in place. Check that those plans integrate into the community’s plans and the hospital’s plan. 7. Encourage family disaster planning. Many resources are available to help families plan for disaster. These resources can be downloaded from ready.gov or obtained from the American Red Cross.

Summary Children make up approximately 29% of our population and will invariably be involved in disasters. Many community disaster plans presently do not adequately address the needs of large numbers of critically injured or sick children. As discussed, there are distinctive characteristics and challenges involved in providing mass casualty care for children. It is imperative that emergency physicians share this information with local emergency planners to guarantee that community plans include policies and procedures to provide optimal care for childhood victims of disasters. REFERENCES *1. Freishtat RJ: Issues in children’s hospital disaster preparedness. Clin Pediatr Emerg Med 3:224–230, 2002. 2. Redlener I, Markenson D: Disaster and terrorism preparedness: what pediatricians need to know. Dis Mon 50:6–40, 2004. *3. American Academy of Pediatrics, Committee on Environmental Health and Committee on Infectious Disease: Chemical-biological terrorism and its impact on children: a subject review. Pediatrics 105:662– 670, 2000. 4. UNICEF Executive Director statement. New York Times, December 28, 2004. 5. United States Geological Survey: Most Recent Natural Disasters Were Not the Century’s Worst. Available at http://geography.about.com/ library/misc/blcenturyworst.htm (accessed December 31, 2004). 6. Azarian A: Baseline assessment of children traumatized by the Armenia earthquake. Child Psychol Hum Dev 29:29–41, 1996.

*Suggested readings.

7. U.S. Census Bureau: 2000 Census Data. Washington, DC: U.S. Census Bureau, 2000. 8. Hogan DE, Waeckerle JF: Emergency department impact of the Oklahoma City terrorist bombings. Ann Emerg Med 34:160–167, 1999. 9. Beslan School Crisis Assistance. Available at www.moscowhelp.org/en/ index.html (accessed December 30, 2004). 10. Satter D: A small town in Russia. Wall Street Journal, September 7, 2004. 11. Waisman Y, Aharonson-Daniel L, Mor M, et al: The impact of terrorism on children: a two-year experience. Prehosp Disaster Med 18:242– 248, 2003. 12. Timeline of Recent Worldwide School Shootings. Available at www. infoplease.com/ipa/a0777958.html 13. Centers for Disease Control and Prevention: Youth risk behavior surveillance. MMWR Mrob Mortal Wkly Rep 49:1–94, 2000. 14. Van Amerogen RH, Fine JS: The Avianca plane crash: an emergency medical system’s response to pediatric survivors of a disaster. Pediatrics 92:105–110, 1993. 15. White SR, Henretig FM: Medical management of vulnerable populations and co-morbid conditions of victims of bioterrorism. Emerg Med Clin North Am 20:365–392, 2002. *16. Franz DR, Sidell FR, Takafuji ET: Meciala Aspects of Chemical and Biological Warfare. In Textbook of Military Medicine, Part 1: Warfare, Weaponry, and the Casualty. Washington, DC: Borden Institute, Walter Reed Army Medical Center, 1997. 17. Food and Drug Administration: Center for Drug Evaluation and Research: Guidance: Potassium Iodide as a Thyroid Blocking Agent in Radiation Emergencies. Washington, DC: Department of Health and Human Services, 2001. 18. Azarian A, Skriptchenko-Gregorian V: Children in Natural Disasters: An Experience of the 1988 Earthquake in Armenia. American Academy of Experts in Traumatic Stress web site. Available at www.aaets.org/ arts/art38.htm *19. California Emergency Medical Services Authority: The Hospital Emergency Incident Command System. Available at http://www.emsa. cahwnet.gov/dms2/heics_main.asp (accessed January 14, 2004). 20. Bush GW: Management of domestic incidents. Homeland Security Presidential Directive, Feb. 28, 2003. Washington, DC: Department of Homeland Security. 21. California Emergency Medical Services Authority: The HEICS 4 Project. Available at http://www.emsa.cahwnet.gov/dms2/heics4project. asp 22. Joint Commission on the Accreditation of Healthcare Organizations: Emergency Management Standards, E.C.1.4 and E.C. 2.9.1. January 1, 2003. Available at http://www.jcrinc.com/subscribers/perspectives.asp? durki=2914&site=10&return=2897 (accessed January 2, 2005). 23. McCaig LF, Burt CW: National Hospital Ambulatory Medical Care Survey: 2002 emergency department summary. Adv Data (340):1–34, 2004. 24. Super G, Groth S, Hook R: START: A Triage Training Module. Newport Beach, CA: Hoag Memorial Hospital Presbyterian, 1984. 25. Romig LE: Pediatric triage: a system to JumpSTART your triage of young patients at MCIs. JEMS 27(7):52–63, 2002. 26. Henretig FM, Cieslak TJ, Eitzen EM: Biological and chemical terrorism. J Pediatr 141:311–326, 2002. 27. Centers for Disease Control and Prevention: Update: investigation of bioterrorism related anthrax and interim guidelines for clinical evaluation of persons with possible anthrax. MMWR Morb Mortal Wkly Rep 50:941–948, 2001. 28. Centers for Disease Control and Prevention: Investigation of anthrax associated with intentional exposure and interim public health guidelines. MMWR Morb Mortal Wkly Rep 50:889–893, 2001. 29. Torok TJ, Tauxe RV: A large community outbreak of salmonellosis caused by intentional contamination of restaurant salad bars. JAMA 278:389–395, 1997. *30. Centers for Disease Control and Prevention, Strategic Planning Group: Biological and chemical terrorism: strategic plan for preparedness and response. MMWR Morb Mortal Wkly Rep 49(RR-4):1–14, 2000. 31. Cieslak TJ: Bioterrorism: agents of concern. J Public Health Manag Pract 6(4):19–29, 2000. 32. Bowlware KL, Stull T: Antibacterial agents in pediatrics. Infect Dis Clin North Am 18:513–531, 2004. 33. American Academy of Pediatrics: Fluoroquinolones, tetracyclines. In Pickering LK (ed): 2000 Red Book: Report of the Committee on

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34. 35.

36. 37. 38.

Infectious Diseases, 25th ed. Elk Grove Village, IL: American Academy of Pediatrics, 2000, pp 645–646. Freifeld A, Pizzo P: Use of fluoroquinolones for empirical management of febrile neutropenia in pediatric cancer patients. Pediatr Infect Dis 16:140–145, 1997. Centers for Disease Control and Prevention: Update: interim recommendations for antimicrobial prophylaxis for children and breastfeeding mothers and treatment of children with anthrax. MMWR Morb Mortal Wkly Rep 50:1014–1016, 2001. Okumura T, Takasu N: Report on 640 victims of the Tokyo subway sarin attack. Ann Emerg Med 28:129–135, Aug 1996. Macintyre AG, Christopher GW, Eitzen E: Weapons of mass destruction events with contaminated casualties: effective planning for health care facilities. JAMA 283:242–249, 2000. Food and Drug Administration: FDA approves pediatric doses of AtroPen. Talk Paper 03-45, June 20, 2003. Washington, DC: Department of Health and Human Resources, 2003.

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39. AtroPen Package Insert NDA 17-106/S-028. Columbia, MD: Meridian Medical Technologies, 2004. 40. Amitai Y, Almog S, Singer R, et al: Atropine Poisoning in Children During the Persian Gulf Crisis: A National Survey in Israel. JAMA 268:630–632, 1992. 41. U.S. Army Soldier and Biological Chemical Command (SBCCOM): Domestic Preparedness Training Program (DPT-8), p M5-33. Natick, MA: SBCCOM. 42. U.S. Nuclear Regulatory Commission: Policy Issue Paper: Status of Potassium Iodide Activities (SECY-01-0208). Rockville, MD: U.S. Nuclear Regulatory Commission. 43. Food and Drug Administration: Potassium Iodide as a Thyroid Blocking Agent in Radiation Emergencies. December 2001. Available at http://www.fda.gov/cder/guidance/4825fnl.htm 44. Food and Drug Administration: Home Preparation Procedure for Emergency Administration of Potassium Iodide Tablets to Infants and Small Children. Available at http://www.fda.gov/cder/drugprepare/kiprep.htm

Chapter 153 Family Presence Mirna M. Farah, MD

Key Points Family presence during resuscitation and procedures meets the family’s emotional needs of being informed, feeling accepted, and being able to provide comfort to the patient. An organized and properly studied approach is essential to the success of a family presence program. Written guidelines that balance staff’s concerns about providing care and families’ need to be present are among the crucial initial steps towards establishing a family presence curriculum. A family support person is essential to assess and prepare family members prior to and after entering the treatment room.

Introduction and Background The concept of family presence during resuscitation emerged in the mid-1980s when the emergency department staff at a Michigan hospital questioned a policy that excluded families from the resuscitation room.1 Initially opinions about family presence were mixed; however, the trend of subsequent literature has moved toward acceptance of the process.2 Currently, several organizations promote family presence, including the American Academy of Pediatrics, the American Heart Association, the Emergency Nurses Association, and the federally funded Emergency Medical Services for Children program.3-6 Parents play an integral role in the health and well-being of their child. Supporting and integrating the family into the emergency care process is vital to meeting the full spectrum of the patient’s needs. The fear that family presence would hinder medical care can be eliminated by properly assessing and preparing families prior to entering the resuscitation room. The more experience health care providers (HCPs) have with family presence and dealing with distressed families, and the more comfort they have in their clinical skills, the higher the acceptance and success of family presence.

Issues There are several compelling reasons to consider offering the option for family presence (Table 153–1). Including the family 1076

in the care plan, promotes collaboration among medical providers, patients, and family members. Both pediatric patients and their parents are significantly less distressed when the parents are present during a procedure.7-9 Regardless of the patient’s condition, parents seem to focus on their child comforting role rather than the logistics of medical care.10 The patient becomes less anxious, and therefore more compliant, so the procedure has the potential to go more smoothly.11 Even if the parents decide not to be at their child’s bedside, knowing that they have that option fosters trust and positive communication. Even when the patient is likely to die, family presence remains extremely beneficial.11 Family presence allows parents to be by their loved one until the last minute. Parents can touch their child, express their love, and say good-bye while there is still a chance that the patient can hear. Family presence brings a sense of reality to the treatment efforts and clinical status of the patient, avoiding a prolonged period of denial.12 Parents can see for themselves the tremendous effort put into the resuscitation attempt, and this has far more meaning then being told: “Everything possible was done.”1 Family presence facilitates the grieving process, and may be one of the most powerful interventions that can be offered to a grieving family.1,13-16 The manner in which HCPs care for and respect the wishes of both the dying patient and their parents is crucial in helping the family accept the death and deal with the crisis. There are many perceived barriers to family presence.17 It often represents breaking a tradition. Family presence challenges basic assumptions and long-standing practices. In the past, parents were routinely excluded from visitation and were never permitted to view resuscitations. The more informed HCPs are about the process of family presence, the higher the acceptance for family presence.12,18-20 There are concerns that family presence may increase staff anxiety or hinder performance. Patient care is always a top priority, and it may be harder for a resuscitation team to work with an audience.1 Confidence in procedural and cardiopulmonary resuscitation (CPR) skills, and experience with family presence, quickly decrease the anxiety level.12 The majority of HCPs who offer family presence do not report a change in their performance or a change in the outcome of the procedure or CPR.7-9,11,12 Worries that family presence may distract staff or obstruct medical care are unfounded. Disruptions and occurrences of family members becoming physically involved in the resuscitation attempt have not been consistently reported.13,21 Most family members are awed by the activity in the resuscitation room and frequently have to be led to the bedside

Chapter 153 — Family Presence

Table 153–1

Rationale for Offering the Option for Family Presence

• Promotes collaboration and fosters trust between medical providers, patients, and family members • Reduces anxiety and sense of helplessness • Allows parents to comfort and support their child • Meets the family's need of being informed and feeling accepted • Facilitates the grieving process • Allows families to be by their loved one until the last minute and be able to say good-bye • Brings a sense of reality to the treatment efforts and clinical status of the patient

and encouraged to touch and speak with their loved ones.21 Regardless of their background, family members understand the need for appropriate behavior so that their presence does not impede the care of the person they are trying to help. It may be harder to end an unsuccessful resuscitation when family members are expressing grief.21 Stressing that every possible intervention has been done, and allowing time for family members to say what they need to say before ending the resuscitation, may help them accept the death. Witnessing CPR helps family members understand how grave the patient’s condition is, and allows them to feel confident that everything was done to save the patient.1,12,21 Staff may be traumatized by witnessing the family grieving, bringing emotions to the surface and making it harder to forget and move on. However, this is unavoidable, and taking the time after a resuscitation to talk and vent these feelings can make the circumstances easier to deal with.21 Family presence may also be very traumatic for the family. No matter how often people see HCPs providing CPR on television, witnessing these procedures on a loved one is not the same. Family presence should be offered as a choice so parents can participate in the decision about their presence. Being present during invasive procedures or resuscitation is not something all families want. Patients who choose not to have family members present, or family members who desire not to participate, must be supported in their decision without judgment. Even though a parents’ desire to stay decreases as procedures becomes more invasive, the majority still wish to be present.22 Even family members who have witnessed CPR say that they would participate again.12,13,15,23 It may be difficult to teach trainees in the presence of family members. We must remain professional and careful with our choice of words in the presence of family. Family presence should be viewed as an opportunity to learn about how to address and support distressed parents. Family presence during resuscitation and procedures does not increase litigation.24,25 In fact, family presence may decrease disputes by improving communication, increasing openness, and decreasing doubt about the adequacy of care.26,27 Family presence should be presented as an option by letting parents know that they can leave the room any time if they wish to avoid further stress.

Solutions Institutional/Systems Requirements Family presence requires the availability of critical staff members and institutional resources to succeed. A family

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presence program needs a family presence champion who will write guidelines that are institution specific, delineate roles and responsibilities, survey and educate staff members, and monitor progress and provide feedback. A family support person (FSP) is an individual who will provide most or all of the clinical support when family presence occurs. This individual must understand grief reactions, be competent at supporting distressed families, and have training in the explanation of medical care and in assessment and preparation of family members. The designated FSP can be a social worker, nurse, or chaplain who has no direct patient care responsibility, and is assigned exclusively to assist the family. Duties will include screening and preparing families prior to entering the treatment area, and remaining present with the family at all times in the resuscitation room. Follow-up services, especially when death occurs, should be established. Staff can be defused or debriefed, informally or through a critical incident stress management program. Security personnel should be available at all times to prevent serious disruption by family members. A family room adjacent to the resuscitation room works well as a staging area, and there must be adequate space in the treatment room. Any family presence program should have dedicated resources and funding for staff education and a mechanism for feedback. Setting Up a Family Presence Program One or more family presence champions must fi rst be identified. These are individuals who believe in the benefits of family presence and have good knowledge of the literature. They are committed to initiate and motivate change and act as the driving force behind the establishment of the family presence program. They help to increase awareness and role model family support interventions. A project team assists the family presence champion and should be assembled from a number of disciplines to assure consideration of all perspectives. Input is sought from a broad constituency, including nursing, medicine (emergency department, trauma, critical care, anesthesia, residents, fellows), transport personnel, social work, pastoral care, child life, administration, risk management, respiratory therapy, and technicians. Family member representation on the team should be encouraged. Team members meet regularly and help develop and implement the family presence program. Next, barriers to family presence within the institution should be identified. The project team should assess institutional resources and identify root causes that prevent the practice of family presence. They should survey a broad group of colleagues for suggestions, concerns, and educational needs. Based on this information, guidelines that are institution specific can be written. These should help delineate staff roles and responsibilities during a family presence event. Support procedures must be addressed for all hours of the day. HCP involvement in both resuscitation situations and invasive procedures that vary in complexity and need for personnel should be specified. The guidelines should balance the staff’s concerns about providing care and the families’ need to be present in the treatment room. They also need to stress that family presence should remain an option both for the family and for the staff and that the decision to participate must be supported without judgment. A sample guideline is provided in Table 153–2.

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SECTION VI — The Practice Environment

Table 153–2

Guidelines for Family Presence during Invasive Procedures and Resuscitations

Family Support Person (FSP) Prior to Patient’s Arrival: • Inquire about patient’s status and anticipated interventions • Prepare the space where family members will stay Patient and Family Assessment: • Promptly communicate known information about the patient’s status to the family. • Assess the family’s reaction: • Acceptable behaviors for family presence:
Quiet
Distressed, crying but consolable
Distracted but able to focus and answer questions
Anxious or angry but cooperative and follows instructions • Worrisome behaviors:
Uncooperative
Physically aggressive, combative
Threatening and argumentative
Extremely unstable emotionally, hysterical, loud, cannot be redirected or calmed
Altered mental status, intoxicated A family member’s ability to participate can progress or regress throughout their presence in the emergency department. Continuous assessment and intervention are critical for the success of family presence. • Assess the patient’s desire for family members to be present when applicable. • Assess the family’s desire/willingness to participate, and comfort with being present from previous experiences with similar situations (blood draws, procedures performed on a loved one, etc.). • Inform the HCP of the family’s arrival and request to be present in the treatment area. Preparation of the Patient and Family: Prior to entering the treatment room: • Families should be told: • How many family members may enter the room at one time • Where they will stand/sit initially and when they will be able to move to the bedside • That they may leave the room if they feel the need to step out, and that they are welcome to reenter • Why they may be asked to step out of the room:
At the request of the HCP
Obstruction of care: violent behavior, uncontrolled outbursts, etc. Security will join the FSP in moving the family out of the treatment area.
Need for medical assistance: fainting, chest pain, etc. In this case an HCP not involved in the care of their child will assist them. In the treatment room: • During resuscitations, an FSP must always remain with the family in the treatment area. During invasive procedures, the HCP will assign an FSP as needed. • The family must be clearly informed of the status of their loved one and be prepared for the interventions that are in progress. • Explain the procedures being performed. • Potential responses the patient may exhibit. • Explain the patient’s role during the procedure (i.e., holding still etc.). • Family members’ role in providing comfort and reassurance. • Interpret medical jargon. • Provide opportunity to ask questions and clarify details: The FSP should mainly describe the procedures performed. The physicians will explain indications and outcomes. Health Care Professional (HCP) Attending Physician: • Communicates with the FSP known information about the patient’s status and anticipated plan of care. • Approves/disapproves family presence, indicates to the FSP when to bring the family in. • The attending physician and the trauma chief will retain the option to allow the family to enter the treatment room or be escorted away from the bedside and/or out of the room if deemed necessary. • Notifies family of outcome of procedures and/or resuscitation as soon as practical. Emergency Department Charge Nurse: • Assures FSP is contacted for resuscitation situations. • Designates a staff member to act in the FSP role until support staff arrives. • Provides the FSP with clinical information and helps answering questions. All Care Providers: • Interact with the family as soon as practical. • Address the patient by name. • Offer and provide comfort measures: Assist the family in making phone calls, provide a place to sit down, water, tissues, etc. • Use terminology appropriate to the person’s level of understanding. • Provide opportunities for the family to see and speak with the patient. • Provide for patient and family privacy. • Maintain professional behavior and language at all times. Situational Constraints • When space is critically limited, it may be necessary to limit the number of family members to one at a time, or ask the family to step out temporarily. • When multiple patients need the resuscitation room simultaneously, family members may not be allowed in the room. Accommodations to bring the family to the bedside should be made as soon as practical, even if only briefly. Copyright 2006 the Children’s Hospital of Philadelphia, all rights reserved. Permission to use or adapt must be obtained from CHOP: [email protected]

Chapter 153 — Family Presence

Educating staff is a large part of the creation of a family presence program. The purpose of this education is to provide the skills necessary to support distressed families, become familiar with grief reactions, and introduce the guidelines and respective roles of the staff. Support personnel need to have a strong psychosocial background and some understanding of common invasive procedures and CPR. Other personnel need to be comfortable assessing families’ needs and initiating appropriate interventions and consultation. A variety of formats may be used, including lectures and workshops, role play exercises, videotaped presentations, self-study modules, and case reviews. A date should be designated for the program to begin. Implementation of a family presence program will take time and will require a shift in the culture of the department. Assessing staff readiness and ensuring adequate resources are essential steps in changing practice and integrating a familycentered care approach. Once the program is in place, the project team should monitor progress, provide feedback, and customize the guidelines. Evaluation is an essential step to validate the efficacy of the strategies implemented. Input should be sought from HCPs, support staff, and families. This helps to identify further educational needs, problems, and potential revisions of the guidelines. The mechanisms for evaluation may include surveys, postevent questionnaires, interviews, and open forum discussions. The timing of the evaluation should take into consideration the clinical situation and outcome. Opinions from staff may be solicited within days of an event and after several weeks to months from families who lost a loved one. Knowledge of the program should be spread within and outside the institution among all parties, including prehospital care providers.

Summary Due to perceptions, attitudes, previous exposures, and biases, many HCPs overlook the benefits of family presence. When planned properly, family presence helps meet the family’s needs without disrupting medical care. However, this type of change requires great commitment, adequate resources, continuing education, careful planning, and time. The greater the depth of experience with family presence, the greater the likelihood of supporting the process. As patient advocates, HCPs should strive for widespread establishment of family presence. REFERENCES *1. Doyle CJ, Post H, Burney RE, et al: Family participation during resuscitation: an option. Ann Emerg Med 16:673–675, 1987. *2. Boudreaux ED, Francis JL, Loyacano T: Family presence during invasive procedures and resuscitations in the emergency department: a critical review and suggestions for future research. Ann Emerg Med 40:193–205, 2002. 3. American Academy of Pediatrics Committee on Pediatric Emergency Medicine, American College of Emergency Physicians Pediatric Emer-

*Selected readings.

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gency Medicine Committee, O’Malley P, Broun K, Mace SE: Patient and family centered care and the role of the emergency physician providing care to a child in the emergency department. Pediatrics 118:2242–2244, 2006. 4. Emergency Nurses Association: Family Presence at the Bedside During Invasive Procedures and/or Resuscitations, 2nd ed, 2001. Available at http://www.ena.org 5. Henderson DP, Knapp JF: Report of the national consensus conforence on Family Presence during Pediatric Cardio pulmonary Resuscitation and Procedures. J Emerg Nurs 32(1):23–29, 2006. 6. Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 102(8):I-19, 2000. *7. Wolfram RW, Turner ED, Philput C: Effects of parental presence during young children’s venipuncture. Pediatr Emerg Care 13:325– 328, 1997. 8. Bauchner H, Vinci R, Bak S, et al: Parents and procedures: a randomized controlled trial. Pediatrics 98:861–867, 1996. 9. Powers KS, Rubenstein JS: Family presence during invasive procedures in the pediatric intensive care unit. Arch Pediatr Adolesc Med 153:955– 958, 1999. 10. Barratt F, Wallis DN: Relatives in the resuscitation room: their point of view. J Accid Emerg Med 15:109–111, 1998. *11. Sacchetti A, Lichenstein R, Carraccio CA, et al: Family member presence during pediatric emergency department procedures. Pediatr Emerg Care 12:268–271, 1996. *12. Meyers TA, Eichhorn DJ, Guzzetta CE, et al: Family presence during invasive procedures and resuscitation. Am J Nurs 100(2):32–43, 2000. *13. Belanger MA, Reed S: A rural community hospital’s experience with family-witnessed resuscitation. J Emerg Nurs 23:238–239, 1997. 14. Williams AG, O’Brien DL, Laughton KJ, et al: Improving services to bereaved relatives in the emergency department: making health care more human. Med J Aust 173:480–483, 2000. 15. Robinson SM, Mackenzie-Ross S, Campbell Hewson GL, et al: Psychological effect of witnessed resuscitation on bereaved relatives. Lancet 352:614–617, 1998. 16. Eichhorn DJ, Meyers TA, Mitchell TG, Guzzetta CE: Opening the doors: family presence during resuscitation. J Cardiovasc Nurs 10:59– 70, 1996. 17. Helmer SD, Smith SR, Dort JM, et al: Family presence during trauma resuscitation: a survey of AAST and ENA members. J Trauma 48:1015– 1024, 2000. *18. Bassler PC: The impact of education on nurses’ beliefs regarding family presence in a resuscitation room. J Nurses Staff Dev 15(3):126– 131, 1999. *19. Mitchell MH, Lynch MB: Should relatives be allowed in the resuscitation room? J Accid Emerg Med 14:366–369, 1997. 20. Sacchetti A, Carraccio C, Leva E, et al: Acceptance of family member presence during pediatric resuscitations in the emergency department: effects of personal experience. Pediatr Emerg Care 16:85–87, 2000. *21. Hanson C, Strawser D: Family presence during cardiopulmonary resuscitation: Foote Hospital emergency department’s nine-year perspective. J Emerg Nurs 18:104–106, 1992. *22. Boie ET, Moore GP, Brummett C, et al: Do parents want to be present during invasive procedures performed on their children in the emergency department? A survey of 400 parents. Ann Emerg Med 34:70–74, 1999. 23. Meyers TA, Eichhorn DJ, Guzzetta CE: Do families want to be present during CPR? A retrospective survey. J Emerg Nurs 24:400–405, 1998. 24. Forster H, Schwartz J, Derenzo E: Reducing legal risk by practicing patient-centered medicine. Arch Intern Med 162:1217–1219, 2002. 25. Brown JR: Letting the family in during a code: legally it makes good sense. Nursing 19(3):46, 1989. 26. Tsai E: Should family members be present during cardiopulmonary resuscitation? N Engl J Med 346:1019–1021, 2002. 27. Trout A, Magnusson R, Hedges JR: Patient satisfaction investigations and the emergency department: what does the literature say? Acad Emerg Med 7:695–709, 2000.

Chapter 154 The Child-Friendly Emergency Department: Practices, Policies, and Procedures Susan Fuchs, MD

Key Points There are suggested minimum pediatric emergency department (ED) equipment, supplies, and medication. There are many different staff training options. Continuous quality improvement and creating a safe environment are essential for any pediatric ED. Key pediatric policies, procedures and external agreements must be available 24 hours a day, 7 days a week in all pediatric EDs.

Introduction and Background What is Emergency Department Preparedness? Emergency department (ED) preparedness means that the “Emergency Department must have the staff and resources to evaluate all persons presenting to the ED.”1 However, when it comes to pediatric patients, this is not always the case. A national survey concluded that only 10% of U.S. hospitals have a pediatric intensive care unit, 25% of hospitals without a pediatric trauma service admit critically injured children, and 7% of hospitals without a pediatric ward admit children.2 A Canadian study of ED preparedness demonstrated deficiencies in equipment needed to resuscitate a critically ill pediatric patient.3 Not all children are, or need to be, seen in a pediatric ED. In fact, of the approximately 35 million pediatric ED visits per year, only 10% seek care initially in a children’s hospital/ pediatric ED. What this means is that the other 31.5 million children seek care in general and community EDs, which have varying abilities to care for them. In most community EDs, pediatric patients account for 20% to 35% of the patient visits. This chapter reviews the issues involved in prepared1080

ness, possible solutions, suggested policies and procedures, and additional information that may prove beneficial to create an ED appropriately prepared for infants, children, and adolescents. Facility Categorization While most physicians and nurses are familiar with terms such as a Level I trauma center or a burn center, the terminology for pediatric centers is new, and often varies from state to state, if it exists at all. “Categorization is the assessment of a facility based on its ability to manage certain categories of patients.” 4 The levels of categorization are usually based upon state (e.g., Level I vs. II adult/pediatric trauma center) or national (e.g., burn center) standards. This can lead to a “designation,” or the assignment of responsibility for care of certain categories of patients to specific institutions based upon compliance with standards as well as on their catchment area.4 The designation is conferred by an outside agency once the facility has gone through a site survey or other process to verify that it meets the existing standards. A hospital can also voluntarily agree to adopt a set of standards as its own, without an outside agency involved, and can be “confirmed.”4 Another important distinction is the method by which states categorize hospitals and EDs. In many states there are comprehensive EDs. This is an ED with at least one physician available 24 hours a day, 7 days a week (24/7), with specialty services, and with ancillary services such as radiology, laboratory, and pharmacy staffed at all times.5 A basic ED has at least one physician 24/7, limited specialty services, and ancillary services staffed or “on call.” A standby ED has a registered nurse, nurse practitioner, or physician’s assistant available for emergency services 24/7, and a physician who is “on call.”5

Issues In 1995, the American Academy of Pediatrics (AAP) issued guidelines for pediatric emergency care facilities. This document established four levels of care: standby, basic, general

Chapter 154 — The Child-Friendly Emergency Department: Practices, Policies, and Procedures

emergency facilities, and comprehensive regional pediatric center.6 It included recommendations on personnel, medical specialist consultants, surgical specialists, equipment and supplies, and facilities for each level. It also covered topics such as access, triage, transfer and transport, education, training, research, quality assessment and improvement, administrative support and hospital commitment.6 This guideline added the requirement that the physician be competent in the care of pediatric emergencies. This could be demonstrated by the successful completion of Pediatric Advanced Life Support (PALS) or Advanced Pediatric Life Support (APLS) courses.6 This set the foundation for the development of a national policy statement in 2001 (see later).7 In February 1995, the American College of Emergency Physicians (ACEP) issued a policy statement on pediatric equipment guidelines. These were recommended for equipment of pediatric patients in a general ED. This list included monitoring devices, vascular access supplies and equipment, respiratory equipment and supplies, medications, related supplies/equipment, miscellaneous equipment, specialized pediatric trays, and fracture management devices.8 The equipment and medications listed in this document and the AAP 1995 document are similar. In 1998, the Committee on Pediatric Equipment and Supplies for Emergency Departments of the National Emergency Medical Services for Children Resource Alliance developed a consensus statement regarding pediatric resuscitation medication and minimum equipment and supplies.9 They based their recommendations on previously published lists, including the two documents by the AAP and ACEP.6,8 The article mentioned that the ED may choose to modify this list, and that ED health care providers should be trained in the use of all equipment and supplies. The committee also took into account financial factors when recommending items, and occasionally provided some equipment options. In 2001, the AAP and ACEP, along with the federal Emergency Medical Services for Children (EMSC) program, developed a joint policy statement: “Care of Children in the Emergency Department: Guidelines for Preparedness.”7 In addition to these organizations, this statement was supported by numerous national organizations and agencies. While this document does list medications, equipment, and supplies (adapted from the 1998 list9), its strength lies in the agreement on personnel staffing and training, administration and coordination for pediatric emergency care, quality improvement (QI), and ED policies, procedures, protocols, and support services. The information in this policy provides a framework for many of the areas to be discussed in the “Solutions” section later in this chapter. State Guidelines In 1994, the California Emergency Medical Services Authority compiled a list of recommended equipment, supplies, and medications for the care of pediatric patients in the ED.10 In 1999, the Los Angeles County Department of Health Services’ Emergency Medical Services (EMS) division published Emergency Department Approved for Pediatrics (EDAP) standards.4,11 These standards include administration, coordination, personnel, policies, procedures and protocols, QI, support services, equipment, supplies, and medications. Pediatric Critical Care Center (PCCC) was another category

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designation that was added. This designation is achieved if a hospital meets requirements for an EDAP, has a trauma center, and has a California Children’s Services–approved pediatric intensive care unit.11 In 2004, there were 57 EDAPs and 9 PCCCs in Los Angeles County.11 In 2002, the State of Illinois added a section to the Emergency Medical Services and Trauma Center Code to include facility recognition criteria for EDAPs and the Standby Emergency Department Approved for Pediatrics (SEDP).12,13 Although this is a voluntary process, since these rules have been in effect the EMSC facility recognition process has recognized 114 (out of a possible 200) hospitals. These criteria cover topics similar to the Los Angeles County criteria, but include recommended equipment lists as well as professional staff (nurse, physician, nurse practitioner, physician assistant) qualifications, continuing medical education (CME) requirements, a multidisciplinary QI committee, and a pediatric continuous QI liaison.12-14 Another important part of this document was the development of interfacility pediatric trauma and critical care consultation and/or transfer guidelines.15

Solutions Triage When a child enters an ED with his or her parent(s), the first encounter they have with a health professional is at triage. It is important for that person to be comfortable assessing a child, to have the necessary equipment (e.g., scales, thermometer, appropriate-sized blood pressure cuffs, and pulse oximeter probes), as well as to have some criteria on which to base the child’s triage category assessment. Published criteria for children are based upon age-related norms, signs, and symptoms, and are divided into three or five categories.16-18 Triage criteria provide a guide as to the level of acuity of the patient, which in turn provide a time frame in which the patient should be seen (see Chapter 155, Triage). Physical Space (Child Friendly) While a designated pediatric care area is not feasible in many facilities, it may be possible to make the ED child friendly in several simple ways. Just separating pediatric patients from adult patients in the waiting room may protect them from some of the sights, language, and other inappropriate behavior of adults. It can also provide some separation between children who may have a contagious disease and elderly adults, who are very susceptible to these illnesses. It is important to childproof the waiting room by avoiding sharp corners on chairs and tables, locking cabinets, covering electrical outlets, and covering trash cans.19 If pediatric-size furniture is available, it is important to keep it clean after use. This is also true of any toys used in a play area. Some simple solutions are to provide coloring books and crayons, or books to read, all of which can be taken home. If a separate pediatric room or care area is available, simple decorations can brighten the room and provide distractions for children. This can be a cheerful wall border, hanging pictures, or ceiling drawings. While one could argue that a teenager will not enjoy being in a room decorated with Mickey Mouse or Sesame Street characters, they can still provide distractions during an examination. This room

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SECTION VI — The Practice Environment

should also be childproofed by placing all medical equipment out of reach of a child, providing bed rails with child guards, and assuring that there are no sharp objects or corners at an infant or roaming child level. Another option is to provide a TV/VCR/DVD player in the room. The TV can have limited channels, and the VCR or DVD can be utilized to view cartoons, movies, or even educational tapes.19 As a convenience to parents, having diapers, skin wipes, and blankets in the room can help them provide care or comfort for their child while waiting to be seen. Staffing Creating a child-friendly environment should involve the staff. While many pediatric hospitals allow brightly colored shirts/blouses/scrub tops, these may not look professional to an adult entering the ED. Each hospital has dress code regulations that determine the use of scrubs outside of the operating room. The ability of clerical, ED, and ancillary staff to deal with patients of various ages cannot be overstressed. Education and training sessions on how to communicate and interact with pediatric patients should be available to all the staff involved in their care. Many emergency nurses work in different hospital locations before they seek employment in the ED, but their exposure to pediatrics may have been limited to nursing school rotations. If there is a pediatrics ward in the hospital, having them spend some time with pediatric nurses (and vice versa) can be an invaluable experience. There are specific CME courses, including the Emergency Nurse Pediatric Course (ENPC) offered through the Emergency Nurses Association, APLS, and PALS, that can help them improve their assessment, technical, and treatment skills.20 The specific number of staff is based upon the hospital designation (comprehensive vs. standby) as well as the usual census, but will include at least one nurse present 24/7. Physician attitude and training are also crucial. Once again, depending upon the physician’s specialty, his or her last exposure to pediatrics may have been in medical school. Residency-trained emergency physicians are trained in the acute and emergent care of pediatric patients. Additionally, each state may have additional CME requirements for physicians, some being specific for topics such as pain management, end-of-life issues (California), and child maltreatment (New York). Specific physician staffing is based upon hospital designation (e.g., for a standby hospital, the physician may be on call but promptly available, whereas a basic facility has an emergency physician present 24/7). The ACEP emergency care guidelines contains specific staffing and credentialing requirements for physicians and nurses.9 The availability of specialists (surgical and medical) varies based upon the hospital designation. The AAP guidelines for pediatric emergency care facilities include a table that lists these physicians, and whether they are essential in the hospital or promptly available, based on hospital designation.6 Competency The issue of developing staff competency is difficult to define. Courses that do exist do not guarantee competency, but provide certification that one has completed the course. Becoming competent requires experience, ongoing training, practice, and education. There are no set number of times a

physician must suture a laceration, or a nurse must start an intravenous line, to prove he or she is competent. The requirements for board certification in all medical specialties are undergoing change to include the following: physicians must maintain active licensure, pass a written examination, read current literature, obtain CME credits, and receive an evaluation of their practice performance. While this does not prove competency either, it is a multilayered process that is more rigorous than previous requirements. For those staff who do not have pediatric experience, available courses can help educate them about common pediatric illnesses and injuries, resuscitation skills, and procedural techniques. These classes include ENPC and APLS or PALS for nurses, and PALS or APLS for physicians.18,20,21 Equipment/Supplies Even with all of the expertise and training of the staff, an ill infant cannot be cared for appropriately if the right-size equipment is not present. This can include basic equipment such as a sphygmomanometer with an infant-sized blood pressure cuff, or a 22- or 24-gauge intravenous catheter, or a 10F chest tube. While there are several published equipment lists, the equipment/supply list published by the AAP and ACEP is based upon the consensus of many organizations7 (Table 154–1). Medications The majority of the medications required in the ED can be used in children.1,9 However, there are some unique concentrations for children, such as sodium bicarbonate (4.2%), and dextrose (10%, 25%).9 It is important to have frequently used medications readily available in the ED, and a process for obtaining those used less frequently in a short time frame (Table 154–2). Quality Improvement The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) requires that hospitals improve patient safety and perform QI activities. Each year JCAHO establishes national patient safety goals and quality indicators.22 Common ED QI monitors include deaths, transfers, and ED returns visits within 48 or 72 hours. Additional pediatric QI indicators can include pediatric resuscitations, intubations, and patients admitted to the general pediatric ward who require transfer to a pediatric intensive care unit. More specific QI ideas can include timing to administration of antipyretics, or pain assessment and management.23 It is important to include some out-of-hospital QI indicators such as appropriate airway management (airway adjunct or assisted ventilation), delivery of 100% oxygen to a child in respiratory distress, establishment of vascular access, appropriate immobilization for trauma, and appropriate sized equipment used. The Institute of Health Care Improvement has defined the four essential components of a high-performing quality program as follows: (1) focus on identifying appropriate indicators, developing a plan for improvement (plan); (2) implement this plan (do); (3) collect and analyze the data (study); and (4) reach conclusions and make recommendations (act). It is also important to have a multidisciplinary QI team, as different perspectives will be obtained and many lessons learned (see Chapter 149, Patient Safety, Medical Errors, and Quality of Care).

Chapter 154 — The Child-Friendly Emergency Department: Practices, Policies, and Procedures

Table 154–1

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Recommended Equipment and Supplies

Monitoring • Cardiorespiratory monitor with strip recorder • Defibrillator (0–400 J) with pediatric (4.5-cm) and adult (8-cm) paddles or corresponding adhesive pads • Pediatric and adult monitor electrodes • Pulse oximeter with sensors for children • Sphygmomanometer • Doppler blood pressure device • Blood pressure cuffs (neonatal, infant, child, adult arm and thigh cuffs) • Stethoscope • Thermometer (must be able to measure from 25° C to 44° C) • Endotracheal tube placement monitor (disposable CO2 detector, electronic waveform or measurement, or for children ≥ 20 kg or ≥5 yr, esophageal detector device) Airway Management • Portable oxygen regulators/canisters • Oxygen masks • clear simple face masks—neonatal, infant, child, adult • Venturi masks—neonatal, infant, child, adult • partial non-rebreathing masks—neonatal, infant, child • rebreathing masks—child, adult • Oropharyngeal airways (sizes 0–5) • Nasopharyngeal airways (sizes 12F–30F) • Bag-valve-mask resuscitator—self-inflating (450- and 1000-ml sizes) • Nasal cannulae (infant, child, adult) • Endotracheal tubes • uncuffed (sizes 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, and 6.0 mm) • cuffed (sizes 6.5, 7.0, 7.5, 8.0, and 9.0 mm) • Stylets (pediatric and adult) • Laryngoscope handle (pediatric and adult) • Laryngoscope blades: straight/Miller (sizes 0, 1, 2, and 3) and curved/Macintosh (sizes 2 and 3) • Magill forceps (pediatric and adult) • Nasogastric/feeding tubes (sizes 5F–18F) • Suction catheters—flexible (sizes 6F–16F) • Yankauer suction tip • Bulb syringe Vascular Access • Butterfly needles (sizes 19G–25G) • Catheter-over-needle devices (sizes 14G–24G) • Intraosseous needles (two sizes, between 13G and 18G)

• Intravenous fluids • Rate-limiting infusing device and tubing • Fluid/blood warmer Fracture Management • Cervical immobilization equipment (backboard with straps, and head immobilizer) • Semi-rigid cervical collars (sizes to fit infant, child, and adolescent) Miscellaneous Equipment • Length-based resuscitation tape (precalculated drug or equipment list based on weight) • Pediatric urinary catheters (sizes 5F–16F) • Infant and standard scales • Towel rolls, blanket rolls • Resuscitation board • Medical photography capability Specialized Pediatric Trays • Lumbar puncture • Tube thoracotomy with water seal drainage capability • Venous cutdown kit • Needle cricothyrotomy tray Essential Equipment That Can Be Shared (Nursery, Floor, Operating Room), but Is Readily Available to the Emergency Department • Umbilical vein catheters (3.5F, 5F [but size 5F feeding tube can also be used]) • Chest tubes (sizes 8F–40F) • Seldinger vascular access technique kit (3F, 5F, 8F) • Extremity splints • Femur splints (child and adult) • Tracheostomy tubes (sizes 00–6) • Obstetrics pack • Newborn delivery kit • Umbilical vessel cannulation supplies • Surgical airway kit (tracheostomy or surgical cricothyrotomy kit) • Infant formula and oral rehydrating solutions • Heating source (infrared lamps or overhead warmer) • Sterile linen Equipment That Is Desirable • Laryngeal mask airways (sizes 1, 1.5, 2, 2.5, 3, 4, and 5)

Adapted from American Academy of Pediatrics, Committee on Pediatric Emergency Medicine; and American College of Emergency Physicians, Pediatric Committee: Care of children in the emergency department: guidelines for preparedness. Pediatrics 107:777–781, 2001.

Table 154–2

Recommended Medications

Activated charcoal Adenosine Antibiotics (parenteral) Anticonvulsants Antidotes Antipyretics Atropine Bronchodilators Calcium chloride Corticosteroids Dextrose (25%, 50%) Epinephrine (1:1000, 1:10,000) Inotropic agents Lidocaine Naloxone hydrochloride Neuromuscular blocking agents Oxygen Sedatives Sodium bicarbonate (4.2%, 8.4%)

Transfer Criteria While many ill and injured children can be cared for in local EDs and hospitals, some require transfer to a specialized care center. There are hospitals that offer specialized care for newborns, critical care services, pediatric trauma, and burns. They offer 24-hour consultation with the appropriate specialist, and may have their own interfacility transport service. The decision to transfer pediatric patients depends upon the ED and hospital capabilities, but guidelines have been developed to help physicians identify which patients would benefit from specialized care. It is important for the referring physician to consult with the receiving physician, so the appropriate method of transport and the required personnel can be determined. Transfer guidelines can be based upon physiologic criteria, anatomic criteria, burn criteria, or diagnostic criteria. An example of these guidelines has been developed for the Illinois EMSC program.24

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SECTION VI — The Practice Environment

Policies and Procedures Policies, procedures, and protocols that specifically deal with the emergency care of children should be developed for use in the ED and hospital. These include policies on child maltreatment and consent issues. Other protocols may be integrated into ED/hospital policies, procedures, and protocols, but pediatric-specific components should be included. This includes policies on death in the ED, do-not-resuscitate orders, injury and illness triage, sedation and analgesia, immunization status, mental health emergencies, physical or chemical restraint of patients, family issues (e.g., family presence during care), communication with the patient’s primary care provider, and transfer policies.7 Restraints (Chemical and Physical) JCAHO has behavioral health care restraint and seclusion standards that apply to patients in the ED who are being restrained or secluded for behavioral health reasons.25 Restraint, whether chemical or physical, should be a method of last resort. It should never be used as a means of discipline, coercion, or retaliation or for convenience. Restraint is often considered when the patient’s or another’s safety is a concern. Included in this policy should be the use of seclusion. When restraint or seclusion is considered, the patient’s caregivers should be involved in the treatment decision. If this is not possible, they should be notified. Each use of restraint or seclusion must be based on the patient’s needs, age, and past medical history. The restraint policy should cover definitions and exceptions to restraints (e.g., intravenous infusion armboards, temporary immobilization for procedures). When restraint or seclusion is utilized, there need to be written orders by a physician, time limits for the written orders, patient assessment parameters (constant visualization, vital signs, nutrition, hydration, and safety every 15 minutes), and a re-evaluation time for renewal of the restraint order.25 During restraint or seclusion, documentation should include a physician order, completion of a nursing or trained staff form/flowsheet, notification of the patient’s legal guardian, and documentation of monitoring/ vital signs. All staff are required to have ongoing education in the proper use of restraint devices and seclusion techniques, as well as alternative methods for handling behaviors that may lead to the use of restraint or seclusion. The ED medical records of those patients who require restraint or seclusion should be reviewed as part of the department’s QI plan. Procedural Sedation and Analgesia The use of sedation and analgesia for pediatric procedures should be standard in the ED. According to JCAHO and the American Society of Anesthesiologists (ASA), there are only two levels that are appropriate for the ED: minimal sedation (anxiolysis), and moderate sedation/analgesia (“procedural sedation”).26 The fact that two children may respond differently to the same dose of medication necessitates advanced planning on the part of the ED staff. The procedural sedation and analgesia policy should include the following: preparation (patient history and physical examination, information about allergies, prior sedation and analgesia procedures, last meal and liquids), monitoring parameters, “nothing by mouth” guidelines, appropriate candidates for sedation (ASA

Physical Status Classification classes I and II), parental consent, and discharge criteria.26 Depending upon the level of sedation planned, the monitoring parameters may change, as will the equipment available in the room and the personnel present26-29 (see Chapter 159, Procedural Sedation and Analgesia). Drug Testing The use of drug testing for alcohol, drugs of abuse, controlled substance, or other toxins should be written in an ED policy. In some states, the state police can request that a physician perform this test, even without the patient’s consent. In some states, the emergency physician is required to obtain drug testing if the physician believes the patient was given a controlled substance without his or her consent. If it is unclear that the patient was given a drug, then asking the patient for consent is appropriate. The consent form for a toxicology screen should be completed by the patient/ legal guardian, and witnessed, timed, and dated. It may also be possible for the patient/legal guardian to sign the consent later, and to revoke the consent (both within 48 hours). Health Care–Acquired Infection One of the 2004 JCAHO safety parameters is to reduce the risk of health care–acquired infection.22 This can be accomplished by complying with the Centers for Disease Control and Prevention (CDC) hand hygiene guidelines.30 Items in these guidelines include limiting the use of artificial nails, keeping natural nails short, and using alcohol-based hand cleaners.22,30 In addition, nosocomial infections that result in unanticipated death or major permanent loss of function should be managed as sentinel events.22 Infectious Diseases In the United States, state laws and regulations mandate which diseases are reportable, and this varies from state to state. Local and/or state departments of health collect this information. The CDC maintains a list of notifiable infectious diseases that is released every year that allows the CDC to follow trends in reportable disease across the United States during a given year, and from year to year. This list currently contains 60 diseases such as acquired immunodeficiency syndrome, anthrax, gonorrhea, hepatitis (types A, B, and C), Lyme disease, meningococcal disease, pertussis, salmonellosis, shigellosis, smallpox, syphilis, and tuberculosis.31,32 Recently, diseases such as erhlichosis, giardiasis, severe acute respiratory syndrome (SARS), smallpox, and vancomycinintermediate and -resistant Staphylococcus aureus have been added.31 The use of standard precautions took on a heightened awareness during the early days of acquired immunodeficiency syndrome/human immunodeficiency virus infection, and this has continued. In order to reduce the number of needle sticks, there has been an increased use of needleless systems and retractable needles. With new and emerging infections such as SARS, this has progressed to include special respiratory masks (N-95), rather than simple paper/procedure masks. The ED should have policies regarding the use of isolation rooms, negative pressure rooms (if available), and patient decontamination. There should also be a policy regarding

Chapter 154 — The Child-Friendly Emergency Department: Practices, Policies, and Procedures

exposure to potential blood-borne pathogens, which includes reporting, testing, and prophylaxis. EMTALA The Emergency Medical Treatment and Labor Act (EMTALA) is a federal law that forbids a hospital, physician, dentist, or other health care provider to refuse to provide emergency care based upon a patient’s inability to pay33 (see Chapter 150, Emergency Medical Treatment and Labor Act [EMTALA]). This legislation, often referred to as the Comprehensive Omnibus Budget Reconciliation Act or “anti-dumping” legislation, is included in Title XVII of the Social Security Act. Any hospital that received Medicare funding must comply with these regulations, even for non-Medicare patients. A hospital can be fined up to $50,000 per violation, and the hospital’s or physicians’ Medicare and Medicaid agreements may be terminated by the Centers for Medicare & Medicaid Services.33,34 EMTALA applies when a person comes to a hospital with an ED and requests care for an emergency medical condition. It also applies if a parent is requesting care for his or her child. An emergency medical condition is an illness or injury that manifests itself by acute symptoms requiring immediate attention to avoid placing the health of the person in serious jeopardy.33 In terms of a woman in labor, this constitutes inadequate time to transfer her prior to delivery. However, the existence of an “emergency medical condition” is based upon the definition of a prudent layperson, not a health care professional.33 In order to fulfi ll the EMTALA obligation, a patient must be screened and, if necessary, stabilized. If a patient cannot be stabilized, he or she must be transferred to an appropriate facility, with the receiving facility aware of and accepting the transfer.33 The ED and hospital should have an EMTALA policy that addresses items such as what constitutes a screening examination, who can perform the screening examination, which parts of the hospital/main campus qualify under EMTALA, and who responds to medical emergencies outside of the ED.33,34 A revised aspect of EMTALA is the “on-call” requirement. Each hospital must have an on-call schedule and written policies related to the schedule, including response times. This policy applies to emergency physicians as well as medical and surgical specialists34 (see Chapter 150, Emergency Medical Treatment and Labor Act [EMTALA]). Transfer Policies and Procedures A transfer policy should be in place for hospitals that do not have pediatric intensive care units, inpatient beds, or pediatric trauma capabilities/specialists, or when specialized pediatric care is not available. It is helpful to have a list of referral hospitals and contact numbers placed prominently in the ED. It is preferable to have transfer agreements with several hospitals in the region for similar or different categories of patients (e.g., trauma vs. medical). These agreements should be signed by the hospital cheif executive officer and updated as needed. In some cases, these agreements are extremely important for reimbursement if the transfer involves crossing state lines. In rare cases, the receiving facility may have no available beds, but can assist the transferring hospital in finding another appropriate

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facility. Before the patient is transferred, there should be physician-to-physician and nurse-to-nurse communication. Written documentation, including consent to transfer, method of transfer, and reason for transfer, should be included.35 Hospital Overcrowding In 2003, there were nearly 114 million ED visits, a 26% increase over the last 10 years.36 Yet at the same time, the number of EDs decreased by 10%.36 This is just one of the many causes of hospital overcrowding, a situation in which the identified need for emergency services exceeds the available resources in the ED.37 This problem can affect child-friendly EDs and can result in ambulance diversion, where an ED does not have the capability to accept an EMS/ ambulance patient, and prolonged ED stays after admission or transfer decisions are made due to a lack of inpatient beds (“ED boarders”).37,38 This may mean that an ill child will be transported by EMS to another ED that may be further away, and perhaps not child friendly. It can also mean that, even after an ill or injured child has been stabilized, there may be no available beds at the pediatric centers. While there are no easy solutions to this problem, utilizing QI indicators to track time on EMS diversion, ED boarding time, ED waiting room time, the number of patients who left without being seen, and the number of times when patients could not be transferred in a timely manner will help those outside the ED realize there is a problem, and help advocate for change.

Summary The process of developing ED preparedness for children is not a new issue. Over the last 20 years, the goal of the EMSC program was to assure that children were included in the entire scope of care, including out-of-hospital care, the ED, and hospital care. Many of the policies and programs developed over the past 10 years were the result of this initiative.7,9,12-15 By being inclusive rather than exclusive, many national organizations have supported the idea of pediatric ED guidelines for preparedness. It is unrealistic to expect that a rural community hospital that lacks pediatric inpatient beds would have the same ED equipment and supplies as a large suburban community hospital with pediatric inpatient beds, or even an urban, freestanding children’s hospital. The goal is to provide some ideas, solutions, and examples that will improve the care of children everywhere. The Future: An ACEP/AAP Implementation Kit The AECP, through a grant from the federal EMSC program, is developing an implementation kit for ED preparedness.39 This kit contains information such as a copy of the AAP/ ACEP paper “Care of Children in Emergency Departments: Guidelines for Preparedness”7; 12 model emergency department policies for care of children, including child maltreatment, consent, and death in the ED; relevant ACEP and AAP pediatric clinical care guidelines and policies; a pediatric medication calculator; and a pediatric preparedness checklist. Prior to wide dissemination, the implementation kit is currently being evaluated, and will be refi ned based on evidence generated (Table 154–3).

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Table 154–3

ACEP/AAP Implementation Kit for ED Preparedness

• A copy of “Care of Children in the Emergency Department: Guidelines for Preparedness.”7 • 12 model ED policies for the care of children • Pediatric Medication Calculator • Pediatric Preparedness Checklist Abbreviations: AAP, American Academy of Pediatrics; ACEP, American College of Emergency Physicians; ED, emergency department.

REFERENCES *1. American College of Emergency Physicians: Emergency care guidelines. Ann Emerg Med 29:564–571, 1997. 2. Athey J, Dean JM, Ball J, et al: Ability of hospitals to care for pediatric emergency patients. Pediatr Emerg Care 17:170–174, 2001 3. McGillivray D, Nijssen-Jordan C, Kramer MS, et al: Critical pediatric equipment availability in Canadian hospital emergency departments. Ann Emerg Med 37:371–376, 2001. 4. The community hospital emergency department. In Seidel JS, Knapp JF (eds): Childhood Emergencies in the Office, Hospital, and Community: Organizing Systems of Care. Elk Grove Village, IL: American Academy of Pediatrics, 2000, pp 133–150. 5. State of Illinois, Administrative Code: Illinois Department of Public Health, Emergency Services and Highway Safety, Section 515.100: Defi nitions. Available at http://www.ilga.gov/commission/jcar/ admincode/077/077005150A01000R.html *6. Committee on Pediatric Emergency Medicine, American Academy of Pediatrics: Guidelines for pediatric emergency care facilities. Pediatrics 96:526–537, 1995. *7. American Academy of Pediatrics, Committee on Pediatric Emergency Medicine; and American College of Emergency Physicians, Pediatric Committee: Care of children in the emergency department: guidelines for preparedness. Pediatrics 107:777–781, 2001. [also published in Ann Emerg Med 37:423–427, 2001] *8. American College of Emergency Physicians. Pediatric equipment guidelines. Ann Emerg Med 25:307–309, 1995. *9. Committee on Pediatric Equipment and Supplies for Emergency Departments, National Emergency Medical Services for Children Resource Alliance: Guidelines for pediatric equipment and supplies for emergency departments. Ann Emerg Med 31:54–57, 1998. 10. State of California, Health and Welfare Agency, Emergency Medical Services Authority: Administration, Personnel and Policy Guidelines for the Care of Pediatric Patients in the Emergency Department (EMSA#182). Sacramento: Emergency Medical Services Authority, 1994. 11. Los Angeles County Department of Health Services, Emergency Medical Services Agency. Available at http://www.dhs.co.la.ca.us/ems 12. State of Illinois, Administrative Code: Illinois Department of Public Health, Emergency Services and Highway Safety, Section 515.4000: Facility Recognition Criteria for the Emergency Department Approved for Pediatrics (EDAP). Available at http://www.luhs.org/depts/emsc/ EDAPres/02crf515.400.doc 13. State of Illinois, Administrative Code: Illinois Department of Public Health, Emergency Services and Highway Safety, Section 515.4010: Facility Recognition Criteria for the Standby Emergency Department Approved for Pediatrics (SEDP). Available at http://www.luhs.org/ depts/emsc/EDAPres/03sec515.4010.doc 14. State of Illinois, Administrative Code: Illinois Department of Public Health, Emergency Services and Highway Safety, Section 515: Appendix L, Pediatric Equipment Recommendations for Emergency Departments. Available at http://www.luhs.org/depts/emsc/stndrd-edguideline.htm 15. State of Illinois, Administrative Code: Illinois Department of Public Health, Emergency Services and Highway Safety, Section 515: Appendix M, Interfacility Pediatric Trauma and Critical Care Consultations and/or Transfer Guideline. Available at http://www.luhs.org/depts/ emsc/stndrd-transfer.htm *Suggested readings.

*16. Triage Curriculum. Emergency Nurses Association web site. Aailable at http://www.ena.org 17. Emergency Severity Index (ESI). Emergency Nurses Association web site. Available at http://www.ena.org *18. Seidel J, Knapp JF: Preparedness for pediatric emergencies. In GauscheHill M, Fuchs SD, Yamamoto L (eds): APLS: The Pediatric Emergency Medicine Resource, 4th ed. Boston: Jones and Bartlett, 2004, pp 1–17. 19. Making the environment child friendly. In Seidel JS, Knapp JF (eds): Childhood Emergencies in the Office, Hospital, and Community: Organizing Systems of Care. Elk Grove Village, IL: American Academy of Pediatrics, 2000, pp 151–158. 20. Emergency Nurses Pediatric Care Course. Emergency Nurses Association web site. Available at http://www.ena.org 21. Illinois Emergency Medical Services for Children: Pediatric Educational Recommendations for Professional Healthcare Providers. Available at http://www.luhs.org/depts/emsc/stndrd-edu.htm *22. 2004 National Patient Safety Goals. Joint Commission on Accreditation of Healthcare Organizations web site. Available at http://www. jointcommission.org/PatientSafety/NationalPatientSafetyGoals/2004_ npsgs.htm 23. Illinois Emergency Medical Services for Children. Continuous Quality Improvement. http://www.luhs.org/depts/emsc/quality.htm. 24. Illinois Emergency Medical Services for Children. Interfacility Pediatric Trauma and Critical Care Consultation and/or Transfer Guideline. http://www.luhs.org/depts/emsc/stndrd-transfer.htm. 25. Behavioral Health Care Standards on Restraint and Seclusion. Joint Commission on Accreditation of Healthcare Organizations web site: http://www.jointcommission.org/accreditationprograms/ behavioralhealthcare/standards 26. Sacchetti A: Procedural sedation and analgesia. In Gausche-Hill M, Fuchs SD, Yamamoto L (eds): APLS: The Pediatric Emergency Medicine Resource, 4th ed. Boston: Jones and Bartlett, 2004, pp 498–523. 27. American Academy of Pediatrics, Committee on Drugs: Guidelines for monitoring and management of pediatric patients during and after diagnostic and therapeutic procedures. Pediatrics 89:1110–1115, 1992. *28. Mace SE, Barata IA, Cravero JP, et al: Clinical policy: Evidence-based approach to pharmacologic agents used in pediatric sedation and analgesia in the emergency department. Ann Emerg Med 44:342–377, 2004. 29. American Society of Anesthesiologists Task Force on Sedation and Anesthesia by Non-Anesthesiologists: Practice guidelines for sedation and analgesia by non-anesthesiologists. Anesthesiology 94:1004–1017, 2002. 30. Centers for Disease Control and Prevention: Guidelines for hand hygiene in health care settings: recommendations of the Healthcare Infection Control Practices Advisory Committee and the HICPAC/ SHEA/APIC/IDSA Hand Hygiene Task Force. MMWR Morb Mortal Wkly Rep 51(RR-16): 26–34, 2002. 31. Centers for Disease Control and Prevention. Nationally Notifiable Infectious Diseases, United States, 2005. Available at http://www.cdc. gov/epo/dphsi/PHS/infdis2005.htm 32. Centers for Disease Control and Prevention: Case defi nition for infectious conditions under public health surveillance. MMWR Recomm Rep 46(RR-10):1–55, 1997. (Also available at http://www.cdc.gov/epo/ dphsi/casedef/index.htm) 33. Emergency Medical Treatment and Labor Act (EMTALA). Fed Reg 68(174):53222, 2003. 34. CMS Interpretive Guidelines on EMTALA. Centers for Medicare & Medicaid Services web site. Available at http://www/cms/hhs.gov/ providers/emtala 35. The pediatric critical care center. In Seidel JS, Knapp JF (eds): Childhood Emergencies in the Office, Hospital, and Community: Organizing Systems of Care. Elk Grove Village, IL: American Academy of Pediatrics, 2000, pp 159–172. 36. McCraig LF, Burt CW: National Hospital Ambulatory Medical Care Survey: 2003 emergency department summary. Adv Data 358:1–38, 2005. 37. American Academy of Pediatrics, Committee on Pediatric Emergency Medicine: Overcrowding crisis in our nation’s emergency departments: Is our safety net unraveling? Pediatrics 114:878–888, 2004. *38. American College of Emergency Physicians, Crowding Resources Task Force: Responding to Emergency Department Crowding: A Guidebook for Chapters. Dallas: American College of Emergency Physicians, 2002. 39. American College of Emergency Physicians. Care of Children in the Emergency Department: Guidelines for Preparedness-Implementation Kit. Available at http://host.acep.org.tmp3.secure-xp.net/aapacep

Chapter 155 Triage Sharon E. Mace, MD and Thom A. Mayer, MD

Key Points Triage is the prioritization of care based on illness/ injury, severity, prognosis, and resource availability. Triage identifies patients who cannot wait to be seen, prioritizes all patients, and initiates diagnostic and therapeutic measures. Disaster triage differs from emergency department triage. During a disaster with limited resources, patients with little or no chance of survival are not resuscitated. The disaster triage categories are red (most urgent, first priority), yellow (urgent, second priority), green (nonurgent, walking wounded, third priority), and black (dead or catastrophic).

Introduction and Background Triage is the prioritization of patient care (or victims during a disaster) based on illness/injury, severity, prognosis, and resource availability. The purpose of triage is to identify patients needing immediate resuscitation; to assign patients to a predesignated patient care area, thereby prioritizing their care; and to initiate diagnostic/therapeutic measures as appropriate. The term triage originated from the French verb trier which means to sort. During the time of Napoleon, the French military used triage to serve as a battlefield clearing hospital for wounded soldiers. The U.S. military’s first use of triage was during the Civil War. Triage on the battlefield was a distribution center from which injured soldiers were sorted or distributed to various hospitals. For the military during World Wars I and II, triage was the procedure that determined which injured soldiers were able to be returned to the battlefield. Military triage continued to evolve during the Korean and Vietnam wars with the tenet of doing the “greatest good for the greatest number of wounded and injured.”1 Refinements in battlefield medicine and military triage have continued during more recent conflicts, including Iraq.

Other situations in which the triage process has been employed, in addition to the battlefield, are during disasters, following mass casualty incidents (MCI), and in emergency departments (EDs). Triage during a disaster involves field triage, which sorts disaster victims into categories ranging from the walking wounded to those with injuries who are salvageable to the unsalvageable and the dead.

Issues and Solutions The Triage Process The nurse assesses and determines priority of care (triages) based not only on the patient’s physical, developmental, and psychosocial needs but also on parameters of patient flow in the emergency care system and of health care access. According to the Emergency Nurses Association (ENA), triage should be done by an experienced nurse with competency in triage.2,3 The nurse should accomplish the following during triage: take history appropriate to the severity of the complaint, obtain vital signs, ask predetermined ED/hospitalrequired screening questions, and assign patient priority. Triage may be either focused or comprehensive. Comprehensive triage refers to taking a complete history, checking vital signs, determining allergies, and, where appropriate, performing a physical examination. Focused triage is generally used for more minor illnesses or injuries and includes a more limited history and screening prior to assessing patient priority. Triage bypass, which is addressed more fully later in this chapter, refers to an approach that places patients directly into ED rooms at times when space and staffing allow, and triage is performed at the bedside. The advantages of comprehensive triage include immediate identification of patients with life-threatening or emergent conditions and administration of basic first aid measures. In addition, the patient (and family) are met by an experienced nurse who can address the patient/family’s physical, psychosocial, and emotional issues. One criticism of a comprehensive triage system is that it takes too much time, thereby creating a “logjam” of patients backed up waiting to be seen by the triage nurse.4 This has led to a two-tier triage system with the triage nurse determining, from the chief complaint and an observation or “across the room” assessment, who is taken immediately to the patient care area versus waiting for additional assessment and registration. The two-tiered triage system includes a primary 1087

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nurse and a sorter nurse, and may be used to achieve comprehensive triage during high-volume periods. Pediatric and geriatric patients take more time to triage than other patients. Comprehensive triage is said to take only 2 to 5 minutes, although one study found that this occurred only 22% of the time.5 A concern has been expressed that this 2- to 5-minute time frame for triage may be unrealistic.4 There have also been studies indicating inconsistency in triage assessment among experienced triage personnel and between nurses and physicians.6-10 Whether focused triage, comprehensive triage, or triage bypass is used, performance improvement data should be monitored to assess efficacy. Triage Categories Emergency department triage has several functions, including (1) identification of patients who should not wait to be seen, and (2) prioritization of incoming patients. This is accomplished by determining the patient’s illness/injury severity or acuity. Acuity is the degree to which the patient’s condition is life- or limb-threatening and whether immediate treatment is needed to alleviate symptoms. There are various triage acuity systems ranging from two to five levels (Table 155–1). In the United States, a three-level triage system is most commonly used (69%), with 12% of EDs using a four-level system, 3% using a five-level model, and 16% using no acuity system or nonresponding according to an ENA survey done in 2001.11 There is some evidence that a five-level triage system is more effective than a three-level triage system.12 Specific Triage Systems Various triage systems have been used throughout the world: the Australian Triage Scale, the Manchester Triage Scale, the Canadian Triage and Acuity Scale, and the Emergency Sever-

Table 155–1

ity Index (ESI)13-21 (Table 155–2). All four of these scales have been validated for reliability and validity in adults.14-17 Emergency Severity Index The ESI is a five-level triage system developed in the United States that uses a flowchart-based triage algorithm.18-21 The ESI uses patient acuity (stability of vital signs, degree of distress), as well as expected resource intensity and timeliness (expected staff response, time to disposition), to define the five categories (Table 155–3). Pediatric Triage Of the approximately 110.2 million patients seen in EDs in the United States in 2002, about 30% were pediatric patients, with 85% of those seen in general EDs.22 Furthermore, there is some evidence that, in a general ED, adults may be “seen sooner than equally ill pediatric patients, resulting in unacceptable waiting times for seriously ill pediatric patients” unless triage criteria are modified for pediatric patients.23 Improvement in pediatric patient flow with an increase in pediatric triage acuity levels (e.g., a significant increase in the emergent and urgent pediatric patients) resulted from incorporating specific pediatric acuity markers and from posting age-specific abnormal signs and symptoms.23 Issues relevant to pediatric triage include inapplicability of adult triage criteria to pediatric patients; the often subtle and difficult-to-recognize signs and symptoms of illness/injury in young children and infants, especially those less than 1 to 2 years of age; the frequent unreliability of the clinical impression (even with experienced triage personnel); physiology and behavior in children and infants, particularly in infants, different from that in adults; greater morbidity and mortality in pediatric patients than in adults for similar diseases; and symptom variability during a given illness. Because

Triage Acuity Systems by Level

2 Levels

3 Levels

4 Levels

5 Levels

5 Levels

Emergent Nonemergent

Emergent Urgent Nonurgent

Life threatening Emergent Urgent Nonurgent

Resuscitation Emergent Urgent Nonurgent Referred

Critical Emergent Urgent Nonurgent Fast track

Table 155–2

International Triage Systems

Australasian

Level

Physician/ Staff Response Time (min)

1 = Resuscitation

0 (Immediate)

2 = Emergency

≤10

3 = Urgent

≤30

4 = Semi-Urgent

≤60

5 = Nonurgent

≤120

Manchester (United Kingdom)

Level 1 = Immediate (Red) 2 = Very Urgent (Orange) 3 = Urgent (Yellow) 4 = Standard (Green) 5 = Nonurgent (Blue)

Physician/ Staff Response Time (min) 0 (Immediate)

Canadian

Emergency Severity Index

Level

Physician/ Staff Response Time (min)

Level

Physician/ Staff Response Time (min)

1 = Resuscitation

0 (Immediate)

1 = Unstable

0 (Immediate)

≤10

2 = Emergent

≤15

2 = Threatened

Minutes

≤60

3 = Urgent

≤30

3 = Stable

≤60

≤120

4 = Less Urgent

≤60

4 = Stable

≤240

5 = Nonurgent

≤120

5 = Stable

Could be delayed Could be delayed

Chapter 155 — Triage

Table 155–3 Stability of vital functions (ABCs) Life threat or organ threat Requires resuscitation Severe pain or severe distress

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Emergency Severity Index (ESI) ESI-1

ESI-2

ESI-3

ESI-4

ESI-5

Unstable

Threatened

Stable

Stable

Stable

Obvious

Reasonably likely

Unlikely (possible)

No

No

Immediately

Sometimes

Seldom

No

No

Yes

No

No

No

Medium: multiple diagnostic studies; or brief period of observation; or complex procedure Up to 1 hr

Low: one simple diagnostic study; or one simple procedure

Low: examination only

Could be delayed

Could be delayed 1 hr

Expected resource intensity

Maximum: staff at bedside continuously; mobilization of outside resources

Physician/staff response Expected time to disposition Examples

Immediate team effort

Yes (sufficient, but not necessary for this category) High: multiple, often complex diagnostic studies; frequent consultation; continuous (remote) monitoring Minutes

1.5 hr

4 hr

6 hr

2 hr

Cardiac arrest, intubated trauma patient, severe drug overdose

Most chest pain, stable trauma (mechanism concerning), elderly pneumonia patient, altered mental status, behavioral disturbance (potential violence)

Most abdominal pain, dehydration, esophageal food impaction, hip fracture

Closed extremity trauma, simple laceration, cystitis, typical migraine

of the difficulties in determining acuity for infants less than 6 months old, some have recommended that EDs that see relatively few pediatric patients assign all children less than 6 months old to the emergent category.24 Triage Categories and Triage Systems for Pediatric Patients Various acuity systems for specific diseases, illnesses, and injuries in pediatric patients have been developed. Multiple pediatric trauma scoring systems exist.25 Scoring systems for specific respiratory diseases, such as “Croup Scores,” have also been developed.26 Various scales for assessment of the young infant with fever, such as the Yale observational scale, have been used to specifically evaluate the febrile infant.27 Unfortunately, a comprehensive pediatric triage assessment tool that applies to all types of pediatric illnesses and injuries throughout the entire range of pediatric age groups (newborns, infants, toddlers, preschool age, early school years, and adolescence) has yet to be developed and validated in extensive numbers of pediatric patients.24 However, several pediatric triage and/or assessment tools are available. A commonly used triage acuity classification for pediatric patients uses four levels28 : Class 1—critical: life- or limb-threatening illness/injury that needs immediate care Class 2—acute: significant alteration in physical or mental health that could potentially become life or limb threatening and needs intervention as soon as possible Class 3—urgent: significant physical or mental health problems that are not life threatening and need intervention in a timely fashion Class 4—nonurgent: may receive care when convenient These are similar to the adult four-level acuity classifications. More recently, a five-level system has been suggested, again similar to the adult five-level acuity classifications: level 1 =

Sore throat, minor burn, recheck

critical, level 2 = emergent, level 3 = urgent, level 4 = nonurgent, and level 5 = fast track 29 (see Table 155–1). Several important caveats have also been suggested. All immunocompromised pediatric patients should be considered as being seriously ill even if their presenting symptoms are not critical.30 Immunocompromised patients include those on corticosteroids or immunosuppressives; patients with chronic illnesses, malignancy, and sickle cell disease; and the very young (particularly young infants), who may not have the typical signs and symptoms of a serious or lifethreatening illness early during the course of their illness. Such high-risk patients, including patients with a history of premature birth, chronic illness, and being immunocompromised, may initially “look well” and then rapidly deteriorate. Child maltreatment should be considered in the differential diagnosis of all pediatric complaints. Key elements of the suspected child abuse or neglect (SCAN) triage interview include detailed documentation of a thorough history with quotes, and an exact description of findings and observations.28,31 Many of the specific pediatric triage systems are based on the primary survey (airway, breathing, and circulation [ABCs]) and a secondary survey from the American College of Surgeons Committee on Trauma28,32,33 (Tables 155–4 and 155–5). A primary and secondary pediatric triage survey using an A-to-J alphabetized mnemonic is included in the Emergency Nursing Pediatric Course28 (see Table 155–4). All of these various triage systems, whether adult or pediatric, need to be validated for reliability and validity in large numbers of pediatric patients. There is evidence that application of the adult triage systems (see Table 155–2) may not be valid for pediatric patients without the addition of pediatric clinical observations and pediatric vital signs, which may lead to a more reliable triage of younger children.23,34-36

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Table 155–4

Primary and Secondary Pediatric Triage Survey Primary

A = Airway

Secondary

✔ Patency, positioning for air entry, audible sounds, airway obstruction (blood, mucus, edema, foreign body) ✔ Increased or decreased work of respiration, quality of breath sounds; nasal flaring; use of accessory muscles; pattern; quality; rate ✔ Color and temperature of skin; capillary refill; strength and rate of peripheral pulses Placement of a cervical collar when indicated ✔ Level of consciousness (Glasgow Coma Scale); response to environment; muscle tone; pupil response

F = Find

Find out underlying history of current illness or injury

G = Get vital signs

Obtain vital signs, obtain orthostatic vital signs if condition warrants

H = Head-to-toe assessment

D = Dextrose

✔ Serum glucose level in patients with altered mental status

I = Intervention

E = Expose

Expose patient by undressing to identify underlying injuries

J = Judgment

Perform a head-to-toe assessment for a complete and thorough examination Initiate the Triage Documentation Record Assess patient for rashes, communicable diseases, or immunosuppression, and place in appropriate isolation Perform triage interventions (first aid, medication administration, diagnostic studies) Make appropriate triage classification of patient acuity

B = Breathing

C = Circulation C = Cervical collar C = Consciousness

Table 155–5

Triage Observation Tool Triage Observation Tool (No/Yes)

Airway Breathing

Circulation

Disability

Expose Risk Factors

Obstructed airway (blood, vomit, foreign bodies, facial burn) Allergic reaction Increased respiratory effort Fatigue, nasal flaring Tachypnea Tracheal tug, chest recession Wheeze, stridor, grunting Bradypnea, hypoventilation O2 saturation higher than expected for degree of respiratory effort Tachycardia, bradycardia Capillary return >2 sec Pale, mottled, or cyanosed Peripheral pulses or perfusion Obvious bleeding out Sunken eyes, dry oral mucosa Decreased feeding, decreased urine output Irritable or drowsy and hard to wake Responds only to pain High-pitched cry Obvious pain Purpura Chickenpox or measles Oncology patient or immunosuppressed Cardiac history Infant 41°)? Hypothermia (36°)?

Immune System

Sickle cell? AIDS? Corticosteroids?

Level of Consciousness

Irritable? Lethargic? Pain only? Convulsing? Unresponsive?

Dehydration

Hollow eyes? Capillary refill? Cold hands, feet? Voiding? Severe diarrhea? Vomiting: projectile, bilious, persistent? Dry mucous membranes?

SAVE: Observations made prior to touching the child CHILD: History from caretaker and brief exam FIGURE 155–1. SAVE-a-CHILD triage system for recognition of the seriously ill pediatric patient.

implementing diagnostic/therapeutic measures and reassessing the patient. SOAPIE stands for subjective data (chief complaint); objective data such as vital signs; analysis of data, leading to assigning acuity; plan, or what is to be done; initiating diagnostic/therapeutic interventions per protocols and nursing practice; and evaluation, which indicates that triage is a dynamic process with constant evaluation and re-evaluation. Triage interventions range from beginning diagnostic studies, such as radiologic studies and an electrocardiogram, to initiating therapeutic measures, including giving oral pain medications and antipyretics and applying dressings. Other triage measures include applying topical anesthetics to

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wounds (to be sutured later) and to potential intravenous sites for children and infants who will likely needs intravenous fluids and/or medications. Such treatment interventions in triage have been shown to decrease ED turnaround time, thereby improving ED flow. Triage-initiated protocols can expedite care and improve patient/family satisfaction. Customer Service at Triage Customer service has become an increasingly emphasized aspect of the provision of emergency medical care, and is especially pertinent to the care of children. Virtually every hospital in the country has some patient satisfaction tool, which is used to assess the patient’s and family’s perception of the care that they received in the ED. While the axiom “You never get a second chance to make a first impression” was not meant to specifically describe ED triage, it might well have been. Nearly 75% of patients presenting to the ED undergo triage, which is their first contact with the medical care system. For that reason, triage nurses and other personnel assisting in the process should be trained in the importance of delivering customer service excellence at the earliest appropriate time. Mayer and Cates have suggested that this comprises three elements39 : • Making the customer service diagnosis as well as the clinical diagnosis • Negotiating agreement and resolution of expectations • Building moments of truth into the clinical encounter By way of simple example, one of the most common clinical presentations in the pediatric and general ED is the child with fever. While the clinical diagnosis is often apparent, even at triage, the customer service diagnosis comprises the fear of more serious illness on the part of the parents and perhaps even the child. Addressing those concerns at triage by providing reassurance at the earliest time is an extremely important part of maximizing patient satisfaction. Similarly, the parent’s expectations are often dramatically different from those of experienced health care providers, since the parents often are concerned that the child may have seizures, meningitis, or another life-threatening illness, whereas an experienced clinician may understand from simple observation of the child that these diagnoses are not likely. In order to assure that the best customer service is provided, negotiating these expectations is important, and can also begin at triage. Finally, the concept of “moments of truth” was originally described by Jan Carlzon in a book of that same name. Carlzon pointed out that customer perceptions are usually not based on technical aspects, but rather comprise what he described as “50,000 Moments of Truth per day, created by the service provider himself.”40 Thus the institution is not assessed so much on the detailed provision of clinical care, but on the moments of truth provided by the nurses, physicians, technicians, and other ED personnel. For example, simple statements (“scripts”) can be made, such as, “I have three children of my own, and I remember how concerned I was the first time one of them developed a fever in the middle of the night.” Delivering excellent customer service and assuring patient satisfaction require the same proactive approach that one would apply to clinical guidelines or protocols. The customer service aspects of triage should be discussed among the providers of clinical care, so that such scripts and procedures can be proactively developed.

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SECTION VI — The Practice Environment

Newer Concepts of Triage Virtually all EDs encounter times when they are severely capacity constrained. A number of creative process improvements have been made to help assure that triage functions expeditiously, even at times when there are a large number of patients to be seen. These include advanced triage/advanced initiatives (AT/AI), Team Triage and Treatment, triage bypass, Triage Away, and secondary triage. Each of these is designed to be used in various ways and addresses the substantial capacity constraint issues faced by many EDs, including both general and pediatric EDs. AT/AI consists of a set of medically approved standing orders and initiatives that may be implemented at the triage area at times when rooms are not available in the treatment area. These include protocols for minor extremity trauma, urinary tract infections, abdominal pain, neutropenic patients with fever, and pretreatment of lacerations with topical anesthetic agents. Each of these protocols is discussed in advance between the medical and nursing staff of the ED, approved jointly, and implemented after training of the triage nurses. Triage bypass is utilized at times when several patients have presented to triage, but there are adequate numbers of physicians, nurses, and support personnel in the treatment area to care for such patients in a timely fashion. Since these patients will be seen by the same ED staff in the same treatment areas, they bypass triage, are registered in the room, and are triaged and treated by the same nurses and physicians who will be caring for them. Because of the nature of patient flow and the fact that most EDs become capacity constrained by the mid-morning or afternoon hours, triage bypass is predominantly utilized during the early to mid-morning hours. Team Triage and Treatment is a unique and innovative approach to dealing with capacity constraints by assigning an emergency physician (or physician assistant/nurse practitioner), nurse, technician, and, in some cases, registrar to the triage area at times when there are predictable delays in patient care due to the number of treatment rooms available. Following initial triage by the triage nurse, acutely ill or injured patients are sent directly back to the treatment area. Similarly, patients with minor (fast track) problems are sent to such an area. The remainder of the patients are then evaluated at the triage area by the team triage members. In a busy level I trauma center that sees over 80,000 patients per year, team triage is utilized approximately 8 hours per day and substantially decompresses patient waiting times, improves patient satisfaction, improves patient safety, and offers better access to care for patients (T. Mayer, personal communication, May 2005). These data indicate that one third of such patients are evaluated, treated, and have their treatment completed at the triage area, including patients with sufficient severity of abdominal pain to warrant an abdominal computed tomography scan. While this program requires an investment in resources, the reduction in patients left without treatment and the capacity for increasing volume more than offset the cost of the investment in the program. Triage Away is a program used in some EDs that have chosen to evaluate patients at triage and, when it is determined that they have a minor illness or injury, simply triage them away to other facilities. In some communities such

programs can be effective; however, it does require a clearly specified primary health clinic or public health facility to which the patients can be safely and efficiently triaged. Such Triage Away programs are unusual, precisely because the safety net capacity of the ED is not backed up by such primary care or public health facilities in most communities. Secondary triage refers to the combined effort of the emergency physicians and nurses to re-triage patients who are already in treatment rooms either to alternate rooms or to hallway spaces at times when their workup and treatment have not been completed, but additional patients are in need of treatment areas in which they can be evaluated. Emergency physicians and nurses should prospectively design protocols and procedures to assure that such secondary triage is safe, efficient, and in the patient’s best interest. Legal Considerations According to the Consolidated Omnibus Budget Reconciliation Act passed in 1985, hospitals receiving Medicare funds are mandated to evaluate all patients who arrive in the ED and treat anyone with an emergent medical problem or any woman in active labor. In addition, any transferred patients must be stabilized and the receiving institution must have agreed to accept the patient. Under the Emergency Medical Treatment and Labor Act (EMTALA), patients can be transferred only when they need a higher level of care (or a service not provided at the institution at which they present) and only after an appropriate “screening” evaluation and stabilization (see Chapter 150, Emergency Medical Treatment and Labor Act [EMTALA]). It is inappropriate for a nurse or any other medical personnel to arbitrarily triage a patient to another facility. After an appropriate medical screening examination, usually by the responsible physician, it is possible that triage nurses, while following written protocols, could redirect patients to predesignated areas such as an outpatient clinic. However, precise documentation and preestablished written protocols are mandatory. Indeed, many experts recommend that a chart be generated for any patient presenting to the ED regardless of whether or not they are evaluated and treated. Prehospital Triage Field triage by Emergency Medical Services (EMS) personnel is the assessment of individual patients with the purpose of determining the most appropriate receiving facility. The development of trauma systems led to trauma triage in prehospital care. This is based on the principle that patients with life-threatening or serious multisystem injuries from trauma have a better outcome when transported directly to a facility staffed and equipped to provide resuscitation and definitive treatment. The aim is to send all seriously injured patients to a trauma center without overwhelming the resources of the trauma center by over-triaging. Occasionally a trauma patient may bypass the closest hospital to be transported directly to the trauma center. System-wide prehospital EMS trauma protocols provide guidelines to prehospital care providers for differentiating which trauma patient is transported to the trauma center or to the closest hospital for treatment. With the advent of more sophisticated therapies and specialized hospitals, such as chest pain centers with aroundthe-clock cardiac catheterization capabilities or stroke centers capable of delivering organ/region-specific thrombolytics,

Chapter 155 — Triage

the expansion and increased importance of “prehospital” or “field” triage are likely. Disaster Triage A disaster is an event that exceeds the capabilities of the response (e.g., the need is greater than the resources), resulting in disruption of normal function.41,42 In order to more concisely describe and reflect the degree (or stage) of disaster, the Potential Injury Causing Event (PICE) nomenclature has been developed.43 Triage during a disaster is different from ED triage. The purpose of ED triage is to identify critically ill patients and assure that they receive immediate resuscitation, while the principle of disaster management is to “do the most good for the most people.”1 It is possible during a disaster with limited response resources that, in order to maximize care for the majority of victims, some patients who have little or no chance of survival will not be not resuscitated.44 It is often a difficult concept for health care providers to ration resources and not expend efforts to resuscitate patients who are considered near death in order to save others. Comfort care should be provided to the dying patients when resources become available. As with ED triage, there is no universally accepted standardized system for disaster or MCI triage, although several

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triage systems have been suggested. One MCI/disaster triage tool is the Simple Triage and Rapid Treatment (START) technique.45 This is based on a rapid assessment of respiration, perfusion, and mental status (RPM). Casualties who are ambulatory are asked to move away from the immediate area of the incident. These “walking wounded” are categorized as “green” or minor. The remaining patients are sorted into unsalvageable, immediate, and delayed (Fig. 155–2). If the patient has a patent airway and is breathing, by assessing the respiratory rate (>30 per minute or < 30 per minute), the radial pulse (present or absent), and the mental status (follows commands: yes or no), the patient can be categorized. Unsalvageable patients are patients who are not breathing even after positioning their airway and are classified “black” or deceased. “Red” (immediate) patients have an immediate threat to life or limb but, if given immediate care, will probably survive. Examples include a patient with altered mental status, labored respirations, or shock. “Yellow” (delayed) patients have significant injuries but can probably tolerate a 45- to 60-minute wait without undue risk. This color-coded four-category system is probably the most common disaster/MCI triage system in the United States. “Red” casualties are the first priority and are “most urgent.” Patients classified “Yellow” are the second priority and are “urgent.” “Green” patients comprise the “walking

Start triage

Respirations

Yes

No

Position airway

FIGURE 155–2. Simple Triage and Rapid Treatment (START) tool.

No

Yes

Unsalvageable

Immediate

≥30

13 yr: