CURRENT Diagnosis and Treatment Critical Care, Third Edition

a L A N G E medical book

CURRENT

Diagnosis & Treatment Critical Care THIRD EDITION Edited by Frederic S. Bongard, MD Professor of Surgery David Geffen School of Medicine University of California, Los Angeles Chief, Division of Trauma and Critical Care Director of Surgical Education Harbor-UCLA Medical Center Torrance, California

Darryl Y. Sue, MD Professor of Clinical Medicine David Geffen School of Medicine University of California, Los Angeles Director, Medical-Respiratory Intensive Care Unit Division of Respiratory and Critical Care Physiology and Medicine Associate Chair and Program Director Department of Medicine Harbor-UCLA Medical Center Torrance, California

Janine R. E. Vintch, MD Associate Clinical Professor of Medicine David Geffen School of Medicine University of California, Los Angeles Divisions of General Internal Medicine and Respiratory and Critical Care Physiology and Medicine Harbor-UCLA Medical Center Torrance, California

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Copyright © 2008 by The McGraw-Hill Companies, Inc. All rights reserved. Manufactured in the United States of America. Except as permitted under the United States Copyright Act of 1976, no part of this publication may be reproduced or distributed in any form or by any means, or stored in a database or retrieval system, without the prior written permission of the publisher. 0-07-164300-1 The material in this eBook also appears in the print version of this title: 0-07-143657-X. All trademarks are trademarks of their respective owners. Rather than put a trademark symbol after every occurrence of a trademarked name, we use names in an editorial fashion only, and to the benefit of the trademark owner, with no intention of infringement of the trademark. Where such designations appear in this book, they have been printed with initial caps. McGraw-Hill eBooks are available at special quantity discounts to use as premiums and sales promotions, or for use in corporate training programs. For more information, please contact George Hoare, Special Sales, at [email protected] or (212) 904-4069. TERMS OF USE This is a copyrighted work and The McGraw-Hill Companies, Inc. (“McGraw-Hill”) and its licensors reserve all rights in and to the work. Use of this work is subject to these terms. Except as permitted under the Copyright Act of 1976 and the right to store and retrieve one copy of the work, you may not decompile, disassemble, reverse engineer, reproduce, modify, create derivative works based upon, transmit, distribute, disseminate, sell, publish or sublicense the work or any part of it without McGraw-Hill’s prior consent. You may use the work for your own noncommercial and personal use; any other use of the work is strictly prohibited. Your right to use the work may be terminated if you fail to comply with these terms. THE WORK IS PROVIDED “AS IS.” McGRAW-HILL AND ITS LICENSORS MAKE NO GUARANTEES OR WARRANTIES AS TO THE ACCURACY, ADEQUACY OR COMPLETENESS OF OR RESULTS TO BE OBTAINED FROM USING THE WORK, INCLUDING ANY INFORMATION THAT CAN BE ACCESSED THROUGH THE WORK VIA HYPERLINK OR OTHERWISE, AND EXPRESSLY DISCLAIM ANY WARRANTY, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. McGraw-Hill and its licensors do not warrant or guarantee that the functions contained in the work will meet your requirements or that its operation will be uninterrupted or error free. Neither McGraw-Hill nor its licensors shall be liable to you or anyone else for any inaccuracy, error or omission, regardless of cause, in the work or for any damages resulting therefrom. McGraw-Hill has no responsibility for the content of any information accessed through the work. Under no circumstances shall McGraw-Hill and/or its licensors be liable for any indirect, incidental, special, punitive, consequential or similar damages that result from the use of or inability to use the work, even if any of them has been advised of the possibility of such damages. This limitation of liability shall apply to any claim or cause whatsoever whether such claim or cause arises in contract, tort or otherwise. DOI: 10.1036/007143657X

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Contents Authors Preface 1. Philosophy & Principles of Critical Care Darryl Y. Sue, MD, & Frederic S. Bongard, MD General Principles of Critical Care Role of the Medical Director of the Intensive Care Unit Critical Care Scoring Current Controversies & Unresolved Issues

2. Fluids, Electrolytes, & Acid-Base Darryl Y. Sue, MD, & Frederic S. Bongard, MD Disorders of Fluid Volume Disorders of Water Balance Disorders of Potassium Balance Disorders of Phosphorus Balance Disorders of Magnesium Balance Disorders of Calcium Balance Acid-Base Homeostasis & Disorders

3. Transfusion Therapy Elizabeth D. Simmons, MD Blood Components Blood Component Administration Complications of Transfusion Current Controversies & Unresolved Issues

4. Pharmacotherapy Darryl Y. Sue, MD Pharmacokinetic Parameters Pharmacokinetic Considerations Medication Errors & Prevention in the ICU

vii xi

6. Nutrition John A. Tayek, MD Nutrition & Malnutrition in the Critically Ill Patient Nutritional Therapy Nutritional Support in Specific Diseases New Treatment Strategies for the Malnourished Critically Ill Patient

1 1 8 10

7. Imaging Procedures 12

Kathleen Brown, MD, Steven S. Raman, MD, & Nam C. Yu, MD Imaging Techniques Iodinated Contrast Agents Use of Central Venous Catheters for Contrast Injection Imaging of Support & Monitoring Devices in the ICU Imaging in Pulmonary Diseases Imaging in Pleural Disorders Imaging of the Abdomen & Pelvis Imaging of Acute Gallbladder & Biliary Tract Disorders Imaging in Emergent & Urgent Genitourinary Conditions

14 14 22 34 42 47 51 56

71 71 79 79

8. Intensive Care Monitoring

88 88 88 95

97

Tai-Shion Lee, MD, & Biing-Jaw Chen, MD Physiologic Effects of Anesthesia in the Critically Ill Airway Management Pain Management in the ICU Muscle Relaxants in Intensive Care Sedative-Hypnotics for the Critically Ill Malignant Hyperthermia

97 101 103 106

117 126 130 134

137

137 138 139 139 144 161 167 181 184

187

Kenneth Waxman, MD, Frederic S. Bongard, MD, & Darryl Y. Sue, MD Electrocardiography 187 Blood Pressure Monitoring 188 Central Venous Catheters 193 Pulmonary Artery Catheterization 196 Cardiac Output 199 Pulse Oximetry 201 203 Airway CO2 Monitoring Transcutaneous Blood Gases 204 Respiratory Mechanics 204 Respired Gas Analysis 206 Clinical Applications 206

82

5. Intensive Care Anesthesia & Analgesia

117

9. Transport Samuel J. Stratton, MD, MPH Interhospital Transport Equipment & Monitoring Education & Training Reimbursement Standards & Costs Current Controversies & Unresolved Issues

110 115

iii

208 208 211 212 213 214

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CONTENTS

10. Ethical, Legal, & Palliative/End-of-Life Care Considerations 215 Paul A. Selecky, MD Ethical Principles Conflicts Between Ethical Principles Ethical Decision Making Advance Care Planning Medicolegal Aspects of Decision Making Withholding & Withdrawing Life Support Organ Donation Role of the Health Care Professional Web Sites for Health Care Ethics Information & Policies

11. Shock & Resuscitation Frederic S. Bongard, MD Hypovolemic Shock Distributive Shock Cardiac Shock

12. Respiratory Failure Darryl Y. Sue, MD, & Janine R. E. Vintch, MD Pathophysiology of Respiratory Failure Treatment of Acute Respiratory Failure Acute Respiratory Failure from Specific Disorders

13. Renal Failure Andre A. Kaplan, MD Nondialytic Therapy for Acute Renal Failure Dialytic Therapy for the Critically Ill Patient Critical Illness in Patients with Chronic Renal Failure

14. Gastrointestinal Failure in the ICU Gideon P. Naudé, MD Pancreatitis Bowel Obstruction Obstruction of the Large Bowel Adynamic (Paralytic) Ileus Diarrhea & Malabsorption Pancreatic Insufficiency Lactase Deficiency Diarrhea

15. Infections in the Critically Ill Laurie Anne Chu, MD, & Mallory D. Witt, MD Sepsis Community-Acquired Pneumonia Urosepsis Infective Endocarditis

215 216 216 217 217 218 219 219

Necrotizing Soft Tissue Infections Intraabdominal Infections Infections in Special Hosts Principles of Antibiotic Use in the ICU Evaluation of the ICU Patient with New Fever Nosocomial Pneumonia Urinary Catheter–Associated Infections Intravenous Catheter–Associated Infections Clostridium Difficile–Associated Diarrhea Hematogenously Disseminated Candidiasis Antimicrobial Resistance in the ICU Botulism Tetanus

370 372 373 376 379 379 382 384 386 388 389 392 394

221

222 222 230 242

247 247 253 280

314 330 334 342

345 345 351 354 355 356 357 357 357

359 359 362 365 367

16. Surgical Infections Timothy L. Van Natta, MD Evaluation and Management of Infection by Body Site

17. Bleeding & Hemostasis Elizabeth D. Simmons, MD Approach to the Bleeding Patient Current Controversies & Unresolved Issues

18. Psychiatric Problems

397

400

409 427 427

431

Stuart J. Eisendrath, MD, & John R. Chamberlain, MD Delirium Depression Anxiety & Fear Staff Issues

431 436 438 440

19. Care of the Elderly Patient

443

Shawkat Dhanani, MD, MPH, & Dean C. Norman, MD Physiologic Changes with Age Management of the Elderly Patient in the ICU Special Considerations

443 445 447

20. Critical Care of the Oncology Patient

451

Darrell W. Harrington, MD, & Darryl Y. Sue, MD Central Nervous System Disorders 451 Metabolic Disorders 457 Superior Vena Cava Syndrome 465

21. Cardiac Problems in Critical Care

467

Shelley Shapiro, MD, PhD, & Malcolm M. Bersohn, MD, PhD Atrial Arrhythmias Ventricular Arrhythmias

486 488

CONTENTS Heart Block Cardiac Problems During Pregnancy Toxic Effects of Cardiac Drugs

22. Coronary Heart Disease Kenneth A. Narahara, MD Physiologic Considerations Myocardial Ischemia (Angina Pectoris) Acute Coronary Syndromes: Unstable Angina and Non-ST-Segment-Elevation Myocardial Infarction Acute Myocardial Infarction with ST-Segment Elevation

23. Cardiothoracic Surgery

491 493 494

498 498 499

502 505

514

Edward D. Verrier, MD, & Craig R. Hampton, MD Aneurysms, Dissections, & Transections of the Great Vessels 514 Postoperative Arrhythmias 518 Bleeding, Coagulopathy, & Blood Product Utilization 520 Cardiopulmonary Bypass, Hypothermia, Circulatory Arrest, & Ventricular Assistance 525 Postoperative Low-Output States 529

24. Pulmonary Disease Darryl Y. Sue, MD, & Janine R. E. Vintch, MD Status Asthmaticus Life-Threatening Hemoptysis Deep Venous Thrombosis & Pulmonary Thromboembolism Anaphylaxis Angioedema

25. Endocrine Problems in the Critically Ill Patient

534 534 540 545 562 563

566

Shalender Bhasin, MD, Piya Ballani, MD, & Ricky Phong Mac, MD Thyroid Storm Myxedema Coma Acute Adrenal Insufficiency Sick Euthyroid Syndrome

566 570 572 576

26. Diabetes Mellitus, Hyperglycemia, & the Critically Ill Patient

581

Eli Ipp, MD, & Chuck Huang, MD Diabetic Ketoacidosis Hyperglycemic Hyperosmolar Nonketotic Coma Management of the Acutely Ill Patient with Hyperglycemia or Diabetes Mellitus

581 593 594



Hyperglycemia Hypoglycemia Other Complications of Diabetes Mellitus

27. HIV Infection in the Critically Ill Patient Mallory D. Witt, MD, & Darryl Y. Sue, MD Complications of HIV Disease: An Overview Other Infectious Causes of Pneumonia and Respiratory Failure

28. Dermatologic Problems in the Intensive Care Unit

v 594 595 597

598

598 604

609

Kory J. Zipperstein, MD Common Skin Disorders Drug Reactions Purpura Life-Threatening Dermatoses Cutaneous Manifestations of Infection

609 612 619 623 626

29. Critical Care of Vascular Disease & Emergencies

632

James T. Lee, MD, & Frederic S. Bongard, MD Vascular Emergencies in the ICU Critical Care of the Vascular Surgery Patient

30. Critical Care of Neurologic Disease

632 651

658

Hugh B. McIntyre, MD, PhD, Linda Chang, MD, & Bruce L. Miller, MD Encephalopathy & Coma 658 Seizures 662 Neuromuscular Disorders 666 Cerebrovascular Diseases 673

31. Neurosurgical Critical Care Duncan Q. McBride, MD Head Injuries Aneurysmal Subarachnoid Hemorrhage Tumors of the Central Nervous System Cervical Spinal Cord Injuries

32. Acute Abdomen Allen P. Kong, MD, & Michael J. Stamos, MD Specific Pathologic Entities Current Controversies & Unresolved Issues

680 680 686 688 690

696 700 701

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CONTENTS

33. Gastrointestinal Bleeding Sofiya Reicher, MD, & Viktor Eysselein, MD Upper Gastrointestinal Bleeding Lower Gastrointestinal Bleeding

34. Hepatobiliary Disease Hernan I. Vargas, MD Acute Hepatic Failure Acute Gastrointestinal Bleeding from Portal Hypertension Ascites Hepatorenal Syndrome Preoperative Assessment & Perioperative Management of Patients with Cirrhosis Liver Resection in Patients with Cirrhosis

35. Burns

703 703 710

714 714 716 717 719 720 720

723

David W. Mozingo, MD, William G. Cioffi, Jr., MD, & Basil A. Pruitt, Jr., MD I. Thermal Burn Injury 723 Initial Care of the Burn Patient 727 Principles of Burn Treatment 730 Care of the Burn Wound 735 Postresuscitation Period 741 Nutrition 743 II. Chemical Burn Injury 749 III. Electrical Burn Injury 750

36. Poisonings & Ingestions Diane Birnbaumer, MD Evaluation of Poisoning in the Acute Care Setting or ICU Treatment of Poisoning in the ICU Management of Specific Poisonings

752

752 754 757

37. Care of Patients with Environmental Injuries

786

James R. Macho, MD, & William P. Schecter, MD Heat Stroke 786 Hypothermia 788 Frostbite 791 Near-Drowning 793 Envenomation 795 Electric Shock & Lightning Injury 798 Radiation Injury 800

38. Critical Care Issues in Pregnancy Marie H. Beall, MD, & Andrea T. Jelks, MD Physiologic Adaptation to Pregnancy General Considerations in the Care of the Pregnant Patient in the ICU Management of Critical Complications of Pregnancy

39. Antithrombotic Therapy Elizabeth D. Simmons, MD Physical Measures Antiplatelet Agents Anticoagulants New Anticoagulants Defibrinating Agents Oral Anticoagulants Thrombolytic Therapy Antithrombotic Therapy in Pregnancy Antiphospholipid Antibody Syndrome Thrombosis in Cancer Patients Future Directions

Index

802 802 804 807

821 821 821 825 831 832 832 836 838 839 840 840

843

Authors Piya Ballani, MD

Kathleen Brown, MD

Southern California Endocrine Medical Group, Anaheim, California [email protected] Endocrine Problems in the Critically Ill Patient

Professor of Clinical Radiology, David Geffen School of Medicine, University of California, Los Angeles, California [email protected] Imaging Procedures

Marie H. Beall, MD Clinical Professor of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles; Vice Chair, Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, Torrance, California [email protected] Critical Care Issues in Pregnancy

John R. Chamberlain, MD

Malcolm M. Bersohn, MD, PhD

Linda Chang, MD

Professor of Medicine, David Geffen School of Medicine, University of California, Los Angeles; Director, Arrhythmia Service, Veterans Administration Greater Los Angeles Health Care System, Los Angeles, California [email protected] Cardiac Problems in Critical Care

Professor of Medicine, John A. Burns School of Medicine, University of Hawaii; Queens Medical Center, Honolulu, Hawaii [email protected] Critical Care of Neurologic Disease

Assistant Clinical Professor, Department of Psychiatry, University of California, San Francisco; Assistant Director, Psychiatry and the Law Program, University of California, San Francisco, San Francisco, California [email protected] Psychiatric Problems

Biing-Jaw Chen, MD Shalender Bhasin, MD

Clinical Associate Professor, David Geffen School of Medicine, University of California, Los Angeles, Harbor-UCLA Medical Center, Torrance, California [email protected] Intensive Care Anesthesia & Analgesia

Professor of Medicine, Boston University School of Medicine; Chief, Section of Endocrinology, Diabetes, and Nutrion, Boston Medical Center, Boston, Massachusetts [email protected] Endocrine Problems in the Critically Ill Patient

Laurie Anne Chu, MD Diane Birnbaumer, MD, FACEP

Southern California Permanente Medical Group, Kaiser Bellflower Medical Center, Bellflower, California [email protected] Infections in the Critically Ill

Professor of Clinical Medicine, David Geffen School of Medicine, University of California, Los Angeles; Associate Residency Program Director, Harbor-UCLA Medical Center, Torrance, California [email protected] Poisonings & Ingestions

William G. Cioffi, Jr., MD J. Murray Beardsley Professor & Chairman, Department of Surgery, Brown Medical School; Surgeon-in-Chief, Department of Surgery, Rhode Island Hospital, Providence, Rhode Island [email protected] Burns

Frederic S. Bongard, MD Professor of Surgery, David Geffen School of Medicine, University of California, Los Angeles; Chief, Division of Trauma and Critical Care, Director of Surgical Education, Harbor-UCLA Medical Center, Torrance, California [email protected] Philosophy & Principles of Critical Care; Fluids, Electrolytes, & Acid-Base; Intensive Care Monitoring; Shock & Resuscitation; Critical Care of Vascular Disease & Emergencies

Shawkat Dhanani, MD, MPH Associate Clinical Professor, David Geffen School of Medicine, University of California, Los Angeles; Director, Geriatric Evaluation and Management Unit, Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, California [email protected] Care of the Elderly Patient

vii Copyright © 2008 by The McGraw-Hill Companies, Inc. Click here for terms of use.

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AUTHORS

Stuart J. Eisendrath, MD

Allen P. Kong, MD

Professor of Clinical Psychiatry, Department of Psychiatry, University of California, San Francisco; Director of Clinical Services, Langley Porter Psychiatric Hospital and Clinics, San Francisco, California [email protected] Psychiatric Problems

Resident Physician, Department of Surgery, University of California, Irvine, Orange, California [email protected] Acute Abdomen

Viktor Eysselein, MD Professor of Medicine, David Geffen School of Medicine, University of California, Los Angeles; Clinical Professor of Medicine, Harbor-UCLA Medical Center, Torrance, California [email protected] Gastrointestinal Bleeding

Craig R. Hampton, MD Staff Surgeon, St. Luke’s Cardiothoracic Surgical Associates, St. Luke's Hospital, Duluth, Minnesota [email protected] Cardiothoracic Surgery

Darrell W. Harrington, MD Chief, Division of General Internal Medicine, Harbor-UCLA Medical Center, Torrance, California [email protected] Critical Care of the Oncology Patient

James T. Lee, MD Fellow, Peripheral Vascular and Endovascular Surgery, Division of Vascular Surgery, Harbor-UCLA Medical Center, Torrance, California [email protected] Critical Care of Vascular Disease & Emergencies

Tai-Shion Lee, MD Clinical Professor, David Geffen School of Medicine, University of California, Los Angeles, Harbor-UCLA Medical Center, Torrance, California [email protected] Intensive Care Anesthesia & Analgesia

Ricky Phong Mac, MD Clinical Endcrinology Fellow, Division of Endocrinology, Metabolism and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, California Endocrine Problems in the Critically Ill Patient

James R. Macho, MD, FACS Chuck Huang, MD Private Practice, Internal Medicine and Endocrinology, Grants Pass, Oregon Diabetes Mellitus, Hyperglycemia, & the Critically Ill Patient

Eli Ipp, MD Professor, David Geffen School of Medicine, University of California, Los Angeles; Head, Section of Diabetes and Metabolism, Harbor-UCLA Medical Center, Torrance, California [email protected] Diabetes Mellitus & the Critically Ill Patient

Andrea T. Jelks, MD Associate Clinical Professor, Stanford University Medical Center; Maternal Fetal Medicine Specialist, Santa Clara Valley Medical Center, San Jose, California [email protected] Critical Care Issues in Pregnancy

Andre A. Kaplan, MD Professor of Medicine, University of Connecticut Health Center; Chief, Blood Purification, John Dempsey Hospital, Farmington, Connecticut [email protected] Renal Failure

Emeritus Professor of Surgery, University of California, San Francisco; Director, Bothin Burn Center and Chief of Critical Care Medicine, Saint Francis Memorial Hospital, San Francisco, California [email protected] Care of Patients with Environmental Injuries

Duncan Q. McBride, MD Associate Professor of Clinical Neurosurgery, Department of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles; Chief, Division of Neurosurgery, Harbor-UCLA Medical Center, Torrance, California [email protected] Neurosurgical Critical Care

Hugh B. McIntyre, MD Professor of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Harbor-UCLA Medical Center, Torrance, California [email protected] Critical Care of Neurologic Disease

AUTHORS



ix

Bruce L. Miller, MD

Sofiya Reicher, MD

Clausen Distinguished Professor of Neurology, University of California, San Francisco; Memory and Aging Center, San Francisco, California [email protected] Critical Care of Neurologic Disease

Assistant Clinical Professor of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California [email protected] Gastrointestinal Bleeding

David W. Mozingo, MD

William P. Schecter, MD

Professor of Surgery and Anesthesiology, University of Florida; Chief, Division of Acute Care Surgery, Director, Shands Burn Center, Gainesville, Florida [email protected] Burns

Professor of Clinical Surgery and Vice Chair, University of California, San Francisco, San Francisco, California; Chief of Surgery, San Francisco General Hospital, San Francisco, California [email protected] Care of Patients with Environmental Injuries

Kenneth A. Narahara, MD Professor of Medicine, David Geffen School of Medicine, University of California, Los Angeles, School of Medicine; Assistant Chair for Clinical Affairs, Department of Medicine, Director, Coronary Care, Division of Cardiology, Harbor-UCLA Medical Center, Torrance, California [email protected] Coronary Heart Disease

Paul A. Selecky, MD Clinical Professor of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California; Medical Director, Pulmonary Department, Hoag Hospital, Newport Beach, California [email protected] Ethical, Legal, & Palliative/End-of-Life Care Considerations

Shelley Shapiro, MD, PhD Gideon P. Naudé, MD Chairman, Department of Surgery, Tuolumne General Hospital, Sonora, California [email protected] Gastrointestinal Failure in the ICU

Clinical Professor of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California [email protected] Cardiac Problems in Critical Care

Dean C. Norman, MD

Elizabeth D. Simmons, MD

Chief of Staff, Veterans Administration Greater Los Angeles Healthcare System; Professor of Medicine, University of Southern California, Los Angeles, California [email protected] Care of the Elderly Patient

Partner, Southern California Permanente Medical Group, Los Angeles, California [email protected] Transfusion Therapy; Bleeding & Hemostasis; Antithrombotic Therapy

Basil A. Pruitt, Jr., MD, FACS, FCCM

Michael J. Stamos, MD

Clinical Professor, Department of Surgery, University of Texas Health Science Center at San Antonio; Consultant, U.S. Army Institute of Surgical Research, San Antonio, Texas [email protected] Burns

Professor of Surgery and Chief, Division of Colon and Rectal Surgery, University of California, Irvine, Orange, California [email protected] Acute Abdomen

Steven S. Raman, MD Associate Professor, Department of Radiology, David Geffen School of Medicine, University of California, Los Angeles, California [email protected] Imaging Procedures

Samuel J. Stratton, MD, MPH Professor of Emergency Medicine, University of California Irvine, Orange, California [email protected] Transport

x



AUTHORS

Darryl Y. Sue, MD

Janine R. E. Vintch, MD

Professor of Clinical Medicine, David Geffen School of Medicine, University of California, Los Angeles, California; Director, Medical-Respiratory Intensive Care Unit, Division of Respiratory and Critical Care Physiology and Medicine, Associate Chair and Program Director, Department of Medicine, Harbor-UCLA Medical Center, Torrance, California [email protected] Philosophy & Principles of Critical Care; Fluids, Electrolytes, & Acid-Base; Pharmacotherapy; Intensive Care Monitoring; Respiratory Failure; Critical Care of the Oncology Patient; Pulmonary Disease; HIV Infection in the Critically Ill Patient

Associate Clinical Professor of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Divisions of General Internal Medicine and Respiratory and Critical Care Physiology and Medicine, Harbor-UCLA Medical Center, Torrance, California [email protected] Respiratory Failure; Pulmonary Disease

John A. Tayek, MD

Mallory D. Witt, MD

Associate Professor of Medicine-in-Residence, David Geffen School of Medicine, University of California, Los Angeles, Harbor-UCLA Medical Center, Torrance, California [email protected] Nutrition

Professor of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California; Associate Chief, Division of HIV Medicine, HarborUCLA Medical Center, Torrance, California [email protected] Infections in the Critically Ill; HIV Infection in the Critically Ill Patient

Timothy L. Van Natta, MD Associate Professor of Surgery, David Geffen School of Medicine, University of California, Los Angeles, Harbor-UCLA Medical Center, Torrance, California [email protected] Surgical Infections

Hernan I. Vargas, MD Associate Professor of Surgery, David Geffen School of Medicine, University of California, Los Angeles, California; Chief, Division of Surgical Oncology, HarborUCLA Medical Center, Torrance, California [email protected] Hepatobiliary Disease

Edward D. Verrier, MD William K. Edmark Professor of Cardiovascular Surgery, Vice Chairman, Department of Surgery, University of Washington, Seattle, Washington; Chief, Division of Cardiothoracic Surgery, University of Washington, Seattle, Washington [email protected] Cardiothoracic Surgery

Kenneth Waxman, MD Director of Surgical Education, Santa Barbara Cottage Hospital, Santa Barbara, California [email protected] Intensive Care Monitoring

Nam C. Yu, MD Resident Physician, Department of Radiology, David Geffen School of Medicine, University of California, Los Angeles, California [email protected] Imaging Procedures

Kory J. Zipperstein, MD Chief, Department of Dermatology, Kaiser-Permanente Medical Center, San Francisco, California [email protected] Dermatologic Problems in the Intensive Care Unit

Preface The third edition of Current Diagnosis & Treatment: Critical Care is designed to serve as a single-source reference for the adult critical care practitioner. The diversity of illnesses encountered in the critical care population necessitates a well-rounded and thorough knowledge of the manifestations and mechanisms of disease. In addition, unique to the discipline of critical care is the integration of an extensive body of medical knowledge that crosses traditional specialty boundaries. This approach is readily apparent to intensivists, whose primary background may be in internal medicine or one of its subspecialties, surgery, or anesthesiology. Thus a central feature of this book is a unified and integrated approach to the problems encountered in critical care practice. Like other books with the Lange imprint, this book emphasizes recall of major diagnostic features, concise descriptions of disease processes, and practical management strategies based on often recently acquired evidence.

INTENDED AUDIENCE Planned by two internists and a surgeon to meet the need for a concise but thorough source of information, Current Diagnosis & Treatment: Critical Care is intended to facilitate both teaching and practice of critical care. Students will find its consideration of basic science and clinical application useful during clerkships on medicine, surgery, and intensive care unit electives. House officers will appreciate its descriptions of disease processes and organized approach to diagnosis and treatment. Fellows and those preparing for critical care specialty examinations will find those sections outside their primary disciplines particularly useful. Clinicians will recognize this succinct reference on critical care as a valuable asset in their daily practice. Because this book is intended as a reference on various aspects of adult critical care, it does not contain chapters on pediatric or neonatal critical care. These areas are highly specialized and require entire monographs of their own. Further, we have not included detailed information on performing bedside procedures such as central venous catheterization or arterial line insertion. Well-illustrated pocket manuals are available for readers who require basic technical information. Finally, we have chosen not to include a chapter on nursing or administrative topics, details of which can be found in other works.

ORGANIZATION Current Diagnosis & Treatment: Critical Care is conceptually organized into three major sections: (1) fundamentals of critical care applicable to all patients, (2) topics related primarily to critical care of patients with medical diseases, and (3) essentials of care for patients requiring care for surgical problems. Early chapters provide information about the general physiology and pathophysiology of critical illness. The later chapters discuss pathophysiology using an organ system– or disease-specific approach. Where appropriate, we have placed the medical and surgical chapters in succession to facilitate access to information.

OUTSTANDING FEATURES Concise, readable format, providing efficient use in a variety of clinical and academic settings Edited by both surgical and medical intensivists, with contributors from multiple subspecialties  Illustrations chosen to clarify basic and clinical concepts  Careful evaluation of new diagnostic procedures and their usefulness in specific diagnostic problems  Updated information on the management of severe sepsis and septic shock, including hydrocortisone therapy  New information on the serotonin syndrome  Carefully selected key references in Index Medicus format, providing all information necessary to allow electronic retrieval  

ACKNOWLEDGMENTS The editors wish to thank Robert Pancotti and Ruth W. Weinberg at McGraw-Hill for unceasing efforts to motivate us and keep us on track. We are also very grateful to our families for their support. Frederic S. Bongard, MD Darryl Y. Sue, MD Janine R. E. Vintch, MD July 2008

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Philosophy & Principles of Critical Care Darryl Y. Sue, MD Frederic S. Bongard, MD

Critical care is unique among the specialties of medicine. While other specialties narrow the focus of interest to a single body system or a particular therapy, critical care is directed toward patients with a wide spectrum of illnesses. These have the common denominators of marked exacerbation of an existing disease, severe acute new problems, or severe complications from disease or treatment. The range of illnesses seen in a critically ill population necessitates well-rounded and thorough knowledge of the manifestations and mechanisms of disease. Assessing the severity of the patient’s problem demands a simultaneously global and focused approach, depends on accumulation of accurate data, and requires integration of these data. Although practitioners of critical care medicine—sometimes called intensivists—are often specialists in pulmonary medicine, cardiology, nephrology, anesthesiology, surgery, or critical care, the ability to provide critical care depends on the basic principles of internal medicine and surgery. Critical care might be considered not so much a specialty as a “philosophy” of patient care. The most important development in recent years has been an explosion of evidence-based critical care medicine studies. For the first time, we have evidence for many of the things that we do for patients in the ICU. Examples include low tidal volume strategies for acute respiratory distress syndrome, tight glycemic control, prevention of ventilatorassociated pneumonia, and use of corticosteroids in septic shock (Table 1–1). The resulting improvement in outcome is gratifying, but even more surprising is how often evidence contradicts long-held beliefs and assumptions. Probably the best example is recent studies that conclude that the routine use of pulmonary artery catheters in ICU patients adds little or nothing to management. Much more needs to be studied, of course, to address other unresolved issues and controversies. Do intensivists make a difference in patient outcome? Several studies have shown that management of patients by full-time intensivists does improve patient survival. In fact,

1

1

several national organizations recommend strongly that fulltime intensivists provide patient care in all ICUs. It can be argued, however, that local physician staffing practices; interactions among primary care clinicians, subspecialists, and intensivists; patient factors; and nursing and ancillary support play large roles in determining outcomes. In addition, recent studies show that patients do better if an ICU uses protocols and guidelines for routine care, controls nosocomial infections, and provides feedback to practitioners. The general principles of critical care are presented in this chapter, as well as some guidelines for those who are responsible for leadership of ICUs.

GENERAL PRINCIPLES OF CRITICAL CARE  Early Identification of Problems Because critically ill patients are at high risk for developing complications, the ICU practitioner must remain alert to early manifestations of organ system dysfunction, complications of therapy, potential drug interactions, and other premonitory data (Table 1–2). Patients with life-threatening illness in the ICU commonly develop failure of other organs because of hemodynamic compromise, side effects of therapy, and decreased organ function reserve, especially those who are elderly or chronically debilitated. For example, positive-pressure mechanical ventilation is associated with decreased perfusion of organs. Many valuable drugs are nephro- or hepatotoxic, especially in the face of preexisting renal or hepatic insufficiency. Older patients are more prone to drug toxicity, and polypharmacy presents a higher likelihood of adverse drug interactions. Just as patients with acute coronary syndrome and stroke benefit from early intervention, an exciting finding is the evidence that the first 6 hours of management of septic shock are very important.

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CHAPTER 1

Table 1–1. Recent developments in evidence-based critical care medicine.

Table 1–2. Recommendations for routine patient care in the ICU.

• Corticosteroids improve outcome in exacerbations of chronic obstructive respiratory disease (COPD).

• Assess current status, interval history, and examination.

• A low tidal volume strategy decreases mortality in acute respiratory distress syndrome (ARDS).

• Review medication record, including continuous infusions: Duration and dose Changes in dose or frequency based on changes in renal, hepatic, or other pharmacokinetic function Changes in route of administration Potential drug interactions

• A lower hemoglobin decision point for transfusion of red blood cells in many ICU patients results in similar outcome and greatly reduced use of blood products. • Tight glycemic control in postoperative surgical patients, most of whom did not have diabetes, resulted in less mortality and fewer complications. • Elevating the head of the bed to 30–45 degrees in ICU patients reduces the incidence of nosocomial pneumonia. • Daily withholding of sedation in the ICU decreases the number of ICU days and results in fewer evaluations for altered level of consciousness. • Daily spontaneous breathing trials lead to faster weaning from mechanical ventilation and shorter duration of ICU stay. • Low-dose (physiologic) vasopressin may reduce the need for pressors in septic shock. • Fluid resuscitation using colloid-containing solutions is not more beneficial than crystalloid fluids. • Low-dose dopamine does not improve renal function or diuresis and does not protect against renal dysfunction.

• Review vital signs for interval period (since last review).

• Correlate changes in vital signs with medication administration and other changes by use of chronologic charting. • Integrate nursing, respiratory therapists, patient, family, and other observations. • Review, if indicated: Respiratory therapy flow chart Hemodynamics records Laboratory flowsheets Other continuous monitoring • Review all problems, including adding, updating, consolidating, or removing problems as indicated. • Periodically, review supportive care: Intravenous fluids Nutritional status and support Prophylactic treatment and support Duration of catheters and other invasive devices • Review and contrast risks and benefits of intensive care.

• Acetylcysteine or sodium bicarbonate protect against radiocontrast material–induced acute renal failure. • Patients with bleeding esophageal varices have a higher rebleeding risk if they have infection, especially spontaneous bacterial peritonitis. • Noninvasive positive-pressure ventilation decreases the need for intubation in patients with COPD exacerbation. • Noninvasive positive-pressure ventilation is associated with fewer respiratory infections than conventional ventilation. • Early goal-directed therapy for sepsis (specific targets for central venous pressure, hemoglobin, and central venous oxygen content during the first 6 hours of care) decreases mortality.

Identifying and acting on new problems and complications in the ICU demands frequent and regular review of all information available, including changes in symptoms, physical findings, and laboratory data and information from monitors. In some facilities, early identification and treatment are provided by rapid-response teams. Once notified that a patient outside the ICU may be deteriorating, the team is mobilized

to provide a mini-ICU environment in which critical care can be delivered early, even before the patient is actually transferred.

 Effective Use of the Problem-Oriented Medical Record The special importance of finding, tracking, and being aware of ICU issues demands an effective problem-oriented medical record. In order to define and follow problems effectively, each problem should be reviewed regularly and characterized at its current state of understanding. For example, if the general problem of “renal failure” subsequently has been determined to be due to aminoglycoside toxicity, it should be described in that way in an updated problem list. However, even the satisfaction of identifying a cause of the renal failure may be short-lived. The same patient subsequently may develop other related or unrelated renal problems, thereby forcing reassessment. In our opinion, ICU problems must not be restricted to “diagnoses.” We list intravascular catheters and the date they

PHILOSOPHY & PRINCIPLES OF CRITICAL CARE were inserted on the problem list. This helps us to remember to consider the catheter as a site of infection if the patient has a fever. Other “nondiagnoses” on our problem list include nutritional support, prevention of deep vein thrombosis and decubitus ulcers, drug allergies, patient positioning, and prevention of stress ulcers. It may be useful to include nonmedical issues as well so that they can be discussed routinely. Examples are psychosocial difficulties, unresolved end-of-life decisions, and other questions about patient comfort. Finally, we share the patient’s problem-oriented record with nonphysicians caring for the patient, a process that enhances communication, simplifies interactions between staff members, and furthers the goals of patient care.

 Monitoring & Data Display A tremendous amount of patient data is acquired in the ICU. Although ICU monitoring is often thought of as electrocardiography, blood pressure measurements, and pulse oximetry, ICU data include serial plasma glucose and electrolyte determinations, arterial blood gas determinations, documentation of ventilator settings and parameters, and body temperature determinations. Taking a daily weight is invaluable in determining the net fluid balance of a patient. Flowcharts of laboratory data and mechanical ventilator activity, 24-hour vital signs, graphs of hemodynamic data, and lists of medications are indispensable tools for good patient care, and efforts should be made to find the most effective and efficient ways of displaying such information in the ICU. Methods that integrate the records of physicians, nurses, respiratory therapists, and others are particularly useful. Computer-assisted data collection and display systems are found increasingly in ICUs. Some of these systems import data directly from bedside monitors, mechanical ventilators, intravenous infusion pumps, fluid collection devices, clinical laboratory instruments, and other devices. ICU practitioners may enter progress notes, medications administered, and patient observations. Advantages of these systems include decreased time for data collection and the ability to display data in a variety of formats, including flowcharts, graphs, and problem-oriented records. Such data can be sent to remote sites for consultation, if necessary. Computerized access to data facilitates research and quality assurance studies, including the use of a variety of prognostic indicators, severity scores, and ICU decision-making tools. Computerized information systems have the potential for improving patient care in the ICU, and their benefit to patient outcome continues to be studied. The next step is to integrate ICU data with treatment, directly and indirectly. One excellent example is glycemic control so that up-to-date blood glucose measurements will be linked closely to insulin protocols—at first with the nurse and physician “in the loop” but potentially with



3

real-time feedback and automated adjustment of insulin infusions.

 Supportive & Preventive Care Many studies have pointed out the high prevalence of gastrointestinal hemorrhage, deep venous thrombosis, decubitus ulcers, inadequate nutritional support, nosocomial and ventilator-associated pneumonias, urinary tract infections, psychological problems, sleep disorders, and other untoward effects of critical care. Efforts have been made to prevent, treat, or otherwise identify the risks for these complications. As outlined in subsequent chapters, effective prevention is available for some of these risks (Table 1–3); for other complications, early identification and aggressive intervention may be of value. For example, aggressive nutritional support for critically ill patients is often indicated both because of the presence of chronic illness and malnutrition and because of the rapid depletion of nutritional reserves in the presence of severe illness. Nutritional support, prevention of upper gastrointestinal bleeding and deep venous thrombosis, skin care, and other supportive therapy should be included on the ICU patient’s problem list. To these, we have added glycemic control because of recent data indicating reduced morbidity and mortality in medical and surgical patients whose plasma glucose concentration is maintained in a relatively narrow range. Because of expense and questions of effectiveness and safety, studies of preventive treatment of ICU patients continue. For example, a multicenter study reported that clinically important gastrointestinal bleeding in critically ill patients was seen most often only in those with respiratory failure or coagulopathy (3.7% for one or both factors). Otherwise, the risk for significant bleeding was only 0.1%. The authors suggested that prophylaxis against stress ulcer could be withheld safely from critically ill patients unless they had one of these two risk factors. On the other hand, about half the patients in this study were post–cardiac surgery patients, and the majority of patients in many ICUs have one of the identified risk factors. Thus there may not be sufficient compelling evidence to discontinue the practice of providing routine prophylaxis for gastrointestinal bleeding in all ICU patients. Other routine practices have been challenged. For example, several studies show that routine transfusion of red blood cells in ICU patients who reached an arbitrary hemoglobin level did not change outcome when compared with allowing hemoglobin to fall to a lower value. Further studies are needed to define the role of other preventive strategies. Important questions include differences in the need for glycemic control, critical differences in the intensity and type of therapy needed to prevent thrombosis, the optimal hemoglobin for patients with myocardial infarction, and the benefit of tailored nutritional support.

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CHAPTER 1

Table 1–3. Things to think about and reminders for ICU patient care. Things To Think About

Reminders

General ICU Care 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12.

Nosocomial infections, especially line- and catheter-related. Stress gastritis. Deep venous thrombosis and pulmonary embolism. Exacerbation of malnourished state. Decubitus ulcers. Psychosocial needs and adjustments. Toxicity of drugs (renal, pulmonary, hepatic, CNS). Development of antibiotic-resistant organisms. Complications of diagnostic tests. Correct placement of catheters and tubes. Need for vitamins (thiamine, C, K). Tuberculosis, pericardial disease, adrenal insufficiency, fungal sepsis, rule out myocardial infarction, pneumothorax, volume overload or volume depletion, decreased renal function with normal serum creatinine, errors in drug administration or charting, pulmonary vascular disease, HIV-related disease.

1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.

Discontinue infected or possibly infected lines. Need for H2 blockers, antacids, or sucralfate. Provide enteral or parenteral nutrition. Change antibiotics? Chest x-ray for line placement. Review known drug allergies (including contrast agents). Check for drug dosage adjustments (new liver failure or renal failure). Need for deep venous thrombosis prophylaxis? Pain medication and sedation. Weigh patient. Give medications orally, if possible. Does patient really need an arterial catheter? Give thiamine early.

Nurition 1. 2. 3. 4. 5. 6. 7. 8. 9.

Set goals for appropriate nutrition support. Avoid or minimize catabolic state. Acquired vitamin K deficiency while in ICU. Avoidance of excessive fluid intake. Diarrhea (lactose intolerance, low serum protein, hyperosmolarity, drug-induced, infectious). Minimize and anticipate hyperglycemia during parenteral nutritional support. Adjustment of rate or formula in patients with renal failure or liver failure. Early complications of refeeding. Acute vitamin insufficiency.

1. Calculate estimated basic caloric and protein needs. Use 30 kcal/kg and 1.5 g protein/kg for starting amount. 2. Regular food preferred over enteral feeding; enteral feeding preferred over parenteral in most patients. 3. Increased caloric and protein requirements if febrile, infected, agitated, any inflammatory process ongoing, some drugs. 4. Adjust protein if renal or liver failure is present. Adjust again if dialysis is used. 5. Measure serum albumin as primary marker of nutritional status. 6. Give vitamin K, especially if malnourished and receiving antibiotics. 7. Consider volume restriction formulas (both enteral and parenteral). 8. Give phosphate early during refeeding. 9. Control hyperglycemia (glucose 100 mm Hg Delayed capillary refill or 85 2; UFH if high risk for thromboembolism until 6 hours before surgery.

VTE = venous thromboembolism.

protein C or protein S. Patients who are known to be deficient in protein C or protein S should receive warfarin only with simultaneous administration of heparin for at least 5 days to allow for depletion of all the vitamin K–dependent coagulation proteins to prevent skin necrosis. Warfarin is teratogenic, resulting in a fetal embryopathy associated with multiple anomalies when is administered during the first trimester of pregnancy (estimated incidence 7–28%). Warfarin crosses the placenta and may result in fetal bleeding. Because of these negative fetal effects, warfarin is contraindicated between weeks 6 and 12 of pregnancy, and because it may cause fetal bleeding, it should be avoided near term. Women of reproductive age who are taking warfarin should be advised of the teratogenic effects of the drug, and if pregnancy is contemplated, UFH or LMWH should be substituted prior to pregnancy (except for women with mechanical heart valves; see “Antithrombotic Therapy in Pregnancy”). Warfarin does not cause anticoagulation in infants who are breastfed by mothers taking warfarin. Other infrequent side effects of warfarin include alopecia, GI discomfort, rash, and liver dysfunction. In patients with underlying arterial vascular disease, warfarin therapy has been associated rarely with the development of atheroembolic complications, including ischemic toes, livedo reticularis,

gangrene, abdominal pain, and renal and other visceral infarctions owing to cholesterol emboli. Early reports suggested that chronic warfarin therapy may increase the risk of bone fractures and osteoporosis, but a meta-analysis of available studies failed to show a definite association.

Anisindione Patients who cannot tolerate warfarin may be treated with anisindione, an oral anticoagulant that is structurally unrelated to warfarin but works by a similar mechanism, namely, inhibition of γ-carboxylation of the vitamin K–dependent coagulation factors. The drug is well absorbed from the GI tract, is highly protein-bound, and is metabolized to inactive metabolites that are excreted in the urine. These metabolites may cause a red-orange discoloration of the urine. The anticoagulant response of anisindione occurs within 20–72 hours, and it is cleared slowly from circulation with a half-life of 3–5 days. Like warfarin, its anticoagulant effect can be reversed by vitamin K and fresh-frozen plasma. Anisindione crosses the placenta and causes fetal malformations and fetal bleeding, so it should be avoided during pregnancy. Anisindione is FDA approved for use in myocardial infarction and venous thrombosis, but there is a lack of good

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clinical studies to support its use as a substitute for warfarin except for patients who are truly intolerant of warfarin. In those patients, a loading dose of 300 mg on day one, 200 mg on day two, and 100 mg on day three is followed by daily maintenance of 50–250 mg, adjusted according to the INR. Anisindione may cause myelosuppression, dermatitis, jaundice, and renal insufficiency, which have limited its use.

 Thrombolytic Therapy Thrombolytic (fibrinolytic) agents differ from other antithrombotic agents in that they actually dissolve established clots rather than interfering with initiation and propagation of thrombosis. The mechanism of action of these agents is complex and involves many components of the naturally occurring fibrinolytic system. Activation of plasminogen to plasmin (the major fibrinolytic enzyme) is enhanced by these drugs, accompanied by increased consumption of its inhibitor (α2-antiplasmin). The net effect is an increase in free plasmin, which results in degradation of fibrin and other coagulation factors.

All the available agents cause varying degrees of systemic activation of the fibrinolytic mechanism and therefore induce generalized fibrinolysis and fibrinogenolysis and some degree of platelet dysfunction owing to proteolysis of key membrane receptors by plasmin, although some are more specific for plasmin bound to clot (fibrin-specific). These drugs work best when given soon after onset of symptoms (eg, within 3–4 hours in acute arterial thrombosis, 48 hours for pulmonary thromboembolism, and 7 days for DVT), before thrombi are highly cross linked and more resistant to thrombolysis. Five thrombolytic agents are approved for use in the United States. Selected features of these agents are outlined in Table 39–10. Thrombolytic therapy may be used in the treatment of acute arterial thrombosis, including myocardial infarction and peripheral arterial occlusion, and in the treatment of severe VTE (eg, massive pulmonary thromboembolism with hemodynamic compromise, massive DVT, or phlegmasia cerulea dolens). Thrombolysis can improve neurologic function in patients with acute nonhemorrhagic stroke if patients at high risk for bleeding are excluded and if

Table 39–10. Comparison of selected fibrinolytic agents. Drug Alteplase

∗

FibrinSpecific

t1⁄2 (min)

Indications (FDA-Approved)

Neutralizing Antibodies∗

Typical Dose†

Estimated Cost

5

Yes (2+)

Myocardial infarction, acute No cardiovascular accident, pulmonary thromboembolism

Myocardial infarction: 100 mg $2200 infusion over 90 minutes to 3 hours; cerebrovascular accident: 0.9 mg/kg (maximum 90 mg) infused over 60 minutes with 10% of total dose given as an initial bolus

Tenecteplase

18–20

Yes (3+)

Myocardial infarction.

No

Single bolus, 30–50 mg depending on weight in kg

Reteplase

13–16

Yes (1+)

Myocardial infarction

No

Two bolus injections, 10 units $2200 each given 30 minutes apart

Streptokinase

20

No

Myocardial infarction (intra- Yes venous or intracoronary), deep vein thrombosis, pulmonary thromboembolism, catheter thrombosis, peripheral arterial occlusion

1.5 million units infused over $300 30–60 minutes intravenously OR 20,000 units by intracoronary bolus followed by 2000 to 4000 units/min for 30 to 90 minutes

Urokinase

20

No

Myocardial infarction (intracoronary), pulmonary thromboembolism, catheter thrombosis

6000 units/min infused intracoronary for up to 2 hours OR 4400 units/kg infused over 10 minutes followed by 4400 units/kg/hr for 12 hours OR 5000 units for catheter thrombosis

No

$2200

$4000–$6000 (myocardial infarction, pulmonary embolus) $60 (catheter thrombosis)

Presence of neutralizing antibodies precludes repeat use within 6–24 months, possibly longer, because of allergic reactions and decreased effectiveness of the agent. † Doses may vary depending upon clinical situation.

ANTITHROMBOTIC THERAPY administered within 3 hours of onset of symptoms. Thrombolytic agents are also used to reestablish patency of clotted indwelling venous catheters and vascular grafts. Indications, timing of administration, use of adjunctive antithrombotic agents, and choice of specific agent for thrombolytic therapy are evolving. Thrombolysis reduces mortality from acute myocardial infarction by about 20–50%. In patients not undergoing percutaneous transthoracic coronary angioplasty for acute myocardial infarction, alteplase may be more effective than streptokinase. Bolus fibrinolytic agents, reteplase and tenecteplase, are potentially advantageous because they can be given quickly and could be available in the prehospital setting. Reteplase appears to be equivalent in safety and efficacy to alteplase, whereas tenecteplase has a somewhat lower rate of major bleeding. Any available fibrinolytic agent may be used with acute myocardial infarction. Although the newer agents are much more expensive than streptokinase, the contribution of drug costs to the overall cost of care—particularly for acute myocardial infarction—has not been shown to be significant. When cost-effective analyses have been done, streptokinase appears to be marginally more cost-effective than the other agents but should not be given to patients previously treated with streptokinase owing to its antigenicity. Urokinase is used primarily for dissolution of catheter thromboses. The principal goal of fibrinolytic therapy is to reestablish patency of an occluded blood vessel (or indwelling catheter). Fibrinolytic therapy for myocardial infarction results in angiographically confirmed patency about 50% of the time. Additional antithrombotic therapy may be required to improve reperfusion. The role of heparin combined with fibrinolytics for patients with acute myocardial infarction is controversial, and the combination appears to be associated with a high rate of major bleeding. Ongoing studies are required to define the optimal use of heparin (UFH or LMWH) or other anticoagulants such as the hirudin derivatives and heparinoids in combination with fibrinolytic therapy. Antiplatelet agents have been shown to be very important as an adjunct to fibrinolytic therapy. Platelets play a key role in the development of coronary thrombosis. Aspirin and platelet GP IIb/IIIa inhibitors potentiate fibrinolysis and improve coronary artery patency rates, although bleeding complications also may be increased when streptokinase is combined with GP IIb/IIIa inhibitors. Large trials recently completed will provide additional information about the safety and efficacy of various combinations of antiplatelet agents and fibrinolytics in the treatment of acute myocardial infarction. In addition, the combination of reduced-dose fibrinolytic therapy with invasive coronary interventions (eg, angioplasty) may improve outcomes. Further study in this area is needed to define optimal dosing to enhance coronary artery patency while maintaining an acceptable rate of hemorrhage. Alteplase is approved for use in acute nonhemorrhagic stroke and is effective when administered intravenously within 3 hours of the onset of symptoms. The risk of intracerebral hemorrhage is 3%, but because it can lead to improved



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neurologic function, this may be an acceptable risk. Only an estimated 2% of all stroke patients are able to receive alteplase within the 3-hour time frame, limiting its potential impact on outcomes from stroke. Streptokinase increases early mortality and intracerebral hemorrhage when used in the treatment of acute stroke and is not recommended. Recently, MRI to locate arterial occlusions, followed by superselective intraarterial thrombolysis, has been suggested as a potentially beneficial approach for patients with acute stroke who are more than 3 hours from the onset of symptoms. This approach has an even higher risk of hemorrhage (10% overall), but in centers equipped with a stroke unit and all necessary personnel and technologic support quickly available, it may prove to increase the number of patients who could benefit from thrombolysis for acute stroke. Fibrinolytic therapy is of limited value in the treatment of massive PE. Hemodynamic instability and radiographic changes improve more rapidly than with anticoagulation only, but there does not appear to be any significant improvement in overall outcome compared with anticoagulation alone. Fibrinolytic therapy of PE should be considered for patients with hemodynamic instability, severe gasexchange abnormalities, or significant impairment in right ventricular function. Echocardiography to assess right ventricular function plays a key role in determining the potential benefit of fibrinolytic therapy or other means of reducing clot burden (eg, thromboembolectomy). Fibrinolytic therapy for DVT has not improved outcome over anticoagulation in most patients, with the possible exception of patients with severe venous occlusion and threatened gangrene of the limb. Despite a high rate of clot lysis, there is no good evidence that thrombolytic therapy reduces the rate of postphlebitic syndrome following DVT. Furthermore, hemorrhagic complications are much higher than with standard anticoagulation in the treatment of VTE. Fibrinolytic therapy is effective in the treatment of acute arterial thrombus in medium and large peripheral arteries. A fibrinolytic agent administered through a catheter proximal to the clot dissolves it completely about 75% of the time. Catheter-directed intraarterial administration appears to be superior to intravenous administration. Thrombolysis should be considered prior to revascularization surgery as long as the affected limb is still salvageable. Surgery can be avoided in 35% of these patients, and overall mortality appears to be somewhat better than with immediate surgery. Urokinase, 5000 units, may be instilled into an occluded venous catheter without excessive pressure, which could dislodge the clot or rupture the catheter. Because venous catheters may be occluded by substances other than clots (eg, drug precipitate), urokinase is not always effective. The most common complication of thrombolytic therapy is hemorrhage (3–40%). Hemorrhagic complications can be minimized if patients are selected properly and monitored carefully. The use of other antithrombotic agents—particularly heparin—increases the risk of bleeding. Contraindications to thrombolytic therapy include major ischemic changes or

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signs of intracranial hypertension on CT scan, seizure at the onset of a stroke, previous stroke or serious head injury within the preceding 3 months, active or recent visceral bleeding, aortic dissection, major surgery, trauma, arterial or lumbar puncture in the preceeding 2 weeks, severe uncontrolled hypertension (>180/110 mm Hg), significant thrombocytopenia (platelet count