The 2002 Official Patient's Sourcebook on Respiratory Failure

THE 2002 OFFICIAL PATIENT’S SOURCEBOOK on ESPIRATORY AILURE J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D...

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THE 2002 OFFICIAL PATIENT’S SOURCEBOOK

on

ESPIRATORY AILURE

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

ii

ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright Ó2002 by ICON Group International, Inc. Copyright Ó2002 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Tiffany LaRochelle Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher’s note: The ideas, procedures, and suggestions contained in this book are not intended as a substitute for consultation with your physician. All matters regarding your health require medical supervision. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation, in close consultation with a qualified physician. The reader is advised to always check product information (package inserts) for changes and new information regarding dose and contraindications before taking any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960The 2002 Official Patient’s Sourcebook on Respiratory Failure: A Revised and Updated Directory for the Internet Age/James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary and index. ISBN: 0-597-83172-6 1. Respiratory Failure-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem or as a substitute for consultation with licensed medical professionals. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors or authors. ICON Group International, Inc., the editors, or the authors are not responsible for the content of any Web pages nor publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this sourcebook for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications are copyrighted. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs or other materials, please contact us to request permission (e-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this sourcebook.

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Dedication To the healthcare professionals dedicating their time and efforts to the study of respiratory failure.

Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this sourcebook which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which directly or indirectly are dedicated to the study of respiratory failure. All of the Official Patient’s Sourcebooks draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this sourcebook. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany LaRochelle for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for the Official Patient’s Sourcebook series published by ICON Health Publications.

Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for the Official Patient’s Sourcebook series published by ICON Health Publications.

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About ICON Health Publications In addition to respiratory failure, Official Patient’s Sourcebooks are available for the following related topics: ·

The Official Patient's Sourcebook on Asthma

·

The Official Patient's Sourcebook on Bronchopulmonary Dysplasia

·

The Official Patient's Sourcebook on Chronic Obstructive Pulmonary Disease

·

The Official Patient's Sourcebook on Cystic Fibrosis

·

The Official Patient's Sourcebook on Idiopathic Pulmonary Fibrosis

·

The Official Patient's Sourcebook on Primary Pulmonary Hypertension

·

The Official Patient's Sourcebook on Pulmonary Lymphangioleiomyomatosis

·

The Official Patient's Sourcebook on Sarcoidosis

To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

Contents vii

Table of Contents INTRODUCTION ................................................................................................................. 1 Overview .................................................................................................................................... 1 Organization ............................................................................................................................. 3 Scope ............................................................................................................................................ 3 Moving Forward ...................................................................................................................... 4

PART I: THE ESSENTIALS ..................................................................... 7 CHAPTER 1. THE ESSENTIALS ON RESPIRATORY FAILURE: GUIDELINES .......................................................................................................................... 9 Overview .................................................................................................................................... 9 What Is Respiratory Failure? ............................................................................................. 11 Who Can Get Respiratory Failure? .................................................................................. 12 Breathing and Respiratory Failure ................................................................................... 12 What Happens During Respiratory Failure?................................................................ 14 Conditions That May Progress to Respiratory Failure .............................................. 15 Symptoms of Respiratory Failure ..................................................................................... 15 Diagnosis of Respiratory Failure ...................................................................................... 16 Management of Respiratory Failure ................................................................................ 16 More about Some Common Lung Diseases Leading to Or Characterized by Respiratory Failure................................................................................................................ 20 Additional Information ........................................................................................................ 23 More Guideline Sources....................................................................................................... 23 Vocabulary Builder ............................................................................................................... 27

CHAPTER 2. SEEKING GUIDANCE ................................................................. 33 Overview .................................................................................................................................. 33 Associations and Respiratory Failure .............................................................................. 33 Finding Associations ............................................................................................................ 34 Finding Doctors ..................................................................................................................... 36 Selecting Your Doctor .......................................................................................................... 37 Working with Your Doctor................................................................................................. 38 Broader Health-Related Resources.................................................................................... 39 Vocabulary Builder ............................................................................................................... 39

CHAPTER 3. CLINICAL TRIALS AND RESPIRATORY FAILURE ......................................................................................................................................................... 41 Overview .................................................................................................................................. 41 Recent Trials on Respiratory Failure ............................................................................... 44 Benefits and Risks .................................................................................................................. 48 Keeping Current on Clinical Trials .................................................................................. 51 General References................................................................................................................. 52 Vocabulary Builder ............................................................................................................... 53

viii Contents

PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL ....................................................................... 57 CHAPTER 4. STUDIES ON RESPIRATORY FAILURE .......................... 59 Overview .................................................................................................................................. 59 The Combined Health Information Database ................................................................ 59 Federally-Funded Research on Respiratory Failure .................................................... 60 E-Journals: PubMed Central .............................................................................................. 73 The National Library of Medicine: PubMed.................................................................. 74 Vocabulary Builder ............................................................................................................... 75

CHAPTER 5. BOOKS ON RESPIRATORY FAILURE ............................. 83 Overview .................................................................................................................................. 83 Book Summaries: Federal Agencies .................................................................................. 83 Book Summaries: Online Booksellers............................................................................... 84 The National Library of Medicine Book Index .............................................................. 88 Chapters on Respiratory Failure ....................................................................................... 92 General Home References .................................................................................................... 94 Vocabulary Builder ............................................................................................................... 94

CHAPTER 6. MULTIMEDIA ON RESPIRATORY FAILURE ............ 97 Overview .................................................................................................................................. 97 Bibliography: Multimedia on Respiratory Failure....................................................... 97

CHAPTER 7. PERIODICALS AND NEWS ON RESPIRATORY FAILURE ................................................................................................................................ 101 Overview ................................................................................................................................ 101 News Services & Press Releases ...................................................................................... 101 Newsletters on Respiratory Failure................................................................................ 109 Academic Periodicals covering Respiratory Failure .................................................. 110 Vocabulary Builder ............................................................................................................. 111

CHAPTER 8. PHYSICIAN GUIDELINES AND DATABASES ....... 113 Overview ................................................................................................................................ 113 NIH Guidelines .................................................................................................................... 113 NIH Databases ..................................................................................................................... 116 Other Commercial Databases ........................................................................................... 121 The Genome Project and Respiratory Failure ............................................................. 121 Specialized References ........................................................................................................ 126 Vocabulary Builder ............................................................................................................. 127

CHAPTER 9. DISSERTATIONS ON RESPIRATORY FAILURE .... 129 Overview ................................................................................................................................ 129 Dissertations on Respiratory Failure ............................................................................. 129 Keeping Current................................................................................................................... 130

PART III. APPENDICES .......................................................................... 131

Contents

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APPENDIX A. RESEARCHING YOUR MEDICATIONS .................. 133 Overview ................................................................................................................................ 133 Your Medications: The Basics.......................................................................................... 134 Learning More about Your Medications ...................................................................... 136 Commercial Databases ....................................................................................................... 137 Contraindications and Interactions (Hidden Dangers) ........................................... 142 A Final Warning.................................................................................................................. 143 General References............................................................................................................... 144 Vocabulary Builder ............................................................................................................. 144

APPENDIX B. RESEARCHING ALTERNATIVE MEDICINE ........ 147 Overview ................................................................................................................................ 147 What Is CAM? ..................................................................................................................... 147 What Are the Domains of Alternative Medicine? ..................................................... 148 Can Alternatives Affect My Treatment?...................................................................... 151 Finding CAM References on Respiratory Failure ..................................................... 152 Additional Web Resources ................................................................................................ 157 General References............................................................................................................... 168

APPENDIX C. RESEARCHING NUTRITION ........................................... 171 Overview ................................................................................................................................ 171 Food and Nutrition: General Principles ....................................................................... 172 Finding Studies on Respiratory Failure........................................................................ 176 Federal Resources on Nutrition ....................................................................................... 178 Additional Web Resources ................................................................................................ 178 Vocabulary Builder ............................................................................................................. 184

APPENDIX D. FINDING MEDICAL LIBRARIES ................................... 187 Overview ................................................................................................................................ 187 Preparation ............................................................................................................................ 187 Finding a Local Medical Library ..................................................................................... 188 Medical Libraries Open to the Public ............................................................................ 188

APPENDIX E. YOUR RIGHTS AND INSURANCE ............................... 195 Overview ................................................................................................................................ 195 Your Rights as a Patient.................................................................................................... 195 Patient Responsibilities ...................................................................................................... 199 Choosing an Insurance Plan............................................................................................. 200 Medicare and Medicaid ...................................................................................................... 202 NORD’s Medication Assistance Programs ................................................................. 205 Additional Resources .......................................................................................................... 206

ONLINE GLOSSARIES............................................................................. 207 Online Dictionary Directories ......................................................................................... 208

RESPIRATORY FAILURE GLOSSARY........................... 209

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Contents

General Dictionaries and Glossaries .............................................................................. 227

INDEX ................................................................................................................................... 229

Introduction

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INTRODUCTION Overview Dr. C. Everett Koop, former U.S. Surgeon General, once said, “The best prescription is knowledge.”1 The Agency for Healthcare Research and Quality (AHRQ) of the National Institutes of Health (NIH) echoes this view and recommends that every patient incorporate education into the treatment process. According to the AHRQ: Finding out more about your condition is a good place to start. By contacting groups that support your condition, visiting your local library, and searching on the Internet, you can find good information to help guide your treatment decisions. Some information may be hard to find—especially if you don’t know where to look.2 As the AHRQ mentions, finding the right information is not an obvious task. Though many physicians and public officials had thought that the emergence of the Internet would do much to assist patients in obtaining reliable information, in March 2001 the National Institutes of Health issued the following warning: The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading.3

Quotation from http://www.drkoop.com. The Agency for Healthcare Research and Quality (AHRQ): http://www.ahcpr.gov/consumer/diaginfo.htm. 3 From the NIH, National Cancer Institute (NCI): http://cancertrials.nci.nih.gov/beyond/evaluating.html. 1 2

2

Respiratory Failure

Since the late 1990s, physicians have seen a general increase in patient Internet usage rates. Patients frequently enter their doctor’s offices with printed Web pages of home remedies in the guise of latest medical research. This scenario is so common that doctors often spend more time dispelling misleading information than guiding patients through sound therapies. The Official Patient’s Sourcebook on Respiratory Failure has been created for patients who have decided to make education and research an integral part of the treatment process. The pages that follow will tell you where and how to look for information covering virtually all topics related to respiratory failure, from the essentials to the most advanced areas of research. The title of this book includes the word “official.” This reflects the fact that the sourcebook draws from public, academic, government, and peerreviewed research. Selected readings from various agencies are reproduced to give you some of the latest official information available to date on respiratory failure. Given patients’ increasing sophistication in using the Internet, abundant references to reliable Internet-based resources are provided throughout this sourcebook. Where possible, guidance is provided on how to obtain free-ofcharge, primary research results as well as more detailed information via the Internet. E-book and electronic versions of this sourcebook are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). Hard copy users of this sourcebook can type cited Web addresses directly into their browsers to obtain access to the corresponding sites. Since we are working with ICON Health Publications, hard copy Sourcebooks are frequently updated and printed on demand to ensure that the information provided is current. In addition to extensive references accessible via the Internet, every chapter presents a “Vocabulary Builder.” Many health guides offer glossaries of technical or uncommon terms in an appendix. In editing this sourcebook, we have decided to place a smaller glossary within each chapter that covers terms used in that chapter. Given the technical nature of some chapters, you may need to revisit many sections. Building one’s vocabulary of medical terms in such a gradual manner has been shown to improve the learning process. We must emphasize that no sourcebook on respiratory failure should affirm that a specific diagnostic procedure or treatment discussed in a research study, patent, or doctoral dissertation is “correct” or your best option. This sourcebook is no exception. Each patient is unique. Deciding on appropriate

Introduction

3

options is always up to the patient in consultation with their physician and healthcare providers.

Organization This sourcebook is organized into three parts. Part I explores basic techniques to researching respiratory failure (e.g. finding guidelines on diagnosis, treatments, and prognosis), followed by a number of topics, including information on how to get in touch with organizations, associations, or other patient networks dedicated to respiratory failure. It also gives you sources of information that can help you find a doctor in your local area specializing in diagnosing and treating respiratory failure. Collectively, the material presented in Part I is a complete primer on basic research topics for patients with respiratory failure. Part II moves on to advanced research dedicated to respiratory failure. Part II is intended for those willing to invest many hours of hard work and study. It is here that we direct you to the latest scientific and applied research on respiratory failure. When possible, contact names, links via the Internet, and summaries are provided. It is in Part II where the vocabulary process becomes important as authors publishing advanced research frequently use highly specialized language. In general, every attempt is made to recommend “free-to-use” options. Part III provides appendices of useful background reading for all patients with respiratory failure or related disorders. The appendices are dedicated to more pragmatic issues faced by many patients with respiratory failure. Accessing materials via medical libraries may be the only option for some readers, so a guide is provided for finding local medical libraries which are open to the public. Part III, therefore, focuses on advice that goes beyond the biological and scientific issues facing patients with respiratory failure.

Scope While this sourcebook covers respiratory failure, your doctor, research publications, and specialists may refer to your condition using a variety of terms. Therefore, you should understand that respiratory failure is often considered a synonym or a condition closely related to the following: ·

Apnea

·

Cardiorespiratory Failure

4

Respiratory Failure

·

Respiratory Arrest

·

Stopped Respiration

In addition to synonyms and related conditions, physicians may refer to respiratory failure using certain coding systems. The International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) is the most commonly used system of classification for the world’s illnesses. Your physician may use this coding system as an administrative or tracking tool. The following classification is commonly used for respiratory failure:4 ·

799.1 respiratory arrest

For the purposes of this sourcebook, we have attempted to be as inclusive as possible, looking for official information for all of the synonyms relevant to respiratory failure. You may find it useful to refer to synonyms when accessing databases or interacting with healthcare professionals and medical librarians.

Moving Forward Since the 1980s, the world has seen a proliferation of healthcare guides covering most illnesses and conditions. Some are written by patients or their family members. These generally take a layperson’s approach to understanding and coping with an illness or disorder. They can be uplifting, encouraging, and highly supportive. Other guides are authored by physicians or other healthcare providers who have a more clinical outlook. Each of these two styles of guide has its purpose and can be quite useful. As editors, we have chosen a third route. We have chosen to expose you to as many sources of official and peer-reviewed information as practical, for the purpose of educating you about basic and advanced knowledge as recognized by medical science today. You can think of this sourcebook as your personal Internet age reference librarian. Why “Internet age”? All too often, patients with respiratory failure will log on to the Internet, type words into a search engine, and receive several Web 4 This list is based on the official version of the World Health Organization’s 9th Revision, International Classification of Diseases (ICD-9). According to the National Technical Information Service, “ICD-9CM extensions, interpretations, modifications, addenda, or errata other than those approved by the U.S. Public Health Service and the Health Care Financing Administration are not to be considered official and should not be utilized. Continuous maintenance of the ICD-9-CM is the responsibility of the federal government.”

Introduction

5

site listings which are mostly irrelevant or redundant. These patients are left to wonder where the relevant information is, and how to obtain it. Since only the smallest fraction of information dealing with respiratory failure is even indexed in search engines, a non-systematic approach often leads to frustration and disappointment. With this sourcebook, we hope to direct you to the information you need that you would not likely find using popular Web directories. Beyond Web listings, in many cases we will reproduce brief summaries or abstracts of available reference materials. These abstracts often contain distilled information on topics of discussion. While we focus on the more scientific aspects of respiratory failure, there is, of course, the emotional side to consider. Later in the sourcebook, we provide a chapter dedicated to helping you find peer groups and associations that can provide additional support beyond research produced by medical science. We hope that the choices we have made give you the most options available in moving forward. In this way, we wish you the best in your efforts to incorporate this educational approach into your treatment plan. The Editors

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PART I: THE ESSENTIALS

ABOUT PART I Part I has been edited to give you access to what we feel are “the essentials” on respiratory failure. The essentials of a symptom typically include the definition or description of the symptom, a discussion of who it affects, the diseases that are associated with a given symptom, tests or diagnostic procedures that might be specific to the symptom, and treatments for the symptom. Your doctor or healthcare provider may have already explained the essentials of respiratory failure to you or even given you a pamphlet or brochure describing respiratory failure. Now you are searching for more indepth information. As editors, we have decided, nevertheless, to include a discussion on where to find essential information that can complement what your doctor has already told you. In this section we recommend a process, not a particular Web site or reference book. The process ensures that, as you search the Web, you gain background information in such a way as to maximize your understanding.

Guidelines

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CHAPTER 1. THE ESSENTIALS ON RESPIRATORY FAILURE: GUIDELINES Overview Official agencies, as well as federally-funded institutions supported by national grants, frequently publish a variety of guidelines on respiratory failure. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. The great advantage of guidelines over other sources is that they are often written with the patient in mind. Since new guidelines on respiratory failure can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

The National Institutes of Health (NIH)5 The National Institutes of Health (NIH) is the first place to search for relatively current patient guidelines and fact sheets on respiratory failure. Originally founded in 1887, the NIH is one of the world’s foremost medical research centers and the federal focal point for medical research in the United States. At any given time, the NIH supports some 35,000 research grants at universities, medical schools, and other research and training institutions, both nationally and internationally. The rosters of those who have conducted research or who have received NIH support over the years include the world’s most illustrious scientists and physicians. Among them are 97 scientists who have won the Nobel Prize for achievement in medicine.

5

Adapted from the NIH: http://www.nih.gov/about/NIHoverview.html.

10 Respiratory Failure

There is no guarantee that any one Institute will have a guideline on a specific condition or disease, though the National Institutes of Health collectively publish over 600 guidelines for both common and rare conditions and disorders. The best way to access NIH guidelines is via the Internet. Although the NIH is organized into many different Institutes and Offices, the following is a list of key Web sites where you are most likely to find NIH clinical guidelines and publications dealing with respiratory failure and associated conditions: ·

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

·

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines available at http://www.nlm.nih.gov/medlineplus/healthtopics.html

·

National Heart, Lung, and Blood Institute (NHLBI); guidelines at http://www.nhlbi.nih.gov/guidelines/index.htm

Among these, the National Heart, Lung, and Blood Institute (NHLBI) is particularly noteworthy. The NHLBI provides leadership for a national program in diseases of the heart, blood vessels, lung, and blood; blood resources; and sleep disorders.6 Since October 1997, the NHLBI has also had administrative responsibility for the NIH Woman’s Health Initiative. The Institute plans, conducts, fosters, and supports an integrated and coordinated program of basic research, clinical investigations and trials, observational studies, and demonstration and education projects. Research is related to the causes, prevention, diagnosis, and treatment of heart, blood vessel, lung, and blood diseases; and sleep disorders. The NHLBI plans and directs research in development and evaluation of interventions and devices related to prevention, treatment, and rehabilitation of patients suffering from such diseases and disorders. It also supports research on clinical use of blood and all aspects of the management of blood resources. Research is conducted in the Institute’s own laboratories and by scientific institutions and individuals supported by research grants and contracts. For health professionals and the public, the NHLBI conducts educational activities, including development and dissemination of materials in the above areas, with an emphasis on prevention. Within the NHLBI, the Division of Lung Diseases (DLD) maintains surveillance over developments in pulmonary research and assesses the Nation’s need for research on the causes, prevention, diagnosis, and This paragraph has been adapted from the NHLBI: http://www.nhlbi.nih.gov/about/org/mission.htm. “Adapted” signifies that a passage is reproduced exactly or slightly edited for this book. 6

Guidelines 11

treatment of pulmonary diseases.7 Also within the purview of the Division are: technology development, application of research findings, and research training and career development in pulmonary diseases. The DLD plans and directs the research and training programs which encompass basic research, applied research and development, clinical investigations, clinical trials, and demonstration and education research. Two programs comprise the Division of Lung Diseases, Airway Biology and Disease Program, and the Lung Biology and Disease Program. The following patient guideline was recently published by the NHLBI and the DLD on respiratory failure.

What Is Respiratory Failure?8 Almost everyone who has a critically ill friend or relative may expect to hear the term, respiratory failure. Although failure to breathe normally was recognized even in ancient times as an ominous sign, the term, “respiratory failure,” did not appear in the medical literature until the 1960s. Doctors now understand that respiratory failure is a serious disorder caused by a variety of different medical problems that may or may not start in the lung. Healthy people as well as patients with either pulmonary (lung) or nonpulmonary diseases can develop respiratory failure. The recognition of respiratory failure as a life-threatening problem led to the development of the concept of the intensive care unit (ICU) in modern hospitals. ICU personnel and equipment support vital functions to give patients their best chance for recovery. Today’s sophisticated ICU facilities with their novel mechanical life support devices evolved as doctors and scientists learned more and more about the causes of respiratory failure and how to treat it. This pamphlet is a brief overview of the unique changes in lung function that are typical of respiratory failure and the widely different medical conditions that can cause those changes. It also discusses the methods that are used to restore normal respiration and prolong life, and the related dilemma of deciding if and when to withdraw or withhold life support from a hopelessly sick patient. Medical terms are shown in italic print and are explained in the text or in the glossary.

7 Adapted from the DLD: http://www.nhlbi.nih.gov/about/dld/index.htm. For more information, contact: Division of Lung Diseases; National Heart, Lung and Blood Institute; ATTN: Web Site Inquiries; Two Rockledge Center, Suite 10122, 6701 Rockledge Dr., MSC 7952; Bethesda, Maryland 20892-7952. 8 Adapted from The National Heart, Lung, and Blood Institute: http://www.nhlbi.nih.gov/health/public/lung/other/res_fail.htm.


Who Can Get Respiratory Failure? Many different medical conditions can lead to respiratory failure. Listed below are a few examples of people who may develop respiratory failure. ·

A patient with a long history of asthma, emphysema, or chronic obstructive lung disease

·

A patient who is undergoing major surgery in the abdomen, heart, or lung

·

A person who has taken an overdose of sleeping pills or certain depressant drugs

·

A pre m a t u re baby who weighs less than 3 pounds

·

A baby with bronchopulmonary dysplasia

·

A patient suffering from AIDS

·

A person who has received multiple physical injuries

·

A person who has suffered extensive burns

·

A person who has bled extensively from a gunshot wound

·

A person who has almost drowned

·

A patient with severe heart failure

·

A patient with severe infections

·

A person who is extremely obese

Breathing and Respiratory Failure The term, “respiratory failure,” is used when the lungs are unable to perform their basic task—gas exchange. This process involves transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs, with the result that the arterial blood, blood circulating through the body from the heart, has enough oxygen to nourish the tissues. Gas exchange occurs in tiny air sacs in the lung, called alveoli. When a person breathes in (inspiration), air is brought into the alveoli by the action of the respiratory muscles—the diaphragm, the muscles between the ribs, and the accessory muscles (those between the neck and the chest wall). These are collectively called “the ventilatory apparatus.” The activity of the respiratory muscles is controlled by respiratory centers in the brain. The brain’s

Guidelines 13

respiratory centers in turn are controlled by chemoreceptors, special cells that are sensitive to the amounts of carbon dioxide or oxygen in the blood. The chemoreceptors that are sensitive to oxygen concentration are located in the large arteries in the neck in the carotid bodies. When they sense a fall in the level of oxygen in the blood, they send messages that stimulate the respiratory center in the brain so that there will be an increase in the rate or depth of breathing. Whenever any part of the ventilatory apparatus and/or the respiratory centers fails to work properly, the result can be respiratory failure. Both adults and babies can develop respiratory failure. In infants, however, respiratory failure occurs mostly in premature babies whose lungs have not yet fully developed. Transfer of oxygen of inhaled air into the blood and of waste carbon dioxide of blood into the lungs occurs in the alveolus.


What Happens During Respiratory Failure? When the process of gas exchange is faulty, there is not enough oxygen in the blood (hypoxemia) to fuel the body’s metabolic activity. In addition, sometimes there is also an accumulation of carbon dioxide, a waste product of metabolism, in the blood and tissues (hypercapnia). Hypercapnia makes blood more acidic; this condition is called acidemia. Eventually the body tissues become acidic. This condition, called acidosis, injures the body’s cells and interferes with the functions of the heart and central nervous system. Ultimately, lack of oxygen in the blood causes death of the cells in the brain and other tissues. If not adequately treated, respiratory failure is fatal.

Hypoxemic Respiratory Failure When a lung disease causes respiratory failure, gas exchange is reduced because of changes in ventilation (the exchange of air between the lungs and the atmosphere), perfusion (blood flow), or both. Activity of the respiratory muscles is normal. This type of respiratory failure which results from a mismatch between ventilation and perfusion is called hypoxemic respiratory failure. Some of the alveoli get less fresh air than they need for the amount of blood flow, with the net result of a fall in oxygen in the blood. These patients tend to have more difficulty with the transport of oxygen than with removing carbon dioxide. They often overbreathe (hyperventilate) to make up for the low oxygen, and this results in a low CO2 level in the blood (hypocapnia). Hypocapnia makes the blood more basic or alkaline which is also injurious to the cells.

Hypercapnic Respiratory Failure Respiratory failure due to a disease of the muscles used for breathing (“pump or ventilatory apparatus failure”) is called hypercapnic respiratory failure. The lungs of these patients are normal. This type of respiratory failure occurs in patients with neuromuscular diseases such as myasthenia gravis, stroke, cerebral palsy, poliomyelitis, amyotrophic lateral sclerosis, muscular dystrophy, postoperative situations limiting ability to take deep breaths, and in depressant drug overdoses. Each of these disorders involves a loss or decrease in neuromuscular function, inefficient breathing and limitation to the flow of air into the lungs. Blood oxygen falls and the carbon dioxide increases because fresh air is not brought into the alveoli in needed amounts. In general, mechanical devices that help move the chest wall help these patients.

Guidelines 15

Conditions That May Progress to Respiratory Failure Almost all lung diseases including asthma, chronic obstructive pulmonary disease (COPD), AIDS-related pneumonia, other pneumonias and lung infections, and cystic fibrosis may eventually lead to respiratory failure particularly if the diseases are inadequately treated. These patients find it very hard to breathe and the result is low oxygen and high carbon dioxide blood levels. People whose normal lungs have been injured, such as from exposure to noxious gases, steam, or heat during a fire, can subsequently go into respiratory failure. Adult respiratory distress syndrome (ARDS), also referred to as acute respiratory distress syndrome, is a form of acute respiratory failure caused by extensive lung injury following a variety of catastrophic events such as shock, severe infection, and burns. ARDS can occur in individuals with or without previous lung disease. Hyaline membrane disease or respiratory distress syndrome of the newborn (RDS), the most common respiratory illness affecting premature babies, is another kind of respiratory failure. In this condition, the baby’s lungs do not have enough surfactant, a substance that makes it possible for air to pass into the alveoli by lowering surface tension and preventing their collapse.

Symptoms of Respiratory Failure The clinical features of respiratory failure vary widely in individual patients because so many different conditions can lead to this disorder. There are no physical signs unique to respiratory failure. At extremely low arterial oxygen (PaO2) levels, patients have rapid heart rates, rapid breathing rates, and they are confused, sweaty, and cyanotic (blue). Chronically low arterial oxygen makes patients irritable, and elevated carbon dioxide produces headaches and sleepiness. Difficult, rapid, or labored breathing (dyspnea) is a consistent symptom in the awake patient. The functions of the heart and blood vessels are often severely impaired in patients with respiratory failure. In some cases, chronic hypoxemia produces narrowing of the blood vessels in the lung which, along with the lung damage or the associated treatments, may weaken the heart and the circulatory system. Some of the signs of inadequate circulation are constriction of blood vessels in the skin, cold extremities, and low urine output.


Diagnosis of Respiratory Failure It is impossible to estimate the extent of hypoxemia and hypercapnia by observing a patient’s signs and symptoms, and mild hypoxemia and hypercapnia may go entirely unnoticed. Blood oxygen must fall markedly before changes in breathing and heart rate occur. The way to diagnose respiratory failure, therefore, is to measure oxygen (PaO2) and carbon dioxide (PaCO2) in the arterial blood. However the levels that indicate respiratory failure are somewhat arbitrary. Depending on age, a PaO2 less than 60 mm Hg or PaCO2 greater than 45 mm Hg generally mean that the patient is in respiratory failure.

Management of Respiratory Failure The patient with respiratory failure cannot be adequately treated in the general care areas of the hospital. Therefore, patients in severe respiratory failure are usually treated in the intensive care unit. Current therapy for all forms of respiratory failure attempts, first, to provide support for the heart, lungs, and other affected vital organs; and second, to identify and treat the underlying cause. Since the immediate threat to patients with respiratory failure is due to the inadequate level of oxygen delivered to the tissues, oxygenation is the basic therapy for acute respiratory failure due to lung disease. Oxygen-enriched air is usually given to the patient by nasal prongs, oxygen mask, or by placing an airtube into the trachea (windpipe). Since prolonged high oxygen levels can be toxic, the concentration of oxygen must be carefully controlled for both short- and long-term treatment. Assisted ventilation with mechanical devices may be the first priority for neuromuscular disease patients going into respiratory failure. Additional treatments employ ventilation which helps to keep the lungs inflated at low lung volumes (positive end-expiratory pressure, PEEP), and fluid and nutritional management. Endotracheal Intubation Endotracheal intubation involves insertion of a tube into the trachea. It permits delivery of precisely determined amounts of oxygen to the lungs and removal of secretions, and ensures adequate ventilation. Combined with

Guidelines 17

mechanical ventilation, endotracheal intubation is the cornerstone of therapy for respiratory failure.

A tube inserted into the windpipe helps delivery of oxygen into the lungs. Mechanical Ventilation If the patient is tiring despite ongoing therapy, a mechanical ventilator, also called a respirator, is used. The ventilator assists or controls the patient’s breathing.

Positive End-Expiratory Pressure (PEEP) Positive end-expiratory pressure is used with mechanical ventilation to keep the air pressure in the trachea at a level that increases the volume of gas remaining in the lung after breathing out (expiration). This keeps the alveoli open, reduces the shunting of blood through the lungs, and improves gas exchange. Most ventilators have a PEEP adjustment.

Extracorporeal Membrane Oxygenator (ECMO) The extracorporeal membrane oxygenator (ECMO) is essentially an artificial lung. It is an appropriately cased artificial membrane which is attached to the patient externally (extracorporeally), through a vein or artery. Although the best substitute for a diseased lung that cannot handle gas exchange adequately is a healthy human lung, such substitution is often not possible. Circulating the patient’s blood through the ECMO offers another approach. Gas exchange using ECMO keeps the patient alive while the damaged lungs have a chance to heal. In 1974, the National Heart, Lung, and Blood Institute


(NHLBI) organized a carefully designed clinical trial, to determine the effectiveness of ECMO for patients with acute respiratory distress syndrome. In this study, ECMO appeared to be no more useful than conventional therapy. On the other hand, ECMO seems to be an effective option in some infants with respiratory failure when treatment with mechanical ventilation fails. However ECMO is expensive, is associated with nonrespiratory complications, and is available only in a few specialized centers. Management of Fluids and Electrolytes Pulmonary edema, the buildup of abnormal amounts of fluid in the lung tissues, often occurs in respiratory failure. Therefore fluids are carefully managed and monitored to maintain fluid balance and avoid fluid overload which may further worsen gas exchange. Pharmacologic Therapy Because respiratory failure may be the end result of several different diseases, no single drug therapy is effective in all situations. ·

Antibiotics help when infections (sepsis) as well as pneumonia are involved in respiratory failure.

·

Bronchodilators, for example, theophylline compounds, sympathomimetic agents (albuterol, metaproterenol, isoproterenol), anticholinergics (ipratropium bromide), and corticosteroids, reverse bronchoconstriction and reduce tissue inflammation.

·

Other drugs, such as digitalis, improve cardiac output, and drugs which increase blood pressure in shock can improve blood flow to the tissues. Bronchoscopy

Patients with respiratory failure who have excessive lung secretions are sometimes helped by fiberoptic bronchoscopy, a technique for accessing the interior of the bronchi, the larger air passages of the lungs. The bronchoscope is a flexible tube with a light at the end that is passed through the nose or mouth into the trachea and bronchi. Fluid or tissue can be removed from the bronchi (aspiration), and cells for microscopic examination can be obtained by washing the interior of the larger breathing tubes (lavage). Bronchoscopy is useful for placing or removing endotracheal tubes, removing foreign bodies from the lung, and collecting tissue samples for diagnosis.

Guidelines 19

Intravenous Nutritional Support Nutritional supplementation is essential to maintain or restore strength when weakness and loss of muscle mass prevent patients from breathing adequately without ventilatory support. Appropriate nutrients (fats, carbohydrates, and predigested proteins) are fed intravenously for this purpose.

Physiotherapy Physiotherapy includes chest percussion (repeated sharp blows to the chest and back to loosen secretions), suction of airways, and regular changes of body position. It helps drain secretions, maintains alveolar inflation and prevents atelectasis, incomplete expansion of the lung.

X-Ray Monitoring X-ray images of the chest help the doctor monitor the progress of lung and heart disease in respiratory failure. The portable chest radiograph taken with an x-ray machine brought to the bedside is often used for this purpose in the intensive care unit.

Lung Transplantation Lung transplantation currently offers the only hope for certain patients with end-stage pulmonary disease. The shortage of suitable donors and the high cost of the procedure continue to be major obstacles that limit its use.

Complications of Treatment Oxygen toxicity, pulmonary embolism (closure of the pulmonary artery or one of its branches by a blood clot or a fat globule), cardiovascular problems, barotrauma (injury to the lung tissue from excessive ventilatory pressure), pneumothorax (air in the pleural space), and gastrointestinal bleeding are some of the complications of treatment. They result from fluid overload, mechanical ventilation, PEEP, and other procedures used in the management of respiratory failure.


Weaning the Patients from Ventilators The process of returning the patient to unassisted and spontaneous breathing is called weaning. Weaning is a complex process that requires the understanding and cooperation of the patient. It can cause great fatigue and depression in patients because of the slow- and long-term nature of the treatment procedures. Weaning a patient too rapidly or prematurely can be dangerous. Some patients, particularly those who had severe underlying cardiac disease and prolonged episodes of acute illnesses, may require weeks to months to wean. The doctor considers weaning only when the patient is awake, has good nutrition, and is able to cough and breathe deeply. Discontinuation of Ventilatory Support The difficult question of whether and when to discontinue life-sustaining mechanical ventilation to the patient who is not responding to any treatment is sometimes faced by the doctor and the family. The legal, ethical, and financial implications of continuing or withholding treatment to the patient in terminal respiratory failure are important issues addressed at family, professional, and government levels. Respecting the rights and wishes of the patient and helping the patient achieve a dignified and peaceful end while continuing to assure care and comfort is a responsibility shared by both the caregivers and the family. The family with a good understanding of respiratory failure in all its dimensions is best equipped to play its part in sharing this responsibility.

More about Some Common Lung Diseases Leading to Or Characterized by Respiratory Failure Asthma The hallmarks of asthma are obstruction to air flow and bronchoconstriction, tightening of the muscles in the walls of the bronchi, that is usually relieved by drugs called bronchodilators. Acute asthma attacks that persist, do not respond to bronchodilator therapy, and threaten life are referred to as status asthmaticus. Due to the heavy work of breathing, patients eventually tire and decrease their respiratory efforts. Patients in this condition are prone to develop respiratory failure. Respiratory failure is more common in women

Guidelines 21

with asthma, in patients over 40 years of age, and in patients in whom treatment is delayed, or oral corticosteroid therapy is stopped suddenly. During an attack of asthma, airways obstruction from mucus secretions and thickened bronchial tissue can lead to severe hypoxemia, hypercapnia, and acidosis. Other potential complications are pneumonia and accumulation of air in pleural spaces. Patients with hypercapnia are at increased risk of death. In children with asthma, respiratory muscle fatigue and interrupted breathing (apnea) are indications of existing or developing respiratory failure.

Chronic Obstructive Pulmonary Disease (COPD) COPD patients may develop acute respiratory failure when their chronic airway obstruction is complicated by infections, pulmonary emboli, heart failure, and drug-induced respiratory depression. Influenza often precipitates respiratory failure even without evidence of pneumonia in COPD patients. The hallmark of respiratory failure in COPD is increasing dyspnea and worsening blood gas abnormalities. Depending on the triggering event, various other clinical features may appear. The most dire sign is a decline in the patient’s condition associated with PaO2 of less than 50 mm Hg and a PaCO2 greater than 50 mm Hg during air breathing. Uncontrolled administration of oxygen to patients with COPD and acute respiratory failure without therapy directed at reducing the work of breathing can result in further hypercapnia, acidosis, stupor, and coma.

Pneumonia Patients with very severe pneumonia go into respiratory failure because of lung inflammation and accumulation of fluid that interferes with gas exchange. They breathe hard and become exhausted; their respiratory muscles are unable to keep up the pace. Blood carbon dioxide rises and oxygen in the blood falls further. Sedation, at the time of respiratory stress, may worsen the situation by depression of the brain activity which is needed to keep respiratory muscles working at high levels. This, in turn, decreases the amount of breathing and may promote the development of respiratory failure.


Respiratory Distress Syndrome of the Newborn One type of respiratory failure in the newborn infant, especially those born prematurely, is commonly referred to as “respiratory distress syndrome.” It is also called hyaline membrane disease because of the formation of an abnormal, hyaline (glassy and transparent under the microscope), proteincontaining membrane in alveoli. RDS may also occur in full-term babies born to diabetic mothers. The causes of RDS are complex, but it is believed that the major problem is a poorly developed lung. Surfactant, a unique fatcontaining protein necessary to reduce the surface tension in the alveoli of the lung to prevent their collapse, is deficient in RDS babies. The most effective treatment for RDS is the administration of surfactant. Surfactant replacement therapy for RDS, available since 1989, has brought about a 30 percent reduction in death rate for neonatal RDS in the United States (from 89.9 deaths per 100,000 live births in 1989 to 58.3 deaths per 100,000 in 1992). The National Heart, Lung, and Blood Institute (NHLBI) is supporting the development and testing of several different surfactant preparations useful in replacement therapy for RDS.

Adult or Acute Respiratory Distress Syndrome Acute respiratory failure in adults as a clinical entity was first reported in 1967. Respiratory failure usually occurred following a catastrophic event in individuals with no previous lung disease and who did not respond to ordinary methods of respiratory support. Regardless of the event causing the lung injury, the patients exhibited common signs and symptoms, x-ray findings, and tissue changes. Because many of its features resembled the respiratory distress syndrome of the newborn, RDS, the adult disease was called “ARDS.” As with RDS, there is increasing evidence that loss of surfactant function may also be associated with ARDS. Inhalation of gastric contents (aspiration), pulmonary infections, shock, trauma, burns, extrapulmonary sepsis, inhalation of toxic gases, drug overdose, and neardrowning are some of the different situations that can cause ARDS. An estimated 150,000 cases of ARDS occur yearly in the United States. The estimated mortality rate of ARDS is 50-70 percent. ARDS is often associated with multiple organ failure (heart, liver, kidneys, and lungs). Patient survival usually depends on the number of organs which fail, the degree and nature of damage, and the age and previous health status of the patient. The incidence of multiple organ failure is particularly high

Guidelines 23

when sepsis or hypotension from loss of blood are the underlying causes of ARDS. Research designed to clarify the events that underlie the development of ARDS is of high priority to the NHLBI. This knowledge should lead to new strategies for the prevention and treatment of ARDS.

Additional Information Additional information on respiratory failure can be obtained from: National Heart, Lung, and Blood Institute Office of the Director, Division of Lung Diseases Two Rockledge Center 6701 Rockledge Drive MSC 7952 Bethesda, MD 20892-7952 Telephone: (301) 435-0230

More Guideline Sources The guideline above on respiratory failure is only one example of the kind of material that you can find online and free of charge. The remainder of this chapter will direct you to other sources which either publish or can help you find additional guidelines on topics related to respiratory failure. Many of the guidelines listed below address topics that may be of particular relevance to your specific situation or of special interest to only some patients with respiratory failure. Due to space limitations these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly.

Topic Pages: MEDLINEplus For patients wishing to go beyond guidelines published by specific Institutes of the NIH, the National Library of Medicine has created a vast and patientoriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages.” You can think of a health topic page as a guide to patient guides. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html.


If you do not find topics of interest when browsing health topic pages, then you can choose to use the advanced search utility of MEDLINEplus at http://www.nlm.nih.gov/medlineplus/advancedsearch.html. This utility is similar to the NIH Search Utility, with the exception that it only includes material linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search their site located at http://www.guideline.gov by using the keyword “respiratory failure” or synonyms. The following was recently posted: ·

Apnea of prematurity. Source: National Association of Neonatal Nurses.; 1999; 22 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1373&sSearch_string=respiratory+failure

Healthfinder™ Healthfinder™ is an additional source sponsored by the U.S. Department of Health and Human Services which offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: ·

A1AD Related Emphysema Summary: This online consumer health information fact sheet provides basic information about this respiratory disorder which is caused by an inherited lack of a protective protein called alpha1-antitrypsin Source: American Lung Association http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=2470

Guidelines 25

·

Allergy, Asthma & Immunology Online Summary: This site functions as an information and news service for patients and their families, purchasers of group health care programs, and the news media. Source: American College of Allergy, Asthma & Immunology http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=2881

·

American Academy of Allergy, Asthma and Immunology Physician Referral Database Summary: Use this database to search for an Amer member physician in your area. You may search this database in four ways: by distance, state, country, physician name and physician specialty. Source: American Academy of Allergy, Asthma and Immunology http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=4938

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Asthma & Physical Activity in the School Summary: Designed for use by classroom teachers, physical education teachers and coaches, this publication is meant to assist them to help in managing and controlling their students' asthma so that he or she Source: National Heart, Lung, and Blood Institute, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=843

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Asthma and Allergy Statistics Summary: This fact sheet provides statistical information about asthma in the United States including prevalence, mortality rates, and treatment costs. Source: National Institute of Allergy and Infectious Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=825


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Asthma Education: Interactive Guidelines Summary: An interactive program designed to facilitate the incorporation of the current National Asthma Education Guidelines into clinical practice and to quickly obtain individualized patient recommendations. Source: Educational Institution--Follow the Resource URL for More Information http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=4102

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Asthma Information Home Page Summary: Browse this site for general and in-depth information about asthma including asthma and older people, teens and asthma, asthma in young children, asthma medicines, asthma triggers and attacks, peak Source: American Lung Association http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=2472

The NIH Search Utility After browsing the references listed at the beginning of this chapter, you may want to explore the NIH Search Utility. This allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEBSPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to respiratory failure. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific conditions or disorders, or when using highly targeted searches. To use the NIH search utility, visit http://search.nih.gov/index.html.

Additional Web Sources A number of Web sites that often link to government sites are available to the public. These can also point you in the direction of essential information. The following is a representative sample: ·

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

Guidelines 27

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drkoop.comÒ: http://www.drkoop.com/conditions/ency/index.html

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Family Village: http://www.familyvillage.wisc.edu/specific.htm

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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

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Med Help International: http://www.medhelp.org/HealthTopics/A.html

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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

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WebMDÒHealth: http://my.webmd.com/health_topics

Vocabulary Builder The material in this chapter may have contained a number of unfamiliar words. The following Vocabulary Builder introduces you to terms used in this chapter that have not been covered in the previous chapter: Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Acidemia: Increased acidity of blood. [NIH] Acidosis: Pathologic condition resulting from accumulation of acid in the blood and tissues. [NIH] Airways: Tubes that carry air into and out of the lungs. [NIH] Albuterol: A racemic mixture with a 1:1 ratio of the r-isomer, levalbuterol, and s-albuterol. It is a short-acting beta2-adrenergic agonist with its main clinical use in asthma. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alveoli: Tiny sac-like air spaces in the lungs where transfer of carbon dioxide from blood into the lungs and oxygen from air into blood takes place. [NIH] Antibiotic: A drug that kills or inhibits the growth of bacteria. [NIH] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Apnea: A transient absence of spontaneous respiration. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body.


Aspiration: The act of inhaling. [EU] Atelectasis: Incomplete expansion of the lung. [NIH] Barotrauma: Injury following pressure changes; includes injury to the eustachian tube, ear drum, lung and stomach. [NIH] Bronchi: Larger air passages of the respiratory system. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchoconstriction: Tightening of the muscles surrounding the bronchi, the tubes that branch from the windpipe. [NIH] Bronchodilator: A drug that relaxes the smooth muscles in the constricted airway. [NIH] Bronchopulmonary: Pertaining to the lungs and air passages. [NIH] Bronchoscope: A long, narrow tube with a light at the end that is used by the doctor for direct observation of the airways, as well as for suction of tissue and other materials. [NIH] Bronchoscopy: A technique for visualizing the interior of bronchi and instilling or removing fluid or tissue samples by passing a lighted tube (bronchoscope) through the nose or mouth into the bronchi. [NIH] Carbohydrates: A nutrient that supplies 4 calories/gram. They may be simple or complex. Simple carbohydrates are called sugars, and complex carbohydrates are called starch and fiber (cellulose). An organic compound—containing carbon, hydrogen, and oxygen—that is formed by photosynthesis in plants. Carbohydrates are heat producing and are classified as monosaccharides, disaccharides, or polysaccharides. [NIH] Cardiac: Pertaining to the heart. [EU] Cardiovascular: Pertaining to the heart and blood vessels. [EU] Cell: Basic subunit of every living organism; the simplest unit that can exist as an independent living system. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Chemoreceptors: Specific molecules within a cell or on its surface, which are excited by other chemical substances that bind to them. [NIH] Chronic: Of long duration; frequently recurring. [NIH] Collapse: 1. a state of extreme prostration and depression, with failure of circulation. 2. abnormal falling in of the walls of any part of organ. [EU] Constriction: The act of constricting. [NIH] Corticosteroids: Drugs that mimic the action of a group of hormones produced by adrenal glands; they are anti-inflammatory and act as bronchodilators. [NIH] Cyanotic: Bluish color of the skin due to insufficient oxygen. [NIH]

Guidelines 29

Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Digitalis: A drug used to increase the force of the heart's contraction and to regulate specific irregularities of heart rhythm. [NIH] Dysplasia: Abnormal development or growth. [NIH] Dyspnea: Shortness of breath; difficult or labored breathing. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] ECMO: Extracorporeal membrane oxygenator, a device that acts as an artificial lung, oxygenating the blood that passes through it from the patient’s blood vessels. [NIH] Edema: Abnormal fluid accumulation in body tissues. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Embolism: A sudden blocking of an artery by an embolus (clot or a foreign material such as a fat globule) brought to the site by the blood flow. [NIH] Emphysema: Chronic lung disease in which there is permanent destruction of alveoli. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Extracorporeal: Situated or occurring outside the body. [EU] Fatal: Causing death, deadly; mortal; lethal. [EU] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH] Fibrosis: Process by which inflamed tissue becomes scarred. [NIH] Gastrointestinal: Pertaining to or communicating with the stomach and intestine, as a gastrointestinal fistula. [EU] Hypercapnia: Excess carbon dioxide in blood. [NIH] Hyperventilate: To breathe abnormally fast and deep; results in the intake of excessive amounts of oxygen into the lung and reduced carbon dioxide levels in the blood. [NIH] Hypocapnia: Low levels of carbon dioxide in the blood. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypoxemia: Too little oxygen in the blood. [NIH] Inflammation: Response of the body tissues to injury; typical signs are swelling, redness, and pain. [NIH]


Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Intravenous: Within a vein or veins. [EU] Intubation: Insertion of a tube into an organ in the body. [NIH] Ipratropium: A muscarinic antagonist structurally related to atropine but often considered safer and more effective for inhalation use. It is used for various bronchial disorders, in rhinitis, and as an antiarrhythmic. [NIH] Isoproterenol: Isopropyl analog of epinephrine; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant. [NIH] Lavage: To wash the interior of a body organ. [NIH] Membrane: Thin, flexible film of proteins and lipids that encloses the contents of a cell; it controls the substances that go into and come out of the cell. Also, a thin layer of tissue that covers the surface or lines the cavity of an organ. [NIH] Mucus: A thick fluid produced by the lining of some organs of the body. [NIH]

Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Neuromuscular: Pertaining to muscles and nerves. [EU] Oral: Pertaining to the mouth, taken through or applied in the mouth, as an oral medication or an oral thermometer. [EU] Overdose: 1. to administer an excessive dose. 2. an excessive dose. [EU] Oxygenation: To provide with oxygen. [NIH] PaCO2: Carbon dioxide tension of arterial blood. [NIH] PaO2: Oxygentension of arterial blood. [NIH] PEEP: Positive End-Expiratory Pressure. A method of mechanical ventilation in which pressure is maintained to increase the volume of gas remaining in the lung at the end of expiration, thus keeping the alveoli open and improving gas exchange. [NIH] Perfusion: The passage of fluid through an organ. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pneumonia: Inflammation of the lungs. [NIH] Pneumothorax: Accumulation of air or gas in the space between the lung and chest wall, resulting in partial or complete collapse of the lung. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific

Guidelines 31

sequence of amino acids determines the shape and function of the protein. [NIH]

Pulmonary: Relating to the lungs. [NIH] Respiration: Process of exchanging oxygen from the air for carbon dioxide from the body; includes the mechanical process of breathing, gas exchange, and oxygen and carbon dioxide transport to and from the cells. [NIH] Respiratory: Pertaining to respiration. [EU] Sclerosis: A induration, or hardening; especially hardening of a part from inflammation and in diseases of the interstitial substance. The term is used chiefly for such a hardening of the nervous system due to hyperplasia of the connective tissue or to designate hardening of the blood vessels. [EU] Secretion: 1. the process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. any substance produced by secretion. [EU] Sepsis: The presence of disease-causing organisms or their toxins in the blood. [NIH] Sinusitis: Inflammation of a sinus. The condition may be purulent or nonpurulent, acute or chronic. Depending on the site of involvement it is known as ethmoid, frontal, maxillary, or sphenoid sinusitis. [EU] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH] Sympathomimetic: 1. mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. an agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Toxic: Pertaining to, due to, or of the nature of a poison or toxin; manifesting the symptoms of severe infection. [EU] Toxicity: The quality of being poisonous, especially the degree of virulence


of a toxic microbe or of a poison. [EU] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transplantation: The grafting of tissues taken from the patient's own body or from another. [EU] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Ventilation: The process of exchange of air between the lungs and the atmosphere leading to exchange of gases in the blood. [NIH]

Seeking Guidance 33

CHAPTER 2. SEEKING GUIDANCE Overview Some patients are comforted by the knowledge that a number of organizations dedicate their resources to helping people with respiratory failure. These associations can become invaluable sources of information and advice. Many associations offer aftercare support, financial assistance, and other important services. Furthermore, healthcare research has shown that support groups often help people to better cope with their conditions.9 In addition to support groups, your physician can be a valuable source of guidance and support. Therefore, finding a physician that can work with your unique situation is a very important aspect of your care. In this chapter, we direct you to resources that can help you find patient organizations and medical specialists. We begin by describing how to find associations and peer groups that can help you better understand and cope with respiratory failure. The chapter ends with a discussion on how to find a doctor that is right for you.

Associations and Respiratory Failure As mentioned by the Agency for Healthcare Research and Quality, sometimes the emotional side of a condition or disorder can be as taxing as the physical side.10 You may have fears or feel overwhelmed by your situation. Everyone has different ways of dealing with disease or physical injury. Your attitude, your expectations, and how well you cope with your Churches, synagogues, and other houses of worship might also have groups that can offer you the social support you need. 10 This section has been adapted from http://www.ahcpr.gov/consumer/diaginf5.htm. 9


condition can all influence your well-being. This is true for both minor conditions and serious illnesses. For example, a study on female breast cancer survivors revealed that women who participated in support groups lived longer and experienced better quality of life when compared with women who did not participate. In the support group, women learned coping skills and had the opportunity to share their feelings with other women in the same situation.

Finding Associations There are a number of directories that list additional medical associations that you may find useful. While not all of these directories will provide different information than what is listed above, by consulting all of them, you will have nearly exhausted all sources for patient associations.

The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about respiratory failure. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. DIRLINE A comprehensive source of information on associations is the DIRLINE database maintained by the National Library of Medicine. The database comprises some 10,000 records of organizations, research centers, and government institutes and associations which primarily focus on health and biomedicine. DIRLINE is available via the Internet at the following Web site: http://dirline.nlm.nih.gov/. Simply type in “respiratory failure” (or a synonym) or the name of a topic, and the site will list information contained in the database on all relevant organizations.

The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and

Seeking Guidance 35

“respiratory failure”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” By making these selections and typing in “respiratory failure” (or synonyms) into the “For these words:” box, you will only receive results on organizations dealing with respiratory failure. You should check back periodically with this database since it is updated every 3 months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by specific conditions and diseases. You can access this database at the following Web site: http://www.rarediseases.org/cgi-bin/nord/searchpage. Select the option called “Organizational Database (ODB)” and type “respiratory failure” (or a synonym) in the search box.

Online Support Groups In addition to support groups, commercial Internet service providers offer forums and chat rooms for people with different illnesses and conditions. WebMDÒ, for example, offers such a service at their Web site: http://boards.webmd.com/roundtable. These online self-help communities can help you connect with a network of people whose concerns are similar to yours. Online support groups are places where people can talk informally. If you read about a novel approach, consult with your doctor or other healthcare providers, as the treatments or discoveries you hear about may not be scientifically proven to be safe and effective. The following Internet sites may be of particular interest: ·

Med Help www.medhelp.org/HealthTopics/Lung.html

·

Omaha Support Groups www.omahasupportgroups.com/Articles/MDMA.html

·

Women’s Health www.members.shaw.ca/samasutra/womenshealth.html


Finding Doctors One of the most important aspects of your treatment will be the relationship between you and your doctor or specialist. All patients with respiratory failure must go through the process of selecting a physician. While this process will vary from person to person, the Agency for Healthcare Research and Quality makes a number of suggestions, including the following:11 ·

If you are in a managed care plan, check the plan’s list of doctors first.

·

Ask doctors or other health professionals who work with doctors, such as hospital nurses, for referrals.

·

Call a hospital’s doctor referral service, but keep in mind that these services usually refer you to doctors on staff at that particular hospital. The services do not have information on the quality of care that these doctors provide.

·

Some local medical societies offer lists of member doctors. Again, these lists do not have information on the quality of care that these doctors provide.

Additional steps you can take to locate doctors include the following: ·

Check with the associations listed earlier in this chapter.

·

Information on doctors in some states is available on the Internet at http://www.docboard.org. This Web site is run by “Administrators in Medicine,” a group of state medical board directors.

·

The American Board of Medical Specialties can tell you if your doctor is board certified. “Certified” means that the doctor has completed a training program in a specialty and has passed an exam, or “board,” to assess his or her knowledge, skills, and experience to provide quality patient care in that specialty. Primary care doctors may also be certified as specialists. The AMBS Web site is located at http://www.abms.org/newsearch.asp.12 You can also contact the ABMS by phone at 1-866-ASK-ABMS.

·

You can call the American Medical Association (AMA) at 800-665-2882 for information on training, specialties, and board certification for many licensed doctors in the United States. This information also can be found in “Physician Select” at the AMA’s Web site: http://www.amaassn.org/aps/amahg.htm.

This section is adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm. While board certification is a good measure of a doctor’s knowledge, it is possible to receive quality care from doctors who are not board certified.

11 12

Seeking Guidance 37

If the previous sources did not meet your needs, you may want to log on to the Web site of the National Organization for Rare Disorders (NORD) at http://www.rarediseases.org/. NORD maintains a database of doctors with expertise in various rare conditions and diseases. The Metabolic Information Network (MIN), 800-945-2188, also maintains a database of physicians with expertise in various metabolic diseases.

Selecting Your Doctor13 When you have compiled a list of prospective doctors, call each of their offices. First, ask if the doctor accepts your health insurance plan and if he or she is taking new patients. If the doctor is not covered by your plan, ask yourself if you are prepared to pay the extra costs. The next step is to schedule a visit with your chosen physician. During the first visit you will have the opportunity to evaluate your doctor and to find out if you feel comfortable with him or her. Ask yourself, did the doctor: ·

Give me a chance to ask questions about respiratory failure?

·

Really listen to my questions?

·

Answer in terms I understood?

·

Show respect for me?

·

Ask me questions?

·

Make me feel comfortable?

·

Address the health problem(s) I came with?

·

Ask me my preferences about different kinds of treatments for respiratory failure?

·

Spend enough time with me?

Trust your instincts when deciding if the doctor is right for you. But remember, it might take time for the relationship to develop. It takes more than one visit for you and your doctor to get to know each other.

13 This

section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.


Working with Your Doctor14 Research has shown that patients who have good relationships with their doctors tend to be more satisfied with their care and have better results. Here are some tips to help you and your doctor become partners: ·

You know important things about your symptoms and your health history. Tell your doctor what you think he or she needs to know.

·

It is important to tell your doctor personal information, even if it makes you feel embarrassed or uncomfortable.

·

Bring a “health history” list with you (and keep it up to date).

·

Always bring any medications you are currently taking with you to the appointment, or you can bring a list of your medications including dosage and frequency information. Talk about any allergies or reactions you have had to your medications.

·

Tell your doctor about any natural or alternative medicines you are taking.

·

Bring other medical information, such as x-ray films, test results, and medical records.

·

Ask questions. If you don’t, your doctor will assume that you understood everything that was said.

·

Write down your questions before your visit. List the most important ones first to make sure that they are addressed.

·

Consider bringing a friend with you to the appointment to help you ask questions. This person can also help you understand and/or remember the answers.

·

Ask your doctor to draw pictures if you think that this would help you understand.

·

Take notes. Some doctors do not mind if you bring a tape recorder to help you remember things, but always ask first.

·

Let your doctor know if you need more time. If there is not time that day, perhaps you can speak to a nurse or physician assistant on staff or schedule a telephone appointment.

·

Take information home. Ask for written instructions. Your doctor may also have brochures and audio and videotapes that can help you.

This section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.

14

Seeking Guidance 39

·

After leaving the doctor’s office, take responsibility for your care. If you have questions, call. If your symptoms get worse or if you have problems with your medication, call. If you had tests and do not hear from your doctor, call for your test results. If your doctor recommended that you have certain tests, schedule an appointment to get them done. If your doctor said you should see an additional specialist, make an appointment.

By following these steps, you will enhance the relationship you will have with your physician.

Broader Health-Related Resources In addition to the references above, the NIH has set up guidance Web sites that can help patients find healthcare professionals. These include:15 ·

Caregivers: http://www.nlm.nih.gov/medlineplus/caregivers.html

·

Choosing a Doctor or Healthcare Service: http://www.nlm.nih.gov/medlineplus/choosingadoctororhealthcareserv ice.html

·

Hospitals and Health Facilities: http://www.nlm.nih.gov/medlineplus/healthfacilities.html

Vocabulary Builder The following vocabulary builder provides definitions of words used in this chapter that have not been defined in previous chapters: Cardiomegaly: Cardiac hypertrophy. [EU] Enzyme: Substance, made by living cells, that causes specific chemical changes. [NIH] Hepatomegaly: Enlargement of the liver. [EU] Hypotonia: A condition of diminished tone of the skeletal muscles; diminished resistance of muscles to passive stretching. [EU] Infantile: Pertaining to an infant or to infancy. [EU] You can access this information at: http://www.nlm.nih.gov/medlineplus/healthsystem.html.

15


Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH]

Clinical Trials 41

CHAPTER 3. CLINICAL TRIALS AND RESPIRATORY FAILURE Overview Very few medical conditions have a single treatment. The basic treatment guidelines that your physician has discussed with you, or those that you have found using the techniques discussed in Chapter 1, may provide you with all that you will require. For some patients, current treatments can be enhanced with new or innovative techniques currently under investigation. In this chapter, we will describe how clinical trials work and show you how to keep informed of trials concerning respiratory failure.

What Is a Clinical Trial?16 Clinical trials involve the participation of people in medical research. Most medical research begins with studies in test tubes and on animals. Treatments that show promise in these early studies may then be tried with people. The only sure way to find out whether a new treatment is safe, effective, and better than other treatments for respiratory failure is to try it on patients in a clinical trial.

The discussion in this chapter has been adapted from the NIH and the NEI: www.nei.nih.gov/netrials/ctivr.htm.

16


What Kinds of Clinical Trials Are There? Clinical trials are carried out in three phases: ·

Phase I. Researchers first conduct Phase I trials with small numbers of patients and healthy volunteers. If the new treatment is a medication, researchers also try to determine how much of it can be given safely.

·

Phase II. Researchers conduct Phase II trials in small numbers of patients to find out the effect of a new treatment on respiratory failure.

·

Phase III. Finally, researchers conduct Phase III trials to find out how new treatments for respiratory failure compare with standard treatments already being used. Phase III trials also help to determine if new treatments have any side effects. These trials--which may involve hundreds, perhaps thousands, of people--can also compare new treatments with no treatment. How Is a Clinical Trial Conducted?

Various organizations support clinical trials at medical centers, hospitals, universities, and doctors’ offices across the United States. The “principal investigator” is the researcher in charge of the study at each facility participating in the clinical trial. Most clinical trial researchers are medical doctors, academic researchers, and specialists. The “clinic coordinator” knows all about how the study works and makes all the arrangements for your visits. All doctors and researchers who take part in the study on respiratory failure carefully follow a detailed treatment plan called a protocol. This plan fully explains how the doctors will treat you in the study. The “protocol” ensures that all patients are treated in the same way, no matter where they receive care. Clinical trials are controlled. This means that researchers compare the effects of the new treatment with those of the standard treatment. In some cases, when no standard treatment exists, the new treatment is compared with no treatment. Patients who receive the new treatment are in the treatment group. Patients who receive a standard treatment or no treatment are in the “control” group. In some clinical trials, patients in the treatment group get a new medication while those in the control group get a placebo. A placebo is a harmless substance, a “dummy” pill, that has no effect on respiratory failure. In other clinical trials, where a new surgery or device (not a medicine) is being tested, patients in the control group may receive a “sham

Clinical Trials 43

treatment.” This treatment, like a placebo, has no effect on respiratory failure and does not harm patients. Researchers assign patients “randomly” to the treatment or control group. This is like flipping a coin to decide which patients are in each group. If you choose to participate in a clinical trial, you will not know which group you will be appointed to. The chance of any patient getting the new treatment is about 50 percent. You cannot request to receive the new treatment instead of the placebo or sham treatment. Often, you will not know until the study is over whether you have been in the treatment group or the control group. This is called a “masked” study. In some trials, neither doctors nor patients know who is getting which treatment. This is called a “double masked” study. These types of trials help to ensure that the perceptions of the patients or doctors will not affect the study results. Natural History Studies Unlike clinical trials in which patient volunteers may receive new treatments, natural history studies provide important information to researchers on how respiratory failure develops over time. A natural history study follows patient volunteers to see how factors such as age, sex, race, or family history might make some people more or less at risk for respiratory failure. A natural history study may also tell researchers if diet, lifestyle, or occupation affects how a disease or disorder develops and progresses. Results from these studies provide information that helps answer questions such as: How fast will a condition or disorder usually progress? How bad will the condition become? Will treatment be needed? What Is Expected of Patients in a Clinical Trial? Not everyone can take part in a clinical trial for a specific condition or disorder. Each study enrolls patients with certain features or eligibility criteria. These criteria may include the type and stage of a condition or disorder, as well as, the age and previous treatment history of the patient. You or your doctor can contact the sponsoring organization to find out more about specific clinical trials and their eligibility criteria. If you are interested in joining a clinical trial, your doctor must contact one of the trial’s investigators and provide details about your diagnosis and medical history. If you participate in a clinical trial, you may be required to have a number of medical tests. You may also need to take medications and/or undergo


surgery. Depending upon the treatment and the examination procedure, you may be required to receive inpatient hospital care. Or, you may have to return to the medical facility for follow-up examinations. These exams help find out how well the treatment is working. Follow-up studies can take months or years. However, the success of the clinical trial often depends on learning what happens to patients over a long period of time. Only patients who continue to return for follow-up examinations can provide this important long-term information.

Recent Trials on Respiratory Failure The National Institutes of Health and other organizations sponsor trials on various conditions and disorders. Because funding for research goes to the medical areas that show promising research opportunities, it is not possible for the NIH or others to sponsor clinical trials for every disease and disorder at all times. The following lists recent trials dedicated to respiratory failure.17 If the trial listed by the NIH is still recruiting, you may be eligible. If it is no longer recruiting or has been completed, then you can contact the sponsors to learn more about the study and, if published, the results. Further information on the trial is available at the Web site indicated. Please note that some trials may no longer be recruiting patients or are otherwise closed. Before contacting sponsors of a clinical trial, consult with your physician who can help you determine if you might benefit from participation. ·

Early Inhaled Nitric Oxide for Respiratory Failure in Newborns Condition(s): Hypertension, Pulmonary; Respiratory Insufficiency; Infant, Newborn, Diseases; Meconium Aspiration; Persistent Fetal Circulation Syndrome; Pneumonia, Aspiration; Respiratory Distress Syndrome Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Child Health and Human Development (NICHD); Canadian Institutes of Health Research; INO Therapeutics Purpose - Excerpt: Inhaled nitric oxide reduces the risk of temporary lung bypass in term and near-term infants with severe respiratory failure. Term and near-term infants with mild to moderate respiratory failure on a ventilator are randomized to inhaled nitric oxide to 100 percent oxygen to determine if administration of inhaled nitric oxide earlier in their course or to infants with less severe respiratory failure decreases the incidence of death or ECMO. The neurodevelopment of infants will be evaluated at 18 to 24 months of age.

17

These are listed at www.ClinicalTrials.gov.

Clinical Trials 45

Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00005773 ·

Incorporating Flow Limitation into the Diagnosis and Quantification of Sleep Disordered Breathing Condition(s): Sleep-Disordered Breathing Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR) Purpose - Excerpt: The diagnosis and treatment of sleep disordered breathing have come to the forefront of clinical medicine following recognition of the high prevalence and associated morbidity of sleep apnea. The effects on quality of life as well as societal costs have been well documented. The NYU Sleep Research Laboratory has spent the last several years working on the problem of improving the diagnosis of mild sleep disordered breathing which manifests as the upper airway resistance syndrome. Our approach has been to develop a non-invasive technique to detect increased upper airway resistance directly from analysis of the airflow signal. A characteristic intermittent change of the inspiratory flow contour, which is indicative of the occurrence of flow limitation, correlates well with increased airway resistance. Currently all respiratory events are identified manually and totaled. This is time consuming and subject to variability. The objective of the present project is to improve upon the manual approach by implementing an artificially intelligent system for the identification and quantification of sleep disordered breathing based solely on non-invasive cardiopulmonary signals collected during a routine sleep study. The utility of other reported indices of sleep disorded breathing obtained during a sleep study will be evaluated. Successful development of an automated system that can identify and classify upper airway resistance events will simplify, standardize and improve the diagnosis of sleep disordered breathing, and greatly facilitate research and clinical work in this area. Using a physiological based determination of disease should allow better assessment of treatment responses in mild disease. Study Type: Interventional Contact(s): Dr. Indu Ayappa, c/o Tina Flores 1-212-263-8423; New York; NYU Sleep Disorders Center, New York, New York, 10016, United States; Recruiting Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00004569


·

Epidemiology of Sleep Disordered Breathing in Children Condition(s): Lung Diseases; Sleep apnea syndromes Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To collect fundamental data regarding the distribution of measures of sleep disordered breathing (SDB) in a pediatric population, prevalence of clinically significant SDB in children, risk factors, and associated co-morbidity. Study Type: Epidemiology Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00005516

·

Epidemiology of Sleep-Disordered Breathing in Adults Condition(s): Lung Diseases; Sleep apnea syndromes Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To characterize the natural history and biologic spectrum of sleep disordered breathing (SDB) and test hypotheses regarding SDB causes and consequences. Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00005557

·

Extracorporeal Support for Respiratory Insufficiency (ECMO) Condition(s): Acute Respiratory Failure; Lung Diseases Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To evaluate indications for the use and efficacy of extracorporeal membrane oxygenators (ECMO's) for the support of patients with potentially reversible acute respiratory failure. Phase(s): Phase III Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00000562

Clinical Trials 47

·

Incidence and Severity of Cardiorespiratory Events in Infants at Increased Epidemiological Risk for Sudden Infant Death Syndrome (SIDS) Condition(s): Sudden Infant Death Syndrome; Apnea Study Status: This study is completed. Sponsor(s): National Institute of Child Health and Human Development (NICHD); Yale University Purpose - Excerpt: Objectives: I. Assess and compare the incidence and severity of cardiorespiratory events documented by home monitoring in infants at increased epidemiological risk for sudden infant death syndrome (SIDS). II. Determine the antecedent medical, demographic, physiologic, and behavioral characteristics that predict the incidence of cardiorespiratory events documented by home monitoring. Study Type: Observational Contact(s):. Study chairs or principal investigators: George Lister, Study Chair; Yale University Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00004392

·

Inhaled Nitric Oxide Study for Respiratory Failure in Newborns. Condition(s): Hypertension, Pulmonary; Respiratory Insufficiency; Infant, Newborn, Diseases; Meconium Aspiration; Persistent Fetal Circulation Syndrome; Pneumonia, Aspiration; Respiratory Distress Syndrome Study Status: This study is terminated. Sponsor(s): National Institute of Child Health and Human Development (NICHD); Medical Research Council of Canada Purpose - Excerpt: Respiratory failure in term newborns is associated with increased rates of death and long-term neurodevelopmental problems. This large international multicenter trial randomized newborns who had failed to respond to intensive care, including high levels of ventilator support, to receive either inhaled nitric oxide (iNO) or 100 percent oxygen to test whether iNO would decrease their risk of dying or requiring temporary lung bypass. Infants were followed during their initial hospitalization; their outcome was assessed at 18 to 24 mos of age. Phase(s): Phase III Study Type: Interventional Contact(s): Linda L. Wright 1-301-402-0830 [email protected]. Study chairs or principal investigators: Richard A. Ehrenkranz, MD, Principal


Investigator; Yale University; Neil N. Finer, MD, Principal Investigator; University of California, San Diego Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00005776 ·

The Safety and Effectiveness of Methylprednisolone in the Treatment of Pneumocystis carinii Pneumonia (PCP) in Children with AIDS Condition(s): Pneumonia, Pneumocystis carinii; HIV Infections Study Status: This study is terminated. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID); Upjohn Purpose - Excerpt: To determine the effect of methylprednisolone on respiratory failure in HIV-infected patients with presumed or confirmed pneumocystis carinii pneumonia who are stratified for presence or absence of respiratory failure at the time of randomization to the study. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00000741

Benefits and Risks18 What Are the Benefits of Participating in a Clinical Trial? If you are interested in a clinical trial, it is important to realize that your participation can bring many benefits to you and society at large: ·

A new treatment could be more effective than the current treatment for respiratory failure. Although only half of the participants in a clinical trial receive the experimental treatment, if the new treatment is proved to be more effective and safer than the current treatment, then those patients who did not receive the new treatment during the clinical trial may be among the first to benefit from it when the study is over.

·

If the treatment is effective, then it may improve health or prevent diseases or disorders.

This section has been adapted from ClinicalTrials.gov, a service of the National Institutes of Health: http://www.clinicaltrials.gov/ct/gui/c/a1r/info/whatis?JServSessionIdzone_ct=9jmun6f2 91. 18

Clinical Trials 49

·

Clinical trial patients receive the highest quality of medical care. Experts watch them closely during the study and may continue to follow them after the study is over.

·

People who take part in trials contribute to scientific discoveries that may help other people with respiratory failure. In cases where certain conditions or disorders run in families, your participation may lead to better care or prevention for your family members. The Informed Consent

Once you agree to take part in a clinical trial, you will be asked to sign an “informed consent.” This document explains a clinical trial’s risks and benefits, the researcher’s expectations of you, and your rights as a patient. What Are the Risks? Clinical trials may involve risks as well as benefits. Whether or not a new treatment will work cannot be known ahead of time. There is always a chance that a new treatment may not work better than a standard treatment. There is also the possibility that it may be harmful. The treatment you receive may cause side effects that are serious enough to require medical attention. How Is Patient Safety Protected? Clinical trials can raise fears of the unknown. Understanding the safeguards that protect patients can ease some of these fears. Before a clinical trial begins, researchers must get approval from their hospital’s Institutional Review Board (IRB), an advisory group that makes sure a clinical trial is designed to protect patient safety. During a clinical trial, doctors will closely watch you to see if the treatment is working and if you are experiencing any side effects. All the results are carefully recorded and reviewed. In many cases, experts from the Data and Safety Monitoring Committee carefully monitor each clinical trial and can recommend that a study be stopped at any time. You will only be asked to take part in a clinical trial as a volunteer giving informed consent.


What Are a Patient’s Rights in a Clinical Trial? If you are eligible for a clinical trial, you will be given information to help you decide whether or not you want to participate. As a patient, you have the right to: ·

Information on all known risks and benefits of the treatments in the study.

·

Know how the researchers plan to carry out the study, for how long, and where.

·

Know what is expected of you.

·

Know any costs involved for you or your insurance provider.

·

Know before any of your medical or personal information is shared with other researchers involved in the clinical trial.

·

Talk openly with doctors and ask any questions.

After you join a clinical trial, you have the right to: ·

Leave the study at any time. Participation is strictly voluntary. However, you should not enroll if you do not plan to complete the study.

·

Receive any new information about the new treatment.

·

Continue to ask questions and get answers.

·

Maintain your privacy. Your name will not appear in any reports based on the study.

·

Know whether you participated in the treatment group or the control group (once the study has been completed).

What about Costs? In some clinical trials, the research facility pays for treatment costs and other associated expenses. You or your insurance provider may have to pay for costs that are considered standard care. These things may include inpatient hospital care, laboratory and other tests, and medical procedures. You also may need to pay for travel between your home and the clinic. You should find out about costs before committing to participation in the trial. If you have health insurance, find out exactly what it will cover. If you don’t have health insurance, or if your insurance company will not cover your costs, talk to the clinic staff about other options for covering the cost of your care.

Clinical Trials 51

What Should You Ask before Deciding to Join a Clinical Trial? Questions you should ask when thinking about joining a clinical trial include the following: ·

What is the purpose of the clinical trial?

·

What are the standard treatments for respiratory failure? Why do researchers think the new treatment may be better? What is likely to happen to me with or without the new treatment?

·

What tests and treatments will I need? Will I need surgery? Medication? Hospitalization?

·

How long will the treatment last? How often will I have to come back for follow-up exams?

·

What are the treatment’s possible benefits to my condition? What are the short- and long-term risks? What are the possible side effects?

·

Will the treatment be uncomfortable? Will it make me feel sick? If so, for how long?

·

How will my health be monitored?

·

Where will I need to go for the clinical trial? How will I get there?

·

How much will it cost to be in the study? What costs are covered by the study? How much will my health insurance cover?

·

Will I be able to see my own doctor? Who will be in charge of my care?

·

Will taking part in the study affect my daily life? Do I have time to participate?

·

How do I feel about taking part in a clinical trial? Are there family members or friends who may benefit from my contributions to new medical knowledge?

Keeping Current on Clinical Trials Various government agencies maintain databases on trials. The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide patients, family members, and physicians with current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with


most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to their Web site (www.clinicaltrials.gov) and search by “respiratory failure” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: ·

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

·

For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

·

For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

General References The following references describe clinical trials and experimental medical research. They have been selected to ensure that they are likely to be available from your local or online bookseller or university medical library. These references are usually written for healthcare professionals, so you may consider consulting with a librarian or bookseller who might recommend a particular reference. The following includes some of the most readily available references (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): ·

A Guide to Patient Recruitment : Today’s Best Practices & Proven Strategies by Diana L. Anderson; Paperback - 350 pages (2001), CenterWatch, Inc.; ISBN: 1930624115; http://www.amazon.com/exec/obidos/ASIN/1930624115/icongroupinterna

·

A Step-By-Step Guide to Clinical Trials by Marilyn Mulay, R.N., M.S., OCN; Spiral-bound - 143 pages Spiral edition (2001), Jones & Bartlett Pub; ISBN: 0763715697; http://www.amazon.com/exec/obidos/ASIN/0763715697/icongroupinterna

·

The CenterWatch Directory of Drugs in Clinical Trials by CenterWatch; Paperback - 656 pages (2000), CenterWatch, Inc.; ISBN: 0967302935; http://www.amazon.com/exec/obidos/ASIN/0967302935/icongroupinterna

Clinical Trials 53

·

The Complete Guide to Informed Consent in Clinical Trials by Terry Hartnett (Editor); Paperback - 164 pages (2000), PharmSource Information Services, Inc.; ISBN: 0970153309; http://www.amazon.com/exec/obidos/ASIN/0970153309/icongroupinterna

·

Dictionary for Clinical Trials by Simon Day; Paperback - 228 pages (1999), John Wiley & Sons; ISBN: 0471985961; http://www.amazon.com/exec/obidos/ASIN/0471985961/icongroupinterna

·

Extending Medicare Reimbursement in Clinical Trials by Institute of Medicine Staff (Editor), et al; Paperback 1st edition (2000), National Academy Press; ISBN: 0309068886; http://www.amazon.com/exec/obidos/ASIN/0309068886/icongroupinterna

·

Handbook of Clinical Trials by Marcus Flather (Editor); Paperback (2001), Remedica Pub Ltd; ISBN: 1901346293; http://www.amazon.com/exec/obidos/ASIN/1901346293/icongroupinterna

Vocabulary Builder The following vocabulary builder gives definitions of words used in this chapter that have not been defined in previous chapters: Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH]

Adverse: Harmful. [EU] Anaphylaxis: An acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death. [NIH] Antecedent: Existing or occurring before in time or order often with consequential effects. [EU] Beclomethasone: An anti-inflammatory, synthetic glucocorticoid. It is used topically as an anti-inflammatory agent and in aerosol form for the treatment of asthma. [NIH] Cardiopulmonary: Pertaining to the heart and lungs. [EU] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU]

Coronary: Encircling in the manner of a crown; a term applied to vessels;


nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Glucose: D-glucose, a monosaccharide (hexose), C6H12O6, also known as dextrose (q.v.), found in certain foodstuffs, especially fruits, and in the normal blood of all animals. It is the end product of carbohydrate metabolism and is the chief source of energy for living organisms, its utilization being controlled by insulin. Excess glucose is converted to glycogen and stored in the liver and muscles for use as needed and, beyond that, is converted to fat and stored as adipose tissue. Glucose appears in the urine in diabetes mellitus. [EU] Hepatic: Pertaining to the liver. [EU] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hypertension: High blood pressure (i.e., abnormally high blood pressure tension involving systolic and/or diastolic levels). The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure defines hypertension as a systolic blood pressure of 140 mm Hg or greater, a diastolic blood pressure of 90 mm Hg or greater, or taking hypertensive medication. The cause may be adrenal, benign, essential, Goldblatt's, idiopathic, malignant PATE, portal, postpartum, primary, pulmonary, renal or renovascular. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Infarction: 1. the formation of an infarct. 2. an infarct. [EU] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulindependent diabetes mellitus. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Invasive: 1. having the quality of invasiveness. 2. involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU]

Clinical Trials 55

Meconium: The thick green-to-black mucilaginous material found in the intestines of a full-term fetus. It consists of secretions of the intestinal glands, bile pigments, fatty acids, amniotic fluid, and intrauterine debris. It constitutes the first stools passed by a newborn. [NIH] Neurologic: Pertaining to neurology or to the nervous system. [EU] Orlistat: A lipase inhibitor used for weight loss. Lipase is an enzyme found in the bowel that assists in lipid absorption by the body. Orlistat blocks this enzyme, reducing the amount of fat the body absorbs by about 30 percent. It is known colloquially as a "fat blocker." Because more oily fat is left in the bowel to be excreted, Orlistat can cause an oily anal leakage and fecal incontinence. Orlistat may not be suitable for people with bowel conditions such as irritable bowel syndrome or Crohn's disease. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Snoring: Rough, noisy breathing during sleep, due to vibration of the uvula and soft palate. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Standardize: To compare with or conform to a standard; to establish standards. [EU] Steatosis: Fatty degeneration. [EU] Tolerance: 1. the ability to endure unusually large doses of a drug or toxin. 2. acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU]

57

PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL

ABOUT PART II In Part II, we introduce you to additional resources and advanced research on respiratory failure. All too often, patients who conduct their own research are overwhelmed by the difficulty in finding and organizing information. The purpose of the following chapters is to provide you an organized and structured format to help you find additional information resources on respiratory failure. In Part II, as in Part I, our objective is not to interpret the latest advances on respiratory failure or render an opinion. Rather, our goal is to give you access to original research and to increase your awareness of sources you may not have already considered. In this way, you will come across the advanced materials often referred to in pamphlets, books, or other general works. Once again, some of this material is technical in nature, so consultation with a professional familiar with respiratory failure is suggested.

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CHAPTER 4. STUDIES ON RESPIRATORY FAILURE Overview Every year, academic studies are published on respiratory failure or related conditions. Broadly speaking, there are two types of studies. The first are peer reviewed. Generally, the content of these studies has been reviewed by scientists or physicians. Peer-reviewed studies are typically published in scientific journals and are usually available at medical libraries. The second type of studies is non-peer reviewed. These works include summary articles that do not use or report scientific results. These often appear in the popular press, newsletters, or similar periodicals. In this chapter, we will show you how to locate peer-reviewed references and studies on respiratory failure. We will begin by discussing research that has been summarized and is free to view by the public via the Internet. We then show you how to generate a bibliography on respiratory failure and teach you how to keep current on new studies as they are published or undertaken by the scientific community.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and respiratory failure, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the


format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type in “respiratory failure” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box.

Federally-Funded Research on Respiratory Failure The U.S. Government supports a variety of research studies relating to respiratory failure and associated conditions. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.19 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally-funded biomedical research projects conducted at universities, hospitals, and other institutions. Visit the CRISP Web site at http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket. You can perform targeted searches by various criteria including geography, date, as well as topics related to respiratory failure and related conditions. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally-funded studies use animals or simulated models to explore respiratory failure and related conditions. In some cases, therefore, it may be difficult to understand how some basic or fundamental research could eventually translate into medical practice. The following sample is typical of the type of information found when searching the CRISP database for respiratory failure: ·

Project Title: Computerized Management of Childhood Respiratory Failure Principal Investigator & Institution: Maloney, Christopher G.; Medical Informatics; University of Utah 110 Park Bldg Salt Lake City, Ut 84112 Timing: Fiscal Year 2001; Project Start 6-SEP-2001

19 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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Summary: This proposal outlines a strategy for weaning children from mechanical ventilation, using a computerized protocol. This proposal has two major goals: 1) Integration of a computerized decision support tool that accesses existing database servers at Primary Children's Medical Center. 2) Evaluation of the feasibility and utility of a computerized protocol to assist with weaning children with acute respiratory failure from mechanical ventilation. In the first specific aim, a consensus panel of pediatric critical care practitioners will develop a weaning algorithm that is simple and reasonable. The protocols and incorporated logic will be examined, at the bedside, using paper-flow diagrams for applicability in weaning children from mechanical ventilation. These protocols will then be programmed using network technology to access existing database servers. Practitioners involved in weaning children, with acute respiratory failure, from mechanical ventilation will then evaluate the validity of the protocols. In the second specific aim, children will be entered into a prospective, randomized, controlled clinical trial to evaluate the utility of a computerized protocol to wean critically ill children from mechanical ventilation. Children with acute respiratory failure requiring mechanical ventilation will be entered into either a computerized protocol driven weaning strategy arm or the "standard" physician driven weaning arm. These studies will yield information regarding the feasibility of using computerized protocols in pediatric critical care and potentially allow for the development of advanced protocols to assist physicians in managing critically ill children in a more efficient manner. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Enhanced Long-Term Care of Severe Respiratory Failure Principal Investigator & Institution: Nemser, Stuart M.; ; Compact Membrane Systems, Inc. 325 Water St Wilmington, De 19804 Timing: Fiscal Year 2000; Project Start 1-MAR-2000; Project End 1-AUG2001 Summary: (Adapted from the Investigator's Abstract) The current management of life-threatening hypoxemia/hypercarbia in severe acute respiratory failure (ARF) is suboptimal. Arteriovenous carbon dioxide removal (AVCO2R) in combination with mild ventilation for introduction of oxygen has shown promise. AVCO2R is a mild pumpless technique using existing low pressure drop membrane oxygenators which is less labor intensive, less costly, less complex, and less stressful to the patient. While AVCO2R has shown promise for short duration, ARF therapy requires systems that can operate continuously for weeks. The long-term objective of this program is to develop a long-term AVCO2R system. In


Phase I of this program existing AVCO2R membrane oxygenators will be modified to enhance long-term capability from a few hours to in excess of two weeks. Phase I activity will include demonstration that these techniques will maintain initial performance while improving long-term performance and enhancing biocompatibility. Phase II will optimize performance, perform detailed biocompatibility tests, and carry out animal studies. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Respiratory Failure in a Model of P. Carinii Pneumonia Principal Investigator & Institution: Paine, Robert; Internal Medicine; University of Michigan at Ann Arbor Ann Arbor, Mi 48109 Timing: Fiscal Year 2000; Project Start 1-JUL-2000; Project End 0-JUN2005 Summary: (from applicant's abstract): It is hypothesized that infection with P. carinii renders the alveolar epithelium more susceptible to secondary insults, particularly hyperoxia, leading to respiratory failure in patients with PCP. To evaluate this hypothesis, the investigators will utilize a well-established CD4 depleted mouse model of P. carinii pneumonia, which is subsequently exposed to hyperoxia as a prototypical stress for alveolar wall injury. They propose that P. carinii infected mice will develop more severe lung injury following exposure to hyperoxia. They also postulate that GM-CSF, a potent cytokine generated by alveolar epithelial cells and macrophages, is critical in ameliorating this response. GM-CSF expression induced in response to P. carinii infection exerts a protective effect to limit lung injury. They postulate that inhibition of lung GM-CSF expression as a result of hyperoxia is a critical event promoting lung injury and respiratory failure. Four specific aims will be undertaken. Initially they will characterize the response of P. carinii infected mice to hyperoxia. Next, they will determine the expression of GM-CSF in this animal infection model and in mice that genetically lack GM-CSF following exposure to PCP and hyperoxic conditions. They will further determine whether direct interaction of P. carinii and alveolar epithelial cells through integrins induces GM-CSF expression. Finally, they will evaluate the protective effect of GM-CSF in P. carinii pneumonia and in subsequent progression of lung injury following hyperoxia. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

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·

Project Title: Surgical Studies of Severe Respiratory Failure Principal Investigator & Institution: Zwischenberger, Joseph B.; Professor; Surgery; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77550 Timing: Fiscal Year 2001; Project Start 1-MAY-2001; Project End 0-APR2005 Summary: (Verbatim from the applicant's abstract) Severe respiratory failure affects approximately 150,000 patients a year in the United States, and is still associated with a 40 degrees about mortality despite recent advances in critical care. Unfortunately, mechanical ventilation targeted to restore normal blood gases causes high peak airway pressure with iatrogenic barotrauma or volutrauma to relatively compliant normal lung tissue, exacerbating lung injury. Therefore, "kind, gentle ventilation" in which peak inspiratory pressures (PIP) and fraction of inspired oxygen are minimized, accepts the obligate increase in arterial pCO2 levels, termed "permissive hypercapnia." Adverse effects of permissive hypercapnia and the associated respiratory acidosis include increased cardiac output, organ blood flow and intracranial pressure. Arteriovenous carbon dioxide removal (AVCO2R) utilizing a lowresistance gas exchanger in a simple percutaneous arteriovenous shunt achieves near-total extracorporeal removal of CO2 production with only 800-1200 mL/min flow. From our animal and initial patient safety trials, AVCO2R allows decreased respiratory rate, tidal volume, and peak airway pressures such that PIP is predictably less than 30 cm H20 and respiratory rate 4 about breaths/minute with no significant decrease in WBC, platelets, plasma Hgb, or increased complement levels. AVCO2R, therefore, is capable of providing near-total extracorporeal removal of carbon dioxide production during acute respiratory failure, while rnaintaining CO2 and pH homeostasis. We will test the hypothesis that severe respiratory failure is best treated with AVCO2R for respiratory support to promote lung recovery. Specifically, we will conduct a prospective, randomized, controlled, unblinded, multicenter outcomes study to compare percutaneous arteriovenous extracorporeal carbon dioxide removal (AVCO2R) in acute hypercapnic respiratory failure to standardized "gentle" ventilation on all cause mortality and ventilator free days in patients with ARDS who require standardized pressure controlled mechanical ventilation (SMV) with perrnissive hypercapnia. The secondary objectives are: characterization of the safety of AVCO2R versus SMV and assessment of the effects of AVCO2R relative to SMV on oxygenation, pulmonary mechanics, ventilator settings, acute blood/surface mteractions (platelet count, complement C3a, Csa, TNFa, IL-1b, IL , IL-10), and long-term morbidity including safety (overall


mortality, adverse events, neuropsychologic testing), oxygenation (oxygenation index), PaO2, FiO2, CO2 removal (PaCO2), total duration of mechanical ventilation (time to unassisted ventilation), proportion of patients alive and off the ventilator, multiple organ dysfunction score, ALI/ARDS "time to resolution," chronic lung disease, and psychological assessment. The principle end-points of AVCO2R assessment include: changes in PaCO2 and pH, decreases in level of mechanical ventilatory support, and changes m PaCO2 and pH associated with "trials-off'. The knowledge gained will establish the gas exchange capabilities of lowpressure (gentle) mechanical ventilation with pH-controlled permissive hypercapoia compared to percutaneous AVCO2R to improve outcomes in patients with severe respiratory failure from ARDS. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Airway Perfusion Assisted Liquid Ventilator Principal Investigator & Institution: Parker, James C.; Professor of Physiology; Mallard Medical Co., Inc. 20268 Skypark Dr Redding, Ca 96002 Timing: Fiscal Year 2001; Project Start 1-APR-1999; Project End 1-JUL2003 Summary: (provided by applicant): We have developed and patented (U.S. Pat No. 5,706,830) a new type of closed circuit perfluorocarbon (PFC) liquid ventilator with enhanced capabilities for gas exchange and exudates clearance from the lungs. This system has potential application to rescue of patients in acute respiratory failure and treatment of cystic fibrosis. The system employs a continuous isovolumetric perfusion (bias flow) of oxygenated PFC through one lumen of a double lumen endotracheal catheter that is superimposed on tidal liquid ventilation (liv). Phase I studies in newborn piglets indicate that bias flow significantly improved blood gases and increased the clearance of a five percent albumin solution from the lung by over 3-fold. During Phase II we propose to finalize the prototype design and control system software for ventilatory parameters and a feedback control of lung liquid volume based on measurements of end-expiratory stop-flow pressures. High performance pulseless pumps, an oxygenator and vapor recovery system will be included as well as protective algorithms and relief valves to limit airway pressure excursions. Phase II experimental studies in piglets and rabbits will examine novel applications of TLV with bias flow for sustaining arterial blood gases during oleic acid lung injury, increasing the clearance rate of five percent albumin solution and mucus-like gels from the lung, and enhancing the homogeneity of gene expression for a reporter gene introduced during TLV. We will also apply for an

Studies 65

Investigational Device Exemption (IDE) from the Food and Drug Administration during Phase II to distribute ventilator prototypes to research institutions. PROPOSED COMMERCIAL APPLICATION: This liquid ventilator will be used in infant and adult intensive care units to treat end-stage respiratory failure as a lower cost alternative to extracorporeal oxygenation. Other applications include continuous intrapulmonary administration of drugs and anesthetics and clearance of material from the lungs. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: CORE--Clinical Core Principal Investigator & Institution: Rosenberg, Adam A.; ; University of Colorado Hlth Sciences Ctr 4200 E 9Th Ave Denver, Co 80262 Timing: Fiscal Year 2000 Summary: (Adapted from the applicant's abstract) The clinical core of this SCOR will direct the management of clinical studies of the pathogenesis and treatment of acute respiratory failure in the term and pre-term infant. The core will identify appropriate patients for study, be responsible for informed consent and management of the patient as pertains to the conduct of the study. The core will handle collection of and distribution to the basic science investigators of clinical samples. Central data collection and analysis facilities along with dedicated biostatistical consultation will be provided. Arrangements with collaborators to facilitate and augment the clinical studies will be the responsibility of the core. The most important goal of this core is to facilitate the smooth transition of results of bench research of the basic science investigators to studies and/or therapeutic trials in the nursery. The core will collaborate on these investigators on the design of clinical projects and will work with the Institutional Review board to assure proper protection for the infants participating in these studies. Acute respiratory failure with associated pulmonary hypertension is a major cause of morbidity and mortality in both term and pre-term infants. In the pre-term infant, the use of surfactant replacement therapy has decreased mortality from respiratory disease. However, some infants fail to respond or respond poorly to the administration of exogenous surfactant. Associated pulmonary hypertension contributes to the severity of illness in these infants. One focus of the clinical core will be to examine the hypothesis that severe respiratory failure in the pre-mature infant is in part related to vascular abnormalities and pulmonary hypertension. The pathogenesis of the condition will be studies using echocardiography and measurement of mediators of vascular regulation and oxidant injury. The study of pathogenesis will take place within the context of a placebo controlled


study of the safety and efficacy of the specific pulmonary vasodilator, inhaled nitric oxide. The core will also expand upon previous success upon previous success with new management strategies in the term infant with respiratory failure. Inhaled nitric oxide has been shown to be a useful therapy in many of these infants. However, some infants respond poorly or only partially to this therapy. The focus of the core in these infants will be to understand the pathogenesis of a poor response and the development of adjunctive therapy to augment the response to inhaled nitric oxide in this group of infants. Finally, the core will run a follow up program for all infants treated in therapeutic trials treating respiratory failure in pre-term and term infants to assess the safety of the new therapies in the context of neurodevelopmental and cardiopulmonary outcomes. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Clearance

Dopamine-Mediated Regulation of Lung Edema

Principal Investigator & Institution: Sznajder, Jacob I.; Professor; Medicine; Northwestern University 303 E Chicago Ave Chicago, Il 60611 Timing: Fiscal Year 2000; Project Start 1-SEP-1999; Project End 1-AUG2003 Summary: Acute hypoxemic respiratory failure (AHRF) is a life threatening condition associated with significant morbidity and mortality. Initially during AHRF, lung edema accumulates and impairs alveolar oxygen exchange unless mechanisms for edema clearance become effective. Recent studies have suggested that rapid edema clearance is associated with better outcomes in mechanically ventilated patients with AHRF. Lung edema clearance is driven predominantly by active Na+ transport out of the alveoli, mediated by apical Na+ channels and the basolaterally located Na,K-ATPases. Previous studies have demonstrated that increases in Na,K-ATPase activity in the alveolar epithelium are associated with increased lung edema clearance. Dopamine is frequently used in critically ill patients to increase diuresis; this effect is mediated by inhibition of renal Na,K-ATPase. However, we have demonstrated that dopamine increases edema clearance in the lungs. Thus, the focus of this application is to determine the mechanisms of dopamine-mediated regulation of lung edema clearance. We propose four specific aims to study the role of dopamine in the regulation of Na,K-ATPase in alveolar epithelial cells and its effects on active Na+ transport and lung edema clearance. In Specific aim number 1, we will determine whether dopamine regulates Na,K-ATPase function via dopaminergic receptors in alveolar epithelial cells. In Specific Aim

Studies 67

number 2, we will determine whether dopamine (short-term) regulates Na,K-ATPase function by recruiting Na+ pumps from preexisting intracellular pools into the basolateral membrane of alveolar epithelial cells. In Specific Aim number 3, we will determine whether dopamine (long term) regulates Na,K-ATPase function in alveolar epithelial cells via mitogen activated protein kinase (MAPK) pathways by increasing transcription of Na,K-ATPase genes. In Specific Aim number 4, we will determine whether dopamine increases active Na+ transport and lung edema clearance in normal and injured rat lungs by upregulating alveolar epithelial cell Na,K-ATPase. Studies have been conducted for each of the specific aims and the preliminary results support our hypotheses and the feasibility of the proposed studies. Completion of the proposed experiments will provide novel information on the role of dopamine in the regulation of Na,K-ATPase and active Na+ transport in the alveolar epithelium which will help with the design of new strategies to enhance lung edema clearance in patients with hypoxemic respiratory failure. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Early Inhaled Nitric Oxide Therapy in Term/Near Term Infants W/Respiratory Failure Principal Investigator & Institution: Crowley, Mark; ; University of New Mexico Albuquerque Albuquerque, Nm 87131 Timing: Fiscal Year 2000; Project Start 1-MAY-1976; Project End 0-NOV2002 Summary: The purpose of this study is to determine if administration of INO earlier in the course of respiratory failure or to infants with less severe respiratory failure, decreases the incidence of EMCO or death, as suggested by the sub-group analysis of the original NINOS trial. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

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Project Title: Inhaled NO for the Prevention of Chronic Lung Disease Principal Investigator & Institution: Kinsella, John P.; Pediatrics; University of Colorado Hlth Sciences Ctr 4200 E 9Th Ave Denver, Co 80262 Timing: Fiscal Year 2000; Project Start 9-SEP-2000; Project End 1-AUG2004 Summary: Inhaled nitric oxide (iNO) therapy is a safe and effective treatment for term newborns with persistent pulmonary hypertension and hypoxemic respiratory failure. However, little is known about the potential role of iNO in the treatment of premature newborns with


respiratory failure. Premature newborns are particularly susceptible to the adverse effects of ventilator- induced lung injury, oxygen toxicity, and lung inflammation which contribute to the development of chronic lung disease (CLD). Despite treatment with exogenous surfactant and steroids, CLD remains a major cause of morbidity and mortality in premature newborns. Early clinical observations suggest that low-dose iNO improves oxygenation and decreases the need for mechanical ventilator support in the premature infant. In addition to its effects on gas exchange, recent laboratory and clinical observations suggest that iNO may also act as a lung-specific anti- inflammatory treatment and reduce the contribution of lung inflammation to the evolution of acute and chronic lung injury in premature infants. We recently conducted a masked, randomized, controlled pilot study of low- dose iNO in premature newborns with severe hypoxemic respiratory failure. Eighty patients from 12 centers were randomized to treatment with iNO (5 ppm) or placebo. Low-dose iNO caused acute improvement in oxygenation and reduced ventilator days. Moreover, important trends in CLD reduction were noted in this pilot trial, without an increased incidence of adverse events (e.g. intracranial hemorrhage). Based on the beneficial effects of iNO on gas exchange and lung inflammation, we hypothesize that early treatment with low-dose iNO may reduce the incidence of CLD in premature newborns with respiratory failure. To test this hypothesis, we have designed a multicenter, randomized, controlled, masked trial without crossover. Specific aims of this study are to determine if: l) iNO reduces CLD in premature newborns (gestational age

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