(BQ) Part 1 book Pediatric critical care medicine presents the following contents: The cell, endocrinology and metabolism, hematology and oncology, cardiac physiology and pathophysiology, pulmonology, neurosciences, nephrology, shock and shock syndromes.
Pediatric Critical Care Medicine EDITORS ANTHONY D SLONIM, MD, DRPH, FCCM Executive Director, Center for Clinical Effectiveness Attending Physician, Critical Care Medicine Children’s National Medical Center Associate Professor and Vice Chairman of Pediatrics The George Washington University School of Medicine Washington, DC MURRAY M POLLACK, MD, MBA, FCCM Executive Director, Center for Hospital-Based Specialities Division Chief, Critical Care Medicine Children’s National Medical Center Professor of Pediatrics The George Washington University School of Medicine Washington, DC SECTION EDITORS Michael J Bell, MD John T Berger III, MD Joseph A Carcillo Jr, MD Heidi J Dalton, MD, FCCM Jonathan S Evans, MD Mark J Heulitt, MD, FAARC, FCCP Richard A Jonas, MD Paul Kaplowitz, MD, PhD Naomi L C Luban, MD Robert E Lynch, MD, PhD, FCCM JoAnne Natale, MD, PhD Daniel A Notterman, MD, FCCM David M Steinhorn, MD Edward C Wong, MD Acquisitions Editor: Anne Sydor/Brian Brown Managing Editor: Nicole Dernoski/Fran Murphy Developmental Editor: Molly Connors, Dovetail Content Solutions Project Manager: Nicole Walz Senior Manufacturing Manager: Ben Rivera Senior Marketing Manager: Angela Panetta Design Coordinator: Terry Mallon Cover Designer: Joseph DePinho Production Services: Laserwords Private Limited Printer: Edwards Brothers 2006 by Lippincott Williams & Wilkins, a Wolters Kluwer business 530 Walnut Street Philadelphia, PA 19106 WWW.LWW.COM All rights reserved This book is protected by copyright No part of this book may be reproduced in any form or by any means, including photocopying, or utilizing by any information storage and retrieval system without written permission from the copyright owner, except for brief quotations embodied in critical articles and reviews Printed in the United States Library of Congress Cataloging-in-Publication Data Pediatric critical care medicine / [edited by] Anthony D Slonim, Murray M Pollack —1st ed p ; cm Includes bibliographical references and index ISBN 0-7817-9469-2 Pediatric intensive care I Slonim, Anthony D II Pollack, Murray M [DNLM: Critical Care—Child Critical Care—Infant WS 366 P3684 2006] RJ370.P28 2006 618.92 0028—dc22 2005032133 Care has been taken to confirm the accuracy of the information presented and to describe generally accepted practices However, the authors, editors, and publisher are not responsible for errors or omissions or for any consequences from application of the information in this book and make no warranty, expressed or implied, with respect to the currency, completeness, or accuracy of the contents of the publication Application of this information in a particular situation remains the professional responsibility of the practitioner The authors, editors, and publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accordance with current recommendations and practice at the time of publication However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions This is particularly important when the recommended agent is a new or infrequently employed drug Some drugs and medical devices presented in this publication have Food and Drug Administration (FDA) clearance for limited use in restricted research settings It is the responsibility of health care providers to ascertain the FDA status of each drug or device planned for use in their clinical practice The publishers have made every effort to trace copyright holders for borrowed material If they have inadvertently overlooked any, they will be pleased to make the necessary arrangements at the first opportunity To purchase additional copies of this book, call our customer service department at (800) 638-3030 or fax orders to (301) 223-2320 International customers should call (301) 223-2300 Lippincott Williams & Wilkins customer service representatives are available from 8:30 am to 6:30 pm, EST, Monday through Friday, for telephone access Visit Lippincott Williams & Wilkins on the Internet: http://www.lww.com 10 This work is dedicated to my family, friends, colleagues, and patients, all of whom have had a material impact on my development as a physician A.D.S This work is dedicated to my wife, Mona, who exemplifies persistence and courage; my children Seth and Haley, who make me want to be a better physician; and the Critical Care Division at CNMC who teach me every day about clinical excellence and the values of being a physician M.M.P Contents List of Contributors ix Preface xvii Acknowledgments xix 5.3 Electrophysiology 220 John T Berger III and Jeffrey P Moak PART I: PHYSIOLOGY AND PATHOPHYSIOLOGY 5.5 Pathophysiology of Chronic Myocardial Dysfunction 230 J Carter Ralphe The Cell Barry Weinberger, Nazeeh Hanna, Diane E Heck, and Daniel A Notterman Endocrinology and Metabolism 32 Murray M Pollack and Paul Kaplowitz Immunology, Inflammation, and Infectious Diseases 59 Anthony D Slonim and Nalini Singh 3.1 Immunology 60 Anthony D Slonim 3.2 Inflammation 80 Anthony D Slonim 3.3 Infectious Diseases 98 Anthony D Slonim and Nalini Singh Foundations of Infectious Diseases in the Pediatric Intensive Care Unit 98 Anthony D Slonim, Wendy Turenne, and Nalini Singh The Microbial Agents 102 Anthony Yun Lee and Anthony D Slonim The Clinician and the Clinical Microbiology Laboratory 124 Joseph M Campos The Antimicrobial Agents 134 Sumati Nambiar and John N van den Anker Hematology and Oncology 157 Edward C Wong and Naomi L C Luban Cardiac Physiology and Pathophysiology 196 John T Berger III and Richard A Jonas 5.4 Cardiopulmonary Interactions 225 John T Berger III 5.6 Cardiopulmonary Resuscitation 235 Vinay Nadkarni and Robert A Berg Pulmonology 242 Heidi J Dalton and Mark J Heulitt 6.1 Airway Structures and Functions 243 Heidi J Dalton 6.2 Embryologic and Postnatal Airway and Lung Development 245 Angela T Wratney, Ronald C Sanders Jr, and Heidi J Dalton 6.3 Defense Mechanisms of the Pulmonary Tree 251 K Alex Daneshmand, Ronald C Sanders Jr, and Heidi J Dalton 6.4 Movement of Fluids and Solutes and Blood Flow within the Lung 253 Angela T Wratney and Heidi J Dalton 6.5 Alveolar Function 256 Douglas F Willson 6.6 Pulmonary Gas Exchange 259 Angela T Wratney and Ira M Cheifetz 6.7 Respiratory System Physiology 264 Mark J Heulitt and Paul Ouellet 6.8 Mechanical Breathing 277 Mark J Heulitt, Paul Ouellet, and Richard T Fiser 6.9 Cardiorespiratory Interactions 303 Cindy Sutton Barrett and Ira M Cheifetz 6.10 Acute Lung Injury 308 Ronald C Sanders Jr and K Alex Daneshmand Neurosciences 318 Michael J Bell and JoAnne E Natale 5.1 Cardiomyocyte Function 197 Steven M Schwartz Nephrology 378 Robert E Lynch 5.2 Cardiac Performance 205 John T Berger III Gastroenterology 416 David M Steinhorn and Jonathan S Evans vi Contents 10 Shock and Shock Syndromes 438 Joseph A Carcillo, Jefferson Pedro Piva, Neal J Thomas, Yong Y Han, John C Lin, and Richard Andrew Orr PART II: CLINICAL DISORDERS 473 Section A: Endocrine Disorders 474 Murray M Pollack and Paul Kaplowitz 11 Endocrine Disorders of Water Regulation 475 Susan B Nunez 26 Coagulation Disorders 577 W Tait Stevens 27 Oncologic Emergencies 585 Edward C Wong and Anne L Angiolillo 28 Therapeutic Apheresis 597 Anne F Eder 29 Bone Marrow Transplantation 605 Edward C Wong, Evelio D Perez-Albuerne, and Naynesh R Kamani Section D: Cardiac Diseases 615 John T Berger III and Richard A Jonas 14 Adrenal Disorders 492 Christiane O Corriveau 30 Principles of Postoperative Care 616 Melvin C Almodovar 31 Congenital Heart Disease 623 John T Berger III, Steven M Schwartz, and David P Nelson 32 Myocardial Disease 633 Christopher F Spurney 15 Disorders of Micronutrients 497 Angela A Hsu and Cynthia L Gibson 33 Pericardial and Endocardial Disease 639 George Ofori-Amanfo 16 Inborn Errors of Metabolism 505 Dina J Zand and Cynthia J Tifft 34 Dysrhythmias 644 Jeffrey P Moak 12 Diabetic Ketoacidosis 481 Rajani Prabhakaran and Lynne L Levitsky 13 Thyroid Disorders 488 Audrey Austin Section B: Disorders of Host Defense 517 Anthony D Slonim 17 Immune Complications of Transplantation 518 Mark D Sorrentino 18 Immunosuppression Induced by Therapeutic Agents 522 William T Tsai and John N van den Anker 19 Allergic, Vasculitic, and Rheumatologic Illnesses 527 David C Stockwell and Aditi Sharangpani 20 Immunodef iciency Syndromes in Children 539 Thomas J Cholis III and Anthony D Slonim 21 Pediatric Acquired Immunodeficiency Syndrome in the Pediatric Intensive Care Unit 547 Sophia R Smith and Hans M L Spiegel 22 Health Care–Associated Infections 553 Jennifer Hurst and Nalini Singh 23 Systemic Inflammatory Response Syndrome 559 M Nilufer Yalindag-Ozturk and Oral Alpan Section C: Hematologic and Oncologic Disorders 564 Naomi L C Luban and Edward C Wong 35 Pacemakers 659 Russell R Cross and Jeffrey P Moak 36 Vasoactive Agents 664 Ronald A Bronicki and Paul A Checchia Section E: Respiratory Disorders 670 Heidi J Dalton and Mark J Heulitt 37 Pulmonary Diagnostic Procedures 671 Natan Noviski and Parthak Prodhan 38 Asthma 678 Regina Okhuysen-Cawley and James B Fink 39 Disorders of the Lung Parenchyma 683 Angela T Wratney, Ira M Cheifetz, James D Fortenberry, and Matthew L Paden 40 Pulmonary Hypertension 694 Asrar Rashid and D Dunbar Ivy 41 Disorders of the Chest Wall and Respiratory Muscles 705 Angela T Wratney and Ira M Cheifetz 42 Gases and Drugs Used in Support of the Respiratory System 717 Angela T Wratney and Ira M Cheifetz Oxygen, Monitoring, Hypoxic Gas or Carbon Dioxide, and Heliox 717 Angela T Wratney and Ira M Cheifetz 24 Sickle Cell Disease 565 Karen E King Inhaled Nitric Oxide 722 Emily L Dobyns and Eva Nozik Grayck 25 Thrombotic and Fibrinolytic Disorders 571 Guy Young Surfactant 724 Douglas F Willson Contents vii 43 Mechanical Ventilation 730 Mark J Heulitt, Basem Zafer Alsaati, Richard T Fiser, and Sylvia Găothberg 55 Maintenance and Support of Kidney Function in Critical Illness 816 Mohammad Ilyas and Eileen Ellis 44 Extracorporeal Techniques 744 Steven A Conrad and Heidi J Dalton 56 Acute Renal Failure 821 Craig William Belsha Section F: Neurologic Disorders 754 Michael J Bell and JoAnne E Natale 57 Hemolytic Uremic Syndrome 826 Ellen G Wood 45 Global/Regional Ischemia 755 Rebecca N Ichord 58 Renal Replacement Therapy 831 Stuart L Goldstein 46 Disorders of Muscle 760 JoAnne E Natale and Michael J Bell 59 Renal Pharmacology 836 Douglas L Blowey and James D Marshall 47 Neurological Emergencies 767 Roger J Packer and Derek A Bruce Section H: Gastrointestinal Disorders 842 David M Steinhorn and Jonathan S Evans 48 Altered Mental Status 773 Leticia Manning Ryan and Stephen J Teach 60 Gastrointestinal Bleeding 843 Franziska Mohr and Marsha Kay 49 Central Nervous System Infections 778 Andrew M Bonwit 61 Reflux and Other Motility Disorders 850 Victor M Pineiro-Carrero 50 Status Epilepticus 783 Tammy Noriko Tsuchida, Steven L Weinstein, and William Davis Gaillard 62 Gastrointestinal Trauma 855 Riccardo A Superina and Lisa P Abramson 51 Brain Death 790 I David Todres 52 Brain and Spinal Cord Trauma 796 JoAnne E Natale and Michael J Bell 53 Sedation for Procedures and Mechanical Ventilation in Children with Critical Illness 804 Yewande J Johnson and Julia C Finkel Section G: Renal Disorders 810 Robert E Lynch 54 Fluid Management and Electrolyte Disturbances 811 Alok Kalia and Amita Sharma 63 Hepatic Failure 862 David M Steinhorn 64 Gastrointestinal Failure 868 David M Steinhorn 65 Nutritional Support in Critical Illness 872 Donald E George, Laura T Russo, and David M Steinhorn 66 Acute Pancreatitis 878 Ruba K Azzam and Miguel Saps Appendix 884 Index 891 List of Contributors LISA P ABRAMSON, MD Pediatric Surgery Fellow, Division of Pediatric Surgery, Children’s Memorial Hospital, Chicago, Illinois MELVIN C ALMODOVAR, MD Assistant Professor, Department of Pediatrics, University of Colorado Health and Science Center; Director of Cardiac Intensive Care, The Children’s Hospital Heart Institute, The Children’s Hospital Denver, Denver, Colorado ORAL ALPAN, MD Director, Center for Allergy, Asthma, and Immune Disorders, South Riding, Virginia BASEM ZAFER ALSAATI, MD Assistant Professor, Department of Pediatrics, Queen’s University; Attending Physician, Department of Pediatrics, Kingston General Hospital, Kingston, Ontario, Canada ANNE L ANGIOLILLO, MD Associate Professor, Department of Pediatrics, The George Washington University School of Medicine; Attending Physician, Division of Hematology and Oncology, Center for Cancer and Blood Disorders, Children’s National Medical Center, Washington, DC AUDREY AUSTIN, MD Assistant Professor, Department of Pediatrics, The George Washington University School of Medicine and Health Sciences; Endocrinologist, Department of Pediatrics, Children’s National Medical Center, Washington, DC RUBA K AZZAM, MD Assistant Professor, Department of Pediatric Gastroenterology and Hepatology, The University of Chicago, Comer Children’s Hospital, Chicago, Illinois CINDY SUTTON BARRETT, MD Senior Fellow in Pediatric Critical Care, Pediatric Critical Care Fellow, Department of Pediatric Critical Care, Duke University Medical Center, Durham, North Carolina MICHAEL J BELL, MD Associate Professor of Pediatrics and Critical Care Medicine, Department of Pediatrics, Division of Critical Care Medicine, The George Washington University School of Medicine; Director, Neurocritical Care, Department of Pediatrics, Division of Critical Care Medicine, Children’s National Medical Center, Washington, DC CRAIG WILLIAM BELSHA, MD Associate Professor, Department of Pediatrics, St Louis University; Director, Hypertension Program, Division of Pediatric Nephrology, SSM Cardinal Glennon Children’s Hospital, St Louis, Missouri ROBERT A BERG, MD Associate Dean for Clinical Affairs, Professor, Department of Pediatrics, The University of Arizona College of Medicine; Pediatric Intensivist, Department of Pediatrics, University Medical Center and Tucson Medical Center, Tucson, Arizona JOHN T BERGER III, MD Assistant Professor, Department of Pediatrics, The George Washington University School of Medicine; Director, Cardiac Intensive Care, Department of Critical Care Medicine and Cardiology, Children’s National Medical Center, Washington, DC DOUGLAS L BLOWEY, MD Associate Professor, Departments of Pediatric Nephrology and Clinical Pharmacology, University of Missouri—Kansas City School of Medicine, Children’s Mercy Hospitals and Clinics, Kansas City, Missouri ANDREW M BONWIT, MD Assistant Professor, Department of Pediatrics, The George Washington University School of Medicine; Attending Pediatrician, Children’s National Medical Center, Washington, DC RONALD A BRONICKI, MD Assistant Clinical Professor, Department of Pediatrics, Harbor—University of California Los Angeles Medical Center, University of California Los Angeles School of Medicine; Attending Physician, Cardiac Intensive Care, Children’s Hospital of Orange County, Orange, California DEREK A BRUCE, MB, CHB Professor of Neurosurgery and Pediatrics, Department of Neurosurgery, The George Washington University School of Medicine; Attending Neurosurgeon, Departments of Neuroscience and Behavioral Medicine, Children’s National Medical Center, Washington, DC JOSEPH M CAMPOS, PhD Professor, Departments of Pediatrics, Pathology, and Microbiology/Tropical Medicine, The George Washington University Medical Center; Director, Microbiology Laboratory and Laboratory Informatics, Department of Laboratory Medicine, Children’s National Medical Center, Washington, DC x List of Contributors JOSEPH A CARCILLO, MD Associate Professor, Department of Critical Care Medicine, University of Pittsburgh, Center for Clinical Pharmacology; Associate Director, Pediatric Intensive Care Unit, Department of Critical Care Medicine, Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania K ALEX DANESHMAND, DO Pediatric Intensive Care Fellow, Department of Pediatric Critical Care Medicine, University of Florida; Pediatric Intensive Care Fellow, Department of Pediatric Critical Care Medicine, Shands Children’s Hospital, Gainesville, Florida EMILY L DOBYNS, MD PAUL A CHECCHIA, MD Assistant Professor of Critical Care and Cardiology, Department of Pediatrics, Washington University School of Medicine; Chief, Pediatric Cardiac Critical Care Service, Co-director, Pediatric Intensive Care Unit, St Louis Children’s Hospital, St Louis, Missouri IRA M CHEIFETZ, MD, FCCM, FAARC Division Chief, Critical Care Medicine, Associate Professor, Department of Pediatrics, Duke University School of Medicine, Duke University Medical Center; Medical Director, Pediatric Intensive Care Unit, Medical Director, Pediatric Respiratory Care and ECMO, Department of Pediatrics, Duke Children’s Hospital, Duke University Medical Center, Durham, North Carolina Associate Professor, Section of Critical Care Medicine, Department of Pediatrics, University of Colorado Denver Health Sciences Center; Medical Director, Pediatric Critical Care Unit, Department of Pediatric Critical Care Medicine, The Children’s Hospital, Denver, Colorado ANNE F EDER, MD, PhD Executive Medical Officer, Biomedical Headquarters, American Red Cross, Washington, DC EILEEN ELLIS, MD Professor, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas; Professor, Department of Pediatrics, Arkansas Children’s Hospital, Little Rock, Arkansas JONATHAN S EVANS, MD THOMAS J CHOLIS III, MD Clinical Instructor, Department of Pediatrics, The George Washington University School of Medicine, Children’s National Medical Center, Washington, DC Staff Physician, Division of Pediatric Gastroenterology and Nutrition, Nemours Children’s Clinic, Jacksonville, Florida JAMES B FINK, MS, RRT, FAARC STEVEN A CONRAD, MD, PhD, FCCM Professor, Departments of Medicine, Pediatrics, Emergency Medicine, and Anesthesiology, Louisiana State University Health Sciences Center; Director, Critical Care Service, and Extracorporeal Life Support Program, Louisiana State University Hospital, Shreveport, Louisiana CHRISTIANE O CORRIVEAU, MD Assistant Professor, Department of Pediatrics, The George Washington University Medical Center; Director, Departmental Education and Fellowship Training, Divison of Critical Care Medicine, Children’s National Medical Center, Washington, DC RUSSELL R CROSS, MD, MSBME Assistant Professor, Department of Pediatrics, The George Washington University School of Medicine; Attending Physician, Department of Pediatric Cardiology, Children’s National Medical Center, Washington, DC HEIDI J DALTON, MD, FCCM Professor, Department of Pediatrics, The George Washington University School of Medicine and Health Sciences; Director, Pediatric Intensive Care Unit and Pediatric ECMO, Department of Critical Care Medicine, Children’s National Medical Center, Washington, DC Fellow, Respiratory Science, Department of Scientific Affairs, Aerogen, Inc., Mountain View, California JULIA C FINKEL, MD Associate Professor, Departments of Anesthesiology and Pediatrics, The George Washington Universtiy School of Medicine; Director, Anesthesia Pain Management Service, Children’s National Medical Center, Washington, DC RICHARD T FISER, MD Associate Professor, Departments of Pediatric Critical Care and Cardiology, University of Arkansas for Medical Sciences—College of Medicine, Little Rock, Arkansas; Medical Director, ECMO, Arkansas Children’s Hospital, Little Rock, Arkansas JAMES D FORTENBERRY, MD, FCCM, FAA Clinical Associate Professor, Department of Pediatrics, Emory University School of Medicine; Division Director, Department of Critical Care Medicine, ECMO, Children’s Healthcare of Atlanta, Atlanta, Georgia WILLIAM DAVIS GAILLARD, MD Professor, Departments of Neurology and Pediatrics, The George Washington University School of Medicine; Director, Comprehensive Pediatric Epilepsy Program, Department of Neurology, Children’s National Medical Center, Washington, DC 458 Part I: Physiology and Pathophysiology (JET) is the most common arrhythmia causing cardiogenic shock in the postoperative period The rapid heart rate and lack of co-ordinated atrial and ventricular contraction can lead to a life-threatening low cardiac output state because of inadequate stroke volume This condition generally responds to volume loading and cooling Because hypothermia obscures many of the clinical signs of normal perfusion, serum lactate level, base deficit, superior venous oxygen saturation, and AVDO2 should be monitored when titrating inotrope and vasodilator therapies Children with septal hypertrophy may be treated with β blockers, such as esmolol, or calcium channel blockers, such as nicardipine, to slow heart rate, reduce contractility, and improve ventricular stroke volume Careful titration of afterload therapies is required in these children Children with valve replacement surgery or coarctation of the aorta repair need afterload reduction therapy to prevent any incident of hypertension The single ventricle patient with shock presents with important challenges In the prerepair state, shock can be caused by pulmonary overcirculation This usually occurs when oxygen is administered to the infant for a low arterial oxygen saturation This increases arterial saturation but simultaneously widens AVDO2 because, as blood preferentially flows to the low-resistance pulmonary vascular bed, it is being ‘‘stolen’’ from the circulation Despite increasing oxygen saturation, the patient becomes tachypnic, tachycardic, and cold, with a prolonged capillary refill and lactic acidosis This can be remedied by providing room air or hypoxic gas mixtures, which increase pulmonary vascular resistance and restore systemic circulatory blood flow Arterial oxygen saturation decreases as the AVDO2 narrows and shock resolves In the postoperative period after the first stage of correction, cardiogenic shock occurs for the most part because of increased SVR (see preceding text) Wide AVDO2 can be narrowed by treating with systemic vasodilators including nitroprusside, chlorpromazine, milrinone, enoximone, or phenoxybenzamine Vasodilator toxicity can be reversed with vasopressor; however, continued inotrope support will be required as well.39 Attention must also be paid to the maintenance of high hemoglobin concentrations to maintain adequate oxygen delivery in the presence of arterial saturation, which normally ranges from 70% to 80% Because oxygen saturation is reduced by 20% to 30% in these patients, hemoglobin concentrations must be increased by 20% to 30% to maintain oxygen content and oxygen delivery without demanding high output from the already ischemic heart This point is crucial not only in single ventricle patients but also in patients with cyanotic heart disease and shock After total correction, patients are left with a Fontan physiology Cardiogenic shock in these patients can be precipitated by conditions that reduce preload, including dehydration, increased pulmonary vascular resistance, and increased intrathoracic pressure from positive-pressure ventilation Because patients with Fontan or hemi-Fontan correction have no functioning atrial kick, they are completely dependent on venous pressure–generated preload for perfusion of the right ventricle Therapy for these patients in shock includes volume resuscitation, as little positive pressure as possible, and pneumatic devices to increase venous return These children require high CVPs for perfusion Primary, Persistent, or Acquired Pulmonary Hypertension–Induced Shock Systemic pulmonary blood pressures can be associated with right ventricular failure and shock Right ventricular failure is usually associated with secondary left ventricular failure caused by septal bowing into the left ventricle and an inability to fill during diastole These patients have dilated right ventricular failure and inadequate left ventricular stroke volume The treatment strategy is to reduce the afterload in the right ventricle The most selective pulmonary vasodilator is iNO This gas stimulates soluble guanylate cyclase, increases cGMP, reduces calcium in the smooth muscle cell, and induces vasodilation The nitric oxide is then absorbed by circulating hemoglobin/red blood cells and reduced to an inactive form, preventing significant systemic effects Inhaled prostacyclin is a good second-line drug if iNO is unsuccessful Intravenous prostacyclin (cAMP drug), milrinone (cAMP), and nitroglycerin (cGMP) also have some selectivity for the pulmonary vasculature and can be effective adjuncts Nitroglycerin tachyphylaxis can be treated by giving N-acetylcysteine (Mucomyst), which replaces the sulfhydryl group to allow further production of biologically active nitrosothiols Isoproterenol is an effective inotrope and pulmonary vasodilator as well It improves right ventricular contractility while promoting pulmonary and systemic vasodilation The use of α-adrenergic agents should be carefully monitored Many believe that pulmonary hypertension can be exacerbated Norepinephrine is advocated to improve right ventricular filling in adults with right ventricular failure due to right-sided infarction; however, these patients rarely have systemic pulmonary artery hypertension Acute failure of the right side of the heart and cardiogenic shock caused by pulmonary embolus should be treated with tissue plasminogen activator and subsequent heparinization Septic Shock Outcomes in neonatal and pediatric sepsis have improved with the advent of neonatal and pediatric intensive care The University of Minnesota reported a 97% mortality rate from gram-negative sepsis in 1968.40 In 1985, the National Children’s Medical Center reported a 60% mortality rate in all cause septic shock.3 By 1999, the mortality rates from severe sepsis had dropped to 9% in a US sample estimate.41 Several reports in the 21st century suggest further improvement, with the implementation of resuscitation practices now being recommended in the American College of Critical Care (ACCM)/PALS guidelines and clinical practice parameters for hemodynamic support of pediatric Chapter 10: Shock and Shock Syndromes and newborn sepsis Booy et al reported a decrease in mortality from meningococcemia from 22% to 2% when they implemented early recognition and treatment with aggressive volume resuscitation and inotrope use.42 Ngo et al reported 100% survival from dengue shock in Vietnamese children when aggressive fluid resuscitation was given.11 Kutko et al reported 100% survival in all cause septic shock in previously healthy children and 85% survival in children with chronic illness, predominantly cancer-related.43 Lin et al reported similar results with the implementation of the ACCM/PALS guidelines Twenty-eight–day survival was 97% and hospital survival was 94%.44 The hemodynamic response to newborn and pediatric septic shock is different from the ‘‘classically’’ described hemodynamic response of adults Opinion holds that the predominant cause of mortality in adult septic shock is vasomotor paralysis Adults have myocardial dysfunction manifested as a decreased ejection fraction; however, cardiac output is usually maintained or increased by two mechanisms, tachycardia and ventricular dilation Adults who not develop this adaptive process to maintain cardiac output have a poor prognosis This dogma may not be entirely correct because Rivers et al have recently shown that adults with sepsis, normal blood pressure, and decreased superior vena cava oxygen saturation, a condition of low cardiac output and elevated SVR, have increased multiple organ failure and mortality.5 Importantly, inotrope and fluid therapy directed at increasing cardiac output with a goal of attaining a ScvO2 saturation >70% prevented multiple organ failure and improved survival Pediatric septic shock is associated with severe hypovolemia, and children frequently respond well to aggressive volume resuscitation; however, the hemodynamic response of fluid-resuscitated children appears diverse compared to that classically attributed to adults Contrary to the adult experience, low cardiac output, and not low SVR, is associated with mortality in pediatric septic shock Attainment of the therapeutic goal of cardiac index 3.3 to L/minute/m2 is associated with improved survival.3 Also, contrary to adults, oxygen delivery, and not oxygen extraction, is the major determinant of oxygen consumption in children.45 Attainment of the therapeutic goal of VO2 >200 mL/minute/m2 is also associated with improved outcome In 1998, investigators reported positive outcome when aggressive volume resuscitation (60 mL per kg fluid in the first hour) and goal-directed therapies4 (the goal was a cardiac index 3.3 to L/minute/m2 and normal pulmonary capillary wedge pressure) were applied to children with septic shock Ceneviva et al reported 50 children with fluidrefractory (≥60 mL per kg of fluid resuscitation in the first hour), dopamine-resistant shock.4 Most children (58%) showed a low cardiac output/high SVR state and 22% had low cardiac output and low vascular resistance Hemodynamic states frequently progressed and changed over the first 48 hours Persistent shock occurred in 33% of the patients There was a significant decrease in cardiac function 459 over time, requiring addition of inotropes and vasodilators Although decreasing cardiac function accounted for most patients with persistent shock, some showed a complete change from a low-output state to a high-output/low SVR state Inotropes, vasopressors, and vasodilators were directed at maintaining normal cardiac index and SVR in the patients Mortality from fluid-refractory, dopamineresistant septic shock in this study (18%) was markedly reduced compared to the mortality in the 1985 study (58%),4 in which aggressive fluid resuscitation was not used Neonatal septic shock can be complicated by the lack of physiologic transition from fetal to neonatal circulation In utero, 85% of fetal circulation bypasses the lungs through the patent ductus arteriosus and foramen ovale Prenatally, this flow pattern is maintained by suprasystemic pulmonary artery pressures At birth, inhalation of oxygen triggers a cascade of biochemical events that ultimately result in reduction of pulmonary artery pressure and transition from fetal to neonatal circulation, with blood flow now being directed through the pulmonary circulation Closure of the patent ductus arteriosus and foramen ovale complete this transition Pulmonary artery pressures can remain elevated and the ductus arteriosus can remain open for the first weeks of life, whereas the foramen ovale may remain probe patent for years Sepsis-induced acidosis and hypoxia can increase pulmonary artery pressure and maintain patency of the ductus arteriosus, resulting in persistent pulmonary hypertension of the newborn (PPHN) and persistent fetal circulation (PFC) Neonatal septic shock with PPHN is associated with increased right ventricle work Despite in utero conditioning, the thickened right ventricle may fail in the presence of systemic pulmonary artery pressures Decompensated right ventricular failure can be clinically manifested by tricuspid regurgitation and hepatomegaly Newborn animal models of group B streptococcal and endotoxin shock have also documented reduced cardiac output and increased pulmonary resistance, mesenteric resistance, and SVR Therapies directed at the reversal of right ventricle failure, through reduction of pulmonary artery pressures, are commonly needed in neonates with fluid-refractory shock and PPHN The hemodynamic response in premature, very low– birth weight infants with septic shock (40 mL per kg.42 The SAFE trial was recently completed in adult critical illness There was a tendency toward improved survival in the sepsis population resuscitated with albumin (p = 0.05).10 The use of blood as a fluid expander has been examined in two small pediatric studies, but no recommendations were given by the investigators.48,49 Although there are no published studies of, or recommendations on, targeted hemoglobin concentration in children, an emergency room protocol directed at maintenance of hemoglobin at 10 g per dL in adults with a superior vena cava oxygen saturation 70% Observe in PICU Catecholamine-resistant shock Not at risk? At risk of adrenal insufficiency? 60 Do not give hydrocortisone Give hydrocortisone Normal blood pressure cold shock ScvO2 sat