Texas Children's Hospital Handbook of Pediatrics and Neonatology

Texas Children’s Hospital Handbook of Pediatrics and Neonatology Notice

Medicine is an ever-changing science. As new research and clinical experience broaden our knowledge, changes in treatment and drug therapy are required. The authors and the publisher of this work have checked with sources believed to be reliable in their efforts to provide information that is complete and generally in accord with the standards accepted at the time of publication. However, in view of the possibility of human error or changes in medical sciences, neither the authors nor the publisher nor any other party who has been involved in the preparation or publication of this work warrants that the information contained herein is in every respect accurate or complete, and they disclaim all responsibility for any errors or omissions or for the results obtained from use of the information contained in this work. Readers are encouraged to conﬁ rm the information contained herein with other sources. For example and in particular, readers are advised to check the product information sheet included in the package of each drug they plan to administer to be certain that the information contained in this work is accurate and that changes have not been made in the recommended dose or in the contraindications for administration. This recommendation is of particular importance in connection with new or infrequently used drugs. Texas Children’s Hospital Handbook of Pediatrics and Neonatology

Editor Adam W. Lowry, MD Clinical Postdoctoral Fellow, Cardiology Texas Children’s Hospital Department of Pediatrics Baylor College of Medicine Houston, Texas

Associate Editors Kushal Y. Bhakta, MD Assistant Professor, Pediatrics Section of Neonatology Texas Children’s Hospital Department of Pediatrics Baylor College of Medicine Houston, Texas

Pratip K. Nag, MD, PhD Assistant Professor, Pediatrics Section of Hospital and Emergency Medicine Texas Children’s Hospital Department of Pediatrics Baylor College of Medicine Houston, Texas

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Except as permitted under the Copy- right Act of 1976 and the right to store and retrieve one copy of the work, you may not decompile, disassemble, reverse engineer, reproduce, modify, create derivative works based upon, transmit, distribute, disseminate, sell, publish or sublicense the work or any part of it without McGraw-Hill’s prior consent. You may use the work for your own noncommercial and personal use; any other use of the work is strictly prohibited. Your right to use the work may be terminated if you fail to comply with these terms. THE WORK IS PROVIDED “AS IS.” McGRAW-HILL AND ITS LICEN- SORS MAKE NO GUARANTEES OR WARRANTIES AS TO THE AC- CURACY, ADEQUACY OR COMPLETENESS OF OR RESULTS TO BE OBTAINED FROM USING THE WORK, INCLUDING ANY INFOR- MATION THAT CAN BE ACCESSED THROUGH THE WORK VIA HYPERLINK OR OTHERWISE, AND EXPRESSLY DISCLAIM ANY WARRANTY, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIM- ITED TO IMPLIED WARRANTIES OF MERCHANTABILITY OR FIT- NESS FOR A PARTICULAR PURPOSE. McGraw-Hill and its licensors do not warrant or guarantee that the functions contained in the work will meet your requirements or that its operation will be uninterrupted or error free. Neither McGraw-Hill nor its licensors shall be liable to you or anyone else for any inaccuracy, error or omission, regardless of cause, in the work or for any damages resulting therefrom. McGraw-Hill has no responsibility for the content of any information accessed through the work. Under no circumstances shall McGraw-Hill and/or its licensors be liable for any indirect, incidental, special, punitive, consequential or similar damages that result from the use of or inability to use the work, even if any of them has been advised of the possibility of such damages. This limitation of liability shall apply to any claim or cause whatsoever whether such claim or cause arises in contract, tort or otherwise. Between 1977 and 2008, more than 5000 students earned Doctor of Medicine degrees from the Baylor College of Medicine, and approximately 1200 new pediatricians graduated from the Baylor/Texas Children’s Hospital pediatric residency training program. Every one of these individuals was shaped in some way by Dr. Ralph D. Feigin. Simply stated, Dr. Feigin’s contributions to the science and practice of pediatrics, his leadership roles in a multitude of national professional organizations, and his mentorship of thousands of young medical students and pediatric trainees made him one of the most infl uential and important pediatricians of the past 30 years. I trained in pediatrics at Baylor and Texas Children’s with Dr. Feigin. And along the way, I collected a thousand memories and stories. For sure, I was witness to his legendary memory and unpar- alleled skills as a physician and diagnostician. I remember one trip I made with him to another top U.S. medical center, where the chief of pediatrics presented the case of a critically ill child he described as having “baffl ed the best minds at the university.” A wink and an elbow from Dr. Feigin less than fi ve minutes into the presentation told me that he already had made the diagnosis. His diagnosis was correct, of course, and the child was treated and survived. I remember another trip we made together to the Mayo Clinic. Dr. Feigin correctly predicted the number of seconds our accelerat- ing jet airliner would require for takeoff, based on the type of air- craft, the number of passengers, the amount of fuel required to fl y to Minnesota, and the approximate weight of the luggage he had seen loaded into the belly of the plane. Then, he pointed out, by number or name, nearly every major highway we fl ew over between Houston and Minnesota, as if he had memorized the national interstate highway system. Exaggeration was never necessary when one was describing Dr. Feigin. I remember fondly all of our runs together at Houston’s Memo- rial Park, Dr. Feigin on one occasion exhorting me to run faster so that we would pass a group of U.S. Marines on a six-mile training run. We did, or rather, he did pass every one of them. And I remember a hundred examples of Dr. Feigin’s eternal opti- mism, his ability to dissect down and solve the most complex challenges, and his knack for seeing the best and the value in everyone. I remember well his admonition to “treat everyone with kindness, especially the people who have no power over you,” and his reminder that “you will meet the same people on the way down that you met on the way up.” Working with Dr. Feigin was one of the greatest honors and privileges of my life. He always led by example, always set priorities straight, and never failed to emphasize that we are here for the children. Dr. Feigin had our admiration, our respect, our affection, and most of all, our love. He was simply the best—not one in one million, not even one in one billion, but rather the fi nest mentor, role model, and boss that any of us ever had. Texas Children’s Hospital Handbook of Pediatrics and Neonatology is dedicated gratefully and lovingly to his memory.

Mark W. Kline, MD J.S. Abercrombie Professor and Chairman Ralph D. Feigin Chair Department of Pediatrics Baylor College of Medicine Physician-in-Chief Texas Children’s Hospital Houston, Texas

Dedications

I would like to recognize the mentors, friends, and family in my life, particularly my father Gregory and mother Sharon; I am indebted to each of you for your guidance, encouragement, and unconditional support.

—Adam W. Lowry

To my beautiful wife Leena, our darling daughter Anya, and our little girl we’re expecting in October: thanks for understanding all the long nights, and even more so, thanks for always being supportive in this enormous endeavor. I love you guys dearly.

—Kushal Y. Bhakta

Thanks to my wonderful wife Sue, our sons, and my loving and supportive family and friends for all their unconditional support and encouragement to get me where I am today.

—Pratip K. Nag Contents

Contributors ...... ix Preface ...... xvii Abbreviations ...... xviii

Section 1: General Clinical Information 1. Clinical Pearls for the Wards ...... 1 2. Analgesia and Sedation ...... 11 3. Procedures ...... 21

Section 2: Nutrition, Growth and Formula 4. Neonatal and Pediatric Nutrition ...... 35 5. Assessment of Nutrition and Growth...... 49

Section 3: Pediatrics 6. Adolescent Medicine ...... 51 7. Allergy and Immunology ...... 60 8. Cardiology ...... 66 9. Critical Care ...... 83 10. Dentistry and Oral Health ...... 106 11. Dermatology ...... 109 12. Ear, Nose, and Throat ...... 125 13. Emergency Medicine ...... 130 14. Endocrinology ...... 143 15. Fluids, Electrolytes, and Acid–Base Balance ...... 153 16. Gastroenterology ...... 169 17. Genetics ...... 184 18. Hematology ...... 196 19. High-Yield Ambulatory Care ...... 209 20. Infectious Disease ...... 218 21. Nephrology ...... 250 22. Neurology ...... 268 23. Oncology ...... 289 24. Orthopedics and Sports Medicine ...... 301 25. Pulmonology ...... 312 26. Rheumatology ...... 327 27. Toxicology ...... 340 viii Contents Section 4: Neonatology 28. Newborn Nursery ...... 348 29. Fetal Assessment and Prenatal Diagnosis...... 354 30. Stabilization, Delivery Room Care, and Initial Treatment of the VLBW Infant ...... 363 31. Discharge Planning ...... 376 32. Cardiology ...... 379 33. Dermatology ...... 386 34. Endocrinology ...... 392 35. Gastroenterology ...... 409 36. Genetics ...... 421 37. Hematology ...... 425 38. Infectious Diseases ...... 437 39. Nephrology ...... 445 40. Neurology ...... 448 41. Pain Management ...... 456 42. Pulmonology ...... 458 43. Surgical Disorders ...... 471

Index ...... 479 Contributors

All contributors are afﬁ liated with Texas Children's Hospital and Baylor College of Medicine, Houston, Texas, except where noted.

Authors

Fahd A. Ahmad, MD Michael C. Chapman, MD Resident, Pediatrics Clinical Postdoctoral Fellow, Pediatric Sports Medicine G. Todd Alonso, MD Instructor, Pediatric Emergency Daniel C. Chelius, MD Medicine Resident, Otolaryngology

Jeffrey Alten, MD Catherine Cibulskis, MD Assistant Professor, Pediatrics and Clinical Postdoctoral Fellow, Critical Care Medicine Neonatology University of Alabama at Birmingham Birmingham, Alabama Craig A. Coleby, MD Clinical Postdoctoral Fellow, Primary Mary Goodwin Altobelli, MD Care Sports Medicine Resident, Pediatrics Kendra J. Conkright, MD Amy S. Arrington, MD, PhD Resident, Internal Medicine and Resident, Pediatrics Pediatrics

Ioanna Athanassaki, MD Christopher Cotroneo, MD Assistant Professor, Pediatric Resident, Pediatrics Endocrinology Ashley M. Cox, MD Claire E. Bocchini, MD Resident, Pediatrics Clinical Postdoctoral Fellow, Pediatric Infectious Disease Shani H. Cunningham, DO Resident, Pediatrics John P. Breinholt, III, MD Assistant Professor, Pediatric Cardiology Tamara Cunningham, MD Indiana University School of Medicine Resident, Pediatrics Indianapolis, Indiana Natalie J.M. Dailey, MD Callie Byrd, MD Resident, Internal Medicine and Resident, Pediatrics Pediatrics

Waldemar F. Carlo, MD Carrie A. Danner, MD Clinical Postdoctoral Fellow, Pediatric Resident, Pediatrics Cardiology x Contributors

Jamie A. Decker, MD Brent D. Kaziny, MD Assistant Professor, Pediatric Cardiology Resident, Pediatrics

Kristin H. Dillard, MD Jarrod D. Knudson, MD, PhD Clinical Postdoctoral Fellow, Pediatric Clinical Postdoctoral Fellow, Pediatric Allergy and Immunology Cardiology

Ankhi Dutta, MD, MPH Kristin C. Koush, MD Clinical Postdoctoral Fellow, Pediatric Chief Resident in Pediatrics Infectious Disease W. Buck Kyle, MD Lisa Ecroyd, MD Chief Resident in Pediatrics Resident, Pediatrics Jennifer C. Lee, MD Erik G. Ellsworth, MD Resident, Pediatric Neurology Clinical Postdoctoral Fellow, Pediatric Cardiology Kathryn Leung, MD Assistant Professor, Peter Ermis, MD Pediatric Hematology and Oncology Resident, Pediatrics Kim Little, MD Angela Flores, MD Instructor, Pediatrics Clinical Postdoctoral Fellow, Neonatology Charles G. Macias, MD, MPH Associate Professor, Pediatric Kathleen Blue Fung, MD Emergency Medicine Resident, Pediatrics Thaddeus D. May, MD Morey W. Haymond, MD Resident, Pediatrics and Internal Professor, Pediatric Endocrinology Medicine

Kelly Hicks, MD J. Chase McNeil, MD Resident, Pediatrics Clinical Postdoctoral Fellow, Pediatric Infectious Disease Lindsey Hoffman, DO Resident, Pediatrics Mona L. McPherson, MD, MPH Associate Professor, Pediatric Zsoﬁ a Intody, MD, PhD Critical Care Resident, Pediatrics Suzanne Melancon-Kyle, MD Nick A. Jernigan, MD Resident, Pediatrics Resident, Internal Medicine and Pediatrics Barbara A. Montagnino, MS, Jamil Joyner, MD RN, CNS Resident, Pediatrics Clinical Nurse Specialist, Progresssive Care Unit Meena Rao Julapalli, MD Resident, Dermatology Contributors xi

Elizabeth H. Muth, MD Danielle Rios, MD Resident, Internal Medicine and Resident, Pediatrics Pediatrics John M. Robertson, MD Duyen K. Nguyen, DO Pediatric Pulmonology Clinical Postdoctoral Fellow, Pediatric Houston Pediatric Pulmonary and Allergy and Immunology Sleep Associates Houston, Texas Trung C. Nguyen, MD Assistant Professor, Pediatric Critical Amber J. Robinett, MD Care Medicine Resident, Pediatrics

Alison E. Niebanck, MD Christian P. Schaaf, MD, PhD Chief Resident in Pediatrics Clinical Postdoctoral Fellow, Molecular and Human Genetics Kelly Ann Olson, MA, MD Resident, Pediatrics Margaret D. Schefﬂ er, MD Resident, Pediatrics Gloria Oramasionwu, MD, MPH Clinical Postdoctoral Fellow, Pediatric Heidi Schwarzwald, MD, MPH Infectious Disease Associate Professor, Pediatric Retrovirology and Global Health Michelle Parker, MD Resident, Pediatrics Geeta Singhal, MD, MEd Assistant Professor, Pediatrics Rod Pellenberg, MD Resident, Pediatrics Justin Smith, MD Resident, Pediatrics Britt Peña, MD Chief Resident in Pediatrics Mary Nell Suell, MD Assistant Professor, Pediatric Nina Poliak, MD, MPH Hematology and Oncology, Pathology Clinical Postdoctoral Fellow, Pediatric Allergy and Immunology Sarat Susarla, MD Pediatric Pulmonology Vandana Raman, MD Houston Pediatric Pulmonary and Clinical Postdoctoral Fellow, Pediatric Sleep Associates Endocrinology Houston, Texas

Monica Ramos, MD Daniel T. Swarr, MD Clinical Postdoctoral Fellow, Neonatology Resident, Pediatrics

Damitra D. Ramos-Patel, MD Bridget Sweeney Gotsch, MD Chief Resident in Internal Medicine Resident, Pediatrics and Pediatrics Jun Teruya, MD, DSc Rebecca Rawalt, MD Associate Professor, Pathology, Clinical Postdoctoral Fellow, Neonatology Pediatrics, and Internal Medicine xii Contributors

Ashaunta R. Tumblin, MD Katherine J. Weiss, MD Resident, Pediatrics Chief Resident in Pediatrics

Irene T. Tung, MD Megan A. Westbrook, MD Resident, Pediatrics Resident, Pediatrics

Katri V. Typpo, MD Angus A. Wilfong, MD Assistant Professor, Pediatric Critical Associate Professor, Pediatric Care Medicine Neurology

Jamie Varughese, MD Wojciech Wiszniewski, MD, PhD Clinical Postdoctoral Fellow, Adolescent Clinical Postdoctoral Fellow, Molecular and Sports Medicine and Human Genetics

Shannon Wai, MBChB Amber E. Young, MD Clinical Postdoctoral Fellow, Pediatric Resident, Pediatrics Emergency Medicine Suyearn Hong Yu, MD Michael F. Wangler, MD Resident, Pediatrics Clinical Postdoctoral Fellow, Molecular and Human Genetics

Consulting Editors

Kaashif A. Ahmad, MBBS, MSc Teresa K. Duryea, MD Clinical Postdoctoral Fellow, Neonatology Associate Professor, Pediatrics

Carlos A. Bacino, MD Eric C. Eichenwald, MD Associate Professor, Molecular and Associate Professor, Neonatology Human Genetics Elaine K. Fielder, MD Patricia A. Baxter, MD Clinical Postdoctoral Fellow, Pediatric Instructor, Pediatric Hematology and Emergency Medicine Oncology Ricardo J. Flores, MD Maria A. Carrillo-Marquez, MD Clinical Postdoctoral Fellow, Pediatric Clinical Postdoctoral Fellow, Pediatric Hematology and Oncology Infectious Disease Amy Bennett Good, MD Daniel C. Chelius, MD Clinical Postdoctoral Fellow, Resident, Otolaryngology Neonatology

Cathrine Constantacos, MD W. Eddie Gordon, MD Clinical Postdoctoral Fellow, Pediatric Clinical Postdoctoral Fellow, Pediatric Endocrinology Critical Care Medicine University of North Carolina at Chapel Hill J. Nina Ham, MD Chapel Hill, North Carolina Assistant Professor, Pediatric Endocrinology Contributors xiii

Leslie L. Harris, MD Siby Moonnumakal, MD Assistant Professor, Neonatology Assistant Professor, Pediatric Pulmonology

Lana Hattar, MD James Owens, MD, PhD Clinical Postdoctoral Fellow, Pediatric Assistant Professor, Pediatric Neurology Gastroenterology, Hepatology, and Nutrition Faria A. Pereira, MD Ryan W. Himes, MD Assistant Professor, Pediatric Clinical Postdoctoral Fellow, Emergency Medicine Gastroenterology, Hepatology, and Nutrition Muralidhar H. Premkumar, MBBS, DNB, MRCPCH Emma M. Jones, MD Clinical Postdoctoral Fellow, Neonatology Clinical Postdoctoral Fellow, Pediatric Hematology and Oncology Andrea A. Ramirez, MD Research Postdoctoral Fellow, Pediatric Roshni Kandyil, MD, PhD Rheumatology Clinical Postdoctoral Fellow, Allergy and Immunology Stefanie P. Rogers, MD Clinical Postdoctoral Fellow, Neonatology Erin C. Kish, MD Clinical Postdoctoral Fellow, Brian R.E. Schultz, MD Adolescent and Sports Medicine Clinical Postdoctoral Fellow, Pediatric Emergency Medicine Federico R. Laham, MD Instructor, Pediatric Infectious Disease Timothy Slesnick, MD Assistant Professor, Pediatric Cardiology Fong W. Lam, MD Clinical Postdoctoral Fellow, Pediatric Hannah Fouts Smitherman, MD Critical Care Medicine Pediatric Emergency Medicine Cook Children’s Physician Network Katherine Leaming-Van Zandt, MD Fort Worth, Texas Clinical Postdoctoral Fellow, Pediatric Emergency Medicine Poyyapakkam Srivaths, MD Assistant Professor, Pediatric Nephrology Joyce Li, MD, MPH Clinical Instructor, Pediatric V. Reid Sutton, MD Emergency Medicine Associate Professor, Molecular and Harvard Medical School Human Genetics Boston, Massachusetts Carl Tapia, MD, MPH Charles G. Macias, MD, MPH Assistant Professor, Pediatrics Associate Professor, Pediatrics Sharonda Alston Taylor, MD Seema Mehta, MD Assistant Professor, Adolescent and Clinical Postdoctoral Fellow, Gastroenter- Sports Medicine ology, Hepatology, and Nutrition xiv Contributors

Keita Terashima, MD Katri V. Typpo, MD Clinical Postdoctoral Fellow, Pediatric Assistant Professor, Pediatric Critical Hematology and Oncology Care Medicine

Ann Thomas, MD K. Lynette Whitﬁ eld, MD Associate Professor, Pediatrics Clinical Postdoctoral Fellow, George Washington University Gastroenterology, Hepatology, and Washington, DC Nutrition

Senior Reviewers

James M. Adams, Jr., MD Lindsay H. Chase, MD Professor, Neonatology Assistant Professor, Pediatric Hospital Medicine Coburn H. Allen, MD Assistant Professor, Pediatric Joseph N. Chorley, MD Emergency Medicine, Pediatric Associate Professor, Adolescent and Infectious Disease Sports Medicine

Diane M. Anderson, PhD Annabelle N. Chua, MD Associate Professor, Neonatology Assistant Professor, Pediatric Nephrology Julie A. Boom, MD Associate Professor, Pediatrics Murali Chintagumpala, MBBS Professor, Pediatric Hematology and Eileen D. Brewer, MD Oncology Professor, Pediatric Nephrology William J. Craigen, MD, PhD K. Dawn Bunting, RD, CSP, LD Associate Professor, Molecular and Assistant Director, Clinical Nutrition Human Genetics Services Michael C. Distefano, MD Gerardo Cabrera-Meza, MD Assistant Professor, Pediatric Associate Professor, Neonatology Emergency Medicine

Judith R. Campbell, MD Jan E. Drutz, MD Associate Professor, Pediatric Infectious Professor, Academic General Pediatrics Disease Daniel I. Feig, MD, PhD A. Bruce Carter, DDS Associate Professor, Pediatric Nephrology Attending Periodontist Caraciolo J. Fernandes, MD, MBBS See Wai Chan, MD, MPH Associate Professor, Neonatology Assistant Professor, Neonatology Ellen M. Friedman, MD Binoy Chandy, MD Professor, Otolaryngology Assistant Professor, Otolaryngology Contributors xv

Joseph A. Garcia-Prats, MD Julie P. Katkin, MD Professor, Neonatology Associate Professor, Pediatric Pulmonology Mark A. Gilger, MD Professor, Gastroenterology, Moise L. Levy, MD Hepatology, and Nutrition Clinical Professor, Dermatology and Pediatrics Nancy Glass, MD, MBA Professor, Pediatric Anesthesiology Laura L. Loftis, MD Associate Professor, Pediatric Critical Stuart L. Goldstein, MD Care Medicine Professor, Pediatric Nephrology Timothy E. Lotze, MD Imelda Celine Hanson, MD Assistant Professor, Pediatric Professor, Pediatric Allergy and Neurology Immunology Donald H. Mahoney, Jr., MD Morey W. Haymond, MD Professor, Pediatric Hematology and Professor, Pediatric Endocrinology Oncology

Albert C. Hergenroeder, MD Tiffany M. McKee-Garrett, MD Professor, Adolescent and Sports Assistant Professor, Neonatology Medicine Kenneth J. Moise, MD Anthony Johnson, DO Professor, Obstetrics and Gynecology Associate Professor, Obstetrics and Gynecology Kathleen J. Motil, MD, PhD Associate Professor, Gastroenterology, Karen E. Johnson, MD Hepatology, and Nutrition Associate Professor, Neonatology Eyal Muscal, MD, MS Yvette R. Johnson, MD, MPH Assistant Professor, Pediatric Assistant Professor, Neonatology Rheumatology

Juan Juarez, Jr., MD Barry L. Myones, MD Assistant Professor, Pediatric Associate Professor, Pediatric Emergency Medicine Rheumatology

Henri Justino, MD Steven R. Neish, MD, SM Assistant Professor, Pediatric Associate Professor, Pediatric Cardiology Cardiology

Arundhati S. Kale, MBBS Oluyinka A. Olutoye, MBChB, PhD Associate Professor, Pediatric Associate Professor, Pediatric Surgery, Nephrology Obstetrics and Gynecology

Sheldon L. Kaplan, MD Lu-Ann Papile, MD Professor, Pediatric Infectious Disease Professor, Neonatology xvi Contributors

Mary E. Paul, MD Susanne Trout, RD, LD, IBCLC, Associate Professor, Pediatric Allergy RLC and Immunology Clinical Dietitian, Clinical Nutrition Services Sarah M. Phillips, MD Instructor, Pediatric Gastroenterology, Mohan Pammi Venkatesh, MD Hepatology, and Nutrition Assistant Professor, Neonatology

Lori A. Sielski, MD Lakshmi Venkateswaran, MD Associate Professor, Neonatology Assistant Professor, Pediatric Hematology and Oncology Geeta Singhal Das, MD Assistant Professor, Pediatrics David E. Wesson, MD Professor, Pediatric Surgery Timothy Slesnick, MD Assistant Professor, Pediatric Eric A. Williams, MD Cardiology Assistant Professor, Pediatric Critical Care Medicine Marianna M. Sockrider, MD, DrPH Associate Professor, Pediatric Mark L. Winter, PhD, DABAT Pulmonology Assistant Professor, Pharmacology and Toxicology Michael E. Speer, MD University of Texas Medical Branch Professor, Neonatology and Ethics Galveston, Texas

C. Philip Steuber, MD Teresa S. Wright, MD Professor, Pediatric Hematology and Assistant Professor, Pediatrics, Oncology Dermatology

V. Reid Sutton, MD Parvin Yazdani-Kachooei, MD Associate Professor, Molecular and Assistant Professor, Pediatric Human Genetics Endocrinology

M. Hossein Tcharmtchi, MD Robert S. Zeller, MD Associate Professor, Pediatric Critical Professor, Pediatric Neurology Care Medicine

Laura Torres, MD Associate Professor, Pediatric Anesthesiology Preface

Texas Children’s Hospital Handbook of Pediatrics and Neonatology is unlike any other pediatrics pocket manual. It is compact and concise, yet it thoroughly addresses both neonatology and pediatrics. It is written specifi cally to serve as an actual point-of-care tool; clinical algorithms, fi gures, and tables are abundant, promising rapid access to the information needed at the bedside. There is a remarkable online component to this handbook, in which the reader can freely access additional topics, updates, and supplementary information. This text is compact enough to comfortably carry in a white coat pocket; in fact, key medications and dosages are cited in-text in lieu of a separate formulary section. In addition, a critical care rapid reference card is included—an invaluable resource that provides immediate access to critical information in emergencies. Authored and reviewed by over 125 interns, residents, fellows, and faculty at Texas Children’s Hospital in Houston, Texas, Texas Children’s Hospital Handbook of Pediatrics and Neonatology collectively embodies the experiences and clinical pearls that are most helpful for students, trainees, and junior faculty. Distinguished faculty in virtually every pediatric discipline have authored and reviewed the content to ensure that this text refl ects the current clinical practice at our institution. The practice of medicine is often as much an art as it is a science, and in areas where robust evidence does not exist, the opinions and recommendations of our experts at Texas Children’s Hospital are included. Many chapters and sections in this text are not found in other handbooks: eg, Clinical Pearls for the Wards; Neonatal and Pediatric Nutrition including “TPN in 10 Steps;” and Stabilization, Delivery Room Care, and Initial Treatment of the VLBW Infant, to name a few. You will fi nd that Texas Children’s Hospital Handbook of Pediatrics and Neonatology offers concise, evidence-based information in an easy-to-access format that is directly applicable to bedside care of the patient in both pediatrics and neonatology. Although digital and electronic media have supplanted, in some cases, physical documents, handbooks, and texts, an effective pocket manual remains a crucial training tool, both as a repository for personal clinical experiences and as a point-of-care reference. We are certain that within this handbook you will fi nd the most important and relevant information for the white-coat of the trainee in pediatrics and neonatology. Wherever possible, helpful resources, including internet addresses and literature ref- erences, have been included directly in the text. Texas Children’s Hospital Handbook of Pediatrics and Neonatology will continue to evolve; current updates, as well as a vast amount of additional content, are available at www.AccessPediatrics.com. We are confi dent that you will fi nd this pocket manual invaluable as you learn the art and science of pediatrics and neonatology. Adam W. Lowry Kushal Y. Bhakta Pratip K. Nag Abbreviations

↔, nl normal ↓ decreased, decreasing, depressed, down → causes, results in, next ± possibly, consider ♀ female ♂ male Δ change in

1,25(OH)2-D 1,25-dihydroxy vitamin D 2/2 secondary to 2,3-DPG 2,3-diphosphoglycerol 25(OH) D 25-hydroxy vitamin D 5′-NT 5′-nucleotidase 6-MP 6-mercaptopurine AAA anti-actin antibody

A-aDO2 alveolar–arterial oxygen tension difference AAP American Academy of Pediatrics AAT α1 antitrypsin Ab antibody ABC airway, breathing, circulation abd abdominal ABER auditory brainstem-evoked response ABG arterial blood gas ABNL abnormal ABPA allergic bronchopulmonary aspergillosis ABR auditory brainstem response abx antibiotics AC assist control ACEI angiotensin-converting enzyme inhibitor ACL anterior cruciate ligament acL anticardiolipin ACOG American College of Obstetricians and Gynecologists ACS acute chest syndrome ACTH adrenocorticotropic hormone AD autosomal dominant ADA adenosine deaminase ADC apparent diffusion coefﬁ cient ADEM acute disseminated encephalomyelitis ADH antidiuretic hormone ADHD attention deﬁ cit hyperactivity disorder ADL activity of daily living AED antiepileptic drug AET atrial ectopic tachycardia AFB acid-fast bacilli Abbreviations xix

AFI amniotic fl uid index AFP α-fetoprotein AG anion gap Ag antigen AGE acute gastroenteritis AGEP acute generalized erythematous pustulosis AHA American Heart Association AHI apnea-hypopnea index (number of apneas + hypopneas per hour on polysomnography) AI aortic insuffi ciency; autoimmune AIDS acquired immune defi ciency syndrome AIH autoimmune hepatitis AIHA autoimmune hemolytic anemia AIN acute interstitial nephritis AKA alcoholic ketoacidosis AKI acute kidney injury Al+++ aluminum Ala alanine ALCAPA anomalous left coronary artery arising from the pulmonary artery ALD adrenoleukodystrophy Alk Phos alkaline phosphatase ALL acute lymphoblastic leukemia ALP alkaline phosphatase ALT alanine aminotransferase ALTE apparent life-threatening episode AMA antimitochondrial antibody AML acute myelogenous leukemia AMMoL acute myelomonocytic leukemia amox amoxicillin amp ampicillin ampho B amphotericin B AN anorexia nervosa ANA antinuclear antibody ANCA antineutrophil cytoplasmic antibody ANLL acute nonlymphoblastic leukemia anti-dsDNA Ab anti-double stranded DNA antibody anti-GAD Ab anti-glutamic acid decarboxylase antibodies anti-LC1 Ab anti-liver cytosol-antibody anti-LKM1 Ab anti-liver/kidney microsome antibody anti-LKM-1 antibodies to liver/kidney microsomes anti-SLA/LPAb anti-soluble liver/liver pancreas antigen antibody anti-TPOAb anti-thyroid peroxidase antibodies AOM acute otitis media AP anterior posterior; aortopulmonary APC antigen-presenting cell APTT activated partial thromboplastin time AR aortic regurgitation; autosomal recessive xx Abbreviations

ARB angiotensin receptor blocker ARDS acute respiratory distress syndrome ARF acute renal failure AROM artiﬁ cial rupture of membranes ARR absolute risk reduction ARVC arrhythmogenic right ventricular cardiomyopathy AS aortic stenosis ASA aminosalicylic acid (aspirin) ASD atrial septal defect ASMA anti–smooth muscle antibody Asp aspartate AST aspartate aminotransferase asx asymptomatic ATFL anterior taloﬁ bular ligament AT-II angiotensin-II ATN acute tubular necrosis ATP adenosine triphosphate ATRA all trans retinoic acid AUS abdominal ultrasound AV arteriovenous; atrioventricular AVB atrioventricular block AVCD atrioventricular canal defect AVM arteriovenous malformation AVN avascular necrosis AVP arginine vasopressin AXR abdominal X-ray BA bone age BAL British antilewisite; bronchoalveolar lavage BAS balloon atrial septostomy BCG bacillus Calmette-Guérin BCx blood culture BDG bidirectional Glenn BE barium enema β-HCG beta human chorionic gonadotropin BG blood glucose BID twice daily BiPAP bilevel positive airway pressure B/L bilateral BLS basic life support BM bowel movement BMA bone marrow aspirate BMD Becker muscular dystrophy; bone mineral density BMI body mass index BMP basic metabolic panel (see Chem 7) BMT bone marrow transplant BN bulimia nervosa Abbreviations xxi

BNP b-type natriuretic peptide BP blood pressure BPD bronchopulmonary dysplasia BPM beats per minute BPO benzoyl peroxide BSA body surface area BTS Blalock-Taussig shunt BUN blood urea nitrogen BV bacterial vaginosis BVH biventricular hypertrophy BW birthweight Bx biopsy C Celsius Ca calcium CA chronological age CAA coronary artery aneurysm CAD coronary artery disease CAH congenital adrenal hyperplasia CAIS complete androgen insensitivity syndrome CA-MRSA community-associated methicillin-resistant Staphylococcus aureus c-ANCA cytoplasmic antineutrophil cytoplasmic antibody cap refi ll capillary refi ll CAP community-acquired pneumonia CAVC complete atrioventricular canal CBC complete blood count CBD common bile duct CBG capillary blood gas CCAM congenital cystic adenomatoid malformation CCB calcium channel blocker CCK cholecystokinin CD clusters of differentiation; Crohn’s disease CDC Centers for Disease Control and Prevention CDH congenital diaphragmatic hernia CEA carcinoembryonic antigen CF complement fi xation; cystic fi brosis CFL calcaneofi bular ligament CFTR cystic fi brosis transmembrane conductance regulator CGA corrected gestational age CGD chronic granulomatous disease CH50 total hemolytic complement titer CHAOS congenital high airway obstruction syndrome CHB complete heart block; congenital heart block CHD congenital heart disease

Chem 7 chemistry panel (Na, K, Cl, HCO3, BUN, Cr, glucose) xxii Abbreviations

Chem 10 chemistry panel including all items of Chem 7 + Ca, Mg, Phos CHF congestive heart failure CHO carbohydrate chol cholesterol CI cardiac index; confi dence interval CK creatine kinase Cl chloride CLD chronic lung disease cm centimeter CMA chromosome microarray analysis CML chronic myeloid leukemia CMV cytomegalovirus CN cranial nerve CNS central nervous system CO carbon monoxide; cardiac output CONS coagulase-negative Staphylococcus COPD chronic obstructive pulmonary disease CP cerebral palsy CPAP continuous positive airway pressure CPD citrate–phosphate–dextrose CPK creatine phosphokinase CPP cerebral perfusion pressure CPR cardiopulmonary resuscitation CPS carbamoylphosphate synthase Cr creatinine CREST calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias CRF corticotropin-releasing factor CRI chronic renal insuffi ciency CRMO chronic recurrent multifocal osteomyelitis CRP C-reactive protein CRPS complex regional pain syndrome CRS congenital rubella syndrome CRT capillary refi ll time CS coronary sinus C-section caesarean section CSF cerebrospinal fl uid CT computed tomography CTA computed tomographic angiography CTD connective tissue disease CV cardiovascular CVA costovertebral angle CVL central venous line CVP central venous pressure CVS cardiovascular system Cx culture CXR chest X-ray Abbreviations xxiii cys cysteine d day d/c discontinue d/o disorder(s) D10 10% dextrose D10W 10% dextrose in sterile water D25 25% dextrose DA ductus arteriosus DBP diastolic blood pressure DC direct Coombs test DCM dilated cardiomyopathy DDAVP deamino-8-d-arginine vasopressin (desmopressin) DDH developmental dysplasia of the hip DDx differential diagnosis DEXA dual energy x-ray absorptiometry DFA direct fl uorescent antibody DFS disease-free survival DH direct hyperbilirubinemia DHEA dehydroepiandrosterone DHEAS dehydroepiandrosterone sulphate DHN dehydration DHS drug hypersensitivity syndrome DI diabetes insipidus DIC disseminated intravascular coagulation diff differential DILV double-inlet left ventricle DIOS distal intestinal obstruction syndrome DIP distal interphalangeal div divided DKA diabetic ketoacidosis DKS Damus-Kaye-Stansel dL deciliter DLCO diffusing lung capacity DM diabetes mellitus; dermatomyositis DMARD disease-modifying antirheumatic drug DMD Duchenne muscular dystrophy DMSA dimercaptosuccinic acid DMSO dimethyl sulfoxide DNA deoxyribonucleic acid DOL day of life DORV double-outlet right ventricle DRESS drug reaction with eosinophilia and systemic symptoms DSD disorders of sex differentiation DSM-IV Diagnostic and Statistical Manual of Mental Disorders, 4th ed DTaP diphtheria toxoid, tetanus toxoid, and acellular pertussis xxiv Abbreviations d-TGA d-transposition of the great arteries DTR deep tendon refl ex DUB dysfunctional uterine bleeding DVT deep venous thrombosis DWI diffusion weighted imaging dx diagnosis dz disease EB epidermolysis bullosa EBM evidence-based medicine, expressed breast milk EBV Epstein-Barr virus eCCl estimated creatinine clearance ECF extracellular fl uid ECG electrocardiogram ECHO echocardiogram ECMO extracorporeal membrane oxygenation ED emergency department EEC ectodermal dysplasia, ectrodactyly, cleft EEG electroencephalogram EFS event-free survival eg for example EGD esophagogastroduodenoscopy EHK epidermolytic hyperkeratosis EIA enzyme immunoassay EKG electrocardiogram ELBW extremely low birth weight ELISA enzyme-linked immunoassay EM electron microscopy EMA endomysial antibodies EMB ethambutol EMG electromyogram endo endocrine ENT Ears, nose, and throat EOG electrooculogram EPAP expiratory positive airway pressure EPS extrapyramidal symptoms ERCP endoscopic retrograde cholangio– pancreatography ERV expiratory reserve volume ESR erythrocyte sedimentation rate ESRD end-stage renal disease

ETCO2 end-tidal carbon dioxide ETEC enterotoxigenic Escherichia coli ETOH alcohol (ethanol) ETT endotracheal tube EUS endoscopic ultrasonography EWS Ewing sarcoma F Fahrenheit f/b followed by Abbreviations xxv

FB foreign body FDA Food and Drug Administration FDP ﬁ brin degradation product FE fractional excretion

FEF25%–75% forced midexpiratory ﬂ ow rate

FENa fractional excretion of sodium

FEV1 forced expiratory volume in 1 second FFP fresh-frozen plasma FHx family history

FiO2 fractional inspired oxygen FISH fl uorescent in-situ hybridization fL femtoliter FLAIR fl uid attenuated inversion recovery FOB fecal occult blood FOC frontal–occipital circumference Fr French FRC functional residual capacity FS fi ngerstick FSBG fi ngerstick blood glucose FSGS focal segmental glomerulosclerosis FSH follicle-stimulating hormone FT4 free thyroxine FTA-ABS fl uorescent treponemal antibody absorption FTT failure to thrive f/u follow-up FUO fever of unknown origin FVC forced vital capacity Fx fracture g gram G6PD glucose-6-phosphate dehydrogenase GA gestational age GABA γ-aminobutyric acid GABHS group A β-hemolytic streptococcus GALT galactose-1-phosphate uridyltransferase GAS group A streptococcus GBM glioblastoma multiforme GBS group B streptococcus; Guillain-Barré syndrome GC glucocorticoid; gonococcus GCS Glasgow Coma Scale GCSF granulocyte colony-stimulating factor GCT germ cell tumor GDM gestational diabetes mellitus GE gastroenteritis GER gastroesophageal refl ux GERD gastroesophageal refl ux disease GFR glomerular fi ltration rate GGT γ-glutamyl transpeptidase GH growth hormone xxvi Abbreviations

GHB δ-hydroxybutyrate GHBP growth hormone binding protein GI gastrointestinal GIR glucose infusion rate Glc glucose Gln glutamine Glu glutamic acid Gly glycine GN glomerulonephritis GNR gram-negative rod GnRH gonadotrophin-releasing hormone GSD glycogen storage disease GT genotype GU genitourinary GVHD graft-versus-host disease h hour H&P history and physical examination HO house ofﬁ cer h/o history of H+/K+ ATPase hydrogen/potassium adenosine triphosphatase (proton pump) H2RA histamine-2-receptor antagonist HA headache HAV hepatitis A virus Hb hemoglobin HBcAb hepatitis B core antibody HBeAg hepatitis B e antigen Hb F hemoglobin F HBIG hepatitis B immune globulin HBsAg hepatitis B surface antigen HCC hepatocellular carcinoma hCG human chorionic gonadotropin HCM hypertrophic cardiomyopathy − HCO3 bicarbonate HCV hepatitis C virus HD hemodialysis; Hirschsprung’s disease; Hodgkin’s disease HDAg hepatitis D antigen HDL high-density lipoprotein HDV hepatitis D virus HEENT head, eyes, ears, nose, and throat HELLP hemolytic anemia, elevated liver enzymes, low platelets Hep B hepatitis B HEV hepatitis E virus HFOV high-frequency oscillatory ventilation HbA1C glycosylated hemoglobin A1c HH hereditary hemochromatosis Abbreviations xxvii

HHRH hereditary hypophosphatemic rickets with hypercalciuria HHS hyperglycemic hyperosmolar state HHV human herpesvirus Hib Haemophilus infl uenzae type b HIDA hepatobiliary iminodiacetic acid HIE hypoxic-ischemic encephalopathy HIG human immune globulin HIT heparin-induced thrombocytopenia HIV human immunodefi ciency virus HLH hemophagocytic lymphohistiocytosis HLHS hypoplastic left heart syndrome HMG-CoA 3-hydroxy-3-methylglutaryl–CoA HOCM hypertrophic obstructive cardiomyopathy HPA human platelet antigen HPF high-power fi eld HPV human papillomavirus HR heart rate hr hours HRCT high-resolution computed tomography HSCT hematopoietic stem cell transplant HSM hepatosplenomegaly HSP Henoch-Schonlein purpura HSR hypersensitivity reaction HSV herpes simplex virus ht height HTN hypertension HUS hemolytic uremic syndrome HVA homovanillic acid Hx history I&D incision and drainage IA insulin antibodies IAA insulin autoantibody; interrupted aortic arch IAP intrapartum antibiotic prophylaxis IBD infl ammatory bowel disease IBS irritable bowel syndrome IBW ideal body weight I:C insulin to carbohydrate IC inspiratory capacity iCa ionized calcium ICA islet cell antibody ICD implantable cardioverter/defi brillator ICP intracranial pressure ICS inhaled corticosteroids ICU intensive care unit ID infectious disease IDDM insulin-dependent diabetes mellitus IDM infant of a diabetic mother xxviii Abbreviations ie that is I:E ratio of inspiratory time to expiratory time IE infective endocarditis IEM inborn errors of metabolism IF immunofl uorescence IFA immunofl uorescent antibody IGFBP-3 insulin-like growth factor binding protein 3 Ig immunoglobulin IgA immunoglobulin A IgE immunoglobulin E IGF insulin-like growth factor IGF-BP insulin-like growth factor binding protein IgG immunoglobulin G IgM immunoglobulin M IGT impaired glucose tolerance IHA indirect hemagglutination assay IHS International Headache Society IHST immediate hypersensitivity skin test ILD interstitial lung disease Ile isoleucine IM intramuscular INH isoniazide iNO inhaled nitric oxide INR International Normalized Ratio IO intraocular; intraosseous IP interphalangeal IPAP inspiratory positive airway pressure IPV intrapulmonary percussive ventilation IR internal rotation IRT immunoreactive trypsinogen IRV inspiratory reserve volume IT iliotibial; intrathecal ITP idiopathic thrombocytopenic purpura Itra itraconazole IU international units IUD intrauterine device IUGR intrauterine growth restriction IV intravenous IVC inferior vena cava IVDU IV drug user IVF intravenous fl uids; in-vitro fertilization IVH intraventricular hemorrhage IVIG intravenous immunoglobulin IVS intact ventricular septum; interventricular septum JAS juvenile ankylosing spondylitis JCA juvenile chronic arthritis JDMS juvenile dermatomyositis Abbreviations xxix

JEB junctional epidermolysis bullosa JIA juvenile idiopathic arthritis JIIM juvenile idiopathic inﬂ ammatory myopathies JMML juvenile myelomonocytic leukemia JRA juvenile rheumatoid arthritis JVD jugular venous distension JVP jugular venous pulse or pulsation K potassium KCl potassium chloride KD Kawasaki disease kg kilogram KI potassium iodide KOH potassium hydroxide KUB kidneys, ureters, and bladder x-ray (abdominal x-ray) L liter LA left atrium; lupus anticoagulant LABA long-acting β-agonist LCT long-chain triglycerides LAD lymphadenopathy; left axis deviation; left anterior descending (coronary artery) LAE left atrial enlargement lb pounds LBBB left bundle branch block LBW low birthweight LCA left coronary artery LCFA long-chain fatty acids LCH Langerhans cell histiocytosis LDH lactate dehydrogenase LDL low-density lipoprotein LES lower esophageal sphincter Leu leucine LFT liver function test (liver panel); generally includes at a minimum albumin, total protein, bilirubin (total and direct), alanine and aspartate aminotransferases, alkaline phosphatase LGA large for gestational age LH luteinizing hormone Li lithium LIP lymphoid interstitial pneumonia LLSB left lower sternal border LM light microscopy LMP last menstrual period LMWH low-molecular-weight heparin LOC level of consciousness LP lumbar puncture LPA left pulmonary artery xxx Abbreviations

LQTS long QT syndrome LR lactated Ringer’s solution; likelihood ratio LRT lower respiratory tract LRTI lower respiratory tract infection LTBI latent tuberculosis infection LUSB left upper sternal border LV left ventricular LVEDP left ventricular end-diastolic pressure LVH left ventricular hypertrophy LVNC left ventricular noncompaction LVOT left ventricular outfl ow tract LVOTO left ventricular outfl ow tract obstruction Lys lysine Lytes electrolytes (Na, K, Cl, often includes bicarbonate) m2 meter squared MAC Mycobacterium avium complex MAG-3 mercaptoacetyltriglycine MAI Mycobacterium avium intracellulare MAP mean airway pressure MAS macrophage activation syndrome; meconium aspiration syndrome MCD minimal change disease mcg microgram MCH mean corpuscular hemoglobin MCL medial collateral ligament MCP metacarpophalangeal MCT medium-chain triglycerides MCTD mixed connective tissue disease MCV mean corpuscular volume MD myotonic dystrophy MDI metered-dose inhaler MDS myelodysplastic syndrome MEE middle ear effusion MELAS mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes MEN multiple endocrine neoplasia mEq milliequivalent Met methionine Mg magnesium mg milligram MGN membranous glomerulonephritis MH microscopic hematuria MHA-TP microhemagglutination assay for antibodies to Treponema pallidum MHC major histocompatibility class MIBG methyliodobenzylguanidine micro microanalysis; microscopic Abbreviations xxxi min minutes MIVF maintenance intravenous fl uids mL milliliter MM mucous membrane MMR measles, mumps, rubella mo months MODY maturity onset diabetes of youth MPA main pulmonary artery; milk protein allergy MPGN membranoproliferative glomerulonephritis MPH mid-parental height MPO myeloperoxidase MPS mucopolysaccharidosis MR mitral regurgitation MRA magnetic resonance angiography MRCP magnetic resonance cholangiopancreatography MRD minimal residual disease MRI magnetic resonance imaging MRS magnetic resonance spectroscopy MRSA methicillin-resistant Staphylococcus aureus MRV magnetic resonance venogram MS mental status; mitral stenosis MSAFP maternal serum alpha-fetoprotein MSG monosodium glutamate MSM men who have sex with men MSSA methicillin-sensitive Staphylococcus aureus MSUD maple syrup urine disease MT metatarsal MTB Mycobacterium tuberculosis MTHFR methyltetrahydrofolate reductase MTP metatarsophalangeal MTX methotrexate MV minute volume; mitral valve MVA motor vehicle accident MVP mitral valve prolapse Na sodium N/A not applicable NAAT nucleic acid amplifi cation test NAC N-acetylcysteine NAI non-accidental injury NAIT neonatal alloimmune thrombocytopenia NAS neonatal abstinence scoring NASH nonalcoholic steatohepatitis NASPGHAN North American Society for Pediatric Gastroenterology, Hepatology and Nutrition NAT non-accidental trauma NB nota bene NBL neuroblastoma NBS newborn screen xxxii Abbreviations

NC nasal cannula NCPAP nasal continuous positive airway pressure NEC necrotizing enterocolitis NF neuroﬁ bromatosis ng nanograms NG nasogastric NGT nasogastric tube

NH3 ammonia NHL non-Hodgkin’s lymphoma NICU neonatal intensive care unit NIH National Institutes of Health NIV noninvasive ventilation NK natural killer nl normal NLE neonatal lupus erythematosus NMB neuromuscular blockade NMJ neuromuscular junction NMT nebulized mask treatment NNT number needed to treat NPO nil per os (nothing by mouth) NS normal saline NSAID nonsteroidal antiinﬂ ammatory drug NSR normal sinus rhythm NTB nontuberculous NTD neural tube defect N/V nausea/vomiting O&P ova and parasite

O2 oxygen OA organic acids OAE otoacoustic emissions OCD obsessive–compulsive disorder; osteochondritis dissecans OCP oral contraceptive OCRG oxycardiorespirogram OEIS omphalocele, cloacal exstrophy, imperforate anus, spinal defects OG orogastric OGES oral glucose–electrolyte solution OGTT oral glucose tolerance test OHV obesity hypoventilation syndrome OI obesity imperfecta OLT orthotopic liver transplantation OME otitis media with effusion ONTD open neural tube defect OP organophosphate ophth ophthalmic solution ORIF open reduction with internal ﬁ xation Orn ornithine Abbreviations xxxiii

ORS oral rehydration solution Osm obstructive sleep apnea OSAS obstructive sleep apnea syndrome Osm osmolality OT occupational therapy OTC ornithine transcarbamylase; over-the-counter oz ounces Phos phosphorus P2 pulmonic component of second heart sound PA postero-anterior; pulmonary atresia; pulmonary artery PAA plasma amino acids PAB pulmonary artery band

PaCO2 arterial carbon dioxide tension (partial pressure) PAF platelet-activating factor PAH pulmonary artery hypertension PA/IVS pulmonary atresia with intact ventricular septum PALS pediatric advanced life support PAN polyarteritis nodosa p-ANCA perinuclear antineutrophil cytoplasmic antibody

PaO2 partial pressure of oxygen in arterial blood Pap Papanicolaou PAPP-A pregnancy-associated plasma protein A PAPVC partial anomalous pulmonary venous connection PAPVR partial anomalous pulmonary venous return PAS periodic acid-Schiff

PB barometric pressure (~760 mm Hg at sea level) PBF pulmonary blood ﬂ ow PC platelet count; pressure control PCA patient-controlled analgesia PCL posterior collateral ligament of knee PCN penicillin PCOS polycystic ovarian syndrome PCP phencyclidine; primary care provider PCR polymerase chain reaction PCV packed cell volume PCV7 7-valent pneumococcal conjugate vaccine PD peritoneal dialysis PDA patent ductus arteriosus PDD pervasive developmental disorder PDE phosphodiesterase PE physical exam; pulmonary embolism, pulmonary edema PEEP positive end-expiratory pressure PEF peak expiratory ﬂ ow PEG polyethylene glycol xxxiv Abbreviations

PEG 3350 polyethylene glycol powder (Miralax) PEP positive expiratory pressure PET positron emission tomography PFC persistent fetal circulation PFO patent foramen ovale PFT pulmonary function testing

PGE1 prostaglandin E1 PHA pseudohypoaldosteronism Phe phenylalanine Phos phosphorous PI primary immunodefi ciency, protease inhibitor PICC percutaneously inserted central catheter PICU pediatric intensive care unit PID pelvic infl ammatory disease PIE pulmonary interstitial emphysema PIGN post-infectious glomerulonephritis PIP peak infl ation pressure; peak inspiratory pressure; proximal interphalangeal PIV peripheral intravenous (catheter) PK pyruvate kinase PKD polycystic kidney disease PKU phenylketonuria PMA postmenstrual age PMD primary medical doctor PMH past medical history PMI point of maximal impulse PML promyelocytic leukemia PMN polymorphonuclear cells PNET primitive neuroectodermal tumor PNH paroxysmal nocturnal hemoglobinuria PO per os (by mouth)

PO2 partial pressure of oxygen POC point of care POPE postobstructive pulmonary edema PPD puriﬁ ed protein derivative PPHN persistent pulmonary hypertension of newborn PPI proton pump inhibitor PPNET peripheral primitive neuroectodermal tumor PPROM preterm prolonged rupture of membranes PPS peripheral pulmonary stenosis PPV positive predictive value; positive pressure ventilation PR per rectum; pityriasis rosea; pulmonary regurgitation PRBC packed red blood cell Pro proline PROM passive range of motion; prolonged rupture of membranes Abbreviations xxxv

PS pressure support; pulmonary stenosis PSC primary sclerosing cholangitis PSG polysomnography PSH past surgical history pSLE pediatric systemic lupus erythematosus pt patient PT physical therapy; prothrombin time PTFL posterior talofi bular ligament PTH parathyroid hormone PTHrP persistent parathyroid hormone–related peptide PTSD posttraumatic stress disorder PTT partial thromboplastin time PTX pneumothorax PUBS percutaneous umbilical blood sampling PUD peptic ulcer disease pulm pulmonary PUV posterior urethral valve PUVA psoralen with ultraviolet A PVL periventricular leukomalacia PVM pulmonary vascular markings PVR pulmonary vascular resistance PWS port-wine stain Px prognosis PZA pyrazinamide Q every Qhs every night QID four times a day QIg quantitative immunoglobulins Qp pulmonary blood fl ow Qs systemic blood fl ow QTc corrected QT interval RA rheumatoid arthritis, right atrium RAA right atrial appendage RAD right axis deviation RAE right atrial enlargement RAST radioallergosorbent test RBBB right bundle branch block RBC red blood cell RCA right coronary artery RCM restrictive cardiomyopathy RCT randomized, controlled trial RDEB recessive dystrophic epidermolysis bullosa RDS respiratory distress syndrome RDW red cell distribution width RES reticuloendothelial system resp respiratory retic reticulocyte RF rheumatoid factor xxxvi Abbreviations

RHD rheumatic heart disease RIA radioimmunoassays RIF rifampin RNA ribonucleic acid RNC radionuclide cystogram RNP ribonucleoprotein r/o rule out ROM range of motion ROP retinopathy of prematurity ROS review of systems RP Raynaud’s phenomenon RPGN rapidly progressive glomerulonephritis RPR rapid plasma reagin rpt repeat RR respiratory rate; risk ratio RRR relative risk reduction RSV respiratory syncytial virus RTA renal tubular acidosis RUQ right upper quadrant RV residual volume; right ventricle RVEDP right ventricular end-diastolic pressure RVH right ventricular hypertrophy RVOT right ventricular outﬂ ow tract RVOTO right ventricular outﬂ ow tract obstruction Rx prescription; treatment rxn reaction SAA serum amino acids; serum amyloid A SABA short-acting β-agonist

SaO2 systemic arterial oxygen saturation SAPHO syndrome of synovitis, acne, pustulosis, hyperostosis, and osteitis SBBO small bowel bacterial overgrowth SBE subacute bacterial endocarditis SBFT small bowel follow-through SBI serious bacterial infection SBP systolic blood pressure SBS short bowel syndrome SCD sickle cell disease; sudden cardiac death SCFE slipped capital femoral epiphysis SCID severe combined immunodeﬁ ciency SCM sternocleidomastoid SCT stem cell transplant SD standard deviation SE side effects SEM systolic ejection murmur SES socioeconomic status SG speciﬁ c gravity SGA small for gestational age Abbreviations xxxvii

SGS short gut syndrome SHBG steroid hormone–binding globulin SI sacroiliac SIADH syndrome of inappropriate antidiuretic hormone secretion SIDS sudden infant death syndrome SIMV synchronized intermittent mandatory ventilation SIRS systemic inﬂ ammatory response syndrome SJS Stevens-Johnson syndrome SLE systemic lupus erythematosus SMA spinal muscular atrophy; superior mesenteric artery SMV superior mesenteric vein SOB shortness of breath SPECT single-photon emission computed tomography

SpO2 oxygen saturation s/p status post spp. species SSRI selective serotonin reuptake inhibitors SSTI skin and soft tissue infections Staph staphylococcus STI sexually transmitted infection STS soft tissue sarcoma sub-Q subcutaneous SVC superior vena cava

SVCO2 superior vena cava oxygen saturation SVR systemic vascular resistance SVT supraventricular tachycardia SWI susceptibility weighted imaging sx symptoms T&A tonsillectomy & adenoidectomy T1DM type 1 diabetes mellitus T3 triiodothyronine

T4 thyroxine TA tricuspid atresia; truncus arteriosus TAPVC total anomalous pulmonary venous connection TAPVR total anomalous pulmonary venous return TAR thrombocytopenia with absent radius TB tuberculosis TBG thyroid-binding globulin TBI traumatic brain injury TBSA total body surface area TBW total body water TCA tricyclic antidepressant TcB transcutaneous bilirubin TCH Texas Children’s Hospital TCI topical calcineurin inhibitor TCS topical corticosteroid xxxviii Abbreviations

Td tetanus toxoid, diphtheria toxoid TDID total daily insulin dose TDx-FLM (commercial fetal lung maturity assay)

Te expiratory time TEE transesophageal echocardiography TEF tracheoesophageal ﬁ stula TEG thromboelastography platelet mapping TEN toxic epidermal necrolysis TFPI tissue factor pathway inhibitor TFT thyroid function test TG triglycerides TGA transposition of the great arteries TH thyroid hormone

Ti inspiratory time TIBC total iron-binding capacity TID three times daily TIPS transjugular intrahepatic portosystemic shunt TLC total lung capacity TLSO thoracic lumbosacral orthosis TM tympanic membrane TMJ temporomandibular joint TMP trimethoprim TMP/SMX trimethoprim/sulfamethoxazole TNF tumor necrosis factor TOA tubo-ovarian abscess TOF tetralogy of Fallot TOF/PA tetralogy of Fallot with pulmonary atresia TORCH toxoplasmosis, other (varicella, parvovirus), rubella, cytomegalovirus, herpes, HIV, syphilis tox toxicology TP total protein tPA tissue plasminogen activator TPN total parenteral nutrition TR tricuspid regurgitation TRALI transfusion-related acute lung injury TRH thyroid-releasing hormone TS tricuspid stenosis TSB total serum bilirubin TSH thyroid-stimulating hormone TSS toxic shock syndrome TST tuberculin skin test

TT4 total thyroxine TTE transthoracic echocardiography TTG tissue transglutaminase TTN transient tachypnea of newborn TTP thrombotic thrombocytopenic purpura TV tricuspid valve; tidal volume tx therapy Abbreviations xxxix

Tyr tyrosine UA urinalysis UAC umbilical arterial catheter UAG urine anion gap UAW upper airway UC ulcerative colitis UCL ulnar collateral ligament UDCA ursodeoxycholic acid UFH unfractionated heparin UGI upper gastrointestinal series UGT uridine diphosphate glucuronosyltransferase U/L upper to lower body segment ratio UOA urine organic acids UOP urine output

UProt:UCr urinary protein to urinary creatinine ratio UPJ ureteropelvic junction UPT urine pregnancy test URAP unidirectional retrograde accessory pathway URI upper respiratory infection URTI upper respiratory tract infection US ultrasonography UTI urinary tract infection UV ultraviolet UVB ultraviolet B UVC umbilical venous catheter V/D vomiting/diarrhea VACTERL vertebral anomalies, anal atresia, cardiovascular anomalies, tracheoesophageal ﬁ stula, esophageal atresia, renal or radial anomalies, and limb defects Val valine VATER vertebral anomalies, anal atresia, tracheoesophageal ﬁ stula, esophageal atresia, and renal or radial anomalies VATS video-assisted thoracoscopic surgery VBG venous blood gas VC vital capacity; volume control

VCO2 CO2 production VCUG voiding cystourethrography; voiding cystourethrogram

VD dead space VDRL Venereal Disease Research Laboratory VG volume guarantee VHL von Hippel-Lindau VIP vasoactive intestinal polypeptide VLBW very low birth weight VLDL very low-density lipoprotein VMA vanillylmandelic acid xl Abbreviations

VO2 oxygen uptake VOD veno-occlusive disease VPA valproic acid VPS ventriculoperitoneal shunt V/Q ventilation-perfusion VRE vancomycin-resistant Enterococcus VS volume support VSD ventricular septal defect

VT tidal volume VT ventricular tachycardia VTE venous thromboembolism VU vesicoureteral VUR vesicoureteral reﬂ ux vWD von Willebrand disease vWF von Willebrand factor VZIG varicella zoster immunoglobulin VZV varicella zoster virus w/u work up WBC white blood cell WBG whole-blood glucose wk week WNL within normal limits WPW Wolff-Parkinson-White syndrome WT Wilms tumor wt weight XLHR X-linked hypophosphatemic rickets XR X-ray y year yo years old yr years ZES Zollinger-Ellison syndrome GENERAL CLINICAL INFORMATION ) 2 restrictions Preoperative studies Diet: NPO/IVF after midnight, and so on Consent form signed and on chart H&P reviewed return, where to return, and so on monitoring, and so on Discharge instructions: When and why to Follow-up appointments Discharge medications Special needs: Home health needs, system based) Problem list (prioritized) Assessment or plan (problem based or • • • • • • • • • • 1 edications: Name, dose (also specify mg/kg), frequency, route, duration, reason edications: Name, dose (also specify mg/kg), frequency, route, ursing/respiratory: strict I/O, daily weights, turn patient q shift, dressing care and ursing/respiratory: strict I/O, iagnoses (prioritized) requirements (ie, ADA, low fat, low calorie), iet: Regular, clear liquid, special ondition: Good, fair, poor, guarded, critical ondition: Good, fair, poor, guarded, itals and monitoring: Frequency of monitoring (eg, q4, q shift, per routine), type of itals and monitoring: Frequency llergies: Medication and food ctivity: Ad lib, bed rest with or without bathroom privileges, crib with side rails up, ctivity: Ad lib, bed rest with or dmit to: Floor, service, MD abs tudies VF: Type, volume, rate (specify mL/hr for all; for infants, also specify mL/kg/d) VF: Type, volume, rate (specify bjective: limitations, and so on Admit date Admit diagnoses (prioritized) Hospital course summary Physical examination Discharge: When, to where Diagnoses (prioritized) Diet Condition Activity: Ad lib, bedrest, physical (ie, 2-g sodium renal diet), NPO change from previous) orders) restrictions, ambulate TID, and so on restrictions, ambulate TID, and Foley care, suctioning, pulmonary toilet changes, drain care, NG care, monitoring (eg, continuous oximetry, telemetry, arterial line, CVP, end-tidal CO monitoring (eg, continuous oximetry, I/O: Totals and components of IVF, PO intake, emesis, residuals, urine, stool, drains I/O: Totals and components of IVF, PO intake, emesis, residuals, Vitals: Temperature, HR, RR, blood pressure, oxygen saturation, weight (including Vitals: Temperature, HR, RR, blood pressure, oxygen saturation, Diagnoses (prioritized) Procedure Preoperative labs (including blood bank A I M C L V N D A D S A ubjective: Patient comments or complaints, nursing comments, relevant events ubjective: Patient comments or complaints, nursing comments, • • • • • • • • • • • NOTES On-Service Note Progress Note (SOAP Note) S O Discharge Orders • • • • • Preoperative Orders • • • • • • • • • CHAPTER 1 Pearls for the Wards Clinical ORDERS Admission Orders (ADC VANDALISM) • Section 1: General Clinical Information Clinical 1: General Section 2 General Clinical Information

• Physical examination (focused) • Medicines: All current medicines with weight-based dose (scheduled and prn) • Laboratory and test data: New or pending Assessment: Analysis of above, including differential dx or tentative dx Plan (problem based or system based) Discharge Summary (usually dictated) • Admission and discharge date • Disposition: To outside hospital, home, • Admission and discharge diagnoses hospice, and so on (prioritized) • Discharge medications: Name, • Service: Service name, attending physician, formulation, dosage, length of resident(s) treatment, reﬁ lls • Consulting services • Discharge activity • Procedures • Discharge diet • Physical examination and vitals (admission) • Discharge instructions: Dressing or • Hospital course (system based or problem cast care, symptoms to warrant further based, pertinent labs and studies) treatment, where to return for further • Physical examination and vitals (discharge) treatment, and so on • Discharge condition: Improved, good • Follow-up appointments PRESCRIPTION WRITING: ESSENTIAL COMPONENTS

Identifying Information: Name, date, weight, DOB Rx: Drug name, strength, formulation (ie, amoxicillin 250mg/5mL suspension)

SIG: Quantity (mL, tablets, capsules, puﬀ s, and so on), route, frequency, duration (specify mg/kg when possible) DISP: Number or volume to be dispensed Other: Number of reﬁ lls? Substitution acceptable? Flavoring acceptable? Language?

GROWTH PEARLS WEIGHT, HEIGHT, AND HEAD CIRCUMFERENCE: 5TH, 50TH, AND 95TH PERCENTILES

Boys Age∗ Height (cm) Weight (kg) FOC (cm) 0 mo 46-50-54 2.5-3.5-4.3 32-36-39

0.5 mo 49-53-57 3.0-4.0-4.9 34-37-40 1.5 mo 53-57-61 3.8-4.9-6.0 36-39-42 3.5 mo 58-62-67 5.2-6.4-7.8 39-42-44 6.5 mo 64-68-73 6.7-8.2-9.9 42-44-46 9.5 mo 68-72-77 7.9-9.5-11.4 43-45-48 1 yr 72-76-81 8.8-10.5-12.6 44-46-48 2 yr† 82-88-94 10.7-12.7-15.3 46-49-51 3 yr 89-95-102 12.0-14.3-17.4 47-50-52 4 yr 96-103-110 13.6-16.3-20.3 — 5 yr 101-109-117 15.2-18.5-23.5 —

10 yr 128-139-150 24.9-32.1-46.1 —

(continued on next page) GENERAL INFORMATION CLINICAL

Clinical Pearls for the Wards 3

Girls Age∗ Height (cm) Weight (kg) FOC (cm) 0 mo 46-49-54 2.5-3.4-4.2 32-35-38

0.5 mo 48-52-56 2.9-3.8-4.6 34-36-39

1.5 mo 51-55-59 3.5-4.5-5.5 36-38-41

3.5 mo 56-60-65 4.7-5.9-7.1 38-40-43

6.5 mo 62-66-70 6.1-7.5-9.0 41-43-45

9.5 mo 66-71-75 7.2-8.7-10.4 42-44-46

1 yr 69-74-79 8.1-9.7-11.6 43-45-47

2 yr† 80-86-92 10.3-12.1-14.7 45-48-50 3 yr 88-94-101 11.6-13.9-17.2 46-49-51

4 yr 94-101-108 13.1-15.9-20.4 —

5 yr 100-108-116 14.7-18.0-23.8 —

10 yr 127-138-150 24.8-33.1-48.2 —

∗Data available in half-month increments; thus, values for 1 year are actually for 12.5 m, 2-year values are for 24.5 mo, and so on. †Data obtained from a 0- to 36-month-old cohort; values are slightly diﬀ erent in the 2- to 20-year cohort.

Weight • Average birth weight: 3.2 kg (girls); 3.6 kg (boys) • Regain birthweight by 7 to 14 days (7–10 days for term infants; 10–14 days for preterm infants) • Doubles in 4 mo, triples in 12 mo, quadruples in 24 mo Weight (Rate of Gain) • 0–3 mo → 20–30 g/d • 2 yr–puberty → 0.5 lb/mo or 2 kg/yr∗ • 3 mo–6 mo → 20 g/d (∗Abnormal prepubertal velocity = <1 kg/yr wt • 6 mo–1 yr → 10 g/d or 1 lb/mo gain)

Height • Average birth length, 50 cm • Doubles in 3 to 4 years; triples by 13 years • Infant growth rate, 0.8 to 1.1 cm/wk • Often grow in 8-wk spurts separated by periods of slow growth or stasis (~18 d) • Reach half of adult height by 2 to 2.5 years (see Endocrinology chapter for more detail) • First 6 mo: Growth rate infl uenced by intrauterine environment • Male growth spurt during Tanner 4–5; female during Tanner 3–4 Height (Rate of Gain) • Rule of thumb: 10-4-3-3-2 (inches gained per year until 5 years) • Gain average of 10 inches in fi rst year of life, 4 inches in second year, 3 inches in third year, 3 inches in fourth year, and 2 inches in fi fth and each subsequent year until puberty • Abnormal prepubertal height velocity <2 in/yr ht gain

Head Circumference (FOC) • Average birth FOC: Girls, 35 cm; boys, 36 cm • Usually 1 to 2 cm greater than chest circumference at birth • Most head growth complete by 4 years • Brain weight doubles by 4 to 6 months and triples by 1 year (similar to overall weight) 4 General Clinical Information

FOC (Rate of Gain) • 0–3 mo → 2 cm/mo • 6–12 mo → 0.5 cm/mo • 3–6 mo → 1 cm/mo • 12–24 mo → 2 cm total Fontanelle • The posterior fontanelle closes by age 4 mo. • The anterior fontanelle is smaller by age 6 mo and is closed by age 9 to 18 mo (workup if open at 18 mo).

Sutures • Usually all closed by age 12 to 24 mo, ossiﬁ ed by 8 years, and, completely fused by early adulthood PREMATURITY • Catch-up: FOC by 18 mo, weight by 24 mo, height by 40 mo (correct for gestational age until these age limits when plotting) • Exception: VLBW (very low-birth weight) infants: Girls catch up by 20 years, but boys remain shorter and lighter than control subjects TEMPERATURE AND WEIGHT CONVERSION °F = (°C × 9/5) + 32 °C = (°F − 32) × 5/9 Kg = lb/2.2 Pounds = kg × 2.2 Grams = lb × 454 BODY SURFACE AREA Quick Approximation #1 (Using Weight Only) 1–5 kg BSA = (wt in kg × 0.05) + 0.05 6–10 kg BSA = (wt in kg × 0.04) + 0.1 11–20 kg BSA = (wt in kg × 0.03) + 0.2 21–40 kg BSA = (wt in kg × 0.02) + 0.4 > 40 kg BSA = (wt in kg × 0.01) + 0.8 Quick Approximation #2 (Using Weight Only) (most accurate >10 kg) BSA = (kg × 4) + 7/(90 + kg)

Mosteller’s Formula (N Engl J Med. 1987;317(17):1098)

height(cm)× weight(kg) BSA(m2 )= 3,600

PRE-PROCEDURAL DIET GUIDELINES

Procedure Diet Recommendations

Barium enema Normal∗

Bone scan Normal

Bronchoscopy NPO: 4–6 h

(continued on next page) GENERAL INFORMATION CLINICAL

Clinical Pearls for the Wards 5

Procedure Diet Recommendations

CT scan with contrast: Abdomen, NPO: 6 h, food and formula; 4 h, EBM; 2 h, clears body

CT scan with or without contrast: Normal Head 3-D CT scan: Head NPO: 6 h, food and formula; 4 h, EBM; 2 h, clears Echocardiography (sedated) NPO: 4 h, food and formula; 2 h, EBM and clears Fluoroscopy Normal Gastric emptying study NPO: 4 h HIDA scan <6 mo, normal; >6 mo, NPO 4 h Interventional radiology procedure NPO: 6 h, food and formula; 4 h, EBM; 2 h clears Milk scan NPO: 4 h MRI (when sedation is necessary) NPO: 6 h, food and formula; 4 h; EBM; 2 h, clears NG / NJ tube insertion Normal Renal ﬂ ow with magnesium Normal Renal scan DMSA Normal Renal scan with Lasix Normal Swallow study NPO: 2–3 h Ultrasonography, abdominal NPO: 4 h Ultrasonography, hip Normal Ultrasonography, renal Normal Upper GI (UGI) with or without NPO: 4 h small bowel follow-through VCUG Normal

∗no speciﬁ c pre-procedural limitations/restrictions

EAR WAX MANAGEMENT Why Not Remove Cerumen? • Natural cerumen turnover: Produced in the outer third of the external canal; daily chewing and growth of the ear canal lining slowly transition cerumen outward • Contains natural bacteriostatic agents • Protects the eardrum from external debris • Protects the lining of the ear canal Cerumen Impaction Affects ~10% of children, 5% adults, and 35% of adults and children with mental retardation; often secondary to anatomy; increased number of external auditory canal hairs, use of devices such as cotton swabs or ear candles Cerumen Removal (evidence limited) • Indicated: Cerumen impaction, hearing loss 2/2 cerumen, physical examination of the outer ear structures or tympanic membrane. • Methods: Manual, ceruminolytics, irrigation. • In trials, no ceruminolytic is consistently superior to saline; therefore, saline is the ﬁ rst- line ceruminolytic; it can be left in the ear canal for 15 to 30 min after failed irrigation attempt before repeating (Br J Gen Pract. 2004;54:862–867). 6 General Clinical Information

• First irrigation unsuccessful → Ceruminolytic for 15 to 30 min; repeat • Second irrigation unsuccessful → Ceruminolytic BID for 2 to 3 d; repeat • Third irrigation unsuccessful → Consider ENT referral

CERUMINOLYTIC PREPARATIONS∗

Non oil, Water Based Oil Based Non–Water Based (Increase Miscibility) (Lubricate) (Increase Miscibility) Docusate sodium (Colace™ liquid)† Almond oil Carbamide peroxide † Triethanolamine (Cerumenex™)† Olive oil (Debrox™) 3% Hydrogen peroxide Peanut oil Glycerol 2.5% Acetic acid Mineral oil 10% Sodium bicarbonate 10% oil of turpentine Normal saline‡ (Cerumol™)

∗None of these drugs are FDA approved for use in children. †Recommended second-line agent or for prescription home use. ‡Recommended ﬁ rst-line agent.

Ear Wax Removal Indicated

Manual Removal Ceruminolytics* Irrigation* • Metal or plastic loop • Fill ear canal on • Use body or spoon (never affected side, cotton temperature water pointed or sharp) ball in canal (35–38°C) with • Difficult if • Saline † rubber ear syringe, uncooperative recommended as Water-Pik™ on low patient or if cerumen first line trial setting, or impacted • Wait 15–30 min improvised device‡ prior to irrigation • Irrigate repeatedly • Use 2–3 days BID if until water return is unsuccessful clear

Figure 1-1 Ear wax removal methods. ∗Avoid in all patients with tympanostomy tubes, suspected perforation of the tympanic membrane, or vertigo. †Ceruminolytic use before irrigation dramatically increases the success rate. ‡A 20- to 30-cc syringe with a plastic catheter from a butterﬂ y needle or an 18-gauge plastic IV catheter.

Indications for ENT Referral Irrigation ineffective; manual removal not possible; patient has vertigo, hearing loss, or severe pain

Hygiene and Prophylactic Care • Cotton swabs should only be used for cleaning the outer ear structures. • Normal hygiene: Cleaning the ear with running water while bathing or showering is usually sufﬁ cient. • Occasionally, a ceruminolytic may be used once or twice weekly on a regular basis to prevent excessive cerumen buildup in patients with recurrent impaction.

DRAWING LABS: TUBE COLORS, STANDARD PANELS, HEMOLYSIS Hematology: EDTA tubes (purple) Chemistry: Heparin tubes (green) Coagulation: Citrate tubes (blue) GENERAL INFORMATION CLINICAL

Clinical Pearls for the Wards 7

COLLECTION TUBE TYPES FOR SELECTED LAB SAMPLES*

Purple Green Red Blue

CBC Chem 7/10 Chem 7/10 Bartonella titer PT/INR/PTT

ESR Liver panel Liver Panel Hepatitis panel Fibrinogen

ABO/Rh Amylase Amylase HIV Western PTT Hepzyme blot

Coombs Lipase CRP RPR D-dimer

Crossmatch Gentamicin Gentamicin Rubella IgG/IgM Unfractionated peak, trough, (peak, trough, heparin level random random)

Reticulocyte CRP TSH/free T4 Bilirubin (total, Antithrombin count direct, indirect)

HgbA1C Blood fungus LH/FSH Monospot Rubella IgG culture

Hemoglobin HIV ELISA EBV titers/EBNA Drug screen, proﬁ le antibody serum

EBV, CMV, Rubella IgG CMV titers Osmolality, serum adenovirus: quantitative PCR

Amylase Lipid panel Iron panel CK, CKMB

HIV: DNA PCR, Bilirubin (total, Quantitative Vancomycin RNA, viral load direct, indirect) immuno- (random, peak, globulins trough)

Rubella IgG Osmolality, ANA/ANA Most serum drug serum proﬁ le levels

CK, CKMB C3/C4

Vancomycin HCG (random, peak, trough)

Ammonia (on ice) ASO titer

∗Some labs may be drawn in multiple collection tube types.

POTENTIAL EFFECTS OF HEMOLYSIS ON SELECTED LABORATORY VALUES

Increase with hemolysis Bilirubin,∗ albumin, protein, ALT, AST, LDH, alk phos, CK, phosphate, iron, ammonia, Ca, K ∗ Decrease with hemolysis Bilirubin, haptoglobin, thyroxine (T4), troponin T, RBC, HCT

∗May increase or decrease with hemolysis. 8 General Clinical Information

SI LAB VALUE CONVERSION TABLE

Lab US SI US SI Value Unit Unit Factor* Lab Value Unit Unit Factor*

Chemistry Blood Gas

ALT, AST U/L μkat/L 0.0167 PaCO mm Hg kPa 0.133

Alk phos U/L μkat/L 0.0167 PaO mm Hg kPa 0.133

Amylase U/L nkat/L 0.0167 Toxicology & Drug Monitoring

Bilirubin mg/dL μmol/L 17.1 Acetaminophen mcg/mL μmol/L 6.62

BUN mg/dL mmol/L 0.357 Carbamazepine mcg/mL μmol/L 4.23

Calcium mg/dL mmol/L 0.25 Digoxin ng/mL nmol/L 1.28

Cholesterol mg/dL mmol/L 0.0259 Gentamicin mcg/mL μmol/L 2.09

Cortisol mcg/dL nmol/L 27.6 Phenytoin mcg/mL μmol/L 3.96

Cr Kinase U/L μkat/L 0.0167 Salicylate mg/L mmol/L .00724

Creatinine mg/dL μmol/L 88.4 Theophylline mcg/mL μmol/L 5.55

Glucose mg/dL mmol/L 0.0555 Tobramycin mcg/mL μmol/L 2.14

LDH U/L μkat/L 0.0167 Valproate mcg/mL μmol/L 6.93

Lipase U/dL μkat/L 0.167 Vancomycin mcg/mL μmol/L 0.690

Mg2+ mEq/L mmol/L 0.5 Hematology

Phos mg/dL mmol/L 0.322 Folate ng/mL nmol/L 2.27

T4 mcg/dL nmol/L 12.9 Hemoglobin g/dL mmol/L 0.621 μ T3 mcg/dL nmol/L 0.0154 Iron, TIBC mcg/dL mol/L 0.179 μ Uric acid mg/dL mol/L 59.5 Vit B12 pg/mL pmol/L 0.738

∗Factor to convert from standard to SI units.

ACETAMINOPHEN DOSING

Drops Elixir Chewable (80 mg/ (160 mg/ Tablets (80-mg Age∗ Weight 0.8 mL)† 5 mL) tablets)

0–3 mo 6–11 lb (2.7–5 kg) 0.4 mL — —

4–11 mo 12–17 lb (5.5–7.7 kg) 0.8 mL 1/2 tsp 1 tab

1–2 yr 18–23 lb (8.2–10.5 kg) 1.2 mL 3/4 tsp 1 1/2 tabs

2–3 yr 24–35 lb (10.9–15.9 kg) 1.6 mL 1 tsp 2 tabs

4–5 yr 36–47 lb (16.3–21.4 kg) 2.4 mL 1 1/2 tsp 3 tabs

∗Age is provided as a convenience only; dosing should be based on weight. †5 mL = 1 tsp. GENERAL INFORMATION CLINICAL

Clinical Pearls for the Wards 9

• Dosages may be repeated every 4 h but should not be given more than ﬁ ve times in 24 h. • Alternating acetaminophen and ibuprofen: An alternating treatment regimen of acetaminophen (12.5 mg/kg/dose) and ibuprofen (5 mg/kg/dose) every 4 h for 3 d is more effective than monotherapy in lowering fever in infants and children (Arch Pediatr Adolesc Med. 2006;160:197).

Dosages

Children: 10–15 mg/kg/dose every 4–6 h prn; maximum, 15 mg/kg/dose or 75 mg/kg/d or 2.6 g/d

Adults: 325–650 mg every 4–6 h prn or 1000 mg 3–4 times/d prn; maximum, 4 g/d

IBUPROPHEN DOSING

Drops Elixir Chewable (40 mg/ (100 mg/ Tablets (50 mg Age∗ Weight 1.5 mL)† 5 mL) tablets)

6–11 mo 12–17 lb (5.5–7.7 kg) 1 dropper — —

1-2 yr 18–23 lb (8.2–10.5 kg) 1 1/2 droppers — —

2-3 yr 24–35 lb (10.9–15.9 kg) 2 droppers 1 tsp —

4-5 yr 36–47 lb (16.3–21.4 kg) — 1 1/2 tsp 3 tablets

∗Age is provided as a convenience only; dosing should be based on weight. †5 mL =1 tsp. Doses may be repeated every 6 to 8 h but should not be given more than four times in 24 h.

• Alternating acetominophen and ibuprofen: An alternating treatment regimen of acetaminophen (12.5 mg/kg/dose) and ibuprofen (5 mg/kg/dose) every 4 h for 3 d is more effective than monotherapy in lowering fever in infants and children (Arch Pediatr Adolesc Med. 2006;160:197).

Dosages

Mild to moderate temperature or pain: 5 mg/kg every 6–8 h as needed; maximum, 40 mg/kg/d

Severe temperature or pain: 10 mg/kg every 6–8 h as needed; maximum, 40 mg/kg/d

SYSTEMIC CORTICOSTEROID EQUIVALENCIES

Relative Relative Anti- Sodium Approximate infl ammatory Duration Retaining Equivalent Compound Potency of Action Potency Dose (mg)∗

Cortisone 0.8 S 0.8 25

Hydrocortisone 1 S 1 20

Prednisone 4 I 0.8 5

Prednisolone 4 I 0.8 5

Methyl prednisolone 5 I 0.5 4

(continued on next page) 10 General Clinical Information

Relative Relative Anti- Sodium Approximate infl ammatory Duration Retaining Equivalent Compound Potency of Action Potency Dose (mg)∗ Triamcinolone 5 I 0 4

Fludrocortisone 10 S 125 —

Betamethasone 25 L NA 0.6–0.75

Dexamethasone 25 L 0 0.75

∗These dose relationships apply only to oral or IV administration. These values, which correlate with individual systemic corticosteroids, are used to create a ratio for switching between diﬀ erent corticosteroids (IM or IV only; same route when switching between classes). I = intermediate or 12- to 36-h half-life; L = long or 36- to 72-h half-life; NA = data not available; S = short or 8- to 12-h biological half-life.

Available at www.AccessPediatrics.com • Evaluation and feedback • Breaking bad news • Medication compliance: helping kids take medicines • Inﬁ ltrations, extravasation, and vesicant injury • Epidemiology and statistics: the basics GENERAL CLINICAL INFORMATION 8th ed. 10 Hurts worst 2005;23:393) repeat dosing repeat 5 mm from mucous mucous 5 mm from 8 > membranes (especially in neonates and infants) Laceration should be Laceration Seizures Coma Respiratory depression Irregular heart beats Methemoglobinemia Do not (continued on next page) • • • • • • • Hurts whole lot Wong’s Essentials of Pediatric Nursing, Emerg Med Clin North Am 6 5 kg: 1 g ( 5 kg: 2 g < > more 10 kg: 10 g 20 kg: 20 g > Hurts even > 11 3 mL on gauze or cotton or cotton 3 mL on gauze 7 yr and ≤ pad in direct contact with wound Maximum intact dosing to skin ELA-Max; (30 min for EMLA): 60 min for Birth–3 mo or 3–12 mo and 1–6 yr and > 4 more Hurts little 2 bit Hurts little LET (lidocaine, epinephrine, suturing tetracaine) solution ELA-Max, L.M.X. 4% (lidocaine) or EMLA (eutectic mixture of lidocaine and prilocaine) FACES pain scale. (From Hockenberry MJ, Wilson D. FACES pain scale. (From Hockenberry 0 No hurt messages from the brain end-capillary circulation). circulations (eg, pinna, digits, nose, penis, and other areas of hypnosis education chiropractic regulation, transcutaneous electrical nerve stimulation, acupuncture, therapy, immobilization increased minute ventilation, hypertension increased minute ventilation, Behavioral: Relaxation techniques, biofeedback exercises, breathing control, distraction, Behavioral: Relaxation techniques, biofeedback exercises, breathing and comfort, temperature Physical: Hot and cold compresses, massage or touch, position receptors or excitatory Gate control hypothesis: Close the “pain gates” via nonpainful Formulations containing epinephrine should NOT be used in terminal capillary Formulations containing epinephrine should NOT be used Physiologic parameters: Tachycardia, vasoconstriction, diaphoresis, pupil dilatation, diaphoresis, pupil dilatation, Tachycardia, vasoconstriction, Physiologic parameters: Cognitive: Music, guided imagery, distraction, positive reinforcement, decentralization, Cognitive: Music, guided imagery, Category local DrugTopical anesthetic Dosage Warnings PHARMACOLOGIC PREPARATION General Principles • NONPHARMACOLOGIC PAIN CONTROL NONPHARMACOLOGIC • • • • Figure 2-1 Analgesia and Sedation Analgesia TOOLS PAIN ASSESSMENT • CHAPTER 2 St. Louis: Mosby; 2009. Used with permission. Copyright Mosby.) St. Louis: Mosby; 2009. Used with permission. 12 General Clinical Information

Category Drug Dosage Warnings Ethyl chloride Spray at target area 3–9 in • Irritation at site topical spray away for 3–7 s until skin • Pigmentation changes turns just white; immedi- to application site ate onset

Injectable Lidocaine (with Maximum dose: • Methemoglobinemia local or without 4.5 mg/kg (especially in neonates anesthetic epinephrine) Buﬀ er 1:10 with sodium and infants) bicarbonate (8.4%) to • Irregular heart beats reduce burning sensation at injection site • Seizures • Coma Bupivacaine Maximum dose: 2.5 mg/kg • Respiratory depression Buﬀ er with 1:30 with so- • If it must be used in dium bicarbonate (8.4%) neonates and infants, to reduce burning sensa- in general, reduce tion at injection site dosing by 30%

ORAL AND INTRAVENOUS ANALGESIA • Avoid salicylates because of their association with Reye syndrome. • Oral sucrose: Neonates and infants younger than age 6 months during procedures such as heel sticks, venipunctures, and LPs up to 1 mL for three doses. • Nonopioid analgesics: For mild to moderate pain if the FACES pain scale below 5 or objective pain scale or numeric pain scale below 6. • Nonopioid analgesics are used very infrequently in the NICU and should be used only after discussion with the attending physician.

NONOPIOID ANALGESICS

Drug Dosage Comments

Acetaminophen PO or PR 10–15 mg/kg q 4–6 h • Not anti-inﬂ ammatory (nonsalicylate) Maximum dosage: 1000 mg • Caution in patients with q 6 h liver disease

Ibuprofen (NSAID) PO 4–10 mg/kg q 6-8 h (not for • Caution with renal use in patients younger than insuﬃ ciency 6 mo of age) • Increased risk of GI ulcers or Maximum dosage: 800 mg bleeds q 6 h

Ketorolac (NSAID) IV or IM 0.5–1.0 mg/kg q 6 h • Keep patient well hydrated followed by 0.5 mg/kg q 6 h • Caution with renal Maximum dosage, 30 mg q 6 h; insuﬃ ciency no more than 5 days/mo • Only parenteral NSAID

Naproxen (NSAID) PO 5–7 mg/kg q 8–12 h (not • Increased risk of for use in patients younger cardiovascular events and GI than 2 yr of age) ulcers or bleeds Maximum dosage: 500 mg q 8 h

Indomethacin (NSAID) PO 1 mg/kg q 6–8 h • See comments on other Maximum dosage: 50 mg q 6 h NSAIDS GENERAL INFORMATION CLINICAL

Analgesia and Sedation 13

• Opioid analgesics: For moderate to severe pain if pain scales above 6; bind μ-receptors in the CNS. • Opiates may cause severe respiratory depression, hypotension, CNS depression, bladder retention, ileus, pruritus, nausea and vomiting. • Opiate antagonist Naloxone: For intoxication, use 0.1 mg/kg up to 2 mg IV/IM; for respiratory depression, use 0.01 mg/kg, which may be repeated every 2 to 3 minutes up to 0.05 mg/kg if needed.

OPIOID ANALGESICS*

Drug Dosage Comments

Codeine PO 0.5–1 mg/kg q 4–6 h Commonly combined with Maximum dose: 60 mg acetaminophen

Fentanyl IV 1–2 mcg/kg/dose < 12 yr Muscle rigidity and chest IV 0.5–1 mcg/kg/dose ≥ 12 yr wall spasm (may require a nondepolarizing muscle relaxant) IV onset: 4–5 min Duration: 20–60 min

Hydrocodone PO 2.5–5.0 mg q 6-8 h Commonly combined with acet- Maximum dose: 10 mg aminophen

Hydromorphone IV 0.015 mg/kg q 3–4 h High potential for abuse PO 0.03–0.08 mg/kg q 3–4 h Maximum dose: 2 mg

Methadone PO 0.1 mg/kg q 4–12 h Used in narcotic detoxiﬁ cation Maximum dose: 20 mg May cause QT prolongation

Morphine IV 0.05–0.2 mg/kg q 2–4 h Do not crush or chew PO 0.1–0.5 mg/kg q 4–6 h controlled-release tablets MS Contin: Can give q 8–12 h IV onset: 5–10 min Maximum dosage: IV 15 mg, Duration: 2–4 h PO 30 mg

Oxycodone PO IR 0.2 mg/kg q 3–4 h Do not use sustained-release PO SR 10–20 mg q 12 h tablets as a PRN analgesic Maximum dose: 30 mg

∗Medications that are italicized indicate routine use in the NICU.

PATIENT-CONTROLLED ANALGESIA (PCA) • Use in patients with moderate to severe recurrent pain who may need a continuous infusion of opiates and have the capacity to understand and push the PCA button to self-administer interval boluses of opioid. May also be administered by a nurse or parent. • Patients with sickle cell disease or severe chronic pain may require higher doses. • Patients may need continuous monitoring, especially if younger than age 6 months. • A background infusion should only be considered for patients with severe or chronic pain, including those with scoliosis, sickle crises, or cancer-related pain. These patients may require a higher 4-h maximum. 14 General Clinical Information

Maximum Agent Loading Dose Single Dose Continuous Infusion

Morphine 0.05–0.1 mg/kg 10 mg 0.01–0.03 mg/kg/h

Fentanyl 1–3 mcg/kg 25 mcg 0.15–0.3 mcg/kg/h

Hydromorphone 0.005–0.015 mg/kg 2 mg 0.003–0.005 mg/kg/h

PCA Lockout 4 Hours Agent Interval Dose Interval Maximum

Morphine 0.015–0.025 mg/kg 6–12 min 0.25–0.35 mg/kg

Fentanyl 0.14–0.28 mcg/kg 6–10 min 2.8 mcg/kg

Hydromorphone 0.003–0.005 mg/kg 6–12 min 0.05–0.06 mg/kg

Conversion Between Opiates • Calculate the 24-h opioid requirement. • Example: Patient receiving morphine 30 mg PO q8 h and want to change to hydromorphone as continuous infusion. 30 mg × 3 = 90 mg • Calculate the equinalgesic dose by using the table below for a given route of administration.

⎡ 10 mg IV morphine × mg IV mmorphine ⎤ ⎢ = ⎥ →×=15 mg ⎣60 mg PO morphine 90 mg PO morphine⎦ • Convert to the new opioid.

⎡ 10 mg IV morphine 15 mg IV morphine ⎤ ⎢ = ⎥ →→×=225.mg ⎣1.5 mg IV hydromorphone × mg IV hydromorphone⎦ • Calculate the required dose. • The new dose would be 2.25 mg/24 h = 0.1 mg/h IV hydromorphone. • With PCAs, the total 24-h dose needs to be calculated including continuous infusion and all interval doses. Then convert.

Drug IV or IM (mg) PO (mg)

Codeine 120 200

Fentanyl 0.1 NA

Hydrocodone NA 15–20

Hydromorphone 1.5 7.5

Methadone 10 20

Morphine 10 30–60

Oxycodone NA 30

Weaning Opiates (for habituated patients, please see Guidelines for Weaning Habituated Patients from Chronic Sedatives and Analgesics” below) • All pain medicines need to be converted to one medicine in the same group via the conversion technique described above. GENERAL INFORMATION CLINICAL

Analgesia and Sedation 15

• Choose a reasonable weaning factor (eg, 10%–20% of the initial dose) and wean by weaning factor every day or every other day (opiate-naive patients who have undergone a relatively short therapetic course may be weaned more rapidly). • Example: To wean a morphine dose of 20 mg/d, decrease the morphine by 2 mg every day or every other day. • To change PCA to PO medicines, administer the ﬁ rst PO dose (dose calculated via the method described above), stop the continuous infusion 30 to 60 minutes later, reduce bolus doses by 25% to 50% with each dose, discontinue PCA after no boluses are required for 6 h, or may need to increase new PO dose if unable to wean PCA boluses.

SEDATION Continuum of Sedation (Ped Clin N Am 2006;53:279) • Sedation occurs along a spectrum, and patients can move through all degrees of sedation (anxiolysis → moderate sedation → deep sedation → general anesthesia) easily without affecting their vital signs. • The depth of sedation should be monitored regularly with verbal and tactile stimuli because a patient’s ability to protect the airway becomes increasingly more impaired with increasing levels of sedation. • Attending personnel should be trained to rescue a patient from one level above the intended level of sedation.

Patient Preparation for Sedation • AMPLE history: Allergies, Medications, Past medical history (including risks for abnormal airway and aspiration), Last food/drink, Events (including prior sedation history, and recent or current illnesses including respiratory infections). • Check NPO status (last meal): There is an increased aspiration risk during sedation for patients who have had solids or non-breast milk within 6 h, breast milk within 4 h, and clear fl uids within 2 h. • Discuss the risks and benefi ts with the patient and family and outline the plan, including planned medications, before starting. • Assess for risk factors for complications, including signifi cant underlying disease, abnormal airway, age younger than 6 years, active respiratory infection or fever, dehydration, or use of multiple sedation medicines. • ASA Physical Status Classifi cation: Patients classifi ed at ASA of 3 to 4 are at an increased risk from sedation. AMERICAN SOCIETY OF ANESTHESIOLOGISTS PHYSICAL STATUS CLASSIFICATION

Class Description Examples I Normal, healthy patient — II Mild systemic disease Asthma, controlled diabetes III Moderate systemic disease Stable angina, diabetes with hyperglycemia, moderate COPD IV Severe systemic disease Unstable angina, diabetic ketoacidosis V Moribund — +E Modiﬁ er added to any classiﬁ ca- All ED patients tion indicating “emergency” status

Adapted from the American Society of Anesthesiologists.

• Physical exam focusing on identifying patients with potentially difﬁ cult airways, cardiopulmonary compromise, decreased neurologic baseline, and loose teeth or poor dentition. • Determine Mallampati classiﬁ cation: Visibility of oral cavity used to predict the ease of intubation. 16 General Clinical Information

CLASS 1 CLASS 2 CLASS 3 CLASS 4

MALLAMPATI CLASSIFICATION Class 1: Soft palate, uvula, tonsillar pillars visible* Class 2: Soft palate, majority of uvula visible. Class 3: Soft palate, base of uvula visible. Class 4: Soft palate not visible. Figure 2-2 Mallampati classiﬁ cation. *The original Mallampati classiﬁ cation (Can Anaesth Soc J 1985;32:429) was based on observation of the oropharynx of the patient while seated; the patient extends the tongue as far forward as possible and observations are made of the structures of the pharynx (tonsillar pillars, soft palate and base of the uvula). (Adapted from Brunicardi FC, Andersen DK, Billiar TR, et al: Schwartz’s Principles of Surgery, 9th Edition. Copyright © The McGraw-Hill Companies, Inc. All rights reserved.)

• Prepare emergency equipment (SOAP): Suction, oxygen, provide IV access, pharmacy and medications, oral airway, bag or mask, laryngeal mask airway, intubation supplies including ETT and laryngoscope, NG tubes, crash cart nearby, and two health care providers trained in resuscitation must be present during the procedure.

Weight/Age ETT Size <1000 g 2.5 1000–2500 g 3.0 Term Neonate to 6 mo 3.0–3.5 6 mo–1 yr 3.5–4.0 1–2 yr 4.0–5.0 >2 yr [Age (in yrs) / 4] + 4

Laryngoscope Weight/Age Size (Type) <2.5 kg May need 00 (Miller) 2.5 kg 0 (Miller) 0–6 mo 1 (Miller) 6 mo–3 yr 1.5 (Miller) 3 yr–12 yr 2 (Miller or MacIntosh) >12 yr 3 (Miller or MacIntosh)

• Place patient on continuous cardiopulmonary monitoring (monitor presedation vitals, q5–10 min during the procedure, and q5–15 minutes after the procedure until the patient is awake and alert). Also monitor the airway and ventilation and level of consciousness during the procedure.

• Some institutions require end-tidal CO2 monitoring even for moderate sedation. GENERAL INFORMATION CLINICAL

Analgesia and Sedation 17

Sedation Medications • Procedural sedation and analgesia includes the use of sedative–hypnotic, analgesic, or dissociative anesthetics during unpleasant diagnostic or therapeutic procedures. • Medications should be chosen based on the degree of pain caused by the procedure, the duration of the procedure, immobilization needed for the procedure, underlying medical problems, and physician familiarity and experience with the medications. • Benzodiazepines: Sedative–hypnotic agents with potential amnestic effect, no analgesic properties, bind GABA receptors. • Cause CNS depression, dose-dependent respiratory depression, and (less frequently) hypotension. • Patients may experience paradoxical agitation. • Benzodiazepine antagonist: Flumazenil 0.01 mg/kg up to 0.2 mg IV; repeat doses at 0.005 to 0.01 mg/kg up to 1 mg cumulative dose.

Dose and Adverse Drug Route Onset Duration Eff ects Comments IM or IV 0.04–0.2 mg/kg IM 15 min Intermediate Blood • Active Maximum single IV 2–3 min IM 2–4 h dyscrasias metabolite accumulation dose, 10 mg IV 30–90 min Throm- may prolong

Diazepam bophlebitis sedation <12 yr PO 30–60 min Long acting Blurred • Use with IM or PO 0.05 mg/kg IM 10–20 min PO 2–8 h vision caution in patients with IV 0.01–0.03 mg/kg IV 3–5 min IM 2–6 h Hallucina- tions renal or liver Maximum dose, 2 mg IV 2–6 h disease Restlessness >12 yr • Ideal for Drowsiness PO 2–4 mg prolonging Lorazepam Confusion sedation or IM or IV: 0.05 mg/kg anxiolysis Maximum dose, 4 mg and seizure treatment <6 mo PO 10–20 min Short acting Bitter taste • Cardiac arrest PO 0.5–1.0 mg/kg IM 15 min PO 2 h Amnesia and hypotension have IV 1–2 min IN 60 min Blurred Maximum dose, 20 mg occurred after IN: 0.2 mg/kg vision IN 0.2 mg/kg IM or IV premedica- Maximum dose, 15 mg 2–6 h Headache tion with a narcotic, but IM 0.07–0.08 mg/kg Hiccoughs fewer cardiac Maximum dose, 10 mg Nausea or vomiting complications • Coughing Excellent for muscle >6 mo and <12 yr relaxation or IV 0.05–0.1 mg/kg prolonged sedation

Midazolam Maximum dose, 10 mg > • IV injection 12 yr painful IV 0.5–2 mg/dose • Only benzodiazepine FDA approved for use in neonates; rapid administration may cause myoclonic activity 18 General Clinical Information

• Opiates: See Analgesia section. • Barbiturates (Pentobarbital): Sedative, hypnotic, and anticonvulsant, no analgesic properties, binds GABA receptor. • Ketamine: Anxiolytic, analgesic, amnestic, dissociative anesthesia; phencyclidine derivative that acts on cortex and limbic system and antagonizes NMDA receptor; watch for “emergence phenomena” in older children. • Chloral hydrate: Sedative, no analgesic properties, trichloroethanol active metabolite with unknown mechanism, long acting. • Propofol: Amnestic, sedative and anticonvulsant, no analgesic properties, alkyl phenol that reaches high concentrations in the brain. • Etomidate: Sedative and hypnotic, no analgesic properties, carboxylated imidazole, inhibits 11-β-hydroxylase. α • Dexmedetomidine: Sedative, selective 2-adrenoceptor agonist Adverse Drug Dose/Route Onset Duration Eff ects Comments

PO or PR 30–60 min 4–8 h Unpleasant taste • Contraindicated > 50–100 mg/kg GI irritation in myocardial depression, Maximum dose, 1 g Disorientation airway obstruc- Delirium tion, apnea, and Headache renal or hepatic impairment

Chloral hydrate Respiratory depression • 30%–40% failure rate

>3 mo only PO 20–45 PO 1–2 h Increased • Potent analgesia PO 6–10 mg/kg min IM 12–25 systemic, • Rapid sedation intracranial, IM 3–4 min • Bronchial smooth IM 3–7 mg/kg and intraocular min IV 10–15 muscle relaxation IV 0.5–1 mg/kg; may pressures (con- IV 1–2 min min (use in patients repeat ≤2 mg/kg in traindications) with asthma) 1-h time period Nystagmus Maximum dose, 100 mg • Rare respira- Tachycardia tory depression, Diplopia maintains airway Hypersalivation well (may pretreat • Eyes may remain Ketamine with atropine or open glycopyrrolate) • Movement may Hallucinations occur Emergence • Use with caution reaction in patients with (tx with mida- head trauma, zolam) seizures, WPW, Laryngospasm and HTN

IM 2–6 mg/kg IM 10–15 Variable Agitation (some- • 3%–7% of pa- IV 1–3 mg/kg; may min times “rage tients have sig- repeat IV 1 min phenomenon”) niﬁ cant oxygen desaturation Maximum dose, Confusion 200 mg or 6 mg/kg Nausea or • Contraindicated vomiting in liver impairment Pentobarbital Apnea or bradycardia • Provides immobility Hypotension

(continued on next page) GENERAL INFORMATION CLINICAL

Analgesia and Sedation 19

Adverse Drug Dose/Route Onset Duration Eff ects Comments

Only used for deep IV <1 min IV 5–10 min Hypotension • Good for quick sedation in some Apnea sedation and institutions∗ rapid recovery Arrhythmia IV 0.5 – 1 mg/kg • Mandatory use Pruritus Maximum dose, 50 mg of capnography followed by an infusion Rash and continuous of 50–150 mcg/kg/min Signiﬁ cant pulse oximetry respiratory

Propofol Adults and children >50 kg: bolus in 20- to depression 50-mg increments, followed by infusion as above

Children IV 1 min IV 4–8 min Apnea • Does not cause > 10 yr Myoclonic jerks hypotension or increased ICP IV 0.1–0.4 mg/kg Adrenal sup- For general pression • Caution in patients with anesthesia: Nausea or

Etomidate adrenal insuf- IV 0.2–0.6 mg/kg fol- vomiting ﬁ ciency lowed by an infusion Hiccups of 5–20 mcg/kg/min

Bradycardia • Contraindicated Hypertension in patients with (in rapid admin- renal failure, istration) severe hepatic impairment, Hypotension heart block, Nausea hypotension,

Dexmedetomidine and severe ventricular failure

• For diagnostic imaging, immobilization, and nonpainful procedures: Pentobarbital, chloral hydrate, benzodiazepines, propofol, etomidate, or dexmedetomidine. • For painful procedures such as orthopedic reductions, large lacerations, or abscess incision and drainages: choices include ketamine/benzodiazepine, benzodiazepine/ opioid, propofol/opioid, or etomidate/opioid. Particularly when combining sedatives, close monitoring of patient is required.

Postsedation Monitoring • Monitor heart rate, blood pressure, respiratory rate, oxygen saturation, level of consciousness, and sedation score q 5 to 15 min for 30 min postsedation. • If fl umazenil or naloxone administration was necessary, then the patient must be closely monitored in an increased level of care (eg, PICU, NICU) for a duration of time at least 2-3 half-lives of the medication that was reversed. • Full term infants younger than age 1 mo or premature infants younger than 52 to 60 postmenstrual weeks (per local institutional policy) need to be monitored for 12 apnea- free hours. • Discharge criteria: CV function and airway patency stable, easily arousable and protective refl exes intact, can talk if verbal, can sit if appropriate, and can drink fl uids with adequate hydration status. 20 General Clinical Information

RECOMMENDED POST-SEDATION DISCHARGE CRITERIA

• Patient is alert and oriented; infants and those with underlying abnormal mental status are at their baseline level of functioning. • Vital signs are stable and within age-appropriate limits, including pain level. • Protective reﬂ exes are intact (gag, cough, swallow) • Patient does not have protracted nausea and vomiting. • Patient is able to ambulate at the preprocedural level. • Patient is discharged to the company of a responsible adult. • Written instructions given for postsedation diet, medications, activities, and contact phone number in case of emergency.

• At discharge, provide patient with discharge instructions and ensure that pain and side effects from the pain medicines will be adequately controlled at home. Guidelines for Weaning Habituated Patients from Chronic Sedatives and Analgesics Midazolam to Ativan Wean • Day 1: If midazolam >0.3 mg/kg/h, decrease by 0.5 mg/kg/h q 12 h. • Once midazolam <0.3 mg/kg/h, start lorazepam at 0.1 mg/kg q 4 h PO (may use IV if PO not tolerated). • After each lorazepam dose, decrease the midazolam infusion by 50% until it is discontinued after the second lorazepam dose. • If the patient shows signs of withdrawal, increase lorazepam to 0.2 mg/kg q 4 h. • Calculate the lorazepam weaning factor (10% of initial lorazepam dose). • Day 2: Continue q 4 h lorazepam dose. • Day 3: Change lorazepam to q 6 h at same dose. • Day 4: Decrease lorazepam dose by lorazepam weaning factor at same q 6 h interval. • Day 5: Continue to decrease by weaning factor daily at same q 6 h interval until dose is 0.8 mg × 24 h, then decrease to 0.5 mg × 24 h, then 0.2 mg × 24 h, then discontinue lorazepam (if patient’s weight >5 kg, discontinue after dose is 0.5 mg × 24 h). Fentanyl to Methadone Wean • Day 1: If fentanyl >10 mcg/kg/h, decrease by 1 mcg/kg/h q 12 h. • When fentanyl <10 mcg/kg/h, start methadone at 0.1 mg/kg q 6 h PO (may use IV if PO not tolerated). • After each methadone dose starting after second dose, decrease the fentanyl infusion by 25% until it is discontinued 6 h after the fourth methadone dose. • If the patient shows signs of withdrawal, increase the methadone dose to 0.2 mg/kg q 6 h. • Calculate the methadone weaning factor (20% of initial methadone dose). • Day 2: Change methadone to q 12 h. • Day 3: Continue q 12 h methadone dose. • Day 4: Decrease the methadone dose by methadone weaning factor at the same q 12 h interval. • Day 5: No change. • Day 6: Continue to decrease by weaning factor daily at same q 12 h interval until dose is 0.5 mg × 48 h, then decrease to 0.2 mg × 48 h, then discontinue methadone (if patient’s weight >5 kg, discontinue after dose is 0.5 mg × 48 h). • If the patient shows signs of withdrawal during the wean, give extra lorazepam at the same dose of the current day and hold the wean for 24 h.

Available at www.AccessPediatrics.com • Principles of pain management GENERAL CLINICAL INFORMATION 4 × usion usion usion or empyema ap-valve for further Malignant pleural eff Recurrent pleural eff Recurrent or agents with sclerosing Treatment pleurodesis eff Parapneumonic Chylothorax after coronary (eg, care Postoperative or lobectomy) thoracotomy, bypass, needle catheter (IV catheter) gauzes and tape) gauzes Local anesthetics: 1% lidocaine drawn up Local anesthetics: 1% lidocaine Occlusive dressing (vaseline gauze, 4 (vaseline gauze, dressing Occlusive 16- to 20-gauge needle or plastic-over-the- 50-mL syringe with a stopcock • • • • 21 xed to skin to create a one-way fl 2007;357:e15. NEJM Pneumothorax, bleeding, nerve damage, infection Pneumothorax, bleeding, nerve (1) Tension pneumothorax gown, face and eye shield monitor Povidone-iodine, Chlorhexidine) Povidone-iodine, Large pneumothoraces Large Personal protection equipment: Gloves, Personal protection equipment: Pulse oximeter and cardiorespiratory mask Oxygen supply via nonrebreather Recurrent or persistent pneumothorax or persistent Recurrent secondary chest trauma Pneumothorax to Antiseptic skin prep solution (eg, Antiseptic skin (eg, solution prep In all patients on mechanical ventilation pneumothorax after needle decompression Tension site (preferably with 3 of 4 sides fi below the intercostal space (third rib). decompression). Penetrate the skin over the superior edge of the rib using a 16- to 20-gauge IV catheter. Penetrate the skin over the superior edge of the rib using a Obtain a CXR to assess the results of the procedure. Withdraw desired air, releasing further tension. Prep the skin using sterile techniques if patient is stable. Prep the skin using sterile techniques wheal with 1% lidocaine over the superior edge of the rib If the patient is stable, raise a is released). Remove the needle (a rush of air may be audible as tension Attach a syringe with a stopcock to the hub of the catheter. Pneumothorax • • • • • Hemopneumothorax the with gastric leak into Esophageal rupture pleural space Emergent Non-emergent Equipment Needed for Needle Decompression of Pneumothorax Equipment Needed for Needle • • • • Withdraw the needle at the end of the procedure and apply an occlusive dressing to theWithdraw the needle at the end of the procedure and apply an Advance the IV catheter gradually until a pop is heard or felt on entry of the pleural space. Advance the IV catheter gradually until a pop is heard or felt Attach the patient to a cardiorespiratory monitor and apply oxygen per nonrebreather mask. Attach the patient to a cardiorespiratory second intercostal space at the midclavicular line. On the affected side, locate the Complications: Indications: Reproduced with permission from: with permission from: Reproduced • • • CHEST TUBE PLACEMENT INDICATIONS FOR CHEST TUBE PLACEMENT • • • • • • • • Procedure Procedures OF PNEUMOTHORAX NEEDLE DECOMPRESSION • • Setup CHAPTER 3 CHAPTER 22 General Clinical Information

• Complications: Bleeding; hemothorax; perforation of visceral organs (lungs, heart, liver, spleen); intercostal neuralgia caused by trauma of neuromuscular bundles; subcutaneous empyema; infection, occlusion of chest tube with blood, pus, or debris • Additional information: NEJM 2007;357:e15.

Setup

Equipment Needed for Chest Tube Placement

• Personal protection equipment: Gloves, • Chest tube tray, including correct size chest gowns, face and eye shield tube, a #11 scalpel blade and handle, a curved • Medications for sedation and systemic Kelly clamp, needle driver, and scissors analgesia • Chest tube suction unit, including tubing • Antiseptic skin prep solution (eg, and wall suction hookup Povidone-iodine, Chlorhexidine) • Nonabsorbable 10 silk suture • 1% lidocaine with epinephrine • Occlusive dressing (vaseline gauze, 4 × 4 gauze and tape)

CHEST TUBE SIZE

Chest Tube Size Age (French) Preterm infants 8 Term infants 10 1–3 years 12 >3–10 years 16–18 >10–15 years 20–28 >15 years 28

Procedure (Figure 3-1) • Place the patient in the supine position with the ipsilateral arm raised above the head. • Locate the fourth or ﬁ fth intercostal space in the anterior axillary line at the level of the nipple. • Prep the skin using antiseptic solution; arrange a sterile ﬁ eld if patient is stable. • Anesthetize the skin, subcutaneous tissue, muscles, and pleura: Raise a wheal with 1% lidocaine over the superior edge of the rib that is below the selected intercostal space (the inferior portion of the selected intercostal space to avoid neurovascular bundle); insert needle and anesthetize by injecting lidocaine as the needle is withdrawn. • Make a 1- to 2-cm incision parallel to the rib with #11 scalpel.

Figure 3-1 Chest tube placement. (Reproduced with permission from: Hall JB, Schmidt GA, Wood LDH: Principles of Critical Care, 3rd ed. Copyright © The McGraw-Hill Companies, Inc. All rights reserved.) GENERAL INFORMATION CLINICAL

Procedures 23

• Use a Kelly clamp to bluntly dissect the sub-Q tissue and intercostal muscles down to the pleura. • Insert your index ﬁ nger or Kelly clamp through the incision, palpating within the pleural layer, ensuring that the lung falls away from the pleura. • Clamp the distal end of the chest tube with a Kelly clamp. • Grasp the proximal end of chest tube with Kelly clamp and insert tube through the incision. • When the tube has entered the thoracic cavity, remove the Kelly clamp and advance the chest tube until all of the tube fenestrations are within the thoracic cavity. • Aim the tube apically/anteriorly for pneumothorax and basally/posteriorly for ﬂ uid collection. • Use a continuous, purse-string suture (purse-string) to secure chest tube. • Tape the chest tube to the side of the patient. • Wrap petroleum gauze around the tube at the point where it enters the skin, and cover it with sterile gauze. • Secure the site with pressure dressings. • Attach the chest tube to suction unit and then unclamp the distal end. • Obtain a CXR to confirm placement and adjust the tube accordingly in a sterile fashion (once unsterile, tube can be withdrawn but never advanced).

Removal of the Chest Tube • Sutures, sterile gauze, and a suture kit should be available at bedside. • Cut the skin sutures. • Ask the patient to exhale fully and pull the tube out at end-expiration. • Quickly occlude the site with sterile gauze. • Additional sutures may be required to close the opening. • Secure the site with pressure dressing. • Obtain a CXR 4 to 6 h after the chest tube is removed. If abnormalities are seen then repeat another CXR in approximately 24 h after removal.

LUMBAR PUNCTURE • Indications: (1) Obtain CSF sample for diagnostic studies, (2) measurement of opening pressure, (3) administration of anesthesia, (4) administration of medications for chemotherapy, (5) CSF drainage for symptomatic relief of benign intracranial hypertension • Contraindications: Overlying skin infection, suspected intracranial mass, suspected spinal cord mass or defect (eg, spina bifida), bleeding diathesis (relative contraindication) • Complications: Herniation, cardiorespiratory compromise, local or referred pain, headache, bleeding, infection, leakage of CSF, subarachnoid epidermal cyst • Additional information: NEJM 2006;354:e16.

Setup

Equipment Needed for Lumbar Puncture

• Personal protection equipment: Sterile gloves • A 20 to 22-gauge spinal needle with (gown, face and eye shield as indicated) a stylet (NEEDLE LENGTH < 2yr: 1.5 in; • Topical anesthetic cream 2-12yr: 2.5 in; >12yr: 3.5 in) • Oral sucrose solution for neonates • Manometer (if measurement of opening pressure is indicated). • Antiseptic skin prep solution (eg, Povidone- iodine, Chlorhexidine) • Sterile tubes for collection of CSF • Adhesive bandage

Procedure (Figure 3-2) • Anesthetize the patient by topical anesthetic cream at the intended site and wait 30 minutes or for infants give ≤2 ml oral sucrose solution 2 minutes before the LP. 24 General Clinical Information

Dura L4

Subarachnoid space L5 Cauda equina

Figure 3-2 Needle insertion during an LP. (Reproduced with permission from Gomella LG, Haist SA: Clinician’s Pocket Reference, 11th ed. Copyright © The McGraw-Hill Companies, Inc. All rights reserved.) • Position the child. • Use the lateral recumbent position with the neck fl exed and the knees to the chest. Use this position when measuring opening pressure (the child has to be as relaxed as possible). • The sitting position is an option in young children or when not measuring opening pressure. • Identify the L4 spinous process (a line between the iliac crests). • Identify the L4–L5 (or L3–L4) space by palpating above or below the L4 spinous process. • Sterilize the anticipated puncture site with antiseptic solution; start at the proposed site and work outward in a circular manner. Repeat 2-3 times. • Drape the area with sterile drapes. • Check the child’s position to ensure correct spine fl exion, maximizing the interlaminar space. • Using a 20 or 22-gauge needle and a stylet with the bevel pointed cephalad, puncture the skin midway between the spinous processes of L4–L5 (or L3–L4). Remove the stylet (Ann Emerg Med 2007;49(6):762). • Advance the needle perpendicularly in the midline and sagittal plane, aimed slightly cephalad. • Advance the needle until a “pop” is felt and CSF starts fl owing. (If the needle does not advance, withdraw it slightly and redirect the angle.) • If measuring opening pressure: Reinsert the stylet and ask the patient to straighten the legs and neck. Remove the stylet, connect the manometer to the spinal needle, and measure the opening pressure prior to specimen collection. • Allow CSF to drip into the collecting tubes. • When CSF collection is complete, replace the stylet and withdraw the needle. • Cover the site with an adhesive bandage. • Clean the antiseptic solution off the skin with damp warm towel. • Ideally, instruct the child to stay in the supine position for 4 to 6 hours to lessen the risk of a post-LP headache.

INTRAOSSEOUS (IO) ACCESS • Indications: (1) Immediate access to vasculature via the intramedullary veins for delivery of ﬂ uids, drugs, or blood products in children 0 to 7 years of age; (2) emergent situations when PIV is unobtainable; (3) during CPR when access is needed without interrupting CPR GENERAL INFORMATION CLINICAL

Procedures 25

• Contraindications: Overlying skin infection, fracture of the limb, congenital musculoskeletal abnormalities (eg, osteogenesis imperfecta), previous insertion attempt in the same extremity • Complications: Fat or bone embolism, growth plate injury, tissue necrosis from ﬂ uid extravasation, soft tissue abscess, or osteomyelitis (risk ↓ if IO removed within 3 h of placement)

Setup

Equipment Needed for Intraosseous Access • Personal protection equipment: • 16- or18-gauge IO needle or EZ-IO (for Gloves, (gowns, face and eye shield as 3–39 kg use: 15 mm, 15 gauge; ≥40 kg use needed) 25 mm, 15 gauge) or 16- or 18-gauge spinal • Pillow or rolled towels needle with stylet • Povidone-iodine solutions, alcohol swabs • Extension tubing with three-way stopcock • 1% lidocaine in a 3-cc syringe with a • 5- or 10-cc syringe 27-gauge needle for local anesthesia • NS ﬂ ush syringes (optional) • Long armboard • Tape

Procedure • Determine the appropriate site of insertion: (1) The anteromedial surface of the proximal tibia (2 cm below the tibial tuberosity), (2) the medial surface of the distal tibia (2 cm above the medial malleolus), or (3) the distal femur along the midline (3 cm above the lateral condyle), (4) iliac crest, or (5) sternum in older children/adults. • Position the patient in supine, frog-leg position with a pillow or towels behind the knee. • Cleanse the skin with povidone-iodine solution followed by alcohol swabs. • If time permits, infi ltrate the skin and down to the periosteum with 1% lidocaine. • Prepare IV tubing with a three-way stopcock and fl uids. • Hold the IO needle with the stylet ball in the palm of your hand and place the tip of your index fi nger 1.5 to 2.0 cm from the tip of the needle. • Direct the needle perpendicular to the bony surface. • Insert the needle through the skin, aiming away from the growth plate. • When the needle reaches the periosteum, exert downward pressure in a fi rm, twisting manner until decreased resistance is felt, indicating the needle is in the marrow space. • Unscrew the cap and remove the inner stylet. • Verify position by (1) attaching the 5- or 10-cc syringe and attempting to draw back blood or marrow and/or (2) fl ushing with NS to ensure there is no resistance or extravasation of fl uid. • Secure the needle and the tubing with adequate tape and clear dressing. • Secure the leg to the long armboard. • Attach the IV tubing and allow IV fl uids to fl ow. Secure tubing to the leg with tape.

CENTRAL VENOUS LINE (CVL) ACCESS • Indications: (1) peripheral sites are inaccessible, (2) emergent situation requiring large- bore IV catheter to deliver rapid ﬂ uid boluses or concentrated/vasoactive medications, (3) central venous pressure measurement, (4) placement of pulmonary wedge catheters, (5) placement of transvenous pacemakers, (6) for hemodialysis or plasmapheresis • Contraindications: Infection over the insertion site, venous thrombosis, fracture or suspected fracture close to site • Relative contraindication: Coagulopathy • Complications: Vessel laceration, vessel thrombosis, bleeding, infection, air or catheter embolism, cardiac arrhythmias, cannulation of artery. • Additional information: NEJM 2007;356:e21. 26 General Clinical Information

Setup

Equipment Needed for Central Venous Line Access • Personal protection equipment: Sterile • 1% lidocaine in a 3-mL syringe with a gloves, gown, face and eye shield 25-gauge needle • Cardiopulmonary monitor • Sedation and analgesia medications • Sterile drapes • A rolled-up blanket/towel • Antiseptic skin prep solution (eg, Povidone- • IV tubing and IV ﬂ uid Iodine, Chlorhexidine) • Heparinized NS ﬂ ushes (1 unit heparin • Central line kit with appropriate catheter size per mL NS) (2 Fr for neonates; 3 or 4 Fr for children 1-5 years • Sterile occlusive dressing (Veni-Gard), Tape old; 5 Fr for older children) • Bedside ultrasound (if available)

Identifying a Central Line Site Subclavian Vein (SCV) • The SCV is located inferior and posterior to middle third of the clavicle and runs parallel to it. The subclavian artery is superior and posterior to the vein. • Place the child supine in a 20- to 30-degree Trendelenburg position and hyperextend the spine with a towel rolled underneath the shoulder. Turn the head away from the site of insertion. • Site of insertion: Just inferior and lateral to the middle third of the clavicle (where the clavicle angles posteriorly); aim the needle toward the midline or the sternal notch. • The right SCV approach is generally preferred. Internal Jugular Vein (IJ) • The IJ lies at the apex of the imaginary triangle formed by the sternal and the clavicular heads of the sternocleidomastoid muscle and the clavicle. • Place the patient in a 15- to 20-degree Trendelenburg position and hyperextend the neck with a rolled blanket under the shoulders. Turn the head away from the site of insertion. • Site of insertion: Apex of the triangle; aim caudally toward the ipsilateral nipple. Femoral Vein (Figure 3-3) • The femoral vein lies medial to the femoral artery in the femoral sheath. • Place the child supine with the hip ﬂ exed and abducted in a frog-leg position. • If necessary, place a roll underneath the hip or buttock to expose the inguinal area. • Site of insertion: Identify the midpoint of the inguinal ligament, and locate the femoral artery pulse immediately distal; the femoral vein is medial and parallel to the artery.

Procedure • Sedate the patient if necessary (see Chapter 2). • Position the patient according to the chosen CVL site as described above. • Flush the IV tubing with heparinized NS and attach it to the IV fl uid. • Wear sterile gown, gloves, a surgical cap, and a mask. • Flush the central venous catheter with heparinized NS. • Cleanse the site with antiseptic solution and drape adequately. • If appropriate, anesthetize the intended path with 1% lidocaine. • Use the 22-gauge introducer needle on a 3 or 5 cc empty “slip tip” syringe to locate the vein (aspirate as the needle is advanced until a fl ash of blood returns). If CVP is low (eg. hypovolemia), a fl ash of blood may not readily return with needle penetration of the vein; it may be necessary to apply negative pressure to a 3 or 5 cc syringe of heparinized NS while attempting to locate the vein. • Stabilize the introducer needle, remove the syringe, and immediately occlude the hub of the needle (maintain a “closed system”). • Thread about half of the J wire into the introducer needle. (The wire should pass easily without resistance; when threading into an IJ or subclavian vein, monitor for arrhythmia, which denotes wire position in the atrium or ventricle.) GENERAL INFORMATION CLINICAL

Procedures 27

Femoral nerve Femoral artery Femoral vein Empty space

Figure 3-3 Location of the femoral vein. (Reproduced with permission from Stone CK, Humphries RL: Current Diagnosis & Treatment: Emergency Medicine, 6th ed. Copyright © The McGraw-Hill Companies, Inc. All rights reserved.)

• Hold the J wire in place and remove the introducer needle. • Using a scalpel, make a small incision in the skin adjacent to the entry site of the J wire. • Thread the dilator over the wire; then remove dilator while leaving the J wire in place. • Thread fl ushed CVL over the wire, twisting it gently while advancing into the vein. • Leave 5 to 10 cm of the catheter outside the skin. • Carefully remove J wire and confi rm backfl ow of blood from each port. • Flush each port with heparinized NS and attach the IV tubing. • Secure the catheter to the skin using single interrupted sutures. • Place a sterile occlusive dressing over the catheter. • Obtain a STAT postprocedure CXR after IJ or subclavian line placement, and an abdominal X-ray after a femoral line placement (evaluate for placement and complications).

UMBILICAL ARTERY CATHETERIZATION (UAC) • Indications: (1) hemodynamic instability; (2) continuous blood pressure monitoring; (3) administration of resuscitation ﬂ uids, concentrated or vasoactive medications, and exchange transfusions or (4) anticipated frequent arterial blood draws • Contraindications: Omphalitis, peritonitis, NEC, impetiginous skin lesions near umbilicus, omphalocele, gastroschisis, abdominal trauma • Complications: Infection, vasospasm, thrombosis, infarction, hypertension from renal artery stenosis, hemorrhage, vessel perforation, hypertension from renal artery thrombosis or stenosis 28 General Clinical Information

Setup

Equipment Needed for Umbilical Artery Catheterization

• Personal protection equipment: Sterile gloves, • Needle holder gowns, face and eye shield, surgical cap • Nonthrombogenic, molded-tip umbilical • Radiant warmer with a light source artery catheters (3.5 Fr for infants <1.2 kg; • Cardiopulmonary monitor and pulse 5.0 Fr for infants >1.2 kg) oximeter • 3-0 or 4-0 silk suture on a curved needle • Sterile drapes • Linen umbilical tape • Scalpel (#11 or #15) • Adhesive tape • Antiseptic skin prep solution (eg, • 10-mL syringe ﬁ lled with heparinized NS Povidone-iodine, Chlorhexidine) (1 unit herparin per 1 mL NS) • Curved, nontoothed iris forceps • IVF infusion setup • Small, smooth, curved hemostats • IV tubing and infusion pump • Straight Crile forceps • Three-way stopcock • Iris scissors

Figure 3-4 Course of the UAC and UVC. GENERAL INFORMATION CLINICAL

Procedures 29

Procedure • Determine the length of catheter to be inserted so that the tip lies above the diaphragm at the level of T6–T9: UAC insertion length in centimeters = (Birth weight in kg × 3) + 9

• Evidence does not support the use of “low catheterization” at the L3–L4 level. • Position the patient in a radiant warmer with the extremities in a supine frog-legged position. • Place the patient on cardiopulmonary monitors. • Consider sedation/analgesic medication to minimize patient movement and agitation. • Wear sterile surgical gown, gloves, a cap, and a mask. • Clean the abdomen and umbilical cord with antiseptic solution. • Drape the umbilical area in a sterile fashion. (Leave the infant’s head exposed for observation.) • Tie a surgeon’s knot loosely with the umbilical tape at the base of the umbilical cord. • Using forceps, grasp the cord in full thickness between 0.5 and 2 cm from its base. • Using a scalpel, cut the cord transversely along the top edge of the forceps. • Identify the two umbilical arteries (smaller with a thicker wall, located 4 and 7 o’clock). • Use a curved hemostat to grasp the end of the umbilicus to hold it steady and upright. • Use forceps to open and dilate the UA. • Insert a catheter to the predetermined length using gentle constant pressure to overcome resistance (a slight twisting motion may help). If there is resistance because of vasospasm, wait 1 to 2 minutes. (Signifi cant force should not be used.) • Aspirate the catheter when in position to verify blood return. • Connect the catheter to the fl uid and IV tubing. • Remove the umbilical tape. • Obtain abdominal radiograph to confi rm the position and make adjustments to the catheter length (catheter may only be advanced under sterile conditions; once sterile fi eld is broken down catheter may only be withdrawn). • Place a purse-string suture at the base of the umbilical cord, wrap the ends of the suture around the catheter, and tie. • Place a piece of adhesive tape perpendicular to the umbilical stump, incorporating both the catheter and the suture. Secure the tape to the abdominal wall.

UMBILICAL VEIN CATHETERIZATION (UVC) • Indications: (1) Rapid administration of resuscitation ﬂ uids, (2) administration of blood products or concentrated, caustic, or vasoactive medications, (3) exchange transfusions, or (4) anticipation of frequent blood draws • Contraindications: Omphalitis, peritonitis, NEC, impetiginous skin lesions, omphalocele, gastroschisis • Complications: Infection, thrombotic or embolic events hepatic necrosis if the catheter tip remains in the portal system, cardiac arrhythmia, portal hypertension, NEC

Setup

Equipment Needed for Umbilical Vein Catheterization

• See Equipment Needed for Umbilical Artery Catheterization • Nonthrombogenic, molded-tip umbilical vein catheters (5.0 Fr for infants <3.5 kg; 8.0 Fr for infants >3.5 kg)

Procedure • Determine the length of the catheter to be inserted. The tip of the catheter should lie above the diaphragm at the junction of the IVC and the right atrium: UVC insertion length in centimeters = Half the UAC length calculated above + 1 or UVC insertion length in centimeters = Birth weight in kg × 7 30 General Clinical Information

• Position the patient in a radiant warmer with the extremities in a supine frog-legged position. • Place the patient on cardiopulmonary monitors as well as a pulse oximeter. • Wear sterile surgical gown, gloves, a cap, and a mask. • Clean the abdomen and umbilical cord with antiseptic solution. • Drape the umbilical area in a sterile fashion. (Leave the infant’s head exposed for observation.) • Tie a surgeon’s knot loosely with the umbilical tape at the base of the umbilical cord. • Using forceps, grasp the cord in full thickness between 0.5 and 2 cm from its base. • Using a scalpel, cut the cord transversely along the top edge of the forceps. • Identify the umbilical vein (usually the larger fl oppy wall vessel close to the periphery of the stump). • Use a curved hemostat to grasp the end of the umbilicus to hold it steady and upright. • Use forceps to open and dilate the umbilical vein. • Insert a catheter to the predetermined length using gentle constant pressure to overcome resistance. There should be minimal resistance. (Signifi cant force should not be used.) • Aspirate when the catheter is in position to verify blood return. • Connect the catheter to the fl uid and IV tubing. • Obtain an abdominal radiography to confi rm the position and make adjustments. • Place a purse-string suture at the base of the umbilical cord, wrap the ends of the suture around the catheter, and tie. • Place a piece of adhesive tape perpendicular to the umbilical stump, incorporating both the catheter and the suture. Secure the tape to the abdominal wall.

LACERATION REPAIR • Indications: (1) Primary closure of a wound, (2) restore perfusion to injured tissue • Contraindications: Grossly contaminated wounds, wounds required to heal by secondary intention (eg, bites), facial wounds oldermore than 24 h old, all other wounds oldemorer than 12 h old, complex lacerations involving substantial destruction of underlying structures • Complications: Infection, wound dehiscence, hypertrophic scars, retained foreign body

Setup

Equipment Needed for Laceration Repair

• Personal protection equipment: Sterile • Sterile gauze gloves (gowns, face and eye shield, surgical • 60-mL syringe with a splash guard or NS cap as needed) spray bottle for irrigation • Sterile drapes • Towels and bowl • Scalpel • Appropriate bicarbonate buff ered anes- • Antiseptic skin prep solution such as chlor- thesia (see Laceration Management table) hexidine or povidone-iodine solution in a 3-mL syringe with a 25- or 27-gauge • Laceration repair kit, including a needle needle holder, tooth forceps, and scissors • Suture materials appropriate for wound • Sterile NS (see Laceration Management table)

LACERATION MANAGEMENT

Superfi cial Suture Special Location Anesthesia* Deep Suture Suture Dressing Removal Note

Scalp 1% lidocaine 3–0 or 4–0 4–0 or 5–0 Bacitracin, 5–7 days Pressure with Vicryl Nylon air dressing epinephrine if early hematoma

(continued on next page) GENERAL INFORMATION CLINICAL

Procedures 31

Superfi cial Suture Special Location Anesthesia* Deep Suture Suture Dressing Removal Note Pinna 1% lidocaine 5–0 Vicryl in 6–0 Nylon Bacitracin 5 days Light perichondrium pressure dressing Eyelid or 1% lidocaine 5–0 Vicryl 5–0 or 6–0 Bacitracin, 4–5 days Do not eyebrow Nylon air shave hair Lip 1% lidocaine 5–0 Vicryl 6–0 Nylon Air NA Care with with (rapid) vermillion epinephrine border Face or 1% lidocaine 5–0 Vicryl 6–0 Nylon Bacitracin, 4–6 days Care with forehead with air facial epinephrine nerve Neck 1% lidocaine 4–0 Vicryl 5–0 Nylon Bacitracin, 4–6 days Through with air Platysma epinephrine Trunk 1% lidocaine 4–0 Vicryl 4–0 or 5–0 Bacitracin 7–10 days Rule out with Nylon abdominal epinephrine pathology Extremi- 1% lidocaine 4–0 or 5–0 4–0/5–0 Bacitracin, 7–10 days ties or with Vicryl Nylon xeroform 10–14 buttocks epinephrine 3–0 for over days if joints over joints Hands 1% lidocaine None 5–0 or 6–0 Bacitracin, 7–10 days Nylon xeroform 10–14 5–0 rapid if days <5 yr old if over joints Nailbeds 1% lidocaine None 6–0 Vicryl Bacitracin, NA Splint xeroform fi nger, antibiotics Feet or 1% lidocaine None 3–0, 4–0, or Bacitracin, 10–14 Kling wrap sole 5–0 Nylon xeroform days Scrotum 1% lidocaine None 5–0/6–0 Bacitracin, NA Vicryl air, 4 x 4 5–0 gut fl uff scrotal support Penis 1% lidocaine None 5–0 Nylon Bacitracin, 6–8 days air

*Use bicarbonate-buﬀ ered lidocaine or lidocaine with epinephrine.

Procedure • Position the patient appropriately with adequate lighting. • Consider consulting a Child Life specialist and using procedural sedation or restraints as appropriate. • Assess the neurovascular status distal to the injured area to be repaired. • Clean the area around the wound in an outward circular fashion with antiseptic solution. • Anesthetize in the plane between the dermis and the sub-Q tissue. Consider nerve blocks (eg, lip laceration, ﬁ ngers, toes). • Use a 60-mL syringe with a splash guard or NS spray bottle and irrigate the wound (100 mL of NS per cm of laceration). 32 General Clinical Information

• Drape the area adequately. • Using forceps, explore the wound for foreign bodies and injuries to the tendons, nerves, and vessels. • Remove devitalized tissue, but not adipose tissue, by sharp dissection. • Grasp the needle perpendicular to the needle driver at the junction of proximal to middle third of needle. • Place the ﬁ rst stitch in the center of the wound so that it bisects the laceration. • Use the forceps to evert the wound edge but do not pinch the tissues. • Insert needle into skin at a 90-degree angle in a curvilinear path through the dermis and sub-Q tissue. • Use forceps to secure the exposed needle tip, then grasp it with the needle holder to pull the suture through, leaving a 3-cm tail. • Evert the wound edges with forceps to ensure proper healing and accurate apposition. • Repeat the process on the opposite side, making sure the bite depth and width are equal on both sides and the depth of the suture path is greater than the width. • Hold the suture at the needle end with the nondominant hand, allowing the needle to rest on the drape. • Wrap the suture over the needle holder twice. • Use a needle holder to grasp the tail of the suture on the other side, pulling the ends in opposite direction and approximating the wound edges. • Wrap the suture over the needle holder once, grasp the tail of the suture with the needle holder, and pull the ends in opposite direction; repeat this step four times. • Pull the knot off to one side of the laceration. • Cut the suture with scissors, leaving 1-cm tails. • Place additional sutures as needed. • Wipe off remaining antiseptic solution. • Cover the repaired laceration (except on the face and scalp) with a sterile, nonadherent dressing. • Assess tetanus immunization status and administer tetanus prophylaxis as indicated.

TETANUS PROPHYLAXIS IN WOUND MANAGEMENT

Clean, Minor Wounds All Other Wounds Number of Prior Adsorbed Tetanus Toxoid Doses Td or Tdap TIG Td or Tdap TIG <3 or unknown Yes No Yes Yes ≥3 (last >10 yr ago) Yes No Yes No ≥3 (last 5–10 yr ago) No No Yes No ≥3 (last <5 yr ago) No No No No

Td = adult-type diphtheria and tetanus toxoids vaccine; Tdap = booster tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis; TIG = tetanus immune globulin (human).

Follow-up • Instruct the patient or parent to change the dressing daily and to keep the wound dry and clean. • Prophylactic antibiotics are indicated only in patients with grossly contaminated wounds, bite wounds, crush injuries, open fractures, tendon injuries, or immunosuppression. • Instruct the patient to return for sutures removal.

INCISION AND DRAINAGE OF ABSCESS (I&D) • Indications: (1) Abscess in skin or subcutaneous tissue, (2) unsuccessful treatment with antibiotics (for empiric management of suspected Staphylococcus aureus skin and soft tissue infections, see Chapter 20: Infectious Disease). GENERAL INFORMATION CLINICAL

Procedures 33

• Contraindications: Very large or deep abscesses, abscesses in very sensitive areas (supralevator, ischiorectal, perirectal areas), palmar or plantar areas, nasolabial folds • Complications: Bleeding, nerve damage, recurrent abscess formation, progression to surrounding cellulitis, lymphangitis

Setup

Equipment Needed for Incision and Drainage of Abscesses

• Personal protection equipment: Sterile gloves, • #11 scalpel blade with a handle gown, face and eye shield, surgical cap • A curved hemostat and scissors • Sterile drapes • Wound-packing material, 0.25-inch pack- • 1% lidocaine with epinephrine for local anes- ing strips (eg “iodoform” gauze ribbon) thesia (in 10-cc syringe with 25-gauge needle) • NS spray for irrigation • Sedation medications • Gauze • Antiseptic skin prep solution (eg, Povidone- • Tape iodine, Chlorhexidine) • Culture swab

Procedure • Give adequate analgesia and consider procedural sedation (see Chapter 2). • Position the patient so that the area for drainage is fully exposed and easily accessible. • Cleanse the area over the abscess with povidone-iodine skin prep in an expanding circular motion. • Drape to create a sterile fi eld. • Infi ltrate a wide area around the abscess with buffered 1% lidocaine at 12, 3, 6, and 9 o’clock positions. Allow at least 2 to 3 minutes for effect. • Incise directly over the center of the abscess with a #11 blade, cutting through the skin into the abscess cavity. Incise parallel to skin fold lines whenever able while making the incision. • Purulent fl uid will drain when the abscess cavity is successfully entered. • Use a culture swab to take culture of abscess contents, swabbing inside the abscess cavity. • Extend the incision to create an opening adequate for drainage and to prevent recurrence. • Use gauze to soak up drainage and blood. • Use a hemostat to gently explore abscess cavity, breaking up any loculations within the abscess. • Irrigate the abscess cavity with NS spray until the effl uent is clear. • Consider using a packing strip to pack the abscess cavity to keep the incision walls open. • Place a gauze dressing lightly over the wound and tape in place. • Assess tetanus immunization status and administer tetanus prophylaxis as indicated (see above). • Schedule a follow-up appointment 2 to 3 days after the procedure to remove packing, if done.

RECOMMENDED RESOURCE Videos in Clinical Medicine. N Engl J Med. Available at http://content.nejm.org/misc/ videos.shtml.

Available at www.AccessPediatrics.com • Nasogastric and enteral feeding tube placement • Peripheral intravenous cannulation • External jugular vein • Radial artery access This page intentionally left blank NUTRITION, GROWTH AND FORMULA rst 3 kg > 2006; Pediatr Rev 2005;115(2):496. ed:57. th 8

, Pediatrics 2500 g: Iron (2 mg/kg/d) beginning after 2500 g: Iron (2 mg/kg/d) beginning higher iron for 2500 g: No recommendation 2500 g: Iron (2 mg/kg/d) beginning after 2500 g: Iron (2 mg/kg/d) beginning higher iron for 2500 g: No recommendation < > < > 35 BW until age 1 year age 2 weeks BW this group needs for BW until age 1 year age 2 weeks BW this group needs for None indicated Triple vitamin (A, D, C) the fi at 1 mL/d within D, vitamin (A, Triple of life days few Not indicated 3kg) 3 kg) 3 Multivitamin (1 mL/d) until weight > < Pediatric Nutrition Reference Guide Nutrition Reference Pediatric ed formulatransitional ed None indicated HMF ed with (weight ed formula (weight ed formula milked human All: Multivitamin (1 mL/d) infant, expressing milk for the baby to be fed via bottle. After treatment has begun and infant, expressing milk for the baby to be fed via bottle. After breastfeeding.) the mother is allowed to be with her infant, she can resume Maternal HIV infection (in developed countries) Galactosemia in an infant Active maternal illegal drug use be separated from her Active, untreated maternal tuberculosis (The mother should Preterm Infants Preterm Human milk fortifi Feeding RegimenFeeding Supplementation Recommended Unfortifi Premature iron-fortifi Premature formula Premature iron-fortifi Premature iron-fortifi Term Term iron-fortifi Term Term Infants Term Human milk exclusively starting Iron (1 mg/kg/d) at age 4–6 months HMF is not to be used at discharge. HMF is not to ∗ with permission from Reproduced 27(11):409. American Academy of Pediatrics Policy Statement. • Chandran L & Gelfer P. Breastfeeding: the essential principles. Chandran L & Gelfer P. Breastfeeding: the essential principles. Contraindications to Breastfeeding • • • BREASTFEEDING CHAPTER 4 Nutrition and Pediatric Neonatal MINERAL SUPPLEMENTATIONVITAMIN AND PRETERM NEONATES IN TERM AND Section 2: Nutrition, Growth and Formula Growth 2: Nutrition, Section 36 Nutrition, Growth and Formula

• Active HSV lesions on the breast; feeding can be continued on the unaffected breast • Maternal use of certain radioactive isotopes, cancer chemotherapy agents, and a small number of other medications (see below)

Medications and Breastfeeding • Extensive list of dangerous and safe drugs in breastfeeding: American Academy of Pediatrics Policy Statement in Pediatrics 2001;108(3):776 and at LactMed - http://toxnet. nlm.nih.gov

Normal Voiding and Stooling While Breastfeeding • Nurse at least 8 to 12 times per day or every 1 to 3 hours for the ﬁ rst week(s) of breastfeeding. • Have no more than one 4-hour sleep period in 24 hours during the ﬁ rst week of breastfeeding.

Storage of Human Breast Milk

STORAGE DURATION OF HUMAN MILK FOR USE WITH HEALTHY FULL-TERM INFANTS AT HOME

Location Temperature Duration Comments

Countertop ≤77°F (≤25°C) 6–8 h Cover all containers and keep as cool as possible; likelihood of contamination ↑ without refrigeration

Insulated cooler bag 5° 39°F (−15°–4°C) 24 h Keep ice packs in contact with milk container at all times

Refrigerator 39°F (4°C) 5 d Store milk in back of refrigerator, where temperature is coolest

Freezer

Freezer portion of 5°F (−15°C) 2 weeks Store milk in back of freezer; refrigerator over time, the lipids in milk degrade

Freezer portion of 0°F (−18°C) 3–6 mo refrigerator with separate doors

Upright deep freezer −4°F (−20°C) 6–12 mo

Reproduced with permission from Pediatric Nutrition Reference Guide, 8th ed:41

Reconstituted commercial formula from powder or liquid should be refrigerated immediately and discarded after 24 hours.

ENTERAL FEEDING METHODS AND MONITORING General Principles • The benefi ts of trophic feedings has been well established. • Enteral nutrition helps maintain normal gut fl ora and immunity. • A wide range of commercially available formulas have made it signifi cantly easier to ensure adequate nutrition for children with virtually any impairment of intestinal function. Neonatal And Pediatric Nutrition 37

Indications for Enteral Feeding • May be the primary method of delivering nutrition or may be used as an adjunct with parenteral nutrition. • The gut should always be used if at all clinically possible. • Impaired ability to achieve adequate caloric or nutrient intake (because of any reason, including neurologic impairment, children with any disorder requiring increased caloric intake, disorders of GI motility). • Impaired ability of the GI tract to normally digest and absorb nutrients may require specialized formulas. • Failure to thrive associated with chronic disease is the most common indication for enteral nutrition support in the pediatric population. NUTRITION, AND GROWTH FORMULA Establish need for enteral nutrition support patient unable to take adequate PO due to: • ↑Energy requirement • Physiologic impairment

No GI tract functional? Consider TPN

Ye s

Normal gut function: Abnormal gut function: • Human milk Determine • Protein hydrolysate • Standard infant/ appropriate • Peptide based pediatric/ adult formula • Elemental formula • Human Milk

Determine location of feed (Gastric vs. Trans-pyloric)

Determine method of feeding (Bolus vs. Continuous)

Determine daily nutrient requirements

Initiate feeds per guidelines

Monitor feeding for complications

Figure 4-1 Algorithm for determining enteral intake. (Reproduced with permission from Pediatric Nutrition Reference Guide, 8th ed:72.) 38 Nutrition, Growth and Formula

Feeding Methods

Site Delivery Route Indications Complications

Stomach Orogastric or • Short term (6–8 wk) nutri- • Aspiration nasogastric tion support • Nasal mucosal • Inadequate oral intake ulceration • Refusal to eat • Tube occlusion • Nocturnal feeds • Pneumothorax • Inability to suck or • Bleeding swallow • Epistaxis

Gastrostomy• Long-term nutrition • Dislodgement support • Aspiration • Congenital anomalies of • Tube deterioration the GI tract • Bleeding • Esophageal injury or obstruction • Tube occlusion • Failure to thrive • Pneumoperitoneum • Wound infection • Stoma leakage

Transpyloric Nasoduodenal • Congenital upper GI • Pneumatosis intestinalis Nasojejunal anomalies • Bleeding Gastrojejunal • Inadequate gastric • Dislodgement motility Jejunostomy • Tube deterioration • High aspiration risk • Tube occlusion • Severe GER • Bowel obstruction • Functioning intestinal tract with proximal • Stomal leakage obstruction • Wound infection

Reproduced with permission from Pediatric Nutrition Reference Guide, 8th ed:73.

Method of Enteral Feeding

Type Indications Advantages Disadvantages

Bolus or • Dysphagia • Physiologic method of feeding • May increase risk intermittent • Anorexia • Increased patient mobility of aspiration feeds • Supplement to • May not require a pump • Poorly tolerated in patients who oral intake • Flexible feeding schedule cannot tolerate volume (severe GER or delayed gastric emptying)

Continuous • Delayed gastric • Preferred method for small • Requires feeding feeds emptying bowel feeding pump • Increased risk of • Slow infusion may improve • Patient is attached aspiration tolerance to the pump for • Limited absorp- • May be given nocturnally to the duration of tive surface area lessen the interruption of day- feeding time schedule and oral intake

Reproduced with permission from Pediatric Nutrition Reference Guide, 8th ed:73. Neonatal And Pediatric Nutrition 39

Monitoring Enteral Feeding

Problem Prevention or Intervention

Diarrhea or abdominal • Decrease delivery rate. cramping • Recognize or avoid drugs that may cause diarrhea. • Consider increasing ﬁ ber content of feeds. • Consider osmolarity and addition of modular additives. • Give semi-elemental or elemental formula if indicated.

Vomiting or nausea • Ensure formula is at room temperature before initiating tube feedings. NUTRITION, AND GROWTH FORMULA • Elevate head of bed. • Consider transpyloric feeding.

Hyperglycemia• Reduce rate of feeding. • Use formula with minimal simple sugar. • Consider insulin if clinically indicated.

Constipation• Ensure optimal ﬂ uid intake. • Increase free water intake. • Change to ﬁ ber-containing product.

Gastric retention of • Monitor for correct tube placement. formula • If residuals are high (>2-h volume of feeds), hold feeds and recheck residual in 1 h. • Consider continuous transpyloric feeding. • Position patient with the right side down.

Clogged feeding tube• Ensure that tube is ﬂ ushed after checking residual check, bolus feed, and Q4–8 h when on continuous feeds. • Ensure appropriate tubing size for patient and formula being used. • Consider transpyloric or continuous feeds.

Reproduced with permission from Pediatric Nutrition Reference Guide, 8th ed:74.

PRETERM INFANT NUTRITION OVERVIEW Enteral Nutrition • For infants >1800 g and >34 wk gestation: Human milk or term formula indicated for all infants >1800 g and 34 wk (at a goal volume of 180 mL/kg/d) • For infants <1800 g and <34 wk gestation: Human milk with human milk fortiﬁ er or preterm formula • Premature transitional formula with iron indicated for premature infants postdischarge with birth weight <1800 g • Consider higher caloric formulas in infants with congenital heart disease (in whom ﬂ uid must often be restricted)

Total Parenteral Nutrition Total parenteral nutrition (TPN) is complete IV nutrition that bypasses the GI tract. TPN is used to provide carbohydrates, protein, lipids, vitamins, and minerals. 40 Nutrition, Growth and Formula

TPN in Ten: A Step By Step Guide 1. Calculate the IV ﬂ uid (IVF) requirement for the patient based on weight. Fluid requirements for neonates (in mL/kg/d)

Birthweight (g) Days 1–2 Day 3 Day 5 and Beyond < 1000 100 140 150 1001–1500 80–100 100–120 150 >1501 65–80 100 150

For children beyond the neonatal period • The total goal fl uids must be tailored to address individual clinical requirements (eg, children with increased fl uid losses from any source; children in renal failure or other fl uid overload states). • If the patient’s weight is <10 kg, approximately 100 mL/kg/d is considered maintenance. • If the patient’s weight is >10 kg, use BSA × 1600 mL/m2/d to calculate maintenance fl uid (See chapter 1 for BSA calculations). This is the total volume of fl uid the patient would require in 1 day. 2. Calculate the total energy required for the patient. • Use the table below to calculate the daily energy requirement. • For children with increased caloric requirement, you can multiply by a “stress factor;” see the table below.

Age Total Energy DRI (kcal/kg/d)∗ Preterm† 110–130 kcal/kg/d enterally 90–100 kcal/kg/d parenterally

0–3 mo 102 4–6 mo 82 7–12 mo 80 13–35 mo 82 3 yr 85 4 yr 70 5–6 yr 65 7–8 yr 60 Boys 9–13 yr 47 Boys 14–18 yr 38 Boys >18 yr 36 Girls 9–13 yr 40 Girls 14–18 yr 32 Girls >18 yr 34

∗For children with adequate nutrition; use their weight in kilograms. For malnourished or obese children, use ideal body weight (IBW; BMI at 50th percentile). These DRI values are based on healthy (nonhospitalized) children; note that DRI values to not apply to preterm infants. Activity level, preexisting malnutrition, and concomitant medical or surgical conditions must all be accounted for in determining energy and protein goals. † Guidelines for premature infants reproduced with permission from AAPCON Nutritional Needs of the preterm infant. In Klienman RE (ed). Pediatric Nutrition Handbook, 6th ed; 2009. Data from Pediatric Nutrition Reference Guide, 8th ed:79. Neonatal And Pediatric Nutrition 41

Stress Factors Stress factors should be used in conjunction with an estimation of resting energy expenditure such as the Schoﬁ eld method or WHO; they should not be used with the DRIs above.

Fever 12% for each degree >37°C

Cardiac failure 1.15–1.25

Major surgery 1.20–1.30

Sepsis 1.40–1.50

Catch-up growth 1.50–3.00 NUTRITION, AND GROWTH FORMULA Burns 1.50–2.00

Reproduced with permission from Pediatric Nutrition Reference Guide, 8th ed:19.

• Calculation of basal metabolic rate or resting energy expenditure by the Schoﬁ eld method:

Basal Metabolic Rate (kcal/d)∗

Male Female

0–3 yr (0.167 × wt) + (15.174 × ht) – 617.6 (16.252 × wt) + ( 10.232 × ht) – 413.5

3–10 yr (19.59 × wt) + (1.303 × ht) + 414.9 (16.969 × wt) + (1.618 × ht) + 371.2

10–18 yr (16.25 × wt) + (1.372 × ht) + 515.5 (8.365 × wt) + ( 4.65 × ht) + 200

>18 yr (15.057 × wt) − (1.004 × ht) + 705.8 (13.623 × wt) + (2.83 × ht) + 98.2

∗Weight is expressed in kilograms; height is expressed in centimeters. Reproduced with permission from Pediatric Nutrition Reference Guide, 8th ed:19.

3. Calculate the required protein.

Age Protein DRI (g/kg/d)

Preterm infants∗ Start at 1.5–2 and advance as tolerated to goal (3.5 parenterally or 3.5–4 enterally)

0–3 mo 1.52

4–6 mo 1.52

7–12 mo 1.20

13–35 mo 1.05

3 yr 1.05

4 yr 0.95

5–6 yr 0.95

7–8 yr 0.95

Boys 9–13 yr 0.95

Boys 14–18 yr 0.85

(continued on next page) 42 Nutrition, Growth and Formula

Age Protein DRI (g/kg/d)

Boys >18 yr 0.80

Girls 9–13 yr 0.95

Girls 14–18 yr 0.85

Girls >18 yr 0.80

∗Guidelines for premature infants reproduced with permission from AAPCON Nutritional needs of the preterm infant. In Klienman RE (ed). Pediatric Nutrition Handbook. 6th ed; 2009. Reproduced with permission from Pediatric Nutrition Reference Guide, 8th ed:79.

4. Calculate lipids and the rate for lipids. • The usual infusion is 20% lipid emulsion. • Fat should be approximately 30% of calories. • Minimum of 5% of calories as fat to avoid essential fatty acid deﬁ ciency • Maximum of 60% of calories as fat to avoid ketosis

Energy from fat = Total energy (kcal/d) × 0.3

• The rate of the lipid is calculated by:

[Energy from fat (kcal/d)]/[2 kcal/mL] = mL/d of lipid (Divide by 24 to get the hourly rate.) Example: Patient who requires 2000 kcal/d:

2000 × 0.3 = 600 kcal is energy from fat [600 kcal/d]/[2 kcal/mL] = 300 mL/d of lipid (300 mL/d of lipid)/(24 h) = 12.5 mL/h of lipid • Prematurity or concern for lipid intolerance: Begin with 1 g/kg/d (5 mL/kg/d) and advance by 1 g/kg/d (5 mL/kg/d) daily until energy needs from lipids are met and lipid tolerance is achieved. Check serial measurement of serum triglyceride level as indicated. Goal: 15 mL/kg/d (=3 g/kg/d) for neonates and up to 20 mL/kg/d (4 g/kg/d) for older infants. 5. Calculate the solution strength of carbohydrates and amino acids and their rate. • 70% of calories should come from dextrose and protein. Energy from dextrose and amino acid (kcal/d) = Total energy (kcal/d) × 0.7 • Restrict dextrose to maximum 12.5% and amino acids to maximum of 3% if infusing through a peripheral IV line (This is our practice at Texas Children’s Hospital. Most institutions will use a osmolality limit for use in a peripheral line; the AAP recommends no more than 900 mOsm.) • If concerns of glucose tolerance (ie, extreme low birth weight), initiate at a GIR of 4.5 to 6.0 mg/kg/min. • Do not exceed 4 g protein/kg/d. • The amino acids, dextrose, electrolytes, minerals, and vitamins are all in one solution. • Prematurity: 5% dextrose if <25 to 26 wk gestation and <1000 g; 10% dextrose if >25 to 26 wk gestation and >1000 g. • This is for the starter TPN only (for DOL 1 and 2); the standard solution is 12.5% dextrose, but it can be adjusted depending on the infant’s glucose tolerance. • After the ﬁ nal concentration of carbohydrates and amino acids has been determined (in %), the table below can be used for verifying that the solution will provide adequate caloric supply over 24-h period. Neonatal And Pediatric Nutrition 43

ENERGY DENSITY OF TOTAL PARENTERAL NUTRITION BASED ON DEXTROSE AND AMINO ACID CONTENT IN kcal/cc OF TOTAL PARENTERAL NUTRITION SOLUTION

% Amino Acids

% Dextrose 1 2.2 2.4 2.8 3 3.5 4 5 6

7.5 0.30 0.34 0.36 0.37 0.38 0.40 0.42 0.46 0.50

10 0.38 0.43 0.44 0.45 0.46 0.48 0.50 0.54 0.58

12.5 0.47 0.51 0.51 0.54 0.55 0.57 0.59 0.63 0.67 NUTRITION, AND GROWTH FORMULA 15 0.55 0.60 0.61 0.62 0.63 0.65 0.67 0.71 0.75

17.5 0.64 0.68 0.69 0.71 0.72 0.74 0.76 0.80 0.84

20 0.72 0.77 0.78 0.79 0.80 0.82 0.84 0.88 0.92

25 0.89 0.94 0.95 0.96 0.97 0.99 1.01 1.05 1.09

30 1.06 1.11 1.12 1.13 1.14 1.16 1.18 1.22 1.26

35 1.23 1.28 1.29 1.30 1.31 1.33 1.35 1.39 1.43

40 1.40 1.45 1.46 1.47 1.48 1.50 1.52 1.56 1.60

Reproduced with permission from Pediatric Nutrition Reference Guide, 8th ed:80.

6. Calculate electrolytes. Daily electrolyte requirements

Sodium (NaCl) 2–3 mEq/kg/d

Potassium (KCl) 1– mEq/kg/d

Chloride (Cl) 2–3 mEq/kg/d

Phosphorus (K2PO4) 0.65–2 mmol/kg/d

Magnesium (MgSO4) 0.13–0.5 mEq/kg/d Calcium (Ca gluconate) 0.3–2 mEq/kg/d

Reproduced with permission from Pediatric Nutrition Reference Guide, 8th ed:81.

Electrolyte conversion

Ca 1 mmol = 2 mEq = 40 mg

P 1 mmol = 2 mEq = 31 mg

Na 1 mmol = 1 mEq = 23 mg

K 1 mmol = 1 mEq = 39 mg

Mg 1 mmol = 2 mEq = 24 mg

Cl 1 mmol = 1 mEq = 35 mg

Reproduced with permission from Pediatric Nutrition Refer- ence Guide, 8th ed:81. 44 Nutrition, Growth and Formula

If the patient has acidosis, consider adding a base to TPN such as Na acetate or K acetate. Bicarbonate will change the pH and result in calcium and phosphorus precipitation in the TPN. 7. Vitamins, minerals, trace elements.

A B1 B2 B6 B12 C D E K Additional Product (IU) (mg) (mg) (mg) (mg) (mg) (IU) (IU) (μg) information

Infuvite® 3300 6 3.6 6 5 200 200 10 150 Biotin 60 mcg (adult) Folic acid 600 mcg Niacinamide 40 mg Dexpanthenol 15 mg

Infuvite® 2300 1.2 1.4 1 1 80 400 7 200 Biotin 20 mcg (pediatric) Folic acid 140 mcg Niacinamide 17 mg Dexpanthenol 5 mg

IU = International Units; values are expressed as per 10 mL. Adapted from Texas Children’s Hospital Formulary.

Trace minerals added to TPN are zinc, copper, selenium, chromium, and manganese. (Iodine and molybdenum are not added in TPN solutions.) Most hospitals automatically add the trace minerals to TPN, but check with your institution. Most hospitals also automatically add vitamins based on the patient’s weight; check with your institution. 8. Special circumstances. • TPN cholestasis is an incompletely understood complication of TPN characterized by cholestasis, liver injury, cirrhosis, and progressive dysfunction. An elevated serum GGT level may herald an increasing conjugated bilirubin. Ursodeoxycholic acid has been used to mitigate liver injury (the exact mechanism of action in humans has not been fully described, although several theories exist) when cessation of TPN is not feasible. Preventive measures include cycling TPN and feeding enterally when possible (although the efﬁ cacy of TPN cycling has not been determined in a randomized, controlled trial). • Hypertriglyceridemia may occur from rapid infusions of IV fats or intolerance to IV fat infusion (eg, because of altered metabolism as in premature infants). Triglycerides are elevated in patients on steroids, those with sepsis or pancreatic disease, and in patients with diabetes. Always check baseline TG before starting TPN in patient with any of these problems. Then check the level in 4 hours. Consider decreasing the rate of lipids if TG level is >200 to 250 mg/dL. • Hyperglycemia may occur with high infusion rates and may be exacerbated by corticosteroids, sepsis, or trauma. It is important to remember that excess carbohydrate administration may cause increased carbon dioxide production. • Carnitine may assist with fat metabolism. Add L-carnitine (10–20 mg/kg/d) if an infant will be on exclusive TPN for more than 2 weeks. 9. Final check. • Calculate the total caloric content of TPN (kcal/kg/d) based on the amount of dextrose and protein and lipids (a standard 20% lipid emulsion provides 2 kcal/cc) • Does 70% of the calories come from dextrose and protein? Neonatal And Pediatric Nutrition 45

• Is the GIR in an acceptable range? A GIR of 6 to 15 mg/kg/min is generally well tolerated; however, the initial GIR should be 4.5 to 6.0 mg/kg/min. (For premature infants, start at a GIR of 4.5 to 6.0 mg/kg/min and advance as tolerated to a goal of 8 to 12 mg/kg/min.) GIR = [% Dextrose (g/100 mL)] × [Volume (mL/kg/d)]/1.44 • Does 30% of calories come from fat? Remember that fat should be at least 5% of calories to prevent essential fatty acid deﬁ ciency. • Have I exceeded 4 g protein/kg/d? If so, the patient may develop azotemia. • Are there any electrolyte abnormalities that I need to correct? • Do I need to check triglycerides 4 hours after initiating TPN? • Have I written for monitoring labs based on my patient’s need?

10. Lab monitoring (neonates and pediatric and adolescent populations) and advancement. NUTRITION, AND GROWTH FORMULA

Initially (Until TPN Composition is Stable) Follow-up

Intake and Output Daily Daily

Electrolytes, BUN 2–3 times/wk Weekly

Ca, P, Mg Weekly Weekly to every other week

Prealbumin∗ Weekly Weekly

Albumin∗ Baseline Every 3 weeks

Triglycerides 4 h after initiating infusion 4 h after infusion rate change

ALT (SGPT) Baseline Every other week

Bilirubin (direct and indirect) Baseline Weekly to monthly

∗As clinically indicated. Reproduced with permission from Pediatric Nutrition Reference Guide, 8th ed:83.

FORMULA SELECTION OVERVIEW • Human milk • Ideal form of nutrition. • AAP recommends all babies be exclusively breastfed at least until age 6 months and continued with addition of complimentary foods until 12 months of age. • Contains protein, energy, and cellular and humoral immunologic factors.

• First 5 days: Colostrum, which is rich in immunoglobulins • After 5 days: Transitional with increased fat and lactose • Contains approximately 20 kcal/oz. • May be used in LBW infants but does not have enough calcium, protein, and phosphorus to meet the needs of VLBW infants. • VLBW infants on human milk require the addition of a human milk fortiﬁ er. • Protein as 20% casein, 80% whey. • Carbohydrate is lactose. • Must supplement vitamin D if breastfeeding. • Contraindications • Galactosemia in an infant. • Mothers receiving radioactive isotopes. • Maternal HIV. • Mothers using drugs of abuse. 46 Nutrition, Growth and Formula

• Active untreated TB. • Active herpes simplex lesions on the breast. • Maternal human T-cell lymphotrophic virus type I or II infection. • For safety profi le of medications while breastfeeding. see www.toxnet.nlm.nih.gov (click LactMed). • Cow’s milk–based term formulas • Most useful for term infants with no special nutritional or GI requirements, if human milk is not available. • Protein: Various whey:casein ratios (60:40, 48:52, 100:0, 18:82) • Carbohydrate is lactose. • Soy-Based Formula • Lactose free. • Indications: Galactosemia, parental vegetarian diet preference or congenital lactase defi ciency (extremely rare). • Frequently misused for infants with cow’s milk protein (CMP) allergy. An unacceptably high proportion of CMP allergic infants (~30%) will cross-react to soy protein. • Cow’s milk–based premature formulas. • Protein: Whey, 60%; casein, 40% • Carbohydrate is a combination of glucose polymers and lactose. This is easier to absorb than lactose alone. • Fat is a mixture of long chain triglycerides and medium chain triglycerides. • Increased vitamins A and D, calcium, phosphorus, and electrolytes. • Premature infant follow-up formulas. • Recommended for former premature infants from 2 kg to 1 year of age. • Protein is whey, 50% to 60%; casein, 50% to 40%. • CHO is 50:50 mix of glucose polymers and lactose. • Fat is MCT:LCT 25:75. • Protein hydrolysate formulas. • Indicated in infants with known cow’s milk protein allergy or galactosemia. • Protein is hydrolyzed to shorter peptides and thought to be less allergenic than intact proteins. • Free amino acid formulas. • Used when protein hydrolysate fails to remedy symptoms of cow’s milk protein allergy. • Lactose-free formulas. • For infants with primary or secondary lactose intolerance. • Low-carbohydrate formulas. • Indicated for children with severe disaccharidase defi ciency or carbohydrate intolerance. • Carbohydrate in the form of glucose polymers or fructose must be added to make these formulas nutritionally complete. • Metabolic formulas • For patients with inborn errors of metabolism to bypass the enzymatic defects.

Formula Mixing Guide

Caloric Density Liquid Mead Johnson Nestle Abbott (kcal/oz) Concentrate∗ Powder† Powder† Powder†

All brands Enfamil Lipil, AR,‡ Nestle Good Similac Advance, LactoFree Lipil, Start Similac Sensitive, ProSobee, Next Lactose Free, Isomil Step and Isomil 2, Similac 2, Alimentum or PM 60/40

(continued on next page) Neonatal And Pediatric Nutrition 47

Caloric Density Liquid Mead Johnson Nestle Abbott (kcal/oz) Concentrate∗ Powder† Powder† Powder†

20 1 oz conc. + 1 oz 1 unpacked 1 unpacked 1 unpacked scoop + sterile water scoop + 2 oz sterile scoop + 2 oz 2 oz sterile water = water = 2.2 oz sterile water = 2 oz (60 mL) formula (65 mL) formula 2.25 oz (67.5 mL) formula

24 3 oz conc. + 2 oz 3 unpacked 3 unpacked 3 unpacked scoops + 5 + + sterile water scoops 4.8 oz scoops 4.9 oz (150 mL) sterile NUTRITION, AND GROWTH FORMULA (144 mL) sterile oz (145 mL) water = 6 oz (180 mL) water = 5.6 oz sterile water = formula (168 mL) formula 5.6 oz (164 mL) formula

27 2 oz conc. + 1 oz 2 unpacked 3 unpacked 3 unpacked scoops sterile water scoops + 3 oz scoops + 4.3 + 4.25 oz (127.5 mL) (90 mL) sterile oz (127 mL) sterile water = 5 oz water = 3.5 oz sterile water = (150 mL) formula (105 mL) formula 4.9 oz (146 mL) formula

∗Preparation from concentrate does not vary from brand to brand. Use sterile water to reconstitute powdered formula for all infants younger than age 3 mo. †Must use the scoop provided with the container. ‡Do not concentrate Enfamil AR to more than 24 kcal/oz because of increased viscosity. Reproduced with permission from Pediatric Nutrition Reference Guide, 8th ed:44.

Human Milk Concentration with Infant Formula Powder

Caloric Density (kcal/oz)∗

Human Milk + Powder to Yield ã 22 24 27 30 g powder/tsp

Similac NeoSure Advance with Iron 1.3 2.6 4.5 6.5 2.1

Enfamil EnfaCare Lipil with Iron 1.4 2.7 4.8 6.8 2.4

Nestle Good Start Supreme with DHA 1.3 2.6 4.6 6.5 2.2 and ARA

Similac Advance with Iron 1.3 2.5 4.4 6.3 2.1

Enfamil Lipil with Iron 1.3 2.6 4.5 6.4 2.3

∗All values represent the number of grams of powder preparation to add per 100 mL of human milk to make the desired caloric concentration. Reproduced with permission from Pediatric Nutrition Reference Guide, 8th ed:42. 48 Nutrition, Growth and Formula

Human Milk Fortiﬁ er (HMF)

g 4 packets mg (mEq)/4 packets VitD Product CHO Fat Prot Na K Ca P Fe (IU / dL)

Enfamil <0.4 1 1.1 16 29 90 50 1.44 150 HMF (Mead (0.7) (0.8) (4.5) Johnson)

Similac HMF 1.8 0.4 1 15 63 117 67 0.4 120 (Abbott (0.7) (1.6) (5.9) Nutrition)

Source of Product CHO Fat Prot

Enfamil HMF Corn syrup High-oleic Whey protein hydrolysate, milk (Mead Johnson) solids sunﬂ ower, protein isolate (whey:casein ratio, soy, MCT and 60:40) coconut oils

Similac HMF Corn syrup MCT oil Whey protein concentrate, nonfat (Abbott Nutrition) solids dry milk (whey:casein ratio, 60:40)

Reproduced with permission from Pediatric Nutrition Reference Guide, 8th ed:131.

• Note that it is not recommended that HMF be used for fortiﬁ cation of human milk after discharge. • Recommended for infants weighing less than 1800 g who require higher caloric density and supplemental fat, protein, calcium, phosphorus, and vitamins. Derived from cow’s milk with a whey–to-casein ratio of 60:40.

Available at www.AccessPediatrics.com • General diet guidelines, birth to age 18 years • Formula selection guide • Formula additives guide NUTRITION, GROWTH AND FORMULA 2 %ile %ile tth th × × ) 100 eat50 1985;60;932. g g 1986;30:150. 1996;96:680. 1988;113:318. 49 c. 1978;61:564. 1978;93:435. percentile are considered obese. th Pediatrics percentiles are considered overweight. Actual wt(k Clin Genet Actual ht (cm) 100 th Arch Dis Child ected wt for ht at 50 Pediatrics ected ht for a p J Pediatr percentile are considered underweight. p J Am Diet Assoc th Ex Ex to 95 th 36 mo. uenced by nutritional status until age BMI = (Weight in kg)/(Height in m) BMI = (Weight in kg)/(Height 90% (normal) 95% (normal) ≥ ≥ Grade I: 80%–89% (mild) Grade I: 90%–94% (mild) Children who are at or above the 95 Children who are at or above Grade III: <70% (severe) Changes in height may be an indicator of chronic malnutrition. Grade 0: Grade II: 85%–89% (moderate) Grade III: <85% (severe) Head circumference is inﬂ These criteria are appropriate for children ages 1 to 3 years. Changes in weight may be an indicator of acute malnutrition. Grade 0: Grade II: 70%–79% (moderate) Down Syndrome Growth Chart: Down Syndrome Growth Chart: For children, BMI is age and gender speciﬁ For children, BMI is age and gender Children who are at the 85 Body mass index (BMI) is calculated as follows: Body mass index not a diagnostic one. BMI is an effective screening tool, Children who are below the 5 or www.accesspediatrics.com BMI charts: www.cdc.gov/growthcharts Achondroplasia Growth Chart: Williams Syndrome Growth Chart: Cerebral Palsy Growth Chart: Turner Syndrome Stature Chart: Noonan Syndrome Growth Chart: • • • • • • • • • • • • Specialized Growth Charts • • • • • • MALNUTRITION Waterlow Criteria • • • • • GROWTH CHARTS at www.cdc.gov/growthcharts or www.accesspediatrics.com. Standard growth charts are available Assessment of Nutrition and Growth of Nutrition Assessment AGE BODY MASS INDEX FOR CHARTS OF • • CHAPTER 5 50 Nutrition, Growth and Formula

Fetal-Infant growth chart for preterm infants* 65 65

60 60 97% 90% 55 55 50% Length 10% 50 3% 50

45 45 Centimeters 40 97% 40 90% 50% 35 Head circumference 10% 6 3% 30 5.5 97% Centimeters 25 90% 5

20 4.5 50% 4 4 t

3.5 Weigh 10% 3.5 3% 3 3

2.5 2.5 (kilograms) Weight

2 2

1.5 Plot growth in terms of completed weeks of 1.5 gestation.

Weight (kilograms) Weight Sources: Intrauterine weight - Kramer MS et al 1 (ePediatr 2001); Length and Head circumference - 1 Niklasson A et al (Acta Pediatr Scand 1991) and Beeby PJ et al (J Paediatr Child Health 1996); Post term sections - 0.5 the CDC Growth Charts, 2000. The smoothing of 0.5 the disjunction between the pre and post term sections generally occurs between 36 and 46 weeks. 0 0 22 24 26 28 30 32 34 36 38 40∗ 42 44 46 48 50 Gestational age (weeks) Figure 5-1 Fetal-infant growth chart for preterm infants. ∗The use of regular CDC growth charts is recommended after an infant reaches 40 weeks gestation. On these charts, values should be plotted based on corrected gestational age (CGA = # weeks since birth - # weeks premature); CGA adjustment for prematurity should continue until age 18 mo for FOC, 24 mo for wt, 36-40 mo for length. (Reproduced with permission from BMC Pediatr. 2003. Available at http://www.biomedcentral.com/1471-2431/3/13.)

Available at www.AccessPediatrics.com • Vitamin and mineral defi ciencies and toxicities • Standard growth charts PEDIATRICS nger. nger into the distal vagina and nger (Kegel maneuver). Then insert pH paper mounts wet and saline for 10% KOH lubricant Water-soluble gloves Disposable nonsterile slips cover glass slides, Microscope, if appropriate chaperone, Female Cotton-tip swabs Cotton-tip • • • • • • • consider exam under cult to examine; 51 Patients with physical or mental disability, abnormal anatomy, or physical Patients with physical or mental xative; ThinPrep™ kits or ThinPrep™ xative; against the fi nger (middle) and ask the patient to contract ask the patient to voluntarily contract against the fi pressure. Enter the speculum completely. and majora, clitoris, introitus, perineal body, Bartholin glands, Skene’s glands, and and majora, clitoris, introitus, perineal body, Bartholin glands, urethral meatus. a second fi Palpate for tenderness and adenopathy. Slowly insert an appropriately sized speculum into the vagina while applying downward Slowly insert an appropriately sized speculum into the vagina Examine hair distribution (note sexual maturity rating), skin changes, labia minora Examine hair distribution (note sexual maturity rating), skin Let the patient know the gel is cold; insert an index fi hernias, organomegaly, masses, tenderness. Abdomen (inspection, auscultation, palpation, percussion): Examine for skin changes, Abdomen (inspection, auscultation, palpation, percussion): External genitalia Internal genitalia (speculum exam) • • • • containers or fi containers able; otherwise culture systems other Pap Spatula or cytobrush for Pap test, Pap slide Pap test, Pap Spatula or cytobrush for Gown and drape to cover the patient cover and drape to Gown Exam table with ankle support Examination light Speculum medium or NAAT Gonorrhea culture if avail- NAAT test– screening Chlamydia immaturity with an intact hymen may be diffi immaturity with an intact hymen general anesthesia. her slide her buttocks to the edge of the exam table and relax her legs into abduction. her slide her buttocks to the edge of the exam table and relax in sexually active young women, menstrual disorders, undiagnosed lower abdominal pain, menstrual disorders, undiagnosed lower abdominal pain, in sexually active young women, mass, request by the patient. sexual assault, suspected pelvic Gynecology. 2009; 114(6):1409). sexual history (Obstetrics and For Pap smear: Cervical cancer screening should begin at age 21, not sooner, regardless of screening should begin at age 21, not sooner, regardless of For Pap smear: Cervical cancer Explain each step of the exam as you proceed. Remember to wash your hands and use gloves. Have the patient empty the bladder before the exam. in ankle supports and have Place the draped patient in the supine position with her feet For pelvic exam: Symptoms of vaginal or uterine infection, asymptomatic STI screening For pelvic exam: Symptoms of Examination inspection, speculum exam, and/or, bimanual examination Examination inspection, speculum • • • • • • • • • • Considerations: Procedure • • • • • • • Equipment GYNECOLOGIC EXAM EQUIPMENT NEEDED FOR CHAPTER 6 Medicine Adolescent EXAM GYNECOLOGIC • Indications Section 3: Pediatrics Section 52 Pediatrics

• Open the speculum to identify and examine the cervix and lock the speculum in place. • Use two cotton-tip swabs to obtain a sample of vaginal discharge from the vaginal walls (document the volume, color, consistency, and any odor) for wet mounts and pH. • Place a sample into 1 drop of saline on one slide and on one drop of 10% KOH on another slide. • Apply a swab to pH paper. • Collect endocervical sample for cervical culture or NAAT for GC and Chlamydia. • Collect endocervical cells for Pap smear by rotating the brush or spatula against the cervix. Place the sample in a Pap container, following the instructions speciﬁ c to the Pap system being used. • Upon completion of the exam, unlock the speculum and slowly back off the cervix. Close the blades as you remove the speculum completely. • Bimanual exam • Use your nondominant hand on the abdomen to sweep the pelvic organs downward while inserting the index and middle ﬁ ngers of your dominant hand into the vagina to examine the vagina, cervix, uterus, adnexa, and cul de sac. Assess size, shape, symmetry, mobility, and position of the ovaries and uterus. • Assess for cervical motion tenderness and adnexal and uterine tenderness. Attempt to distract the patient by palpating with the other hand on the abdomen, asking her if it hurts while simultaneously performing cervical motion and adnexal palpation. If the patient has cervical pain, despite the distraction maneuver, cervical motion tenderness (PID) should be considered. • Complication: A small amount of bleeding after the Pap smear is normal.

GENITOURINARY INFECTIONS Vulvovaginal Disorders • Symptoms: Itching, vaginal discharge, dysuria, erythema and edema of the vulva and vagina • Etiology • Noninfectious causes: Trauma, foreign body, labial adhesions, chemical irritant or allergen (douches, powders, bubble bath), nylon underwear, masturbation • Infectious causes: Bacterial overgrowth of enteric organisms or normal vaginal ﬂ ora, Neisseria gonorrhea, Trichomonas spp., β-hemolytic streptococcus, Chlamydia, pinworms, HSV, HPV, Candida spp. • Evaluation • Examine the external genitalia for scratches, tears, erythema, discharge, and swelling. • Use wet prep or STI testing if indicated (based on history or during external genitalia exam). • Suspect a foreign body when foul-smelling discharge is present. • Treatment for nonspeciﬁ c vaginitis • Remove the irritating agent (foreign body, douche, bubble bath, etc). • Provide hygiene instructions. • Sitz baths may be helpful. • Consider empiric treatment for common organisms based on presentation treatment for common organisms

CHARACTERIZATION AND TREATMENT OF COMMON CAUSES OF VAGINITIS

Yeast Bacterial Trichomonas Vaginitis Vaginosis vaginalis Infection

Symptoms Itching and burning Foul discharge Itching and burning

Discharge Thick and white Watery, positive Frothy, ± positive “whiﬀ ” “whiﬀ ” test result∗ test∗

(continued on next page) Adolescent Medicine 53

Yeast Bacterial Trichomonas Vaginitis Vaginosis vaginalis Infection

Microscopy Hyphae seen on KOH Clue cells on saline Trichomonads on saline prep prep prep

Vaginal pH <5 5–7 5–7

Treatment Intravaginal Metronidazole 500 mg Metronidazole 2 g PO once × antifungal cream, PO BID 7 d or tablet, or suppository or (clotrimazole 1%, Tinidazole 2 g PO once miconazole 2%, Metronidazole gel or 0.75%: 1 applicator terconazole 0.4%) Metronidazole 500 mg used as directed intravaginally daily × × 5 d PO BID 7 d or or Fluconazole 150 mg PO x1 Clindamycin cream 2%: 1 applicator intravaginally QHS × 7 d or Clindamycin 300 mg PO BID × 7 d or Clindamycin ovules 100 g intravaginally QHS × 3 d

∗ A positive "whiﬀ " test occurs when a ﬁ shy or foul odor is noted upon addition of KOH to the discharge sample on the slide.

Sexually Transmitted Infections • For detailed recommendations: http://www.cdc.gov/std/treatment

DIAGNOSIS AND TREATMENT OF SEXUALLY TRANSMITTED PEDIATRICS INFECTIONS∗

Disease Laboratory Treatment for (Organism) Clinical Features Diagnosis Adolescents † Uncompli- Many are asymptomatic Positive urine Ceﬁ xime 400 mg cated Urethritis‡ is common in young men leukocyte es- PO once N. Gonorrhea terase result Rectal infection (usually asymptomatic or infection of but may have pruritus, mucopurulent Gram stain cervix, urethra Ceftriaxone rectal discharge) demonstrating 125 mg IM once or rectum intracellular Mucopurulent cervicitis (yellow-green Test for reinfec- (Neisseria gram-negative discharge, friable cervix, >30 PMNs on tion in 3-6mo gonorrhea) diplococci Gram stain) Cell culture is Note: If chla- PID (see below) gold standard mydial infection Perihepatitis (Fitz-Hugh-Curtis syn- has not been ELISA drome; RUQ pain, liver tenderness) ruled out, DNA probes treat for both Bartholin or Skene gland abscesses PCR (swab Chlamydia and Pharyngitis (usually asymptomatic) and urine gonorrhea. Disseminated gonococcal infection in tests 1%–3% available)

(continued on next page) 54 Pediatrics

Disease Laboratory Treatment for (Organism) Clinical Features Diagnosis Adolescents † Chlamydia Many are asymptomatic Positive urine Azithromycin (Chlamydia Urethritis is common in young men leukocyte es- 1 g PO once terase result trachomatis) Mucopurulent cervicitis or Cell culture is Epididymitis (gradual onset of Doxycycline gold standard × red, edematous scrotum in area of 100 mg PO BID epididymis) ELISA 7–10 d PID DFA Test for reinfec- tion in 3–6mo Perihepatitis DNA probes PCR (swab and urine tests available) Herpes 1- to 2-mm vesicles in clusters that may Tzanck prep: See table: Treat- simplex coalesce with an erythematous base; multinucle- ment for Herpes (Herpes sim- painful; tender lymphadenopathy ated cells Simplex Virus plex virus) Viral culture Infections (see below) HSV PCR Syphilis 5- to 15-mm solitary papule with sharp Dark fi eld Treatment for (Treponema base and induration; nontender; bilat- microscopy primary, second- pallidum) eral nontender lymphadenopathy RPR, VDRL ary, and early latent disease: FTA-ABS, MHA-TP Penicillin G benzathine 50,000 U/kg IM, up to adult dose of 2.4 million U in a single dose Chancroid 2- to 20-mm multiple papules or pus- Culture Azithromycin (Haemophilus tules that may coalesce; ragged border; 1 g PO once ducreyi) purulent; tender; unilateral tender or lymphadenopathy Ceftriaxone 250 mg IM once or Ciprofl oxacin 500 mg PO BID × 3 d or Erythromycin base 500 mg PO TID × 7 d Lym pho- 2- to 10-mm solitary papule/vesicle; Complement Doxycycline granuloma ±painful; unilateral tender lymphade- fi xation 100 mg PO × Venereum nopathy Immunofl uo- BID 21 d (Chlamydia rescent anti- or trachomatis) body serologic Erythromycin testing base 400 mg PO QID × 21 d

∗ If an STI is detected/treated, it is strongly recommended to test for co-infections (HIV, HBV, syphilis). † Partners of patients diagnosed with STIs should also be screened and treated accordingly. ‡ Urethritis: Inﬂ ammation of the urethra; more common in men; Ureaplasma urealyticum may also be a causative organism; may also complain of dysuria, polyuria, or mucopurulent urethral discharge; may be asymptomatic; diagnosis: >5 WBCs on Gram stain, positive urine leukocyte esterase result, conﬁ rmed with cell culture or NAAT. Adolescent Medicine 55

TREATMENT OF HERPES SIMPLEX VIRUS INFECTIONS

Primary Suppressive Outbreak Recurrence∗ Therapy Acyclovir 400 mg PO TID × Acyclovir 800 mg PO Acyclovir 400 mg PO BID† † × 7–10 d BID 5 d or or or Valacyclovir 500 mg/d PO† × † Valacyclovir 1 g PO BID 7–10 d Acyclovir 800 mg PO or TID × 2 d or Valacyclovir 1 g/d PO† × or Famciclovir 250 mg PO TID or 7–10 d Valacyclovir 500 mg PO BID × 3 d Famciclovir 250 mg PO BID or Valacyclovir 1 g/d PO × 5 d†

∗Therapy should begin within 1 day of appearance of lesion or during prodrome preceding outbreak for greatest beneﬁ t. †Per CDC guidelines.

Pelvic Infl ammatory Disease • Defi nition: Infection or infl ammation of part or all of the upper genital tract (includes including endometritis, salpingitis, tubo-ovarian abscess, pelvic peritonitis). • Epidemiology: 10% to 15% of women of reproductive age will have at least one episode. • Risk factors: First sexual activity at a young age, multiple partners, lack of condom use, prior gynecologic surgery. • Etiology: Polymicrobial, most commonly N. gonorrhea and Chlamydia spp. • Clinical features and diagnosis: • Lower abdominal pain is the most common presenting symptom. • Other symptoms include dyspareunia, dysuria, and DUB. • Minimum criteria: Abdominal pain and adnexal tenderness or cervical motion tenderness or uterine tenderness • Additional criteria: Fever (>38.3°C), abnormal vaginal discharge, laboratory evidence of PEDIATRICS Chlamydia or N. gonorrhea infection, WBCs on vaginal wet prep, elevated ESR or CRP. • More specifi c criteria: Endometrial biopsy with evidence of endometritis, transvaginal ultrasonography or MRI demonstrating thickened tubes, free pelvic fl uid, tubo-ovarian abscess. • Complications: Disease recurrence (one episode predisposes to more episodes); chronic abdominal pain; increased risk of ectopic pregnancy; increased risk of infertility; tubo- ovarian abscess; perihepatitis • Treatment: • Hospitalization should be considered for the following reasons: presence of adnexal mass, tx compliance concerns patient unable to tolerate PO, uncertainty of diagnosis, pregnancy, and failed outpatient management. • If anaerobes are suspected (i.e. prolonged symptoms before seeking treatment, TOA) or if BV or trichomonads are present, metronidazole should be added to the treatment regimen.

TREATMENT REGIMENS FOR PELVIC INFLAMMATORY DISEASE

Parenteral: Regimen A Cefotetan 2 g IV q12h or Cefoxitin 2 g IV q6h plus Doxycycline 100 mg PO or IV q12 h × 14 d

(continued on next page) 56 Pediatrics

Parenteral: Regimen B∗ Clindamycin 900 mg IV q8h plus Gentamicin 2 mg/kg loading dose IV or IM followed by 1.5 mg/kg maintenance dose q8h with or without Metronidazole 500 mg PO BID × 14 d

Ambulatory regimen Ceftriaxone 250 mg IM once or Cefoxitin 2 g IM once plus probenecid 1 g PO once or Other parenteral third-generation cephalosporins plus Doxycycline 100 mg PO BID × 14 d with or without Metronidazole 500 mg PO BID × 14 d

∗ Parenteral therapy may be discontinued after 24 h if the patient has improved clinically. Continued oral therapy should consist of doxycycline 100 mg PO BID or clindamycin 450 mg PO 4× daily to complete 14 d. Adapted from Red Book. 2009:500.

Human Papillomavirus • DNA virus; responsible for genital warts (condyloma acuminata). • Responsible for the majority of Pap smear (cervical cytology) abnormalities. Types 16, 18, 31, and 45 are linked to cervical cancer. • DDx: Molluscum contagiosum, condyloma lata. • Clinical features: Single or multiple; soft, ﬂ eshy papillary or sessile lesions; growths around the perineum, vulvovaginal area, penis, or urethra; no lymphadenopathy. • Diagnosis: Characteristic clinical appearance; Pap smear reveals typical cytologic changes. • Treatment: • Patient application: Podoﬁ lox 0.5% solution or gel; Imiquimod 5% cream • Provider application: Cryotherapy, podophyllin resin 10% to 25%, trichloroacetic acid, bichloracetic acid, or surgical removal (Red Book 28th ed. 2009;477). • Prevention: HPV vaccine. Pediculosis Pubis (Lice) • Clinical features: Pruritic papules with nits (eggs) on pubic hair • Treatment: 0.5% malathion lotion (in >6yo), 1% permethrin rinse or overnight application of 5% cream, or Ivermectin (200 mcg/kg PO once; may repeat in 7–10 days). Also wash bedding in hot water. Scabies • Clinical features: Pruritis (worse at night and with hot bath); small erythematous papules with excoriations or crusting in the GU area, on interdigital webs, wrist, ankles, feet, axilla, buttocks, areolae. May see vesicles, burrows. May present on scalp and face in infants. • Treatment: Apply 5% Permethrin cream applied overnight (neck down), rinse in AM (for infants <1m: include scalp and limit application to 6h); or ivermectin (200 mcg/kg) PO once; may repeat in 7–10 days.

EATING DISORDERS Anorexia Nervosa (AN) • DSM-IV diagnostic criteria • Refusal to maintain body weight at or above a minimally normal weight for age and height or failure to make expected weight gain during a period of growth, leading to body weight <85% of that expected Adolescent Medicine 57

• Intense fear of gaining weight or being fat, although underweight • Disturbance in the way one’s body weight or shape is experienced, undue infl uence of body shape and weight on self-evaluation, or denial of the seriousness of current low body weight • In postmenarchal women, amenorrhea, or absence of at least three consecutive menstrual cycles; a woman is considered amenorrheic if her periods return only after hormone administration • Types • Restricting type: No regular binge eating or purging during current episode of AN • Binge eating or purging type: Regular binge eating or purging during current episode of AN Bulimia Nervosa (BN) • DSM-IV diagnostic criteria • Recurrent episodes of binge eating characterized by both of the following: • Eating, in a discreet period of time, an amount of food that is defi nitely larger than most people would eat during a similar period of time and under similar circumstances. • A sense of lack of control over eating during the episode. • Recurrent inappropriate compensatory behavior to prevent weight gain, such as self- induced vomiting; misuse of laxatives, diuretics, enemas, or other medications; fasting; or excessive exercise. • The binge eating and inappropriate compensatory behaviors both occur, on average, at least twice a week for 3 months. • Self-evaluation is unduly infl uenced by body shape and weight. • The disturbance does not occur exclusively during episodes of AN. • Types • Purging type: Regular self-induced vomiting or misuse of laxatives, diuretics, or enemas during current episode of BN. • Nonpurging type: No regular self-induced vomiting or misuse of laxatives, diuretics, or enemas; use of other inappropriate compensatory behaviors, such as fasting or excessive exercise, during current episode of BN. Eating Disorders Not Otherwise Specifi ed • Patients with disorders of eating who do not fulfi ll the criteria for AN or BN. • Examples include:

• For females, all the criteria for AN are met except that the individual has regular menses. PEDIATRICS • All the criteria for AN are met except that, despite signiﬁ cant weight loss, the individual’s current weight is in the normal range. • All the criteria for BN are met except that the binge eating and inappropriate compensatory mechanisms occur at a frequency of <2x week or for a duration <3 mo. • The regular use of inappropriate compensatory behavior by an individual of normal body weight after eating small amounts of food (eg, self-induced vomiting after consumption of 2 cookies). • Repeatedly chewing and spitting out, but not swallowing, large amounts of food. • Binge-eating disorder: recurrent episodes of binge eating in the absence of the regular use of inappropriate compensatory behaviors characteristic of BN.

CLINICAL FEATURES AND POTENTIAL COMPLICATIONS OF EATING DISORDERS

Anorexia Nervosa Bulimia Nervosa

General Cold intolerance, weakness, fatigue, dry Weakness, fatigue, weight and hyperkeratotic skin, lanugo, hypo- ﬂ uctuations, calluses on the thermia, acrocyanosis, edema dorsum of hands, painless parotid gland enlargement, dental enamel erosion and caries, edema

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Anorexia Nervosa Bulimia Nervosa

CNS Poor concentration, muscle weakness, Headaches, muscle cramps, peripheral neuropathies, seizures, cortical seizures atrophy, cognitive processing diﬃ culties

CV Postural dizziness and fainting with Arrhythmias, cardiomyopathy orthostatic hypotension, sinus bradycardia, arrhythmias, low-voltage ECG changes, prolonged QTc interval, T-wave inversions, ST-segment depression, ↓ cardiac size and ventricular wall thickness, ↓ contractility, cardiomyopathy, MVP, pericardial eﬀ usion, CHF

Endocrine Amenorrhea, pubertal delay, poor Irregular menses growth, low bone mineral density, euthyroid sick syndrome, low IGF-1 level, low basal LH and FSH levels, low 24 h LH secretion, blunted response to GnRH, low estradiol or testosterone, ↓ response of ACTH to CRH

GI Abdominal discomfort, constipation, de- Abdominal discomfort, nau- layed gastric emptying, SMA syndrome, sea, esophagitis, Mallory-Weiss acute fatty necrosis tears, rupture of esophagus or stomach, acute pancreatitis, paralytic ileus

Hematologic Leukopenia, anemia, thrombocytopenia, Platelet dysfunction decreased C3 and ESR

Metabolic Dehydration; low phosphorus, mag- Dehydration; low phosphorus, nesium, calcium, potassium, sodium, potassium, sodium levels zinc, copper, glucose, vitamin A; high cholesterol, carotene

Psychological Perfectionist, “type A” personality, Impulsive, prone to acting out, introverted, poor self-esteem, denial of outgoing, poor self-esteem, problem aware of problem and seeks help

Renal Elevated BUN, decreased GFR, nephro- Elevated BUN with excessive genic DI, metabolic alkalosis, alkaline vomiting, metabolic alkalosis, urine alkaline urine

• Differential Diagnoses: IBD, malabsorptive conditions, celiac disease, hyperthyroidism, renal disease, hypopituitarism, Addison’s disease, IDDM or DI, malignancy • Diagnosis: Based on history, complete physical exam (including height, weight, vital signs, BMI, ideal body weight). Laboratory testing helpful in identifying comorbidities: CBC, CHEM10, TSH, ESR, ECG. • Indications for hospitalization: • Severe malnutrition (<75% IBW) or ongoing weight loss • Failure of outpatient management • Acute food refusal • Severe electrolyte abnormalities • Vital sign compromise: HR <50 bpm during the day, HR <45 while asleep, BP <80/50 mm Hg, temperature <96°F, orthostatic change in HR (>20 bpm) or BP (>10 bpm) from lying to standing after 5 minutes; arrhythmias; rapid weight loss; psychiatric emergencies • General Treatment Guidelines (Pediatr Rev. 27(1):5) Adolescent Medicine 59

• Interdisciplinary approach with medical provider, mental health provider, and dietician. • Avoid IV fl uid boluses; could potentially precipitate heart failure. • Start low with caloric intake (~ 30 kcal/kg/d) and advance slowly with goal weight gain of 2 to 3 lb/wk. • Fluid retention and low basal metabolic rate responsible for rapid weight gain in early refeeding. • Watch for signs of refeeding syndrome during the fi rst 2 to 3 weeks of refeeding (Br Med J. 2008;336:1495). • Occurs when patients with severe malnutrition are rapidly refed and insulin levels increase. • Causes fl uid and electrolyte disturbances (hypophosphatemia, hypomagnesemia, and hypokalemia). • May lead to dysrhythmias, cardiovascular collapse, rhabdomyolysis, and neurologic compromise. • Treat prophylactically with potassium phosphate to replenish electrolytes.

Emergency Contraception • Progestin-only methods (Plan B): Two single doses of 0.75-mg levonorgestrel taken 12 h apart or a single dose of 1.5-mg levonorgestrel taken once • Superior efﬁ cacy if taken within 72 h after unprotected intercourse (89%); after 120 h after unprotected intercourse (50%) • Fewest contraindications and side effects

Available at www.AccessPediatrics.com • Adolescent health screening • Pelvic pain and dysmenorrhea • Abnormal vaginal bleeding • Contraception PEDIATRICS CHAPTER 7 Allergy and Immunology

GELL AND COOMBS CLASSIFICATION OF HYPERSENSITIVITY IMMUNE RESPONSES

Type Mechanism Examples

I: Anaphylactic or IgE-mediated mast Anaphylaxis, allergic rhinitis, allergic immediate hyper- cell degranulation and asthma, acute urticaria, insect sting sensitivity activation allergy

II: Antibody- IgM or IgG against Autoimmune or drug-induced hemo- mediated cytolytic antigens bound to cell lytic anemia, Goodpasture’s disease, Rh reactions membrane structures hemolytic disease

III: Immune- Complexes of IgM or IgG Serum sickness, SLE, vasculitis, poststrep- complex mediated and circulating antigens tococcal glomerulonephritis

IV: Delayed hyper- T lymphocytes Tuberculin skin test reactions, GVHD, sensitivity contact dermatitis

Allergy Testing • Immediate hypersensitivity skin test (IHST): Stop antihistamines for 5 days before testing. Use the prick technique (introduce antigen intracutaneously via pricking or puncturing). Positive predictive value is good for inhalants, moderate for foods (high rate of false- positive results); negative predictive value is excellent for foods and inhalants. • Serum tests: Serum eosinophilia is often present (low diagnostic value); serum IgE is often elevated with atopic dermatitis (low diagnostic value); serum allergen-specifi c IgE assays (eg, RAST) measure circulating Ag-specifi c IgE and have similar predictive value to skin testing. Anaphylaxis • Defi nition: A serious allergic reaction that is rapid in onset and may cause death • Differential Diagnosis: • Vasovagal syncope, panic attack, hyperventilation, systemic mastocytosis, scombroid fi sh poisoning. Rare causes include carcinoid syndrome, pheochromocytoma, and idiosyn- cratic causes. • Anaphylactoid reactions, which have complement activation, but are not IgE mediated. • Example: Radiocontrast media, drugs (NSAIDS, opiate), blood products, exercise induced, and idiopathic. Clinical presentation and treatment are the same as for anaphylaxis. • Major Trigger: Food (most commonly peanut, tree nuts, shellfi sh, fi sh, eggs, milk), insect venom, latex, drugs, immunotherapy • Pathophysiology: Production of IgE in a susceptible individual (sensitization)→ IgE- sensitized mast cells and basophils→ exposure of allergen and then allergen binding leads to mast cell degranulation. • Clinical Symptoms and PE • Variable symptoms: Angioedema, shortness of breath, wheezing, fl ushing, urticaria, pruritus, hypotension, chest pain, syncope, abdominal pain, vomiting, diarrhea, aura of impending doom. • Time pattern: Uniphasic, biphasic (recur up to 8 h later in 3%–20%), or protracted syndrome.

60 Allergy and Immunology 61

• Diagnostic Studies • Markers of mast cell degranulation, including plasma histamine (only elevated for 1 h after the onset of symptoms), urinary histamine and metabolites (elevated for longer), or serum tryptase level (peaks is 90 minutes and stays elevated for as long as 5 h) may be useful when the diagnosis is uncertain. Undetectable levels do not rule out anaphylaxis (tryptase is positive <50%). • In vitro allergen-specifi c IgE assays or IHST may be used later to confi rm. IHST may not be reliably positive in sensitized individuals for up to 4 to 6 weeks after an episode of anaphylaxis. In sensitized individuals, the test should be repeated if results are negative. • Treatment • Monitor patients with mild reactions limited to fl ushing, urticaria, angioedema, and mild bronchospasm in the ED for a minimum of 6 to 8 hours. Consider longer observation of patients with mild symptoms who have received epinephrine because epinephrine may have minimized the symptoms. • Provide prolonged observation of patients with moderate to severe reactions, asthma with wheezing, ingested antigen with the possibility of continued absorption, or a history of biphasic response. • See table below.

TREATMENT REGIMEN FOR A PATIENT EXPERIENCING ANAPHYLAXIS

Agent Dose Comments

Epinephrine 0.01 mg/kg (0.01 mL/kg of 1:1000 solution); Immediate eﬀ ect, IM or Sub Q every 3–5 min as needed; ﬁ rst-line therapy maximum dose, 0.5 mg, Adult: 0.3–0.5 mg (0.3–0.5 mL of 1:1000 solution) repeat every 3–5 min as needed If 1:10,000 solution) available

Albuterol 2.5–5 mg nebulized as needed Airway management

Methylprednisolone 2 mg/kg IV No immediate eﬀ ect, or hydrocortisone 0.5–2.0 mg/kg IV (maximum dose, 250 mg) prevention of second wave of symptoms PEDIATRICS

Diphenhydramine 1–2 mg/kg IV/IM over 5 min (maximum Adjunctive therapy (H1 blocker) dose, 50 mg) q6h as needed

Ranitidine (H2 blocker) 1 mg/kg IV (maximum dose, 50 mg) q6h Adjunctive therapy as needed

• Anaphylaxis Prevention: Identify trigger; avoidance; wear identiﬁ cation; carry epinephrine auto-injector; and provide patient and family school education.

Urticaria and Angioedema • Deﬁ nition: Urticaria is extravasation of plasma into dermis (wheal ± erythema); angioedema is plasma extravasation into subcutaneous tissue. • Epidemiology: The prevalence of urticaria/angioedema in the United States is 15% to 20%. • Differential Diagnosis: Erythema multiforme minor, bullous pemphigoid, dermatitis herpetiformis and mastocytosis • Classiﬁ cation • Acute: ≤6 to 8 weeks; viral infections, insect stings, foods, drugs (ACEI angioedema) • Chronic: > 8 weeks; physical urticaria (cold, cholinergic, pressure, vibratory, dermog- raphism, exercise); urticarial vasculitis (biopsy for dx); autoimmune urticaria (anti-IgE receptor antibody, anti-thyroglobulin antibody, antimicrosomal antibody); chronic idiopathic urticaria (most likely cause autoimmune) 62 Pediatrics

• Hereditary angioedema (HAE): AD heredity as well as spontaneous mutations (50%); painless, nonpruritic, nonpitting swelling following trauma or stress. • HAE I: ↓C1 esterase inhibitor (C1-INH) level; ↓C2, C4 level • HAE II: C1-INH level is normal or high, but function is ↓; ↓C2, C4 level • HAE III (estrogen dependent): Normal C1-INH level and function; normal C2, C4 • Acquired angioedema (AAE): Acquired C1-INH defi ciency • AAE type I: Very rare lymphoproliferative disorder; monoclonal gammopathy • AAE type II: Very rare; anti-IgG to C1-INH • Low C1q level in addition to depletion of C4 and C2 • Diagnosis • Workup is based on the history and clinical presentation. • Consider removal of exacerbating agents (drugs) and use elimination from diet approach. • Consider CBC, UA, CXR, ESR, LFT, TSH or T4, ANA, and antithyroid antibodies (with strong FHx). • Consider autologous skin testing (using patient’s serum) to dx autoimmune urticaria. • C4 level and qualitative and quantitative C1-INH to evaluate HAE. • C1q in addition to C4 and C2 level to evaluate AAE. • Treatment • Treatment depends on the etiology of urticaria/angioedema. • Antihistamine (H1 blocker) works best for acute types (preferably nonsedating form). • Ranitidine, montelukast, cyproheptadine, and doxepin can be considered as adjunct therapy. • Reserve steroids and other immunosuppressants for severe or refractory urticaria. • Treatment for HAE includes supportive care ± FFP during acute attacks; prophylactic da- nozol with epsilon aminocaproic acid is an option. Recombinant human C1-INH is FDA approved in the United States for prophylaxis. Allergic Rhinitis • Defi nition: Allergen-driven infl ammation of the mucosa of the upper respiratory tract • Differential Diagnosis • Perennial versus seasonal allergic rhinitis, nonallergic rhinitis • Infectious rhinitis, vasomotor rhinitis, drugs, nasal polyps, anatomic causes • Nonallergic rhinitis with eosinophilia syndrome (NARES), hormonal rhinitis • Diagnosis: Most often based on clinical presentation. • Clinical symptoms and physical exam • Sx: Watery rhinorrhea, sneezing, and nasal congestion with itchy and watery eyes • PE: Reveals a transverse crease across the bridge of the nose (the “allergic salute”); folds inferior to the lower eyelid (Dennie’s lines); periorbital darkening (“allergic shiners”); conjunctivitis; and pale, edematous nasal turbinates • Diagnostic Studies: IHST are less expensive and more specifi c than serum assays for allergen-specifi c IgE for aeroallergens. Total serum IgE and nasal cytology is rarely done. CT scan may be done for evaluation of refractory sinusitis. • Treatment • Minimizing exposure to allergens (eg, dust mite, per dander) is important for reducing symptoms.

TREATMENT OPTIONS FOR ALLERGIC RHINITIS

Agents Example of Medication Comments Intranasal Mometasone furoate, Mainstay of therapy steroids ﬂ uticasone Antihistamine Loratadine, fexofenadine, Avoid the use of sedating ﬁ rst- cetirizine generation antihistamines

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Agents Example of Medication Comments Nasal deconges- Pseudoephedrine Use judiciously because of rebound tants congestion if used >5–7 days

PO and IM Prednisolone, prednisone Rarely used due to systemic side steroids eﬀ ects

Mast cell stabilizer Cromolyn sodium Intranasal use

Leukotriene re- Montelukast sodium Typical use in association with ceptor antagonist asthma

Immunotherapy Administration of speciﬁ c Use when medical management and (subcutaneous) perennial or seasonal allergen(s) environmental controls failed identiﬁ ed as associated with Success rate, 80% rhinitis in the patient Discontinue after 3–5 yr for patients Sublingual immunotherapy not with good response FDA approved

PRIMARY IMMUNODEFICIENCY • Defi nition: Primary immunodefi ciencies (PIs) are inherited disorders of immune system function. • Epidemiology: The incidence is one in 2000 to 10,000 births. Most are single-gene defects, but polygenic inheritance may also occur. • Classifi cation: Classifi ed based on immunologic mechanism that is disrupted. Defect in, B cell only (50%) >B and T cell (including SCID, 20%) >phagocyte (10%–18%) >T cell (10%) = other (10%) >complement defi ciency (2%). • Diagnosis: Consider work up if two or more warning signs are present (see table below). A genetic defect can often be identifi ed in individuals with PI.

TEN WARNING SIGNS OF PRIMARY IMMUNODEFICIENCY

Eight or more new ear infections within 1 year PEDIATRICS Two or more serious sinus infections within 1 year

Two or more months on antibiotics with little eﬀ ect

Two or more pneumonias within 1 year

Failure of an infant to gain weight or grow normally

Recurrent, deep skin or organ abscesses

Persistent thrush in mouth or elsewhere on skin after 1 year of age

Need for IV antibiotics to clear infections

Two or more deep-seated infections

Family history of a primary immunodeﬁ ciency

Data from http://www.INFO4PI.org.

COMPLEMENT DEFICIENCY

• Diagnosis: History and clinical presentation; total hemolytic complement titer (CH50) should be sent; consider alternate pathway hemolytic titer (AH50) to evaluation alternate pathway. 64 Pediatrics

CLINICAL PRESENTATION OF COMPLEMENT DEFICIENCY

Defi ciency Presentation Early components of the classic Autoimmune inﬂ ammatory pathology (eg, SLE) pathway (C1q, C1r, C2, C4) Terminal components C5–C8 Recurrent infections with Neisseria meningitides; rheumatic disease C9 Two clinical phenotypes: asymptomatic or recurrent Neisserial spp. infections C3, central component Recurrent infections, membranoproliferative glomerulonephritis, vasculitis Factor H deﬁ ciency Recurrent infections and familial relapsing HUS

C1-INH deﬁ ciency Hereditary angioedema (not PI; see Urticaria/Angioedema section)

COMPLEMENT DEFICIENCY • Treatment • Supportive care. • In emergency situations, FFP may be used to replace complement. • Vaccines: Pneumococcal (defect in early component) and meningococcal (defect in early and terminal components) vaccines are recommended. Secondary Immunodefi ciency • Defi nition: Acquired defect of the immune system as a result of an extrinsic factor (eg, infections, malnutrition, drugs, malignancy, biochemical abnormalities). More common than primary immunodefi ciencies. • Etiologies: See table below. PATHOPHYSIOLOGY OF EXAMPLES OF SECONDARY IMMUNODEFICIENCIES

Causes of Secondary Immunodefi ciency Pathophysiology and Clinical Caveats Congenital conditions • Down syndrome: ↓ T-cells, NK cells, lymphoproliferative response; ↓ immune response to vaccines • Turner syndrome: Same as above; also ↓IgM and IgG levels • Sickle cell disease: Spleen microinfarctions → autosplenectomy (see asplenia and hyposplenism below) Asplenia and hyposplenism • ↓IgM production → ↑ capsulated bacterial infections (Streptococcus pneumoniae, Haemophilus infl uenza, Neisseria meningitidis) → daily antibiotic prophylaxis with penicillin V or amoxicillin; pneumococcal and meningococcal vaccine should be given Age • Prematurity: Absence of maternal IgG transfer before 32 wk gestation; ↓ NK cell function, ↓ neutrophil numbers, and ↓ humoral immunity; impaired complement production Metabolic diseases • Diabetes mellitus: ↓ Cellular immunity; therefore, more prone to viral and fungal infections; ↓ immune response to vaccines • Uremia: ↓ Phagocytosis → six to 16-fold ↑ TB, ↓ immune response to vaccines • Liver failure: More susceptible to bacterial peritonitis and sepsis

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Causes of Secondary Immunodefi ciency Pathophysiology and Clinical Caveats

Malnutrition • Occurs in individuals with protein-calorie malnutrition, vitamin A defi ciency, pyridoxine defi ciency, zinc or selenium defi ciency, alcoholism • ↓ T-cell number and function, cutaneous anergy; severe malnutrition associated with ↓ B-cell function, ↓ IgG, and poor vaccine response; ↑ pneumonia and gastroenteritis

Autoimmune diseases • Patients with SLE have ↓ neutrophil, T-cell, NK-cell numbers and ↓ phagocytosis → ↑ susceptibility to infections and hypergammaglobulinemia

Surgery, trauma • ↑ Cortisol levels, vascular permeability or loss of skin barrier (burns, surgery) → ↑ risk of infections

Protein loss • Nephrotic syndrome: ↓ T-cell number and function, ↓ IgG levels → ↑ risk for infections, ↓ response to vaccines • Intestinal lymphangiectasia: Dilatation of lymphatics in the gut → loss of lymph with immunoglobulins → ↑ susceptibility to infections

Infectious causes • HIV, TB, candidiasis, hepatitis C, congenital rubella, CMV, EBV → suppresses immune system or upregulates immune system to a nonresponsive state

Malignancy • Malignancies or treatment for malignancies may lead to bone marrow suppression

Pregnancy • ↓ Cellular immunity (secondary to progesterone) → ↑ susceptibility to viral, fungal, protozoal, and helminthic infections

Drugs • Immunosuppressive, chemotherapy, and antirheumatic drugs directly aﬀ ect bone marrow production of B and T cells

Environmental • Ultraviolet B: Exposure causes ↑ T-cell apoptosis and release PEDIATRICS of tolerogenic cytokines from skin APCs → ↓ cellular immunity • Ionizing radiation (x-ray, gamma ray): B cell > T cell apoptosis, bone marrow suppression → ↓ cellular and humoral immunity • Sleep deprivation, chronic hypoxia, high altitude → ↑ cortisol levels → ↓ cellular and humoral immunity

Stress • Mechanism unknown but maybe related to ↑ cortisol; ↑ URI, herpes reactivation

Data from J Allergy Clin Immunol. 2008;121(suppl 2):S388.

Available at www.AccessPediatrics.com • Drug allergy • Clinical features, diagnosis, and treatment of patients with phagocyte defects • Clinical features, diagnosis, and treatment of patients with B-cell defects • Cellular deﬁ ciencies CHAPTER 8 Cardiology

EVALUATION OF SUSPTECTED CONGENITAL HEART DISEASE See Chapter 32.

STRUCTURAL HEART DISEASE Congenital heart diseases are the most common birth defects, with a frequency of approximately 8 in 1000 liveborn children. Acyanotic Heart Disease Atrial Septal Defect (ASD) • Ostium secundum: Defi ciency in the septum primum that normally covers the ostium secundum; 70% of ASDs. • Ostium primum: A type of AV septal defect; 20% of ASDs. • Sinus venosus: Located at cavoatrial junction (SVC or IVC); 10% of ASDs; associated with partial anomalous pulmonary venous drainage. • Physiology: Left-to-right shunt, pulmonary overcirculation, right heart dilation. • Presentation: Typically asymptomatic in childhood; possibly mild exercise intolerance. • Physical exam: Fixed split S2 (caused by low pulmonary impedance); SEM LUSB (pulmonary fl ow). • CXR: Cardiomegaly if the RV is signifi cantly enlarged; dilated central PAs, typically without pulmonary edema. • EKG: Classically, rSR’ in V1; may have RAD or RVH. • Treatment: Pharmacologic therapy is rarely needed. Small or moderate secundum defects detected in neonates often close spontaneously. If there is a persistent shunt and right heart volume overload, the ASD should be closed electively. Ventricular Septal Defect (VSD) • Prevalence: Most common form of CHD other than bicuspid aortic valve; 20% of all CHD (frequency in population, ~0.2%–0.4%). • Location: Perimembranous (80%), muscular (5%–20%), supracristal (5%–8% in the United States), and inlet muscular (often classifi ed with AV septal defects). • Physiology: Left-to-right shunt; magnitude depends on the size of the defect, pulmonary overcirculation; left heart dilatation. • Presentation: Depends on the magnitude of the shunt; small defects are typically asymptomatic but large defects in infants (increasing shunt as PVR drops) result in tachypnea, FTT, and poorly tolerated lower respiratory tract infections; older children manifest exercise intolerance. • Physical exam: Relatively small (restrictive) VSDs have a typical holosystolic murmur, plateau in quality, loudest LLSB, may have a thrill; moderate VSDs may have diastolic rumble (increased fl ow from the left atrium into the LV, typically indicating Qp:Qs over 2:1); large, unrestrictive VSDs may have only soft pulmonary fl ow murmur but a prominent gallop and hyperactive precordium. • CXR: Cardiomegaly, increased pulmonary vascular markings and/or pulmonary edema in moderate to large shunts, normal CXR for small shunts. • EKG: LVH for moderate to large shunts. If RVH is present, consider RV outfl ow obstruction or increased PVR. • Treatment: • Defi nitive treatment: Surgical closure (or transcatheter closure), which is indicated for unrestrictive, large defects, symptoms, aortic valve distortion, or persistent cardiomegaly. Smaller defects may close spontaneously, particularly muscular VSDs. • Temporizing or medical therapy: Diuretics + afterload reduction, caloric supplementation for moderate to large shunts. 66 Cardiology 67

Atrioventricular Septal Defect (AV Canal) (Figure 8-1) • Results from incomplete fusion of endocardial cushions • Complete: Primum ASD, inlet VSD, and a common AV valve spanning the inlets to both ventricles • Partial: Ostium primum ASD with cleft mitral valve. • Frequently associated with Down syndrome • Physiology: Large left-to-right shunt, pulmonary overcirculation, left and right heart dilation • Presentation: Tachypnea, FTT, worsens as PVR drops • Physical exam • Complete AV canal with large VSD component: Hyperdy- namic precordium, holosystolic murmur from AV valve regurgitation, diastolic rumble at apex Figure 8-1 Atrioventricular • Primum ASD: Similar to other ASDs but may have holosys- canal defect. tolic murmur of left AV valve regurgitation • CXR: Cardiomegaly, increased pulmonary vascular markings for moderate to large shunts • EKG: LAD or NW axis; rSR’ in V1, fi rst-degree heart block common • Rx: Medical therapy is the same as for VSD; surgery in the fi rst 6 to 8 months of life (or when symptomatic despite medical therapy) Patent Ductus Arteriosus (PDA)(Also See Chapter 32) • Common in premature infants • Physiology: Left-to-right shunt, pulmonary overcirculation, left heart dilatation • Presentation • Moderate to large shunts: Tachypnea, FTT, pulmonary hemorrhage in premature infants • Small shunts: Asymptomatic • Physical exam: For moderate to large shunts, hyperdynamic precordium, bounding pulses with widened pulse pressure, continuous “machinery” murmur loudest under the left clavicle; or possibly only a soft murmur if the PDA is very large; tiny PDAs may be inaudible • CXR: Cardiomegaly, increased pulmonary vascular markings in moderate to large shunts (normal for small shunts) • EKG: Typically normal; LVH ± RVH if a large shunt is present • Treatment: Indomethacin or surgery for neonates; transcatheter closure or surgery for most other patients PEDIATRICS Cyanotic Heart Disease Tetralogy of Fallot (TOF) (Figure 8-2) • Tetrad: RVH, VSD, overriding aorta, and RVOT obstruction. All four fi ndings are caused by anterior superior deviation of the conotruncal septum. • Most common form of cyanotic heart disease presenting beyond the fi rst week of life. • Hypercyanotic episodes (“Tet spells”): Acute desaturation from worsening RVOT obstruction (dehydration) or decrease in SVR (fever, hypoxemia) leading to decreased pulmonary blood fl ow. • Physiology: Ventricular level shunting (RV blood → aorta), decreased pulmonary blood fl ow. • Presentation: Murmur, progressive cyanosis (including hypercyanotic spells); degree of cyanosis depends on severity of RVOT obstruction; if very severe. RVOT obstruction may Figure 8-2 Tetralogy of Fallot. be ductal dependent for pulmonary blood fl ow. • Physical exam: RV tap, SEM left midsternal border (from RVOT obstruction, not from VSD), classically murmur decreases during Tet spells. • CXR: “Coeur en sabot” with hypertrophied RV and absence of the MPA segment; look for right aortic arch (common association). • EKG: RAD and RVH. • Treatment: PGE1 for severely cyanotic neonates (ductal-dependent pulmonary circulation); β-blockers may decrease the likelihood of tet spells; surgical repair is typically done in the fi rst few months of life. Some severely cyanotic neonates are fi rst treated with a BT shunt. 68 Pediatrics

• Treatment for Tet spells: Knee–chest position, calm infant, morphine, volume resuscitation, oxygen, β-blockers (eg, esmolol infusion), phenylephrine, ketamine ± paralysis and general anesthesia, emergency surgery D-Transposition of the Great Arteries (TGA) (Figure 8-3) • The aorta arises from the RV, and the PA arises from the LV (ventriculoarterial discordance). • Most common form of cyanotic heart disease diagnosed in the fi rst week of life; boys are affected more often than girls. • Physiology: Circulations in parallel; requires mixing. • Presentation: Cyanosis in the fi rst hours of life without respiratory distress. • Physical exam: Often nonspecifi c; typically no murmur; prominent S2 (anterior aorta, closer to the chest wall). • CXR: “Egg on a string” but more commonly nonspecifi c with increased or normal pulmonary vascular markings. • EKG: RAD and RVH; may be normal. • Treatment: PGE1, balloon atrial septostomy, arterial switch Figure 8-3 D-Transposition operation early in life. of the great arteries.

Total Anomalous Pulmonary Venous Return (TAPVR)(Figure 8-4) • All pulmonary veins drain into the systemic veins or RA. • Four types: Supracardiac (drain via innominate vein or SVC; ~50%), cardiac (coronary sinus or right atrium; 25%), infracardiac (IVC, typically via portal system; 20%), mixed (5%). • Unobstructed veins are more common, but all types may become obstructed (most likely in infracardiac type). • Physiology: Complete mixing, obligate right–to-left shunt at the atrial level. • Presentation: Tachypnea; if obstructed: severe cyanosis, pulmonary hypertension, and shock. • Physical exam: RV tap, may have faint SEM LUSB (similar to ASD), ± gallop, ± loud P2. Figure 8-4 Total anomalous pulmonary venous return • EKG: RAD, RAE and RVH. infracardiac type. • CXR: Typically in obstructed TAPVC, the heart size is normal early, with pulmonary edema. Classic “snowman” sign is a late fi nding of unobstructed supracardiac TAPVR (dilated vertical vein → innominate vein → SVC). • Treatment: Surgery required; if obstructed, it is a surgical emergency; if unobstructed, surgery can be delayed for weeks to months. Truncus Arteriosus (Figure 8-5) • Single semilunar valve (truncal valve) and single blood vessel arising from the heart gives rise to systemic, pulmonary, and coronary circulations; this is caused by a lack of conotruncal septation. • The truncal valve typically overrides the VSD. • Physiology: Left–to-right and right-to-left shunt; increased pulmonary blood fl ow. • Presentation: Tachypnea, FTT, often several weeks after birth; the degree of cyanosis (usually mild) depends on the degree of pulmonary edema and the size of the PAs. • Physical exam: RV tap, loud single S2, systolic ejection click, ± murmur increased fl ow across a single semilunar valve and truncal valve stenosis (systolic) or regurgitation (diastolic) , wide pulse pressure. Figure 8-5 Truncus arteriosus. • CXR: Cardiomegaly, increased PVM, absence of MPA segment, absent thymus (DiGeorge syndrome), R aortic orch is common. Cardiology 69

• EKG: RVH or BVH; may have ischemic changes if diastolic runoff and systemic “steal” is signifi cant. • Treatment: High risk for NEC preoperatively. so must be cautious with enteral feeding; complete repair is done during the fi rst few weeks of life. Tricuspid Atresia (Figure 8-6) • Wide range of anatomic arrangements based on the great artery relationship (sometimes associated with TGA) and the degree of pulmonary stenosis. • Most common is normally related great arteries with pulmonary stenosis. • Physiology: Complete mixing; obligate right-to-left shunt at the atrial level. • Presentation: The degree of cyanosis depends on severity of pulmonary outfl ow tract obstruction. • Physical exam: SEM LUSB (from PS; variable, depending on the magnitude of pulmonary blood fl ow). • EKG: LAD, RAE, possibly LVH. • CXR: RA dilation, ± cardiomegaly, PVM depend on the Figure 8-6 Tricuspid atresia. degree of pulmonary outfl ow tract obstruction. • Treatment: Single-ventricle palliation pathway. May require BTS (and PGE1 preoperatively) for ↓ PBF or PAB for ↑ PBF. Hypoplastic Left Heart Syndrome (HLHS) (Figure 8-7) • Spectrum from severe mitral and aortic stenosis to mitral and aortic atresia, LV hypoplasia, coarctation, and subtypes of RV dominant AV septal defects. • Boys are more often affected than girls. In girls, commonly associated with Tumer syndrome. • Physiology: Ductal-dependent systemic circulation; obligate left-to-right shunt at the atrial level. • Presentation: Mild or no cyanosis at birth, progressing to tachypnea, poor perfusion, shock, and cardiovascular collapse with PDA closure, causing systemic hypoperfusion. • Physical exam: Single S2, RV tap, progressing to gallop;

poor perfusion; pallor; weak pulses. PEDIATRICS • CXR: Variable cardiomegaly; increased pulmonary vascular markings. Figure 8-7 Hypoplastic left • EKG: RAD, RAE, RVH. heart syndrome. • Treatment: PGE; note that as ductus closes, the systemic oxygen saturation may increase (contrary to lesions that are ductal dependent for PBF, eg, pulmonary atresia). Single- ventricle palliations: Norwood → BDG → Fontan. Pulmonary Atresia with Intact Ventricular Septum (PA/IVS) (Figure 8-8) • The sizes of the TV and RV are crucial in determining the interventional strategy. • RV pressure is suprasystemic. • May have RV to coronary artery ﬁ stulae; if coronaries have proximal stenoses, coronary circulation is dependent on RV for myocardial perfusion (“RV-dependent coronaries”). • Physiology: Ductal-dependent pulmonary circulation, obligate right-to-left shunt at ASD. • Presentation: Cyanosis from birth; worse as PDA closes. • Physical exam: Single S2.; holosystolic murmur RLSB (TR). • CXR: Nonspeciﬁ c, decreased PVM, rarely cardiomegaly (RA dilatation). • EKG: RAE, LVH. Figure 8-8 Pulmonary atresia • Treatment: PGE1, early cardiac catheterization to with an intact ventricular determine if coronary circulation is RV dependent; if not septum. 70 Pediatrics

RV dependent, open pulmonary valve (transcatheter radiofrequency perforation versus surgical RVOT patch); if RV grows adequately, may require no further procedures for many years; otherwise may undergo BDG with patent RVOT (“1½ ventricle repair”). If coronary circulation is RV dependent, the patient should undergo single-ventricle palliation: BTS → BDG → Fontan.

ACQUIRED HEART DISEASE Myocarditis Inﬂ ammatory inﬁ ltrate of the myocardium with necrosis and degeneration of adjacent cardiac myocytes. Most Figure 8-9 Ebstein anomaly. cases in the developed world are of viral etiology (NEJM 1985;312(14):885). Impaired contractility (acute) leads to ventricular dilation (subacute and chronic), often with acute heart failure. CAUSES OF MYOCARDITIS

Viral Nonviral Noninfectious Common: Bacteria: Toxic: Enteroviruses Rickettsia Scorpion venom esp. Coxsackie B Meningococcus Diphtheria Adenovirus Streptococcus Drugs Parvovirus B19 Tuberculosis Penicillin

Others: Sulfonamides Inﬂ uenza A Protozoans: Amphotericin B Varicella Toxoplasmosis and others Others

Epstein-Barr virus Parasites: Collagen vascular diseases: Herpesvirus Fungi and yeast: Kawasaki disease:

Hepatitis B, C Candida and others Sarcoidosis:

Epidemiology • Usually sporadic, but does occur in epidemics, particularly in infants with coxsackie virus B as the cause. Presentation • Infants: Poor feeding, fever, irritability, listlessness, pallor, and diaphoresis. • Children: Lethargy, fever, pallor, decreased appetite, abdominal pain, diaphoresis, exercise intolerance, and malaise. • Patients often have a recent history of a viral illness in past 10 to 14 days. Physical Exam • Findings consistent with left ± right heart failure (eg, resting tachycardia, gallop, tachypnea, hepatomegaly, JVD, pulmonary crackles, pallor, weak pulses). • Arrhythmias may occur and may be life threatening (J Am Coll Cardiol 1994;24(3):780). Workup • CXR: Cardiomegaly and pulmonary edema. • EKG: Sinus tachycardia, low-voltage QRS complexes, ± inverted T waves. • Echocardiography: Left ± right ventricular dilatation and dysfunction. Pericardial effusion is common. Must rule out other causes of severe myocardial dysfunction, such as ALCAPA in young infants. Cardiology 71

• Cardiac catheterization: Controversial secondary to risks of the procedure; demonstrates low cardiac output and elevated ventricular end-diastolic pressures. • Endomyocardial biopsy: Mononuclear cell infi ltrate with or without evidence of necrosis; classifi ed using the Dallas criteria. (Human Pathology 1987;18(6):619) • Viral studies: Viral PCR from myocardium is considered the gold standard. Treatment • Acute treatment aimed at supporting cardiac output while minimizing myocardial work and wall stress: • Bedrest (may slow cardiac viral replication), IVIG (may increase ventricular function and survival: Circulation 1994;89(1):252), Immunosuppressive agents (controversial, not benefi cial in adults: NEJM 1995;333(5):269), inotropes, diuretics, mechanical circulatory support (ventricular assist devices or ECMO as a bridge to recovery or transplant). • Chronic treatment is similar to other causes of myocardial dysfunction: ACEIs and β–blockers. Prognosis • Poor in newborns; better in children and adolescents, with 10% to 25% dying or requiring transplantation and up to 66% with complete recovery (Cardiol Young 2004;14(5): 488). Pericardial Disease Acute Pericarditis • Causes: Unknown (one-third of cases); infectious causes (viral: coxsackievirus, echovirus, adenovirus, infl uenza; bacterial: Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus infl uenza, Mycobacterium tuberculosis), noninfectious causes (collagen vascular disease, postcardiac surgery, drug induced, rheumatic fever, renal failure, hypothyroidism, chylopericardium, intrapericardial tumors, malignancies, radiation pericarditis, hemopericardium). Chronic Pericarditis • Lasts longer than 3 months. Usually secondary to infl ammatory disease. Constrictive Pericarditis • Thickened, adherent pericardium impairs ventricular fi lling. Management is surgical. Tuberculosis is the leading cause worldwide (Cardiol Clin 1990;8(4):645) Signs and Symptoms of Pericardial Disease • Presentation: Chest pain, possibly improved by leaning forward; tachycardia, fever, shortness of breath in cases of signifi cant pericardial effusion. • Physical exam: Pericardial friction rub = grating sound best heard LSB with patient PEDIATRICS leaning forward (may be absent with signifi cant pericardial effusion). Pulsus paradoxus (exaggeration of normal inspiratory decrease in SBP >10 mm Hg), diminished heart sounds, tachycardia, JVD. Cardiac tamponade may demonstrate Beck’s triad, which includes hypotension, increased CVP, and diminished heart sounds. • ECG: Progression of changes = diffuse ST elevation or PR depression (>80% of patients) → normalization of ST segments → widespread T-wave inversion → normalization of T waves (see below). Stage 1 Stage 2 Stage 3 Stage 4

Figure 8-10 EKG changes in pericarditis. (Reproduced with permission from Allen AD, Driscoll DJ, Shaddy RE, Feltes TF: Moss and Adams’ Heart Disease in Infants, Children, and Adolescents, 7th ed. Copyright © 2008 Wolters Kluwer Health Lippincott Williams & Wilkins.)

• CXR: Heart size may be normal in acute pericarditis without signiﬁ cant effusion. With the presence of effusion, “water-bottle heart” will be seen (enlarged, triangular heart with smoothed-out borders). • Echocardiogram: Effusion location and size should be visualized. There may be evidence of right ventricular free wall collapse. Increased respiratory variation in mitral inﬂ ow may also be demonstrated. • Cardiac enzymes may be elevated. 72 Pediatrics

Treatment of Pericarditis • NSAIDs, corticosteroids, rarely colchicines (Pediatr Cardiol 2000;21(4):395). Treatment of Effusion • Large effusions or evidence of tamponade physiology: Drainage via pericardiocentesis • Bacterial pericarditis or chronic, recurrent effusions: Surgical drainage with pericardial window

CARDIOMYOPATHIES Dilated Cardiomyopathy • Defi nition: Cardiomyopathy with increased ventricular size and reduced contractility in the absence of coronary, valvar, or pericardial disease. • Common associations: Mitral insuffi ciency, ventricular ectopy and tachyarrhythmias. • Newborns and infants have highest rate of disease; boys are more often affected than girls. • Without transplantation, 1-year mortality is approximately 50% (sudden cardiac death or ventricular failure) ( JACC 2010;55(13):1377). Genetics • Approximately one-third of patients with DCM have a familial form. AD (most common is cytoskeletal protein involvement), X-linked (typically occurs in boys with rapid progression; elevated CK-MM), Barth syndrome (LV noncompaction common). • Nearly all genes identifi ed for inherited DCM also cause skeletal myopathy. • Presentation: Shortness of breath, fatigue, orthopnea, diaphoresis, chest pain, palpitations, exercise intolerance, syncope. • Physical exam: Tachypnea, tachycardia, diaphoresis, S3 or S4 gallop, holosystolic murmur (MR), hepatomegaly, ± ascites or peripheral edema.

EVALUATION OF DILATED CARDIOMYOPATHY

Diagnostic Study Key Findings

CXR Cardiomegaly, pulmonary edema, atelectasis from bronchial compression (LA dilation), pleural eﬀ usions

ECG Sinus tachycardia, LAE, ventricular ectopy and arrhythmias, bundle branch block

Echocardiogram Reduced contractility, ventricular dilation, MR, pericardial eﬀ usion

24-hr Holter Ventricular arrhythmia, AV block, or bradycardia

Exercise testing May provide data regarding ventricular arrhythmias and physiologic reserve

Cardiac catheterization Elevated LVEDP, and pulmonary vascular resistance, obtain biopsy specimen for viral PCR and mitochondrial studies

Skeletal muscle biopsy When primary muscle disease is suspected, send microscopy, electron microscopy, electron transport chain biochemistry Metabolic Studies Specifi c Studies

Serum CBC, acylcarnitine proﬁ le (fatty acid oxidation defects), lactate, pyruvate dehydrogenase complex, electrolyte proﬁ le, creatine kinase (+ isoform analysis if elevated), amino acids, genetic testing

Urine Amino and organic acid proﬁ les Cardiology 73

Treatment Outpatient Management • ACE inhibitors and β-blockers (metoprolol/carvedilol): Mainstays of therapy • Diuretics: May be useful for symptomatic edema; no proven long-term beneﬁ t • Digoxin: Now used less often, but may improve symptoms in some patients • Vitamins (coenzyme Q10, carnitine, thiamine, riboﬂ avin): Usually reserved for mitochondrial or metabolic disease in any type of cardiomyopathy Inpatient Management • Inotropic medications avoided whenever possible; reserved for compromised hemodynamic states (milrinone ± low-dose dopamine) • Diuretics: Decrease pulmonary edema acutely; may improve preload in volume overload states • Nesiritide: Recombinant B-type natriuretic peptide infusion; improves urine output • Mechanical circulatory support: Ventricular assist devices and ECMO for those who fail medical management as a bridge to recovery or transplantation • Cardiac transplantation

ELECTROPHYSIOLOGY EKG Interpretation NORMAL PEDIATRIC ELECTROCARDIOGRAM VALUES

Frontal Heart Plane QRS PR ∗∗ Age Rate Vector Interval Q III Q V6 R V1 S V1 R V6 S V6 Group (bpm)∗ (degrees)∗ (sec)∗ (mm)† (mm)† (mm)∗ (mm)∗ (mm)∗ (mm)∗ <1 d 93–154 +59 to 0.08–0.16 4.5 2 5–26 0–23 0–11 0–9.5 (123) –163 (0.11) (14) (8) (4) (3) 1–2 d 107–182 +64 to 0.08–0.14 6.5 2.5 5–27 0–21 0–12 0–9.5 (148) –161 (0.11) (14) (9) (4.5) (3) 3–6 d 107–182 +77 to 0.07–0.14 5.5 3 3–24 0–17 0.5–12 0–10 (148) –163 (0.10) (13) (7) (5) (3.5)

1–3 wk 107–182 +65 to 0.07–0.14 6 3 3–21 0–11 2.5–16.5 0–10 PEDIATRICS (148) +161 (0.10) (11) (4) (7.5) (3.5) 1–2 mo 121–179 +31 to 0.07–0.15 7.5 3 3–20 0–12 5–21.5 0–6.5 (149) +143 (.11) (10) (5) (11.5) (3) 3–5 mo 106–186 +7 to 0.07–0.15 6.5 3 3–20 0–17 6.5–22.5 0–10 (141) +143 (0.11) (10) (6) (13) (3) 6–11 109–169 +6 to 0.07–0.16 6.5 3 1.5–20 0.5–18 6–22.5 0–7 (2) mo (134) +143 (0.11) (9.5) (4) (13) 1–2 yr 89–151 +6 to 0.08–0.16 6 3 2.5–17 0.5–21 6–22.5 0–.5 (119) +143 (0.12) (9) (8) (13) (2) 3–4 yr 73–137 +6 to 0.09–0.16 5 3.5 1–18 0.2–21 8–24.5 0–5 (108) +143 (0.12) (8) (10) (15) (1.5) 5–7 yr 65–133 +11 to 0.09–0.16 4 4.5 0.5–14 0.3–24 8.5–26.5 0–4 (1) (100) +143 (0.12) (7) (12) (16) 8–11 yr 62–130 +11 to 0.09–0.17 3 4.5 0–12 0.3–25 9–25.5 0–4 (1) (91) +114 (0.13) (5.5) (0.5) (16) 12–15 80–119 +11 to 0.09–0.18 3 4.5 0–10 0.3–21 6.5–23 0–4 (1) yr (85) +130 (.14) (4) (11) (14) ∗2nd to 98th percentile (mean). †98th percentile Pediatr Cardiol 1979;1(2):133. 74 Pediatrics

• Verify: Name, date, reason for study, standardization of leads, confi rmation of correct lead placement (apply Einthoven’s law to leads I, II, III [net forces of I + III = II]); compare I and V6 to ensure same net direction of P and T waves [to rule out limb lead reversal]) • Rate: If regular, 300 divided by number of large boxes between two consecutive QRS complexes; if irregular, 60,000 divided by the average RR interval in milliseconds. • Rhythm • NSR: P wave before every QRS, QRS after every P wave, normal sinus P wave axis (upright in leads I and aVF), all P waves are of same morphology. • Junctional rhythm: Narrow complex QRS (similar to sinus QRS), not preceded by P waves. Can be fast (junctional tachycardia) or slow (seen with sinus bradycardia, sinus node dysfunction; may see A-V dissociation). • Ventricular rhythm: Wide QRS complexes (“wide” is defi ned as different from sinus QRS), not preceded by a P wave. May be fast or slow; may see A-V dissociation. • Ectopic atrial rhythms: may be slow (atrial escape) or fast (focal atrial tachycardia), originat- ing in LA or RA (ectopic LA rhythm usually with inverted P wave in lead I, dome-and-dart P wave in VI.) • Low RA rhythm: Inverted P waves in II, III, aVF (normal PR interval is 0.04 s shorter as well); may be a variant of normal SA node. • QRS Depolarization Axis • Use directionality of leads I and aVF to determine the quadrant of the axis and then fi nd the limb lead that is isoelectric to the baseline (equal forces above and below baseline of the QRS complex) → axis is perpendicular to that lead (Figure 8-11). –90° • Northwest axis (–91 to –179) aVR aVL • Extreme LAD (Q in I/aVL, not aVF/II/ –30° III): CAVC, tri atresia, primum ASD, left –150° 0° anterior hemiblock in single ventricle ±180° I • Extreme RAD (Q in aVF/II/III, not I/aVL) • Intervals +60° • P waves (normal width in lead II ≤3yr: +120° +90° 0.03–0.09 s; >3 yr: 0.05–0.1 s; normal ampli- III II tude <3 mm) aVF • PR interval • Prolonged: 1° AV block (PR interval Figure 8-11 Directions of EKG limb leads. >98% for age) • Short: Accessory pathway, enhanced AV node conduction, increased AV node cell size (mannosidosis, Fabry disease, Pompe disease), low RA rhythm • QRS: normally < 0.1 sec for > 1 year and < 0.08 sec for < year • QT interval: Interval from the start of the QRS complex to the end of the T wave measured in leads II or V5 normally (measured from shortest R-R interval) • Must be corrected for heart rate (QTc = QT interval/√preceding R-R interval) • U waves not counted in QT interval unless > 50% of T wave amplitude • Normal <0.445 generally; <0.455 in adolescent girls; <0.47 in newborns or for shortest RR in the presence of sinus arrhythmia • Hypertrophy • RAE (classically “p pulmonale”): Tall P-wave >3 mm in any lead • LAE (classically “p mitrale”): P-wave >0.12 seconds (3 boxes) wide (often notched, biphasic P waves) • LVH: • Child >5 yr: R in V6 >30 mm • Child <5 yr: R in V6 >98% for age • Possible LVH: • Child >5 yr: R in V6 above 98% for age but below 30 mm. • S in V1 more than 5 mm above 98% for age • Q in V6 or III >98% for age + prominent LV forces exist Cardiology 75

• RVH: • R in V1 >98% for age • Upright T wave in V1 between ages 1 wk and 6 yr • QR in V1 (Q wave >1 box wide) • QR in V3r and V4r: Presence of Q and R height >mean for age (R V1 normals) (<5 yr) or >7 mm (5+ yr) • rSR’ with R’ >15 mm (<1 yr) or >10 mm (>1 yr) • Possible RVH: • S in V6 >98% for age • Pure R in V1 in child >6 mo • RAD + prominent RV forces • RV pressure estimate = R in V1 + 47 mm Hg or 5 × R in V1 • RV strain: tall R with asymmetrically inverted T wave in V1 ± ST depression • BVH: • R + S in any lead >60 (<1 yr), >55 (>1 yr) • Possible BVH: • Meets criteria for LVH + exceeds mean values for RVH or meets criteria for RVH + exceeds mean values for LVH precordial voltage normals. • Ischemia and Infarction • Q waves • Abnormal width: >1 box (any lead) • Abnormal height: aVL >2 mm, I >3 mm, II and aVF >4 mm; otherwise variable • PR segment depression ± ST segment elevation: Pericarditis • ST segment • Abnormal: Limb leads: >1 mm above or below baseline (TP segment); precordial leads: >2 mm above or below baseline (TP segment is baseline). • T waves • Should be symmetric, <7 mm in limb leads and <10 mm in precordial leads, inverted in lead V1 and V3R before age 1 wk and upright again by ~ age 6 yr • Low Voltage • Deﬁ nition: R +S wave <5 mm in limb leads or <8 mm in precordial leads • Differential diagnosis: Myocardial edema (myocarditis, myxedema, generalized edema),

increased distance from heart to skin (obesity, PTX, constrictive pericarditis, pericardial PEDIATRICS or pleural effusion), loss of functioning myocardium (CHF, tumor, amyloid)

Arrhythmias (Ped Clin N Am 2006;53(1):85)

DIFFERENTIATION OF SINUS TACHYCARDIA AND SVT

Sinus Tachycardia SVT

Rate Usually < (220 - age) Usually >(220 - age)

P waves Present, normal axis Absent, buried in QRS, or abnormal axis

RR interval (rate variability) Varies Fixed

Onset Gradual Abrupt

Termination Gradual Abrupt

Response to vagal Gradual slowing and gradual ± abrupt termination maneuvers return

Synchronized cardioversion No response Usually abrupt termination 76 Pediatrics

Dysrhythmia

Bradycardia Tachycardia

AV conduction block: Sinus: Normal P Blocked atrial ectopy: • Second degree wave followed by (atrial rate normal or (Mobitz I or II) QRS; QRS after above normal → blocked • Third degree (AV every P at AV node → ventricular dissociation bradycardia) usually not hemodynamically significant

Narrow QRS Wide QRS* • Ventricular tachycardia • Ventricular fibrillation • Antidromic SVT • SVT with aberrancy

Sinus†: Normal P SVT (increased automaticity; SVT (reentry; usually wave followed by usually not adenosine sensitive) adenosine sensitive) QRS; QRS after • Atrial tachycardia (focal or • AVRT: WPW, URAP (or every P chaotic): Abnormal P concealed conduction) wave or P wave axis • AVNRT • Atrial flutter • Atrial fibrillation • JET (tachycardia with AV dissociation)

Figure 8-12 General approach to pediatric dysrhythmias. *Deﬁ nition of wide QRS: QRS complex of any duration that is wider than the patient’s normal QRS complex. †For every 1°C increase in body temperature, expect ↑ HR ~10 bpm; always secondary to another cause such as fever, pain, hypoxia, hypovolemia, hyperthyroidism, drugs or toxins, drugs, shock, MI, PE, anemia, anxiety

ECG Changes from Drugs and Electrolytes Electrolytes • Potassium • Hypokalemia: Decrease in T-wave amplitude, prominent U wave, increased QRS duration. Arrhythmias are rare except in the case of underlying heart disease. • Hyperkalemia • 5.5–6.5 mEq/L: T waves become tall and peaked. • >6.6 mEq/L: Intraventricular conduction delay (widening of QRS) and ST-segment elevation. Increased QRS duration gives the false appearance of ventricular tachycardia. • >7 mEq/L: Prolongation of the P wave. • >8.5 mEq/L: No discernable P wave. • >9 mEq/L: Arrhythmias, AV block, VT, VF. Cardiology 77

• Calcium • Hypocalcemia: Prolongs T wave (and therefore QT interval); may see AV block; other arrhythmias uncommon. • Hypercalcemia: Shortens QT interval; may slow sinus node. • Magnesium • Hypomagnesemia: ECG effects are similar to hypokalemia. • Hypermagnesemia: May prolong the PR interval. Drugs • Tachyarrhythmias • Most antiarrhythmic drugs have proarrhythmic effects. • Drugs that are catecholaminergic may be proarrhythmic. • Drugs that prolong the QT interval (refer to www.torsades.org) may result in torsades de pointes and sudden death in patients with long QT syndrome.

OVERVIEW OF ANTIARRHYTHMICS

Vaughan- Williams Mechanism of Arrhythmia Classifi cation Action Example Target to Treat

Class I A Sodium channel Procainamide, Atrium and AET, AFlutter blockade quinidine, ventricle SVT, VT disopyramide

Class 1B Sodium channel Lidocaine, pheny- Ventricle VT blockade toin, mexiletine

Class 1C Sodium channel Flecainide, Atrium AET, AFlutter, blockade propafenone SVT

Class II β-Blockade Propranolol, SA and AV SVT, AET, VT atenolol, nadolol node

Class III Potassium channel Sotalol, amiodarone Atrium, AET, AFlutter, blocker ventricle Aﬁ b, SVT, VT PEDIATRICS

Class IV Blocks L-type Verapamil, diltiazem SA and AV SVT, VT calcium channels node

Class V Digitalis agents Digoxin SA and AV Rate control node in Aﬁ b

Afi b, atrial fi brillation; Afl , atrial fl utter.

Guide to Pacemakers Who Needs a Pacemaker? • For guidelines for device-based therapy in adults and children see Circulation, 2008;117(21):e350 and for those with CHD, see Pacing Clin Electrophysiol 2008;31 (suppl 1):S17. Types of Pacemakers • Transvenous: Leads inserted through systemic vein onto the endocardial surface; may be single (atrial only or ventricular only) or dual chamber (atrial and ventricular). • Epicardial: Leads placed surgically on the epicardial surface; may be single or dual chamber. Usually placed in smaller children or patients with complex congenital heart disease. • Biventricular: May be epicardial or transvenous; paces both the right and left ventricles; used predominantly in patients with symptomatic heart failure (“resynchronization therapy”). 78 Pediatrics

CHEST PAIN (Pediatr Clin North Am 2004;51(6):1553) The vast majority of pediatric chest pain is benign; often recurrent.

“Red Flags”: (suggestive of cardiac etiology) • History: Pain has crushing quality; associated with syncope, nausea, palpitations; may be exercise induced • Medical history: Kawasaki disease (chest pain in a patient with known CA aneurysms is ischemia until proven otherwise); homozygous familial hypercholesterolemia; aortic stenosis; prior congenital heart surgery involving manipulation of the coronary arteries (eg, arterial switch operation for d-TGA, reimplantation for anomalous origin of a coronary artery, Ross procedure), Marfan syndrome or other connective tissue disease (risk for dissection) • Physical exam: Tachycardia, diaphoresis, pallor, abnormal heart murmur

“Green Flags”: (suggestive of non-cardiac etiology) • History: Pain is brief, infrequent, transient, worse with inspiration, worse after meals, not exercise induced; prolonged history of similar pains (weeks to months). • Medical history: Reactive airways disease (RAD), recent psychosocial stressor, GERD. • Physical exam: Reproducible pain on exam (ie, chest wall tenderness to palpation).

Differential Diagnosis 1. Idiopathic (most common) a. Sharp, recurrent, normal exam 2. Musculoskeletal (second most common) a. Ask about trauma, especially weight lifting, sports, heavy school bag b. Costochondritis: Reproducible pain at costochondral/costosternal junctions; sharp, worse with activity, recurrent c. Chest wall strain d. Precordial catch syndrome: Localized anterior chest pain, sudden onset, very transient (typically lasts only seconds) 3. Psychogenic a. Inquire about recent psychosocial stressors b. Vague, changing, long-standing pain; patient or parent often anxious 4. GI a. GERD: Pain after eating; worse in recumbent position 5. Respiratory a. Exercise-induced RAD: Chest “tightness” with SOB, coughing after exercise, resolves with rest, improves with bronchodilators b. Pneumonia, empyema: Fever, cough, rales and dullness to percussion c. Pneumothorax: Most common in tall, thin boys d. Pulmonary embolus: Rare in children 6. Cardiac a. Myocardial ischemia i. Rare in children, even in children with heart disease ii. Crushing, diffuse, unrelenting, not sharp iii. Seen with anomalous coronary artery, history of coronary aneurysms (Kawasaki disease), cocaine use b. Arrhythmia i. Sustained arrhythmias, especially tachyarrhythmias, may be uncomfortable, often described as chest tightness; younger children often describe this as chest pain; in some studies, the most common cardiac cause of chest pain is arrhythmia c. Inﬂ ammatory i. History of preceding viral illness ii. Pericarditis: Fever, friction rub, worse lying ﬂ at iii. Myocarditis: Tachycardia, gallop rhythm Cardiology 79

d. Structural (very rarely associated with chest pain in children and adolescents) i. Aortic stenosis ii. Hypertrophic obstructive cardiomyopathy iii. Aortic dissection: Particularly in Marfan syndrome Workup • The history and physical exam are sufﬁ cient in most cases. Typically, the ECG is the most useful diagnostic test.

SYNCOPE (Cardiol Clin 1997;15(2):277) • Defi nition: A sudden and transient loss of consciousness and muscle tone that is spontaneously self-terminating • Secondary to insuffi ciency of nutrients or oxygen to the brain (related to blood fl ow), most typically from decrease in systemic arterial pressure beyond the limits tolerated by cerebral autoregulation (typically when cerebral blood fl ow <30%–50% baseline) • At least 20% have one episode of syncope by age 25 yr; variable reports, from 1% to 47% of adolescents and young adults • Workup: Thorough history, including a detailed family history, physical exam, EKG

Cause Circulatory (neurocardiogenic, orthostatic hypotension, postural orthostatic tachycardia syndrome, situational faint), cardiac (arrhythmogenic, structural heart disease, myocardial dysfunction), or noncardiac (epilepsy, psychogenic, migraines) • Neurocardiogenic: 50% to 80% of syncope in children; usually this is spontaneous, or brought on by postural changes. May be evoked by noxious stimuli such as fright, pain, blood, fasting, heat. • Classically, there are three stages. • Prodromal symptoms: Pallor, lightheadedness, sweating, visual disturbances, nausea and vomiting, and SOB. • Syncopal event: Typically <1 minute. Consciousness returns when the patient is recumbent. • Recovery period: Fatigue, dizziness, headache or nausea lasting up to 30 minutes. • Treatment: When prodromal symptoms occur, the patient should lie down with the feet

elevated; chronic therapy includes increased salt and clear fl uid intake and avoidance PEDIATRICS of diuretics (eg caffeine, alcohol); patients occasionally require pharmacotherapy with midodrine. Historically, β-blockers and mineralocorticoids have been used (not recommended for those with typical neurocardiogenic syncope). • Orthostatic intolerance • May only experience dizziness without true loss of consciousness. • Causes: Orthostatic intolerance is a pervasive disease of the autonomic nervous system. • Symptoms: Worse with prolonged standing, prolonged bedrest, and dehydration. Symptoms do not respond to the therapies that are used in neurocardiogenic syncope; often very diffi cult to treat. • Cardiac syncope • ↓ Cardiac output → ↓ cerebral blood fl ow → syncope. • Causes: Congenital heart disease (aortic stenosis, coronary artery anomalies, hypertrophic cardiomyopathy), myocardial dysfunction (DCM, myocarditis), ventricular arrhythmia (ventricular tachycardia, long QT, WPW with ventricular fi brillation), pulmonary hypertension. • There is a higher index of suspicion if: syncope occurs with exercise (versus more common postexercise syncope), palpitations or chest pain precede syncope, no prodromal symptoms. • Family history: Syncope, sudden cardiac death, congenital deafness. • EKG: Helpful in evaluating for long QT, WPW, and ventricular hypertrophy • Treatment: Varies based on the cause. 80 Pediatrics

INFECTIVE ENDOCARDITIS PROPHYLAXIS (Circulation 2007;116(15):1736) Antibiotic prophylaxis is recommended only for patients with select cardiac conditions undergoing select procedures: • Cardiac conditions for which prophylaxis is recommended: • Prosthetic cardiac valve or prosthetic material used in valve repair • Previous infective endocarditis • Cardiac valvulopathy after cardiac transplantation • CHD only in the following categories: • Unrepaired cyanotic CHD and those with palliative shunts or conduits • Completely repaired CHD with prosthetic material or device during the ﬁ rst 6 months after the procedure • Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device • Select invasive procedures for which prophylaxis is recommended for the above populations: • Dental procedures that involve manipulation of gingival tissue or the periapical region of teeth or perforation of the oral mucosa • Incision or biopsy of respiratory mucosa (eg, tonsillectomy, adenoidectomy) • Invasive procedures involving actively infected skin or GI or GU systems (not recommended for routine GI or GU procedures)

ANTIBIOTIC PROPHYLACTIC REGIMENS RECOMMENDED FOR DENTAL PROCEDURES

Regimen: Single Dose 30 to 60 min Before Procedure Situation Agent Adults Children

Oral Amoxicillin 2 g PO 50 mg/kg PO

Unable to take Ampicillin 2 g IM or IV 50 mg/kg IM or IV oral medication or Cefazolin or Ceftriaxone 1 g IM or IV 50 mg/kg IM or IV

Allergic to Cephalexin∗† 2 g PO 50 mg/kg PO penicillins or or ampicillin (oral) Clindamycin 600 mg PO 20 mg/kg PO or Azithromycin or 500 mg PO 15 mg/kg PO clarithromycin

Allergic to penicil- Cefazolin or Ceftriaxone† 1 g IM or IV 50 mg/kg IM or IV lins or ampicillin or (non-oral) Clindamycin 600 mg IM or IV 20 mg/kg IM or IV

∗Or other ﬁ rst- or second-generation oral cephalosporin in equivalent adult or pediatric dosage. † Cephalosporins should not be used in an individual with a history of anaphylaxis, angioedema, or urticaria with penicillins or ampicillin. Reproduced with permission from Circulation 2007;116:1736.

ATHLETIC RESTRICTIONS FOR CHILDREN WITH CARDIOVASCULAR DISEASE • Consensus guidelines from the 36th Bethesda Conference in 2005 are available to guide practitioners in determining athletic eligibility for young athletes. These guidelines address participation eligibility of competitive athletes with heart disease but do not make Cardiology 81

speciﬁ c recommendations for other recreational sports or for the much larger population of non-athletes with cardiovascular disease (J Am Coll Cardiol 2005;45(8):1318). • AHA guidelines in 2004 address recreational activity for patients with genetic forms of cardiovascular disease, but practitioners may need to extrapolate from available guidelines to address questions of participation for other non-athletes (Circulation 2004;109(22):2807).

CONGENITAL HEART SURGERY GUIDE • Arterial switch operation: The aorta and PA are transected above the level of the semilunar valves and relocated to their appropriate respective ventricles. Coronary arteries are reim- planted into the neoaortic root. This establishes the normal ventricular–arterial connection in patients with TGA. • Atrioventriculoseptal defect (AV canal) repair: Patch closure is done of the ASD and VSD with separation of the common AV valve into a left- (mitral) and right- (tricuspid) sided component, including closure of the cleft in left-sided AV valve. • Blalock-Taussig (BT) shunt: A direct, end-to-side anastomosis of the subclavian artery to the PA. A “modifi ed” BT shunt involves the interposition of a synthetic graft between the subclavian artery and the PA. This provides or increases pulmonary blood fl ow (Figure 8-13). • Central shunt (eg, Waterson shunt, Potts shunt): Direct communication between the aorta and a branch PA. Provides or increases pulmonary blood fl ow. • Damus-Kaye-Stansel: End-to side anastomosis of the main PA to the ascending aorta. Requires reestablishment of pulmonary blood fl ow via a systemic to PA shunt or a Figure 8-13 BT shunt in TOF. ventricular to PA conduit. Allows unobstructed systemic outfl ow in the context of single ventricle anatomy and aortic outfl ow obstruction. • Fontan procedure: Typically the fi nal step in the single ventricle palliation pathway. Connects the systemic venous return to the PAs (Figure 8-14). “Fontan completion” refers to a staged procedure in which a bidirectional Glenn procedure is performed fi rst (which is the top half PEDIATRICS of the Fontan) followed at a later surgery by connecting the IVC fl ow into the PAs (Fontan). • Glenn anastomosis (superior cavopulmonary anastomosis): Direct anastomosis of the SVC to the ipsilateral PA. “Bidirectional” implies fl ow from the SVC into both PAs. Provides a source of pulmonary blood fl ow Figure 8-14 Fontan palliation while volume unloading the single ventricle. May be a step in HLHS. in the single ventricle palliation pathway (Figure 8-15). • Konno-Rastan procedure: Enlargement of the LVOT and aortic annulus. A defect is created in the ventricular septum to enlarge the LVOT and is then repaired with a patch. Performed to alleviate subvalvar and annular aortic obstruction. • Norwood procedure (stage I palliation): Involves reconstruction of the aortic arch (often using a DKS variation), atrial septectomy, and creation of a source of pulmonary blood fl ow via either a BT shunt or a ventricular to PA conduit (“Sano modifi cation”) (Figure 8-16). • Hybrid Norwood: A combined surgical and catheter- based initial palliation for some single-ventricle patients, particularly with HLHS. Includes surgical banding of the bilateral branch PAs and transcatheter stenting of the PDA and ASD enlargement. Provides a stable outlet for Figure 8-15 BDG anastomosis. 82 Pediatrics

the systemic output while controlling excessive pulmonary blood fl ow. • PA banding: Constrictive band placed around the main PA. Limits excessive pulmonary blood fl ow, pulmonary artery pressure, or both. • Rastelli operation: Creation of an intracardiac tunnel permitting blood fl ow from the LV to the aorta, patch closure of a VSD, and placement of an RV to PA conduit. The procedure results in separation of the pulmonary and systemic circulations in TGA/VSD/PS. • Ross procedure: Replacement of the aortic valve with the patient’s native pulmonary valve (autograft), and restoration of pulmonary blood fl ow with an RV–PA conduit. If enlargement of the LVOT is also required, often done in combination with a Konno procedure. Figure 8-16 Norwood palliation • Senning or Mustard procedure (atrial switch): Intraatrial with Sano modifi cation. baffl e in patients with d-TGA that directs pulmonary venous blood to the RV and aorta while systemic venous blood is directed to the LV and PA. Previously used to treat TGA (before the advent of the arterial switch operation) (Figure 8-17). • Tetralogy of Fallot repair: Closure of VSD and relief of RVOTO. • Truncus arteriosus repair: Closure of the VSD, division of the PAs from the truncal root, and establishment of RV-to-PA continuity via an RV–PA conduit. Similar to the Rastelli procedure. • Valvotomy: Incision of stenotic valve to relieve obstruction. • Valvuloplasty: Repair of diseased valve. Balloon valvuloplasty refers to transcatheter dilatation of a Figure 8-17 Mustard repair in d-TGA. stenotic valve. Surgical valvuloplasty may be performed to relieve valve stenosis or improve valve competence.

Available at www.AccessPediatrics.com • Rheumatic fever • Hypertrophic cardiomyopathy • Guide to antiarrhythmics • Guide to pacemakers PEDIATRICS 2 O a <50 mm Hg 2 ILD estimated - P 2 O a at sea level is 760 mm Hg; Pulmonary Edema B Diffusion impairment , 2nd ed. Baltimore: Williams 2 The ICU Book corrects 100% O administer hypoxemia † ↑ 83 2 2 O O a i /R (atmospheric pressure or P P F 2 ↓ normal correct CO does not a ↓ A-a gradient ed as one or both of the following: hypoxemia normal V/Q mismatch vascular (PE) vascular 2 – 47) – P B Alveolar to arterial gradient (A–a) gradient = P † (P × airway (asthma, PNA, CHF) (asthma, PNA, airway

2 Low 9-2) brosis) (Figure inspired O Hypoventilation True shunt True estimated = FiO 2 L intracardiac shunt L intracardiac O a Workup of hypoxemia. → Use of accessory muscles of respiration, markedly diminished or absent breath Use of accessory muscles of respiration, markedly diminished R Lethargy, apnea, gasping or agonal respiration, bradycardia, hypotension Lethargy, apnea, gasping or agonal respiration, bradycardia, intrapulmonary shunt (AVM) alveolar collapse/filling (PNA, CHF) collapse/filling alveolar changes (BPD, cystic ﬁ breathing a gas mixture of at least 50% oxygen (Figure 9-1) breathing a gas mixture of at least Hypoxic (type 1): Characterized by failure of gas exchange resulting in PaO Hypoxic (type 1): Characterized Hypercapneic (type II): Characterized as failure of ventilatory pump or chronic structural as failure of ventilatory pump or chronic structural Hypercapneic (type II): Characterized Late: Early: sounds, diaphoresis, inability to speak, AMS, irritability, cyanosis, hypercapnia sounds, diaphoresis, inability to speak, AMS, irritability, cyanosis, Critical Care FAILURE RESPIRATORY is commonly classiﬁ Respiratory failure • • CHAPTER 9 Clinical Predictors of Impending Respiratory Failure • • respiratory quotient R is a unitless number representing basal metabolic rate; 0.7 is typically used in PICUs.) respiratory quotient R is a unitless number representing basal metabolic A normal A–a gradient is ~10 mm Hg. (Adapted from Marino PL: & Wilkins; 1990:349.) Figure 9-1 measured. P 84 Pediatrics

↑ PaCO2

Respiratory effort normal decreased decreased

Lung compliance decreased normal normal

A-a gradient increased normal normal

Vent. Apparatus NM System Respiratory Drive Chest wall Neuropathies Chemoreceptors obesity phrenic nerve metab. alkalosis kyphosis damage 1° neurologic scoliosis Guillain-Barré brainstem stroke Pleura NMJ tumor fibrosis, effusion critical illness hypoventilation Lung parenchyma polyneuropathy 2° neurologic ILD Lambert-Eaton sedatives CHF, PNA Myopathies CNS infection Airways diaphragm injury, asthma, CF, myositis bronchiectasis, musc. dystrophies, bronchiolitis, hypophosphatemia, OSA prolonged paralysis

Figure 9-2 Mechanisms of hypercapnia.

Management of Respiratory Failure OXYGEN DELIVERY MODES AND NONINVASIVE VENTILATION MODALITIES

Risks and Dose and Adverse Modality Indication Administration Advantages Eff ects

† O2 via For non–life- 100% oxygen , typi- Well tolerated, Skin irritation nasal cannula threatening cally no more than easy to use, read- from cannula, (provides roughly conditions, 4 L/min fl ow ily available, drying of na- 25%–40% hypoxemia no associated sal passages, oxygen)∗ (asthma, toxicity nose bleeds (Use humidiﬁ ca- pneumonia, tion system) bronchiolitis)

For non–life- 100% oxygen† at Well tolerated, If ﬂ ow is

O2 via simple threatening no less than 5 L/ easy to use, readily <5 L/min, face mask (pro- conditions, min, typically 5–15 available, no as- “rebreath-

vides roughly hypoxemia L/min sociated toxicity, ing” CO2 may 35%–50% (asthma, provides more occur oxygen)∗ pneumonia, oxygen than nasal bronchiolitis) cannula

Weaning oxy- The fl ow of 100% Well tolerated, Not readily O via Venturi™ 2 gen from high oxygen through the easy to use, no available mask (provides fl ow rates Venturi mask draws in associated toxicity, 24%–50% a controlled, adjust- fi xed and accurate oxygen able amount of room concentration of incrementally) air (21% oxygen) oxygen

(continued on next page) Critical Care 85

Risks and Dose and Adverse Modality Indication Administration Advantages Eff ects

For non–life- 100% oxygen, High-ﬂ ow system Nitrogen O via partial 2 threatening 5–15 L/min readily available, washout rebreathing conditions, provides more may lead to face mask (pro- Maintain reservoir severe hypox- oxygen than atelectasis vides roughly at least half full on emia (asthma, simple face mask 50%–100% inspiration pneumonia, oxygen)∗ bronchiolitis)

Severe 100% oxygen Well tolerated, Nitrogen hypoxemia, 10–15 L/min easy to use, read- washout O via nonre- 2 hemodynami- Maintain reservoir ily available may lead to breather face- cally stable atelectasis mask (provides at least 2/3 full pneumothorax on inspira- ~80%–100% (nitrogen oxygen)∗ tion and allow washout) partial collapse on exhalation

Upper airway Can be admin- Lower density Benefi cial obstruction istered via nasal gas decreases eff ects of He- (croup, bron- cannula and face turbulent fl ow lium not seen ∗ → Heliox , chiolitis) mask increased O2 with <60%; 60%–80% He+ May be ben- Do not use with and medication therefore, not delivery to distal helpful if pa- 20%–40% O2 efi cial in treat- oxygen tent or ment of lower hood airways tient requires airway disease >40% O2 (asthma)

Acute: Respira- Typically administer Overcomes air- Constant tory distress pressures of 5–10 way resistance to pressure ↓ or failure, cm H2O maintain, FRC , throughout ↑ poor lung May give supple- muscle fatigue, respiratory compliance, lung recruitment, cycle; no ↑ mental oxygen as PEDIATRICS obstructive ↓ atelectasis, ↓ with inspira- ‡ needed CPAP airway disease , V/Q mismatch tion. muscle fatigue, Reduced risk of Masks may CHF, asthma, infection and cause skin acute chest local trauma to breakdown syndrome airway compared with chronic Chronic: OSA with ETT use

(same as above Administer via nose Less use of seda- Nasal prongs for CPAP) mask tives and masks may cause IPAP ( 8-20 cm H2O), May prevent EPAP (5-10) cm intubation skin breakdown with H2O, supplemental oxygen as needed chronic use BiPAP‡ Not well tolerated by some patients Distended stomach caused by swallowed air

(continued on next page) 86 Pediatrics

Risks and Dose and Adverse Modality Indication Administration Advantages Eff ects

Respiratory Use a ventilator, set As with BiPAP As with BiPAP Noninvasive distress parameters (rate, Vt May prevent positive pres- or PIP, PEEP) intubation sure ventilation Supplemental O2 as needed

∗The ﬁ nal oxygen concentration delivered by this device depends on the amount of room air that mixes with the supplemental oxygen during respiration. † The FiO2 can be reduced by blending with room air while still maintaining the same ﬂ ow rate. ‡Cognitive behavioral therapy at the beginning of therapy dramatically increases compliance up to 148%. Sleep 2007;30(5):635. 70/30 Heliox is used at our institution.

STEPWISE APPROACH TO MANAGING RESPIRATORY FAILURE

Step 1: Preparation and intubation

Step 2: Pick ventilator mode (choose a familiar mode)

Step 3: Choose control mode (volume vs. pressure)

Step 4: Choose remaining variables

Step 5: Manage patient while intubated

Step 6: Wean and extubate as soon as possible

Step 1: Preparation and Intubation (STATS) 1. Suction 2. Tubes (anticipated ETT size +/size above + below)† 3. Airway adjuncts (oral airways) 4. Tape 5. Scopes: Laryngoscope, stethoscope †See accompanying PICU Pocket card for recommended mediations and equipment sizes. Step 2: Pick Ventilator Mode (How the Patient and Machine Interact) Important Goals • Provide adequate ventilation and oxygenation. • Reduce the work of breathing. • Ensure patient comfort and synchrony with the ventilator.

OVERVIEW OF COMMON MECHANICAL VENTILATION MODALITIES

Support for Patient- Guaranteed Initiated Set Minimum Breaths “Over Mode Rate MV the Vent” Notes

Controlled Y Y N Vent delivers regular, identical mechanical breaths; no spontaneous ventilation breaths allowed (CMV) Rarely used, with the exception of neonatal transport ventilators

(continued on next page) Critical Care 87

Support for Patient- Guaranteed Initiated Set Minimum Breaths “Over Mode Rate MV the Vent” Notes

Assist-control Y Y Y Typically volume control; full ventilation (AC) preset TV is delivered at a preset rate; the patient may initiate additional supported cycles

(also full preset VT); the patient may change MV as needed but cannot resume the work of breathing

Intermittent Y Y N Similar to CMV but allows mandatory ven- patient-triggered breaths in tilation (IMV) between mandatory breaths Patient may change minute ventilation as needed and as vent rate is weaned, the patient can “take over” the work of breathing

Synchronized Y Y N Similar to IMV, but internal cir- intermittent cuitry manipulates mandatory mandatory ven- vent delivered breaths around tilation (SIMV) patient-triggered breaths

Support mode N N Y Set pressure or volume is deliv- (PS, VS) ered for patient-initiated cycles to support patient-initiated breaths (often combined with other modalities or as a weaning modality, i.e. SIMV + PS)

Pressure regu- Y Y Y On some ventilators, these are lated volume AC modes, but in others, they PEDIATRICS control (PRVC, are SIMV modes; ask the RT VC+) Delivers preset rate and Vt, but ﬂ ow characteristics are regulated to deliver target volumes at the lowest possible pressure

High-frequency N/A N/A N/A Escalation of care for patients oscillatory ven- who require high P and have aw tilation (HFOV) failed conventional ventilators Consider when PEEP is 10 cm

H2O or PIP is >35; better sepa- rates control of oxygenation and ventilation

Step 3: Choose Control Mode (Pressure vs. Volume) • Pressure control: Delivers a pressure-limited breath during a preset inspiratory time at

the preset respiratory rate. The VT is determined by the preset pressure limit and the compliance and resistance of the patient’s respiratory system.

• Goal PIP: <35 to 40 cm H2O to reduce ventilator-induced lung injury (barotrauma).

• Does not guarantee VT. • Pressure control may be preferentially used for ELBW or VLBW patients because of

limitations in ventilator ability to consistently deliver or control extremely low VT. 88 Pediatrics

• Volume control: Delivers a preset VT during a preset inspiratory time at the preset respiratory rate and constant inspiratory ﬂ ow.

• Guarantees VT at the expense of variations in PIP.

• Monitor PIP closely; goal is <35 to 40 cm H2O to reduce ventilator-induced lung injury(barotrauma) Step 4: Choose Remaining Variables (Starting Point)

INITIAL SIMV VENTILATOR SETTINGS FOR VARIOUS AGES

SIMV PC SIMV PC SIMV VC SIMV VC (Neonates) (Children) (Children) (Adolescents)

Rate (bpm) 20–30 14–20 14–20 8–14

Ti (sec) 0.2–0.5 0.5–0.8 0.5–0.8 0.75–1

∗ † † ‡ VT (cc/kg) N/A N/A 6–8 6–8

PEEP (cm H2O) 2–5 2–5 2–5 2–5

† † PIP (cm H2O) 20–25 20–25 N/A N/A

PS (cm H2O) 5–10 (in addition to PEEP)

FiO2 Start at 1.0 and wean as aggressively as possible to avoid O2 toxicity (goal <0.6) ∗ Monitor chest rise and titrate to the lowest VT with adequate chest rise (lung protective strategy: 6–8 cc/kg). †Shaded boxes indicate variables that are not set in this mode; values obtained will be based on other set variables. ‡ Large or obese adolescents may require less VT for adequate chest rise.

Step 5: Manage Patient While Intubated

VENTILATOR ADJUSTMENTS AFFECTING OXYGENATION AND VENTILATION

Goal Action Physiology Caveats

Improving Increase Paw (MAP) by PEEP maintains FRC Overdistension with oxygenation ↑ and ↓ V/Q mismatch; PEEP will lead to worsen- PEEP, PIP, or Ti (PEEP has greater eﬀ ect); has >eﬀ ect than PIP: ing oxygenation P × increase FiO2 aw = K(PIP-PEEP) Consider HFOV if PEEP + + [Ti/(Ti Te)] PEEP >10

Improving Increase MV by CO2 directly related Allow for permissive ↑ ↑ ventilation RR or VT (in VC to minute ventilation. hypercapnia (pCO2 ~60 modalities) or PIP Rule of thumb: Current if pH >7.2) to reduce the × (in PC modalities) PaCO2 Current respi- potential for barotrauma ratory rate = Desired With obstructive airway × PaCO2 Desired diseases, reducing the respiratory rate respiratory rate may improve ventilation by

allowing for a longer Te

Sedation and Analgesia • Consider for all intubated patients; neonates may need less than older patients to prevent patient–ventilator asynchrony and accidental extubation. Maintenance Fluids • For all intubated patients not on diuretics, use 75% of maintenance IVF (these patients do not have respiratory insensible loss because of the enclosed humidiﬁ ed ventilator circuit) and follow volume status closely. Critical Care 89

• Nutrition: Start enteral feeds as soon as possible; if contraindicated, start TPN or PPN (ideally, the patient should start receiving adequate calories and nutrition 2–3 days after intubation). Blood Gases and Clinical Parameters • Follow at least qAM blood gases (preferably ABG; may use CBG, or VBG via central line). • Follow oxygenation using pulse oximetry.

• Follow ventilation using end-tidal CO2 if feasible (may be too bulky for neonates) and

correlate or recalibrate daily with pCO2 from AM blood gases. • Follow lung compliance (want higher) and oxygenation index (want lower) daily trends

CDYN = VT/(PIP – PEEP)

CSTAT = VT/(PPLAT – PEEP × × Oxygenation index = (FiO2 Mean airway pressure)/PaO2 100 Diuresis and Metabolic Alkalosis • Diuretics should be considered in all intubated patients given impaired lymphatic or venous return 2/2 immobility: 0.5 to 2.0 mg/kg furosemide IV Q6 to 12 h. Keep balanced intake and output (other diuretics may be used). • Expect metabolic alkalosis. Anticipate depletion of Cl and retention of bicarbonate. • Start replacing Cl when <90. a. First choice: Use KCl (2–4 mEq/L) unless contraindicated (eg, renal insufﬁ ciency, hyperkalemia). b. Second choice: Use NaCl (2–4 mEq/kg); may cause more water retention 2/2 increased Na. c. If a and b have been exhausted and Cl <80 mEq/L, then use ammonia chloride. Dosing

of mEq NH3Cl via the bicarbonate-excess method (refractory hypochloremic metabolic alkalosis):

× × – mEq NH3Cl = 0.5 (L/kg) wt (kg) [Serum HCO3 - 24] → 1 2 Give /2 to /3 of the calculated dose; then re-evaluate (0.5 L/kg is the estimated bicarbonate volume of distribution, and 24 is the average normal serum bicarbonate concentration in mEq/L; use with caution in patients with hepatic insufﬁ ciency.)

d. After Cl >90 (or spot urine Cl suggests saline-resistant alkalosis) while pH is >7.50, use PEDIATRICS acetazolamide (5 mg/kg IV Q8h for 3 doses only; check daily lytes). Monitor for Complications of Mechanical Ventilation • Infection • Decreased cardiac output • Ventilator-induced lung injury (VILI) • Pneumothorax • Subglottic stenosis • Mechanical failure or accidental extubation Step 6: Wean and Extubate as Soon as Possible

WEANING • As the patient’s need for ventilatory support resolves, wean in the following order: → → → FiO2 PIP (if PC ventilation) PEEP Rate (ensure pressure or volume support is provided). • Criteria for extubation readiness (Crit Care Med 2000;28(8):2991 and JAMA 2002;288(20):2561): • PEEP <5 • FiO2 <40%

• Spontaneous effective VT >5 cc/kg • Glasgow Coma Scale >8 (ie, not comatose, sedation has been weaned) 90 Pediatrics

• Tracheal secretions are tolerable (ie, not thick and not requiring >Q1h suctioning) • Appears comfortable on PEEP 5 or pressure support of 5 with no trial failure (see below)

CRITERIA FOR CPAP TRIAL FAILURE

Deﬁ nition of trial: 2 h on respiratory support of CPAP ≤5 cm H2O or T-piece (CPAP = 0) Clinical Criteria Laboratory Criteria

• Diaphoresis • Increase of PETCO2 >10 mm Hg • Nasal ﬂ aring • Decrease of arterial pH to <7.32 • Increasing respiratory eﬀ ort • Absolute decline in arterial pH >0.07

• Tachypnea • PaO2 <60 mm Hg with FIO2 >0.40 (PaO2/FiO2 • Tachycardia (increase in HR >20–40 bpm) ratio <150)

• Cardiac arrhythmias • SpO2 declines >5% • Hypotension • Apnea

(Ped Crit Care Med 2009;10(1):1.)

STATUS ASTHMATICUS IN THE INTENSIVE CARE UNIT • Deﬁ nition: An acute exacerbation of asthma that does not respond to treatment with bronchodilators and corticosteroids. • Symptoms: Chest tightness or pain, dyspnea, dry cough, or wheezing. Ppatients may have nausea, vomiting, difﬁ culty speaking or speaking in single words, or altered mental status as part of the presentation, which indicates greater severity of illness. Risk Factors for ICU Admission and for Sudden Death with Status Asthmaticus • Previous ICU admissions • Previous need for mechanical ventilation with an asthma exacerbation • Syncope during an asthma exacerbation • Seizures during an asthma exacerbation • History of cardiac arrest with asthma exacerbation • Poor adherence to controller therapy • Poor perception of severity of asthma • Comorbid psychiatric disorder • Rapid deterioration with current episode • Use of more than 1 canister of home β-agonist medication per month

CLINICAL RESPIRATORY SCORE AS A GUIDE FOR EVALUATING SEVERITY OF EXACERBATION AND FOLLOWING RESPONSE TO THERAPY

Clinical Respiratory Score (CRS)

Patient Assess Score 0 Score 1 Score 2 Score

Respiratory < 2 mos < 50 < 2 mos 50-60 < 2 mos > 60 Rate 2-12 mos < 40 2-12 mos 40-50 2-12 mos > 50 1-5 yrs < 30 > 1-5 yrs 30-40 > 1-5 yrs > 40 > 5 yrs < 20 > 5 yrs 20-30 > 5 yrs > 30

(continued on next page) Critical Care 91

Clinical Respiratory Score (CRS)

Patient Assess Score 0 Score 1 Score 2 Score

Auscultation Good air move- Decreased air Diminished or absent ment, scattered movement, inspira- breath sounds, severe expiratory tory and expiratory wheezing or rales/ wheezing, loose wheezes or rales/ crackles, or markedly rales/crackles. crackles prolonged expiration.

Use of Acces- Mild to no Moderate intercos- Severe intercostal and sory Muscles use of acces- tal retractions, mild substernal retractions, sory muscles. to moderate use of nasal fl aring. Mild to no accessory muscles, retractions or nasal fl aring. nasal fl aring on inspiration.

Mental Status Normal to Irritable, agitated, Lethargic mildly irritable restless.

Room Air SpO2 > 95% 90 – 95 % < 90%

Color Normal Pale to normal Cyanotic, dusty

Total Score (Sum of the component scores)

THERAPIES FOR THE MANAGEMENT OF STATUS ASTHMATICUS

First-Line Treatment

Type and Medication Mechanism Route Dose

Albuterol SABA (airway Inhaled Nebulization: 0.15–0.5 mg/kg/h or PEDIATRICS smooth muscle (nebulized 10–20 mg/h of continuous therapy; relaxation) or MDI) can give sequential nebulization × 3 (≤5 mg each) Max, 20 mg/h MDI: 4–8 puﬀ s per dose Q20 min × 3; then Q1h

Levalbuterol SABA (levoro- Inhaled MDI: 4–8 puﬀ s Q20 min × 3 then tary enantiomer, (nebulized Q1h airway smooth or MDI) muscle relaxation)

Methylpredni- Steroid∗ (antiin- IV 2 mg/kg IV once; then 1 mg/kg IV Q6h solone ﬂ ammatory) Max, 60 mg/dose

Prednisone Steroid∗ (antiin- PO 2 mg/kg PO once; then 1–2 mg/kg/ ﬂ ammatory) day divided Q12h Max, 60 mg/dose

Prednisolone Steroid∗ (anti PO (tastes 2 mg/kg PO once; then 1 mg/kg inﬂ ammatory) better) PO Q6h Max, 60 mg/dose

(continued on next page) 92 Pediatrics

Second-Line Treatment

Ipratropium Anticholinergic Inhaled <12 yr: Nebulization 250 mcg Q20 bromide (airway smooth (nebulized min × 3 then Q2–4h prn; MDI 4–8 muscle relaxation) or MDI) puﬀ s per dose >12 yr: Nebulization 500 mcg Q30 min × 3 then Q2–4h prn; MDI 4–8 puﬀ s per dose Can “spike” the albuterol nebulization solution with ipratropium bromide dose and give as one treatment

Magnesium sulfate Electrolyte IV 40 mg/kg IV over 20 min; max 2g (smooth muscle Although hypotension is exceed- relaxation) ingly rare, watch for hypotension and be ready to give a 10–20 cc/kg NS bolus if it develops

Terbutaline† β-agonist Sub-Q, IV IV: 10 mcg/kg IV once; then IV (smooth muscle infusion starting at 0.5 mcg/kc/min, relaxation) titrate as HR tolerates to goal 3–6 mcg/kg/min Max, 10 mcg/kg/min

Aminophylline‡ Bronchodilator IV 6 mg/kg load over 20–30 min; then continuous infusion

Ketamine Dissociative IV 0.5–2.0 mg/kg IV; may be used as a anesthetic, continuous infusion bronchodilator May have bizarre dreams, hallucinations; watch for overseda- tion and need for immediate intubation Often reserved as a last medication trial or sedative before intubation

Heliox Gas Inhaled Available as 70/30 or 80/20 concentrations

∗In general, IV or PO steroids are continued as a “burst” over 5 to 7 days and then discontinued. Remember to wean the patient off the steroids if they are continued after 7 days because they may cause adrenal suppression. †The usual doses for IV terbutaline infusion range from 1 to 6 mcg/kg/min. Major side eff ects may include coronary ischemia, chest pain, and arrhythmias. Toxicity will limit the maximum dose for the patient. Closely monitor for side eff ects. ‡Aminophylline levels must be monitored closely to avoid toxicity. Obtain the fi rst level 30 minutes after the end of the 30-minute loading dose. Continuous infusion dosing is based on the age and weight of the child. Repeat levels after the loading dose should be obtained 12 to 24 hours after the continuous infusion begins. There are many medication interactions; check with the pharmacy to avoid medication errors.

Advanced Therapies and Treatment Modalities These therapies are rarely needed in the management of patients with status asthmaticus but may be necessary for a small subset of patients who fail to respond to conventional management. • BiPAP • Intubation and mechanical ventilation • Gas anesthesia with Isoﬂ urane • ECMO Indications for Intubation and Mechanical Ventilation for Patients in Status Asthmaticus • Hypoxemia, severe work of breathing, altered mental status, impending or present respiratory or cardiac arrest Critical Care 93

Intubating Patients with Asthma • Use ketamine for sedation (secondary to its bronchodilatory properties). • Be prepared to give an IVF bolus of NS (10–20 cc/kg) because the patie4nt may become hypotensive or experience cardiac arrest after intubation. • Initial mechanical ventilator settings: Titrate settings for adequate chest rise with the goal

of 6 to 8 cc/kg delivered VT; minimize peak inspiratory pressure; goal plateau pressure <30; ensure completed exhalation between breaths. • Check the ABG or CBG soon after you intubate.

• Tolerate lower pH (>7.25) and higher pCO2 (ie, permissive hypercapnia). Pearls for Monitoring and Managing ICU Patients with Status Asthmaticus Airway and Breathing • The decision to intubate is clinical and should not be determined solely by ABG values. • Most complications for patients intubated for asthma occur during intubation or immediately afterward (pneumothorax, cardiac arrest, hypotension, arrhythmia, among others). • Intubated patients with status asthmaticus may require a very slow respiratory rate to

complete exhalation. Patients with a high pCO2 may require a decrease in ventilator rate

to improve the pCO2. Circulation and Cardiac • Monitor for atrial and ventricular arrhythmias, especially SVT in patients on high-dose β-agonist therapy. • Monitor for cardiac ischemia and chest pain. Obtain a 12-lead ECG. Consider obtaining cardiac enzymes in patients who have chest pain or ECG changes. • Limit β-agonist therapies when excessive tachycardia is present or there is evidence of cardiac ischemia. Fluid, Electrolytes, and Nutrition • Keep the patient NPO. (The patient may deteriorate, have altered mental status, and require mechanical ventilation.) • Check potassium Q6h because high-dose β-agonist therapy may cause hypokalemia. • Patients in status asthmaticus are often dehydrated and may require ﬂ uid resuscitation. Do not be afraid to give ﬂ uid to patients with asthma. • Status asthmaticus has been associated with metabolic and lactic acidosis. PEDIATRICS

SHOCK STATES, SIRS, AND SEPSIS • Shock Deﬁ nition: Inadequate delivery of oxygen and nutrients to meet the metabolic needs of the tissues. Shock is not deﬁ ned by low BP. A patient can have a normal BP and still be in shock.

Stages of Shock • Compensated (warm): Normal to low SBP and low DBP with signs and symptoms of inadequate tissue and organ perfusion. Compensatory mechanisms: ↑HR, ↑ cardiac contractility (↑SV), and ↑ SVR. (Younger children and infants are less able to compensate and rely on tachycardia.) • Clinical signs: Warm extremities with bounding pulses, tachycardia, tachypnea, altered mental status, ↓ UOP. • Physiologic signs: Widened pulse pressure, ↑ CO, ↓ mixed venous saturation, ↓SVR. • Biochemical abnormalities: Hypocarbia, ↑ lactate, ↓ bicarbonate, hyperglycemia. • Decompensated (cold): Systolic hypotension with signs and symptoms of inadequate tissue and organ perfusion. Compensatory mechanisms are overwhelmed. • Clinical signs: Cyanosis, cold and clammy skin, rapid and thready pulses, shallow respirations, obtundation, worsening oliguria or anuria. • Physiologic signs: ↓ Mixed venous sats, ↓ CO, ↓ CVP, ↑ SVR, ↓ UOP, myocardial dysfunction, capillary leak. • Biochemical abnormalities: Worsening metabolic acidosis, hypoxia, coagulopathy, hypoglycemia, thrombocytopenia, DIC. 94 Pediatrics

Defi ning Shock in Sepsis Fluid-Refractory, Dopamine-Resistant Shock • Shock persists despite ≥60 mL/kg fl uid resuscitation in the fi rst hour and dopamine infusion to 10 microg/kg/min. Catecholamine-Resistant Shock • Shock persists despite use of catecholamines (epinephrine or norepinephrine). Refractory Shock • Shock persists despite goal-directed therapy use of inotropic agents, vasopressors, and vasodilators and maintenance of metabolic (glucose and calcium) and hormonal (thyroid and hydrocortisone) homeostasis.

Deﬁ ning Hypotension (SBP <5th Percentile For age) • Term neonates: SBP <60 mmHg • Infants (age 1–12 mo): SBP <70 mmHg • Children age 1–10 yr: SBP <70mmHg + (2 × age in years) • Children age >10 yr: SBP <90 mmHg

DEFINITIONS OF SYSTEMIC INFLAMMATORY RESPONSE SYNDROME, SEPSIS, SEVERE SEPSIS, AND SEPTIC SHOCK

SIRS The presence of at least two of the following four criteria, one of which must be abnormal temperature or leukocyte count: Core temperature of >38.5°C or <36°C Tachycardia in the absence of external stimulus, chronic drugs, or painful stimuli; bradycardia in the absence of external vagal stimulus, β-blocker drugs, or congenital heart disease; or otherwise unexplained persistent depression of HR over a 0.5h time period Tachypnea or mechanical ventilation for an acute process not related to an underlying neuromuscular disease or the receipt of general anesthesia Leukocyte count elevated or depressed for age (not because of chemotherapy) or >10% immature neutrophils

Sepsis SIRS in the presence of or as a result of suspected or proven infection

Severe Sepsis plus one of the following: Cardiovascular dysfunction or acute respiratory sepsis distress syndrome or two or more organ dysfunctions

Septic Sepsis and cardiovascular organ dysfunction shock

Reproduced with permission from Pediatr Crit Care Med 2005;6(1):2.

SUMMARY OF IMPORTANT CLINICAL FINDINGS IN VARIOUS SHOCK STATES

CO SVR MAP CVP Pulse pressure

Hypovolemic ↑↑↔ or ↓ ↓↓↓ Narrow

Cardiogenic ↓↓ ↑↑↑ ↔ or ↓↑↑ Narrow

Obstructive ↓↑↔ or ↓↑↑ Narrow

Distributive ↑↑ ↓↓↓ ↔ or ↓↔ or ↓ Widened

Septic: Early ↑↑↑ ↓↓↓ ↔ or ↓↓ Widened

Septic: Late ↓↓ ↑↑ ↓↓ ↑ or ↔ Narrow Critical Care 95

SUGGESTED CLASSIFICATION AND MANAGEMENT OF SHOCK STATES

Type of Shock Description Initial Management

Hypovolemic Inadequate intravas- ABCs, O2, IV or IO access, monitors, initial glucose, cular volume relative brief history and PE, neurologic status, Foley catheter to the vascular space: Give 20 cc/kg NS rapidly; reassess need for additional Hemorrhage, serum or ﬂ uid plasma loss (diarrhea Labs: Electrolytes, BUN/Cr, glucose, calcium or ionized or vomiting, burns, calcium (maintain iCa >1.2), Mg, Phos, CBC, blood diabetes, nephrotic syn- culture, PT/PTT/INR, ABG with lactate, AST/ALT, drome), medications, albumin, CXR pancreatitis, sepsis Monitor UOP hourly Additional studies and imaging guided by history and PE Central venous access if given 60 cc/kg and the pa-

tient is still in shock; then monitor MVO2, CVP, arterial line; replace blood products for hemorrhage Distributive Inappropriate distribu- Same as hypovolemic + identify cause for tion of blood ﬂ ow: distributive shock Anaphylaxis, spinal cord Treat anaphylaxis with sub-Q or IM epinephrine injury, drugs (antihy- (1:1000) 0.01 mg/kg (max 0.5 mg) or IV or IO pertensive medication epinephrine (1:10,000) 0.01 mg/kg; may need epi- ingestion, barbiturate nephrine infusion, inhaled albuterol or racemic overdose), sepsis, epinephrine, IV/IM corticosteroids (Solumedrol pancreatitis 2 mg/kg), diphenhydramine (1-2 mg/kg IM, IV, or IO over 5 min), histamine blocker (ranitidine) If complete UAW obstruction, perform emergent cricothyroidotomy Obstructive Obstructed cardiac Same as hypovolemic + rapidly identify tampon- output: Cardiac tam- ade (diminished heart sounds, increased JVD, ponade, pneumotho- pulsus paradoxus), or pneumothorax (tracheal rax, aortic dissection, deviation, diminished breath sounds, CXR) PEDIATRICS critical aortic stenosis, large pulmonary embolus (consider this in trauma patients in addition to hypovolemic or distributive shock) Dissociative Unable to deliver Same as hypovolemic + rapidly identify the cause; oxygen to the tissues: send blood cooximetry and cyanide levels to identify Carbon monoxide poi- the cause soning, methemoglo- Speciﬁ c treatments as appropriate: binemia, heat, cyanide, Place on 100% FiO ; aggressively treat fever metabolic (consider this 2 in burn patients in ad- Carbon monoxide toxicity patients look cherry red dition to hypovolemic and pulse oximeters read high, but patients are shock) very acidotic Patients with methemoglobinemia look cyanotic, have symptoms of decreased oxygen delivery, and their blood looks “chocolate brown,” but the pulse oximetry will be falsely elevated, decreasing to only 85% (because of the spectra absorption characteristics of methemoglobin); treatment with methylene blue is initiated at concentrations of methemoglobin ~30%–40%

(continued on next page) 96 Pediatrics

Type of Shock Description Initial Management

Cardiogenic Myocardial dysfunction: ABC’s, O2, IV or IO access, monitors, brief history Dysrhythmias, primary and PE, neurologic status, Foley catheter or secondary cardiac In addition to the above labs, BNP level, cardiac disease, ductal-depen- enzymes, ECG, echocardiogram dent congenital cardiac Monitor for arrhythmias lesions, sepsis, thyrotoxi- cosis, pheochromocy- Identify the cause of cardiogenic shock toma, and in all forms Normalize preload (diuretics) and afterload of prolonged shock reduction regardless of etiology; Inotropes or vasopressors if BP is low and end- patients with enlarged organ is perfusion poor liver, cardiomegaly, gallop rhythm, rales, cool Target BP for end-organ perfusion and UOP >1 extremities, poor UOP cc/kg/h

Monitor mixed venous O2 sat, lactate

COMMONLY USED VASOPRESSORS AND INOTROPES IN SHOCK

Receptors and Drug Infusion Rate Mechanism Eff ect

β α β Epinephrine 0.1–1 mcg/kg/min 1 = 1 < 2 Inotrope (at low doses), chronotrope, vasopressor (at high doses)

α β Norepinephrine 0.05–1 mcg/kg/min Mainly 1, some 1 Vasopressor β Dopamine 2–20 mcg/kg/min Mainly 1 at low doses; Inotrope, chrono- α 1 at high doses (15–20 trope, vasopressor mcg/kg/min)

β Dobutamine 2–20 mcg/kg/min 1 Inotrope, chronotrope

Vasopressin 0.01–0.06 units/kg/h Vascular 1 (V1) receptor Vasopressor agonist: Increases intracellular Ca and causes vasoconstriction

Milrinone 0.125–0.750 mcg/ Phosphodiesterase III Inotrope, vasodilator kg/min inhibitor: Blocks the breakdown of cAMP

Clinical Pearls for Shock and Sepsis Initial Resuscitation • If PIV access only, insert central line or IO line. May use the following via peripheral IV access while obtaining deﬁ nitive access: • Dopamine ≤10 mcg/kg/min • Milrinone ≤1 mcg/kg/min • Epinephrine ≤0.05 mcg/kg/min • Vasopressin ≤0.04 U/kg/h • Dobutamine ≤20 mcg/kg/min • Fluid responsiveness: Does BP transiently increase and HR decrease with RUQ or liver pressure? If neither, then begin titrating pressors, inotropes, or both. Critical Care 97

Recognize decreased mental status and perfusion. 0 min Begin high flow O2. Establish IV/IO access.

Initial resuscitation: Push boluses of 20cc/kg isotonic saline or colloid up to With 2nd and over 60cc/kg until perfusion improves PIV start or unless rales or hepatomagaly develop. 5 min inotrope. Correct hypoglycemia and hypocalcemia. Begin antibiotics. shock not reversed?

15 min Fluid refractory shock: Begin inotrope IV/IO, use Dose range: atropine/ketamine IV/IO/IM to dopamine obtain central access and airway up to if needed. Reverse cold shock by 10 mcg/kg/min, titrating central dopamine or, if epinephrine resistant, titrate central 0.05 to 0.3 epinephrine Reverse warm shock mcg/kg/min. by titrating central norepinephrine. shock not reversed?

60 min Catecholamine resistant shock: Begin hydrocortisone if at risk for absolute adrenal insufficiency Emergency DepartmentEmergency

Monitor CVP in PICU, attain normal MAP-CVP and mixed venous saturation > 70%

Cold shock Cold shock Warm shock with normal with low with low blood pressure: blood pressure: blood pressure: 1° goals: Titrate 1° goals: Titrate 1° goals: Titrate epinephrine, epinephrine, norepinephrine,

MVO2 > 70%, MVO2 > 70%, MVO2 > 70%, PEDIATRICS Hgb > 10g/dL Hgb > 10g/dL 2° goals: Consider 2° goals: Add 2° goals: Add vasopressin, vasodilator* norepinephrine terlipressin or (nitrosovasodilators, Add dobutamine angiotensin milrininone, if MVO2 < 70%, and others) with Consider Add dobutamine or volume loading, milrinone, enoximone low dose epinephrine consider or levosimendan if MVO < 70% levosimendan 2 shock not reversed?

Persistent catecholamine resistant shock: Rule out and correct pericardial effusion, pneumothorax, and intra-abdominal pressure > 12 mm/Hg. Use pulmonary artery catheter, PICCO monitor, FATD and/or doppler ultrasound to guide fluid, inotrope, vasopressor, and hormonal therapies. Goal C.I. > 3.3 and < 6.0 L/min/m2 shock not reversed?

Refractory shock: ECMO (110 mL/kg/min) and/or CRRT (> 35 mL/kg/hr) Pediatric Intensive care unit Pediatric

Figure 9-3 Stepwise management of hemodynamic support in infants and children. (Adapted from Crit Care Med 2009;37(2):666–688.) 98 Pediatrics

• Remember after appropriate fl uid resuscitation and initial dopamine: • Cold shock: β-adrenergic such as epinephrine (treat the poor cardiac output). α • Warm shock” 1 adrenergic such as norepinephrine or vasopressin (vasocontrict the peripheral vessels). • Calcium repletion: Either as bolus dosing or continuous infusion may signifi cantly improve contractility. • Begin antimicrobial coverage ASAP! Use IV cephalosporin and vancomycin initially. Consider covering for Pseudomonas spp. if the airway was previously instrumented. Cardiovascular • Differentiate between cardiogenic shock and other types early; cardiogenic shock treatment does not include ongoing fl uid resuscitation with crystalloids or colloids to improve or maintain BP and perfusion. • Look for signs of fl uid overload and myocardial dysfunction on exam as you resuscitate: Crackles on lung exam, S3, hepatomegaly; if any are present, slow down on the fl uid and titrate up the vasopressors or inotropes. • Hemodynamic goals: BP resulting in end-organ perfusion, normal HR for age, cerebral perfusion pressure normal for age (MAP–CVP, 55–60 cm H O in infants; 65 cm H O for ≥ 2 2 2 yr), MVO2 sat of 70%, CVP 8 to 12, capillary refi ll time <2 sec, UOP >1 cc/kg/h. Respiratory • Intubate patients in shock when AMS is present or GCS is decreasing or <8 (atropine, ketamine, and rocuronium are recommended; see PICU Card for more details). • Avoid etomidate in patients in septic shock because it has been linked to adrenal suppression in patients with sepsis. Hematology • Hemoglobin threshold for transfusion: 7 to 9 g/dL in PICU; may transfuse at higher values as

indicated (low MVO2, need for colloid rather than crystalloid during resuscitation; need for in-

creased O2-carrying capacity). However, there are no data showing that improving O2-carrying

capacity or O2 delivery with PRBC transfusions has improved outcomes in septic shock. • Coagulation abnormalities: FFP, cryoprecipitate, vitamin K for clinically signifi cant DIC; platelets for clinically signifi cant bleeding. Renal • Fluid requirements: Replace insensible losses only if the patient has oliguria after multiple fl uid boluses. • Verify appropriate dosing of medications for renal insuffi ciency. Endocrine • Consider adrenal insuffi ciency if the patient is in fl uid- and catecholamine-refractive shock (hydrocortisone 100 mg/m2. I.V. bolus, then 50–100 mg/m2/day divided Q6–8 hr. • Glucose: Avoid hypo- and hyperglycemia. Treat hyperglycemia with an insulin infusion.

DIABETIC HYPERGLYCEMIC EMERGENCIES: DIABETIC KETOACIDOSIS AND HYPERGLYCEMIC HYPEROSMOLAR STATE • DKA: Blood glucose >300 mg/dL and the presence of acidosis with a serum bicarbonate <15 meq/L or a pH <7.30 • HHS: Blood glucose >600 mg/dL and osmolality >320 with pH >7.3 and absence of ketosis

Prognosis • Mortality rate for DKA is 0.15% to 0.3%; for HHS, it is 14%. • Prognosis is linked to the severity of illness at presentation, degree of dehydration, and electrolyte derangements. • Cerebral edema occurs in 0.5% to 1% of all episodes of DKA and is the most common cause of mortality and morbidity. • Coma is more frequent in HHS, as is long-term morbidity. Critical Care 99

DIAGNOSTIC CRITERIA FOR DIABETIC KETOACIDOSIS AND HYPERGLYCEMIC HYPEROSMOLAR STATE

Hyperglycemic Diabetic Ketoacidosis Hyperosmolar State

Mild Moderate Severe

Plasma glucose (mg/dL) >250 >250 >250 >600

Arterial pH 7.25–7.30 7.00–7.24 <7.00 >7.30

Serum bicarbonate 15–18 10 to <15 <10 >15 (mEg/L)

Urine ketones ++ +Small

Serum ketones ++ +Small

Eﬀ ective serum Variable Variable Variable >320 osmolality (mOsm/kg)

Anion gap >10 >12 >12 Variable

Alteration in sensorial Alert Alert or Stupor Stupor or coma or mental obtundation drowsy or coma

Reproduced with permission from Kitabchi AE, Umpierrez GE, Murphy MB, et al: Hyperglycemic crises in diabetes Diabetes Care 2004;27(suppl 1):S94–S102.

Important History • Polyuria, polydipsia, increased thirst. • May have a illness or infection triggering DKA. • Weight loss. • In a patient with known diabetes mellitus, • Abdominal pain (DKA only) or there may be a history of missed insulin vomiting. doses. • Headache, altered mental status. • Family history of DM or other autoimmune disorders. PEDIATRICS

Correction of Acidosis, Dehydration, and Electrolytes • Correct the dehydration over 36 to 48 hours in addition to maintenance IVF. Initial IVF should be at 2.5 L/m2/d (including initial boluses) for slow correction of dehydration and avoidance of cerebral edema. Some patients may need additional ﬂ uids because of extreme dehydration or hemodynamic compromise. Do not exceed 4 L/m2/d. Determine the degree of dehydration based on physical exam or weight loss (if previous weight is known).

• Do not give NaHCO3 to correct acidosis (associated with worsened outcome in the pediatric population). • Patients with HHS have greater fl uid and electrolyte defi cits than patients with DKA. • Correct hyperglycemia with insulin at a rate of decrease no more than 100 mg/dL/h; faster correction may increase the risk of cerebral edema. • K and Phos may appear normal on initial laboratory examinations, but patients in DKA or HHS are total-body K and Phos depleted; this may become apparent with correction of acidosis. • Red fl ags for cerebral edema: Altered mental status, increased vomiting, incontinence, cranial nerve palsies, abnormal pupillary responses, bradycardia, and increasing or decreasing BP. 100 Pediatrics

Interventions Diagnostic Testing For all patients: Patient off Ye s Β-hydroxybutyrate, glucose, algorithm, treat Patient in CHEM 7, VBG, Hb A1C. as appropriate shock? Calculate and follow anion gap, osmolarity, corrected Na. No New onset diabetes patients Bolus Lactated Ringer's Islet cell, insulin, and anti-GAD 10ml/kg IV over 1 hour. antibodies, C-peptide, insulin, May repeat once if thyroid peroxidase and clinically indicated thyroglobulin antibodies. Celiac panel

On Insulin drip Age <5 or Glucose Q1H (goal not greater Consider No Bicarbonate than 100 mg/dL decrease per hour), subcutaneous ≤ 12, or abnormal electrolytes Q2H, monitor insulin. mental status? real and corrected Na and anion gap.

Ye s

K <5.0?

No Yes

Begin IVF without Begin 2 Bag Fluid additional K system

LR or NS at Total fluid for initial 24 hours 2.5 L/m2/day not to exceed 2.5 L/m2/day not 4 L/m2/day, including initial boluses to exceed Bag A: LR + KPO4 2 mmol/100mL + KCl 1.5 meq/100mL 2 4 L/m /day Bag B: D10LR + KPO4 2 mmol/100mL + KCl 1.5 meq/100mL including initial Total IVF mL/Hour = Bag A mL/Hour + Bag B mL/Hour boluses. Add Blood Glucose Bag (A) Bag (B) dextrose to IVF >300 ___mL/Hour(100%) 0 mL/Hour when blood 251–300 ___mL/Hour(75%) __mL/Hour(25%) glucose <300. 201–250 ___mL/Hour(50%) __mL/Hour(50%) 151–200 ___mL/Hour(25%) __mL/Hour(75%) ≤150 0 mL/Hour __mL/Hour(100%)

Insulin infusion at 0.1units/kg/hour Insulin infusion at 0.1units/kg/hour (0.05units/kg/hour if age less than (0.05units/kg/hour if age less than 5 or hyperosmolar) 5 or hyperosmolar)

Figure 9-4 Suggested algorithm for management of a patient in DKA/HHS. Critical Care 101

INCREASED INTRACRANIAL PRESSURE AND TRAUMATIC BRAIN INJURY • Increased ICP: Any process resulting in the expansion of the space occupied by CSF, blood, or brain tissue will result in increased ICP. • Cerebral edema can be generalized or local, and occurs in three forms. • Vasogenic edema results from increased capillary permeability. Fluid typically accumu- lates in the white matter. Tumors, abscesses, trauma, and hemorrhage are all associated with vasogenic edema. Corticosteroids are theoretically effective but are not proven to be beneﬁ cial in some settings. Osmotic agents have no direct effect but may decrease the volume of normal brain tissue to accommodate the swelling. • Cytotoxic edema is caused by swelling of neurons, glia, and endothelial cells, constrict- ing the extracellular space. Hypoxia, ischemia, infection, DKA, and hyperammonemia are some causes. Corticosteroids do not help, but osmotic agents may reduce brain tissue volume. • Interstitial edema results from transependymal movement of CSF from the ventricular system into the interstitial spaces. Fluid collects primarily in the periventricular white matter. Noncommunicating hydrocephalus is a cause. Corticosteroids and osmotic agents do not help, but the latter may reduce the volume of normal brain tissue in an emergency. Deﬁ nitive treatment involves relieving the obstruction (ie, with a shunt or EVD).

Determine the Cause • Imaging: Head CT without contrast. • Brief history and physical exam to guide further immediate workup: Trauma, evidence for acute liver failure, history of hypoxic ischemic insult, history of intracranial pathology, history of ventricular shunt, history of malignancy (CNS or otherwise), prolonged seizures, fevers, history of hypertension, severe dehydration with risk of thrombosis, history of headaches. • If the caregiver history is not compatible with the pattern of injuries: Inﬂ icted neurotrauma is a common cause of TBI; this should be high on the differential diagnosis list, especially in children younger than 1 year of age. • If previous ventricular shunt: (Feel the scalp for shunt tubing if history not available) → shunt series (plain radiographs to evaluate for breaks or discontinuity of shunt tubing (in addition to head CT). PEDIATRICS • If febrile: Workup for causes of fever (CT head before LP to determine safety of LP).

Principles of Acute Management of Increased ICP or Suspected Herniation Syndrome • Obtain a neurosurgical consultation immediately as you institute these therapies simultaneously: • ABCs, vital signs, place on monitors, IV access. • Supplemental oxygen. • Hyperosmolar therapy. • Mannitol: 0.25–1 g/kg IV, then maintenance dose of, 0.25–0.5 mg/kg q4–6 h; (most effective while serum osmol <320). • 3% saline: 3 to 10 cc/kg IV up to serum OSM 360. • Endotracheal intubation if loss of airway protective reﬂ exes, GCS ≤8, or falling GCS. • Premedicate before intubation with atropine 0.02 mg/kg IV (minimum, 0.1mg/kg; maximum, 1 mg), lidocaine 1 mg/kg IV. • If the patient is normotensive, consider using thiopental for sedation (3–6 mg/kg IV; maximum, 300 mg). If the patient is hypotensive, consider using etomidate (0.2–0.4 mg/kg IV). • Avoid succinylcholine as an NMB agent. • Head midline, head of bed elevated to 30 degrees. • Control of seizures if present with appropriate antiepileptic medication (typically lorazepam 0.1mg/kg IV, fosphenytoin 20 mg/kg IV, or both). 102 Pediatrics

• Aggressive control of fever is present with acetaminophen 10 to 15 mg/kg PR. • Speciﬁ c therapy for treatable causes • Mainly surgical and supportive • Dexamethasone (load 1–2 mg/kg PO, IM, or IV once; then 1.0–1.5 mg/kg/d; maximum, 6 mg/d in divided doses Q4–6h) for intracranial tumors.

Management Caveats for Patients with Traumatic Brain Injury

• ICP goals: aggressively maintain ICP <20 cm H2O. • CPP goals: Avoid hypotension, CPP <40 mmHg in all child age groups associated with worse outcome. CPP >40–60 mmHg in children; >70 mmHg in adults (CPP = MAP – ICP). Hyperosmolar Therapy • Mannitol: 0.25–1 g/kg IV (may repeat Q4–6h while serum osm <320) • Hypertonic (3%) saline: 3–10cc/kg IV or as a continuous infusion from 0.1–1 cc/kg/h while serum osm <360. Airway Management and /Hyperventilation

• Avoid hypoxemia; moderate hyperventilation (after failure of other modalities) to pCO2

30–35 may be benefi cial; severe hyperventilation to pCO2 <30 may cause harm through decreased cerebral blood fl ow. Sedation and Analgesia • Is important to monitor the neurologic exam of a patient with increased ICP, but the use of sedation and analgesia is important for ICP control (especially if intubated). • Use of short-acting sedative agents is preferred over long-acting agents. Neuromuscular Blockade • NMB may be necessary to control ICP in patients who have uncontrollable shivering (the patient must be appropriately sedated). • Consider continuous EEG if the patient is under NMB to the minimize risk of missing seizure activity. Seizure Prophylaxis • Seizure prophylaxis is usually with phenytoin or Fosphenytoin for 7 to 14 days after injury for TBI. (This reduces the occurrence of early posttraumatic seizures but does not impact the onset of late posttraumatic seizures). • Monitor closely for and aggressively treat any seizures. Hypothermia • Avoidance of fevers is important for patients with increased ICP. • It is unknown if induced hypothermia in the setting of traumatic or asphyxial injury with increased ICP is of benefi t. • Hypothermia has been shown to improve neurologic outcomes for adult patients after cardiac arrest. Glucose • Avoid hypoglycemia and hyperglycemia. • Provide initial fl uids without dextrose; monitor serial glucose. • Begin dextrose in IV fl uids if ketosis is present or the patient has decreasing blood glucose; use insulin infusion if the patient is hyperglycemic. Nutrition • Children should have nutrition either enteral (preferred) or parenteral begun by day 2 or 3 after their injury and be on full nutritional support by day 7. Status Epilepticus • Overall mortality rate of 8% in children; 30% in adults. • Among children, the overall incidence of status epilepticus is approximately one to six per 10,000 per year (50% younger than age 3 years). • Status epilepticus represents the fi rst seizure of subsequent epilepsy in ~1/3 of patients; another 1/3 occurs in patients with known epilepsy (often low antiepileptic medication levels). Critical Care 103

• The longer a seizure continues, the lower the probability becomes that it will stop without intervention; after a seizure has lasted >5 minutes, an intervention is warranted (eg, rectal diazepam at home; IV medications in healthcare setting). • All seizures should be treated as status epilepticus until they stop. Types of Status Epilepticus • Status epilepticus: Seizures lasting ≥30 min (including two or more sequential seizures without full recovery of consciousness to baseline between seizures). • Convulsive status epilepticus: Generalized tonic or tonic-clonic seizures lasting ≥30 min. • Minimally convulsive status epilepticus: Persistent convulsive status epilepticus characterized only by minimal clinical signs such as rhythmic eye fl uttering or asymmetrical tone. This condition is also referred to as “subtle status epilepticus.” • Nonconvulsive status epilepticus: Persistent electrographic status epilepticus without any clinical manifestations other than altered awareness or altered mental status. This defi nition encompasses both generalized processes, such as absence nonconvulsive status epilepticus, as well as lateralized or focal nonconvulsive status epilepticus. • Refractory status epilepticus: Status epilepticus that has persisted despite administration of a fi rst-line agent (lorazepam 0.1mg/kg) and a second-line agent (cumulative fosphenytoin 30 mg PE/kg or phenobarbital 20 mg/kg). Causes of Status Epilepticus • Infections with fever • Low antiepileptic drug levels in a patient with epilepsy • Trauma or infl icted neurotrauma, especially in infants • Ingestions • Electrolyte disturbances • Intracranial lesions (tumor, bleeding, stroke) • Increased ICP • Hypoxia or ischemia Clinical Pearls for Status Epilepticus • ABCs, 100% oxygen, stat glucose and chemistry, intubate if necessary, fever control. • If no IV access in 90 seconds, obtain IO access. • Treat fevers. • May quickly stop if you resume a medication that was recently discontinued or for which PEDIATRICS the patient has a subtherapeutic drug level. • Suspect subclinical status epilepticus in all patients who are unresponsive 20 to 30 minutes after cessation of status epilepticus or after receipt of phenobarbital. • If you do not have IV or IO access in the fi rst 5 minutes of status epilepticus, you can administer an intranasal, rectal, or buccal benzodiazepine as the fi rst dose of a benzodiazepine (Figure 9-5).

MEDICATIONS USED FOR REFRACTORY STATUS EPILEPTICUS

Medication Dose Comments

Keppra™ 15–30 mg/kg IV load; then Dose adjustment for renal failure BID not to exceed 60 mg/ kg/day or 1500 mg/dose

Pentobarbital 5–10 mg/kg IV load over May see cardiac and respiratory depression, 1–2h, then infuse 1–6 mg/ hypotension, need for inotropes or vasopres- kg/h titrated to maintain sors; over time will see immunosuppressive burst suppression on EEG. eﬀ ects and may see liver dysfunction

Midazolam 0.15 mg/kg IV load; then May see cardiac and respiratory depression, (Versed)™ infuse 2–6 mcg/kg/min IV hypotension

Propofol 1–2 mg/kg IV load; then Monitor for propofol infusion syndrome; use infuse 3–10 mg/kg/h IV caution in children younger than 12 years old 104 Pediatrics

Medications Monitoring Cardiac Monitor, Pulse Lorazepam 0.1 mg/kg IV (Max dose = 2 Oximetry, Frequent blood mg/dose) If no IV access may give first dose pressure measurements as rectal, intranasal, or buccal benzodiazepine throughout algorithm.

Seizures Stop Seizures continue Fosphenytoin for 5 20 PE/kg IV (A,B) minutes (Max dose 1 gram total)

Monitor for adequate Lorazepam 0.1 mg/kg IV (Max dose = 2 mg/dose) chest rise, ventilation, Fosphenytoin 30 PE/kg IV (A,B) (Max dose 1 adequate circulation, gram total) (Max rate = 150 PE/minute) airway protective reflexes

Seizures continue for 5 minutes after Obtain Phenytoin peak level full dose given 30 minutes after last infusion

Phenobarbital 20 mg/kg IV (C) Obtain Phenobarbital peak (Max dose 800 mg) (Max rate level 4 hours after infusion 50 mg/minute) Seizures continue for 10 minutes after full dose given

Obtain Neurology consult for additional recommendations. Patient may need pharmacologic coma to control seizures. Order STAT EEG (D) Additional medication options include: Keppra 15–30 mg/kg IV Pentobarbital, Propofol, or Versed continuous infusions

Central venous pressure monitoring, arterial pressure Pharmacologic Coma monitoring, continuous EEG. Patient admitted to PICU. Figure 9-5 Suggested management algorithm for status epilepticus. (A) Fosphenytoin should be dosed in phenytoin equivalents (PE), which convert the fosphenytoin dosage into an equivalent number of milligrams of phenytoin (50 mg fosphenytoin = 50 mg PE). The maximal rate of administration of fosphenytoin is 150 mg PE/min. If at all possible, IV phenytoin should not be used given the high likelihood of extravasation and hemodynamic complications. In patients with a documented allergy to phenytoin (Di- lantin), phenobarbital 20 mg/kg should be used after lorazepam. (B) For patients already taking prescription phenytoin, a phenytoin level should be ordered and Phenobarbital should be given after lorazepam instead of fosphenytoin. You may be able to give a fosphenytoin load (10–20 mg PE/kg) if the level returns and is low. (C) The peak efﬁ cacy of phenobarbital is approximately 30 to 60 minutes after administration. It should be administered at a rate equal to or less than 50 mg/min. (D)All patients who receive phenobarbital in the status epilepticus algorithm should have a STAT EEG to rule out subclinical status epilepticus. All patients who remain obtunded or do not demonstrate signs of awakening appropriately after medications should receive a STAT EEG to rule out subclinical status epilepticus. Critical Care 105

Decision Tree for Work-up of Status Epilepticus Patients

Known Seizure Disorder First Seizure

Febrile Afebrile Febrile Afebrile

All Patients All Patients All Patients All Patients Check AED Levels Check AED Levels Brain CT, Brain CT, Neurology Consult Neurology Consult Lumbar Puncture Glucose d-stick, Electrolytes Electrolytes (Obtain extra CSF), Chemistry Panel Glucose d-stick Glucose d-stick CBC, Glucose (Including Calcium, Tracheal Aspirate* d-stick, Chemistry Mg, Panel (Including Phosphorus), Calcium, Mg, Tracheal Aspirate*, Phosphorus), Toxicology Screen, Chest X-Ray, Neurology consult Tracheal Aspirate*, UA+Urine culture, Blood culture, Viral cultures, Consider Neurology consult CBC, Cultures (blood, viral), Brain CT, Lumbar puncture, EEG, Chemistry panel Consider Consider (including Consider Toxicology Screen CBC Calcium, Mg, Toxicology Screen EEG ECG Phosphorus) EEG, Brain CT in Vancomycin/Cefota- EEG infants < 1 year xime/Ceftriaxone Workup for IEM

Figure 9-6 Decision tree for workup of patients with status epilepticus. ∗Only if the patient is intubated. †A neurology consult as well as brain imaging should be obtained immediately for any patient with neurologic deﬁ cits. If head CT demonstrates intracranial pathology concerning for increased ICP, neurosurgical consultation should be obtained immediately. ‡Brain CT is recommended before performing an LP to determine the presence of intracranial pathology that might be a contraindication to LP. PEDIATRICS §When performing an LP, it is ideal to obtain an extra sample of CSF for future studies if they become necessary to determine the cause of status epilepticus. Obtain opening pressure when performing LP. ¶If the LP results are concerning for infection (elevated WBC count, abnormal glucose, elevated protein, elevated RBC count), the patient may need additional studies, which may include CSF viral culture; CSF PCR for HSV, enterovirus, adenovirus; nasal wash or throat swab for viral culture; rapid adenovirus screen; nasal wash for inﬂ uenza A or B (seasonal); stool or rectal swab for viral culture; rapid adenovirus screen; and arbovirus studies (seasonal). CHAPTER 10 Dentistry and Oral Health

ANTICIPATORY GUIDANCE Bottle Weaning • Encourage infants to drink from a cup near age 12 mo; completely wean from bottle by age 18 to 24 mo.

Oral Hygiene • Begins before eruption of fi rst tooth. • Use a pacifi er, not a bottle, as the infant’s means of non-nutritive sucking (no dipping in sweetener; goal wean from pacifi er by age 24 mo; affects alignment of teeth after age 36 mo). • Limit or exclude high-sugar juices (maximum, 1 cup of juice daily), carbonated beverages, and refi ned carbohydrates; no bottle in bed or immediately before sleep. • Wipe the infant’s gums with a moist cloth twice daily before the eruption of the fi rst tooth. • Flossing should be done daily after contact occurs between adjacent teeth. • Toothbrushing with American Dental Association–approved fl uoridated toothpaste (Morbid Mortal Wkly Rep 2001;50(RR-14):1).

Dental Home • Established by age 1 year or 6 mo after ﬁ rst tooth erupts for low-risk patients; earlier for high-risk patients (children with special healthcare needs, any condition impairing salivary production or ﬂ ow). • Subsequent visits biannually for low-risk patients.

Fluoride • Children with optimal fl uoride consumption through adolescence have 50% to 75% less decay (sources: fl uoridated community water, oral supplements, fl uoridated toothpaste). • Slightly over half of the U.S. water supply is fl uoridated (at varying amounts). • Optimal community water supply fl uoridation is 0.7 to 1.2 ppm. • Determine the fl uoride level of the local community water (local water utility or see http://apps.nccd.cdc.gov/MWF). • Adequate daily intake of fl uoride: 0.01 mg/d for age 0 to 6 mo, 0.05 mg/kg/d for children older than 6 mo and adolescents. • Children age 6 mo and older may need oral supplementation, depending on the community water supply (Pediatrics 1995;95(5):777). • On average, 0.3 mg of fl uoride is ingested with each brushing by young children using regular fl uoridated toothpaste; a pea-sized drop of regular fl uoridated toothpaste contains 0.4 to 0.6 mg of fl uoride. • Fluorosis: Excess fl uoride consumption may result in mild, permanent cosmetic effects (streaking, pitting, gray staining) on unerupted teeth; the most vulnerable period between ages 2 and 4 yr. Usually only occurs at amounts exceeding twice the recommended adequate intake (mildest form may occur >0.1 mg/kg/d fl uoride intake).

EARLY CHILDHOOD CARIES • Deﬁ ned as decay in the primary teeth of children younger than age 6 yr. • Most common chronic disease of childhood; 80% of caries are in low-income families; early referral of low-income, high-risk children is important. • Occur in 15% of children ages 2 to 4 yrs; peak at ages 24 to 30 mo.

106 Dentistry and Oral Health 107

• Caries is a process present in all individuals; expression of cavities depends on the level of activity, host resistance, and host factors. • Streptococcus mutans is the most common bacterial agent; it is absent from the oral cavity until primary eruption and is then acquired from caregivers between ages 12 and 36 mo. • Maternal xylitol gum or mint use QID may prevent transmission of cariogenic bacteria to infants. • Begins as chalky white appearing change in enamel leading to brown cratering lesions. • Risk assessment for all patients: See American Academy of Pediatric Dentistry assessment tool at www.aapd.org/media/Policies_Guidelines/P_CariesRiskAssess.pdf. • Control measures: Proper fl uoride exposure, daily fl ossing, twice-daily brushing with fl uoridated toothpaste, limit refi ned carbohydrates, exclude soft drinks, reduce transmission risk from caregivers (avoid food and utensil sharing, caregiver xylitol gum use QID), establishment of a dental home. • Sequelae of untreated disease: Severe pain, language delay, infection, diffi culty chewing, poor weight gain, failure to thrive, risk of dental decay in adult teeth, malocclusion. • Treatment of established disease: extraction, fi llings, dental crowns and fi llings.

NORMAL ERUPTION Teething (Figure 10-1) • Symptoms: Oral (salivation, biting), local (circumoral rash, ear rubbing), systemic (low- grade fever, fussiness, wakefulness, feeding pattern disruption) Treatment • Teething rings, cold washcloth for sucking or chewing. • Acetaminophen as needed. • Topical teething gels are not recommended (risk of systemic toxicity).

Erupt (years) Central incisor 7–8 Lateral incisor 8–9 Erupt Shed Canine (cuspid) 11–12 (months) (years) First premolar 10–11 7 8 910 (first bicuspid) Central incisor 8–12 6–7 6 11 5 12 Second premolar 10–12 E F Lateral incisor 9–13 7–8 D G 4 13 (second bicuspid) C H Canine (cuspid) 16–22 10–12 14 3 Upper teeth First molar 6–7 I 2 15 B First molar 13–19 9–11 Second molar 12–13 PEDIATRICS Upper teeth 1 16 Second molar 25–33 10–12 Third molar 17–21 J A Secondary (wisdom tooth) Primary Third molar 17–21 32 17 (wisdom tooth) 31 18 T K Second molar 23–31 10–12 Lower teeth Second molar 11–13 Lower teeth 30 19 First molar 14–18 9–11 First molar 6–7 S L 29 20 Second premolar 11–12 Canine (cuspid) 17–23 9–12 21 R M 28 (second bicuspid) Q PON Lateral incisor 10–16 7–8 First premolar 10–12 27 22 (first bicuspid) Central incisor 6–10 6–7 26 25 24 23 Canine (cuspid) 9–10 Lateral incisor 7–8 Central incisor 6–7

Figure 10-1 Primary and secondary dentition development sequences. (Adapted with permission from Gomella LG, Haist SA: Clinician’s Pocket Reference, 11th ed. Copyright © The McGraw-Hill Companies, Inc. All rights reserved.)

Primary Eruption (Lettered A through T) • Range for initial tooth eruption is between ages 3 and 16 mo, with an average of 6 mo. • Normally all primary eruptions are complete by age 2 yr. • The ﬁ rst primary eruption is usually the lower central incisor.

Secondary (Permanent) Eruption (Numbered 1 through 32) • Range for secondary tooth eruption is between ages 6 and 8 yr. • The ﬁ rst secondary eruption is usually the lower central incisor. 108 Pediatrics

ABNORMAL ERUPTION Neonatal or Natal Tooth • Natal tooth: Tooth present at birth • Neonatal tooth: Tooth that emerges during the ﬁ rst month of life • Most often the mandibular central incisor • >90% are early-erupting primary teeth; <10% are supernumerary teeth • Remove only when breastfeeding, hypermobile, or risk of trauma to the lip or tongue

Early Eruption • Primary eruption <3 mo of age • Differential diagnosis: Familial, hypothyroidism, precocious puberty, growth hormone excess

Delayed Eruption • Primary eruption occurring age >16 mo • Differential diagnosis: Familial, ectodermal dysplasia, hypothyroidism, hypoparathyroidism, hypopituitarism, rickets, malnutrition, cleidocranial dysostosis, prematurity, trisomy 21, HIV, Gaucher’s disease, complication of radiation or chemotherapy • Management: Expectant management along with co-monitoring in the dental home (in the absence of any speciﬁ c oral pathology, dysmorphism, growth disturbance, bony abnormalities, or ﬁ ndings suggestive of endocrine or genetic disorder)

Odontogenic Infections • An infected tooth may present with pain and sensitivity or as a superﬁ cial orofacial space infection involving the buccal, submental, masticator, canine, or infratemporal spaces. • Suppurative odontogenic infections may extend to potential fascial spaces in the orofacial area, deep in the head and neck (peripharyngeal space infections), into adjacent bone (osteomyelitis), or hematogenously. • Patients with isolated dental abscesses with no clinical suspicion for fascial plane involvement, deep neck infection, osteomyelitis, or hematogenous involvement may be managed on oral antibiotics (high-dose amoxicillin or clindamycin) while the parent promptly arranges for an outpatient dental evaluation.

INFECTIVE ENDOCARDITIS PROPHYLAXIS See Chapter 8.

Available at www.AccessPediatrics.com • Early childhood caries • Dental trauma PEDIATRICS lled, fatigue tenderness Pruritus and Pain Paresthesias Bleeding or chills Fever Malaise or lled, • • • • • • Local Systemic Signs and Symptoms • • uid fi uid lled uid fi uid (continued on next page) Accentuated skin mark- Linear erosion al exposures exposures variation care prod- care ucts mental exposures Seasonal Sick contacts travel Recent Medications Environ- Personal Personal Occupation- Recreational Epidermal (thinning of epi- • • • • • • • • Raised, pus fi cation: Raised, clear, fl Transient, palpable edema Raised, clear, fl Fibrous tissue replacing normal <1 cm >1 cm ings caused by thickening of epidermis; rubbing usually caused by scratching or architecture of dermis dermis) or dermal (decrease in the amount of collagen or causing depression of skin) Bulla: Pustule: Vesicle: Wheal: Atrophy: Excoriation: Lichenifi Scar: • • • • • • • • 109 Since birth?Since Recurrent? How long? How • • • lesions c changes caused by evolution of primary brane involvement surfaces of enon: areas trauma previous Dermatomal mem- Mucous Contact areas extensor vs Flexor Koebner phenom- Symmetry Photodistribution • • • • • • • by disease process c changes caused directly painful break in cial, often Loss of epidermis; heals without Solid, palpable, 1–2 cm, dermal Nonpalpable, <1 cm Superfi Solid, palpable, >2 cm Solid, palpable, <1 cm Solid, palpable, >1 cm, width > Solid, palpable, >1 cm, width ned Nonpalpable, >1 cm Loss of epidermis and part or all of Accumulation of serum, cellular, Accumulation of serum, cellular, Accumulation of loosely adherent Accumulation of loosely adherent guration ill-defi Arrangement Shape vs. Well • • • secondary changes texture Confi Color Consistency and Mobility Primary vs. dermis; heals with scarring keratin epidermis thickness bacterial, and squamous debris over bacterial, and squamous debris damaged epidermis scarring Scale: Macule: Crust: Erosion: Plaque: Tumor: Fissure: Ulcer: Papule: Patch: Nodule: • Description• Distribution• • Duration Exposure • • • • • • • • • • • • CHARACTERIZATION OF SKIN LESIONS Secondary: Nonspecifi Dermatology TYPES OF LESIONS Primary: Specifi CHAPTER 11 110 Pediatrics

Signs and Description Distribution Duration Exposure Symptoms • Discrete • Family • Arthritis or history arthralgias • Localized • Grouped • Disseminated

ATOPIC DERMATITIS AND ECZEMA • Risk factors: Family history, other atopic diseases (asthma, allergic rhinitis), food hypersensitivity, environmental allergens • Clinical manifestations: Pruritic, erythematous, scaly papules and plaques → edema, serous discharge, crusting → licheniﬁ cation, hyperpigmentation, ﬁ ssuring → superinfection (primarily with Staphylococcus aureus; also with HSV)

Distribution • Infantile: Cheeks, forehead, trunk, extensor surfaces • Childhood: Wrist, ankle, antecubital and popliteal fossae • Adolescent and adult: Flexor surfaces, face, neck, hands, feet

ECZEMA COMPLICATIONS

Type Clinical Features Treatment or Prevention S. aureus superinfection Honey-crusted erosions, pus- • Topical or oral antibiotic tules, weeping, acute increase • Obtain culture in erythema Eczema herpeticum (HSV • First-degree lesions: Crops of • Stop TCS or TCI superinfection) vesicles on infl amed base at • Acyclovir or valacyclovir sites of eczema • Source of contact often • Treat for secondary bacterial adult caretaker with • Late: “punched-out” erosions infection if indicated “cold sore” • Common associated symp- • Treat known contacts toms: Fever, malaise, irritability, • Eye exam for periorbital intense itching, eczema fl are involvement • Severe: Widespread viral dissemination with multiorgan • Obtain culture &/or DFA involvement Long-term TCS use• Skin atrophy, ecchymoses, • Limit use for fl ares only striae, telangiectasias, poor (usually <1- 2-wk intervals) wound healing, perioral • Use lower potency TCS for dermatitis or steroid rosacea, face, underarms, and groin hypothalamus–pituitary axis • If indicated, evaluate for suppression with systemic adrenal suppression and treat absorption appropriately Postinfl ammatory pig- • Hypo- or hyperpigmented Sun protection and contin- ment changes macules or patches in areas ued treatment of fl ares of of previous involvement dermatitis • Fades over months to years

TCS, topical corticosteroid; TCI, topical calcineurin inhibitor

Treatment • Maintenance: Short, lukewarm baths or showers under 10 minutes with mild soap; frequent moisturization with thick, bland emollients (cream or ointment) Dermatology 111

• Mild fl are: Class 6 to 7 TCS or TCI BID (approved for ≥2 yo; use for ≤2 weeks at a time; good for face); ointment preferred • Moderate fl are: Midpotency TCS for body BID (eg, triamcinolone 0.1%); ointment preferred; class 6 to 7 TCS or TCI BID for face; oral antihistamines PRN for pruritus • Severe fl are: Midpotency TCS followed by warm, wet wraps BID for at least 15 min; ointment preferred; then application of emollient; oral antihistamines PRN for pruritus and antibiotics for superinfection

CONTACT DERMATITIS

Type Description Causes Course Treatment

Irritant• Acute: Results from contact • May occur after • Avoidance of Erythema, scal- with a substance that single contact irritants ing, edema, chemically or physically with a strong • Emollients, vesicles, damages skin irritant or barrier pustules, • Urine or feces → after repeated creams erosions contact with diaper rash • May consider milder irritants • Chronic: • Lip licking or thumb TCS if no im- Licheniﬁ cation, sucking • Rash minutes provement ﬁ ssures to hours after • Detergents or solvents (controversial) exposure • Topical medications • Battery acid

Allergic (type • Acute: • Poison ivy, oak, sumac • 1° exposure → • May use IV cell- Erythematous, • Nickel (jewelry, metal rechallenged patch testing → mediated scaly, vesicular, clasps, glasses) by allergen to confi rm immune crusted, dermatitis diagnosis • Rubber (shoes, clothing) reaction) weeping • Rhus (poison • Avoidance of • Paraphenylenediamine • Chronic: ivy, oak, sumac): allergen (may (hair dyes, leather, Lichenifi ca- patchy or take >6 wk black-dyed henna) tion, fi ssuring, linear vesicles for complete excoriations • Topical antibiotics (eg, or bullae on ex- clearing of neomycin, bacitracin) posed surfaces rash)

• Emollients 2–7 days after • Topical or PEDIATRICS • TCS exposure, last- systemic cor- ing 3–4wk ticosteroids

Data from Dermatol Ther 2004;17:334.

OTHER ECZEMATOUS OR PAPULOSQUAMOUS ERUPTIONS

Disease Description Course Treatment Other

Sebor- • “Cradle cap”: Greasy • Usually begins • Bathing • Linked with rheic scales on scalp 1 wk after birth • Frequent sebum dermatitis • Disseminated: Bilateral, • May persist for moisturization overproduc- (infantile tion and well-demarcated, sym- months • Ketoconazole form) Malassezia metric pink patches 2% cream if spp. infection and plaques with extensive or scaling in diaper area, persistent retroauricular • Short course areas, neck, trunk, and of low- proximal extremities, potency TCS if prominent in skin inﬂ amed creases/folds

(continued on next page) 112 Pediatrics

Disease Description Course Treatment Other

Keratosis • Skin-colored follicular • May become • No deﬁ nitive • Can be asso- pilaris∗ hyperkeratotic or more pro- treatment ciated with erythematous nounced at • May try ichthyosis papules on the upper puberty (some emollients, vulgaris, arms, thighs, cheeks may improve at lactic acid atopic puberty) or glycolic dermatitis • Often improves acid creams, with age urea cream, • Improvement salicylic acid, in summer; short course worsening in of TCS for winter inﬂ amed areas

Pityriasis • Small, ill-deﬁ ned, • May become Emollients, alba symmetric, hypopig- more obvious low-potency mented patches with in summer on TCS, sunscreen ﬁ ne scales, often on tanned skin cheeks; may be seen • May last for on upper extremities months to years • Resolves spontaneously

Pityriasis • “Herald” patch: Initial • Most common • Reassurance • May have rosea 1- to 10-cm salmon- in adolescents • TCS ± PO mild colored oval patch or and young antihistamine prodrome: plaque with collarette adults PRN for Fever, HA, of ﬁ ne scale, usually • More common pruritus malaise on trunk in spring • Possible • May be • Within days: beneﬁ t of 14- pruritic “Christmas tree” day course of • Lasts distribution of oval, erythromycin† 6–8 wk; hyperpigmented, (controversial) sometimes smaller, thin plaques • UVB light months or papules similar treatment for • May be to a herald patch on severe cases mimicked trunk by syphilis • Face, palms, soles (check RPR if usually spared indicated) • May see oral • Possible erosions association • Inverse pityriasis with HHV-6, rosea: Variant HHV-7 involving axillae and inguinal areas; more common in younger children and darker- skinned patients

(continued on next page) Dermatology 113

Disease Description Course Treatment Other

Psoriasis‡ • Well-demarcated • Guttate type: • Topical cor- • Inverse erythematous Drop-like lesions ticosteroids, psoriasis: papules and plaques on trunk, often calcipotriene, Variant with thick, silvery after streptococ- coal tars, involving scales; often on cal infections, phototherapy, ﬂ exural elbows, knees, scalp, URI methotrexate, areas trunk, but can occur • Localized pustu- cyclosporine, anywhere lar type: Discrete acitretin, • Diaper area in infants pustules, scaly TNF-α inhibitors, my- • Scalp - scaling, pap- plaques on cophenolate ules & plaques palms or soles mofetil • Nail dystrophy - • Generalized • Never use pitting, other pustular type: Erythema with systemic ste- sheets of small roids because pustules, migra- of psoriasis tory annular ﬂ ares when erythematous stopped plaques on tongue, possible after corticosteroid withdrawal, fever, arthralgias • Koebner phenomenon

∗Cutis 2008;82(3):177. †J Am Acad Dermatol 2000;42:241. ‡Pediatr Dermatol 2001;18(3):188.

BACTERIAL INFECTIONS

Type Description Cause Course Treatment Other PEDIATRICS Impetigo• Honey-crusted • S. aureus • Usually no • Gentle • Ecthyma: erosions, super- (non- constitution- cleansing Deep ﬁ cial vesicles bullous, al symptoms • Topical impetigo or bullae at bullous, or • Bullous form antibiotics with ulcer sites of skin pustular) formation, may occur • Systemic breakdown often on • Strepto- on intact skin antibiotics legs, heals • May be pruritic coccus for extensive with scarring • Usually on face, pyogenes cases hands, genita- (usually lia, or scalp nonbullous) Folliculitis• Pustules or red • Usually • Benign • Antibacterial papules origi- S. aureus • Heals with- washes nating from out scarring • Topical hair follicles antibiotics if • Usually on localized scalp, face, • Systemic chest, back, antibiotics if buttocks, extensive or extremities recurrent

(continued on next page) 114 Pediatrics

Type Description Cause Course Treatment Other Abscess• Erythematous, • Usually • May become • Warm, moist • Recurrent: tender, puru- S. aureus fl uctuant and compresses MRSA eradi- lent masses, or GABHS spontane- • If fl uctuant, cation with fairly well- ously drain I&D intranasal circumscribed mupirocin • Systemic TID x 1 wk ± antibiotics if bleach bath indicated Q2-3 d (1/2 cup bleach:20 gallons water) (for patient and contacts) • Other treatments: Daily chlorhexidine washes, rifampin/ doxycycline x 1 wk∗ Cellulitis• Acute, • S. aureus • Prodrome: • Systemic ill-defi ned, or GABHS Fever, chills, antibiotics suppurative through malaise infl ammation of area of deeper subcu- skin break- taneous tissues down or with erythema, hematog- warmth, swell- enous ing, tenderness spread Erysipelas• Progressive, • GABHS • Prodrome: • PCN for • Cover for superfi cial, well- Fever, chills, 10–14 d S. aureus if demarcated malaise (erythromy- no improve- cellulitis • May resolve cin if PCN ment or (primarily with desqua- allergy) atypical involving the mation and • Rest (bullous) dermis) post- • Elevation infl ammatory pigment changes Scarlet • Blanching, • GABHS • Prodrome • PCN for • Monitor fever erythematous (high fever, 10–14 d for other “sandpaper” chills, HA, (erythromy- GABHS rash starting on sore throat, cin if PCN sequelae: central body anorexia) → allergy) peritonsillar and spreading rash devel- abscess, • Circumoral ops within rheumatic → pallor, fl ushed 12–48 h fever, acute cheeks exudative glomerulo- pharyngitis, nephritis strawberry tongue within days → 7–10 d: desquamation lasting 2–6 wk

(continued on next page) Dermatology 115

Type Description Cause Course Treatment Other Toxic • Diff use maculo- • S. aureus • Sudden • Removal of shock papular erythro- or GABHS onset of foreign body syndrome derma on trunk exotoxin high fever, or nidus of with centripetal myalgias, infection spread vomiting • Early, • Erythema or or diarrhea, aggressive edema of palms headache, septic shock or soles pharyngitis treatment → rapid • Desquama- including progression tion of hands early anti- to shock or feet 1–3 wk biotics (see after onset of chapter 9) symptoms Staphy- • Generalized Exfoliative • Prodrome: • Parenteral • Nikolsky sign: lococcal erythema, often toxins of Fever, malaise, antibiotics Mechanical → scalded tender su- S. aureus irritability • Bland pressure skin syn- perfi cial, fl accid • Scaling or emollients induces → drome bullae moist, desquamation for denuded dermal– crusty skin with for 3–5 d after skin epidermal desquamation cleavage bullae forma- • Aggressive • Mucus mem- tion pain control • No organisms branes not • Reepithelializa- seen on skin involved tion in 10–14 d culture or biopsy Meningo- • Petechiae or • Neisseria • Severe system- • IV third- • Treat con- coccemia purpura, ecchy- menin- ic symptoms generation tacts with moses, ischemic gitidis with rapid cephalosporin, rifampin necrosis, hemor- decompensa- PCN, chloram- prophylaxis rhagic bullae tion phenicol Lyme • Erythema • Borrelia • Rash occurs • Doxycycline disease† migrans → burgdorferi ~7–15 d (if >8 yo)

annular after tick • Amoxicillin PEDIATRICS erythematous detached (if <8 yo or plaques, cen- • Lasts ≤6 wk if pregnant) trifugal spread untreated • Dissemi- • Usually on trunk, nated severe axilla, groin, or disease: Third- popliteal fossa generation cephalosporin Rocky • Erythematous • Rickettsia • Fever, • Doxycycline Mountain macules on rickettsii headache, for all ages spotted wrists or ankles through myalgia → fever with centripetal tick bite in rash appears spread spring and on day 3–6 • Maculopapular summer • May develop lesions on palms severe sys- or soles temic symp- • Severe: petechiae, toms with retiform purpura progressive worsening

∗Clin Infect Dis 2009;48(7):922. †Am J Clin Dermatol 2008;9(6):355. Data from Curr Opin Infect Dis 2008;21(2):122 and Paediatr Drugs 2003;5(suppl 1):35. 116 Pediatrics

VIRAL INFECTIONS

Type Description Course Treatment Other

Rubeola • Erythematous • Rash appears • Supportive • Prodrome: or measles maculopapular ~5 days after on- care Malaise, fever, (paramyxo- rash starts on face set of symptoms cough, coryza, virus) and spreads to • Fades over conjunctivitis, trunk or extremities several days in Koplik spots cephalocaudad (gray papules on direction buccal mucosa)

Rubella or • Discrete, erythema- • Rash appears • Supportive • Prodrome: Fever, German tous, maculopapu- within 5 d care headache, URI measles lar eruption on face after onset of symptoms (rubella with spread to body symptoms • Tender poste- virus) over 24 h • Fades over rior cervical and several days in suboccipital LAD cephalocaudad • Forscheimer’s direction spots: Pinpoint rose-colored macules or petechiae on soft palate

Roseola or • Pink macules and • Rash fades over • Supportive • Usually 6 mo to exanthem papules on trunk, a few days care 3 yr age group subitum neck, extremities as (HHV-6) high fever resolves

Erythema • Facial erythema • Usually asymp- • Supportive • Rash may recur infectiosum (“slapped cheeks”) tomatic care with heat (eg, or Fifth’s • Erythematous • May have mild showering) disease reticular, macular, myalgias, low- during course of (parvovirus ± pruritic eruption grade fevers illness B19) on extremities, trunk • Rash may last a few weeks

Hand-foot- • Erythematous • Fever, anorexia, • Monitor mouth patches and oral pain → oral hydration disease vesicles on hands, mucosal ulcers status (coxsackie feet, buttocks, oral • Most spontane- • Carafate PO A16; entero- mucosa ously resolve • Aggressive virus 71) over 2–3 wk pain control

Chickenpox • Crops of vesicles • Incubation: • Symptom- • Contagious (primary with surrounding 10–21 d atic relief from 24 h varicella erythema (“dew • Absent or mild • Immuno- before onset zoster virus drops on rose prodrome compro- of rash until all infection) petal”) → pustules lesions crusted • Resolution in mised or → rupturing with over 10–14 d dissemi- crust formation nated: • Spread via respi- • Lesions in all stages Acyclovir ratory route at same time therapy, • Most commonly • Possible compli- VZIG within on trunk, face, cations: Pneumo- 96 h of proximal nia, encephalitis, exposure extremities staphylococcal superinfection

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Type Description Course Treatment Other

Herpes • Pain, burning, • May dis- • Early treat- zoster or pruritic grouped seminate in ment with shingles vesicles on an ery- immunocom- antivirals (VZV reacti- thematous base promised • Aggressive vation) • Usually unilateral, patients pain control involving one der- • Postherpetic matome neuralgia: Pain lasting weeks to years after resolution of rash

Herpes sim- • Gingivostoma- • Recurrent: • Acyclovir or plex virus titis: Vesicles → Grouped valacyclovir • HSV1: erosions, regional vesicles on at ﬁ rst sign Mostly oral adenopathy erythematous of disease base, heal may abort • HSV2: • Herpetic whitlow: without scarring or shorten Mostly Painful, deep- in 10–14 d; episode genital seated vesicles on ﬁ ngertips pain, burning, • Aggresive tingling, most • Eczema herpeti- pain control often found on cum: Generalized • Acyclovir lips or genitalia; vesicles or erosions for primary often triggered over atopic der- disease in by fever, trauma, matitis children sunlight, • Genital: Venereal menstruation, • Valacyclovir transmission, gastroenteritis, suppressive grouped vesicles stress therapy on erythematous (daily) for base; fever, malaise, those with LAD frequent recurrences

Gianotti- Symmetric, skin- • May be preced- • Supportive • May be as- PEDIATRICS Crosti colored or slightly ed by URI, mild care sociated with (papular erythematous constitutional viral infections acroder- papules on face, symptoms (eg, EBV, HBV, matitis of buttocks, extensor • Spontaneous others), bacte- childhood) (acral) surfaces of resolution rial infections extremities in weeks to (streptococci), months or postvaccination

Verruca • Verrucous, gray- • May occur at • Salicylic • Genital warts vulgaris or pink papules on sites of trauma acid, liquid (condyloma common ﬁ ngers, dorsal • Autoinoculation nitrogen, acuminata) warts (HPV) hands, soles of feet, may occur by trichloroa- • In <2-3yo: genitals manipulating cetic acid, Vertical lesions cantharidin, transmission or podophyllin, • May enlarge or from caregivers imiquimod, multiply in im- with warts destructive munocompro- • Older kids: lasers, other mised patients Consider contact sexual abuse immunotherapy∗

(continued on next page) 118 Pediatrics

Type Description Course Treatment Other

Molluscum • Small, isolated, • Lesions • As for com- contagiosum dome-shaped, contagious and mon warts, (poxvirus) skin-colored pap- autoinoculable also gentle ules with central • May become curettage umbilication inflamed • May involute spontaneously over months to years • Persist, multiply, and enlarge in HIV+ patients

∗Clin Med Res 2006;4(4):273. Data from Dermatol Online J 2003;9(3):4 and Paediatr Drugs 2002;4(1):9.

FUNGAL INFECTIONS

Clinical Disease Description course Treatment Other

Tinea capitis • Scaly patches of • May be associ- • Griseofulvin: May also broken hair or hair ated with pos- 15–20 mg/kg/d consider oral loss on scalp terior cervical for 6–8 wk terbinafi ne, • If becomes infl am- or suboccipital • Selenium fl uconazole, matory → boggy, LAD sulfi de sham- pulse itra- erythematous • Kerion may poo: 2x/wk for conazole tx mass with fol- lead to patient and licular pustules scarring and contacts to (kerion) permanent reduce viable hair loss if left spores and pre- untreated vent spread

Tinea corporis• Pruritic annular • 2- to 4-wk plaque with clear course of topical center and scaly, antifungal BID papulovesicular (eg, clotrima- borders (“advanc- zole, terbinaﬁ ne) ing margin of • Oral treatment if scale”) widespread (eg, Griseofulvin)

Tinea pedis • Interdigital mac- • Colonization • Topical antifun- (“athlete’s eration; dry, scaly aided by gal BID foot”) soles; vesicles warmth and hu- or erosions over midity of shoes instep and sweating

Tinea cruris • Pruritic, often • May have • Topical antifun- • Moist area (“jock itch”) symmetric, well- raised papular gal BID aids coloni- demarcated, scaly, or pustular zation erythematous margin • Often with plaques in inguinal concomi- folds, upper thighs tant tinea • May spread to but- pedis tocks and perianal area

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Clinical Disease Description course Treatment Other Tinea versicol- • Hypo- or hyperpig- • Skin discolor- • Selenium sulfi de or (Malassezia mented macules ation may take or ketoconazole furfur) with fi ne scales months to shampoo, topical on upper torso or resolve azoles for small trunk and neck • Often recurs areas (especially in • Single oral hot, humid ketoconazole summer 400 mg dose (not months) FDA approved in children) • Fluconazole and Itraconazole have also been suggested∗ Candida• Oral (thrush): superfi - • Oral candidiasis • Oral: Nystatin • Risk factors: cial, sometimes ten- in immunocom- solution Prematurity; der, white plaques promised • Intertrigo: Nysta- antibiotic, on oral mucosa; patients may tin powder corticoster- reveals denuded, spread to oid, or OCP • Diaper dermati- erythematous base esophagus, use; diabetes tis: Topical imida- when scraped off causing feeding mellitus; zole or nystatin, (contrast to oral diffi culties immuno- barrier creams, leukoplakia from EBV compro- • Suspect frequent diaper that doesn’t scrape) mised state candidal changes; low- • Intertriginous: superinfection strength topical Erythematous, scaly, if irritant diaper corticosteroids if moist plaques dermatitis does necessary not improve • Diaper area: Beefy, • within sev- Vulvovagi- erythematous nal: topical eral days; often plaques involving in- imidazoles, oral painful with uri- guinal creases, often antifungals for nation, bowel PEDIATRICS with satellite pustules recurrent or movement or red papules refractory cases • Vulvovaginal: Thick, • Vulvovaginal: (eg, fl uconazole white discharge and May cause 150 mg once in white plaques on irri- dysuria and adolescents)† tated, erythematous itching vaginal mucosa

∗J Dermatol Treat 2002;13(2):73. †Chemotherapy 1998;44(5):364. Data from Am Fam Physician 2008;77(10):1415.

MITE INFESTATIONS

Type Description Cause Treatment Other Scabies• Pruritus (worse at Sarcoptes • Permethrin 5% cream: • Secondary bacterial night and with hot scabiei Cover entire body infection common bath) overnight (include • Usually pruritus • Small, erythema- scalp in infants); resolves within a few tous papules with repeat in 1 wk days after treatment excoriations or • Ivermectin: 200 mcg/kg but rash may last crusting on inter- once; may repeat in several weeks digital webs, wrist, 7–10 d

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Type Description Cause Treatment Other • ankles, feet, axillae, • Wash all clothing • May use topical GU area, buttocks, and bed linens in steroids for pruri- areolae, scalp and hot water and dry in tus relief face in infants high heat • Norwegian or • May see vesicles, • All contacts must crusted type: burrows (wrists, be treated at least Highly contagious; ankles) once (twice if symp- seen in immu- tomatic) nocompromised patients

Lice • Intense pruritus Pediculus • Permethrin 1% • May develop (Head) • Nits and lice seen capitis rinse or overnight secondary bacterial on scalp application of 5% infection cream • Excoriations, erythema, scaling of • Repeat in 1 wk scalp and neck • Wash bedding in hot water and dry in high heat • Ivermectin: 400 mcg/kg on day 1 and 8 (in >2yo) • Malathion lotion (in >6 yo)

DRUG REACTIONS

Type Description Pathogenesis Course Treatment

Morbilliform • Symmetric, • PCNs, sulfa, • 4–14 d after • Stop oﬀ end- or exan- erythematous cephalosporins initiation ing agent thematous macules and pap- anticon- • May have if possible; ules on trunk and vulsants, pruritus and desensitization upper extremities allopurinol, low-grade fever if necessary that become others • Resolves in 1–2 • TCS or anti- conﬂ uent wk without histamines for • May be urticarial sequelae pruritus on limbs, purpuric on ankles or feet • Spares mucosa

Urticaria • Pruritic, transient • PCNs, cepha- • Minutes to • Stop oﬀ ending (immediate erythematous, losporins, hours after agent IgE-media- edematous NSAIDs, exposure • Antihistamines ted hyper- papules and monoclonal • Each lesion • Desensitiza- sensitivity) plaques antibodies, usually lasts tion, if drug contrast media, • May have central <24 h necessary others pallor (wheals) • Chronic urticaria >6 wk

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Type Description Pathogenesis Course Treatment

Drug-induced • Pale or pink sub- • ACEIs, PCNs, • Minutes to • Protect airway angioedema cutaneous edema NSAIDs, hours after • Epinephrine of face, extremi- contrast media, exposure • Stop and avoid ties, genitalia monoclonal • Often lasts for oﬀ ending antibodies • May extend to lar- few days agent ynx, oropharynx, • Antihistamines intestinal wall • Chronic: Steroids PO

Anaphylaxis• Urticarial or • PCN, latex • Minutes after • Immediately angioedema • Rarely, local an- exposure stop oﬀ ending lesions + sys- esthetic, topical agent temic symptoms antiseptic • Protect airway (hypotension, • Anaphylactoid: • Systemic corti- tachycardia) Contrast media costeroids • Epinephrine • Avoid drug in future; desensitize if necessary

Serum • Urticarial, morbil- • Cefaclor, • 1–3 wk after • Stop oﬀ ending sickness-like liform, “purple bupropion, exposure agent reaction urticaria” minocycline, • Supportive and • Fever PCNs, propra- symptomatic nolol, others • Joint pain care

Fixed drug • One or few annu- TMP-SMX, • First exposure: • Stop oﬀ ending eruption lar, erythematous NSAIDs, 1–2 wk agent or edematous barbiturates, • Reexposure: • Topical corticos- plaques tetracyclines, within 24–48 h teroid pseudoephed- PEDIATRICS • May have dusky • Fades over sev- rine, others hue or central eral days with blister postinﬂ amma- • Favors face, acral tory pigment sites, genitalia changes • Recurs in same location upon reexposure

Acute • Erythematous • β-lactam • <4 days after • Stop causative generalized edematous antibiotics, exposure, lasts drug exanthema- plaques with macrolides, 1–2 wk, then • Topical corticos- tous small, nonfol- CCBs, antima- superﬁ cial teroids pustulosis licular, sterile larials desquamation • Antipyretics (AGEP) pustules favoring intertriginous areas, trunk, and extremities • May have burning, pruritus

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Type Description Pathogenesis Course Treatment

Drug reaction • Starts morbil- • Antiepilep- • 2–6 wk after • Stop oﬀ ending with eosino- liform on face, tics, sulfa, drug initiation agent philia and upper trunk, allopurinol, mi- • Prominent • Systemic corti- → systemic extremities nocycline, gold eosinophilia costeroids symptoms edema with salts, dapsone, and atypical • Check serial (DRESS), drug follicular accen- antiretrovirals, lymphocytes liver enzymes if hyper- tuation others • Often with elevated sensitivity • May have pustules, lymphadenopa- syndrome blisters, erythro- • Check thyroid thy, arthralgia function tests at (DHS) derma, purpura or arthritis, liver onset of reaction • Often with edema involvement, and 2–3 mo later of face myocarditis, • May require interstitial steroid mainte- pneumonitis, nance treatment interstitial ne- for weeks to phritis, thyroidi- months because tis, GI bleeding of relapses when if allopurinol tapered induced

Erythema • Acrofacial, • Most common: • Abrupt onset • Symptomatic: multiforme grouped or Infection within 24–72 h, Antihistamines; (EM) coalescent target (especially HSV, last ≥7 days bland emollients lesions, ery- Mycoplasma • Most heal with- for erosions; thematous rings spp.) out sequelae diphenhydramine, with dusky or lidocaine and • More rarely: • Occasional crusted centers, Maalox in 1:1:1 Drugs postinﬂ amma- or urticarial mix mouthwash tory pigment for mouth pain • Minimal (only changes one site) or no • Recurrent HSV- • mucosal involve- HSV-associated associated EM: EM may recur ment or systemic Acyclovir 10 mg/ symptoms kg/d in divided doses for ≥6 mo

Stevens- • Irregular, coales- • NSAIDs • Prodrome: URI, • Immediately stop Johnson- cent, erythema- (especially fever, skin pain, causative drug Syndrome tous or dusky oxicams), anti- arthralgias • Supportive care: (SJS) macules, mucosal biotics (sulfa), • Usually occurs Wound care, (<10% BSA) (lips, oral, ocular, antiepileptics, 7–10 d after gentle cleansing, genital) erosions antiretrovirals initiation of bland emollients (two or more sites • Infections drug with nonadher- required) and ten- (eg, HSV, • May develop ent dressings SJS– TEN derness → hours Mycoplasma), LAD, hepatitis, for erosions, eye overlap to days later, ne- immunizations cytopenias, care (10-30% crotic epidermal respiratory or • Diphenhy- BSA) detachment and GI involvement, dramine, fl accid blisters, photophobia, lidocaine, and hemorrhagic odynophagia Maalox in 1:1:1 crusting • Risk of infection, mix mouthwash electrolyte and for mouth pain TEN fl uid imbal- • Monitor fl uids, (>30% BSA) ance, insulin electrolytes, and resistance, mul- vitals tiorgan failure • IVIG: 0.5–1g/kg/d for 3–4 d

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Type Description Pathogenesis Course Treatment

Photodrug• Erythematous • Tetracyclines, • After variable • Stop causative patches, papules, quinolones, amount of sun drug, sun vesicles or bullae NSAIDs, exposure protection, TCS, over sun-exposed antiepileptics, • May cause antihistamines areas amiodarone, scarring • Localized burning, thiazides, itching voriconazole

Data from J Drugs Dermatol 2003;2(3):278.

TOPICAL CORTICOSTEROID GUIDE*

Class Generic Name Brand Names Vehicles I Augmented betamethasone Diprolene Gel, ointment (superpotent) dipropionate 0.05%

Clobetasol propionate 0.05% Clobex, Olux, Shampoo, foam, spray, Temovate, solution, gel, lotion, Cormax cream, ointment

Diﬂ orasone diacetate 0.05% Apexicon, Ointment Psorcon

Fluocinonide 0.1% Vanos Cream Flurandrenolide 4 mcg/cm2 Cordran Tape Halobetasol propionate 0.05% Ultravate Cream, ointment

II Amcinonide 0.1% Cyclocort Ointment (high potency)

Augmented betamethasone Diprolene Lotion, cream

dipropionate 0.05% PEDIATRICS Betamethasone dipropionate Diprosone Ointment 0.05% Desoximetasone 0.25% Topicort Cream, ointment Diﬂ orasone diacetate 0.05% Apexicon, Psorcon Cream

Fluocinonide 0.05% Lidex Solution, gel, cream, ointment Halcinonide 0.1% Halog Solution, cream, ointment Mometasone furoate 0.1% Elocon Ointment III Amcinonide 0.1% Cyclocort Lotion, cream (medium to high potency) Desoximetasone 0.05% Topicort Gel, cream Fluticasone propionate 0.005% Cutivate Ointment Flurandrenolide 0.05% Cordran Lotion, cream, ointment Triamcinolone acetonide 0.5% Kenalog, Aristocort Cream

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Class Generic Name Brand Names Vehicles

IV Betamethasone valerate Luxiq, Beta-Val Foam, lotion, cream (medium potency) Hydrocortisone valerate 0.2% Westcort Ointment Hydrocortisone butyrate 0.1% Locoid Ointment

Mometasone furoate 0.1% Elocon Cream

Triamcinolone acetonide 0.1% Kenalog, Ointment Aristocort

V Fluticasone propionate 0.05% Cutivate Lotion, cream (medium to low potency) Fluocinolone acetonide 0.025% Synalar, Synemol Cream, ointment Fluocinolone acetonide 0.01% Derma-smoothe Oil

Hydrocortisone valerate 0.2% Westcort Cream

Triamcinolone acetonide 0.01% Kenalog, Lotion, cream Aristocort

VI Aclometasone dipropionate Aclovate Cream, ointment (low potency) 0.05%

Desonide 0.05% Desonate, Lotion, foam, gel, Desowen, Locara, cream, ointment Verdeso

Fluocinolone acetonide 0.01% Capex, Synalar Solution, shampoo, cream

Hydrocortisone butyrate 0.1% Locoid Cream

Triamcinolone acetonide Kenalog, Lotion, cream, ointment 0.025% Aristocort

VII Hydrocortisone 2.5% Hytone, Nutra- Lotion, cream, (least potent) cort, Synacort ointment

Hydrocortisone 1% Many over-the- Spray, lotion, cream, counter brands ointment

∗Topical corticosteroids (particularly high-potency classes I to III) should not be used continuously for longer than 2 weeks at a time (or >15 days/mo if used intermittently) to avoid side eﬀ ects. If longer use is required, wait 2 weeks before restarting. Avoid application of high potency TCS on face, underarms, and groin. Data from Am Fam Physician 2009;79(2):135 and Nesbitt LT: Glucocorticosteroids. In Bolognia JL, Jorizzo JL, Rapini RL (eds). Dermatology. London: Elsevier Limited; 2008:1926.

Available at www.AccessPediatrics.com • Acne subtypes • Acne treatment PEDIATRICS

↓

→ spp. (Pre uid level, uid Moraxella 1 AOM ≥ Post PCV7 52%, Pre PCV7 or no movement of TM), ↓ uenzae ( uenzae Diagnosis of AOM is Diagnosis of AOM Uncertain Start antibiotic treatment is non-severe condition the patient’s <39°C [102.2°F] and (temperature mild otalgia); con- Start antibiotics if the patient’s severe to (moderate dition is severe >39°C) and temperature otalgia Observe with follow-up assured Observe with follow-up 125 2004;113:1451) Eustachian tube dysfunction or occlusion Eustachian tube dysfunction or → Haemophilus infl ce visits; by 3 yo, 80% have Pediatrics ammation spp. (Post PCV7 34%, Pre PCV7 25-50%) > spp. (Post PCV7 34%, Pre PCV7 1998;17(6):540). Consider tympanocentesis and bacterial culture for 1998;17(6):540). Consider tympanocentesis Respiratory viruses >> URI or infl Start antibiotic treatment Start antibiotic treatment if assured Observe with follow-up assured Observe with follow-up is condition if the patient’s <39°C (temperature non-severe [102.2°F] and mild otalgia); con- Start antibiotics if the patient’s severe to (moderate dition is severe >39°C) and temperature otalgia Diagnosis of AOM is Diagnosis of AOM Certain Bulging tympanic membrane (TM), purulent material, air-fl Bulging tympanic membrane 33% of all pediatric offi 33% of all pediatric PIDJ infection Pneumococcus Fever (especially increasing fever curve), URI, ear pain or fullness, hearing loss, Fever (especially increasing fever → vomiting, ear drainage or diarrhea. or no movement of TM, otorrhea, ± redness, ± bullae. or no movement of TM, otorrhea, and color ( disease. children with recurrent or chronic Best predictors are position (ie, bulging), mobility of TM ( Best predictors are position (ie, Pain and fever control are the most important interventions. Pain and fever control are the have resolution of symptoms without antibiotics. Within 24 hours, 61% of patients do not change the duration of illness of AOM. Antibiotics (see table below) often Physical exam: History: 6–24 mo ≥ 24 mo <6 mo Age • • • • • • Pathophysiology: Epidemiology: Treatment Diagnosis Etiologic agents: 15-30%) > PCV7 3%–20%) > GABHS > other ( PCV7 3%–20%) > GABHS > other effusion • IN CRITERIA FOR INITIATION OF ANTIBIOTICS CHILDREN WITH AOM • Ear, Nose, and Throat Ear, Nose, MEDIA (AOM) ACUTE OTITIS • • • CHAPTER 12 126 Pediatrics

ANTIBIOTIC CHOICES FOR TREATMENT OF AOM

Temperature Treatment failure at 48–72 h >39°C (102.2°F) Initial antibiotic choice after initial management

No Amoxicillin, 80–90 mg/kg/day Amoxicillin–clavulanate, 90 mg/kg/ (If penicillin allergic: Non– day of amoxicillin with 6.4 mg/kg/ type I: cefdinir, cefuroxime, or day of clavulanate cefpodoxime; type I: azithromycin, (If penicillin allergic: Non–type clarithromycin) I: ceftriaxone for 3 days; type I: clindamycin)

Yes Amoxicillin–clavulanate, 90 mg/kg/ Ceftriaxone for 3 days day of amoxicillin with 6.4 mg/kg/ (If penicillin allergic, tympanocen- day of clavulanate tesis, clindamycin) (If penicillin allergic, ceftriaxone for 3 days)

• Single high-dose azithromycin (30 mg/kg/dose) is equal to amoxicillin in effi cacy. (PIDJ 2005;24:153) • Add topical agents as well for AOM with perforation or if the patient has tympanostomy tubes (eg, Ciprofl oxacin; Ofl oxacin). • Surgical treatment: Consider ENT referral if the patient has >3 episodes in 6 mo or >4 episodes in 1 yr. • Complications: Labyrinthitis, mastoiditis, intracranial extension, conductive hearing loss.

OTITIS MEDIA WITH EFFUSION (OME) • Epidemiology: Highest incidence <2 yo; 80% of <10 yo have had one episode of OME • Pathophysiology: Eustachian tube dysfunction: Resolution of AOM → OME (45% at 1 mo after and 10% at 3 mo after AOM); GER; anatomic (children with cleft palate) • Etiologic agents: Viruses > H. infl uenzae > Moraxella spp., bottle feeding, feeding supine, daycare attendance, allergies, smoke exposure • Diagnosis • Often OME is subjectively asymptomatic → no intervention required if no hearing loss; when symptomatic: • History: ↓ hearing, ear fullness, pressure, pain (rare), recent travel, diving, allergies (environmental) • Physical exam: Air fl uid level, TM retraction or bulging, serous middle ear fl uid, ↓ TM mobility, ± large tonsils, signs of atopy. • Tests: Hearing test if speech or language delay present • Treatment • Most spontaneously resolve → avoid smoke exposure; ↓ bottle feeding, daycare, and allergens. • More aggressive therapy if the child has a speech or language delay, PDD, craniofacial abnormality (eg, Down syndrome, cleft palate), visual impairment, or developmental delay • Antimicrobial agents: Consider amoxicillin, amoxicillin + clavulanate, trimethoprim– sulfamethoxazole, or erythromycin for 2 to 5 wk. • Tympanostomy tube: OME and >40-dB hearing loss → defi nite indication; OME and 21- to 40-dB hearing loss; or persistent effusion >3 mo → relative indications. • Steroids, antihistamines, decongestants, and mucolytics are not effective.

MASTOIDITIS • Defi nition: Suppurative infection of the mastoid air cells. • Pathophysiology: Because the middle ear cavity is contiguous with the mastoid, all middle ear infections cause some degree of mastoid infl ammation. However, when infl ammation Ear, Nose, and Throat 127

leads to occlusion of mastoid aditus → ↑ pressure → relative hypoxia and acidosis → bony erosion into surrounding structures → potential for intra- or extracranial spread of infection.

DIAGNOSIS, ETIOLOGIC AGENTS, AND TREATMENT OF MASTOIDITIS

Etiologic Diagnosis Diagnosis Agents Treatment* Acute Fever (often <2 yrs of age), Pneumococcus ENT consultation;† mastoiditis recent AOM with tempo- spp. (serotype Start, vancomycin/ rary improvement followed 19A is as- clindamycin (oxacillin/ by clinical decline sociated with nafcillin depending on Exam: Postauricular swell- high rates of local prevalence of MRSA) ing, erythema ± ﬂ uctuance, β-lactam resis- and cefotaxime TM suggestive of infection, tance) > GABHS pinna anteriorly displaced > Staphylococ- cus aureus > Test: CT temporal bone others with contrast Chronic Usually with persistent S. aureus, Would also include mastoiditis ear drainage ± fever ± Pseudomonas ticarcillin–clavulanate + postauricular swelling spp., other GNRs, gentamicin and topical Test: CT temporal bone mycobacteria, ear drops (Ciproﬂ oxacin or with contrast fungal; Cortisporin) 80% of chronic cases demonstrate co- infection with anaerobes

* If the patient has an acute onset of symptoms with minimal fl uctuance and no signs of intracranial complications, the patient will likely respond to medical therapy with antimicrobials alone. When there has been favorable response change to PO medications for 3 weeks of total treatment (empiric therapy or guided by cultures/ sensitivities). † Consultation with ENT is always recommended for tympanocentesis early for culture and relief of pressure. Surgery is indicated especially if the patient has signifi cant fl uctuance, vertigo, neurologic symptoms, vomiting, hearing loss, or any other signs/symptoms of intracranial involvement. PEDIATRICS

• Complications: Meningitis, intracranial abscess, hydrocephalus, dural sinus thrombosis, Bezold abscess, hearing loss, osteomyelitis of the temporal bone, and facial nerve palsy.

RHINITIS • Inﬂ ammation of the nasal cavity commonly manifesting as a “runny nose.” • Most common causes: Viral URI and allergic rhinitis (see table below); also consider sinusitis, and if there is unilateral nasal discharge evaluate for foreign body.

ALLERGIC VERSUS INFECTIOUS RHINITIS

Allergic Infectious Onset Subacute to chronic Acute Symptoms Runny, itchy nose; allergic salute or Low grade fever; rhinorrhea or con- shiners; other atopic disease (asthma, gestion; cough; sore throat; possible eczema); red, itchy eyes GI symptoms (diarrhea, vomiting) Etiologic Dust mites, ragweed, grass, dust, Any respiratory virus agents animal dander Treatment Antihistamines, nasal steroids, nasal Frequent nasal saline, encourage saline, leukotriene antagonists ﬂ uid intake, supportive care 128 Pediatrics

SINUSITIS • Pathophysiology: Usually result of bacterial superinfection of viral URI or infl amed nasal mucosa secondary to allergic disease (sinus development: at birth, the maxillary and ethmoid sinuses are present; at age 3 yr, the sphenoid sinus starts developing; the frontal sinus starts developing ~5 yr) • Etiology • Respiratory viruses are the most common cause overall. • Acute bacterial causes: Streptococcus pneumoniae (>30%), H. infl uenzae (~20%), Moraxella catarrhalis (~20%) and GABHS. After PCV 7 vaccine ↓ incidence of pneumococci and ↑ rates of H. infl uenzae (≤40%). • Chronic bacterial sinusitis: Same organisms as acute (lower frequency) as well as α-streptococci, S. aureus, Enterobacteriaceae, and anaerobes (Fusobacterium and Peptostreptococci spp.). Fungi should also be considered, including Alternaria and Aspergillus spp. • Diagnosis • Presence of persistent or severe symptoms: • Persistent symptoms: URI symptoms ≥10 d (includes congestion, postnasal drainage, persistent daytime cough that is worse at night, headache, or sinus pain). • Severe symptoms: Fever ≥102°F + purulent nasal discharge for 3–4 days. • Physical exam is not very helpful in children. • Imaging is not necessary in the diagnosis of acute bacterial disease. • Treatment • AAP recommends antibiotic therapy for children with persistent (>10 d) or severe symptoms. • Start with amoxicillin (if the child is antibiotic naïve over the past 90 days) for 21 days; for chronic sinusitis treat with 3-6 weeks of antibiotics. • If treatment failure or persistent disease, start amoxicillin–clavulanate, cefdinir, cefpodoxime. • In patients allergic to β-lactams, may use azithromycin or clindamycin. • Complications • Chronic disease, orbital cellulitis, intracranial extension (especially in adolescent males), Pott’s puffy tumor.

OBSTRUCTIVE SLEEP APNEA • Affects ~5% children; common age is 5 to 7 yr; second peak in adolescence because of obesity.

CLEFT LIP AND PALATE • Background • Incidence of cleft lip is 1:1000. • Left > right > bilateral > midline; majority (80%) are unilateral. • Girls are affected more often than boys. • There are 3 types: Complete (into ﬂ oor of nose), incomplete (partially through lip), and microform (notch in vermillion border). • About 15% of affected children also have another anomaly. • Incidence of cleft palate is 1:2,500; it always involves the uvula • About 56% of affected children also have another anomaly (most often midline), especially if associated with cleft lip. • Management • Immediate consult of cleft team (ENT, craniofacial surgery, genetics, OT and speech, dental, social work, nutritionist). • Feeding: ↑ Difﬁ culty with cleft palate ± cleft lip than with cleft lip alone; use soft nipple, large opening, squeezable bottle (Haberman or similar); feed in an upright or sitting position with the head slightly tilted back; slow feeding; frequent burping because of ↑ air swallowing. Ear, Nose, and Throat 129

Symptoms or Signs of OSA? YES NO

Cardiac or respiratory Tonsils grade IV? complications?

YES NO YES NO

Expedited Sleep study Continue sleep study & screening at referral to subsequent visits specialist

High risk patient? (underlying craniofacial, neuromuscular or metabolic abnormalities, chronic lung disease or infant)

YES NO

Sleep study and referral to Sleep study specialist PEDIATRICS

Figure 12-1 Management of positive snoring screen in children. (Reproduced with permission from Pediatrics 2002;109:704.)

• Staged repair: Lip at age 2 to 3 mo; palate at age 6 to 24 months ± tympanostomy tubes. Usually, the repair is considered when the child is at least 10 wk of age, weigh at least 10l bs with a Hb of 10 or greater. • Complications • OM, speech difﬁ culty, dental anomalies, hearing loss, poor weight gain

Available at www.AccessPediatrics.com • Pharyngitis • Adenotonsillar hypertrophy • Obstructive sleep apnea • Branchial anomalies CHAPTER 13 Emergency Medicine

FEVER WITHOUT LOCALIZING SIGNS (FWLS)

Temp ê38°C (100.4°F) in patient 0–60 days, no source on exam No antibiotics to be given to this group w/o full workup including blood, urine, and CSF studies (NOTE: Some institutions follow this algorithm for children who are 0–3mo) 0–28 days 29–60 days

Laboratory workup CBC, blood cx, UA with micro & cx1, CSF (cell Toxic? count, Gram stain, glucose, protein) & CSF cx (hold (Lethargy, poor perfusion, YES CSF for viral studies) hypo/hyperventilation, Consider: cyanosis, irritable) • Rapid viral testing (RSV/Influenza/adenovirus) • HSV workup2

NO Any culture Admit to hospital on antibiotics YES (+) 0–28d Ampicillin & gentamicin ê29d Ampicillin & cefotaxime Treat as (meningitis dosing if CSF clinically NO pleocytosis/gram stain abnormal) appropriate Laboratory workup CBC, blood cx, UA1 with micro & cx YES Febrile ê 48h CSF cx/studies, consider rapid viral testing → ceftriaxone IM → High risk?3 YES NO Admit to Observation unit (see Box 1) or inpatient admit

Clinically well & NO NO Inpatient: Cx (–) ≥ 48h Observation: Cx (–) @23h Send home without antibiotics if: • Adequate caregiver education YES • Reliable follow up in 12–24h • PCP & caregiver agree with plan Send home if: • Reliable f/u in 12–24h OR • Adequate caregiver education Admit ± empiric antibiotics • PCP & caregiver agree with plan (Do LP prior to antibiotics)

Box 1 1Urine testing should be done by sterile bladder catheterization or suprapubic aspiration 3High risk: History: prematurity, perinatal antibiotics, tx for unexplained jaundice, previous hospitalization, chronic illness, not sent home with mother after birth, maternal h/o intrapartum fever, antibiotics, GBS positivity. Physical exam: AOM, soft tissue/bone infection. Lab criteria: WBC <5,000 or >15,000, Band count >1,500/microL, Urine nitrite or LE positive, WBC 5–10/hpf, abnormal CSF (see chapter 20 for normal CSF values). Social: No phone, access to nearby hospital &/or physician for follow-up

2HSV and fever workup & management: History: seizure, ill appearing during 2nd week of life, maternal fever 48h prior to delivery, maternal primary HSV infection during gestation. Physical exam: vesicular rash. Lab criteria: ↑CSF mononuclear pleocytosis, ↑LFT Management: Send HSV oral/skin cultures, HSV PCR from CSF, CSF viral culture and start Acyclovir IV. Base duration of treatment on clinical and culture/PCR results.

Figure 13-1 Algorithm for the management of fever without localizing source in patients 0 to 2 months of age. (Adapted from Texas Children’s Hospital: Evidenced based clinical guideline on fever without localizing signs 0–60 days old).

130 Emergency Medicine 131

Temp ê39°C (102.2°F) in patient 2–36 mo, no source on history/physical

Toxic? (Ill-appearing, lethargy, poor YES NO perfusion, hypo/hyperventilation, cyanosis, irritable)

Laboratory workup Identified bacterial source for fever: CBC blood cx, UA with micro & cx, YES AOM, sinusitis, pneumonia, cellulitis, CSF (cell count, Gram stain, glucose, abscess, osteomyelitis, septic arthritis protein) & CSF cx WBC >20,000 or if clinically indicated → CXR Treat source for fever as clinically NO appropriate Admit to hospital on antibiotics Vancomycin and cefotaxime Viral syndrome? ± other indicated antibiotics Bronchiolitis, varicella, croup, YES enterovirus, herpangina, HSV, influenza, stomatitis, viral rashes (URI or AGE don't "count" as a source)

Consider rapid viral testing & in patients with bronchiolitis/influenza do UA with micro and cx if: NO 1. Female ≤ 2 year, 2. Males circumcised ≤6 mo OR uncircumcised ≤12 mo

Received 3 YES doses of PCV7

U/A with micro and cx if: 1. Female ≤ 2 year, NO 2. Males circumcised + ≤6mo or uncircumcised + ≤12mo, 3. History of UTI, GU defect CBC d/p, draw and hold blood cx, UA Send home without antibiotics if: with micro and cx tolerating PO, reliable follow up arranged, caregiver education CBC or UA complete NO abnormal? (OR monitor patient in Observation unit/inpatient admit)

YES

• If WBC > 15,000/mm3 or ANC >10,000 → Send

Send home if: tolerating PO, PEDIATRICS blood cx, ceftriaxone IM, & f/u in ≤24h reliable follow up arranged, • 3 → → caregiver education complete If WBC > 20,000/mm CXR If + treat for pneumonia; if – blood cx, ceftriaxone IM, & f/u in 24h (or monitor patient in observation • → unit/inpatient admit) If + UA PO antibiotics for UTI ± ceftriaxone x 1 and f/u in ≤ 24h

Figure 13-2 Algorithm for the management of fever without localizing signs in patients 2 to 36 months of age. (Adapted from Texas Children’s Hospital: Evidenced based clinical guideline on fever without localizing signs in 2–36 mo.)

SCROTAL PAIN AND SWELLING COMPARISON OF TESTICULAR TORSION, EPIDIDYMITIS, AND TORSION OF TESTICULAR APPENDAGE

Torsion of Testicular Testicular Torsion Epididymitis Appendage

Age group Neonatal, Sexually active 7–14 yo 12–28 yo (66%) adolescents

Onset Sudden Gradual Gradual/sudden

Testicular lie High Low Low

(continued on next page) 132 Pediatrics

Torsion of Testicular Testicular Torsion Epididymitis Appendage

Cremasteric reﬂ ex Usually not present Present Present

Prehn’s sign∗ Negative Positive Variable

Urinalysis Normal +WBCs on UA Normal

Presentation Acute onset of pain, Fever, chills, urethral Pain located in the nausea/vomiting, discharge, nausea, superior pole of purple, swollen, painful neonatal, 12–28 yo testicle; mild erythema testes (66%), edematous or edema; blue and tender dot sign (21%) epididymis

Doppler ultra- ↓ or absent fl ow Normal or ↑ fl ow in Torsed appendage sonography epididymis with ↓ fl ow but normal fl ow to testes

Treatment Emergency surgery: Scrotal support Scrotal support Bilateral ﬁ xation of testes (briefs), NSAIDs (briefs), NSAID (irreversible damage Antibiotics† Resolves within 2–12 possible in 5–6 h) • Prepubertal: Most days Manual detorsion (open commonly no an- book technique) if tibiotics required; timely surgical interven- may consider tion not available Trimethoprim– sulfamethoxazole • Sexually active: Ceftriaxone + azithromycin/ doxycycline

∗Relief of pain with elevation of testicle. † Etiologic agents include coliform bacteria, viruses in prepubertal boys and Neisseria gonorrhea, Chlamydia in adolescents.

LIMPING AND JOINT PAIN • Deﬁ nition: Uneven alteration in natural gait (secondary to pain, weakness, deformity). • Etiology: Trauma is the most common cause of limp. See the table below for causes of limp when there is no history of trauma.

CAUSES OF NON-TRAUMATIC LIMP/JOINT PAIN IN CHILDREN

% of non- traumatic causes Fracture 2%

Overuse (soft tissue injury, muscular strain, Osgood-Schlatter’s 18% disese, hematoma of the thigh)

Osteomyelitis 2% Other (appendicitis, PID, torsion constipation, etc.)

Transient synovitis 40%

Legg-Calve-Perthes syndrome (avascular necrosis of the femoral head) 2%

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% of non- traumatic causes Inﬂ ammation (rheumatologic: JRA, SLE, reactive arthritis or HSP) 3% Infection (skin, soft tissue, joint, septic arthritis) 4% Foreign body Tumor 1% “Toddler’s fracture” (nondisplaced spiral fracture of the tibial shaft) 1% Trauma — SCFE <1% Sickle cell pain crisis

*Adapted from: J Bone Joint Surg Br 1999;81(6):1029.

• Diagnosis • History: Time of onset, mechanism (trauma, change in activity), location, severity, radiation, effect on ADLs, aggravating or alleviating factors. Ask about fever, recent infections (viral or GABHS), weight loss, back, abdominal pain, cough, joint swelling, stiffness, erythema, incontinence, recent IM injection (sterile abscess). Prior h/o of family h/o cellulitis/abscesses or sickle cell disease connective tissue disease, IBD, or bleeding or neuromuscular disorder. • Physical exam • Inspection: Rash, inﬂ ammation, warmth, erythema, deformity, limb length discrepancies • Palpation: Joint or bone tenderness, joint effusion, neurovascular status • ROM: Active and passive ROM, grade strength • Neurovascular exam: Pulse, perfusion, sensation • Other: Do not forget to examine the spine, back, abdomen, and GU area • Laboratory studies: See table below for appropriate workup based on H&P.

CORRELATING HISTORY, PHYSICAL EXAM, AND DIAGNOSTIC STUDIES FOR A CHILD WITH A LIMP PEDIATRICS Physical Examination Laboratory Category History May Reveal Studies Radiology Traumatic High–impact fall Localized pain, None unless X-rays swelling, loss or infection is ↓ ROM suspected Infectious Fever, chills, Guarding, warmth, CBC, ESR, CRP, X-rays, MRI (deep erythema, erythema, indura- blood cx, joint infection or induration, pain tion, discharge aspirate, skin onset <1-2 weeks or abscess prior), bone scan culture (unclear site) Inﬂ ammatory Acute onset Guarding, can bear CBC, ESR, CRP X-rays weight, allows passive ROM ± swelling, ± erythema

Chronic: Pain >6 Warmth or erythema, CBC, ESR, CRP, mo ± FHx of RA one or more joints joint aspiration Neoplastic Night pain, pain Mass, local CBC, ESR, CRP, Alk X-rays, MRI or unrelated to activity, tenderness Phos, calcium, CT, bone scan, not relieved by OTC electrolytes; staging workup meds, ± fever joint aspirate (continued on next page) 134 Pediatrics

Physical Examination Laboratory Category History May Reveal Studies Radiology Congenital Problem since Deformity, leg None X-rays birth length discrepancy, loss of ROM Neurologic Ataxia, loss of ↑ or ↓ muscle tone, CK (if DMD is X-rays balance, ↑ or ↓ DTR, cavus in diﬀ erential disorganized gait foot or claw toes diagnosis) Develop- Painless limp (LCP Loss of ROM in None X-rays mental disease), knee pain joints, asymmetric (LCP disease, SCFE) ROM, pain with ROM

Adapted from Am Fam Physician. 2000;61(4):1011. LCP, Legg-Calve-Perthes

DIFFERENTIATING SEPTIC ARTHRITIS FROM TRANSIENT SYNOVITIS

Septic arthritis Transient synovitis

History and Fever (usually >101.3°F)∗; refusal to Recent URI, low grade to physical exam bear weight*; warm red, swollen joint; normal temperature, allows ↓ ROM (may be rigid); if septic hip (hip passive ROM, can bear some ﬂ exed and abducted); most sxs ~3 days weight duration; recent URI (53%) trauma (31%)

Laboratory CBC∗ (↑ WBC, usually >12,000/mm3), None required; CBC usually normal, studies ↑ ESR∗ (usually >40), ↑ CRP (>2) ESR or CRP mild elevation

Radiologic US of joint (85% show eﬀ usion), MRI ⊕ U/S or Ultrasound, MRI not studies in 88%, radiography (20% reveal joint needed unless need to help space widening) distinguish from septic arthritis. Consider X-rays to rule out femoral neck fractures.

Etiology Staphylococcus aureus (MRSA) > Kingella Postinfectious reactive ﬂ uid > Streptococcus pneumoniae > Salmo- in joint (joint ﬂ uid cx results nella; consider GBS in neonates negative)

Treatment Orthopedic emergency (needs immedi- NSAIDS scheduled until symp- ate drainage), joint aspiration (send for tomatically improved WBC, protein, cx), blood cx Antibiotics: MRSA coverage (eg, vancomycin) + GNR coverage (eg, cefotaxime/ gentamicin) ± MSSA, strep coverage (eg, nafcillin) X-rays → modify based on cx results; usual duration, 3–4 wk total

∗Positive predictive value of septic arthritis using ﬁ ndings in table above denoted by an asterisk: one sign, 3%; two signs, 40%; three signs, 93%; and four signs, 99.6% (J Bone Joint Surg Am 1999;81:1662). In addition, CRP >2 ↑ likelihood of septic arthritis.

BITES • Treatment: • Irrigation is very important for infection prevention (100 mL NS, sterile water, or tap water per cm laceration) • Debride devitalized tissue • If wound appears infected, culture but do not close Emergency Medicine 135

• First-degree closure should be avoided in puncture wounds, wounds on hands and feet, and wounds through cartilage • Antibiotic prophylaxis is not routinely recommended except in special cases (see table below) • Tetanus vaccine status should be verifi ed for all patients and prophylaxis provided as indicated. • Rabies prophylaxis: • Consider when exposure to saliva is suffi cient for infection (bite not required); saliva exposure to bats [most common cause in United States], raccoons, foxes, skunks (uncommon in small rodents (squirrels, rats) and rabbits). • Treatment • No suspicion → no treatment. • Any suspicion → attempt to quarantine and observe animal and discuss with local health department. • High suspicion or animal not in custody → one-time dose of human rabies immunoglobulin (20 IU/kg, with half given IM and half infi ltrated locally at the wound site if feasible) followed by 4 IM injections of human diploid cell vaccine (1 mL) to be given on days 0, 3, 7, and 14 (CDC: ACIP Provisional Recommendations for the Preven- tion of Human Rabies: http://www.cdc.gov/mmwr/pdf/rr/rr5902.pdf or MMWR 2010;59(02):1

CHARACTERISTICS AND TREATMENT RECOMMENDATIONS FOR CAT, DOG, AND HUMAN BITES

Cats Dogs Humans

Percentage 5–10% 80–90% 2–3%

Appearance Puncture wounds Tears and punctures Moon shaped

Suture? Do not close punctures Can close if <12h Can close if <8h old old

Infection rate 50% 30% 60%

Organisms Pasteurella multocida, Streptococcus spp., Streptococcus spp., Staphylococcus spp. Staphylococcus spp., Eikenella PEDIATRICS corrodens, anaerobes

Treat with Prophylaxis for all high risk wounds (deep puncture wounds (e.g cat bites), prophylactic moderate to severe wounds with associated crush injury, wound in area of antibiotics underlying venous and/or lymphatic compromise, wound on the hand or close to a bone or joint, wounds requiring closure, wounds in compromised hosts (eg, immunocompromised, asplenia or splenic dysfunction) First line: Amoxicillin/clavulanate Second line: First-generation cephalosporin PCN allergic: Doxycycline or clindamycin, + Trimethoprim/Sulfamethoxazole

RESPIRATORY DISORDERS Stridor, Asthma and Bronchiolitis • Location of obstruction: Can be determined based on the phase of the stridor. • During inspiration → supraglottic obstruction • During expiration → intrathoracic obstruction • During inspiration and expiration (biphasic) → glottic or subglottic obstruction • Etiology • Foreign body → acute stridor in otherwise healthy child • Infection → croup, retropharyngeal abscess, epiglottitis, tracheitis • Anatomic malformation → laryngomalacia, tracheomalacia, vascular ring 136 Pediatrics

COMMON CHARACTERISTICS AND TREATMENT RECOMMENDA- TIONS FOR INFECTIOUS CAUSES OF STRIDOR

Bacterial Retropharyngeal Feature Epiglottitis Tracheitis Croup Abscess

Age 3–7 yr 5–10 yr 6 mo–3 yr 4–10 yr (median, 3.5 yr)

Prodrome Minimal, none Yes (1–3 days) Yes (1–2 days) Yes

Fever High Yes Yes Yes

Cough No “Brassy” cough Barking cough No

Drool Yes (60%–70%) No No Yes (22%)

Toxic Yes Yes ± ±

Stridor Inspiratory Expiratory Inspiratory or Inspiratory biphasic

Comments Sore throat Sore throat; Croup usually Sore throat, ↓ PO, (50%); respira- thick, purulent preceded by neck stiﬀ ness (59%, tory distress; neck secretions; URI symptoms ↓ ROM of neck), ret- hyperextended; patient prefers ± respiratory ropharyngeal bulge patient prefers being supine distress; sore (43%), neck mass sitting in “tripod” throat (91%), agitation (43%) position

X-ray of neck “Thumbprint Tracheal Subglottic Retropharyngeal (AP & Lat) sign” narrowing narrowing soft tissue swelling (50%) “steeple sign”

Etiology S. pneumoniae , S. aureus, H. Parainfl uenza S. aureus (MSSA or GABHS, S. aureus, infl uenzae type I (60%), II, MRSA), Haemophilus Moraxella (nontypeable; III, IV; infl uenza; spp., GABHS, an- catarrhalis, type B com- adenovirus; aerobes Haemophilus mon before RSV; measles infl uenzae∗ vaccination) (unimmunized Inhalation or caus- host) tic injury, blind fi nger sweep

Management ABC (anticipate ABC (antici- Dexamethasone ABC (rarely requires diffi cult intuba- pate diffi cult (0.6 mg/kg intubation), CT neck; tion), CBC, blood cx intubation), PO or IM; ENT consult for pos- Admit to ICU; ENT airway hu- maximum sible drainage; consult midifi cation, 10 mg), racemic Admit patient on hydration. epinephrine IV antibiotics, ± IVF Admit patient; only if stridor and pain control ENT consult at rest; for possible Other: Heliox, bronchoscopy inhaled budes- for suctioning onide (2 mg) ± Discharge home†

Antibiotic Third-generation Third-generation No MRSA coverage‡ ± cephalosporin cephalosporin + third-generation (eg, ceftriaxone) MRSA coverage‡ cephalosporin

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Bacterial Retropharyngeal Feature Epiglottitis Tracheitis Croup Abscess

Morbidity 6%–10% without ~4%–20% Rare mortality High mortality and mortality intubation (1% (50%) if associated with intubation) with mediastinitis or other complications

∗H. infl uenzae historically caused approximately 90% of pediatric cases of epiglottitis, but this has drastically decreased since the development of the Hib vaccine. †Can send home if clinically well, not requiring frequent racemic epinephrine, PO well, access to follow-up and emergency care. ‡MRSA coverage: clindamycin or vancomycin.

ASTHMA INITIAL ASSESSMENT AND MANAGEMENT OF AN ASTHMA EXACERBATION

Assess severity of asthma exacerbation History: focus on onset, duration of sx, prior ER visits, prior hospital/ICU admissions, h/o inhaled steroid use and compliance. Also evaluate for other causes of wheezing (i.e. foreign body, mass). Physical: Clinical respiratory score (CRS) – See Table below

Mild Moderate Severe Impending/actual (CRS Ä3; (CRS 4–6; (CRS 6–8; respiratory arrest PEF ê60%) PEF ê40%) PEF <40%) (CRS 8–12; PEF Ä25%)

Management ≥ O2 to keep SpO2 92% Ye s Ye s Ye s SABA neb/MDI with spacer <2yr: 2.5mg/4puffs, <2yr: 5mg/6puffs, 5mg/8puffs ≥2yr: 5mg/6puffs ≥2y: 5mg/6–8puffs Frequency of SABA x 1 dose → reassess q20min PRN x 3doses → if no q20min PRN x 3doses improvement start continuous SABA then q1–3h Ipratropium bromide No Consider If no response after1st SABA ADD Ipratropium x 3 doses

Corticosteroid Yes (PO) Yes (PO) Yes (PO/IV)

Admit to ICU PEDIATRICS Frequent reassessment • ≥ O2 to keep SpO2 92% • Continuous SABA • Add ipratropium x 3 doses • IV corticosteroid CRS >3 & <6 or PEF ê40% CRS ê6 or PEF <40% CRS Ä3 or PEF ê60% • Consider IV magnesium and NOT improving and NOT improving tolerating q3–4h SABA • Consider adjunct tx Vital signs stable on room air 1. IV Terbutaline Admit to hospital Admit to hospital (special care 2. NPPV • ≥ O2 to keep SpO2 92% unit) 3. Heliox • Continue SABA tx at • • O to keep SpO ≥ 92% ABG, VBG, or CBG Discharge home frequency required by 2 2 • • Place on continuous SABA Mechanical ventilation as • Continue SABA tx per patient • IV route for steroid needed action plan • Continue PO steroid • Consider adjunct tx • Compete PO steroid • Consider initiation/ 1. IV Terbutaline • Initiate/continue long continue long term 2. NPPV term control medications control medications (if 3. Heliox (if applicable) applicable) • Consider initiation/ • Patient education • Initiate asthma continue long term 1. Review medications education & action plan Impending/actual control medications 2. Drug delivery teaching respiratory arrest • Initiate asthma education 3. Review action plan (CRS 8–12; & action plan 4. Recommend follow-up PEF Ä25%)

Repeatedly assess effect of treatment

Figure 13.3 Management of asthma exacerbation. (Adpated from Texas Children’s Hospital Evidenced Based Clinical Guideline for Asthma.) NPPV, non-invasive positive pressure ventilation 138 Pediatrics

CLINICAL RESPIRATORY SCORE (CRS) Assess Score 0 Score 1 Score 2 Respiratory rate/min <2 mo <50 50–60 >60 2–12 mo <40 40–50 >50 1-5 yr <30 30–40 >40 >5 yr <20 20–30 >30 Auscultation Good AE, ↓ AE, inspiratory and expira- ↓↓ or absent AE, severe scattered tory wheezes wheezing, marked expiratory wheeze prolonged expiration Use of accessory Mild to no use of Moderate intercostal retrac- Severe intercostal muscles accessory tions, mild to moderate use of and substernal retrac- muscles accessory muscles, nasal ﬂ aring tions, nasal ﬂ aring Mental status Normal Irritable, agitated, restless Lethargic

SpO2 on room air >95% 90%–95% <90% Color Normal Normal to pale Cyanotic, dusky

AE, air entry. Adapted from Texas Children’s Hospital evidence based clinical guidelines for asthma.

BRONCHIOLITIS • Defi nition: An infl ammatory disease of the LRT causing obstruction (secondary to edema, necrosis, ↑ mucus, ± bronchospasm) of the small airways. Median duration is 12 days. Frequently occurs in December through March. • Etiology: RSV responsible for 70%; Parainfl uenza viruses (second most common cause), adenovirus, human metapneumovirus, infl uenza virus, Mycoplasma and Chlamydia. • Diagnosis: Made clinically (no testing is required). • History and physical exam: URI with rhinorrhea, cough, ± fever (66%). Higher risk (may require closer monitoring): prior cardiac or pulmonary disease, ± apnea (increased risk in <1 mo), cyanosis, age <12 wk, prematurity, immunodefi ciency as these patients may require closer monitoring. Physical exam should include vital signs, pulse oximetry, respiratory assessment (tachypnea, nasal fl aring, grunting, intercostal retractions, expiratory wheezing, prolonged expiratory phase, crackles or rales). • Laboratory and other testing: CXR not indicated (except when there is an unclear diagnosis, no improvement in expected time period; more severe cases require further evaluation). • CBC is not indicated. • If age ≤60 d + fever perform a workup (See previous fi gure: FWLS 0-60 days). • Consider RSV or infl uenza rapid tests & viral cx if neonate (<28 day) or admitting to hospital (for cohorting/infection control measures). • Treatment • Nasal saline at scheduled intervals with deep or bulb suctioning as needed; teach nasal saline & bulb suctioning to caregivers. If patient is being hospitalized, consider scheduled 5 ml of 3% hypertonic saline nebulization q6h. < • Supplemental O2 (after suctioning) if SpO2 90% while awake. • Hydration (if mild/moderate dehydration attempt PO → if fails, start IVF; if severe consider IVF); also position body at 45° post feeds. • ± single administration of racemic epinephrine or albuterol in patients with signifi cant respiratory distress. If improvement, continue with treatment on prn basis. • Antibiotics only as indicated for children ≤60 d with fever or suspected secondary pneumonia (rare, <2%). • Consider helium/oxygen (Heliox) by nonrebreather mask if the patient is in severe distress → consider BIPAP → if patient in respiratory failure then intubate. • Disposition ≤70 ≥ • Discharge criteria: (1) RR breaths/min; (2) SpO2 90% while awake; (3) parent able to do nasal saline + bulb suction; (4) PO feedings tolerated to maintain hydration, Emergency Medicine 139

(5) parents understand discharge care, risk of passive smoke exposure, proper handwashing techniques, when to follow-up with PCP. • Admission criteria: (1) Not meeting discharge criteria, (2) clinically deteriorating, (3) toxic or severe respiratory distress.

ACUTE ABDOMINAL PAIN Clinical Presentation Diff erential Diagnosis Trauma Perforated viscus, hematoma, hemorrhage, solid organ injury (liver/spleen laceration) Intestinal obstruction Intussusception, mid-gut volvulus, incarcerated hernia Peritonitis Appendicitis, ruptured appendix, tubo-ovarian abscess

Abdominal mass∗ HSM, tubo-ovarian abscess, pregnancy, choledochal cyst, neoplasia (eg, leukemia, lymphoma, neuroblastoma)

Adnexal tenderness, Tubo-ovarian abscess, PID, ovarian cyst, ovarian torsion, abnormal menses pregnancy Fever and abdominal pain AGE, UTI, pneumonia, GABHS pharyngitis, appendicitis, intraabdominal abscess, hepatitis, pyelonephritis Other causes AGE, pancreatitis, mononucleosis, leukemia, lymphoma, pyelonephritis toxin ingestion, constipation, pancreatitis, testicular pain mononucleosis

∗Consider UPT, liver panel, ESR or CRP, CBC, Monospot/EBV IgG/IgM, US of abdomen, and CT or MRI of abdomen based on clinical presentation.

Acute Appendicitis • Epidemiology: Male:female ratio 2:1; primarily in adolescence • Diagnosis: Diagnosis of appendicitis is a clinical diagnosis (see pediatric appendicitis score table). Laboratory data is not necessary if clinical signs/symptoms are consistent with appendicitis. • History and physical exam: Fever, nausea/vomiting, anorexia, Periumbilical pain migrating to right lower quadrant (McBurney’s point, 1/3 between ASIC and umbilicus), positive

psoas sign (pain with hyperextension of the right leg), positive obturator sign (pain with PEDIATRICS internal rotation of the right leg while the patient is lying on back with hip and knee fl exed at 90 degrees), positive Rovsing’s sign (pain on RLQ due to applying pressure on LLQ), or signs of peritonitis (pain with cough, jump, percussion, rebound tenderness, involuntary guarding), anorexia, nausea or vomiting, fever. • Laboratory: CBC, abdominal radiography (calcifi ed fecalith, sentinel loop; neither is sensitive), ultrasonography (⊕ if >6 mm noncompressible appendix, wall thickening (>2 mm), free fl uid, mesenteric thickening, localized tenderness with graded compression, calcifi ed fecalith; sensitivity and specifi city varies by institution), abdominal CT (dilated non-opacifi ed appendix with adjacent infl ammatory changes, appendicolith, target sign, wall thickening (>2 mm), fat stranding, free fl uid; CT is 94% sensitive). • Treatment: Rehydration (IVF), NPO, pain control (eg, Morphine), surgery, start antibiotics in EC if signs of peritonitis (eg, cefoxitin, piperacillin/tazobactam , cefotetan; in patients allergic to PCN give gentamicin AND clindamycin or metronidazole).

PEDIATRIC APPENDICITIS SCORE*

Fever >38oC (100.4oF) 1 Tender RLQ 2 Migration of pain to RLQ 1 Pain with cough, jump, percussion 2 Anorexia 1 Leukocytosis, WBC>10,000 cells/mm3 1 Nausea and vomiting 1 Neutrophils plus bands >7,500 cells/mm3 1

∗PAS ≥6 = highly associated with appendicitis (nearly 100% sensitive); if PAS 3–6, may require further evaluation (observation with serial abdominal exams, US, CT); if PAS ≤2, appendicitis unlikely. Adapted from J Pediatr Surg 2002;37(6):87. 140 Pediatrics

Intussusception • Deﬁ nition: Intestinal obstruction caused by invagination of intestine into an adjoining intestinal lumen. The two types are idiopathic (75%) and lead-point (25%). • Epidemiology: Idiopathic intussusception is the most common cause of obstruction in young children (6-36 mo); approximately 60% are <1yr old and 80% are <2yr old. Lead point intussusception can occur at any age, but have higher suspicion in patients <3mo and >5yr. • Etiology: Idiopathic or lead-point intussusception may occur because of lead points (eg, Meckel’s diverticulum, duplication cysts, tumor, polyps, hematoma, vascular malformation) • Diagnosis • History and physical exam: Usually afebrile, intermittent paroxysmal episodes of colicky abdominal pain (q20–60 min), patient draws up leg, vomiting, currant jelly stool (late sign; rare), ± distension. On PE: palpable “sausage” right mid to RLQ of abdomen, occult blood. • Laboratory and other tests: Guaiac-positive stool (40%), abdominal x-ray (absence of air in right side of abdomen), ultrasonography (“bull’s eye” appearance of intestine, 95%), air/contrast enema is both diagnostic and therapeutic. • Treatment: Surgery consult (Reason: not reducible or for complication from enema), air/ contrast enema (60%–90% successful; 10% recurrence rate so consider observation for 24 hours post-reduction). Avoid enemas in patients with shock, perforation, high-grade obstruction. Consider antibiotics if peritoneal signs are present (rare). • Complications: Bowel ischemia → gangrenous change → perforation → infection. Mortality ~1%. It is important to evaluate for lymphosarcoma if patient >6 yo with intussusception.

Other Surgical Causes of Acute Abdominal Pain • Gallstones: Colicky right abdomen pain post feeding, ± nausea/vomiting, + Murphy’s sign; can result in pancreatitis, ascending cholangitis; consider surgery/GI consult • Renal stones: Colicky, sharp, stabbing pain; ± vomiting; hematuria; consider urology consult for signiﬁ cant hydronephrosis, failed initial treatment. • Malrotation and midgut volvulus: Surgical emergency; duodenal obstruction, volvulus occurs in 30% with malrotation → sudden vomiting (bilious, bloody, coffee grounds), bloody stool • Gastric volvulus: Torsion ≤180°→ partial obstruction ± vomiting; torsion > 180°→ Borchadt’s triad (retching, acute epigastric pain, distention & inability to pass NGT) • Incarcerated hernias: Manual reduction unless there are signs of peritonitis, unstable VS, signiﬁ cant erythema, signs of strangulation • Hirschsprung’s disease: Congenital megacolon, constipation, enterocolitis; diagnosed via barium enema, rectal biopsy • Meckel’s diverticulum: Rule of 2’s: 2% of the population, most common age is 2 yo, boys are ~2 times as likely to be affected, 2 feet from the ileocecal valve, 2 inches in length, 2% are symptomatic, 2 types of common ectopic tissue (gastric and pancreatic) • Annular pancreas: Bilious vomiting; associated with Down syndrome, malrotation, history of polyhydramnios

PYLORIC STENOSIS • Defi nition: Obstruction of pyloric channel due to hypertrophy of circular pyloric muscle. • Epidemiology: Most common surgical disorder of infancy; ages 3 to 5 wk (upper age limit 8 wk); ↑ risk in boys over girls (4:1 male:female ratio); ± h/o perinatal exposure to erythromycin; ± h/o maternal pyloric stenosis. • Diagnosis • History and physical exam: Progressively worsening nonbilious, projectile emesis immediately postprandial. Exam may reveal palpable RUQ olive or peristaltic wave immediately after feeding. Assess dehydration (Pre-illness weight - current weight). ↓ ↑ ↓ • Laboratory and radiology: Chem 7 ( Cl, HCO3, ± K) and imaging pyloric US (pyloric muscle thickness >3 mm and/or pyloric length >14 mm); UGI (“string sign” through pylorus). • Treatment: NPO and start IVF → fl uid resuscitation with NS based on level of dehydration then D5 ½ NS at 1.5 maintenance (add K after confi rming UOP). Emergency Medicine 141

ALTERED MENTAL STATUS AND COMA • Deﬁ nition: ↓ level of consciousness (spectrum from confusion → coma) • Etiology: Common causes of AMS by age group: • Infants: Infection, metabolic, nonaccidental trauma • Children: Ingestion, infection, intussusception, seizure, nonaccidental trauma • Adolescent: Ingestion,trauma, poisoning, psychogenic • Diagnosis and Management • Initial rapid assessment of ABC → stabilization is priority (consider ETT if GCS <9). After stabilization, treat underlying etiology (utilize antidotes if possible; see chapter. • History and physical exam focused on vital signs, GCS (see PICU Pocket Card) and neurologic exam. History focused on questions related to ingestion, trauma, medicine or drug use, and infectious etiology. • Laboratory and radiology: Rapid glucose testing, CBC chem 10, liver panel, ammonia, lactate, ABG, UDS, toxicology screen (ASA, drugs of abuse, acetaminophen, alcohol levels), ± blood/urine/CSF studies (if high suspicion for infection, eg, fever, immunosuppression). When patient stable → head CT, EEG

NONACCIDENTAL TRAUMA (CHILD ABUSE) • Types: Neglect (60%), physical (20%; children <4 yr and boys <1 yr have the highest rate of mortality), sexual (10%), emotional (7%; difﬁ cult to prove) • Risk factors: External (poor housing, social isolation, foster care), poor parenting skills (unwanted or unexpected child, single, h/o parent being abused), vulnerability of child (disabled children, ex-preemies, hyperactive children), psychological (parental mental illness, alcoholism, drug abuse) • Perpetrators: Parents (80%, including step-parents), nonparental relatives (7%), unmarried partners (3%)

Physical Abuse • Diagnosis • Social work evaluation: Involve social services for all suspected cases of abuse. • History and physical exam: Document thorough history including the reported timeline and your opinion on whether injuries are consistent with neglect or abuse, screen for

domestic violence, document complete physical exam with schematic diagrams of inju- PEDIATRICS ries and forensic photography. • Laboratory: Test for bruising or bleeding diathesis, anemia (CBC, PT/PTT), evaluate 2+ for dehydration or malnutrition (chem 10), screen for bone pathology (Ca , PO4, Alk Phos), test of evidence of abdominal trauma (ALT, AST, amylase, lipase, UA, stool guiaic), ferritin (to rule out HLH), toxicology screen, ± skin biopsy to evaluate for osteogenesis imperfecta (if multiple fractures present in different stages of healing). • Radiology: Skeletal survey to evaluate for fractures. If suspecting intracranial hemorrhage then do a head CT. • Low-risk fractures: Clavicle, distal tibial spiral fracture (unless patient is non- ambulatory), supracondylar fractures • High-risk fractures: Fracture in a patient <2 yo, multiple fractures of different ages, posterior rib, scapula, vertebral body, spinous process, sternum, femur fractures (<2 yo), pelvic fractures (without a history of sustaining signiﬁ cant force), nonsupracondylar fractures of the humerus, pelvic fracture, spiral or transverse fractures, metaphyseal fractures (chip or bucket-handle fractures) • Ophthalmology exam: Retinal exam for hemorrhage. • Differential Diagnosis • Bruising: Bleeding disorder, leukemia, neuroblastoma, ITP, platelet disorder, hemophilia, “Mongolian spot,” coining, cupping, urticaria pigmentosa • Fractures: Osteogenesis imperfecta, primary or metastatic tumors (osteoid osteoma), osteomyelitis, rickets • Burns: Impetigo, HSV, contact dermatitis, TEN 142 Pediatrics

Shaken Baby Syndrome (Shaken Impact Syndrome) • <2 yo: Associated with blunt trauma • Leading cause of death from traumatic brain injury in children <2 yo • Mechanisms of injury • Mechanical force of shaking the child → hemorrhage (subdural bleed secondary to tearing of the bridging veins) • Patient is thrown or struck against hard surface • Anoxic injury to the → ↑ ICP → lethargy, vomiting • ± Retinal hemorrhages (not needed for diagnosis) • ± Skull fracture • External evidence often not present • Diagnosis: See above under “Physical abuse” VENTRICULOPERITONEAL AND VENTRICULOPLEURAL SHUNT-RELATED ISSUES Shunt malfunction • Diagnosis • History and physical exam: Signs of ↑ ICP (bulging fontanel, irritability, ↑ FOC in neonates, decreased LOC, nausea/vomiting, headache), CN palsy (sixth CN), intermittent downward gaze (sunset sign). Evaluate shunt course for swelling/pain (obstruction). • Laboratory and radiology studies: Shunt x-ray series to evaluate for shunt breakage; head CT to evaluate for hydrocephalus. Only 80% of shunt malfunctions are detected by these radiologic studies. Diagnostic shunt tap (by neurosurgery) for assessment of pressure, cell count, culture. • Management: ABCs, early neurosurgery consult, NPO with IVF for possible surgical intervention. • Treatment: Surgical revision or replacement of the malfunctioning shunt.

Shunt Infection • Diagnosis • History and physical exam: 70% occur within ≤2 mo of surgical placement or revision. Pay particular attention to fever, abdominal pain, meningeal signs, or warmth along shunt tract. • Laboratory and radiology studies: Shunt tap; CSF for routine studies and cx. Consider radiographic studies to evaluate shunt especially if signs of shunt failure. • Etiology: Staphylococcus epidermidis, Staphylococcus aureus, gram-negative rods. • Treatment: IV antibiotics (vancomycin + third-generation cephalosporin ± gentamicin if GNR; infectious diseases consultation recommended) ± surgical intervention for removal of infected shunt.

Available at www.AccessPediatrics.com • Evidence-based criteria for identifying low-risk patients 29 to 90 days of age with fever • Fever and petechiae • Vomiting PEDIATRICS Char-

‡ (7) (11.1)

† † -cell destruction ≥200 symptoms Diabetes Mellitus mg/dL (mmol/L) ≥126 β (weight loss, polyuria, polydip-

ciency. ∗ 143 Impaired mg/dL (mmol/L) ed. 2006:2115. ed. th 4 ciency caused by autoimmune rmation on another day. <100 (5.6) 100–125 (5.6–6.9) Normal mg/dL (mmol/L) Type IType 2 Type 2003;26(suppl):S1. Acute onset (<1 mo) of classic symptoms >85%) or Usually subacute; many are asymptomatic, overweight (BMI Absolute insulin defi Insulin resistance and relative insulin defi Not recommended (short asymptomatic period; no effective prevention). Not recommended (short asymptomatic period; no effective Screening”. See table “Recommendations For Type 2 Diabetes Mellitus See table “Diagnosing Diabetes Mellitus and Impaired Glucose Regulation.” See table “Diagnosing Diabetes Mellitus and Impaired Glucose (see table ” Establish hyperglycemia and then differentiate from type 1 ~65% of pediatric patients with DM; 5% to 10% of adults with DM. ~65% of pediatric patients with DM; 5% to 10% of adults with DM. ~35% of pediatric patients with DM; 90% to 95% of adults with Plasma glucose level that meets ADA criteria for DM (see table below) level that meets ADA criteria Plasma glucose Diabetes Care Diabetes Care & Practice, Principles Pediatrics: Oski’s nition: obese; absent or mild polyuria; acanthosis nigricans; glucosuria; usually no ketonuria. obese; absent or mild polyuria; acanthosis nigricans; glucosuria; (~90% of cases); idiopathic (~10% of cases). acteristics Suggesting Type 1 versus Type 2 Diabetes Mellitus”). acteristics Suggesting Type 1 versus Type 2 Diabetes Mellitus”). sia ± polyphagia, lethargy, or vaginal yeast infection); 25% present with DKA. sia ± polyphagia, lethargy, or vaginal yeast infection); 25% present Diagnosis: Mechanism: Presentation: Mechanism: Screening: Screening: Diagnosis: Presentation: • • • • • • • • Type 2 DM: Type 1 DM: 2-h OGTTRandom glucose (11.1) <200 <140 (7.8) ≥200 (11.1) 140–199 (7.8–11) ≥200 (11.1) + classic Age of onsetAge Classic symptoms examPhysical or weeks Days Variable racePredominant loss Weight C-peptide level Caucasian or absent Subacute Autoantibodies Pubertal LowKetoacidosis of PCOS features acanthosis nigricans, Obese, Positive Non-caucasian recurrent Common, (~1/3), very recurrent common rarely Less High Negative Fasting plasma glucose Fasting • • Categories Defi Impaired glucose tolerance = prediabetes. tolerance Impaired glucose Classic symptoms include weight loss, polyuria, polydipsia ± polyphagia, lethargy, and vaginal yeast infection. yeast and vaginal lethargy, ± polyphagia, polyuria, polydipsia loss, include weight Classic symptoms Asymptomatic criteria require confi require criteria Asymptomatic Adapted from from Adapted ‡ from Adapted ∗ † • CHARACTERISTICS SUGGESTING TYPE 1 CHARACTERISTICS SUGGESTING VERSUS TYPE 2 DIABETES MELLITUS Endocrinology (DM) DIABETES MELLITUS • MELLITUS AND DIAGNOSING DIABETES IMPAIRED GLUCOSE REGULATION CHAPTER 14 144 Pediatrics

• Prevention: Avoid weight gain into the overweight or obese range. If overweight → weight loss and exercise (independent of weight loss) may delay, prevent, or reverse the course of Type 2 DM.

Recommendations for Type 2 Diabetes Mellitus Screening∗ Age >10 yr or onset of puberty (whichever is earlier) and overweight (BMI >85th percentile or >120% of IBW for height) and any two of the following: • Family history of type 2 DM in ﬁ rst- or second-degree relative • Non-European ethnicity • Signs of insulin resistance (acanthosis nigricans, hypertension, dyslipidemia, PCOS)

∗Screening should be done every 2 years. Adapted from Pediatrics 2000;105:671.

• Secondary causes of DM: Genetic defects of β-cell function (formerly MODY; AD inheritance, multiple family members with hyperglycemia onset <25 yo), gestational DM, drug- induced (eg, L-aspariginase, steroids, tacrolimus, cyclosporine, β-blockers, phenytoin, protease inhibitors), diseases with pancreatic destruction (eg, CF, trauma, pancreatitis), infections (eg, rubella, CMV), genetic syndromes with insulin deﬁ ciency or resistance (eg, Down, Prader-Willi, Turner, Klinefelter syndromes). • Inpatient management • DKA: See chapter 9 for DKA management. • New stable type 1 diabetic (not in DKA): • Criteria for admission to regular ward (vary by institution): Normal mental status, ≥ ≤ ≥ tolerating PO intake, and serum HCO3 16 mEq/L ( 5 yo) or 12 mEq/L (>5 yo). • Orders: see table “Suggested Orders For The New Diabetic”. • Insulin management: See table “Pharmacokinetics of Different Types of Insulin” and table “Insulin Regimens for Controlling Blood Sugar in Patients with Type 1 Diabetes Mellitus”

Suggested Orders for the New Diabetic Insulin regimen: See table Insulin Regimens for Controlling Blood Sugar in Patients with Type 1 Diabetes Mellitus Diet Carbohydrate consistent—3 meals and 2 snacks per day (3 if child <5 yr) Labs • Finger stick blood glucose (FSBG) before breakfast, lunch, dinner, bedtime, and at 2 AM. – • If HCO3 <18 mEq/dL, check serum electrolytes and β-hydroxybutyrate Q3h x 1 and then

Q6h. Notify physician if HCO3 ≤10 mEq/dL. • HbA1c • Diabetes panel: Islet cell antibodies, insulin antibodies, GAD antibodies, insulin level∗, C-peptide. • Urine ketones (or bedside β-hydroxybutyrate level) if FSBG >300 mg/dL (16.7 mmol/L). Notify physician if moderate or large urine ketones or if β-hydroxybutyrate level >0.6 mmol/L. • Celiac panel: anti-tissue transglutaminase antibodies, anti-endomysial antibodies, total serum IgA • Consider thyroid autoantibodies (anti-thyroglobulin antibody, anti-thyroid peroxidase antibodies (TPO)) or thyroid function tests (TSH, free T4). To bedside • Glucagon emergency kit x 1. • One box each: Finger stick β-hydroxybutyrate measuring device (if available) or Ketostix (ie, urine ketone testing strips), lancets, insulin syringes. Consultations • Social services, health psychology team, nutrition, child life specialist, diabetes management team. Initiate diabetes education • Bedside nurse to teach how to check FSBG, ﬁ nger stick ketones or urine ketones, administer insulin and glucagon injections, and count carbohydrates.

∗Insulin level is only useful if drawn before the ﬁ rst dose of insulin is given; this is usually done in the ED. Endocrinology 145

PHARMACOKINETICS OF DIFFERENT TYPES OF INSULIN

Onset Peak Glycemic Duration Types of Insulin (h) Eff ect (h) (h) Rapid Acting

Insulin lispro (Humalog®) 0.2–0.5 1.5–2.5 3–4

Insulin aspart (NovoLog®) 0.2–0.5 1–3 3–5

Insulin glulisine (Apidra®) 0.2–0.5 1.6–2.8 4–5 Short Acting

Insulin regular (Humulin® R, Novolin® R) 0.5 2.5–5 4–12 Intermediate Acting

Insulin NPH (isophane suspension) 1–2 4–12 18–24 (Humulin® N, Novolin® N) Intermediate to Long Acting

Insulin detemir (Levemir®) 3–4 3–14 6–23 Long Acting

Insulin glargine (Lantus®) 3–4 ∗ ≥24 Combinations

Insulin aspart protamine suspension 0.2 1–4 18–24 and insulin aspart (Novolog® Mix 70/30)

Insulin lispro protamine and insulin 0.2–0.5 2–12 18–24 lispro (Humalog® Mix 75/25™)

Insulin NPH suspension and insulin 0.5 2–12 18–24 regular solution (Novolin® 70/30) PEDIATRICS

∗Insulin glargine has no pronounced peak. Adapted from Texas Children’s Hospital formulary.

INSULIN REGIMENS FOR CONTROLLING BLOOD SUGAR IN PATIENTS WITH TYPE 1 DIABETES MELLITUS • Basal/bolus regimen (now favored) • Advantages: Better metabolic control, more ﬂ exible (meal timing, content, size) • Disadvantages: Requires more expertise, more injections • Instructions: • Long-acting insulin: 1/2 of total daily insulin dose (TDID)∗ given Q24h or divided to dose Q12h • Rapid-acting insulin: Give with each meal or snack, or to correct glucose values above goal range; calculate the sum based on: 1. Insulin to carbohydrate ratio (I:C): 450/TDID = X. Give 1 unit rapid-acting insulin per X grams of CHO to be eaten at this meal or snack. 2. Correction factor: 1800/TDID = Y. Give 1 unit rapid-acting insulin per Y mg/dL that FSBG is > target glucose. • Advantages: Requires less understanding (eg, CHO counting), fewer injections

(continued on next page) 146 Pediatrics

• Disadvantages: Less fl exibility (fi xed number of carbohydrates per meal), suboptimal glycemic control • Instructions: • Intermediate-acting insulin: 2/3 of TDID. Of this, give 2/3 before breakfast and 1/3 before dinner or bedtime. • Short-acting insulin: 1/3 of TDID. Of this 1/3, give 2/3 before breakfast and 1/3 before dinner. • Insulin pump (basal/bolus) • Advantages: Better metabolic control than mixed split regimen, fl exibility (meal timing, content, size), fewer injections, variable basal rate • Disadvantages: Requires more expertise, equipment malfunction (may be recognized late) • Instructions • Short-acting insulin only. Basal rate can be changed throughout day. Bolus given at time of meal or snack and FSBG based on I:C ratio and correction factor (see above).

∗Calculate total daily insulin dose (TDID) based on table below. Mixed or split regimen (mix of short-acting + NPH insulin; older regimen, still commonly used for new diabetic patients)

INITIAL TOTAL DAILY INSULIN DOSE (TDID) OF SUBCUTANEOUS INSULIN

Age (yr) Dose (units/kg/d) <5 0.4 5 to 7 0.5 ≥7 0.7

BLOOD GLUCOSE AND HbA1c GOALS FOR INSULIN-DEPENDENT DIABETES MELLITUS BY AGE

Blood Glucose Goal Ranges∗ mg/dL (mmol/L) Age (yr) Preprandial Bedtime/overnight HbA1c (%) <6 100–180 (5.6–10) 110–200 (6.1–11.1) 7.5–8.5 6–12 90–180 (5–10) 100–180 (5.6–10) <8 13–19 90–130 (5–7.2) 90–150 (5–8.3) <7.5

∗Goals should be individualized based on beneﬁ t–risk assessment. Adapted from Diabetes Care 2005; 28:186.

• Management of insulin for special situations • Insulin-dependent patient who is NPO for a procedure: • If for a procedure, do as fi rst case to minimize NPO time (if possible). • NPO according to anesthesiologist recommendations: • ↓ AM basal insulin by 10% (if on pump), 20% (if using long-acting insulin), or 50% (if using intermediate-acting insulin). • Give short or rapid-acting insulin only if on dextrose-containing fl uids; use a conservative correction factor Q4h with FSBG target of 150 mg/dL (8.3 mmol/L). • Check FSBG Q1–2h while the patient is NPO. • Resume usual regimen as soon as the patient resumes eating. • Start dextrose-containing fl uids if NPO > 8h. • May need aggressive hydration and insulin drip if NPO for serious illness. • Sliding scale insulin: • Calculated by correction factor (see table above). Endocrinology 147

• Provide written sliding-scale instructions (eg, list of ranges above normal glucose level and corresponding insulin dose to administer) when simplicity is necessary, such as when inpatient and nursing or primary team uncomfortable with insulin calculations, or when outpatient on mixed or split regimen and patient/caregiver has poor compliance and understanding. • Adjusting insulin doses: • Look for patterns over several days or weeks. • Adjust dose several hours before the time of the undesirable FSBG reading. • Do not change insulin by >2 units or >10% of current dose unless otherwise directed. • Observe FSBG trends ≥2 days before making another change. • Differentiate AM hyperglycemia caused by (1) dawn phenomenon (insulin resistance in the early morning hours due to normal growth hormone surge → FSBG at 2 AM near goal but 7 AM ↑) versus (2) Somogyi effect (excessive insulin during the overnight period causing hypoglycemia → cortisol, glucagon, epinephrine released in response to hypoglycemia → FSBG at 2 AM ↓ and 7 AM ↑). • Honeymoon effect: After initiation of insulin in a new diabetic, the patient may transiently (usually weeks to months) require less insulin. Prepare the patient or family for this. • Upon hospital discharge, expect to lower the insulin dose by 10% (more exercise at home + honeymoon effect). • Hypoglycemia: • Adjust insulin, administer carbohydrates or glucagon. Also see ﬁ gure “Management of hypoglycemia in diabetes”. • Type 2 Diabetes Mellitus • Exercise, dietary changes, and weight loss are essential. • Follow recommendations for nephropathy, hypertension, dyslipidemia, retinopathy, and thyroid disease as for patients with type 1 DM. Type 2 DM patients may need to be referred for evaluation of complications as early as at diagnosis. • Consider insulin in addition to metformin in patients who present with fasting blood glucose >250 mg/dL (13.9 mmol/L) or HbA1c >9%. • Strict glycemic control leads to fewer-long term complications. • Reduce frequency of FSBG checks to two times per day after achieving good glycemic control.

THYROID DISORDERS

Hypothyroidism PEDIATRICS Congenital • See chapter 34. • Acquired: Prevalence is one in 500 to 1000 school-aged children) • Etiology • Primary: Autoimmune lymphocytic thyroiditis (Hashimoto’s thyroiditis); thyroidectomy or radioiodine therapy; irradiation to thyroid; iodide defi ciency; iodide excess (amiodarone), other goitrogens (lithium, cobalt) • Secondary: Thyrotropin (TSH) defi ciency (isolated or associated with other anterior pituitary hormone defi ciencies); thyrotropin-releasing hormone defi ciency (hypothalamic injury or disease); large hemangiomas (consumption hypothyroidism); idiopathic • Clinical features: Growth deceleration, mild weight gain, delayed puberty, constipation, cold intolerance, delayed dental development, mental depression, metromenorrhagia, galactor- rhea, precocious or delayed puberty; dry skin, brittle hair, hypotonia, hypothermia, bradycardia, transient deafness, delayed bone age • Evaluation • ↓ T4 or FT4 with ↑ TSH in primary and decreased to normal TSH with ↓ T4 (or TSH elevation less than expected relative to degree of hypothyroxinemia) in secondary hypothyroidism • Check anti-thyroid peroxidase and anti-thyroglobulin antibodies • Evaluate for any other underlying cause • Management • Levothyroxine (75–100 mcg/m2/d) once → OR NO YES FSBG Give glucagon SubQ: glucagon SubQ: Give 80 mg/dL IV access: 30 minutes ≥ appropriate maintenance (4.4 mmol/L)? D10W water at D10W water Start IV D5W or Recheck FSBG in Recheck 20 kg, 0.5 mg; >20 kg, 1 mg (Note: 20 kg, 0.5 mg; ≤ stable check FSBG as clinically check stable Check FSBG q15 min till Check >100 mg/dL (5.6 mmol/L) Give D50 (1 mL/kg) or D25 (2 Give No IV access: Child NO glucagon effect lasts 1 hr; can cause emesis) lasts 1 hr; glucagon effect taking PO) Give double of double Give initial glucagon q30 min till IV or (Repeat glucagon dose & establish IV dose & establish Conscious? (4.4 mmol/L) Check FSBG to Check see if <80 mg/dL NO YES NO FSBG YES 80 mg/dL ≥ 30 minutes (4.4 mmol/L)? 2 yr: 2 units [20 mcg] 2 yr: ≤ Recheck FSBG in Recheck “Mini dose glucagon” Give Give Mix glucagon according to full dose dose IM using a Give instructions. regular insulin syringe. Dose based on age: Child 1 unit [10 mcg]/yr of age 2-15 yr: 15 units [150 mcg] >15 yr: 100 mg/dL ≥ NO 2 / Monitor FSBG as 1 PO? clinically appropriate until FSBG consistently (5.6 mmol/L) Tolerating Hypoglycemia Headache, hunger, sweating, tachycardia, blurred tachycardia, sweating, hunger, Headache, YES FSBG 80 mg/dL 15 minutes ≥ (4.4 mmol/L)? Recheck FSBG in Recheck YES Management of hypoglycemia. tubes concentrated glucose, or cake glucose, tubes concentrated gums and lips) frosting between FSBG <40 mg/dL (2.2 mmol/L) treatment (eg 1 More aggressive FSBG 50-80 mg/dL (2.8-4.4 mmol/L) CHO 4 oz juice + 15 g complex Give (eg, small sandwich) loss of consciousness seizures, vision, somnolence, Clinical presentation: Figure 14-1

148 Endocrinology 149

• Initially follow TSH and FT4; later TSH and T4 are used for monitoring effectiveness and adjusting the dose over time (if T4 and FT4 correlate) • Follow up: If etiology is autoimmune (especially if multiple family members with autoimmune hypothyroidism) evaluate for other autoimmune disease

Hyperthyroidism Acquired Hyperthyroidism • Etiology: Graves disease, subacute thyroiditis, toxic phase of chronic lymphocytic thyroiditis, TSH-secreting adenoma, toxic multinodular goiter, factitious hyperthyroidism • Clinical features: Hyperactivity, poor concentration, nervousness, emotional lability, fatigue, weight loss, increased sweating, heat intolerance, diarrhea, irregular menses, fi ne tremors, goiter, exophthalmos, palpitations, tachycardia, systolic hypertension, proximal muscle weakness • Evaluation • ↓ TSH (except in TSH-secreting adenoma where TSH ↑); ↑ T3, T4, or FT4 • Check thyroid-stimulating immunoglobulin (TSI) • Thyroid uptake scan (↑ in Graves disease) • Management • β-adrenergic antagonists: For control of symptoms (nervousness, tremors, tachycardia, and hypertension). β-1 specifi c agents preferred (eg, atenolol) • Antithyroid agents (methimazole, propylthiouracil): Interfere with thyroid hormone synthesis. PTU also ↓ T4 → T3 conversion. • Radiation therapy: An appropriate amount of oral I131 in children with Graves disease causes thyroid ablation. More commonly used as fi rst line treatment or for patients who are unresponsive or poorly adherent to antithyroid agents. Give β-adrenergic antagonists during radiation therapy as symptoms worsen with cell lysis ~1-2 wk after ablation. Radiation therapy usually results in hypothyroidism, requiring future thyroid hormone replacement. • Surgical treatment: Rare; indications include very large goiter, suspicious nodule, patients refusing radiation therapy, condition uncontrollable on methimazole or severely thyrotoxic patient requiring immediate intervention. • Iodide: Only for acute management of severely thyrotoxic patient; large dose causes short-lived blockade of thyroid hormone synthesis and release. Continued use will cause a worsening of hyperthyroidism. Thyroid Storm (rare but potentially lethal)

• Clinical features: In a patient with hyperthyroidism, acute onset of hyperthermia, PEDIATRICS tachycardia, restlessness; may progress to delirium, coma, or death if untreated. • Evaluation: Diagnose based on clinical ﬁ ndings and scored using the Burch-Wartofsky criteria (Endocrinol Metab Clin North Am 1993;22:263) • Management: Propanolol (or esmolol), propylthiouracil (PTU), iodine, steroids, cooling.

Other Thyroid Diseases Acute thyroiditis • Incidence/etiology: Rare; common causes GABHS, S. pneumoniae, S. aureus and anaerobes. • Clinical fi ndings: The patient is always toxic with fever and chills. The thyroid gland is large, erythematous, and very tender ± fl uctuance. May have hoarseness or dysphagia. TFT are usually normal. • Treatment: Specifi c antibiotic therapy should be administered and surgical drainage performed if an abscess is present. Subacute thyroiditis (de Quervain thyroiditis) • Incidence/etiology: Rare; common causes are viral infection with mumps, infl uenza, echovirus, coxsackievirus, EBV, or adenovirus • Clinical fi ndings: Onset is generally insidious. Similar to acute thyroiditis, and thyroid is fi rm and enlarged. Sedimentation rate is elevated. May have ↑ TFT. Nonthyroidal illness (sick euthyroid syndrome; low T3 syndrome) • Most common cause of abnormal thyroid tests in hospitalized patients. • ↓ T3, ↓ T4, ↑ reverse T3. • TSH is usually low-normal, but may rise during recovery phase. • Issue of thyroid hormone replacement controversial. 150 Pediatrics

SYNDROME OF INAPPROPRIATE ANTIDIURETIC HORMONE (SIADH) AND CEREBRAL SALT WASTING (CSW) COMPARISON OF SYNDROME OF INAPPROPRIATE ANTIDIURETIC HORMONE AND CEREBRAL SALT WASTING

SIADH CSW∗ Pathophysiology Inappropriate ADH secretion despite Increased urine Na loss, which normal or increased plasma volume, leads to hyponatremic dehydration which results in hyponatremic euvolemia or hypervolemia Etiology CNS: Tumor or injury, surgery, men- CNS injury, tumor, meningitis ingitis, encephalitis, subarachnoid (eg, bacterial, TB), subarachnoid hemorrhage, hydrocephalus or intracerebral hemorrhage, Lung: Pneumonia, TB stroke, craniosynostosis repair Other: HIV/AIDS, neoplasm, thoracic surgery, drug use Clinical Symptoms: Headache, blurred Symptoms: Polyuria, nausea, manifestation vision, nausea and vomiting, muscle vomiting, headache, weight loss, ↑ cramps, weakness, irritability, change thirst, altered mental status, seizures in mental status if severe hyponatremia, coma Signs: Not dehydrated; normal skin Signs: Moderate to severe dehy- turgor; normal or ↑ BP; ± edema, dration (dry mucus membranes, ↓ DTR, asymmetric pupils, low GCS, sunken eye, sunken fontanel), pseudobulbar palsy orthostatic hypotension and ↑ HR, delayed capillary reﬁ ll Diagnostic Euvolemic or hypervolemic on exam Hypovolemic on exam evaluation ↓ Na (< 135 mmol/L), ↓ serum ↓ Na, ↑ serum osmolality, ↓ se- osmolality (<280 mOsm/kg), ↓ serum rum uric acid, ↓ urine osmolality, ↑ ↓ ↑ ↑ uric acid, urine osmolality, UNa, UNa, urine volume ↓ urine volume Management Fluid restriction (start with <75% of Correct intravascular volume and maintenance, ie, 1000 mL/m2/d); if provide sodium replacement no improvement, decrease to 50%, with IVF and so on Demeclocyline or AVP receptor antagonist 3% hypertonic saline only if Na <120 meq/L and child seizing

∗Also known as Renal salt wasting (RSW)

DIABETES INSIPIDUS

Central Nephrogenic Diabetes Insipidus Diabetes Insipidus Etiology CNS injury, tumor, meningitis, Familial: X-linked recessive inheri-

subarachnoid hemorrhage, stroke, tance (V2 receptor gene defect); DIDMOAD (Wolfram) syndrome AR inheritance (aquaporin 2 gene defect). Others: Hypercalcemia, hypokalemia, drugs (eg, lithium), chronic renal disease

(continued on next page) Endocrinology 151

Central Nephrogenic Diabetes Insipidus Diabetes Insipidus Clinical Polyuria, polydipsia, nocturia, Dehydration; infants exhibit manifestation hypernatremia, dehydration, seizure irritability, poor feeding, growth (if severe hypernatremia) failure, vomiting

Diagnostic Low urine osmolality (50–300 mOSm/L) Water deprivation test may be evaluation High serum osmolality (>300 mOsm/L ) needed for defi nitive diagnosis Low urine specifi c gravity <1.010 Nephrogenic DI is resistant to vasopressin Water deprivation test may be needed for defi nitive diagnosis Central DI responds to vasopressin

Management Management of hypernatremia Provision of free water Vasopressin IV for acute DI, coma, Salt-restricted diet post-surgery Drugs: Thiazide diuretics, DDAVP: PO, subcutaneous, or intranasal amiloride, indomethacin

SEXUAL DEVELOPMENT Normal Sexual Development • In girls, thelarche (breast development) starts at 8–13 yr; varies by ethnic group)→ pubarche (pubic hair development) → menarche (2.3 yr ± 1 SD from thelarche) • In boys, gonadarche (testicular enlargement) starts at 9–14 yr → pubarche (secondary sexual characteristics, eg, voice change, growth spurt, pubic hair) occurring approximately halfway through the process Delayed Puberty • Girls: No thelarche by age 13 yr, or no pubarche by age 14 yr, or no menarche by age 16 yr or >5 yr between thelarche and menarche. • Boys: No gonadarche by age 14 yr, or no pubarche by age 15 yr, or >5 yr required to complete testicular enlargement PEDIATRICS • Pubertal arrest = No progress in puberty over two years. Precocious Puberty • Pubertal development in girls before age 8 yr and in boys before age 9 yr (there is ethnic variation for thelarche: caucasian girls as early as age 7 yr and African American girls as early as age 6 yr but without other signs of development).

TANNER STAGES IN GIRLS AND BOYS

Girls Boys Breast B1 : Prepubertal Gonadal G1 : Prepubertal <2.5 cm length

B2 : Breast bud G2: Testes >2.5 cm length or ≥4 cc vol

B3: Breast elevation G3: Testes >3-3.5 cm length

B4: Areolar mound G4: Testes >3.5-4 cm length (“mound on a mound”)

B5: Adult G5: Adult testicular length >4 cm

(continued on next page) 152 Pediatrics

Girls Boys Pubic hair PH1: Prepubertal Pubic hair PH1: Prepubertal PH2: Sparse hair on PH2: At base of penis medial labia PH3: Coarse, curly hair, PH3: Spread to mons pubis spread over mons pubis PH4: Increasing distribu- PH4: Not on thighs tion over labia majora PH5: Adult (on inner thighs) PH5: On thighs

RICKETS LABORATORY DATA IN RICKETS

Calcium Phosphate Alk Phos Calcidiol Calcitriol PTH Vitamin D defi ciency Mild N, ↓ N, ↓ ↑ ↓ N N Moderate N, ↓ ↓ ↑↑ ↓ ↓, N, ↑ ↑ Severe ↓ ↓ ↑↑ ↓↓ ↓ ↑↑ Defi cient 25- ↓↓ ↑↓↓ ↑ hydroxylase Defi cient 1-α- ↓↓ ↓↓ ↑↑↑ N ↓↓↓ ↑↑↑ hydroxylase Vitamin D ↓↓ ↓↓ ↑↑↑ N ↑↑↑ ↑↑↑ end organ resistance X-linked hypo- N ↓↓ ↑ N N, ↓ N phosphatemia HHRH∗ N ↓↓ ↑ N ↑↓

Fanconi N ↓↓ ↑ N ↑↑ syndrome Tumor Induced N ↓↑N ↑ N Phosphate N, ↑↓↓↑↑ N ↑↑ deﬁ ciency Ca deﬁ ciency ↓↓ ↓ ↑↑ N ↑ N, ↑ Hypophos- N, ↑ N,↑↓NN N phatasia

∗HHRH: Hereditary hypophosphatemic rickets with hypercalciuria ↑, high; ↓, low; N, normal. Adapted from: Pediatric Endocrinology, 2nd ed. 2002:647.

Available at www.AccessPediatrics.com • Outpatient management of diabetes mellitus • Adrenal insuffi ciency • Hypothyroidism PEDIATRICS 10 kg) × 10 kg) + (50 mL/kg/d × /d = 1344 mL/d (divide by 24 for /d = 1344 mL/d (divide by 24 2 1957;19:823) duration of IVF greater than 24 h 20 mEq/L to IVF will approximate daily maintenance for all ages K should always be added if anticipated When providing 1x MIVF, adding KCl /d = Daily requirement 2 • • 153 Pediatrics. 1600 mL/m × 2 12% for each °C over 37°C), radiant warmer, ↑ 1500–1600 mL/m or /utilization uid intake or output or energy demand 1960;25:496) × ¼ NS = 0.225% saline = 38 mEq/L ) 2 and and 2 kg) = 1540 mL/d (divide by 24 for hourly rate = 64 mL/h) 2 kg) = 1540 mL/d (divide by × Pediatrics. BSA (m 3–4 mg/kg/min (not calorically uids to prevent protein catabolism, + 20 mL/kg/d Maintenance Daily Fluid Requirements: cations to Normal saline (NS) = 0.9% saline = 154 mEq/L; ½ NS = 0.45% saline = 77 mEq/L; Normal saline (NS) = 0.9% saline = 154 mEq/L; ½ NS = 0.45% Daily (body weight–based method): (100 mL/kg/d Daily (body weight–based method): Adult: 0.5–1.0 mEq/kg/d Infant; 2–3 mEq/kg/d Child: 1–2 mEq/kg/d Adolescent: 1 mEq/kg/d Energy expenditure: Fever ( Fluid losses: Renal (renal tubular injury, hyperglycemia, diuretic administration, Fluid losses: Renal (renal tubular injury, hyperglycemia, diuretic D5W = 5% glucose solution = 5 g glucose/dL = 5 g glucose/100 mL = 50 mg/mL water D5W = 5% glucose solution = 5 g glucose/dL = 5 g glucose/100 demands 20% to 30% above resting energy expenditure. directly affects daily MIVF needs for 0–20 kg and D1/2NS for >20 kg adequate; see TPN section in Chapter 4 for parenteral nutrition). hourly rate = 56 mL/h) mannitol administration, diabetes insipidus), GI (vomiting, diarrhea, NG suction, burns mannitol administration, diabetes insipidus), GI (vomiting, (see Critical Care chapter) hyperthyroidism, hypermetabolic states Any perturbation affecting fl Calculations above are for 1x MIVF, assuming an average, hospitalized patient with caloric Calculations above are for 1x MIVF, assuming an average, hospitalized Maintenance is age dependant. Included in IV fl Maintenance: 2–3 mEq/kg/d See “BSA Nomogram and Calculations” in Chapter 1 for BSA calculation. See “BSA Nomogram and Calculations” 1–10 kg: 100 mL/kg/d Examples (22-kg child): maintenance Na: D1/4NS For 1x MIVF, the following saline concentrations approximate 10–20 kg: 50 mL/kg/d >20 kg: 20 mL/kg/d Daily (BSA-based method): 0.84 m Daily (BSA-based method): 0.84 ↑ ↑ • • • • • Modifi • • MIVF Needs Increased • • Potassium (K) • • Glucose • Sodium (Na) • • • BSA-Based Method ( • • Fluids, Electrolytes, and Acid–Base Balance and Fluids, Electrolytes, ELECTROLYTE REQUIREMENTS IV FLUID (MIVF) AND MAINTENANCE Daily Fluid Requirements Method ( Kilograms of Body Weight–Based • CHAPTER 15 154 Pediatrics

Decreased MIVF Needs • ↓ Fluid losses: Anuric or oliguric renal failure, SIADH, ventilation with humidiﬁ ed air (decreases insensible loss) • ↓ Energy expenditure: Coma, sedation, paralysis, hypothermia, hypothyroidism

REPLACEMENT OF FLUID DEFICITS • All calculations are based on the condition at the time of initiation of ﬂ uids; ongoing losses must be addressed as observed. • End points to follow in all patients: Clinical improvement, weight gain, urine output. • Bicarbonate administration should be avoided for initial replacement and then utilized

only in extreme cases (serum HCO3 <8). × × [Desired HCO3 (24 mEq/L) – current HCO3] 0.5 [wt in kg] = HCO3 to administer slowly over hours to days

Weight-based Determination of Degree of Dehydration • Percentage of total body weight lost acutely is attributable to loss of body ﬂ uid Infant (<15 kg): ≤5% mild, 6–10% moderate, ≥11% severe Older child (≥15 kg): ≤3% mild, 6% moderate, ≥9% severe • Example (child with pre-illness weight of 20 kg who now weighs 19 kg): • Weight loss 1 kg = 1-L ﬂ uid loss/20 kg body wt = 5% dehydration

SYMPTOMATIC DETERMINATION OF DEGREE OF DEHYDRATION*

Symptom Mild Moderate Severe

Mental status Normal and alert Normal to fatigued, Apathetic, lethargic, restless, or irritable unconscious

Thirst Normal or may refuse Thirsty, eager to drink Poor or absent liquids desire to drink

Heart rate Normal Normal to tachycardic Tachycardic → bradycardic

Quality of pulses Normal Normal to decreased Weak, thready

Breathing Normal Normal to tachypneic Deep

Eyes Normal Slightly sunken Deeply sunken

Tears Present Decreased Absent

Mouth and Moist Dry Parched tongue

Skin fold Instant recoil Recoil in <2 sec Recoil in >2 sec

Capillary reﬁ ll Normal Prolonged (>2 sec) Prolonged, minimal

Extremities Warm Cool Cold, mottled, cyanotic

Urine output Normal to decreased Decreased Minimal to none

Blood pressure Normal Orthostatic hypotension Hypotension

∗This table was developed for children with dehydration caused by GI losses; extrapolate to other clinical scenarios only as appropriate. Reproduced with permission from Morbid Mortal Wkly Rep. 2003;52(RR-16):1. Fluids, Electrolytes, and Acid–Base Balance 155

Biochemical Classiﬁ cation of Dehydration • Clinical parameters determine the degree of dehydration, and biochemical parameters (primarily serum sodium) guide the choice of rehydration ﬂ uids.

TYPES OF DEHYDRATION WITH ASSOCIATED FLUID AND SODIUM DEFICITS

Biochemical Characteristics Defi cits* Serum Sodium Serum Osmolality Fluid Type (mEq/L) (mOsm/L) (mL/kg) Na (mEq/kg)

Isonatremic 130–150 280–300 100–120 8–10

Hypernatremic >150 >300 100–120 2–4

Hyponatremic <130 <280 100–120 10–12

∗Deﬁ cits shown are averages to demonstrate the relationship of ﬂ uid (water) to sodium loss. Data from Alario AJ, Birnkrant J, eds. Practical Guide to the Care of the Pediatric Patient, 2nd ed. Elsevier/ Mosby;2007:223.

Correction of Hypernatremic and Hyponatremic Dehydration • See “Hypernatremia” and “Hyponatremia” in this chapter. Correction of Isonatremic Dehydration (Most Common Type of Dehydration) Oral Rehydration for Mild to Moderate Isonatremic Dehydration • Oral rehydration is as efﬁ cacious as IV rehydration for acute gastroenteritis and may result in shorter hospitalization; this is best with one-on-one care from adult caregiver (Cochrane Database 2006(3):CD004390, Pediatrics 1996;97(3):424).

ORAL REHYDRATION STRATEGIES

Rehydration Degree of (Defi cit Replacement of

Dehydration Replacement) Ongoing Losses Nutrition PEDIATRICS

Minimal dehydra- Not applicable Normal daily mainte- If possible, continue tion or prevention nance ﬂ uid (eg, 100 mL/ with breastfeeding of dehydration kg for <10 kg) plus or age-appropriate 60–120 mL (<10 kg) or normal diet after initial 120–240 mL (≥10 kg) hydration, including ORS for each diarrheal adequate caloric intake stool or vomiting (do not restrict diet episode and do not discontinue breastfeeding)

Mild to moderate ORS 50 mL/kg (mild) Same as above Same as above dehydration to100 mL/kg (moderate) over 4 h in small, frequent aliquots (5–10 mL every 5–10 min)

Pediatrics 1996;97(3):424–435 and Morbid Mortal Wkly Rep 2003;53(No. RR-16).

• Resume normal diet as soon as tolerated; do not restrict diet (eg, BRAT diet). • Encourage breastfeeding; do not dilute or change from standard formula. • Generally, a lower osmolality and lower carbohydrate content are tolerated better. Avoid antibiotics, antidiarrheals, and anticholinergics (hyoscyamine). 156 Pediatrics

• IV ondansetron may ↓ emesis (Pediatrics 2002;109:e62). • Oral zinc (15–30 mg/d) ↓ duration of acute or persistent diarrhea in children older than age 6 mo, especially in developing countries, where malnutrition is prevalent (Cochrane Database Syst Rev 2008(3):CD005436, Morbid Mortal Wkly Rep 2003;52 (RR-16):1). • Oral rehydration solution (ORS) should be WHO oral rehydration solution or a solution similar in composition.

COMPOSITION OF SELECTED ENTERAL PRODUCTS

Enteral CHO Na K Ca P Approximate Solution kcal/oz (g/dL) (mEq/dL) (mEq/dL) (mg/dL) (mg/dL) Osmolality

Oral Rehydration Solutions

Enfalyte — 3 5 2.5 0 0 200

Pedialyte — 2.5 4.5 2 0 0 250 (ﬂ avored)

Rehydralyte — 2.5 7.5 2 0 0 310

WHO oral — 2.0 9.0 2 0 0 311 rehydration solution 1975∗

WHO oral -— 1.35 7.5 2 0 0 245 rehydration solution 2006

General Formulas

Boost 30 17 2.4 4.3 64 131 610–670

Human 20 7.1 0.7 1.3 17 14 260 breast milk

Enfamil Lipil 20 7.4 0.8 1.9 26 29 300

Ensure 31 18 3.6 3.9 73 125 590

Jevity 32 15.5 4 4 45 76 300

Milk 12.8 5.3 1.8 3.9 38 95 280 (1%, cow)

Milk (whole, 18 4.6 1.8 3.7 58 93 280 cow)

Nutren 1.0 30 12.7 3.8 3.2 33 67 315–370

Nutren 2.0 60 19.6 5.7 4.9 67 134 745

Nutren Jr. 30 11 2 3.4 50 80 350

PediaSure 30 13.5 1.7 3.3 48 80 430–520

Similac 20 7.3 0.7 1.8 26 28 300 Advance

(continued on next page) Fluids, Electrolytes, and Acid–Base Balance 157

Enteral CHO Na K Ca P Approximate Solution kcal/oz (g/dL) (mEq/dL) (mEq/dL) (mg/dL) (mg/dL) Osmolality

Special Formulas

Neocate 20 7.9 1.1 2.7 42 63 375 infant

Neocate Jr 30 10.4 1.8 3.5 50 94 610

Nepro 54 17 4.6 2.7 53 70 665

Nutramigen 20 7 1.4 1.9 32 43 270 Lipil

Pregestimil 20 6.9 1.4 1.9 39 51 330

Pulmocare 45 10.6 5.7 5 53 106 475

Suplena 60 20 3.4 2.9 139 70 600

Other fl uids

Apple juice 10 11.7 0.1 1 — — 650–750 (Minute Maid)

Colas and 12.1 11.3 0.2 0 — 5.1 390–750 sodas (Coca- Cola Classic)

Chicken ~1–5 — 25 0.8 — — 500 broth

Gatorade: 6.3 5.8 2 0.3 — — 330 Lemon-lime ﬂ avor

∗Monitor for hypernatremia given the high sodium content; developed for rehydration (not maintenance) in areas without IV capability. PEDIATRICS — = no information. MMWR 2003;52(RR–16):1–16.

IV Rehydration • This is for patients with severe isonatremic dehydration, or oral rehydration failure and those unable to tolerate PO. • It is divided into the initial emergent rehydration phase and the subsequent second fl uid hydration phase. • Initial rehydration phase (correction of hypovolemia, mental status, perfusion) • Done over initial 2–4 h using NS or LR (20 cc/kg boluses). • There is no benefi t of using colloid over crystalloid fl uids for resuscitation (Cochrane Database Syst Rev 2000(2):CD000567). • Second phase of rehydration • Administration of maintenance fl uid needs (based on weight), replacement of any additional defi cits not replaced in the initial rehydration phase (estimated by weight loss or clinical evaluation at presentation), replacement of continuing losses (strict input and output recording), correction of electrolyte imbalances. • Choice of fl uids is based on the status of the patient’s sodium and potassium levels and the need to correct electrolyte imbalances. • NS to correct any residual volume defi cits. • 1/2 NS or NS for maintenance fl uids and continued loss replacement. NS is not usually maintenance fl uid; however, it may be benefi cial in preventing hyponatremia from hypotonic fl uids in hospitalized dehydrated pts (due to ↑ ADH in this population). 158 Pediatrics

COMPOSITION OF COMMONLY USED IV FLUIDS

Na Cl Lactate∗ K Ca Total (mEq/L) (mEq/L) (mmol/L) (mEq/L) (mg/dL) mosm/L

ECF† 142 103 1 4 8.5 290

NS (0.9%) 154 154 0 0 0 308

D5 ½ NS (0.45%) 77 77 0 0 0 432

D5 ¼ NS (0.22%) 38 38 0 0 0 355

Hypertonic 513 513 0 0 0 1026 saline (3%)‡

LR 130 109 28 4 3 274

5% albumin 130–160 130–160 0 0 0 265

Isolyte M 36 49 20 (acetate) 35 0 390

Isolyte P 23 20 23 (acetate) 340

D5W 0 0 0 0 0 278

∗Lactate and acetate are converted by the liver to bicarbonate to correct acidosis. †Representative ECF values for average normal individuals are provided for comparison. ‡Hypertonic saline use is limited to patients with severe (symptomatic) hyponatremia.

HYPERKALEMIA ( J Am Soc Nephrol. 1998;9:1535) Symptoms and Signs (generally when serum K >6.5 mEq/L) • General: Fatigue, weakness, paresthesias, tetany, ascending paralysis • Cardiac: Myocardial dysfunction; arrhythmias; ECG changes (directly related to severity): Peaked T waves → prolonged PR interval and loss of P wave → widened QRS interval → sine wave pattern (no perfusion) or ventricular ﬁ brillation → PEA or asystole

Causes • Pseudohyperkalemia (artifactual) • Lab error • Marked thrombocytosis (platelets >1,000,000/μL) • Marked leukocytosis (WBC >200,000/μL) • Ischemic blood draw (ie, clenched fi st during antecubital draw) • Hemolysis during blood draw or capillary sample (fi ngerstick, heelstick) • Familial pseudohyperkalemia (rare familial condition; blood leaks from RBCs while awaiting analysis) • Increased intake (rarely causative in absence of renal disease) • Potassium supplements, no-Na salt substitutes (contain K salts), medications • RBC transfusion • Transcellular shifts (ie, redistribution hyperkalemia) • Acidosis • Hyperosmotic states: Hyperglycemia, mannitol administration • Cellular necrosis and tumor lysis syndrome • Rhabdomyolysis • Hemolysis, hematoma, GI bleed • Drug intoxication: digitalis, fl uoride, β-blockers • Succinylcholine • Vigorous exercise Fluids, Electrolytes, and Acid–Base Balance 159

• Malignant hyperthermia • Autosomal dominant hyperkalemic periodic paralysis • Decreased excretion • Acute renal failure, chronic kidney disease (typically when GFR <20) • Primary adrenal disease (↑ renin, ↓ aldosterone): Congenital adrenal hyperplasia, Addison’s disease, adrenal hypoplasia, aldosterone synthetase deﬁ ciency, adrenoleukodystrophy • Hyporeninemic hypoaldosteronism (↓ renin, ↓ aldosterone): Interstitial nephritis, sickle cell disease, renal transplant • Renal tubular disease: Urinary tract obstruction, sickle cell disease, s/p renal transplant, type I or II pseudohypoaldosteronism • Drugs: ACEIs, ARBs, K-sparing diuretics (amiloride, triamterene, spironolactone), cyclosporine, NSAIDs, trimethoprim

Workup • Stop all IV and enteral K intake, stat ECG, repeat K (without tourniquet). • Repeat K as serum, plasma, or whole blood, paying attention to the way the blood is drawn (venipuncture without tourniquet and no heelstick or fi ngerstick to prevent pseudohyperkalemia). • Stat ECG. • Clinical history: Oral intake; medications; FH; recent major surgery, burns, or muscle injury. • Blood draw history: Diffi culty of blood draw, site (fi ngerstick, heelstick), delay in lab delivery of sample. • Labs: Serum Cr/BUN, blood gas if acidosis is suspected, serum renin and aldosterone level, urine/serum osmolarity and K to calculate transtubular potassium gradient

(TTKG): [Kurine/Kserum]/[OSMurine/OSMserum]. Score >7 suggests normal aldosterone function; score <7 suggests hypoaldosteronism.

Acute Treatment • Stabilize myocardium with calcium, induce intracellular K shift; then remove K. • Stabilize myocardium with either of the following:

• 10% CaCl2: 20 mg/kg (0.2 mL/kg) IV over 2–5 min; for adults, 500 mg–1g or • Ca gluconate: 100 mg/kg (1 cc/kg) IV over 2–5 min; for adults, 500 mg–3 g PEDIATRICS • Induce intracellular K shift with the following (temporizing measures lasting a maximum of 1–2 h until removal therapy can be arranged):

• Sodium bicarbonate: 1–2 mEq/kg IV over 5–10 min (ﬂ ush IV ﬁ rst if CaCl2 is given) • D25 (2 mL/kg CVL) or D10 (5 mL/kg PIV) immediately followed by 0.1 U/kg of regular insulin; monitor blood glucose to prevent hypoglycemia • Albuterol: 5 mg NMT • Remove K from the body. • Lasix: 1–2 mg/kg IV (if hemodynamically stable) • Kayexalate (sodium polystyrene) exchange resin: 1 g/kg in 4 mL 10% glucose (infants) or 10% sorbitol (children) PO or PR • Dialysis

Chronic Treatment • Address the underlying cause.

HYPOKALEMIA (NEJM 1998;339(7):451) Symptoms and Signs • Neuromuscular: Generalized weakness, fatigue, rhabdomyolysis, respiratory muscle dysfunction, paralysis • GI: Constipation, ileus 160 Pediatrics

• Renal: Nephrogenic diabetes insipidus • Cardiac: Arrhythmias, ECG changes (U waves, T-wave fl attening, ST-segment changes, QT prolongation → VT → VF) Causes • Pseudohypokalemia (artifactual): Marked With normal acid–base status leukocytosis (>100,000/μL) and delayed • Diuretic phase of acute tubular analysis necrosis, postobstructive diuresis, • Transcellular shift (redistribution osmotic diuresis hypokalemia) • Tubular toxins: Amphotericin, cis- • Alkalosis platin, aminoglycosides • Insulin administration before sample • Hypomagnesemia (small effect), insulinoma • Interstitial nephritis • Drugs or toxins (barium, theophylline, With metabolic alkalosis toluene, CCB, chloroquine) • ↓ UCl(<10–20 mEq/L): Emesis, NG • β-Agonists suction, chloride-losing diarrhea, • Hypokalemic periodic paralysis CF, posthypercapneic state, prior • Extrarenal losses (random urine K <20 mEq/L) loop or thiazide diuretic use • ↑ • Diarrhea UCl(>20 mEq/L): nl BP: Bartter’s • Sweat syndrome, Gitelman’s syndrome, current loop or thiazide diuretic use • Laxative abuse • ↑ U (>20 mEq/L): ↑ BP: adrenal • Villous adenoma of rectosigmoid colon Cl adenoma or hyperplasia, renin- • Fasting or inadequate intake secreting tumor, licorice ingestion, • Renal losses (random urine K >20 mEq/L) Liddle syndrome, renovascular With metabolic acidosis disease, Cushing syndrome • Distal (type I) or proximal (type II) RTA • Ureterosigmoidostomy • DKA • Carbonic anhydrase inhibitors Workup • Accurate BP, thorough history to determine inciting factors • Blood gas, spot urine and serum K and Osm, 24-h urine K → • TTKG = [Kurine/Kserum]/[OSMurine/OSMserum] TTKG >7 refl ects inappropriate renal loss of K; <3 refl ects appropriate renal K retention

Treatment • Treatment should be determined by the cause. • Serum K levels >3 mmol/L rarely cause signiﬁ cant problems in otherwise healthy individuals; levels <3.0 are associated with an increased risk of arrhythmias.

• Oral replacement: KCl or KPO4, ~2–4 mEq K/kg/d in two to four divided doses; adult dose, 40–100 mEq/d in two to four divided doses ↓ • IV replacement therapy (only in urgent cases, ie, very or ECG changes): KCl or KPO4 0.5–1.0 mEq potassium/kg delivered at 0.1–0.4 mEq/kg/h (maximum rate, 10 mEq/h); must be given in a controlled, monitored setting; concentrations >6 mEq/100 mL must be given via CVL

HYPERNATREMIA (NEJM 2000;342:1493) • Serum Na is a reﬂ ection of TBW more than total body sodium → volume status determination is critical to the evaluation and treatment of sodium disturbances.

Signs and Symptoms • Tachypnea, confusion, muscle weakness or cramping, lethargy, coma, seizures, depressed deep tendon reﬂ exes Fluids, Electrolytes, and Acid–Base Balance 161

Hypernatremia

Hypovolemic Euvolemic Hypervolemic

Hypovolemic Euvolemic Hypervolemic hypernatremia hypernatremia hypernatremia

↓ ↑ UOSM UOSM ↓ ↑ UOSM UOSM ↑FENa nl FENa UNa>20 UNa< 20

Renal Losses Extrarenal • Diabetes • Transient • Exogenous Na • Mineralocorticoid • ATN, diuretic Losses insipidus hypernatremia† administration excess phase • Diarrhea • Hyperaldosteronism • Osmotic • Increased diuresis insensible • Postobstructive losses diuresis • Incorrectly mixed formula (diluted) Figure 15-1 Evaluation of hypernatremia. † Intracellular osmole generation → osmotic water shift → transient ↑ serum Na, as may be seen after vigorous exercise, seizures, etc.

Workup • History of recent vigorous exercise, trauma, dietary intake, polyuria, renal or CNS insult. • Volume status: Vital signs, orthostatic hypotension, dry or wet mucous membranes, peripheral edema, BUN/serum Cr ratio (>20 indicative of hypovolemia). • Labs: Guided by volume status; see Figure 15-1. • Diagnosis of diabetes insipidus: See Chapter 14 or Ann Intern Med 2006;144(3):186.. Treatment • Hypervolemic hypernatremia: Correct underlying cause • Euvolemic hypernatremia: Correct underlying cause • Hypovolemic hypernatremia (dehydration): Results from relative loss of free water compared PEDIATRICS with Na (rarely Na excess); two methods of correction (described in the following sections). Method 1 (Calculation Method) 1. Calculate the free water defi cit. TBW × [(Serum Na – 145)/145] TBW (L) = [Baseline weight in kg × Age-appropriate constant] (0.8 for premature infants; 0.6 for infants, children, and adult males; 0.5 for adult females). • Divide the defi cit by 2 or 3 to correct hypernatremia slowly over 2–3 d to avoid rapid correction and possibility of inducing cerebral edema from rapid water shift from extracellular to intracellular space. 2. Calculate MIVF fl uid rate for 24 hour period. 3. Calculate maintenance Na needs for 24 hr period (2-3 mEq/kg/d) 4. Combine values in steps 1-3 to determine daily IVF fl uid type, volume and rate:

1 Concentration of Na (mEq/L) in D5W = [Maintenance Na]/[ /3 or ½ of free water defi cit volume + Daily maintenance fl uid volume] • Round to standard IV fl uid solution if possible (see table above, “Composition of Com- monly Used IV Fluids”) 162 Pediatrics

Example: (22 kg child, serum Na 165 mEq/L, 10% dehydration = 2.2 L total fl uid defi cit) Defi cit Fluid Na Free water defi cit∗ 1800 mL (free water) 0 mEq

Remaining deﬁ cit† 400 mL (isotonic saline) 56 mEq (= 140 mEq/L × 0.4 L) Maintenance per 24 h 1540 mL 55 mEq (2–3 mEq/kg/day)

∗based on free water deﬁ cit formula above. †based on estimation of percent dehydration (see beginning of chapter)—free water deﬁ cit.

Total Fluid: ½ free water defi cit (900 mL) + remaining defi cit (400 mL) + maintenance fl uid (1540 mL) = Total fl uid 2840 mL/day = 118 mL/h Total Sodium: Na in isotonic remaining defi cit replacement (56 mEq) + maintenance Na (~55 mEq) = Total (111 mEq/day) IVF Na concentration: 111 mEq Na/2840 mL = 39 mEq Na/1000 cc Final fl uid and rate = D5W + 39 mEq Na/L @ 118 cc/h

• Hypocalcemia and rarely tetany may occur with correction of hypernatremia and acidosis; monitor blood ionized Ca and add Ca to IVF if necessary • Hyperglycemia is common in patients with hypernatremia. • Monitor serum Na, ionized Ca, glucose, and urine output closely during rehydration. • Serum Na >180 mEq/L requires slow careful correction and rarely dialysis. Dialysis is usually indicated in the presence of renal failure (elevated serum Cr) and poor urine output. • Under no circumstances should serum Na be allowed to decrease at a rate >10–15 mEq/L per 24-h period (~0.5 mEq/h) because of the risk of cerebral edema) Method 2 (Estimation Method) • Based on estimation of expected change in serum Na given 1 L of fl uid with a specifi ed concentration of Na. (Intensive Care Med 1997;23:309) + [Na]serum per L infused = [ [Na]infusion – [Na]serum ] / [ TBW 1] • Example (30-kg child, serum Na 160, using D5½NS): Δ × + Naserum = [77 – 160]/[(0.6 30 kg) 1] = –4.4 mEq serum sodium change after administration of 1 L of fl uids • Calculate expected change based on different fl uid concentrations (see table below) used for rehydration (must take into account total daily fl uid to be delivered; do not lower serum Na >10–15 mEq/L per 24-h period). HYPONATREMIA (NEJM 2000;342:1581) • Serum Na is a refl ection of TBW more than total body sodium caused by free movement of water across cell membranes. Volume status determination is critical to the evaluation and treatment of patients with sodium disturbances. • Symptoms and signs: Headache, nausea, vomiting, muscle cramps, lethargy, restlessness, disorientation, depressed refl exes, seizure, coma, permanent encephalopathy, respiratory arrest, brainstem herniation. Causes and Workup (Figure 15-2) Treatment • Asymptomatic hyponatremia: See below for treatment based on volume status; rate of correction ≤12 mEq/d (≤ 0.5 mEq/L/h). • Symptomatic hyponatremia: Initial rapid correction of Na to resolve symptomatology (eg, 3 mL/kg 3% NS over 30 minutes to stop seizures, usually accomplished after Na is approximately 120 mEq/L); then continue correct at a rate not to exceed 12 mEq/L/d. • Whether symptomatic or asymptomatic, monitor Na very closely during replacement (eg, Q2–4h) and monitor closely for signs of CNS demyelinization (central pontine myelinolysis): Spasticity, pseudobulbar palsy. Hypervolemic Hyponatremia • Free water restriction, diuretics, increase effective circulatory volume (vasodilators in CHF, colloids in hypoalbuminemic state) Fluids, Electrolytes, and Acid–Base Balance 163

Hyponatremia

Hypertonic Hypotonic Isotonic

† Transcellular H2O Shift* Lab Artifact Hypotonic (effective osmoles) (ineffective osmoles) hyponatremia • Hyperglycemia • Hypertriglyceridemia (true hyponatremia) • Mannitol (>1000 mg/dL) • Hyperproteinemia (>10g/dL) • Glycine/sorbitol bladder irrigation (GU procedures) Hypovolemic Euvolemic Hypervolemic

Hypovolemic Euvolemic Hypervolemic hyponatremia hyponatremia hyponatremia

FENa>1–2% FENa<1% ↓ ↑ FENa>1–2% FENa<1% UOSM (<100) UOSM (>100) UNa>20 UNa< 20 UNa>20 UNa< 20

Renal Losses Extra Renal • 1° polydipsia • SIADH • Renal • CHF • Diuretics Losses • low solute • Hypothyroidism failure • Cirrhosis • Na-wasting • GI losses intake • Adrenal • Nephrotic nephropathy • Increased (malnutrition, insufficiency syndrome • Adrenal insensibles alcoholism, insufficiency • Third-spacing overdiluted • Cerebral salt (eg, pancreatitis) formula) wasting • CF Figure 15-2 Evaluation of hyponatremia. ∗ True hyponatremia occurs with hyperglycemia caused by increased osmolality in the extracellular space and transcellular water shift from intracellular to extracellular space. To calculate the effect on Na in mEq/L: each 100 mg/dL ↑ in glucose above 100 = ↓ [Na] 1.6 mEq/L. † lab artifact or pseudohyponatremia is attributable to excess lipids or protein in the blood altering Na determination in auto- mated analyzers. To calculate the effect on Na in mEq/L: [Triglycerides × 0.002] or [0.25 × (Total protein – 8)]. PEDIATRICS Euvolemic Hyponatremia • Treat the underlying cause. Hypovolemic Hyponatremia Method 1 (Calculation Method) 1. Calculate the fl uid defi cit: (ie, account for isotonic Na losses): % Dehydration × wt (kg) 2. Calculate extra sodium defi cit: × × Absolute Nadefi cit = Distribution factor (135-[Na]serum) weight in kg at baseline (Distribution factor is 0.6 for Na.) 3. Calculate maintenance Na (2–3 mEq/kg/d). 4. Calculate maintenance fl uid total volume. Example: 22-kg child; BSA, 0.87 m2; 10% dehydration = 2.2 L total fl uid defi cit Example: 22 kg child, serum Na 125, 10% dehydration, BSA 0.87 m2 (2.2 L total fl uid defi cit) Defi cit Fluid Na 10% dehydration 2200 mL 308 mEq (140 mEq/L × 2.2 L) (isotonic saline) Extra Na defi cit 132 mEq Maintenance (24 h) 1392 mL 55 mEq 164 Pediatrics

IVF = (308 + 132 + 55) mEq Na in (2200 + 1392) mL D5W = 495 mEq Na in 3592 mL D5W = D5W + 138 mEq Na/L @ 150 cc/h

• May need to combine two different standard IVF infusions to approximate goal Na concentration. Method 2 (Estimation Method) • See above under “Hypovolemic Hypernatremia.”

ACID–BASE DISORDERS Normal Values for Blood Gas Analysis

CO † Listed as pH (± 0.04) P 2 (± 4) PaO2 HCO3 (± 4) ABG 7.4 40 Varies 24

CBG 7.35–7.4 40–45 Varies 24

VBG 7.30–7.35 45–50 Varies 24

† Normal values for PaO2 depend on the FiO2, arterial–alveolar (A–a) oxygen gradient, and age. In general, SpO2 on VBG ~25% less than ABG (remains ↑ sepsis, greater diﬀ erence in ↓ cardiac output states).

General Approach To Acid–Base Disorders (Figure 15-3) ACID–BASE DISORDERS: DIFFERENTIAL DIAGNOSIS AND ADDITIONAL TESTING

Additional Additional Testing Testing Diff erential Diagnosis Ethanol Methanol Ethylene glycol Isopropanol Glycine Glycerol

OSM Gap Present Mannitol 1 Osmolal gap: CKD

Methanol OSM –OSM meas calc Uremia (Normal <10) DKA/AKA Paraldehyde Anion GapAnion Present Metabolic Acidosis INH, Iron Lactic acidosis: ∗ Anion Gap : Type A (hypoxemic) or type B (nonhypoxemic) 2

OSM calculation: OSM Gap Absent Na – (Cl + HCO )† Salicylates 3 [2 × Na (mEq/L)] + (Normal, 8–12) CO [BUN (mg/dL)/2.8] + Toluene [Glu (mg/dL)/18] +

(continued on next page) Fluids, Electrolytes, and Acid–Base Balance 165

Additional Additional Testing Testing Diff erential Diagnosis Renal Pathology: RTA (I or IV) Paraproteinemias 3

+ UAG Br- intoxication Mild CKD Renal Pathology: Urine anion gap‡ : RTA II Extrarenal Causes: (U + U ) – U GI losses of bicarbonate Na K Cl 4 [+]→ renal cause (diarrhea; intestinal or [–] → nonrenal pancreatic ﬁ stula) Anion GapAnion Absent Metabolic Acidosis Dilutional (rapid infusion IVF – UAG

without HCO3) Posthypercapnia Acetazolamide TPN Ureterosigmoidostomy Neuromuscular disorders: Myasthenia gravis, DMD, GBS, NMJ disorders, severe hypophosphatemia 5 CNS depression: Sedatives, trauma, CNS lesions

Acidosis Central sleep apnea, OSAS Respiratory Respiratory Obstructive lung disease Primary Hyperventilation Secondary Hyperventilation CNS: Pain, anxiety (Hypoxia → Hyperventilation) Drugs: Salicylates, progesterone, Pneumonia 6 β-agonists, methylxanthines Asthma exacerbation Pregnancy Pulmonary edema Sepsis Restrictive lung disease PEDIATRICS

Respiratory Respiratory Alkalosis Hepatic failure Altitude sickness Saline (Cl–) Responsive GI losses: vomiting, NG tube Diuretics 7 <10 Posthypercapnia

§ Volume depletion Saline (Cl–) Resistant Hypovolemic: Spot U Cl Diuretic usage Euvolemic: 1° or 2° hyperaldosteronism

>10 ↑ Metabolic Alkalosis ( BP) 8 Moderate to severe ↓ K exogenous alkali Bartter’s syndrome Gitelman’s syndrome

∗Rarely, decreased AG may be noted; diﬀ erential diagnosis includes paraproteinemia, Br- intoxication, hypoalbuminemia, hyponatremia, and hypermagnesemia. †Must add 2.5 to ﬁ nal AG result for each 1 g/dL albumin ↓ below 4. ‡ + Indirect assay for renal NH4 excretion; not applicable if pt volume-depleted or ketotic. If <0 (negative value) with acidemia, implies ↑ renal NH4+ excretion (appropriate). If > 0 (positive value) with acidemia, implies renal failure + to secrete acid as NH4 (NEJM 1988;318:594). §Requires initiating event (loss of acid, exogenous alkali, contraction alkalosis, or posthypercapnia) and maintenance factor (hypovolemia, hypokalemia, hyperaldosteronism). Step 1 Step 2 Step 3 Step 4 2 PaCO ↑ 8 Cl >40 2 = 0.7 mmHg

3 SPOT U SPOT pCO <10 >10 7 HCO ↑ Metabolic alkalosis with respiratory compensation 1 mEq/L (least predictable among disturbances) represented by a boxed number.) alkalosis pH > 7.45 3 3 HCO HCO ↓ ↓ 2 2 <40 6 2 = 2 mEq/L = 5 mEq/L 2 2 PaCO PaCO Δ

× × Δ pCO pCO pCO ↓ ↓ Respiratory alkalosis pH = 0.008 pH = 0.017 Acute 10 mmHg Δ Chronic 10 mmHg Δ ABG 3 3 HCO ↑ HCO ↑ 2 2 >40 5 2 = 1 mEq/L = 3–4 mEq/L 2 2 PaCO PaCO Δ

× × Δ pCO pCO pCO ↑ ↑ Respiratory acidosis pH = 0.008 pH = 0.003 Acute 10 mmHg Δ Chronic 10 mmHg Δ acidosis 2 pH < 7.35 4 ] + 8 PaCO 3 ↓ (–) UAG (+) (–) 3 <40 2 = [1.5 x HCO = last two digits of pH = 1.2 mmHg

2 2 2 3 Anion Gap pCO (+) (–) General approach to acid–base disorders. (Note: See preceding table for a differential diagnosis associated with each disorder HCO ↓ (+) OSM Gap 1 Metabolic acidosis with respiratory compensation Gap (see text) Estimate: PaCO 1 mEq/L Estimate: PaCO ΔΔ Figure 15-3 166 Fluids, Electrolytes, and Acid–Base Balance 167

Step 1: Obtain arterial pH to determine acidosis (<7.35) or alkalosis (>7.45). • Obtain ABG. If not possible, CBG is acceptable but not preferred. Venous blood gas should not be used other than for following daily trends in chronic patients.

Step 2: Identify primary derangement and any compensation. • See Figure 15-4 and compensation table below. Arterial blood [H+] (nmol/L) 100 90 80 70 60 50 40 30 20 60 120 110100 90 80 70 60 50 40 56 52 35 48 Chronic Metabolic 44 respiratory alkalosis 30 acidosis 40 ] (mmol/L) 3 − 36 25 32 Acute 20 28 respiratory acidosis 24 Normal Acute 15 20 respiratory alkalosis 16 Arterial plasma [HCO 10 12 Chronic 8 Metabolic respiratory PCO2(mm Hg) acidosis alkalosis PEDIATRICS 4 0 7.0 7.1 7.2 7.3 7.4 7.5 7.6 7.7 7.8 Arterial blood, pH Figure 15-4 Acid–base nomogram. (Reproduced with permission from Fauci AS, Kasper DL, Braunwald E, et al J: Harrison’s Principles of Internal Medicine, 17th ed. Copyright © The McGraw-Hill Companies, Inc. All rights reserved.)

SIMPLE ACID–BASE DISTURBANCES AND ACID–BASE DISTURBANCES WITH PARTIAL COMPENSATION

PaCO2 pH (mm Hg) HCO3 Acid–Base Status <7.35 >45 Normal Acute respiratory acidosis <7.35 >45 ↑ Respiratory acidosis with partial metabolic compensation

<7.35 35–45 ↓ Acute metabolic acidosis <7.35 <35 ↓ Metabolic acidosis with partial respiratory compensation

(continued on next page) 168 Pediatrics

PaCO2 pH (mm Hg) HCO3 Acid–Base Status 7.35–7.40 >45 ↑ Respiratory acidosis with maximal metabolic compensation 7.35–7.45 35–45 Normal Normal; no acid–base disturbance 7.35–7.40 <35 ↓ Metabolic acidosis with maximal respiratory compensation 7.40–7.45 >45 ↑ Metabolic alkalosis with maximal respiratory compensation 7.40–7.45 <35 ↓ Respiratory alkalosis with maximal metabolic compensation >7.45 >45 ↑ Metabolic alkalosis with partial respiratory compensation >7.45 <35 ↓ Respiratory alkalosis with partial metabolic compensation >7.45 35–45 ↑ Acute metabolic alkalosis >7.45 <35 Normal Acute respiratory alkalosis

Step 3: Identify any concomitant disorder (mixed acid–base disorder). • In simple (single) acid–base disorders, the compensation for the primary disturbance will never overcompensate(ie, a primary acidosis will never be compensated to a pH >7.40, and a primary alkalosis will never be compensated to a pH <7.40). • Effective compensation depends on the appropriate function of the compensating organ system (eg, respiratory system in metabolic disturbances, the kidneys in respiratory disturbances). • Respiratory compensation of metabolic disturbances is accomplished fairly rapidly (minutes to hours), but metabolic compensation of respiratory disturbances may take longer (acute = hours; chronic = days).

• Every disorder with AG >20 or HCO3 <10 will have a component of metabolic acidosis. • For each type of primary disturbance, a compensation equation exists to predict the

expected response. If HCO3 or pCO2 has changed as predicted by the equation, disorder is likely a simple (single) disorder. Otherwise, a superimposed disorder should be sought: ∴ • PaCO2 lower than expected superimposed 1° respiratory alkalosis ∴ • PaCO2 higher than expected superimposed 1° respiratory acidosis ∴ • HCO3 lower than expected superimposed 1° metabolic acidosis ∴ • HCO3 higher than expected superimposed 1° metabolic alkalosis Calculation of ΔΔ Gap in Anion Gap Metabolic Acidosis • Allows determination of simple metabolic acidosis vs. mixed disorder ↓ ↑ • Basis: Serum HCO3 should by 1 for each 1 of AG above normal • Δ Δ HCO3 = (Normal – Measured HCO3), AG = (Calculated – Normal AG) • ΔΔ Δ Δ Gap = HCO3 – AG (>5 is signiﬁ cant) • Δ ≈ Δ → HCO3 AG simple AG metabolic acidosis • Δ Δ → HCO3 > AG AG metabolic acidosis with superimposed metabolic alkalosis • Δ Δ → HCO3 < AG AG metabolic acidosis w/ superimposed non anion gap metabolic acidosis Step 4: Perform additional testing (depending on the type of disorder) and generate a differential diagnosis for the disturbance. See “General approach to acid-base disorders” algorithm.

Available at www.AccessPediatrics.com • Hypercalcemia • Hypocalcemia GENERAL CLINICAL INFORMATION PEDIATRICS

Social history: 1997;151:569). . The clinical presen- ux, atopic disease. infection, refl cient for diagnosis Arch Pediatr Adolesc Med suffi 169 hydrocephalus, presence of shunt), prematurity, Helicobacter pylori tone, ↓ passage of gastric contents into ux (GER) is normal None are required for the diagnosis of GERD. Consider gain. ux, blood in the stool, trends in weight or ↑ A thorough H&P is Reassurance 50% in infants age 0–3 mo; 67% in children age 4 mo; 5% of children 50% in infants age 0–3 mo; 67% of GERD can be divided into three systems: Respiratory (asthma and / of GERD can be divided into may be used for complications (strictures,ux with symptoms; esophagoscopy Gastroesophageal refl Gastroesophageal If step 1 interventions fail, add pharmacologic therapy: H2R antagonist (eg, If step 1 interventions fail, add pharmacologic therapy: H2R pain, irritable, dyspepsia), presence ux symptoms after feeding (regurgitation, Thicken formula or breast milk with rice cereal (add 1 Tbsp/oz of formula), Thicken formula or breast milk with rice cereal (add 1 Tbsp/oz stool antigen testing for children and adolescents if the patient c/o abdominal stool antigen testing for children and adolescents if the patient at a 30- to 45-degree angle, small frequent ux precautions (ie, sleeping supine cosa. Consider use in infants with esophagitis or ulcers. of GER. stemil) if milk-protein allergy is strongly suspected as the cause Surface agents (eg, sucralfate, sodium alginate) help protect ulcerated gastric mu- Surface agents (eg, sucralfate, sodium alginate) help protect Consider changing to casein hydrolysate formula (ie, Nutramigen, Alimentum, Prege- Consider changing to casein hydrolysate formula (ie, Nutramigen, nitions: refl after feeding). feeds, frequent burping, maintain upright position for 30 min PPIs are more ranitidine) or PPI (eg, lansoprazole; not currently FDA approved). before morning effective at acid suppression and are most effective if given 30 min feeds. Tobacco or alcohol use, psychological factors (eg, stressors, anxiety, depression). PMH: ofTobacco or alcohol use, psychological factors (eg, stressors, anxiety, eczema, neurologic issues ( surgery, ENT disease. Family history: HSM, seizures, micro-arrhea, constipation, abdominal pain or distension, fever, lethargy, diseases (eg, HIV). or macrocephaly, FTT, genetic d/o (trisomy 21), other chronic ing feeds (Sandifer syndrome), irritability, and poor weight gain (2° to vomiting or dys- ing feeds (Sandifer syndrome), or chronic cough, recurrent pneumonia, upper phagia). Some present with wheezing stridor), apnea, or ALTE. airway symptoms (eg, recurrent hoarseness of the voice, weight loss, anemia, wheezinggitation. Some present with dysphagia, esophagus (rare). or chronic cough, recurrent pneumonia, food impaction, and Barrett’s tite, refl of blood or bile, force of refl Infants and young children present with recurrent vomiting, arching of the back dur- Infants and young children present History: Ask for details of meals (type, volume and frequency), recent change in appe- History: Ask for details of meals (type, volume and frequency), Signs suggesting non-GER cause of vomiting: Bilious or forceful vomiting, GI bleeding, di- Signs suggesting non-GER cause of vomiting: Bilious or forceful • • Older children and adolescents present with heartburn or retrosternal chest pain and regur- Older children and adolescents Step 2: Step 1: H. pylori r/o anatomical abnormali- pain ± dyspepsia or vomiting. In unclear cases, consider UGI to impedance may be used toties, esophageal pH monitoring or multichannel intraluminal correlate refl esophagitis) and to rule out anatomic abnormalities. chronic cough, apnea and ALTE, recurrent aspiration pneumonia), ENT (hoarseness, chronic cough, apnea and ALTE, recurrent OM), and GI (esophagitis, esophageal laryngitis, sinusitis, dental erosions, esophagus). ulcers, esophageal strictures, Barrett’s tation is based on the age of the child: tation is based on the age of the GERD in infants: • • • • • • Physiological GER: History and physical exam: Complications Laboratory studies/evaluation: the esophagus; GERD consists of symptoms and complications of GER; rumination is the esophagus; GERD consists of gastric contents into the mouth for self-stimulation. voluntary habitual regurgitation The prevalence of GERD is unknown. age 10–12 mo; 1.4–8.2% in children age 3–17 yr ( age 10–12 mo; 1.4–8.2% in children • • • • • Treatment Diagnosis Prevalence of GER: Defi • • • Gastroenterology REFLUX GASTROESOPHAGEAL • CHAPTER 16 170 Pediatrics

• Prokinetic agents are (eg, metoclopramide, bethanechol, erythromycin) generally not helpful. However, in severe cases a trial of bethanechol may be useful. • Surgical intervention: Nissen fundoplication is indicated in patients who failed or cannot be weaned off medical therapy and those with frequent aspiration related issues. • Children and adolescents with GERD: • Lifestyle changes: Sleep on the left side with the head of the bed elevated; avoid caffeine, chocolate, spicy food, tobacco exposure, alcohol; recommend weight loss for obese children; ± psychological evaluation and support; ± intermittent antacids (eg, magnesium hydroxide, aluminum hydroxide, calcium carbonate).

• If above interventions fail, provide a trial of H2RA or PPI. • Surface agents (eg, sucralfate, sodium alginate) help protect ulcerated gastric mucosa. Consider use in children with esophagitis or ulcers.

HEPATITIS Infectious Hepatitis • Most often caused by one of ﬁ ve viruses: Hepatitis A (~30%), B (~50%), C (~20%), D, and E. Other viruses reported to cause hepatitis as part of generalized infection include CMV, HSV, VZV, EBV, rubella, coxsackievirus, and adenovirus.

SEROLOGY AND NUCLEIC ACID TESTING PROFILE FOR HEPATITIS A, B, AND C VIRUSES

HBc HBc HCV HCV Scenario ALT HBsAg IgM IgG HBeAg HBeAb HBsAb HBVDNA Ab RNA Acute HAV∗ ↑ Prior HAV or Normal vaccine∗ Acute HBV ↑ ++––––+ Acute HBV ↑ –+––––± “window period” Chronic HBV, ↑ +–++ – – + active replication Chronic HBV, ↑ +–+–––+ “pre core” mutant Chronic HBV, Normal + – + – + – – carrier Prior HBV Normal – – + – – ± – Prior HBV Normal – – – – – + – vaccine Acute HCV ↑ –+ Chronic HCV Normal ++ or ↑ False + Normal + – HCV or prior infection with eradication

∗Acute HAV: ALT↑, HAV IgM ¢, HAV IgG ; prior HAV or vaccinated: ALT is normal, HAV IgM , HAV IgG ¢. Adapted from: Tarascon Internal Medicine and Critical Care Pocketbook, 4th ed. 2009:68. Gastroenterology 171

Noninfectious Hepatitis NONINFECTIOUS HEPATITIS: CAUSES, DIAGNOSIS, AND TREATMENT

Cause Diagnosis Treatment Comments Hereditary ↑ Transferrin satura- Phlebotomy to keep ferri- Autosomal reces- hemochroma- tion, ferritin, genetic tin <50 ng/mL; chelation sive, ↑ iron absorp- tosis (HH) testing, liver biopsy (deferoxamine) tion from intestine Iron overload ↑ Iron, TIBC, ferritin Phlebotomy to keep fer- Sickle cell disease, (multiple trans- ritin <50 ng/mL; chela- β-thalassemia major, fusions) tion (deferoxamine) aplastic anemia Steatohepatitis Liver US, liver biopsy No current medical treat- ↑ Triglyceride accu- ments; however, modify mulation in liver risk factors (obesity, hyperlipidemia, DM control) Autoimmune Serum ANA, anti- Steroids, azathioprine or Type I AIH: hepatitis (AIH) smooth muscle Ab 6-MP, liver transplant Associated with (ASMA), anti-LKM1 ANA, ASMA antibody, total IgG Type II AIH: Associ- ated with anti-LKM1 Wilson’s AST>ALT; ↓ Cerulo- Chelation: Penicillamine 1 in 30,000 births, disease plasmin (<20 mg/dL); (give pyridoxine); trientine AR defect in ↑ copper in urine is second line; give 1 h hepatocellular (>40 mcg/24 h) and on before or 2 h after meals; copper transport liver biopsy add PO zinc in mainte- (>250 mcg/g dry nance therapy after chela- weight); genetic testing; tion; liver transplantation Kayser-Fleischer rings; for those with fulminant neurologic d/o (35%) hepatic failure `-1-antitrypsin ↓ serum AAT (<80 mg/dL; Liver transplantation In liver, retention of (AAT) defi ciency range, 100–300), mutant AAT protein PI typing leads to demise of hepatocytes PEDIATRICS Muscle ↑ CK, LDH, aldolase, Based on cause Inborn errors of disorders and aminotransferases metabolism or acquired muscle disorder (eg, polymyositis, seizure, heavy exercise) Other causes: Medications and toxins (acetaminophen, alcohol, vinyl chloride, INH, VPA, MTX, phenytoin, herbal preps containing pyrrolizidine alkaloids, mushroom poisoning), hypo- or hyperthyroidism, anorexia nervosa, celiac disease, CF

FULMINANT LIVER FAILURE • Defi nition: Acute impairment of liver function with coagulopathy and hepatic encephalopathy within 8 weeks of the onset of a “hepatitis-like” illness in the absence of known liver disease (Figure 16-1). • Etiology: See noninfectious and infectious causes of hepatitis sections. Also see hepatomegaly section. • Presentation and Management: See Figure 16.1. • Treatment: Treatment of specifi c causes; identifi cation of etiologies amenable to early therapy (eg, acetaminophen, HSV, galactosemia) is imperative. • Prognosis: Usually poor, especially if undetermined hepatitis, non–acetaminophen drug induced, Wilson’s disease, age <10 or >40 yr, encephalopathy stage III or IV, jaundice >1 wk, INR >4, metabolic acidosis with elevated creatinine, factor VII <9%, factor V <20% (Gastroenterology 1989;97(2):439). 172 Pediatrics

Start Investigation for Liver Failure Clinical Presentation Fever, malaise, nausea or vomiting, Labs: CBC, ABG, Chem 10, ammonia, diarrhea, jaundice, HSM, abdominal fibrinogen, ESR, lipid profile, UA with cx, urine distension (± ascites), pain, asterixis, Iytes, osmolality Dupuytren’s contractures, fetor hepaticus, Metabolic screen: SAA; lactate; pyruvate, coagulopathy, ↑ ammonia, acylcarnitine profile; AFP; UA and urine organic encephalopathy (combative, lethargic) acids reducing substances, ketones Autoimmune hepatitis screen: Immunoglobulins, ANA, anti-SM antibody, anti-LKM1 antibody Other screen: AAT, copper level, ceruloplasmin, ferritin, iron panel Laboratory Studies Viral tests: Hepatitis panel, EBV PCR, CMV ↑ ↑ AST, ALT usually >1000, Direct antigenemia, adenovirus PCR and rapid screen, ↑ bilirubin >15–20 mg/dL, PT/PTT/INR, enterovirus PCR, parvovirus B19 titers ↓ Factors V/VII Drug screen: Acetaminophen, aminosalicylic acid, urine/blood drug screen Radiology: Abdominal US with Doppler; head CT Other studies: EEG Fulminant Liver Failure Biopsy: Transjugular liver biopsy + venogram INR >1.5 + encephalopathy or (send tissue for virology, electron microscopy, INR >2 ± encephalopathy histology, antibody staining, enzyme assay and copper/iron stains)

Management 1. ABC 2. Supportive care: a. Manage bleeding: FFP, cryoprecipitate, PRBC, Vitamin K, IV PPI b. Manage hypoglycemia (glucose IV) or electrolyte imbalance if present; plan for early nutrition (eg, TPN) c. Manage encephalopathy: Airway management, cerebral edema (elevate head of bed, hyperventilation, mannitol); no sedation, acetaminophen or NSAIDs; hyperammonemia (low-protein diet, Iactulose) d. Manage infections sepsis, spontaneous bacterial peritonitis e. IV N-acetylcysteine may benefit patients with non-acetoaminophen liver failure (Gastroenterology 2009;137(3):856) 3. Admit to ICU 4. Consult GI or Liver team

Figure 16-1 Diagnosis, workup, and management guidelines for fulminant liver failure.

END-STAGE LIVER DISEASE (ESLD) • Presentation • Children with ESLD may present well compensated or with acute-on-chronic liver failure (see Figure 16.1). • FTT, abdominal distension, HSM, and jaundice are common signs of ESLD in children. Less commonly, digital clubbing, spider angiomata, palmar erythema, Dupuytren’s contractures, gynecomastia, and testicular atrophy are observed. • Etiology: See noninfectious and infectious causes of hepatitis section. Also see hepatomegaly section. • Diagnostic studies: See fulminant liver failure (Figure 16.1). In general, ↓ Na, ↑ ammonia, ↓ albumin, ↑ bilirubin, ↑ PT/INR, ↓ platelets. AST, ALT, and Alk Phos levels are usually elevated but may fall late in the course of disease. • Treatment: Management of complications (listed below), correction of underlying cause if possible, liver transplantation when indicated. • Complications • Portal HTN • Pathogenesis: ↑ Portal resistance, ↑ portal blood ﬂ ow, ↑ cardiac output, ↓ systemic vascular resistance. • Management: Follow physical exam for signs of worsening liver failure and development of ascites or varices; assess for GI bleeding (CBC, hemoccult). Consider serial abdominal US with Doppler. Gastroenterology 173

• Hepatic Encephalopathy • Reversible neurologic abnormalities seen in patients with cirrhosis (see table below). Proposed etiologies include neurotoxicity of ammonia and its metabolites and ↑CNS GABA activity. • May be precipitated by various events, including infection, dehydration, constipation, or medication noncompliance.

STAGES OF HEPATIC ENCEPHALOPATHY

Indicator 0 I II III IV

Level of Normal Confused, Drowsy, Stuporous Comatose consciousness irritable, loss responds to but arous- with or with- of spatial simple com- able, marked out response orientation mands confusion to pain

Refl exes Normal Normal Hyperrefl exic Hyperrefl exic Arefl exic + Babinski sign

EEG Normal Minimal Slow rhythm Grossly Grossly changes with triphasic abnormal abnormal waves with delta waves

Other Altered Dysarthria, Marked Decerebrate sleep habits incontinence, dysarthria, or decorticate asterixis rigidity posturing

• Varices • Pathogenesis: ↑ Portal pressure (>12 mm Hg) causes development of portosystemic collaterals in the stomach and esophagus. Variceal wall tension, diameter, and pressure gradient contribute to the risk of bleeding. • Prevention of bleeding: Propranolol – will ↓ HR, ↓ cardiac output, ↓ portal inﬂ ow, and

blocks vasodilatation. See GI bleed section for treatment of acute variceal bleeding. PEDIATRICS • Hepatorenal Syndrome (Lancet 2003;362(9398):1819) • Deﬁ nition: Cirrhosis or acute liver failure with CrCl <40 mL/min (not caused by volume depletion, infection, renal obstruction, or drug-induced renal injury) and unresponsive to volume expansion and without proteinuria or hematuria (see table below). • HRS Type I: Progressive with creatinine doubling in <2 wk → poor prognosis. • HRS Type II: Slow disease progression. • Treat with vasoconstrictors: Midodrine or Norepinephrine + Octreotide + albumin have been used in adult patients. Transjugular intrahepatic portosystemic shunt (TIPS) for refractory cases as a bridge to liver transplantation. (Hepatology 1999;29:1690)

DIAGNOSTIC APPROACH TO RENAL INSUFFICIENCY IN END-STAGE LIVER DISEASE

Prerenal Hepatorenal ATN

Clinical Signs of hypov- No hypovolemia and olemia; resolves no response to volume with volume expansion; hypothermia; expansion usually accompanied by ascites and hepatic encephalopathy

(continued on next page) 174 Pediatrics

Prerenal Hepatorenal ATN

Labs oratory • Na (urine, mEq/L) <10 <10 >30 • Fractional excretion <1% <1% >3% of Na • UCr/PCr >30 >30 <20 • UOsmol/POsmol >1.1 >1.1 1 • Urine sediment Normal Normal Protein, ↑ in BUN > Cr Proportional ↑ in BUN casts, cellular and Cr debris

• Ascites • Defi nition: Pathologic accumulation of fl uid within the peritoneal cavity. • Pathogenesis: ↑ Na and water retention, portal HTN (↑ hydrostatic pressure), hypoalbuminemia (↓ oncotic pressure). • Presentation: ↑ Abdominal girth and wt gain, shifting dullness on abdominal exam. • Etiology: • At any age: portal HTN, portal vein thrombosis, cirrhosis, acute pancreatitis, hypoalbuminemia, VOD, CHF, vasculitis, peritonitis, mesenteric adenitis, TB, or schistoso- miasis can be a cause for ascites. • However there are some etiologies usually associated with certain age groups: • Children 0–1 yr: Congential abnormality of lymphatics • Children 1–12 yrs: Cardiomyopathy, Meig syndrome • Children 12–18 yrs: Cardiomyopathy, Meig syndrome, Budd-Chiari syndrome, alcoholic hepatitis • Diagnostic studies • Abdominal ultrasound: Diagnose and characterize ascites. • Paracentesis: To analyze the fl uid for TP, albumin, cell count, culture with Gram stain; Serum ascites albumin gradient (SAAG) ≥ 1.1 g/dL → > 95% accuracy that ascites is portal HTN related (Ann Int Med 1992;117:215). If SAAG ≥1.1 g/dL then concentration of ascites fl uid TP (AFTP) helps distinguish between cirrohsis (AFTP <2.5 g/dL) or cardiac (AFTP >2.5 g/dL) as etiology for ascites. (SAAG = albumin concentration of serum - albumin concentration of ascitic fl uid) • Treatment: Treat underlying cause for ascites. Monitor serum and urine lytes, fl uid status, daily wt, strict I/Os, low-sodium diet • Diuretics: Spironolactone (for children, 1–3 mg/kg/day divided BID with a maximum of 5–6 mg/kg/day; for adolescents and adults, 100–200 mg/day divided BID with a maximum of 600 mg/day; assess response with spot urine Na (>20 mEq/L considered appropriate naturesis). • If unresponsive to diuretics, consider fl uid restriction and albumin infusion followed by furosemide • Large-volume paracentesis is considered for ascites causing respiratory compromise or for refractory cases to treatment. • Complications: Spontaneous bacterial peritonitis, pleural effusions, hepatorenal syndrome. • Bacterial Peritonitis • Defi nition: Acute infection of the peritoneal cavity. • Presentation: Subtle signs and symptoms: fever, anorexia, vomiting, abdominal tenderness, rigidity, ↓ bowel sounds, fl uid wave. • Diagnostic studies: Paracentesis with fl uid analysis for cell count, LDH, TP, glucose, Gram stain, and culture. • Management: See table below. Antibiotics, fl uid resuscitation, correction of lytes, NG tube placement. Patients with secondary bacterial peritonitis have a intra-abdominal focus of infection (eg, ruptured viscus, abscess) that may warrant surgical intervention. Gastroenterology 175

DIFFERENTIATION AND TREATMENT OF BACTERIAL PERITONITIS

Type Risk Factors Cell Count Culture Treatment

Primary Ascites: Renal PMN count ≥250 cells/mm3 Usually only Immediately or liver disease TP <1 g/dL one organism start empiric (20% of patients (Escheri- 3rd generation with cirrhosis), chia coli, cephalosporin CHF streptococci, (eg, cefotaxime). staphylococci, Modify anti- enterococci) biotic choice based on Secondary Intraabdominal PMN count ≥250 cells/ Polymicrobial culture. infection mm3 and 2 of the following: TP >1 g/dL or Glucose <50 mg/dL or LDH > upper limit of normal for serum

HYPERBILIRUBINEMIA Direct (Conjugated) • Deﬁ nition: Conjugated bilirubin >2mg/dL or >20% of total bilirubin. Due to differences in technical methodology, direct bilirubin will be higher than conjugated bilirubin at any given level of hyperbilirubinemia. • Diagnosis: • History: Age, vomiting, diet history (poor feeding), irritability, stool consistency and color (acholic), family history (consanguinity), school or social activity, birth and perinatal history, medications, and recent travel. • Physical exam: Well versus ill appearing and irritable versus drowsy (encephalopathy, infection, metabolic disorder), dysmorphism, eye exam (Kayser-Fleischer rings or posterior embryotoxin), systolic murmur of PPS (suggests Alagille syndrome), hepatomegaly

is typically present (small liver may indicate cirrhosis or ESLD), splenomegaly, ascites PEDIATRICS (suggests portal HTN and CLD), dark urine, ataxia, and asterixis. • Laboratory studies/evaluation: • Fractionation of bilirubin, liver panel (ALT and AST ↑ in hepatocellular injury, GGT ± Alk Phos ↑ in obstructive conditions), PT/PTT/INR, chem 10, UA and cx for UTI. • Abdominal, US (gallstones, choledochal cyst, ascites), Doppler US (portal HTN, portal vein thrombosis). • HIDA scan may help distinguish obstructive versus non-obstructive causes. • ERCP, MRCP, percutaneous transhepatic cholangiography (obstruction proximal to common hepatic duct or ERCP precluded). • Liver biopsy may be required for deﬁ nitive diagnosis. • Management/Treatment: Treat based on etiology in consultation with GI service.

Indirect (Unconjugated) • Deﬁ nition: Elevation of unconjugated bilirubin, above age-adjusted normal. Majority are caused by hematologic issues. May be caused by bilirubin overproduction (hemolysis), impaired hepatic uptake (drugs, impaired hepatic blood ﬂ ow eg, CHF), or rarely impaired conjugation (Gilbert syndrome, Crigler-Najjar syndrome, hyperthyroidism, drugs, chronic liver disease). • Diagnosis • History: Age, fever, diet history, jaundice, race or ethnic origin, exposure to medicine, blood products. PMH/FHx of hematologic abnormalities (hemolytic anemia, sickle cell disease, thalassemia), Gilbert or Crigler-Najjar syndrome. 176 Pediatrics

• Physical exam: General appearance (ill-appearing patients should be promptly evaluated for sepsis), icterus (if no scleral icterus, consider carotenemia), large areas of bruising or hematoma formation, splenomegaly (consider hypersplenic state); usually no hepatomegaly. • Laboratory studies/evaluation: CBC, reticulocyte count, Coombs (direct and indirect), peripheral smear, liver panel (usually AST and ALT are normal with ↑ indirect bilirubin). Consider G6PD assay if appropriate risk factors (Mediterranean, African descent, males + family history). • Management/Treatment: Treat based on etiology in consultation with GI service.

PANCREATITIS • Defi nition • Acute: Infl ammatory process resulting from ectopic activation of pancreatic enzymes characterized by abdominal pain, ↑ amylase and lipase, and supportive radiologic fi ndings (see table below). • Chronic: Permanent structural changes of the pancreas (eg, calcifi cation, fi brosis) or its duct (eg, stricture, dilatation); may lead to exocrine or endocrine insuffi ciency. • Epidemiology: Generally seen in children and adolescents; boys and girls are equally affected. Most cases of acute and chronic pancreatitis are idiopathic. Trauma is the most common identifi able etiology of acute pancreatitis. CF and other genetic mutations are the most commonly identifi ed etiologies of chronic pancreatitis.

COMPARISON OF ACUTE AND CHRONIC PANCREATITIS IN CHILDREN

Acute Chronic

Etiology • Idiopathic (23%) • Idiopathic • Traumatic (22%) seat belt, bicycle • Genetic mutations: handlebars, NAT Serine protease 1 gene • Anatomic or obstructive (15%) (PRSS1) pancreas divisum (controversial), Serine protease inhibitor anomalous pancreaticobiliary union, Kazal type 1 choledochal cyst, cholelithiasis, ( ) sphincter of Oddi dysfunction, masses SPINK1 (± clinical manifesta- • Systemic disease (14%) HUS, Kawa- CFTR saki, HSP, Crohn disease, SLE tions of CF) • • Toxins and drugs (12%) azathioprine, Anatomic or obstructive: See 6-MP, L-asparaginase, valproic acid, list under “acute” corticosteroids, some antibiotics • Autoimmune: Secondary and diuretics, scorpion venom, forms (eg, SLE) more com- organophosphate insecticides, mon in children than primary cocaine, ethanol autoimmune pancreatitis • Infection (10%): Usually viral; rarely • Tropical calciﬁ c pancreatitis bacterial, parasitic (eg, Ascaris) • Metabolic (2%) hypertriglyceridemia, hypercalcemia, refeeding syndrome, DM • Familial (2%) (J Clin Gastroenterol 2003;37(2):169) • Miscellaneous: Post-ERCP, malignancy

Pathophysiology Premature activation of pancreatic Repeated episodes of acute enzymes in the acinar cell leads to pancreatitis parenchymal inﬂ ammation, ischemia, Protein plugs or calculi caus- and necrosis ing obstruction and secondary calciﬁ cation Autoimmune vasculitis

(continued on next page) Gastroenterology 177

Acute Chronic

Clinical Abdominal pain: Epigastric classically, Flares of chronic pancreatitis manifestations may radiate to back mimic acute pancreatitis Nausea and vomiting ± intestinal ileus Pancreatic exocrine or endo- Anorexia crine insuﬃ ciency (late signs) Jaundice (with gallstones or biliary Steatorrhea obstruction) Excessive appetite Fever, RUQ pain, and jaundice (Char- Growth failure cot’s triad) indicative of cholangitis

Physical exam Tachycardia, pain, “third spacing” May be normal Abdomen: Inspect for signs of trauma, Chronic abdominal tenderness tenderness ± distension, ascites rarely, may dominate the clinical peritoneal signs, pseudocysts may be picture late in the course of palpable, diminished bowel sounds disease Hemorrhagic necrosis (bluish discoloration): Flanks—Grey Turner’s sign; umbilicus—Cullen’s sign

Diagnosis Physical exam fi ndings of epigastric May present as acute pancrea- pain along with history of vomiting titis; however, amylase and (afebrile) lipase may not be increased Serum amylase and lipase >3 times with progressive parenchymal normal (no correlation to disease destruction severity) Spot fecal fat (increased) Secondary hyperglycemia, Fecal elastase-1 (low) hypocalcemia, hypoalbuminemia, Low vitamins A, D, E, K (rarely) hypertriglyceridemia, and acidosis may be observed KUB: Helpful when calcifi c pancreatitis is suspected LFTs and bilirubin elevated in gall- stone pancreatitis Abdominal US, CT, MRCP by defi nition should refl ect paren- Triglyceride level >1000 mg/dL after chymal or ductal changes the acute episode is suggestive of PEDIATRICS hypertriglyceridemic pancreatitis Endoscopic US: Helpful in select cases when noninvasive Abdominal US, CT if necessary imaging is equivocal to assess for obstructive causes, pseudocysts, abscesses ERCP off ers diagnostic and therapeutic abilities (stent MRCP (after the acute episode): When placement, sphincterotomy, an anatomical lesion is suspected stone removal) Genetic testing: PRSS1, SPINK1, CFTR (Note: Many CFTR mutation screening panels are “pulmonary centric” and will miss some CFTR mutations associated with pancreatitis but not the pulmonary phenotype) Sweat chloride test

(continued on next page) 178 Pediatrics

Acute Chronic

Management • NPO, NG decompression if vomit- • Pain: ing; gastric acid suppression until • Small, low-fat meals; vitamin feeding (especially fat-soluble) • Fluid resuscitation and electrolyte supplementation correction • Pancreatic enzyme supple- • Nutrition: Jejunal feeds are superior ments (enteric coated): to TPN (↓ complications and cost) Restore exocrine enzyme when severity of illness is expected defi ciencies and may reduce to preclude PO feeding for several pain by minimizing CCK- days (Gastroenterol Clin North Am mediated secretory drive 2007; 36(1):65). Initiate low fat diet • Chronic opioids for per- when abdominal pain improves and sistent, signifi cant pain; vomiting resolves long-acting agents are more • Analgesia: NSAIDs (eg, ketorolac), eff ective narcotics; insuffi cient evidence exists • ERCP with sphincterotomy ± to routinely recommend meperidine stent placement over morphine (Am J Gastroenterol. • Surgery 2001;96(4):1266) • Antibiotics: For severe systemic illness or necrosis (cover aerobic and anaerobic enteric organisms) • ERCP: Only indicated acutely for impacted stone removal, sphincterotomy • Surgical management is reserved for some traumatic injuries, necrotic pancreatitis, recalcitrant pseudocysts

Complications Shock and multisystem organ failure Bile duct and duodenal (rare in children) obstruction (5%-10%): Pancreatic necrosis, abscess, or Decompression may reverse pseudocyst formation secondary biliary ﬁ brosis Pseudocysts (~10%): May drain for rapid enlargement, compression of surrounding structures, pain, or infection Splenic vein thrombosis Sequelae of chronic nutrient malabsorption

CONSTIPATION • Deﬁ nition: Delayed or difﬁ cult defecation for >2 wk. • Etiology • Functional: Most cases are functional in older children (ie, withholding of stool that leads to progressive impaction, painful defecation and reinforcement of withholding behavior). • Anatomic: Hirschsprung disease, anal stenosis, malpositioned anus, bowel atresia or stricture, abdominal mass. • Physiologic: Medications (iron, diuretics, anticholinergics, narcotics), milk-protein allergy (infants), CF, neuromuscular disease (CP, MD, hypotonia), spinal cord lesion, hypothyroidism, ↑ Ca++, ↓ K+, botulism, lead poisoning, malnutrition, anorexia nervosa. Gastroenterology 179

• Diagnosis • History: Stool frequency, consistency (hard, soft, diarrheal) and size; blood mixed with or coating stool; abdominal pain; pain with defecation; abdominal distension; time after birth for fi rst bowel movement; urinary incontinence or increased frequency (including enuresis); encopresis; retentive posturing; diet history (especially milk intake, fl uid intake); FTT; emesis; fever. Assess for physical, sexual, or emotional abuse; stress; medication use; family history of GI diseases. • Physical Exam • Abdomen: Usually generalized abdominal pain, ± distension, ± palpable stool. No peritoneal signs. Distension, rebound, rigidity (obstruction), palpable stool. • Rectal: Tone, position, presence of anal wink, impacted stool in vault, fi ssures, perianal abscess, dermatitis to suggest soiling. • Full neurologic exam and back exam (to evaluate for spinal cord lesions, botulism, hypothyroidism); goiter, large tongue, myxedema, skin dryness suggest hypothyroidism. • Management • Successful therapy rests on adequate disimpaction followed by rigorous adherence to a daily maintenance regimen. • Disimpaction • PEG 3350 (Miralax) 0.7–1.5 g/kg/day PO (maximum 17 grams/day) × 2–4 days. • Phosphate enema: <1 yo, 60 mL PR × 1; >1 yo: 6 mL/kg PR (maximum 135 mL daily) for 2–3 days. The risk of hyperphosphatemia is increased in infants and those with hemodialysis. • PEG-electrolyte solution (GoLytely): NG 25–40 mL/kg/h (maximum 1 L/h) until rectal effl uent clear. • Maintenance • PEG 3350 (Miralax) 1 g/kg/day PO and titrate to achieve daily “mashed potato” consistency bowel movements. • Osmotic (adjust to daily bowel movement): Lactulose 1–3 mL/kg/day PO divided BID. • Stimulant (short-term use only): • Senna: 2–6 yo, 2.5–7.5 mL/day PO; 6–12 yo, 5–15 mL/day PO of 8.8 mg/5 mL syrup. • Bisacodyl: >2 yo, 5–10 mg/day PR; 5–15 mg/day PO. • Milk of Magnesia: <2 yo, 0.5 mL/kg/dose q 6–12 h until bowel movement; 2–5 yo, 5–15 mL/day daily or div BID; 6–11 yo, 15–30 mL/day daily or div BID; >12 yo, 30–60 mL/day daily or div BID PEDIATRICS • Other: Increase dietary fi ber and fl uids, educate parents, and provide frequent follow-up. Maintain on therapy for ≥2 months after normal stooling has been established.

MALABSORPTIVE SYNDROMES • Defi nition: Generalized inability to absorb fat, protein, ± carbohydrates. • Etiology: Any condition resulting in ↓ surface area for absorption, impaired motility or mixing, bacterial overgrowth, decreased pancreatic exocrine function, ↓ bile acid production or secretion, or impaired lymphatic or venous drainage (including inherited diseases). • Presentation: Diarrhea, vomiting, anorexia, abdominal pain, FTT, abdominal distension. • Diagnostic studies • Stool: pH, reducing substances, color, occult blood, microscopy, O&P, culture, fecal fat, α lytes, 1-antitrypsin. • Blood: CBC, ESR, LFTs, lytes, PT/PTT/INR, peripheral smear, immunoglobulins (more specifi c tests as indicated), intestinal biopsy. INFLAMMATORY BOWEL DISEASE • Defi nitions • Ulcerative colitis: Chronic, idiopathic superfi cial infl ammation of colonic mucosa starting in the rectum and extending proximally but sparing the upper GI tract. May involve entire colon and the terminal ileum (backwash ileitis) in some patients. • Crohn disease: Chronic, idiopathic transmural infl ammation of any part of the GI tract (from mouth to anus), usually occurring in a noncontiguous fashion (skip lesions) and preferentially affecting terminal ileum and colon. 180 Pediatrics

• Indeterminate colitis: In about 10% of patients with chronic colitis, it is not possible to make a defi nitive diagnosis by clinical presentation, radiologic, endoscopic, or histo- pathologic fi ndings. • These are lifelong diseases characterized by unpredictable exacerbations and remissions. • Etiology • The exact cause is unknown, but consensus is that it is caused by permanent inappropriate activation of the immune response. Multiple factors may contribute, including genetic mutation (NOD2/CARD 15 gene implicated in Crohn’s disease), infectious agents, diet, environmental exposures, and enteric luminal fl ora. • Incidence is highest amongst whites, especially Ashkenazi Jews; however, there is an rising incidence in African American > Hispanics > Asians. • The single greatest risk for the development of IBD is having a fi rst-degree relative with the condition. The estimated risk in these individuals is 30–100 times greater than in the general population. • Pathogenesis • Chronic infl ammation, tissue breakdown, and subsequent fi brosis. • Many types of cells of the immune system are implicated: B cells, T cells, macrophages, and PMNs. • Diagnosis: See table below. EPIDEMIOLOGIC AND CLINICAL FEATURES OF CROHN’S DISEASE AND ULCERATIVE COLITIS

Crohn Disease Ulcerative Colitis Age at onset Bimodal, 15–25 yr and 50–70 yr 16–20 yr Recent studies show unimodal distribution (peak in the 20s–30s with diminishing incidence later) Incidence 4.5/100,000 2.1/100,000 Intestinal Abdominal pain, diarrhea with mucus Abdominal pain, grossly symptoms (bloody, if colonic involvement), n/v, bloody diarrhea, tenesmus, perianal disease, ﬁ stulas, abscess urgency, painful defecation Extraintestinal Fever (50%), arthralgias, weight Fever (50%), arthralgias, symptoms loss (90%), stomatitis, gallstones, weight loss (70%), scleros- kidney stones, uveitis (15%), delayed ing cholangitis, pyoderma growth or sexual development gangrenosum (5%) (30%), erythema nodosum (15%) Adapted from Pediatr Clin North Am 1988;35(1):189.

• Differential diagnosis: See table below.

• Infectious colitis (especially pseudomembranous colitis • HUS (initially before the renal from Clostridium diffi cile, other bacterial enteric patho- failure) gens, viral colitis in immunocompromised patients) • Appendicitis • Allergic colitis • Intestinal lymphoma • Milk protein intolerance of infancy • Rheumatoid arthritis • Hirschsprung’s colitis (before or within months of • Behçet ‘s syndrome (rare in the surgical correction). United States) • Prestenotic colitis • Systemic vasculitis ie, SLE or • Diversion colitis dermatomyositis • Ischemic colitis • Peptic ulcer disease • Radiation proctitis or colitis • Typhlitis • Eosinophilic gastroenteritis • Neonatal necrotizing enterocolitis • Congenital or acquired immunodeﬁ ciency • Laxative abuse syndromes • Malabsorptive syndromes • GVHD in transplant patients • Henoch-Schonlein purpura • Irritable bowel syndrome Gastroenterology 181

• Diagnostic studies: See tables below.

EVALUATION OF CHILD WITH SUSPECTED INFLAMMATORY BOWEL DISEASE

Initial Laboratory Evaluation

CBC, PT/INR, ESR/CRP UA Stool guaiac, bacterial culture, O&P, total fat, C. diffi cile toxin, and in immunocompromised patient viral particles or culture Serum total protein, albumin, transferrin, immunoglobulins

Serum lytes; Ca; Mag Phos; iron; zinc; folate; vitamins A, E, 25-OH vitamin D, B12 Serum AST, ALT, alkaline phosphatase, bilirubin

Additional Testing

α Fecal 1-antitrypsin Lactose breath test Plain ﬁ lms, upper GI with SBFT, CT of the abdomen and pelvis Anti-Saccharomyces cerevisiae antibodies (ASCA): Positive in 40%–60% of patients with Crohn disease Perinuclear antineutrophil cytoplasmic antibodies (P-ANCA): Positive in 60%–70% of patients with ulcerative colitis EGD or colonoscopy with biopsy (gold standard)

RADIOGRAPHIC AND ENDOSCOPIC FEATURES OF CROHN’S DISEASE AND ULCERATIVE COLITIS

Radiographic Endoscopic

Crohn’s disease Longitudinal or trans- Asymmetric or discontinuous PEDIATRICS verse deep ulcerations; involvement; deep, longitudinal skip lesions; strictures; fissures; cobblestone appearance; ﬁ stulae; cobblestone mucosal edema; usually no appearance of mucosa; mucosal friability; strictures (not thumbprinting always present)

Ulcerative colitis Fine, superﬁ cial Uniform involvement beginning at ulcerations; continuous the anorectal junction; very friable involvement from the mucosa; diﬀ use, uniform erythema; rectum; shortening of rectal involvement if active disease; the bowel; symmetric pseudopolyps bowel contour; decreased mucosal pattern; pseudopolyps

• Treatment • Long-term treatment is required. Goals of therapy are induction and maintenance of remission. Medical treatment is not curative. 182 Pediatrics

PHARMACOLOGIC THERAPY OF INFLAMMATORY BOWEL DISEASE

Crohn Disease Ulcerative Colitis

Acute exacerbation Severe to moderate colitis Methylprednisolone 1–2 mg/kg/day IV Methylprednisolone 1–2 mg/kg/day IV divided divided BID–QID for 7–10 days. Change BID–QID for 7–10 days. Change to PO (same to PO (same dose) divided BID; then dose) divided BID; then 1 mg/kg/day PO once 1 mg/kg PO once daily; then 1 mg/kg daily; then 1 mg/kg PO every other day, con- PO every other day, continuing for total tinuing for a total course of 4–6 wk. course of 4–6 wk.

Remission Mild or Localized Distal Colitis Olsalazine 30–40mg/kg/day PO divided Olsalazine 30–40 mg/kg/day oral divided BID BID Folate 1 mg/day Folate 1 mg/day Mesalamine 50 mg/kg/day divided BID or TID Mesalamine 50 mg/kg/day divided BID Mesalamine enemas or rectal suppositories or TID Hydrocortisone enemas

Perianal Disease or Fistula Metronidazole 15 mg/kg/day divided Q8h

Refractory Disease Refractory disease Azathioprine 1–2 mg/kg/day divided Azathioprine 2 mg/kg/day or BID or 6-Mercaptopurine 1.5 mg/kg/d divided BID or 6-Mercaptopurine 1.5 mg/kg/day divided Cyclosporine IV 1–2 mg/kg/d; then PO 4–8 mg/ BID or kg/d or 2 Methotrexate 10 mg/m /week (PO or Tacrolimus or subQ) or Iniﬂ iximab 5–10 mg/kg wk 0, 2, 6, and Iniﬂ iximab 5–10 mg/kg wk 0, 2, 6, and subsequently as needed subsequently as needed

• Correction of nutritional defi ciencies with TPN, vitamins (especially vitamin D), or elemental formulas. • Surgery for disease refractory to medical therapy and complications such as perforation, fi stulas, strictures, abscesses, fulminant colitis, or toxic megacolon. • Prognosis: Beyond the fi rst decade of having UC, the risk of developing colon cancer begins to increase rapidly. Patients need regular surveillance colonoscopies after 8–10 years of disease.

FAILURE TO THRIVE • Defi nition: No consensus defi nition. Working defi nition: Child younger than 2 yo whose wt has fallen to < below 3rd or 5th percentile or whose weight crosses two percentile growth curves on a gestational corrected growth chart appropriate for the child’s age and gender. • Etiology: Inadequate intake, abnormal utilization, or increased metabolism. CAUSES OF FAILURE TO THRIVE IN CHILDREN

Increased Metabolic Inadequate Intake Abnormal Utilization Demand • Food availability • Short bowel syndrome • Congenital heart disease, CHF • Feeding technique • Celiac disease • Chronic inﬂ ammatory states • Dysphagia • Inﬂ ammatory bowel disease • Chronic lung disease • Feeding aversion • NEC • Hyperthyroidism • Pyloric stenosis • Malabsorptive syndrome • CF

(continued on next page) Gastroenterology 183

Increased Metabolic Inadequate Intake Abnormal Utilization Demand • Malrotation • CF • HIV, toxoplasmosis • GERD • Inborn errors of metabolism • Diabetes mellitus • Child abuse or neglect • Chromosomal abnormalities • RTA • Food inappropriate for age • TORCH infections • Malignancy • Incorrect mixing of formula • Lead toxicity • TB

• Diagnosis • History: Detailed pre- and postnatal history (infection risk), diet history (formula mixing, intake, juice and cow’s milk intake), refl ux quantifi cation, sleep–wake cycle, vomiting, diarrhea, bleeding, lead poisoning screen. Obtain weight, height, head circumference trend (from parent or child’s doctor). PMH signifi cant for frequent infections (AOM, pneumonia). FHx signifi cant for malabsorption, CF. • Physical exam: Accurate measurement of weight, length, head circumference (needed for determining the level of malnutrition), parental interaction, assess feeding and swallow, focus on dysmorphic features and detailed neurological exam. • Laboratory studies/evaluation: CBC, Chem 10, UA with culture, follow-up newborn screen prealbumin, ± liver panel. • Management and treatment • FTT is an outpatient workup. • Do labs, 72-h calorie count → ↑ caloric density of formula if no weight gain → weight check → if no weight gain, then initiate further workup. • Classify degree of FTT (see table below). • Admit the patient for the following reasons: Severe malnutrition or dehydration, serious intercurrent illness, child safety, failed outpatient treatment for 2–3 mo, precise documentation of calories, parental impairment, and potential lack of follow-up. • 72-h calorie count, dietician consult, social work consult to assess the home environment and identify needs → after 24h of data → ↑ calorie of formula if required and monitor weight gain. • If weight gain, discharge home 24–48 h after family education with close follow-up and outpatient weight checks. • If no weight gain observed for 24 h, start further workup → occupational therapy PEDIATRICS to evaluate suck/swallow, send liver panel ± thyroid tests. Consider GI and genetics input. The patient will need further workup as clinically indicated, potentially including sweat test, UGI series with SBFT, MRI brain, SAA, UOA, acylcarnitine profi le, chromosomal microarray, stool studies for malabsorption (if diarrhea present).

DETERMINING SEVERITY OF MALNUTRITION IN CHILDREN WITH FAILURE TO THRIVE

Method Normal Mild Moderate Severe Weight for ≥90% of median 80–89% of median 70–79% of median <70% of median height∗ Weight for ≥90% of median 75–89% of median 60–74% of median <60% of median age∗

NOTE: values in table represent the percentage of the median age- and sex-speciﬁ c growth parameters (eg, a child with a weight for age 65% of the median value for his age and sex would fall into the moderate category)

Available at www.AccessPediatrics.com • Dysphagia • Cyclic Vomiting Syndrome CHAPTER 17 Genetics

CLINICAL GENETICS Chromosomal Disorders Trisomy 21 (Down Syndrome) • Most common chromosomal cause of mental retardation. • Three distinct cytogenetic abnormalities can lead to Down syndrome. • 95% of cases are attributable to trisomy 21 (47, XX, +21 or 47, XY, +21) caused by a maternal nondisjunction (an event with a higher risk at advanced maternal age). 75% of these errors are in meiosis I and 25% in meiosis II (Am J Hum Genet 1992; 50(3):544). • 4% are attributable to Robertsonian translocations resulting in a third copy of chromosome 21 translocated onto another acrocentric chromosome (13, 14, 15, 21, or 22). • 1% are attributable to mosaicism. • Clinical manifestations by organ system • Respiratory: Sleep apnea caused by hypotonia or airway narrowing • Facial dysmorphology: Epicanthal folds, Brushfi eld spots, upslanting palpebral fi ssures, short neck with excess nuchal skin, protruding tongue • CNS: Hypotonia, mental retardation • Cardiac defects in 50% of patients (in order of frequency): • Endocardial cushion defect • Ventricular septal defect • Secundum atrial septal defect • Patent ductus arteriosus • Tetralogy of Fallot • Endocrine: Hypothyroidism; women can be fertile • Extremities: Short hands, hypoplastic midphalanx of fi fth fi nger, single transverse palmar crease, sandal gap toe, hallucal arches • GI: Duodenal atresia, annular pancreas, imperforate anus, tracheoesophageal fi stulas, Hirschsprung’s disease • Growth retardation: Special growth charts are used for patients with Down syndrome (Pediatrics 1988;81:102, Am J Med Genet 1992;42: 61) • Hematologic (Am J Med Genet 1990;46(6):1034) • Transient myeloproliferative disorder: Neonatal presence of blasts on peripheral smear; disappears by age 3 mo • Acute myelocytic leukemia (FAB M7 subtype) • Marked increased risk of acute lymphoblastic leukemia (ALL).

HEALTH SUPERVISION IN DOWN SYNDROME

Age Concern Recommendation

Birth–1 mo Hearing loss Auditory brainstem evoked responses (ABER)

Cardiac defects Echocardiogram

Leukemia CBC with peripheral smear

Congenital hypothyroidism Review newborn screens

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184 Genetics 185

Age Concern Recommendation

1 mo–1 yr Otitis media, hearing loss ENT referral if abnormal ABER

Strabismus, cataracts, nystagmus Ophthalmology referral by age 6 mo

Hypothyroidism TSH at 6- and 12-mo visits

Growth Plot on Down syndrome curves

1–5 yr Otitis media, hearing loss Attempt tympanic membrane visualization, audiogram every 6 mo

Vision loss Vision check annual, Ophthalmology every 2 yr

Atlantoaxial instability and Spinal radiography at 3–5 yr subluxation

Hypothyroidism Annual TSH

Sleep apnea Sleep study, ENT referral if necessary

Obesity and osteoporosis Dietary counseling prevention

5–13 yr Hearing loss Annual audiology exam

Vision loss Annual ophthalmology exam

Hypothyroidism TSH annually

Sleep apnea Sleep study, ENT referral if necessary

Reproduction Review contraception, menstruation, recurrence risk

13–21 yr Hearing loss Annual audiology exam PEDIATRICS

Vision loss Annual ophthalmology exam

Hypothyroidism TSH annually

Leukemia CBC annually

Reproduction Review contraception, menstruation, recurrence risk

Pediatrics 2001;107(2):442. CHRONOLOGICAL ORGAN SYSTEM EMBRYONIC DEVELOPMENT FROM WEEKS 3 TO 7

Week CNS Cardiovascular Respiratory Musculoskeletal Gastrointestinal Urogenital Head and Neck Ears Eyes 3 Neural plate Cardiogenic fi eld is Cloaca forms, Cloaca forms Eye grooves appears and established as myo- liver primordium appear begin progresses to blasts migrate from appears to induce sur- neural folds the cranial end of rounding the embryo ectoderm 4 Neural tube Primitive heart Lung bud Sclerotome cells Foregut formation Pronephros, Mandible forma- Optic evagina- closure pro- tube undergoing grows out begin surrounding mesonephric tion, tongue tion forms ceeds cranial looping from foregut the spinal cord, duct formation to caudal (esophagus) transverse septum originates 5 Primary brain Septum primum Lung bud Vertebral ossifi ca- Evagination of Ureteric bud Nasal pits give Otic Lens begins to 186 vesicles form forming branching tion centers, limb thyroid, liver, and sprouts from rise to nasal invagina- invaginate into forebrain, into bronchi bud formation pancreas mesonephric prominences tion lead- optic cup midbrain, (lower limb is always duct and mi- ing to otic hindbrain 1–2 d behind the grates toward vesicle upper) metanephric mesenchyme 6 Pons, Growth of mus- Branches to Limb innervations, Physiologic umbili- Ureteric bud Nasolacrimal Cochlear Lens is fully cerebral cular ventricular main lobes formation of hand cal herniation, gall- branching into swellings conduct, invaginated, development septum, outfl ow of lung are and foot plates bladder formation, metanephric tinue to grow semi- pigmented ongoing, tract septation formed in spleen formation mesenchyme circular cells appear in neural respiratory creating renal canals retina hypophysis tree pelvis and collecting system 7 Optic nerve Septum secun- Tracheal carti- Finger rays form, Gut rotation Poles of Primary palate Pigmented cells dum forming lage forms transverse septum around the superior kidney form, and choana form migrating into completed (compo- mesenteric artery nephrogenesis retina nent of diaphragm) begins Genetics 187

Associations CHARGE • This is now considered a syndrome since the molecular cause was discovered. • The incidence is one in 10,000. • Features (NeoReviews. 2008;9(7):e299) • Colobomas: Retinal is more common than of the iris. • Cranial nerves: Particularly VII, VIII. • Heart defects: Tetralogy of Fallot, interrupted aortic arch, AV canal, double-outlet RV, truncus arteriosus, ASD, VSD. • Atresia choanae: Causes neonatal respiratory distress, chronic sinorespiratory infections. May be complete or partial and unilateral or bilateral. Clues to diagnosis: inability to pass NG tube, polyhydramnios. • Retarded somatic growth and mental retardation. • Genitourinary anomalies: Generally genital but also unilateral renal agenesis, obstructive uropathy. • Ear anomalies: outer, middle, or inner. • Evaluation • Ophthalmology evaluation for retinal colobomas • CT maxillofacial bones for choanal atresia • Echocardiography • Renal US • Hearing screen, temporal bone CT for Mondini dysplasia • Chromosomal microarray (CMA) • Chromodomain helicase DNA-binding protein 7 (CHD7) mutation testing: Conﬁ rmatory molecular test for CHARGE syndrome (in consultation with specialist) • Health maintenance • Eye exam every 6 months • Prompt surgical correction of choanal abnormalities • Cardiology, ENT, renal referrals if indicated VATER/VACTERL Association • Should be treated as an epidemiologic phenomenon rather than as a diagnosis until

chromosomal abnormalities and other syndromes have been ruled out. PEDIATRICS • Vertebral defects • Anal atresia • Cardiac defects • TracheoEsophageal ﬁ stulas • Renal anomalies • Limb defects, particularly of the radius

Morphogenesis • Zygote to blastocyst development (wk 1 and 2): Vigorous cell proliferation; implantation; formation of the two-layered embryonic disc, chorion, amnion, and yolk sac • Teratogen effects: Loss of the pregnancy • Embryonic development (wk 3–8): Gastrulation, organ system development

Teratogen Effects • Major structural birth defects • Fetal development (wk 9+): Growth of the organs and structures of the embryo • Will not cause major structural defects but can lead to growth retardation; mental retardation; neuronal migration abnormalities, and eye, ear, and limb abnormalities 188 Pediatrics

METABOLIC GENETICS MAJOR CLASSES OF INBORN ERRORS OF METABOLISM

Broad Overview: Classes of Inborn Errors of Metabolism Amino acid transport disorders Fatty acid oxidation disorders Mitochondrial disorders Amino acid metabolism Carbohydrate metabolism Inherited neurotrans- disorders disorders mitter disorders Organic acidurias and Peroxisomal metabolism Creatine deﬁ ciency acidemias disorders disorders Lysosomal metabolism Defects in heme pigment Congenital disorders of disorders synthesis protein glycosylation Urea cycle defects Disorders of metal metabolism

Signs and Symptoms Suggestive of Metabolic Diseases Neonatal Period and Infancy • Often nonspecifi c and after a symptom-free interval: Hypotonia, poor sucking refl ex, lethargy, seizures, vomiting, diarrhea, or respiratory distress • Neonatal seizures: Pyridoxine responsive seizures, pyridoxal phosphate responsive seizures, biotinidase or holocarboxylase synthetase defi ciency, glycine encephalopathy, molybdenum cofactor or isolated sulfi te oxidase defi ciency, disorders of creatine metabolism, disorders of purine and pyrimidine metabolism, disorders of neurotransmitter biosynthesis • Hypotonia: Organic acidemias, fatty acid oxidation disorders, peroxisomal disorders, disorders of creatine metabolism, congenital disorders of protein glycosylation • Neurological deterioration or lethargy: Urea cycle defects, organic acidemias, maple syrup urine disease, fatty acid oxidation disorders, mitochondrial disorders, lysosomal storage disorders, peroxisomal disorders • Cardiomyopathy or cardiac conduction defects: Fatty acid oxidation disorders, Pompe disease, mitochondrial disorders • Persistent hypoglycemia (Figure 17-1): Fatty acid oxidation disorders, glycogen storage diseases, hyperinsulinism

• Glycogen storage diseases With hepatomegaly • Gluconeogenesis defects With lachic acidosis • Organic acidurias • Defects of ketolysis Without hepatomegaly • Respiratory chain defects • Disorders of long-chain fatty acid oxidation

• Ketotic hypoglycemia • Organic acidurias With ketosis • Glycogen storage diseases Hypoglycemia type 0 and III • Adrenal insufficiency Without lactic acidosis • Hyperinsulinism • Hypopituitarism Without ketosis • Disorders of fatty acid oxidation • Disorders of ketogenesis

• Fructose intolerance With liver failure • Tyrosinemia type I

Figure 17-1 Differential diagnosis of neonatal hypoglycemia. Genetics 189

• Ketosis: Organic acidemias, tyrosinemia, maple syrup urine disease • Hepatomegaly: Glycogen storage disorders, peroxisomal disorders • Hepatosplenomegaly: Lysosomal storage disorders • Pathologic jaundice, liver failure: Galactosemia, tyrosinemia, citrin deﬁ ciency, congenital disorders of protein glycosylation, hereditary fructose intolerance, mitochondrial DNA depletion • Metabolic acidosis (Figure 17-2): Organic acidurias, ketolysis defects, fatty acid oxidation disorders, ketogenesis defects, some glycogen storage diseases

Hyperammonemia • Organic acidurias (MMA, IVA, PA) Hyperglycemia • Diabetes Normal NH3 • Ketolysis defects

Lactic acidosis • Respiratory chain defects Ketones ⊕ Normoglycemia • Organic acidurias Normal lactate • Late - onset MSUD • Ketolytic defects Lactic acidosis • Glycogen storage disease type 0 Hypoglycemia • Defects of gluconeogenesis • Respiratory chain defects Metabolic Normal lactate • MSUD (late onset) acidosis • Organic acidemias • Adrenal insufficiency Normoglycemia • Pyruvate dehydrogenase Lactic acidosis deficiency Hypoglycemia • Fatty acid oxidation defects Ketones – • Glycogen storage disease type I Normal lactate Normoglycemia • Renal tubular acidosis Figure 17-2 Differential diagnosis of neonatal metabolic acidosis.

• Respiratory alkalosis: Urea cycle defects (although commonly not a neonatal presentation)

• Sepsis: Propionic academia, galactosemia PEDIATRICS • Neutropenia: Organic acidemias, nonketotic hyperglycinemia, carbamoyl phosphate synthetase deﬁ ciency, glycogen storage disease type IB • Thrombocytopenia: Organic acidemias, lysinuric protein intolerance • Hyperbilirubinemia: Galactosemia, hereditary fructose intolerance, tyrosinemia, inherited disorders of bilirubin metabolism (eg, Crigler Najjar Syndrome), α-1 antitrypsin deﬁ ciency • Abnormal hair: Arginosuccinic acidemia, lysinuric protein intolerance, Menkes syndrome • Abnormal body odor: See table below

UNUSUAL URINE AND BODY ODORS

Odor Substance Etiology

Cooked cabbage 2-OH-butyric acid Tyrosinemia type I

Maple syrup Sotolone Maple syrup urine disease

Mousy Phenylacetate Untreated phenylketonuria Treatment with phenylbutyrate

Old ﬁ sh Trimethylamine, Trimethylaminuria dimethylamine Dimethylaminuria

(continued on next page) 190 Pediatrics

Odor Substance Etiology

Sulphur Hydrogen sulﬁ de Cystinuria Methionine Tyrosinemia type I, cirrhosis

Sweaty feet Isovaleric acid Isovaleric acidemia Glutaric aciduria type II

• Abnormal urine color: See table below

DISCOLORATION OF URINE ASSOCIATED WITH VARIOUS CONGENITAL DISORDERS

Urine Color Substance Cause Confi rmation

Homogentisic Alkaptonuria∗ Urine organic acids acid (elevated homogentisic acid)

Brown or Methemoglobin Myoglobinuria Urine dipstick (+ for black blood), CK (elevated)

Hemoglobin Hemoglobinuria Urine dipstick (+ for blood), blood work c/w hemolysis

Erythrocytes Hematuria Urine microscopy

Porphyrins Congenital erythropoi- Porphyrins in urine Red etic porphyria (Günther disease) and hepatic porphyrias

Rifampin Antibiotic treatment with History rifampin Orange Urate† Hyperuricosuria Urine microscopy (urate crystals), uric acid in blood and urine

Indican† Hartnup disorder (trypto- Urine amino acids (increase Green phan malabsorption) of neutral amino acids) or blue Biliverdin Obstructive jaundice Total and direct serum bilirubin elevated

∗Discoloration occurs only upon prolonged air exposure (oxidation) and is not seen in fresh urine. †Urate crystals may be red, pink, or orange. Genetics 191

BROAD OVERVIEW OF INBORN ERRORS OF METABOLISM: CLINICAL AND LABORATORY FINDINGS*

Clinical Finding Aminoacidopathies Acidurias Organic Acidurias Organic “Cerebral” Defects Cycle Urea Diseases Storage Glycogen Mitochondrial Disorders and Oxidation Acid of Fatty Disorders Ketogenesis Metabolism of Lysosomal Disorders Metabolism of Peroxisomal Disorders of Glycosylation Disorders Congenital

Acute onset x x xxxx

Chronic course x xxxxx xxx

Episodic course x xxxx

Mental retardation x x x x (x) x (x) (x) x x

Seizures x x x x (x) x x x x

Failure to thrive x x x x (x) x

Macrocephaly x x

Microcephaly x x

Ophthalmologic xxxxPEDIATRICS ﬁ nding

Abnormal odor x

Hepatomegaly x (x) x x

Liver disease x (x) x (x) x x x

Cardiomyopathy (x) x x x (x) x

Hypoglycemia x (x) x x x

Hyperammonemia x x x x

Metabolic acidosis x x x x

Lactic acidosis x x x x

Respiratory x alkalosis

∗This is a very broad overview; there is great clinical variability within each class. X = typically present, (X) = present only in certain subtypes or mild or secondary ﬁ nding. 192 Pediatrics

Acute and Recurrent Attacks: Late Infancy and Beyond • Episode precipitated by fasting, prolonged exercise, protein catabolism, intercurrent infections. Often normal between attacks. ± developmental delay. • Deteriorates rapidly despite supportive measures in ICU. • Differential diagnosis includes organic acidemias, defects of ketolysis, fatty acid oxidation defects, urea cycle defects, respiratory chain defects, and so on. • During an episode, stop oral intake of potentially toxic compounds (protein, fat), draw acute metabolic laboratory tests (see below), 10% dextrose infusion with GIR of 6–10 mg/kg/min. Chronic and Progressive Symptomatology • GI (chronic vomiting, failure to thrive), muscular (hypotonia, myalgia), or CNS symptoms (developmental delay, encephalopathy with regression) • Macrocephaly: Glutaric aciduria type I, Krabbe disease, Canavan disease • Microcephaly: Maternal PKU, untreated metabolic disorders • Sensorineural hearing loss: Zellweger syndrome, Rhizomelic chondrodysplasia punctata, mitochondrial diseases • Corneal opacifi cations: Galactosemia, Fabry disease, mucopolysaccharidoses • Cataracts: Galactosemia, peroxisomal biosynthesis defects, rhizomelic chondrodysplasia punctata • Dislocation of the lens : Homocystinuria (downward dislocation) • Cherry red spot: Lysosomal storage disorders • Ophthalmoplegia: Mitochondrial disorders, Niemann-Pick type C or D (vertical supranuclear paralysis), Gaucher type III (horizontal supranuclear paralysis) • Retinitis pigmentosa: Peroxisomal disorders, mitochondrial disorders, congenital disorders of protein glycosylation, LCHAD defi ciency • Self-mutilation: Lesch-Nyhan syndrome, untreated phenylketonuria, tyrosinemia type I • Cardiomyopathy or cardiac conduction defects: Fatty acid oxidation disorders, Pompe disease, lysosomal storage disorders, mitochondrial disorders, Barth syndrome • Persistent hypoglycemia: Fatty acid oxidation disorders, glycogen storage diseases, hyperinsulinism, gluconeogenesis defects • Hepatomegaly: Glycogen storage disorders, peroxisomal disorders • Hepatosplenomegaly: Lysosomal storage disorders • Pathologic jaundice, liver failure: Galactosemia, tyrosinemia, citrin defi ciency, congenital disorders of protein glycosylation, hereditary fructose intolerance, mitochondrial DNA depletion Suspected IEM: Initial Laboratory Tests • Arterial blood gas: Specimen on ice, immediate analysis. • Blood glucose to rule out hypoglycemia. • Ammonia: Free-fl owing sample without tourniquet, specimen on ice, immediate analysis.

(NH3 values in specimens sitting for ~15 min at ambient temperature increase by 25 ± 8.7 μmol/L if not on ice (unpublished local data); recommended goal time to lab is <20 min from collection even if on ice.) • Lactate (arterial preferred): Lactic acidosis in patient without hypoxic event: Primary metabolic disorder; (ensure fasting, rested sample, on ice, immediate analysis). • Urine dipstick: Evaluation for ketones and reducing substances. Detects 3-OH-butyrate and acetoacetate. Ketonuria normal during fasting, pathologic in fed state and in all neonates <2 wk of life. Absent or low ketones in a hypoglycemic patients suggests a fatty acid oxidation disorder. • Electrolytes, Ca, Mg: Anion gap calculation. • CBC, differential, smear: Neutropenia in organic acidopathies, WBC inclusions in some storage disorders. • Liver panel: Transaminases, albumin, coagulation proﬁ le, bilirubin (rule out hepatopathy). Genetics 193

Suspected IEM: Speciﬁ c Laboratory Tests • Plasma amino acid analysis: Quantitative analysis by ion exchange chromatography. 3- to 4-h fast recommended. (Many factors may affect results; see table below). Indications: Suspected urea cycle disorder, organic acidemia or aminoacidopathy, hyperammonemia (send with concurrent CSF sample if seizures are present).

FACTORS AFFECTING PLASMA AMINO ACID ANALYSIS

Decreased Increased Amino Acids Amino Acids Underlying Factor

Tyr, Phe, Met, Orn, Lys, Pro, Ala, Gln Leu, Ile, Val Hepatic disease (branched chain AAs)

Asp, Glu, Gly, Orn Arg, Gln Hemolysis

Met, Phe, Cys (coeluting peaks on None Antibiotics (amoxicillin, PAA analysis) ampicillin)

Nondiscriminate: All AAs None Infection

Leu, Ile, Val (branched chain AAs), Gly Ala Starvation or prolonged fasting (1–2 d)

Thr, Ser, and many others None Nonfasting patient <2 yo on formula

Ile, Leu, Val with normal 1:2:3 ratio None Nonfasting patient >2 yo on regular diet

• Urine organic acid analysis: Gas chromatography/mass spectrometry. Recommend >5 cc morning urine sample (iced or frozen). Indications: Unexplained metabolic crisis, metabolic acidosis; suspected organic aciduria, aminoacidopathy, fatty acid oxidation defect or disorder of energy metabolism. (Concomitant lactic acidosis may result in bacterial

overgrowth, and valproate or acetaminophen may affect accuracy.) PEDIATRICS • Acylcarnitine analysis: Tandem mass spectroscopy analysis of total and free carnitine, acylcarnitine proﬁ le, and free fatty acids. Indications: Diagnosis of fatty acid oxidation defects and some organic acidemias.

KEY CHARACTERISTICS OF UREA CYCLE DEFECTS

Disorder Enzyme Defect Inheritance PAA Urine

CPS carbamoyl- AR ↑ Glutamine, Normal or ↓ deﬁ ciency phosphate alanine orotic acid synthetase ↓ Citrulline, arginine

OTC Ornithine transcar- X-linked ↑ Glutamine, ↑↑ Orotic deﬁ ciency bamylase semidominant alanine acid ± (females ↓ Citrulline, symptomatic) arginine

Citrullinemia Argininosuccinate AR ↑↑ Citrulline ↑ Orotic synthetase (ASS) ↓ Arginine acid

(continued on next page) 194 Pediatrics

Disorder Enzyme Defect Inheritance PAA Urine

Arginino- Argininosuccinate AR ↑↑ Argininosuc- ↑↑ Argini- succinic lyase (ASL) cinate nosuccinic aciduria ↑ Citrulline acid ↑ ↓ Arginine Orotic acid

Argininemia Arginase AR ↑↑ arginine ↑↑ Orotic acid

Urine excretion

Benzoate∗ Hippurate Glycine N-Acetylglutamate Glutamate NAGS NH3 ⊕ Carbamoyl OROTIC Glutamate – HCO CPS 1 phosphate ACID NH 3 3 α-keto- Citrulline Ornithine glutarate OTC Aspartate Glutamine Phenyl- acetyl- Ornithine UREA ∗ glutamine ASS Phenylacetate CYCLE

Argininosuccinate Arginase Urine Urea excretion ASL Arginine

Fumarate Figure 17-3 Urea cycle. Notes: N-acetylglutamate synthetase (NAGS), carbamoylphosphate synthetase I (CPS1, which requires activation by N-acetylglutamate), ornithine transcarbamylase (OTC), argininosuccinate synthase (ASS), argininosuccinate lyase (ASL), arginase. *Sodium phenylbutyrate and sodium benzoate as part of the emergency treatment of hyperammonemia in urea cycle disorders.

Acute Management ( J Pediatr 2001;138(suppl):S30, J Pediatr 2001;138(suppl):S46) • Neurologic injury from hyperammonemia correlates with duration, not peak → thus goal for normalization <24 h. • Stop protein intake, typically for 1–2 d; initiate AA in TPN at 1.0–1.5 g/kg/d within 24–48 h. • Reduce catabolism: 10% dextrose infusion (D10W; D10¼NS; D10½NS), GIR of 6–8 mg/ kg/min; insulin infusion as needed; consider intralipids. • Remove ammonia and give sodium benzoate and sodium phenylbutyrate (250 mg/kg for patients ≤20 kg; 5500 mg/m2 for patients >20 kg) over the fi rst 90–120 min followed by a infusion of same dose divided over next 24 h. • Replenish urea cycle intermediates: Citrulline 170 mg/kg/d PO for OTC and CPS; L-Arginine up to 600 mg/kg/d in ASS or ASL defi ciency and up to 200 mg/kg/d in OTC and CPS defi ciencies. • Continuous veno-venous hemodialysis: If ammonia is not decreasing 2 h after treatment

initiation or urgently when NH3 >500 µmol/L (>850 mg/dL). Long-Term Treatment • Maintain anabolic state (avoid fasting; treat infections early). • Limit protein intake; essential AA supplementation; dietician consult. Genetics 195

NEONATAL HYPERAMMONEMIA

Premature neonate Full-term neonate

Citrulline level Abnormal Blood gas analysis (low or high) Normal

Acidosis No acidosis Blood gas analysis

Organic acidemias Urea cycle defects No Acidosis Acidosis

THAN Plasma A.A. analysis

Citrulline↑ Citrulline↑↑ Citrulline low (100–300 μM) (>1000 μM)

Argininosuccinic Urine orotic acid Citrullinemia acidemia

Normal or low Elevated PEDIATRICS

CPS deficiency OTC deficiency

Figure 17-4 Differential diagnosis of neonatal hyperammonemia. THAN, transient hyperammonemia of the newborn. (Modiﬁ ed from Pediatrics 1998;102(6):E69).

• Remove ammonia: Sodium benzoate or sodium phenylbutyrate PO daily. • Arginine: Up to 600 mg/kg/d in ASS and ASL defi ciencies; 100–200 mg/kg/d in OTC and CPS defi ciencies. • Citrulline: 50–150 mg/kg/d OTC and CPS defi ciencies. • Suffi cient fl uid intake, G-tube placement for neurologically impaired, vigilant adherence to immunization schedule with prophylactic antipyretics.

Available at www.AccessPediatrics.com • Edwards syndrome • Patau syndrome • Urea cycle defects • Carbohydrate metabolism disorders • Organic acidurias and acidemias CHAPTER 18 Hematology

ANEMIA (RED BLOOD CELL DISORDERS) • Deﬁ nition: ↓ in Hb, HCT, or RBC count <2 SD below age-speciﬁ c norms • Mechanism: Hemorrhage, hemolysis, ineffective hematopoiesis AGE-SPECIFIC RBC NORMAL VALUES

Hemoglobin Packed Cell (g/dL) Volume (%) MCV (fl ) MCH (pg) Lower Lower Lower Lower Age (Y) Mean Limit Mean Limit Mean Limit Mean Limit

0.5–4 12.5 11.0 36 32 80 72 28 24

5–10 13.0 11.5 38 33 83 75 29 25

11–14& 13.5 12.0 39 34 85 77 29 26

11–14( 14.0 12.0 41 35 85 77 29 26

15–19& 13.5 12.0 40 34 88 79 30 27

15–19( 15.0 13.0 43 37 88 79 30 27

20–44& 13.5 12.0 40 35 90 80 31 27

20–44( 15.5 13.5 45 39 90 80 31 27

Note: Hemoglobin and MCH were obtained by Coulter counter, packed cell volume was obtained by centrifugation, and MCV was obtained from packed cell volume divided by the Coulter red cell count. All date are based on venous blood in caucasians after excluding individuals with laboratory evidence of iron defi ciency or infl ammatory disease Hemoglobin values are rounded out to the nearest 0.5 g/dL. Red cell indices are calculated from combined data for both sexes because of the relatively minor diff erence in values.

Diagnosis • History and physical exam: Determine if acute or chronic bleeding, detailed diet history (milk intake, iron supplementation [breastfed neonates], folate, vitamin B12), infection, drugs, chemicals (lead ingestion), FHx (G6PD, thalassemia, splenomegaly, autoimmune d/o, bleeding d/o, jaundice), other chronic medical conditions. Check vitals (HR, BP, RR) and plot growth parameters (FTT). Perform a CV exam (systolic ejection murmur, gallop, cardiomegaly). Check for hepatomegaly and splenomegaly and signs of hypothyroidism. • Initial lab workup: Primary: CBC d/p, reticulocyte, peripheral smear; secondary (if hemolysis suspected): Bilirubin, LDH, haptoglobin, U/A (urobilinogen).

196 Hematology 197

Classiﬁ cation Anemia (MCV< normal range for age)

Low Normal High (microcytic) (normocytic) (macrocytic)

Iron deficiency See Figure 18-2 Vitamin B12 deficiency Thalassemia minor Folate deficiency Sideroblastic anemia Pernicious anemia Lead toxicity Down syndrome Anemia of chronic disease Normal newborn nadir Chronic renal insufficiency Post-splenectomy Neoplastic Ileal resection Severe malnutrition Drugs Inborn errors of metabolism Hypothyroidism Hemoglobin C variant Aplastic anemia Hemoglobin E variant Diamond-Blackfan anemia Fanconi’s anemia Erythroleukemia Dyskeratosis congenita Paroxysmal nocturnal hemoglobinuria

Further investigations: Further investigations: Iron panel (serum iron, Serum B12 ferritin, TIBC, TIBC % sat) Serum and RBC folate Hb electrophoresis Liver enzymes Lead level PTT Bone marrow aspiration Thyroid panel Newborn screen Hb electrophoresis

Bone marrow aspiration PEDIATRICS

Figure 18.1 Morphologic classiﬁ cation of normocytic, normochromic anemia.

Microcytic, Hypochromic Anemia LABORATORY DIFFERENTIATION OF MICROCYTIC, HYPOCHROMIC ANEMIAS

Bone Serum marrow Mentzer Condition Iron Transferrin Ferritin Iron TIBC Reticulocyte RDW Index∗ Iron Low High Low Absent High Low High <13 defi ciency Thalassemia Normal Normal Normal Normal Normal Normal Normal >13 minor or high or high or high or high Anemia Low Low Normal Normal Normal Normal Normal N/A of chronic or or or disease high high high

∗Mentzer index = MCV/RBC. 198 Pediatrics

Normocytic, Normochromic Anemia

Reticulocyte count∗ LOW HIGH

Bone marrow failure Hemorrhage or hemolysis

Thrombocytopenia or neutropenia? ↑ Bilirubin, LDH

Ye s N o Ye s N o

See Isolated Hemolysis Hemorrhage Pancytopenia RBC aplasia

Acquired: Congenital: Transient erythroblastopenia Diamond-Blackfan syndrome Direct of childhood Coombs Systemic illness (kidney, liver, hypothyroid) Infection Pure RBC aplasia Aplastic crisis (parvovirus B19)

Positive Negative (antibody-mediated) (not antibody-mediated)

Alloimmune hemolytic anemia Extrinsic: Intrinsic: Autoimmune hemolytic anemia Hypersplenism Membrane defect • Cold IgM: Mycoplasma Shear stress • Hereditary spherocytosis • Warm IgG: RA, SLE (mechanical heart valve) • Elliptocytosis Drug-induced hemolytic anemia Chemical agents Hemoglobinopathy • Cephalosporins, penicillins, Hypophosphatemia • Sickle cell anemia quinidine Paroxysmal nocturnal Enzymopathy hemoglobinuria • G6PD deficiency Microangiopathic (schistocytes): • Pyruvate kinase deficiency HUS, TTP, DIC

Figure 18.2 Differential diagnosis algorithm for normocytic, normochromic anemia. ∗Normal reticulocyte values by age: 0-2 days, 3-7%; 3-4 days, 1-3%; 5 days and older, 0.5-1.5%. Normal absolute reticulocyte values by age: 0-2 days 0.140-0.220 × 106/μL, 3-4 days 0.040-0.110 × 106/μL, 5 days and older 0.020-0.080 × 106/μL. Furthermore, a reticulocyte hemoglobin (RET-He), which provides a measure of iron availability for hemoglobin synthesis over the previous 3-4 days, may be helpful in diagnosing iron-deﬁ ciency anemia, or in assessing response to therapy. Normal values: < 2 yrs, 24.5-35.2 pg; 2+ yrs, 27.1-35.4 pg.

Iron-Deﬁ ciency Anemia • Presentation: Usually asymptomatic (screen at 6 and 12 mo or found on random on CBC); may show pallor and fatigue; ↑ HR. Usually caused by increased cow’s milk intake → developmental delay in severe cases. • Pathogenesis: Nutritional (child with ↑ milk intake with poor iron content, malabsorption). In adolescents, rapid growth and poor dietary intake or blood loss. Hematology 199

• Diagnosis: Made by Hx alone with trial of iron supplement, suggested by microcytic anemia on RBC indices, iron studies. • Treatment: Limit cow’s milk intake to 16 oz/d. Start elemental iron (3–4 mg/kg/d) with a small amount of orange juice; treat until Hb is normal and then continue for 1 mo to replete stores. Thalassemia COMPARISON OF THALASSEMIA

β-Thalassemia β-Thalassemia Major Minor α-Thalassemia (Cooley’s, Homozygous) (Heterozygous)

Presentation Varies: Asymptomatic Severe hemolytic anemia in Mild microcytic to hydrops fetalis infancy, hepatosplenomegaly anemia

Pathogenesis Deﬁ ciency in α-globin Complete absence of Reduced or synthesis (severity β-globin synthesis (β0/β0) to abnormal β-globin depends on number partial reduction (β+/β+) synthesis (heterozy- of genes deleted) gous)

Peripheral Microcytic anemia Severe hypochromia and Hypochromia and smear microcytosis, fragmented microcytosis, RBCs, nucleated RBCs,

NBS or Hb Hb Bart (γ4) Hb A (α2β2) absent Increased Hb A2 α electrophore- Hb H (β4) ↑ Hb F (α2γ2) ( 2δ2) sis ﬁ ndings ± ↑ Hb F (α2γ2)

Typical Southeast Asia Europe, Middle East, India, Europe, Middle East, population and Africa India, and Africa

Treatment Folic acid or transfu- Transfusion; splenectomy None necessary sion therapy if severe

Reproduced with permission from Pediatr Clin North Am 2008;55:447. PEDIATRICS Intracellular Defects

Sickle Cell Disease • Description: Autosomal recessive disease; 8% of African Americans have the sickle cell trait (heterozygous); variations cause different severity (SS > Sβ0 thalassemia > SC > Sβ+ thalassemia) • Diagnosis: Often identiﬁ ed on NBS or with positive FHx; send conﬁ rmatory test; hemoglobin electrophoresis. • Presentation: Symptoms occur after 6 mo age; persistence of fetal Hb (>30%) have mild or no sickle symptoms.

CLINICAL PRESENTATION AND TREATMENT OF SICKLE CELL DISEASE

Name Signs and Symptoms Acute Treatment

Pain crises Extremity, abdominal pain Hydration, narcotics, NSAIDs (ibuprofen or ketorolac)

Dactylitis (hand– Painful swelling of the hands Hydration, narcotics foot syndrome) and feet (infancy)

Splenic sequestra- Hypotension, anemia (caused Transfusion (simple or exchange), tion crisis by pooling of RBC in the oxygen, and splenectomy in severe spleen), splenomegaly cases

(continued on next page) 200 Pediatrics

Name Signs and Symptoms Acute Treatment

Acute chest crisis Fever, tachypnea, hypoxia, Hydration, oxygen, transfusion inﬁ ltrate (CXR) (exchange or simple), incentive spirometry, positive-pressure ventilation if severe

Aplastic crisis Severe anemia with reticulo- Transfusion cytopenia

Stroke Focal neurologic deﬁ cits, Exchange transfusion; chronic trans- altered mental status fusion therapy shown to prevent 80% of second strokes in pediatrics

• Secondary manifestations: Gallstones, renal disease, pulmonary hypertension, avascular necrosis, infection, retinopathy (autosplenectomy, 90% by age 6 yr).

HEALTH MAINTENANCE FOR SICKLE CELL DISEASE

Recommended Age Visits Studies Vaccines Screening

0–6 mo Every 2 mo CBC, reticulocyte PCV7 per None count, Hb electropho- regular resis, G6PD test schedule

6–24 mo Every 3–6 mo CBC, reticulocyte Annual None count, Hb electropho- inﬂ uenza resis, LFT, Chem 7, iron studies

2–5 yr Every 6 mo CBC, reticulocyte Pneumococ- Transcranial count, LFT, Chem 7, cal 23-valent Doppler (TCD) Iron studies, U/A and a booster every yr for at age 5 yr HbSS and S-β0 thalassemia; dentist

>5 yr Every 6–12 mo Same as 2–5 yr Annual TCD, retinal inﬂ uenza exam starting at 8 yr, hip X-ray starting at 10 yr, ECHO starting at 10 yr and repeated every 2 yr, dentist

Reproduced with permission from Pediatr Rev. 2007; 28:259.

• Treatment: Prophylactic penicillin VK (start by age 3 mo), folic acid (start by age 1 yr); chronic therapies → transfusion of RBC (goal HCT<30%), hydroxyurea; stem cell transplant may be an option for patients with a matched sibling. Hematology 201

WHITE BLOOD CELL DISORDERS AGE-SPECIFIC WHITE BLOOD CELL NORMAL VALUES∗

Total Leukocytes Neutrophils†

Age Mean Range Mean Range %

Birth —‡ — 4.0 2.0–6.0 —

12 h — — 11.0 7.8–14.5 —

24 h — — 9.0 7.0–12.0 — 1-4 wk — — 3.6 1.8–5.4 — 6 mo 11.9 6.0–17.5 3.8 1.0–8.5 32 1 y 11.4 6.0–17.5 3.5 1.5–8.5 31 2 y 10.6 6.0–17.0 3.5 1.5–8.5 33 4 y 9.1 5.5–15.5 3.8 1.5–8.5 42 6 y 8.5 5.0–14.5 4.3 1.5–8.0 51 8 y 8.3 4.5–13.5 4.4 1.5–8.0 53 10 y 8.1 4.5–13.5 4.4 1.8–8.0 54 16 y 7.8 4.5–13.0 4.4 1.8–8.0 57 21 y 7.4 4.5–11.0 4.4 1.8–7.7 59

Lymphocytes Monocytes Eosinophils Age Mean Range % Mean % Mean % Birth 4.2 2.0–7.3 — 0.6 — 0.1 —

12 h 4.2 2.0–7.3 — 0.6 — 0.1 — PEDIATRICS

24 h 4.2 2.0–7.3 — 0.6 — 0.1 — 1-4 wk 5.6 2.9–9.1 — 0.7 — 0.2 — 6 mo 7.3 4.0–13.5 61 0.6 5 0.3 3 1 y 7.0 4.0–10.5 61 0.6 5 0.3 3 2 y 6.3 3.0–9.5 59 0.5 5 0.3 3 4 y 4.5 2.0–8.0 50 0.5 5 0.3 3 6 y 3.5 1.5–7.0 42 0.4 5 0.2 3 8 y 3.3 1.5–6.8 39 0.4 4 0.2 2 10 y 3.1 1.5–6.5 38 0.4 4 0.2 2 16 y 2.8 1.2–5.2 35 0.4 5 0.2 3

21 y 2.5 1.0–4.8 34 0.3 4 0.2 3

∗Numbers of leukocytes are in X 109/L or thousands per mm3; ranges are estimates of 95% confi dence limits, and percentages refer to diff erential counts. †Neutrophils include band cells at all ages and a small number of metamyelocytes and myelocytes in the fi rst few days of life. ‡Insuffi cient data for a reliable count. Reproduced with permission from Rudolph’s Pediatrics, 21st ed. 2003. 202 Pediatrics

Leukocytosis (Am Fam Physician. 2000;62:2053) • Leukemoid reaction • Deﬁ nition: WBC count >50,000/mm3 with an increase in early neutrophil precursors • Etiology: Drugs (glucocorticoids, G-CSF, ATRA), infections (tuberculosis, pertussis), trisomy 21 in infancy

CAUSES OF LEUKOCYTOSIS

Neutrophilia Lymphocytosis Eosinophilia Monocytosis Primary Reactive Infectious Infl ammation Hereditary Infectious Parasites Infection MDS Mononucleosis HIV Brucellosis CML Pertussis Fungal Tuberculosis Secondary Bartonella Allergic disorders Mononucleosis Infection Toxoplasmosis Allergic rhinitis Rickettsia Inﬂ ammation Babesiosis Asthma Autoimmune Drugs (steroids, Noninfectious Connective tissue disease SLE, RA, IBD β-agonists, lithium) Hypersensitivity Medications Malignancy Asplenia Postsplenectomy Malignancy HD, JMML Malignancy Sarcoidosis Lipid storage disease

PANCYTOPENI DIFFERENTIAL DIAGNOSIS OF PANCYTOPENIA1

Congenital Acquired Fanconi anemia Idiopathic Familial aplastic anemia Leukemia/Tumor inﬁ ltration Dyskeratosis congenita Drugs Schwachman-Diamond syndrome Hypersplenism (sequestration) Chemicals and toxins Radiation Infection (ex EBV, CMV, Parvovirus) Hepatitis Thymoma Nutritional –B12, folate

∗Any patient with two or more abnormal cell lines should have a bone marrow exam. Reproduced with permission from Pediatr Rev. 1984;6:46.

Idiopathic Thrombocytopenic Purpura (ITP) • Diagnosis of exclusion (Pediatr Clin North Am 2008;55:393) • Typical presentation: Abrupt onset bleeding and petechiae after viral illness or immunization → patient well at time of presentation → labs: isolated ↓ platelets • Treatment: Observe (80%–90% of self-limited and resolve in 6 mo); consider treatment (IVIG, steroids, anti-RhD) only if massive bleeding or platelets ≤20,000/microL + risk of bleeding Hematology 203

PLATELET DISORDERS

Platelet disorder suspected Send: CBC, peripheral smear, TEG®

Quantitative defect: Thrombocytopenia Consider bone marrow aspirate Qualitative defect: Thrombocytopathy

Acquired: • Drug induced (aspirin) ↓ ↑ Production Destruction • Uremia • Myeloproliferative disorders

Congenital: Immune mediated: Bone marrow failure: See • Glanzmann’s thrombasthenia • Viral pancytopenia • Giant platelet syndromes • Drugs (antiepileptics, (Bernard-Soulier, Gray antibiotics, heparin) platelet, May-Hegglin) Congenital: • ITP • Amegakaryocytic thrombocytopenia (eg, TAR) • Wiskott-Aldrich syndrome Hypersplenism

Acquired: • Vitamin B12 or folate deficiency • Leukemia or myelodysplasia DIC • Liver failure (thrombopoietin) TTP • Sepsis • Dengue fever

Figure 18-3 Overview of platelet disorders. (Reproduced with permission from Pediatr Clin North Am. 2004;51:1109).

COAGULOPATHIES Diagnosis

DIFFERENTIAL DIAGNOSIS OF COAGULATION PEDIATRICS AND BLEEDING DISORDERS

PT PTT Platelets Diff erential Diagnosis Possible Follow-up Studies

von Willebrand disease PFA-100 Platelet function disorder von Willebrand studies Nl Nl Nl Factor XIII deﬁ ciency Platelet aggregation studies Fibrinolytic defect

↑ Hemophilia A or B PTT mixing study Circulating inhibitor Factor assays (VIII, IX, XI) von Willebrand disease von Willebrand studies Nl Nl Factor XI deﬁ ciency Heparin contamination

↑ Circulating inhibitor PT mixing study Vitamin K deﬁ ciency Factor assays (VII) Warfarin Nl Nl Factor VII deﬁ ciency 204 Pediatrics

• History (Pediatr Clin North Am 49:1239) • Does child bruise easily? (↑ sensitivity, ↓ speciﬁ city) or is there excess bleeding with separation of umbilical cord, circumcision, tooth eruption, dental extractions, minor trauma, menstrual bleeding, or surgery? • Epistaxis ≥30 min or results in ↓ Hb. • FHx of easy bruising or bleeding? Bleeding during childbirth? • Initial labs: CBC, peripheral smear, PT, PTT

BLEEDING DISORDERS • Thrombocytopenia and platelet dysfunction: See platelet disorders section. • Disorders of clotting factors (Blood 1994;84:3) • Hemophilia A (factor 8 deﬁ ciency; one in 5000 males) or hemophilia B (actor 9 deﬁ ciency; one in 25,000 males): X-linked recessive; severity based on the percent of factor present; should be suspected in any male with ↑ PTT.

TREATMENT OF ACUTE BLEEDING IN HEMOPHILIA PATIENTS∗†

Factor 8 Replacement Factor 9 Replacement Event Dose (% correction) Dose (% Correction) Comments Hemarthrosis 40–50 u/kg (80–100) 100–120 u/kg (80–100) Ice x 20 minutes, (any joint) immobilize x 48 hours Hematoma (soft 25–35 u/kg (50–70) 60–85 u/kg (50–70) Local ice pack x 20 tissue) minutes

Head trauma 50 u/kg (100) 120 u/kg (100) Do not wait for neurologic changes CT after ﬁ rst dose Maintain factor >80%

Major surgery 50 u/kg (100) 120 u/kg (100) Maintain factor >50%

Dental extraction 50 u/kg (100) 120 u/kg (100) Amicar 100 mg/kg Q6h x 3–5 d Mucosal, GI, or 35–50 u/kg (70–100) 85–120 u/kg (70–100) Search for cause of GU bleeding bleeding

∗Early therapy is important to minimize destructive changes from prolonged blood exposures. Treat within 45 minutes of suspected bleeding whenever possible. †Suspect inhibitor if the patient is not having the expected response to therapy.

VON WILLEBRAND DISEASE

Type Frequency Defect Diagnosis Treatment∗

1 80% Decreased vWF antigen decreased DDAVP eﬀ ective in vWF (relative) almost all

2 (A/B) 10%–15% Defective vWF vWF activity decreased DDAVP response variable

3 Rare Deﬁ ciency of vWF antigen absent DDAVP ineﬀ ective vWF (absolute)

∗Treatment is based on patient history, response to prior interventions, and severity of bleeding and includes DDAVP, antiﬁ brinolytics (Amicar), plasma-derived vWF concentrates, and cryoprecipitate. Hematology 205

RISK FACTORS FOR THROMBOEMBOLISM

Congenital Acquired

Common • Stasis or immobility: Surgery, trauma • Factor V Leiden • Central venous line • Prothrombin 20210 • Infl ammation: Infection, malignancy, SLE, ↑ factor ↑ Uncommon VIII, vWF ↑ • Antithrombin III defi ciency • Abnormal endothelium: Hyperlipidemia, age • Protein C or S defi ciency • Homocystinuria • Dysfi brinogenemia • Nephrotic syndrome

THROMBOPHILIA • Diagnosis: Patient history: Idiopathic DVT, PE, stroke; multiple or recurrent thrombotic events even if other risk factors present. FHx of DVT, PE, stroke, or MI before 50 yr; multiple pregnancy loss; known thrombophilia. Thrombophilia testing is controversial; consider clinical utility.

ANTICOAGULATION THERAPY∗

Drug Mechanism Route Monitoring Pros Cons

UFH Complexes IV drip PTT goal, Can be stopped Frequent moni- with anti- Rarely 70–100 sec quickly or toring thrombin to sub-Q Anti-Xa activity reversed with Risk of HIT inactivate goal 0.3–0.7 U/mL protamine thrombin

LMWH Inactivates Sub-Q Anti-Xa goal Does not require Not fully factor Xa 0.5–1.0 frequent moni- reversible toring Patient or parent dosing PEDIATRICS Warfarin Inhibits produc- PO INR goal, 2–3† Oral dosing Drug and food tion of vitamin Best option for interactions K–dependent long-term treat- Diﬃ cult to titrate factors (II, VII, ment in small patients IX, X) Teratogen

∗Typical course for DVT or PE: UFH or LMWH for 7–10 d followed by 3–6 mo of LMWH or oral anticoagulants. Therapy should be tailored to the clinical situation. † This is a general range; INR should be based on the degree of anticoagulation needed for the clinical situation. Reproduced with permission from Chest 2008;133(suppl):887S–968S.

BLOOD PRODUCTS Defi nitions • Blood type: Detection of the presence or absence of ABO and Rh antigens • Cross-match: Determine compatibility of donated unit of blood with intended recipient • Ab screen (indirect Coombs): Test for presence of alloantibodies (not bound to RBCs) to blood antigens • Clinically signifi cant major antibodies (those which are likely to cause hemolytic transfusion reactions), in addition to A and B antibodies, include: D, C, c, E, e, K, k, Fya, Fyb, Jka, Jkb, S, s. These may be due to pregnancy, previous transfusions, etc. Antigen-negative, fully crossmatched PRBCs should be ordered in the presence of any of these antibodies. • Clinically insignifi cant antibodies (M, N, P1, Lea, Leb ) rarely cause transfusion reactions. While a full crossmatch with recipient serum and donor PRBCs is still recommended, antigen-negative units are not absolutely required. 206 Pediatrics

• Direct Coombs: Test for autoantibodies (bound to RBCs) to blood antigens • Extended phenotype matching: Test to prevent alloimmunization against C, D, E, and Kell antigens in patients receiving frequent transfusions (eg, sickle cell disease) Blood Component Therapy • Potential risks of blood transfusion • Infectious: HIV-1 (one in 2.1 million), hepatitis C (one in 1.9 million), hepatitis B (one in 205,000–488,000), bacterial contamination (cultured apheresis platelets, one in 75,000; random donor platelets tested by surrogate methods, one in 33,000) • Noninfectious: Acute include hemolysis, fever, allergy, TRALI, transfusion associated circulatory overload (TACO); delayed include hemolysis, transfusion-associated GVHD, transfusion-associated hemosiderosis • Premedication: Diphenhydramine (0.5 mg/kg; maximum dose, 50 mg), acetaminophen (10–15 mg/kg; maximum dose 650 mg), hydrocortisone (1–2 mg/kg, maximum dose 250 mg) (Note: There is no deﬁ nitive evidence to advocate for empiric use.)

Red Blood Cells INDICATIONS FOR PACKED RED BLOOD CELL TRANSFUSION

Hemoglobin (g/dL) Patients Who May Benefi t from Transfusion Intervention >10• Neonates • Underlying pulmonary disease or prolonged ventilation • Underlying cardiac disease 8–10• Undergoing radiation therapy <8• Limited utility of other forms of therapy for anemia • Clinical symptoms related to anemia

• AS-1 unit: HCT 55%–65% (mean 57%); volume 250–350 mL (mean 300 mL); shelf life 42 days • Dosing: Expected Hb rise after transfusion of 10–15 mL/kg is 2 g/dL; expected rise after 5 mL/ kg transfusion is 1 g/dLL

Platelets INDICATIONS FOR PLATELET TRANSFUSION∗

Platelet Count Patients Who May Benefi t from Transfusion (per mm3) Intervention >100,000• Active bleeding with known or suspected platelet dysfunction • Unexplained, excessive bleeding during cardiopulmonary bypass • Bleeding while undergoing ECMO therapy 50,000–100,000• Active bleeding • ECMO • Undergoing invasive procedure 20,000–50,000• Underlying brain tumor • Undergoing radiation therapy <20,000• Symptoms of thrombocytopenia, depending on utility of other forms of therapy • Underlying diagnosis related to bone marrow suppression

∗Not for neonates; decisions for transfusion should be based on clinical situations (eg, no platelet transfusion for patients with ITP + platelets at 10,000/mm3 + no bleeding); however, transfuse a patient with AML + platelets at 10,000/mm3 + no bleeding. Hematology 207

• Dosing: <10 kg = 5–10 mL/kg; ≥10 kg = 1 random U/10 kg; maximum, 6 pooled random donor units or 1 pheresis unit • Expected increase in count is 50,000 platelets/mm3 (ideal recovery); measured 10–60 min after transfusion • Etiology for refractoriness∗ to platelet transfusion: Fever, splenomegaly, bleeding, infection, DIC, history of multiple transfusions, HIT, simultaneous use of amphotericin, or presence of antiplatelet antibodies (Note: Patients who may undergo future SCT but for whom SCT is not an immediate option should receive CMV-safe blood. Autologous SCT does not require CMV-seronegative blood.) • Contraindications: TTP and HIT Plasma • Components: Coagulation factors, antithrombin, protein C, and protein S • 1 U plasma volume = 200–250 mL; 1 jumbo unit = 400–600 mL • Indications: Patients who may benefi t from transfusion intervention: • Active bleeding, surgery, or invasive procedure and • Prolonged PT or PTT caused by defi ciency of coagulation factor(s) (except for fi brinogen, factor 8, factor 9, or factor 13) • PT and PTT studies pending with known or anticipated abnormalities • Massive bleeding (>50% loss of total blood volume within 3 h) • TTP, DIC, Rapid correction of warfarin effect or vitamin K defi ciency • Dosing: 10–15 mL/kg will result in a 15%–20% rise in factor level (assume ideal recovery); this may not be true for factor 5 (labile factor) and factor 7 (short half-life) Cryoprecipitate • Components: Fibrinogen, factor 8, von Willebrand factor, factor 13, and fi bronectin • 1 U of cryoprecipitate volume = 15 mL • Indications: Patients who may benefi t from transfusion intervention: • Active bleeding with hypofi brinogenemia or dysfi brinogenemia • Active bleeding with suspicion of hypofi brinogenemia or dysfi brinogenemia and fi brinogen assay pending • Hypofi brinogenemia or dysfi brinogenemia, undergoing an invasive procedure • Undergoing cardiac surgery with excessive bleeding and fi brinogen assay pending

• Known or suspected factor 13 defi ciency undergoing an invasive procedure or actively bleeding PEDIATRICS • Dosing: 1–2 U/10 kg results in 60–100 mg/dL rise in fi brinogen (assume ideal recovery). Granulocytes • Indications: Neutropenia of neutrophils <0.2 K/mm3 and documented refractory infection failing appropriate antibiotic therapy of >48 h; avoid transfusion within 6 h of amphotericin administration Special Considerations • Leukocyte-reduced blood (=CMV safe) • Purpose: To prevent recurrence of febrile, nonhemolytic transfusion reactions; to reduce CMV transmission in patients at risk of primary CMV infection; and to reduce the risk of alloimmunization to HLA antigens • Indications: (1) Solid organ transplant recipients or candidates; (2) past or present immunocompromised conditions, such as hematologic malignancies; (3) HIV infection; (4) pregnant women (to protect the fetus); (5) neonates and fetuses; (6) patients receiving chronic transfusion therapy • CMV-seronegative blood components • Indications: • Allogenic SCT recipients when both donor and recipient CMV are negative by PCR. (Note: Patients who may undergo future SCT but for whom SCT is not an immediate option should receive CMV-safe blood. Autologous SCT does not require CMV-seronegative blood.) • Patients with suspected or confi rmed primary cellular immunodefi ciency or combined immune defi ciency (eg, DiGeorge syndrome, SCID and Wiskott-Aldrich syndrome) (Note: Patients with partial DiGeorge syndrome may receive CMV-safe blood components.) 208 Pediatrics

• Irradiated blood (consider for PRBC or platelets) • Purpose: to prevent transfusion GVHD in immunosuppressed patients • Indications: • Bone marrow transplant recipients or potential recipients • Past or present immunocompromised conditions (congenital, iatrogenic, or acquired) • HLA-matched or cross-matched platelets • Directed donor units from blood relatives • Suspected or confi rmed primary cellular immunodefi ciency or combined immune defi ciency • Fetuses and neonates

Useful Formulas

Total blood volume (TBV): Preterm neonate = 100 mL/kg; term neonate = 85 mL/kg; 1–4 mo = 75 mL/kg; >4 mo = 70 mL/kg Plasma volume (PV): TBV × (1 – Hct/100) RBC replacement: Volume (mL) = TBV × desired HCT increase ÷ 57% (average HCT of PRBC) • Number of units cryoprecipitate needed for fi brinogen replacement Desired fi brinogen level∗ – Initial fi brinogen level) mg/dL × PV (mL) ÷ 100

250 mg (ﬁ brinogen of 1 U of cryoprecipitate) • Antithrombin (AT) replacement (for patients receiving unfractionated heparin therapy)† [(Desired AT level‡ – Current AT level) × Body weight (kg)]/1.4

∗200 is usually used as the goal ﬁ brinogen level. †May round up to a maximum of 300% of the calculated dose or the amount in one vial, whichever is less. ‡120 is usually used as the desired AT level.

Available at www.AccessPediatrics.com • Folate defi ciency • Vitamin B12 defi ciency PEDIATRICS exes exes dis- ex exes Key Milestones stool First by and void age 24 h of Loss umbilical stump (typically 10 d–3 wk), BW regains wk 2 by Moro, walking/ stepping refl disappear Rooting refl appears Teething begins, neck tonic and palmar grasp refl disappear ng (continued on next page) Injury Prevention Should sleep on the back, Rear-facing car seat Keep home and vehicle smoke never free, shake baby Set water heater to temp <120 ºF leave Never infant unat- tended on high surface Check for of sources lead in the home Baby proofi of home, choking awareness uoride Healthy Healthy Habits um- Allow bilical cord air dry, to ill avoid contacts, use rectal thermom- (fever eter ≥100.4 ºF) Avoid direct sunlight Tummy time while awake No bottle propping Read books with baby Assess fl source 209 Nutrition Breastfeed- ing or formula, start vitamin D for exclusively breastfed infants Breastfeed- ing or formula Breastfeed- ing or formula Breastfeed- ing or formula May introduce cereal Start single- ingredient one foods at a time Universal Screening meta- State bolic screen, newborn hearing screen, height, weight, FOC Height, weight, FOC Height, weight, FOC Height, weight, FOC Height, weight, FOC Oral health, height, weight, FOC xes on xes y fi y exes Developmental Developmental Observations of Periods wakefulness, to responsive voice parent and touch primitive faces, refl prone holds head up when prone, follows coos, visually past midline sounds, turns to own regards hand reaches sounds, objectsfor Age New- born 1 wk Briefl 1 mo Lifts head while 2 mo Social smile, 4 mo rolls, Babbles, 6 mo imitates Sits, High-Yield Ambulatory Care Ambulatory High-Yield OVERVIEW SUPERVISION ROUTINE HEALTH health supervi- guidelines for routine Academy of Pediatrics has established The American are the physical exam, developmental observation, univer- sion visits. Priorities of these visits 19-1 and 19-2) and anticipatory guidance (including sal screening, immunizations (Figures prevention, and evaluation of milestones). nutrition, healthy habits, injury universal screening recommendations see: For complete AAP bright futures http://brightfutures.aap.org/3rd_Edition_Guidelines_and_Pocket_Guide.html CHAPTER 19 210 Pediatrics

Developmental Universal Healthy Injury Key Age Observations Screening Nutrition Habits Prevention Milestones

9 mo Stranger Develop- Finger Brush Lock up Plantar anxiety, object ment, oral foods teeth with poisons, reﬂ ex starts permanence, health, water or cleaners, to disap- feeds self, pulls height, soft tooth- chemicals pear to stand weight, brush FOC

12 mo Waves bye-bye, Anemia, May First May use starts to walk, lead (high introduce dental forward- says “mama” prevalence, cow’s milk visit, start facing car and “dada” Medicaid), instead of bottle seat if 12 (speciﬁ c) height, formula weaning mo and weight, >20 lb FOC

15 mo Speaks two or Height, Three Avoid three words, weight, meals/d nighttime scribbles, walks FOC with snacks bottle well

18 mo Speaks six Develop- Limit juice Consistent Prevent Temper words, runs, ment, au- intake discipline burns (eg, tantrums stacks blocks, tism, height, for teach- hot liquids begin uses spoon weight, ing and on stove), FOC protect- no spank- ing, avoid ing punishing

2 yr Speaks 50 Autism, Transition Limit TV Supervise Toilet train- words, two- lead (high from whole viewing to child ing begins word phrases, prevalence, to low-fat <2 hr/d outside follows two- Medicaid), milk step command, height, pretend play weight, FOC, BMI

2.5 yr Speaks three- Develop- Continue Fire safety to four-word ment, to read phrases, height, with child language weight, understand- FOC, BMI able 50% of the time, throws ball, puts on clothes with help, points to body parts

3 yr Self-care skills Visual acu- Use “time- Switch to (feeding, dress- ity, measure outs” for belt- ing), language blood pres- discipline, positioning understandable sure, height, interactive booster 75% of the time, weight, play seat rides tricycle, FOC, BMI when >40 walks upstairs, pounds alternating feet, and ears copies circle reach top of car seat

(continued on next page) High-Yield Ambulatory Care 211

Developmental Universal Healthy Injury Key Age Observations Screening Nutrition Habits Prevention Milestones

4 yr Tells stories, Visual acu- Promote Teach to Assess names four ity, hearing, healthy swim school colors, speech blood pres- daily readiness mostly under- sure, height, routines standable, cop- weight, BMI ies cross, hops, dresses self

5–6 yr School readi- Visual acu- Breakfast Limit Bike hel- Par- ness skills ity, hearing, before candy, met, teach ticipation in measure school, eat soda, and safe street organized blood pres- 5+ servings high-fat habits activities, sure, height, of fruit and snacks; (crossing transition- weight, BMI veggies per regular and riding ing to kin- day dental school dergarten visits bus)

7 and Physical, cogni- Visual acu- ≥2 cups of Be active Teach 8 yr tive, emotional, ity, hearing low-fat milk at least home social, moral (8-yr visit), or dairy per 60 min/d, safety rules competencies blood pres- day brush for ﬁ re and sure, height, teeth twice emergen- weight, BMI per day cies

9 and Sense of self- Visual acu- Encour- Be active Switch May be 10 yr conﬁ dence, ity, hearing age child at least 60 from starting increasing re- (10-yr visit), to make minutes booster sexual sponsibility and measure healthy per day seat to develop- independence blood pres- food safety belt ment sure, height, choices when belt weight, BMI indepen- ﬁ ts (usu- dently ally when greater than 4’9”) PEDIATRICS

11–14 yr Physical, Vision, 3+ servings Healthy Counsel to Puberty emotional, blood pres- of low-fat eating minimize academic, social sure, height, milk or risks well-being weight, BMI dairy per (drugs, day pregnancy, STIs, guns)

15–17 yr Physical, Vision, Three Protect Assess Driver’s emotional, blood pres- balanced hearing for risky license academic, social sure, height, meals per (head- behavior well-being weight, BMI day, eat phones, with family music)

18–21 yr Physical, Vision, dys- Three Self breast Assess Ability to emotional, lipidemia, balanced and for risky vote, may academic, social blood pres- meals per testicular behavior transition well-being sure, height, day, eat exams to indepen- weight, BMI with family dent living

SELECTIVE SCREENING RECOMMENDATIONS The American Academy of Pediatrics recommends universal screening for a variety of medical conditions. In certain populations, however, selective medical screening is performed if historical or social risk assessment warrants further screening. 212 Pediatrics

Selective Screening Visit Notes

Oral health: 12, 18 mo; Referral to dental home for patients at high risk of Dental home 2, 2.5, 3, 6 yr caries

Oral health - 12, 18 mo; Prescribe oral fl uoride supplementation to children fl uoride 2, 2.5, 3, 6 yr older than age 6 mo whose primary water source is defi cient in fl uoride (see chapter 10)

Blood pressure <3 yr Assess BP in children with history of prematurity, congenital heart disease, recurrent UTI, known renal or urologic disease, transplant, increased ICP, family history of congenital renal disease

Vision All visits when Age-appropriate evaluation for vision problems based universal on history and physical exam; children at high risk of screening not eye problems (eg, those with developmental delay, performed systemic diseases associated with eye abnormalities) should be referred to an ophthalmologist

Hearing 4 mo–3 yr; Young children should be monitored at each visit for 11–21 yr auditory skills, middle ear status, and developmental milestones; if there are concerns, a global screening tool should be used or the patient should be referred to audiology

Anemia 4 and 18 mo; Screen for anemia in infants who were premature then annually and older children who consume a low-iron diet (eg, vegetarians) and do not take an iron supplement; screen adolescent girls every 5–10 yr or annually if heavy menses

Lead 6 mo–6 yr Test blood lead level if screening questionnaire results (when universal are positive for potential lead exposure (lives in home screening for built before 1950, lives in home built before 1978 being high prevalence renovated in past 6 months, or sibling or playmate with or per Medicaid lead poisoning) requirement not done)

Tuberculosis 1, 6, 12, 18 mo; Annual TB skin test for children with HIV or incarcer- then annually ated adolescents; skin test those with risk factors (eg, family member with TB or positive skin test result or child born in, traveled to, or contact with person from high-risk country)

Dyslipidemia 2, 4, 6, 8, 10 yr; Screen children who have family history of premature annually when coronary artery disease, stroke, or peripheral vascular not universally disease (onset age <55 yr) or with parental hyper- screened lipidemia; overweight or obese children may also be screened.

Chlamydia and 11–21y r if Screen sexually active female patients annually gonorrhea sexually active

HIV and 11–21 yr if Screen sexually active patients who have high-risk syphilis sexually active behavior

Cervical 11–21 yr if Screen all sexually active females within 3 years of dysplasia sexually active onset of sexual activity or by age 21 yr

PEDIATRICS

First does may be administered at 9 years for females (HPV4 or HPV2) or males (HPV4) males or HPV2) or (HPV4 females for years 9 at administered be may does First

∗

2010;58(51 and 52):1–4. and 2010;58(51 MMWR from Adapted

2010 Recommended immunization schedule children birth to age 18 yr. Based on vaccination schedules released Jan 8, 2010. For fu For 2010. 8, Jan released schedules vaccination on Based yr. 18 age to birth children schedule immunization Recommended 2010 ll details, see http://www.cdc.gov/vaccines. http://www.cdc.gov/vaccines. see details, ll Figure 19-1 19-1 Figure

groups ages ages

immunization

recommended recommended high-risk

Range of of Range Catch-up Catch-up Certain

HPV series HPV HPV HPV (3 doses) (3 HPV

MCV Meningococcal MCV MCV

Hepatitis A Hepatitis HepA (2 doses) (2 HepA HepA series HepA

series Varicella Varicella Varicella Varicella

ese,mms rubella mumps, Measles, MMR MMR MMR series MMR

Influenza Influenza (yearly) Influenza

213

IPV P IPV IPV IPV IPV series IPV Inactivated poliovirus Inactivated

PPSV Pneumococcal C PCV PCV PCV PCV

yeb type influenzae Haemophilus i Hib Hib Hib Hib

Diphtheria,tetanus,pertussis TPDa DTaP DTaP DTaP DTaP DTaP Tdap Tdap

Rotavirus RV VRV RV

Hepatitis B Hepatitis HepB HepB series HepB HepB series HepB HepB

7–10 yr 7–10 13–18 yr 13–18 yr yr mo mo mo mo mo mo mo mo 11–12 yr 11–12 Vaccine Birth Age

4–6 2–3 19–23 18 15 12 6 4 2 1 214 Pediatrics

Catch-up Vaccination Schedule∗ Minimum Interval Between Doses Minimum Age for Dose 1 to Dose 2 to Dose 3 to Dose 4 to Vaccine Dose 1 Dose 2 Dose 3 Dose 4 Dose 5 Catch-up Vaccination Schedule for Children Aged 4 mo–6 y Hepatitis B Birth 4 wk 8 wk (and ≥ 16 weeks after ﬁ rst dose) Rotavirus∗∗ 6 wk 4 wk 4 wk

Diphtheria, 6 wk 4 wk 4 wk 6 mo 6 M tetanus, pertussis Haemophilus 6 wk 4 wk 4 wk 8 wk (as fi nal infl uenzae (if fi rst dose (if current age dose) type b administered is younger than (This dose at younger 12 mo) only neces- than age 8 wk (as fi nal sary for chil- 12 mo) dose) dren aged 12 8 wk (as fi nal (if current mo–through dose) age is 12 mo 59 mo who (if fi rst dose or older and received 3 administered second dose doses before at age 12-14 administered at age 12 mo) mo) younger than No further age 15 mo) doses needed No further (if fi rst dose doses needed administered (if previous dose at age 15 mo administered or older) at age 15 mo or older) Pneumococcal 6 wk 4 wk 4 wk 8 wk (as fi nal (if fi rst dose (if current age dose) administered at is younger (This younger than than 12 mo) dose only age 12 mo) 8 wk necessary for 8 wk (as fi nal (as fi nal dose children aged dose for healthy for healthy 12 mo–59 children) children) mo who (if fi rst dose (if current age received 3 administered is 12 mo or doses before at age 12 mo or older) age 12 mo or for high-risk older or current No further children who age 24 through doses needed received 3 59 mo) (for healthy doses at any No further children if age) doses needed previous dose (for healthy chil- administered dren if fi rst dose at age 24 mo administered or older) at age 24 mo or older)

(continued on next page) High-Yield Ambulatory Care 215

Catch-up Vaccination Schedule∗ Minimum Interval Between Doses Minimum Age for Dose 1 to Dose 2 to Dose 3 to Dose 4 to Vaccine Dose 1 Dose 2 Dose 3 Dose 4 Dose 5 Inactivated 6 wk 4 wk 4 wk 6 mo poliovirus Measles, 12 mo 4 wk mumps, rubella Varicella 12 mo 3 mo

Hepatitis A 12 mo 6 mo Catch-up Vaccination Schedule for Children Aged 7 to 18 Years Tetanus, 7 yr 4 wk 4 wk 6 mo diphtheria/ (if fi rst dose (if fi rst dose tetanus, administered administered diphtheria, at younger at younger † pertussis than age than age 12 mo) 12 mo) 6 mo (if fi rst dose administered at age 12 mo or older)

Human Papil- 9 yr 4 wk 12 wk (and lomavirus ≥24 wk since 1st dose) Hepatitis A 12 mo 6 mo PEDIATRICS Hepatitis B Birth 4 wk 8 wk (and ≥ 16 wk after 1st dose)

Inactivated 6 wk 4 wk 4 wk 6 mo Poliovirus Measles, 12 mo 4 wk mumps, rubella Varicella 12 mo 3 mo (if <13 y) 4 wk (if ≥ 13 y)

∗This table provides catch-up schedules and minimum intervals between doses for children whose vaccinations have been delayed ≥1 mo. Based on vaccination schedules released Jan 8, 2010. For full details, see http://www. cdc.gov/vaccines. ∗∗Do not initiate series after reaching 15 wk of age; do not give any dose after reaching 8 m of age. †Give all in the form of Td, with the exception of one Tdap between 10–18 yrs of age. Adapted from MMWR 2010;58(51 and 52):1–4.

TRUE AND FALSE CONTRAINDICATIONS TO IMMUNIZATION True contraindications to vaccination are relatively rare but must be appreciated. Several precautions (relative contraindications) exist for the administration of certain immunizations; refer to the current Red Book for population- and immunization-speciﬁ c relative contraindications to vaccination. 216 Pediatrics

For additional vaccine contraindication and precaution information: MMWR 2006;55(RR–15):10–14

False Contraindications True Contraindications (Precaution)

Anaphylaxis to a previous vaccine or Local reaction to a previous vaccine vaccine constituent

Moderate to severe illness Mild acute illness with low-grade fever, mild diar- Fever with signs that might be con- rheal illness in an otherwise well child, currently fused for adverse reaction to vaccine receiving antibiotic therapy, recent exposure to (advised to delay immunization) the vaccine-preventable disease

True Allergies Inﬂ uenza: Nonsevere (eg, contact) allergy to latex Neomycin: MMR, varicella, IPV, OPV or thimerosal Streptomycin: IPV, OPV Polymyxin B: IPV, OPV Gelatin: MMR, varicella, yellow fever Egg: Inﬂ uenza Yeast: Hepatitis B

Pregnancy Pregnancy in a household contact Approved: Tdap/Td, inactivated inﬂ u- enza vaccines Precaution: Hepatitis A, MCV4∗, IPV, and live vaccines†

Immunocompromised Patient Immunocompromised family member or (see “Immunization for Special household contact, asymptomatic or mildly symp- Populations”) tomatic HIV infection, humoral immunodeﬁ ciency (may not be eﬃ cacious)

DTap contraindicated if history of idio- Family history of allergy, seizures, or an adverse pathic encephalopathy within 7 days event after immunization of previous dose or until patient’s Precautions (not contraindications) for pertussis- progressive neurologic disease (in- containing vaccines: fantile spasms, recent or uncontrolled • seizures, progressive encephalopathy) Fever of >40.5 C ≤48 h of receiving previous dose excluded or stabilized • Collapse or shock-like state ≤ 48h of receiving previous dose Tdap contraindicated if history of • Persistent, inconsolable crying for ≥ 3h ≤ 48h of idiopathic encephalopathy within 7 receiving previous dose days of previous dose • Seizures ≤3 d of receiving a previous dose

MMRV is contraindicated in patients Mild acute illness with low-grade fever or mild with active febrile illness >101.3°F or diarrheal illness in an otherwise well child active untreated tuberculosis

Hib is absolutely contraindicated in Prematurity (all can be administered, hepatitis B infants <6 wk of age vaccine does not “count” until 2 kg)

∗No data. †Live virus vaccines: MMR, varicella, OPV, intranasal inﬂ uenza, rotavirus. High-Yield Ambulatory Care 217

IMMUNIZATIONS FOR SPECIAL POPULATIONS

Population Immunization Timing Notes Asplenic children 13-valent conju- 2, 4, 6 mo (including: sickle gate pneumococcal cell disease) vaccine Pneumococcal 2 yr 23-valent vaccine Quadrivalent 2 yr meningococcal polysaccharide vaccine

Pneumococcal 5 yr 23-valent vaccine booster Inﬂ uenza vaccine Annually starting at 6 mo

Immune com- Live viral and Contraindicated For recommendations for promised host bacterial immuniza- specifi c immunodefi cien- (eg. congenital tions cies, see current Red immunodefi ciency Book or Clin Infect Dis disorders) 2009;49:817 Patients receiving Bacterial and live Low dose: ∗ corticosteroids viral immuniza- <10 kg: <2 mg/kg/d (IV or PO only; tions or equivalent excludes inhaled, topical, local) >10 kg: <20 mg/d Administer per regular or catch-up vaccination schedule High dose: Depends on the duration of PEDIATRICS <10 kg: >2 mg/kg/d steroids: >14 d; wait 1 mo or equivalent after discontinuing steroids before administering im- >10 kg: >20 mg/d munization See notes <14 d: consider administration upon discontinuation of steroids or waiting ≤2 wk HIV Patients Inactivated: all Vaccines may be May administer second Live: Measles given if prednisone dose of MMR 4 wk after vaccine if not dose: >2 mg/kg/d the fi rst dose severely immuno- or equivalent or May administer second compromised; vari- >20 mg/d if patient varicella vaccine 3 mo after cella vaccine if CD4 >10 kg and duration the fi rst dose count >15%–25 % of steroids <14 d and patient asymptomatic Hematopoi- (See oncology etic stem cell chapter) transplant (HSCT) recipients

∗Live-virus vaccines: MMR, varicella, OPV, intranasal inﬂ uenza, rotavirus. CHAPTER 20 Infectious Disease

ANTIBIOTIC GUIDE PENICILLINS

Bactericidal: Inhibit bacterial cell wall synthesis via competitive inhibition of transpeptidase Antimicrobial Adverse Class Examples Spectrum Eff ects Miscellaneous

Narrow • Penicillin • Streptococcus • Anaphylaxis • Penicillin V is spectrum G (IV) Group A, B, • Rash acid stable in the (β-lactamase viridans stomach • Benzathine • Drug fever susceptible) penicillin G • Most Streptococ- • Resistance • Bone marrow (IM) cus pneumoniae caused by suppression • Procaine peni- • Treponema degradation of • Hemolytic cillin G (IM) pallidum antibiotic by anemia bacterial penicil- • Penicillin V • Neisseria • Interstitial linases (PO) meningitidis nephritis • Actinomyces spp. • Renal • Pasteurella impairment multocida • Some anaerobes

Aminopeni- • Ampicillin • Streptococcus • GI disturbance • Better PO with cillins (IV, IM, PO) Group A, B, • Elevated LFTs amoxicillin than viridans ampicillin • Amoxicillin • Bone marrow (PO) • S. pneumoniae suppression • Enterococcus spp. • Hemolytic • Listeria monocy- anemia togenes • Allergic • Haemophi- reaction lus infl uenzae • Renal if β-lactamase impairment negative • Kingella kingae • Some gram- negative organisms: Escherichia coli, Salmonella spp., Shigella spp., Proteus spp.

(continued on next page)

218 Infectious Disease 219

Bactericidal: Inhibit bacterial cell wall synthesis via competitive inhibition of transpeptidase Antimicrobial Adverse Class Examples Spectrum Eff ects Miscellaneous

β-Lactamase • Nafcillin (IV) • S. aureus (MSSA) • Interstitial • No activ- resistant (anti- • Oxacillin (IV) • Streptococcus nephritis ity against staphylococcal gram-negative • Dicloxacillin Group A, B, • Renal penicillins) organisms (PO) viridans impairment • S. pneumoniae • Hepatic • Nafcillin causes toxicity more phlebitis than oxacillin • Bone marrow (decreased with suppression slow infusion, • Allergic large-gauge IV) reaction

Anti- • Piperacillin (IV) • Pseudomonas • Platelet • S. viridans and pseudomonal • Ticarcillin (IV) aeruginosa dysfunction Enterococci are penicillins only 30%-60% • Carbenicillin • Streptococcus • High Na load susceptible (PO) Group A, B, • Hypokalemia viridans • Serum • S. pneumoniae sickness • Enterococcus spp. • Bone marrow • Some gram- suppression → negative • Renal impair- Escherichia coli, ment Enterobacter spp., Salmonella spp., Shigella spp., Proteus spp., Citrobacter spp., Haemophilus spp.

• Neisseria spp. PEDIATRICS

Penicillin + • Amoxicillin + • Streptococcus • GI disturbance • S. viridans and β-lactamase clavulanate Group A, B, • Diarrhea Enterococci are inhibitor (PO) viridans (especially only 30%–60% • Ticarcillin + • S. pneumoniae amoxicillin/ susceptible clavulanate clavulanate) to ticarcillin/ • Enterococcus spp. clavulanate and (IV) • Rash • S. aureus (MSSA) piperacillin/ • Ampicillin + • Renal impair- tazobactam sulbactam (IV) • Gram-negative organisms: E. ment • Piperacillin + coli, Klebsiella tazobactam spp., Salmonella (IV) spp., Shigella spp., Proteus spp., Aeromonas spp., Pasteurella multocida • P. aeruginosa (piperacillin/ tazobactam and ticarcillin/ clavulanate) • Anaerobes 220 Pediatrics

CEPHALOSPORINS

Bactericidal: Inhibit bacterial cell wall synthesis via competitive inhibition of transpeptidase; more resistant to β-lactamases; ~10% of patients with a severe allergic reaction to penicillin have allergic reactions to cephalosporins Antimicrobial Adverse Class Examples Spectrum Eff ects Miscellaneous

First • Cefazolin (IV) • Streptococcus • Anaphylaxis • Minimal CSF generation • Cephradine Group A, B, viridans • Rash penetration (IV, PO) • S. pneumoniae • Delayed rash • Renal excretion • Cephalexin • S. aureus (MSSA) • Drug fever • Cephalosporins (PO) have no • Limited gram- • Bone activity against • Cefadroxil (PO) negative activity marrow sup- Enterococcus • Cephapirin (IV) pression spp. • Renal impairment

Second • Cefamandole • Streptococcus • Allergic • Minimal CSF Generation (IV, IM) Group A, B, viridans reaction penetration • Cefuroxime • S. pneumoniae • Coagulation • Renal excretion (IV, PO) • S. aureus (MSSA) disturbance • Decreased • Cefonicid (IV) • Some gram-neg- • Bone gram-positive • Cefaclor (PO) ative organisms: marrow sup- activity pression compared with • Cefprozil (PO) M. catarrhalis, H. infl uenzae, E. coli, • Renal impair- ﬁ rst generation • Cefotetan (IV) Klebsiella spp., ment but improved • Cefoxitin Proteus spp. gram-negative (IV, IM) activity • Some anaerobes (cefotetan, cefoxitin)

Third • Cefotaxime • Streptococcus • Biliary • Good CSF generation (IV, IM) Group A, B, viridans sludging penetration • Ceftizoxime • S. pneumoniae (ceftriaxone) for cefotaxime, ceftriaxone, and (IV, IM) • Decreased anti- • Allergic ceftazidime • Ceftriaxone staphylococcal reaction (IV, IM) activity • Bone • Renal excretion • Ceftazidime • Neisseria spp. marrow sup- • Better gram- pression negative activ- (IV, IM) • Gram-negative ity, less gram- • Ceﬁ xime (PO) organisms: • Renal impair- M. positive activity , ment • Cefpodoxime catarrhalis H. compared with , , (PO) infl uenzae E. coli ﬁ rst- and second- Klebsiella spp., • Cefdinir (PO) generation Enterobacter spp., • Ceftibutin (PO) cephalosporins Salmonella spp., except for Shigella spp., S. pneumoniae Proteus spp., Citrobacter spp., • Ceftriaxone is a Aeromonas spp. strong bilirubin displacer from

• P. aeruginosa albumin, limit- (ceftazidime only) ing its use in neonates

(continued on next page) Infectious Disease 221

Fourth • Cefepime • Pseudomonas • Allergic • Good gram- generation (IV, IM) aeruginosa reaction positive activity • Streptococcus • Bone except ( S. aureus Group A, B, viridans marrow and Enterococ- suppression cus spp.) and • S. pneumoniae gram-negative • Renal • Neisseria spp. activity, impairment • Gram-negative including organisms: M. ca- Pseudomonas tarrhalis, H. infl uen- spp. zae, E. coli, Klebsiella spp., Enterobacter spp., Salmonella spp., Shigella spp., Proteus spp., Citrobacter spp., Aeromonas spp.

AZTREONAM (MONOBACTAMS)

Bactericidal: Inhibit cell wall biosynthesis Adverse Examples Antimicrobial Spectrum Eff ects Miscellaneous

• Aztreonam • Gram-negative organisms • GI disturbance • Good CSF penetration (IV, IM) only: Neisseria spp., • Rash • Renal excretion M. catarrhalis, H. infl uenzae,

• No activity against PEDIATRICS E. coli, Klebsiella spp., Serratia gram-positive organ- spp., Salmonella spp., Shigella isms or anaerobes spp., Proteus spp., Citrobacter spp., Aeromonas spp., Pseudomonas spp.

CARBAPENEMS

Bactericidal: Inhibit cell wall biosynthesis Examples Antimicrobial Spectrum Adverse Eff ects Miscellaneous

• Meropenem • Streptococcus Group A, B, • GI disturbance • Renal excretion (IV, IM) viridans • Allergic reaction • No activity against • Imipenem • S. pneumoniae • Seizures with Enterococcus (IV, IM) • S. aureus (MSSA) imipenem in spp., Burkholderia cepacia, Stenotro- • Anaerobes children with meningitis phomonas • Gram-negative organisms: maltophilia Neisseria spp., M. catarrhalis, H. infl uenzae, E. coli, Klebsiella spp., Serratia spp., Salmonella spp., Shigella spp., Proteus spp., Citrobacter spp., Aeromonas spp., Pseudomonas spp. 222 Pediatrics

VANCOMYCIN (GLYCOPEPTIDES)

Bacteriostatic: Inhibit cell wall biosynthesis (one step earlier than PCN)

Antimicrobial Examples Spectrum Adverse Eff ects Miscellaneous

• Vancomycin • S. aureus (MSSA & MRSA) • Red man syndrome • Renal excretion (IV, PO) • Streptococcus Group A, • Ototoxicity • Activity against B, viridans • Renal toxicity, particu- most gram-positive • S. pneumoniae larly in combination organisms • Enterococcus spp. with other nephro- • No activity against toxic drugs gram-negative • CONS organisms except • Bacillus spp. Flavobacterium • Gram-positive meningosepticum anaerobes: Actinomyces • PO for C. diffi cile spp., Clostridium spp., infections ONLY Peptostreptococcus spp. • Use in high doses as an alternative for treatment of Listeria in a penicillin allergic patient

MACROLIDES AND AZILIDES

Bacteriostatic: Inhibit protein synthesis via binding to 50S ribosomal subunit

Antimicrobial Examples Spectrum Adverse Eff ects Miscellaneous

• Azithromycin • Atypical organisms→ • GI disturbance • Metabolized (IV, PO) Legionella spp., • Rare cholestatic by cytochrome • Erythromycin (IV, Mycoplasma spp., jaundice P450; thus, Chlamydia spp. multiple drug PO, ophthalmic • Prolonged QT interactions ointment) • Bordetella pertussis syndrome • Clarithromycin (PO) • Streptococcus spp. • Can use • Erythromycin eth- azithromycin or ylsuccinate use has • Mycobacterium clarithromycin been associated avium as empiric with pyloric steno- • Gram-negative therapy for cat sis in neonates organisms: Neisseria scratch disease spp., M. catarrhalis, H. infl uenzae, B. henselae Infectious Disease 223

CLINDAMYCIN (LINCOSAMIDES)

Bacteriostatic: Inhibit protein synthesis via binding to 50S ribosomal subunit Antimicrobial Examples Spectrum Adverse Eff ects Miscellaneous • Clindamycin • S. aureus (MSSA & • Pseudomembranous • Bile and urine (IV, IM, PO) MRSA) colitis excretion • Streptococcus Group • Hepatotoxicity • No activity against A, B, viridans • GI disturbance gram-negative organisms • S. pneumoniae • Bone marrow • Anaerobes suppression • No activity against Enterococci • Toxoplasma gondii • Rash • Minimal CSF • Plasmodium penetration falciparum and vivax

LINEZOLID (OXAZOLIDINONES)

Bacteriostatic: Inhibit protein synthesis via binding to 50S ribosomal subunit Antimicrobial Examples Spectrum Adverse Eff ects Miscellaneous • Linezolid • S. aureus (MSSA & • GI disturbance • Metabolized partially (IV, PO) MRSA) • Bone marrow in liver • CONS suppression • Excreted in urine • Streptococcus Group • Lactic acidosis • Expensive A, B, viridans • Peripheral • Side eﬀ ects associated • S. pneumoniae neuropathy with longer use (>4 wk) • Enterococcus spp. • Serotonin syndrome • 100% oral bioavailability (including VRE) • Optic neuritis • Active against some • Nocardia spp. atypical mycobacteria PEDIATRICS

TETRACYCLINS

Bacteriostatic: Inhibit protein synthesis via binding to 30S ribosomal subunit Antimicrobial Examples Spectrum Adverse Eff ects Miscellaneous • Tetracycline • Rickettsia spp. • GI disturbance • Absorption is im- (PO) • Chlamydia spp. • Phototoxic paired by food, milk, Ca, Mg • Doxycycline • Mycoplasma spp. dermatitis (IV, PO) • Renal toxicity • Avoid use in • Entamoeba histolytica children <8 • Minocycline • Hepatic toxicity (PO) • Ehrlichia spp. yr if alternate • Anaerobes • Staining of antibiotic is permanent teeth available except • Streptococcus Group A, B, for treatment of viridans • Fanconi syndrome • Teratogenic Rocky Mountain • S. aureus (MSSA & MRSA) spotted fever • Gram-negative organisms: M. catarrhalis, H. infl uenzae, E. coli, Legionella spp., Brucella spp. • Propionibacterium acnes 224 Pediatrics

AMINOGLYCOSIDES

Bactericidal: Inhibit protein synthesis via binding to 30S ribosomal subunit

Examples Antimicrobial Spectrum Adverse Eff ects Miscellaneous

• Amikacin • Gram-negative enteric organisms • Ototoxicity • Renal excretion (IV, IM) • P. aeruginosa • Renal toxicity • CNS penetration • Gentamicin • Tularemia spp. • Competitive minimal even (IV, IM) when meninges • Yersinia pestis neuromuscular • Streptomy- blockade inﬂ amed cin (IV, IM) • Brucella spp. (plus TMP/SMX or azithromycin) • Tobramycin (IV, IM, • Mycobacterium tuberculosis and inhaled) other atypical mycobacteria • Gram-positive synergy (GBS, E. faecalis, α strep)

FLUOROQUINOLONES

Bactericidal: Inhibition of bacterial DNA gyrase and topoisomerase IV, blocking nucleic acid synthesis Antimicrobial Adverse Class Examples Spectrum Eff ects Miscellaneous

First • Nalidixic acid • Not currently generation (PO) available in the quinolone United States

Second • Ciprofl oxacin • Gram-negative • Damage to • Use of fl uo- generation (IV, PO) organisms cartilage in roquinolones quinolone • Ofl oxacin • P. aeruginosa animals should be (PO, ophthal- • GI disturbance avoided in • Legionella spp., children <18 yr; mic, otic) • CNS symptoms Brucella spp. ciprofl oxacin is • Levofl oxacin • Atypical myco- • Tendonitis FDA approved (IV, PO, oph- bacterium in children <18 yr thalmic) • Clostridium • S. aureus (MSSA) diffi cile colitis for postexpo- sure treatment • S. pneumoniae • Prolonged QT of inhalation for levofl oxacin interval anthrax and • Hepatic dys- complicated function UTI • Rash • Resistance • Drug interac- develops by tions common, point mutations check prior to of DNA gyrase prescribing enzyme Infectious Disease 225

Bactericidal: Inhibition of bacterial DNA gyrase and topoisomerase IV, blocking nucleic acid synthesis Antimicrobial Adverse Class Examples Spectrum Eff ects Miscellaneous

Third • Gatiﬂ oxacin • Streptococcus • Damage to • Resistance generation (PO, ophthal- Group A, B, cartilage in develops by quinolone mic) viridans animals point mutations • S. pneumoniae • GI disturbance of DNA gyrase enzyme • Enterococcus • CNS symptoms spp. UTI • Hyper- and • S. aureus (MSSA hypoglycemia & MRSA) • C. diffi cile colitis • Listeria spp. • Drug interac- • Gram-negative tions common, organisms checked prior • Pseudomonas to prescribing aeruginosa

Fourth • Moxiﬂ oxacin • Streptococcus • Damage to • Treatment of generation (IV, PO, Group A, B, cartilage in choice for open quinolone ophthalmic) viridans animals globe injuries • S. pneumoniae • GI disturbance • Resistance • Enterococcus • CNS symptoms develops by point mutations spp. UTI colitis • C. diffi cile of DNA gyrase (MSSA • S. aureus • Drug interac- enzyme & MRSA) tions common, • Listeria spp. check prior to • Gram-negative prescribing organisms • P. aeruginosa

• Anaerobes PEDIATRICS

SULFONAMIDES

Bacteriostatic: Inhibition of bacterial tetrahydrofolate synthesis, blocking DNA synthesis Antimicrobial Adverse Examples Spectrum Eff ects Miscellaneous

• Trimethoprim/ • Gram-negative enterics • Allergic reaction • Metabolized sulfamethoxazole • S. pneumoniae • Rash in liver (IV, PO) • S. aureus (MSSA & MRSA) • GI disturbance • Renal excretion • Pneumocystis jiroveci • Bone marrow • No Group A Strep activity • Chlamydia spp. suppression • No Enterococcus • Toxoplasma spp. • Stevens- Johnson activity • Nocardia spp. syndrome • Contraindicated • Legionella spp. <3 months of • Brucella spp. age - due to risk of hyperbilirubinemia • Stenotrophomonas maltophilia 226 Pediatrics

METRONIDAZOLE (NITROIMIDAZOLES)

Bactericidal: Indirect DNA damage and protein synthesis inhibition Antimicrobial Examples Spectrum Adverse Eff ects Miscellaneous

• Metronidazole • Anaerobes • Neutropenia • Good CSF (IV, PO) • Clostridium spp. • Metallic taste penetration • Trichomonas • Reversible peripheral • Entamoeba histolytica neuropathy • No aerobic activity • Antabuse eﬀ ect when consumed with alcohol

DAPTOMYCIN (LIPOPEPTIDES)

Bactericidal: Binds to bacterial cell membranes leading to membrane depolarization and nucleic acid and /protein synthesis inhibition Antimicrobial Examples Spectrum Adverse Eff ects Miscellaneous

• Daptomycin (IV) • S. aureus (MSSA • GI disturbance • Renal excretion and MRSA) • Rash • Low lung penetra- • Streptococcus • Headache tion and decreased Group A, B, activity by pulmonary • Insomnia viridans surfactant; should • Myopathy (elevates • S. pneumoniae not be used to treat CK) pneumonia • Enterococcus spp.

RIFAMPIN (RIFAMYCINS)

Bacteriostatic: Inhibits nucleic RNA polymerase and blocks RNA transcription Antimicrobial Adverse Examples Spectrum Eff ects Miscellaneous

• Rifampin • S. aureus (MSSA and MRSA) • Asymptom- • Penetrates into all ﬂ uids (IV, PO) • Streptococcus Group A, B, atic jaundice and tissues viridans • Hepatotoxicity • Excreted via liver • S. pneumoniae • Reddish/ • Rapid development of • CoNS orange dis- resistance when used alone coloration of • Listeria spp. • Synergistic applications urine, sweat, (CONS and S. aureus) • Neisseria spp. tears • Useful in treating device- • M. catarrhalis, related infections H. infl uenzae • Should not be used alone • Brucella spp. to treat infection • M. tuberculosis • Many drug interactions PEDIATRICS culture, xation), fungal the morning, rst urine in tiocytic lymphadenitis) necrotizing pharyngitis, adenitis) ulcer, (SLE, JRA) Histiocytosis Kawasaki disease aphthous (periodic fever, PFAPA Sarcoidosis Postvaccination phenytoin) Drugs (eg, Leukemia and lymphoma Leukemia Connective tissue disorders tissue disorders Connective Kikuchi-Fujimoto syndrome (his- syndrome Kikuchi-Fujimoto • • • • • • • • • ) 2000;21:399. Salmo- , Bacillus spp. , Pediatr Rev Pediatr Yersinia , , nontuberculous , nontuberculous 2007;21:523 and (scrub typhus) Tularemia , Leptospira interrogans Leptospira , (cat-scratch disease) (cat-scratch Peptostreptococcus) ora (eg, Brucella (all part lymphadenopathy) of generalized , GABHS, GBS in neonate (90% of all cases) , GABHS, GBS in neonate See table “Infectious and noninfectious causes of lymphadenitis and See table “Infectious and noninfectious causes of lymphadenitis

culture increase with severity of disease), histopathology, fungal xation; titers Infect Dis Clin North Am fungal infections: c methods for diagnosing (highly infectious), DNA probes iffusion detectable 1–3 wk to 3–4 mo after onset; IgG—immunodiffusion, EIA, comple- iffusion detectable 1–3 wk to 3–4 ment fi EIA, serology, and bone marrow aspirate fungal culture, silver stain, radioimmunoassay, disease) or BAL (most useful in disseminated and serum galactomannan available nescent DNA probes ß-D evaluate for visceral involvement; eye exam; US or CT to KOH prep, endoscopy, monitor treatment in selected invasive candida and zygo- glucan useful to diagnose and mycoses infections Cryptococcosis: India ink stain or antigen test in CSF, culture, latex agglutination, EIA Cryptococcosis: India ink stain Paracoccidioidomycosis: 10% KOH, culture, serology Paracoccidioidomycosis: 10% Blastomycosis: 10% KOH or silver stain, fungal culture from biopsy or BAL; chemilumi- culture from biopsy or BAL; 10% KOH or silver stain, fungal Blastomycosis: 10%–20% Invasive disease: Gram stain, diagnosis of skin infections. Candidiasis: Clinical tests preferred (IgM—latex agglutination, EIA, immunod- Coccidioidomycosis: Serologic Histoplasmosis: Polysaccharide antigen assay on serum and fi Histoplasmosis: Polysaccharide Aspergillosis: 10% KOH prep or silver nitrate stain of tissue or BAL; fungal culture; BAL stain of tissue or BAL; fungal KOH prep or silver nitrate Aspergillosis: 10% rubella, mycobacteria nella typhi Adenovirus, EBV, CMV, HIV, HSV, mumps, measles, measles, mumps, HSV, HIV, CMV, EBV, Adenovirus, Anaerobic oral fl Anaerobic Corynebacterium diphtheria Toxoplasma gondii Toxoplasma Rickettsia tsutsugamushi Rickettsia Mycobacterium tuberculosis Mycobacterium Bartonella henselae Actinomyces israelii Actinomyces Treponema pallidum Treponema Histoplasmosis, blastomycosis, coccidioidomycosis blastomycosis, Histoplasmosis, Zoonoses (rare; (rare; Zoonoses S. aureus lymphadenopathy techniques are used. histopathology with special stains Alert the lab to what organism you are considering so the proper culture and staining Alert the lab to what organism Sporotrichosis: Serologic tests (latex agglutination, complement fi Sporotrichosis: Serologic tests • Parasite • • • • Viruses • Fungi InfectiousBacteria • • • • • • Noninfectious • • • • • • • Specifi Etiology: Data from Data from • LYMPHADENITIS AND LYMPHADENOPATHY • LYMPHADENITIS INFECTIOUS AND NONINFECTIOUS CAUSES OF AND LYMPHADENOPATHY • • COMMON COMMUNITY ACQUIRED FUNGAL INFECTIONS FUNGAL ACQUIRED COMMUNITY COMMON Diagnosing Fungal Infections Methods for The Sanford Anaerobes Anaerobes A, eds. Weakest coverage Atypicals Ceftaz Pseudomonas Spp. enterics Gram (–) Moraxella Moraxella H. flu H. Neisseria Spp.

Listeria Spp. VRE Enterococcus Spp. MRSA MSSA S. pneumoniae S. Sperryville, VA: Antimicrobial Therapy Inc; 2008.) Group A, B, B, A, Group S.viridans Gram (+) Coverage Gram (–) Coverage Anaerobes Strongest coverage ------Empiric antibiotic choice based on organism. (Reproduced with permission from Gilbert DN, Moellering RC, Eliopoulos GM, Sande M PCN PCN inhibitor Penicillin Linezolid Macrolides -Lactamase Amino-PCN Vancomycin Clindamycin Tetracyclines β Sulfonamides Carbapenems Monobactams Cephalosporin Cephalosporin Cephalosporin Cephalosporin First generation Fluroquinolones Third generation Aminoglycosides Fourth generation Anti-pseudomonas Second generation PCN+ Anti-staphylococcus Figure 20-1 Guide to Antibiotic Therapy.

228

PEDIATRICS

, 9 , Microbiology Clinical of Manual PR: Murray from (Adapted group. eld Lanceﬁ determine will typing Antigenic ed, ASM Press; 2007.) Press; ASM ed,

∗ th

Algorithm for identifying gram-positive organisms. organisms. gram-positive identifying for Algorithm Figure 20-2 20-2 Figure

S. viridans S. pneumoniae S.

MSSA MSSA MRSA

Group G Group

Group C C Group resistant susceptible

(group D) Spp. Spp. D) (group A) (group

(group B)* (group susceptible resistant Optochin Optochin

Enterococcus pyogenes S. S. agalactiae S. Oxacillin Oxacillin Oxacillin

Spp. Micrococcus

Hemolysis

Hemolysis Hemolysis S. saprophyticus S.

α β

Hemolysis ) or (

β α γ

S. aureus aureus S. S. epidermidis S.

Spp. Spp. Erysipelothrix

Spp. Arcanobacterium

Spp. Spp. Corynebacterium Spp. Actinomyces

Coagulase Coagulase PYR PYR

– – + +

Spp. Listeria Spp. Lactobacillus

229

Spp. Bacillus

Catalase Catalase – + . spp Staphylococcus Spp. Clostridium Streptococcus

Catalase Spores Catalase Spores – – + +

Cocci Cocci Rods (bacilli) Rods

Gram + Gram –

Cocci Coccobacilli Rods (bacilli)

Neisseria spp. Acinetobacter spp. Moraxella spp. Bordetella spp. Lactose fermenter Lactose nonfermenter Acinetobacter spp. Brucella spp. Francisella spp. Haemophilus spp. Oxidase + Oxidase – Kingella spp. Oxidase – Oxidase+ Oxidase – Moraxella spp.

230 Pasteurella spp. Thayer-Martin media Acinetobacter spp. HACEK group E. coli (indole +) Aeromonas spp. Proteus spp. Growth No growth Enterobacter spp. Burkholderia spp. Morganella spp. Klebsiella spp. Pseudomonas spp. Providencia spp. Citrobacter spp. Salmonella spp. Carbohydrate Serratia spp. Shigella spp. Moraxella spp. acidification tests Stenotrophomonas spp. Yersinia spp.

Maltose Maltose fermenter nonfermenter

N. meningitidis spp. N. gonorrhoae spp.

Figure 20-3 Algorithm for identifying gram-negative organisms. (Adapted from Murray PR: Manual of Clinical Microbiology, 9th ed, ASM Press; 2007.) Infectious Disease 231

• Defi nitions: Lymphadenopathy: enlarged lymph nodes; lymphadenitis: enlarged lymph node secondary to infl ammation or infection • Diagnosis • History and physical exam: Age of patient (see table “Age-specifi c common etiologies of cervical adenitis”), duration of swelling, dental disease, skin lesions, sick contacts, animal or insect exposures, TB exposure, immunization status, travel history; exam should include the oropharynx and dentition, conjunctiva, lymph nodes involved, hepatomegaly, splenomegaly, and skin

AGE-SPECIFIC COMMON ETIOLOGIES OF CERVICAL ADENITIS

Age Organism Neonates 2 mo–1 yr 1–4 yr 5–18 yr GABHS + ++ Group B streptococcus ++ +

S. aureus +++++++ Nontuberculous mycobacteria ++ + Bartonella henselae +++++ Mycobacterium tuberculosis + Toxoplasma gondii ++ Anaerobes + ++ Viruses + +

Reproduced with permission from Principles and Practice of Pediatric Infectious Diseases, 2nd ed. 2003:165.

PRESENTING FEATURES OF LYMPHADENITIS BY REGION OF INVOLVEMENT

Duration Possible Infectious PEDIATRICS of Onset Clinical Presentation Causes Acute bilat- Days Small, rubbery nodes with Viruses eral lymphadenitis little warmth or erythema GABHS (most common) M. pneumoniae Acute unilateral Days Tender, overlying warmth and S. aureus lymphadenitis erythema, ± ﬂ uctuance GABHS GBS B. henselae Subacute Weeks to Preceded by a papule or B. henselae or chronic months pustule, with warm, ery- lymphadenitis thematous node Unilateral small node with M. tuberculosis com- overlying erythematous or vi- plex, Nontuberculous olaceous hue, ± spontaneous mycobacteria drainage with sinus tract Unilateral or generalized M. tuberculosis lymph node involvement, ± complex fever, ⊕TST/IGRA Generalized lymph node T. gondii, Viruses (EBV involvement and CMV) Etiology: Norcardia, HIV, EBV, CMV, Toxoplasma Brucella, Actinomycosis, MTB (+ atypical), Syphilis, TST/ IGRA, HIV (as clinically indicated) test, other viral/ bacterial serology. Radiology: CXR Treatment: Based on etiology Consult: Consider ID Labs: CBC, LFT, Blood cx, Bilateral Systemic? consider Oncology/ Rheumatology consult If no infectious etiology YES NO Etiology: Toxoplasma, Management: Management: Brucella, fungal Chronic TB, Syphilis, S. typhi, Labs: CBC, LFT, Blood cx, TST/ IGRA, HIV (as clinically indicated) test, other viral/ bacterial serology, cx of aspirate Radiology: CXR Treatment: Based on etiology Consult: Consider ID HIV, EBV/CMV, Adenovirus, † or HIV Etiology: Unilateral Management: Bartonella, TB, Atypical MTB, Labs: CBC, LFT, Blood cx, TST/IGRA Bartonella serology, HIV (as clinically indicated), other viral/bacterial serology as clinically warranted Radiology: Consider US or CT Treatment: Based on etiology: • Bartonella: PO TMP/SMX, azithromycin (rifampin if disseminated) • preferred Atypical MTB: Complete Rifampin excision + clarithromycin • HIV: antiretroviral regimen Management: Abscess? Child presents with lymphadenitis PO: cephalexin, clindamycin Labs: None (consider CBC, Blood cx) Radiology: US if unclear Treatment: Empiric antibiotics* → Toxic? Unilateral Etiology: Bacterial (most often) YES NO Management: Acute Labs: None (consider BUN/ Cr if CT needed, CBC, Blood cx) Radiology: US if unclear (or CT) Treatment: Admit, I&D + empiric antibiotics* YES NO 2007;44:1057 Differential diagnosis and management of lymphadenitis lymphadenopathy. Management: Bilateral Etiology: Management: Viral (most often) and supportive care Labs: CBC, LFT, Blood cx, HIV (as clinically indicated) test, viral/ bacterial serology as clinically indicated Radiology: Consider CT Treatment: ABC, IV antibiotics (eg, vancomycin or clindamycin) Empiric bacterial therapy to cover staphylococci and streptococci Reassurance, followup Clin Infect Dis Figure 20.7 ∗ (an antibiotic with activity against MRSA should be selected in regions high prevalence); IV: Cefazolin, nafcillin, clindamycin. †

232 Infectious Disease 233

SKIN AND SOFT TISSUE INFECTIONS AND SUPERFICIAL ABSCESSES TYPES OF SKIN AND SOFT TISSUE INFECTIONS BASED ON CLINICAL PRESENTATION

Skin or Soft Tissue Infection Clinical Presentation Impetigo Superfi cial infection of the skin with little surrounding erythema; lesions can be papules or vesicles, superfi cial pustules, or honey- colored crusted or bullous lesions Folliculitis Superfi cial bacterial infection of the hair follicles localized to the epidermis Furuncle Infection of the hair follicle extending through the dermis into the subcutaneous tissue Carbuncle Coalescence of several infl amed follicles into a single infl ammatory mass Skin abscess Collection of pus within the dermis and deeper skin tissues Cellulitis Infection of the deep dermis and subcutaneous fat without underlying suppurative focus

• Etiology: Community-associated MRSA and MSSA (CA-MRSA and CA-MSSA) are the most common causes in children, followed by Streptococcus pyogenes and other skin ﬂ ora.

BACTERIAL CAUSES OF SKIN AND SOFT TISSUE INFECTIONS BASED ON EXPOSURE

Exposure Pathogen

Human bites S. aureus, Eikenella corrodens, anaerobes

Cat or dog bites S. aureus, Pasteurella spp., anaerobes

Water exposure Aeromonas spp., P. aeruginosa, Vibrio vulnifi cus or other GNR, Mycobac-

terium marinum PEDIATRICS

Soil exposure S. aureus, S. pyogenes, many GNR, anaerobes, Nocardia spp., Actinomy- ces spp., non-TB mycobacteria

Hot tub exposure P. aeruginosa

• Diagnosis • History: History of boils, abscesses, infection or colonization with S. aureus in the patient or close contacts, recent antibiotic use, recent animal or insect bite (many incorrectly diagnosed S. aureus abscesses as spider bites), exposure to ill contacts (S. aureus or S. pyogenes). • Medical history: Children with eczema or hospitalization within the previous year are more likely to have clindamycin-resistant organisms. • Physical exam: General appearance, presence of systemic inﬂ ammatory response signs (fever, tachycardia, hypotension), erythema, swelling, tenderness, warmth of the affected area. • Laboratory studies/evaluation: Wound culture (if purulent material can be obtained) for gram stain, culture, and susceptibility testing (including D-test for inducible resistance to clindamycin), blood cx for patients with systemic involvement. • Treatment • General recommendations for treatment of skin and soft tissue infections (SSTI) in children >30 days old 234 Pediatrics

• Mild superﬁ cial infections (localized impetigo, folliculitis): Topical antibiotic (eg, mupirocin) for 7 days; follow-up 48-72 h • Small abscesses (<5 cm diameter) without systemic signs or underlying conditions: I&D ± oral antibiotics such as clindamycin (if local prevalence of clindamycin-resistant S. aureus is <10%), TMP-SMX (if S. pyogenes is unlikely), doxycycline (if >8 yo and S. pyogenes is unlikely), antistaphylococcal cephalosporin preferred if culture ⊕ for MSSA or if <10% of local S. aureus isolates are methicillin resistant; follow-up in 48 to 72 h • Cellulitis affecting the face, hands or feet, perineum, infections in children with underlying medical problems (eg, immunocompromised), deep abscesses, abscesses >5 cm diameter: May require hospitalization for IV antibiotic therapy (clindamycin if local prevalence of clindamycin-resistant S. aureus is <10% or vancomycin) ± I&D if there is an abscess • Discharge criteria for cellulitis: Lesion is stable or improving after 1 day on PO/IV antibiotics; follow-up in 48 h • Discharge criteria for abscesses: Lesion stable or improving after I&D on PO/IV antibiotics; follow-up in 48 h • Critically ill patients: Empiric IV antibiotic tx with vancomycin + nafcillin • Antimicrobial therapy should be narrowed as soon as susceptibility information becomes available. • Standard duration of therapy: 7–14 days (longer if complications) • Linezolid use restricted to cases where no other therapeutic options are available • General recommendations for treatment of SSTI in infants <30 days of age (limited data): • Afebrile, well-appearing neonates with isolated superﬁ cial pustulosis: May be treated with topical therapy alone with close follow-up • All other neonates with SSTI: Hospitalization, full SBI evaluation (blood cx, CBC, UA with micro and culture, CSF culture and routine CSF studies), empiric IV antibiotic therapy (gentamicin + clindamycin if local prevalence of clindamycin-resistant S. aureus is <10%, or vancomycin) • Discharge criteria: (1) patient is clinically improving; (2) blood, urine, and CSF cultures are negative for >48 h; (3) Causative microorganism susceptibilities of the SSTI are known; (4) reliable follow-up arranged. Complete 7–14 d of therapy with oral antibiotic (eg, clindamycin, cephalexin; avoid TMP-SMX in neonates because of risk of hyperbilirubinemia)

COMMUNITY-ACQUIRED PNEUMONIA/RISK FACTORS • Deﬁ nition: Infection of the lung parenchyma acquired in the community (outside health care setting)

ETIOLOGIC AGENTS FOR COMMUNITY ACQUIRED PNEUMONIA BY AGE AND PRESENTATION

Age Etiologic Agents

Birth–3 wk GBS, GNR, CMV, L. monocytogenes, HSV, T. pallidum, Myco- plasma hominis, Ureaplasma urealyticum

3 wk–3 mo S. pneumoniae, viral agents (RSV, parainﬂ uenza), Bordetella pertussis, Chlamydia trachomatis (2 wk–4 mo; frequently afebrile)

3 mo–5 yr∗ Viruses (RSV, parainﬂ uenza, inﬂ uenza, adenovirus, human metapneumovirus, rhinovirus, coronaviruses, human bocavirus, human echovirus), S. pneumoniae, nontypeable H. infl uenzae, S. aureus, S. pyogenes, M. pneumoniae (age often >2 yo), TB (areas of high prevalence or high rates of HIV infection) Hib,†

Children >5 yr Atypical bacteria: M. pneumoniae, C. pneumoniae Typical bacteria: S. pneumoniae, S. aureus Infectious Disease 235

Presentation or Risk Factors Etiologic Agents

Aspiration pneumonia Anaerobic streptococci, Fusobacterium spp., Bacteroides spp., Prevotella melaninogenica

Eﬀ usion or empyema S. pneumoniae, S. aureus, S. pyogenes, Hib†, anaerobes in aspiration pneumonia (neurologic impairment, neuromuscular disorders, GERD, and others with risk factors for aspiration)

Immunocompromised Usual pathogens plus GNR, S. aureus, Legionella spp., fungal organisms, Pneumocystis jiroveci, viruses

Cystic ﬁ brosis S. aureus, P. aeruginosa, Hib†, B. cepacia, nontuberculous mycobacteria, Aspergillus spp.

Sickle cell anemia Atypical bacteria (M. pneumoniae, C. pneumoniae), S. pneumoniae, S. aureus, Hib†

∗Mixed viral–bacterial infections are common (30%–50%). †HiB pneumonia has been virtually eliminated by use of HiB conjugate vaccine.

• Diagnosis • Symptoms: Fever (may be only symptom in children <5 yr), cough, ↑ work of breathing, ↓ PO, emesis, ↓ activity, chest pain (older children), abdominal pain (lower lobe disease), neck pain (upper lobe disease), ± vomiting/diarrhea • History: Age, recent URI, associated symptoms (atypical agents more likely to have extrapulmonary symptoms, including rash, sore throat, myalgia, joint pain, headache), duration of symptoms, h/o choking suggestive of foreign body or aspiration, seizure disorder, neuromuscular disorder, episodes, immunization history (PCV7, Hib, pertussis, infl uenza), recent antibiotic therapy (dose, duration, response), exposure history (TB, Chlamydia, animal contact), sick contacts, travel, daycare • Physical exam: Fever, tachypnea (most sensitive and specifi c sign—normal RR based on age), ↑ HR, hypoxia, cyanosis, general appearance (mental status, hydration status), ↑ WOB (retractions, fl aring, grunting, accessory muscle use), pulmonary exam (crackles or rales, rhonchi, wheezing [suggests viral and atypical bacterial agents], PEDIATRICS decreased breath sounds, dullness to percussion, egophony, whispered pectoriloquy, tactile fremitus); pleural effusion/empyema: ↓ breath sounds on side with effusion, dyspnea, chest pain with splinting, dullness to percussion, distant breath sounds, pleural friction rub • Laboratory studies/evaluation: Indicated in young infants (evaluate for dissemination), patients with worsening clinical status, patients requiring hospital admission, and patients with an unclear diagnosis • CBC with differential (although not specifi c, WBC >15 or <4.5 × 103/mm3 may indicate a bacterial etiology; leukocytosis with lymphocyte predominance is seen in pertussis, ↑ eosinophils in infants with C. trachomatis) • CRP (↑ more common with bacterial PNA but may occur with adenovirus, infl uenza, other viral agents) • Serum electrolytes (severe dehydration or concern for SIADH) • Microbiology: Blood culture in patients with effusions or empyema (yield, 30%–40%), viral culture or viral rapid tests for suspected viral causes, testing for atypical pathogens in unclear cases 236 Pediatrics

TESTING FOR SPECIFIC PATHOGENS THAT CAUSE COMMUNITY-ACQUIRED PNEUMONIA

Pathogen Specifi c Test

• B. pertussis Nasopharyngeal secretions for culture and PCR • C. trachomatis Conjunctival and nasopharyngeal specimens for testing by DFA or EIA • C. pneumoniae Serologic titers or Chlamydia culture • Mycoplasma spp. IgM/IgG serologies (low speciﬁ city); may consider cold agglutinins TST, IGRA, morning gastric aspirates (x3); see TB section. • Tuberculosis Urine antigen test (results are often negative unless disseminated • Histoplasma spp. disease is present) and serologies

• Pleural fl uid analysis when available (preferably before antibiotics): (1) Gram stain and culture for bacterial pathogens (highest yield with S. aureus and S. pneumoniae); (2) AFB smear and culture; (3) KOH and fungal culture; and (4) protein, glucose, cell count, LDH, pH, cytology (if malignancy suspected). See tables “Pleural fl uid analysis” and “Differential diagnosis of pleural effusions”. • Tracheal aspirate for Gram stain, culture: Intubated patients • Radiology • CXR • Indications: (1) infants <36 mo with fever + WBC >20,000 cells/mm3, (2) severe disease, (3) hospitalization, (4) unclear dx, (5) evaluation for complications • Findings: Lobar infi ltrates → bacterial etiology (not sensitive); diffuse bronchopneu- monia pattern → M. pneumoniae and viruses (however, ≤40% of M. pneumoniae have single lobe involvement); infants with hyperinfl ation or interstitial process → C. trachomatis; hilar adenopathy → fungal pathogens, TB • Lateral decubitus radiography fi lm (affected side down): Evaluate for effusion, determine if free fl owing in chest cavity • US: Evaluate extent of effusion, loculation of effusion, optimal location for thoracocentesis or chest tube placement • Chest CT: Characterization of effusion or empyema when above modalities yield unclear results. Also, may be useful for children with pulmonary abscesses.

PLEURAL FLUID ANALYSIS∗

Measurement Transudate Exudate Speciﬁ c gravity <1.016 >1.016 Protein (g/dL)∗∗ <3.0 >3.0 Fluid:serum ratio <0.5 >0.5 LDH (IU)∗∗ <200 >200 Fluid:serum ratio <0.6 >0.6 WBC (cells/μL)∗∗∗,$ <1000 >1000 RBC (cells/μL) <10,000 Variable Glucose (mg/dL) )∗∗ >40 <40 pH† >7.2 <7.2

∗Order cell count with diff erential (neutrophil predominance consistent with CAP with eff u- sion; lymphocyte predominance suggests TB or malignancy). †Should collect anaerobically in heparinized syringe. ∗∗Always obtain serum for glucose, LDH, protein to compare with pleural fl uid levels. $Infectious workup: Gram stain and cx, anaerobic cx, fungal stain and cx, AFB stain and cx. Consider latex agglutination studies or PCR for specifi c organisms if patient received antibiotics before specimen collection ∗If suspecting pancreatitis send serum and pleural fl uid for amylase. Pleural fl uid:Serum amylase ratio >1 suggests pancreatitis. Infectious Disease 237

• Complications: Pleural effusion, empyema, pneumatoceles, pneumothorax, necrotizing pneumonia, lung abscess, sepsis, SIADH • Outpatient therapy should include anticipatory guidance of worsening or when to return to the PMD or emergency center, adequate hydration, fever, and pain control. • Follow-up: All children treated as outpatients should follow up with their PMD within 24–48 h of starting therapy. • Treatment failure: Not improving within 48 h → consider changing antibiotic, further workup for a complication, reconsideration of diagnosis (eg, viral pathogen, TB, foreign body). Consider hospital admission for expanded work up and IV therapy. EMPIRIC ANTIBIOTIC THERAPY FOR OUTPATIENT MANAGEMENT OF COMMUNITY-ACQUIRED PNEUMONIA

Age Antiviral and antibiotic strategy 2 mo†–3 mo • Bacterial: • Amoxicillin (80-100 mg/kg/day PO divided BID) x 10 days (max, 3g/day) ± • Viral: Supportive therapy • C. trachomatis: azithromycin (10 mg/kg once PO × 1 day, max 500 mg/day followed by 5 mg/kg/day PO × 4 day, max 250 mg/day) • C. pneumonia: azithromycin (10 mg/kg once PO × 1 day, max 500 mg/day followed by 5 mg/kg/day PO × 4 day, max 250 mg/day) • B. pertussis: azithromycin (10 mg/kg/day PO × 5 days, max 500 mg/day) 3 mo–2 yr• Viral: Supportive therapy; consider antivirals for inﬂ uenza within 10 mg/kg once PO × 1 day, max 500 mg/day followed by 5 mg/kg/day PO × 4 day, max 250 mg/day 48 of symptom onset • Bacterial: Amoxicillin∗ (80–100 mg/kg/day PO divided BID) × 7–10 days (max dose, 3 g/day) 2 yr–5 yr• Viral: Same as 3 mo–2 yr • Bacterial: Same as 3mo-2yr ± macrolide for atypical bacterial coverage (azithromycin 10 mg/kg once PO × 1 day, max 500 mg/day followed by 5 mg/kg/day PO × 4 day, max 250 mg/day) Children • Viral: Same as 3mo–2 yr >5 yrs Bacterial: Amoxicillin∗ (80-100 mg/kg/day PO divided BID) × 7-10 days (max, 3 g/day) + macrolide for atypical bacterial coverage (Azithromycin 10 mg/kg PEDIATRICS once PO × 1 day, max 500 mg/day followed by 5 mg/kg/day PO × 4 day, max 250 mg/day) Aspiration Amoxicillin–clavulanate (80-100 mg/kg/day PO of amoxicillin component pneumonia divided BID; max, 3 g/day amoxicillin component) or clindamycin ∗Allergic to PCN or amoxicillin (non-anaphylactoid): Cefdinir, cefpodoxime, or cefuroxime; Allergic to PCN or amoxicillin (anaphylactoid): Clindamycin or azithromycin (Note: pneumococcal resistance to macrolides is ~50%) †Children <2 mo with fever should be evaluated as per the fever without localizing signs algorithm (see chapter 13) Inpatient Management • Management • Consider admitting a patient to the hospital with pneumonia for the following reasons: • Age: Birth-3mo, if bacterial etiology suspected

• O2 saturation (<92%) • Dehydration and unable to take PO to maintain hydration • Toxic appearance, altered mental status • Failure of outpatient therapy • Complication such as effusion or empyema, lung abscess • Moderate to severe respiratory distress • Underlying chronic condition (eg, immunocompromised, preexisting pulmonary or cardiac disease, hemoglobinopathy), or prematurity • Poor follow-up or compliance issues, unsafe to send home • Outpatient management: See table for empiric treatment choices based on age and etiologic agent. 238 Pediatrics

• Consider consultation with an infectious disease or pulmonary specialist for children with preexisting conditions, recurrent infections, medication allergies, clinical worsening despite appropriate empiric therapy or resistant organisms

EMPIRIC ANTIBIOTIC THERAPY FOR INPATIENT MANAGEMENT OF COMMUNITY-ACQUIRED PNEUMONIA

Age Antiviral and antibiotic strategy

2 mo†–3 mo • Viral: Supportive therapy; consider antivirals for inﬂ uenza if symptoms ≤ 48h • Bacterial: • Cefotaxime (150–200 mg/kg/day IV divided Q8h) ± macrolide for atypical organisms) • If S. aureus is in diﬀ erential (skin lesions, pleural involvement, toxic appearing), add vancomycin or clindamycin • C. trachomatis: azithromycin (10 mg/kg once PO × 1 day, max 500 mg/ day followed by 5 mg/kg/day PO × 4 day, max 250 mg/day) • C. pneumonia: azithromycin (10 mg/kg once PO × 1 day, max 500 mg/ day followed by 5 mg/kg/day PO × 4 day, max 250 mg/day) or erythromycin (50 mg/kg/day divided Q6h × 14 days) • B. pertussis: azithromycin (10 mg/kg/day × 5 days, max 500 mg/day)

3 mo–2 yr• Viral: Supportive therapy; consider antivirals for inﬂ uenza symptoms <= 48 h • Bacterial: Ampicillin∗ (200 mg/kg/day IV divided Q6h; max, 12 g/day or, cefotaxime (150–200 mg/kg/day IV divided Q8h; max, 8–10 g/day).

≥ 2 yr–5 yr• Viral: Same as 3 mo–2 yr • Bacterial: Same as 3 mo-2 yr ± macrolide for atypical bacterial coverage (Azithromycin 10 mg/kg once PO × 1 day, max 500 mg/day followed by 5 mg/kg/day PO × 4 day, max 250 mg/day)

Children >5 yrs• Viral: Same as 3–5 yr • Bacterial: Ampicillin∗ (200 mg/kg/day PO divided Q6h max, 12 g/day) + macrolide for atypical bacterial coverage (Azithromycin 10 mg/kg once PO × 1 day followed by 5 mg/kg/day PO × 4 day) Presentation/ risk factor Treatment strategy

Severely ill or IV cefotaxime + IV vancomycin ± azithromycin ICU patients

Eﬀ usion or IV cefotaxime + IV clindamycin, or IV cefotaxime + IV vancomycin (if empyema higher rates of clindamycin-resistant S. aureus in community or patient is toxic appearing)

Aspiration IV clindamycin or IV ampicillin–sulbactam; if child is prone to aspiration pneumonia or has CLD, consider broader coverage (eg, GNR and Pseudomonas coverage)

Immunocom- Broad-spectrum gram-negative and gram-positive coverage: IV promised vancomycin for MRSA, ceftazidime or piperacillin-tazobactam for Pseudomonas spp. and other gram-negative organisms, ± TMP/SMX for P. jiroveci, ± antifungal therapy

∗Allergic to PCN or amoxicillin (anaphylactoid): Clindamycin or azithromycin (Note: pneumococcal resistance to macrolides is ~50%). †Children <2mo with fever should be evaluated as per the fever without localizing source algorithm(see Chapter 13) Infectious Disease 239

• Patients with moderate-large pleural effusions or empyema: • Pleural fl uid should be drained through thoracocentesis (ideally aspiration under US guidance if available) with chest tube placement • Empyema: Debridement of the pleural space via VATS with chest tube placement or thoracocentesis with chest tube placement and fi brinolytic therapy (no difference in length of hospitalization; early VATS may ↓ duration of symptoms and hospital stay) • Duration of therapy: • Outpatient management: 7–10 days. • Inpatient management: Dependent on disease severity, complications, preexisting conditions, organism identifi ed; 7–10 days total for uncomplicated CAP with transition from IV to PO and discharge when clinically improved and able to tolerate PO. Pres- ence of effusion or empyema: 14 days total for S. pneumoniae and S. pyogenes; 21 days for S. aureus.

DIFFERENTIAL DIAGNOSIS OF PLEURAL EFFUSIONS

Transudate CHF, cirrhosis or liver failure, renal disease (nephrotic or nephritic syndrome), myxedema, hypoproteinemia or hypoalbuminemia, volume overload, aggressive ﬂ uid resuscitation, peritoneal dialysis, central venous catheter leak, ARDS

Exudate Infection, subphrenic abscess, malignancy, collagen vascular disease, pancreatitis, sarcoidosis, chylothorax, drug reaction, posttrauma, postsurgical, pulmonary lymphangiectasia, uremic pleuritis, Meig’s syndrome (ovarian tumor)

Data from Encyclopedia of Respiratory Medicine, 4th ed. 2006:353-358.

NOSOCOMIAL OR HOSPITAL-ASSOCIATED PNEUMONIA • Defi nition: Infection of the pulmonary parenchyma acquired after >48 h of hospitalization • Etiology: S. aureus (MRSA); GNR, including Pseudomonas spp. (often multi-drug resistant); anaerobic bacteria; yeast; viral infections (RSV, infl uenza, parainfl uenza) • Risk factors: ICU care, mechanical ventilation, artifi cial airway, indwelling catheters, broad-spectrum antibiotics, postoperative patients

• Clinical features: Fever, cough, ↑ work of breathing, ↓ oxygen saturations, ↑ ventilator support, PEDIATRICS inability to decrease mechanical ventilatory support, ↑ secretions in intubated patients • Workup: CXR, tracheal aspirate for Gram stain and cx, blood cx, CBC, Chem 7 (at risk for SIADH); bronchoscopy, lung biopsy, lung aspiration or BAL with protected specimen brushing may be necessary in speciﬁ c circumstances (unclear diagnosis, immunocompromised, treatment failure) • Empiric Therapy • Vancomycin (MRSA) + aminoglycoside + third- or fourth-generation cephalosporin, ticarcillin–clavulanate, piperacillin–tazobactam, or meropenem • Clindamycin monotherapy may be used if aspiration is most likely • Consider institutional or local organisms and resistance patterns (hospital antibiogram) • Deﬁ nitive therapy should be chosen after culture and sensitivity results are available • Length of therapy is 7–10 days based on the severity of disease and patient response

URINARY TRACT INFECTION • Deﬁ nition: Presence of a pure growth of bacteria ≥100,000 CFU/ml of urine (or >10,000 CFU/ml for catheterized urine, >1,000 CFU/ml for suprapubic aspiration). • Risk factors: Age (especially females <36 mo), time period around “potty training”, obstruction to normal urine ﬂ ow (eg, anatomic abnormalities, neurogenic bladder, extrinsic compression from constipation or masses), h/o VUR, uncircumcised (↑ rate of UTI ×10 in males <12 mo), adolescents with DM, frequent sexual intercourse, pregnancy, HIV with CD4 count <200/mm3 240 Pediatrics

ETIOLOGIC AGENTS FOR URINARY TRACT INFECTIONS AND OTHER RELATED INFECTIONS

Disorder Etiologic agent

UTI • E. coli: 70%–90% of all UTIs and >90% of ﬁ rst UTIs in outpatients • Other GNR (more common with underlying urinary tract abnormalities and h/o multiple previous UTI): Klebsiella, Pro- teus, Pseudomonas, Enterobacter, Citrobacter, Enterococcus spp. • Staphylococcus saprophyticus: >15% of UTIs in adolescent girls • GBS: Rare pathogen in neonates (may be hematogenous) and adolescents • S. aureus: Associated with hematogenous UTIs, renal abscesses

Nosocomial UTI (catheter • GNR, yeast, S. aureus >3 days ↑ risk signiﬁ cantly)

Urethritis • Chlamydia trachomatis, N. gonorrhea, Mycoplasma genitalium, HSV

Hemorrhagic cystitis • E. coli, adenovirus types 11 and 21

• Diagnosis • History: H&P nonspecifi c; cannot reliably differentiate between lower and upper tract infection (25% of children dx UTI by H&P have pyelonephritis by ureteral catheterization). Inquire re: urinary sx, previous UTI, VUR, FHx of UTI, h/o repeated undiagnosed febrile episodes, foreign bodies, trauma, sexual activity, and constipation. • Physical exam: Fever, BP, urethral meatus, suprapubic or CVA tenderness, mass (hydronephrosis). • Common clinical manifestations for UTI • Infants: fever without a localizing source (most common SBI in children 3–36 mo), fussy, ↓ oral intake, ↓ activity, jaundice, vomiting, diarrhea, weight loss, FTT; 5% of infants with bronchiolitis have a concurrent UTI • 2–5 yr: Fever, abdominal pain, ± dysuria, vomiting, bedwetting after achieving conti- nence, foul-smelling urine • >5 yr: Dysuria, urgency, ±fever, ± CVA tenderness (if patient has pyelonephritis) • Laboratory studies/evaluation: Urine collection: suprapubic aspiration (most accurate; infrequently used in infants ≤18 mo), catheterization (infants and children who do not spontaneously void), clean catch (children who can spontaneously void). Allowing samples to sit out at room temperature >10 min decreases sensitivity. • UA/micro: leukocyte esterase (Cath: 86% sensitive/94% specifi c; Bag: 76% sensitive/84% specifi c), nitrite reaction (53% sensitive/98% specifi c), microscopic exam for WBC (73% sensitive/81% specifi c)bacteria (81% sensitive/83% specifi c). Children, especially infants, may have a negative UA/micro with cx-positive UTI. Sterile pyuria (WBCs present, cx negative): TB, urethritis, foreign body, vasculitis, Kawasaki disease (urethral source of WBCs in Kawasaki disease, so collection should be performed by technique other than cath). • Urine cx: ≥ 2 organisms in a child with normal urinary tract anatomy is likely contami- nant → repeat cx. Dx is based on a quantitative colony count of urine which varies by the method of specimen collection (see table “Interpretation of urine culture results”) • Blood cx: If upper tract involvement is suspected • Renal US: If concern for pyelonephritis or perinephric abscess (see Management section) Infectious Disease 241

INTERPRETATION OF URINE CULTURE RESULTS∗

Method of Collection Colony Count Probability of Infection

Suprapubic aspiration Any GNR >99% GPC >1000

Catheterization >100,000 95% 10,000–100,000 Infection likely 1000–10,000 Suspicious; repeat culture <1000 Infection unlikely

Clean Catch Boy >10,000 Infection likely Girl >100,000 in three specimens 95% >100,000 in two specimens 90% >100,000 in one specimen 80% 10,000–100,000 Suspicious, especially if symptomatic; repeat culture <10,000 Infection unlikely

Data from Textbook of Pediatric Infectious Diseases, 6th ed. 2009:559. ∗1%–2% of older infants and children have asymptomatic bacteriuria (with no clinical signiﬁ cance)

• Management • Inpatient management: Admit patient if age <8 wk, vomiting, failed outpatient treatment, or toxic appearing. • IVF if dehydrated • Empiric therapy for hospitalized patients: • Healthy infants: ampicillin + aminoglycoside or ampicillin + third-generation cephalosporin • >4 weeks old: third-generation generation cephalosporin • Duration of antibiotics • Outpatient management: Children ≥2 mo with febrile UTI who do not otherwise require PEDIATRICS hospitalization have equivalent outcome with oral vs. IV therapy • Empiric oral therapy: Cefi xime (8mg/kg/day PO Q12h; max, 400mg/day), Cefpo- doxime proxetil (children ≥ 2mo; 10mg/kg/day PO Q12h; max, 800 mg/day) for 7-14 days based on diagnosis of UTI or pyelonephritis. (Note: ~50% of E. coli resistant to TMP/SMX; ~35% of E. coli resistant to amoxicillin) • UTI: <4 weeks old: 7 days IV antibiotics; >4 weeks old: 7 days IV/PO (PO at discharge) • Pyelonephritis: <4 weeks old: 14 days IV antibiotics; >4 weeks old: 14 days IV/PO (PO at discharge) • Imaging: See the two tables below for available imaging modalities and recommendations for Renal US and VCUG. • Prevention strategy (8%–30% of children with fi rst-time UTI will have one or more recurrent UTI) • Adequate hydration, frequent voiding, perineal hygiene, completion of antibiotic courses, immediate evaluation for future unexplained fever or urinary symptoms. • Urology referral for all patients with GU anatomic abnormalities, dysfunctional voiding, or VUR. • Complications of recurrent UTIs: Renal scarring, HTN, ESRD. • Antibiotic prophylaxis • Goal: Prevention of renal damage from infection and infl ammation caused by refl ux of contaminated urine (controversial) • Common agents: Trimethoprim–sulfamethoxazole (> 6 mo age), amoxicillin (neonates), nitrofurantoin 242 Pediatrics

IMAGING MODALITIES FOR CHILDREN WITH URINARY TRACT INFEC- TION OR PYELONEPHRITIS

Imaging Modality Pros Cons

Renal US• Most useful modality for imaging • Does not provide functional kidneys, ureters, bladder; deﬁ nes information or detect renal renal structure; evaluates for scarring dilatation in collecting system

VCUG and RNC• Deﬁ nes the presence and grade • VCUG has increased radiation of VUR; VCUG detects PUV in male exposure (VCUG 10-fold com- infants pared with RNC), RNC will not detect PUV in male infants

Technetium-99m • Assessment of renal function and • Positive ﬁ ndings may not DMSA scan∗ scarring change management

∗ DMSA scan should be done if identiﬁ cation of renal scarring will change management.

IMAGING RECOMMENDATIONS AFTER FIRST FEBRILE URINARY TRACT INFECTION

Age and Gender Imaging Modality Indication

Birth–24 mo RUS + VCUG∗ First UTI

Girls 2–6 yr and RUS; if RUS is abnormal or the First UTI Boys 2–12 yr patient has any risk factor (sibling with VUR, ↓ renal function, proteinuria, HTN) also obtain VCUG

Girls 6–12 yr RUS Consider based on clinical ﬁ ndings suggestive of upper tract disease or history of repeated infections

∗VCUG can be performed as an outpatient; if inpatient, VCUG can be performed after the patient is on appropriate antibiotics and fever is improving (do not need a repeat UA).

MENINGITIS • Defi nitions • Aseptic meningitis: Infl ammation of meninges with no identifi cation of bacterial or fungal organism • Bacterial meningitis: Acute bacterial infection of the meninges and subarachnoid space • Etiology • Bacterial meningitis: See table below for agents that cause bacterial meningitis Infectious Disease 243

ETIOLOGY OF BACTERIAL MENINGITIS ACCORDING TO AGE AND RISK FACTORS

Age or Risk Factor Organism

Neonatal (0–3 mo) GBS, E. coli and other gram GNR, L. monocytogenes, S. pneumoniae (usually in infants >1 mo)

Non-neonatal (3 mo–18 yr) S. pneumoniae, N. meningitidis, Hib∗

Trauma Penetrating trauma: Staphylococci spp., skin ﬂ ora organisms, GNRs (including Pseudomonas aeruginosa) Animal bites: Pasteurella multocida CSF leak: S. pneumoniae, Hib, GNRs

Immunodeﬁ ciency Terminal complement deﬁ ciency: N. meningitidis Asplenia: S. pneumoniae, N. meningitidis, Salmonella spp. Transplant recipients, T-cell defects: L. monocytogenes HIV: S. pneumoniae, N. meningitidis, Hib, fungal (Cryptococcus)

Direct extension Dermal sinus tracts, meningomyelocele, urinary tract abnormalities: Staphylococci (S. aureus, CONS), GNR, intestinal organisms Otic ﬁ stula, cochlear implants: S. pneumoniae

Neurosurgery Postneurosurgery: S. aureus, CONS, enteric GNR (including E. coli, Klebsiella spp., P. aeruginosa) VPS: Staphylococci (CONS and S. aureus), fungal, S. pneumoniae, Hib, N. meningitidis, diphtheroids

∗ Less common after introduction of Hib vaccine; unlikely in patients with at least two doses of Hib vaccine

• Aseptic Meningitis • Common pathogens: Enteroviruses, arboviruses, HSV, Lyme disease, partially treated bacterial meningitis • Uncommon pathogens: M. tuberculosis, fungi, HIV, adenoviruses, infl uenza, parainfl u- PEDIATRICS enza, EBV, CMV, VZV, mumps, measles, lymphocytic choriomeningitis, Bartonella spp., spirochetes, Leptospira spp., Brucella spp., Mycoplasma spp., rickettsia, parasites, paramen- ingeal bacterial infection • Noninfectious causes: Drugs (NSAIDs, IVIG), systemic immune-mediated diseases, neoplastic diseases, Kawasaki disease • Diagnosis • History • Infants: Inconsolable crying or irritability, lethargy, fever or hypothermia, vomiting, poor feeding, respiratory distress, grunting, apnea, seizures • Children: Fever, lethargy, irritability, myalgia, malaise, headache, anorexia, vomiting, neck and back pain or stiffness, photophobia, mental status changes, seizures (20%–30%; bacterial: S. pneumoniae and Hib; viral: HSV) • Symptom progression: Slow (2–5 d), rapid (1–2 d), or fulminant (shock early in the course of illness) • Physical exam • Infants (<1 yr): Bulging fontanel, irritability, lethargy, hypo- or hypertonicity • Older children (>1 yr): Neck stiffness, photophobia, Kernig’s sign (patient supine, hip and knee fl exed to 90° + if passive extension of knee meets resistance) and Brudzin- ski’s sign (patient supine and limbs extended + if passive neck fl exion results in involuntary hip or knee fl exion), cranial nerve palsies (III, VI, VII), ataxia; papilledema (suggestive of brain abscess, epidural or subdural empyema, or sinus venous thrombosis); petechial or purpuric rash (classically N. meningitidis; also found with S. pneumoniae and Hib; 25% of patients with N. meningitidis with nonspecifi c maculopapular rash very similar to viral exanthem) 244 Pediatrics

• Laboratory studies/evaluation: Electrolytes (r/o SIADH), CBC, DIC evaluation, blood cultures (x 2); CSF analysis (cell count with differential; glucose, protein; Grams stain and bacterial culture; viral studies (see “aseptic meningitis” below). See table below for interpretation of CSF. • Contraindications to urgent LP: Hemodynamic instability, coagulopathy, evidence of increased ICP (focal deﬁ cit on physical exam, papilledema), h/o recent or chronic CNS lesion, h/o recent CNS trauma, h/o CNS shunt (if VPS in place, CSF should be obtained after neurosurgery evaluation from reservoir or by LP) • Aseptic meningitis CSF evaluation considerations: Enterovirus and HSV PCR, viral culture, AFB stain and culture, acute and convalescent arbovirus titers, EBV, CMV, VZV serologies, HIV ELISA, Mycoplasma and Bartonella serologies, inﬂ uenza or adenoviral screens

CEREBROSPINAL FLUID ANALYSIS

WBC/ PMN Protein Glucose ¢ Smear ¢ Culture Additional CSF Finding mm3 Cells (%) (mg/dL) (mg/dL) (%) (%) Considerations

Preterm <25 57 65–150 25–65 newborn

Term <22 60 20–170 35–120 newborn

Healthy child <7 0 20–40 40–80

Viral <1000 20–40∗ WNL <100 WNL‡ HSV: rare; Enterovirus or entero- HSV PCR, virus: arboviral 20-40% serologies

Bacterial >1000† >85–95 >100–150 0–<40 >85 >95

Partially >1000 >80 60–150 <40 40-60 <90 Consider latex treated agglutination bacterial studies¶

Lyme <500 <10 <100 WNL B. burgdorferi (Borrelia (>90% antibodies burgdorferi) monos)

Fungal <500 <10–20 >100-200 <40 <40 >30∗∗ Histoplasma and Cryptococ- cus Ag, India Ink for Cryptococcus

M. tuberculosis <300 <10–20 >200–300 <40 <30 <30 Skin test, chest Contrast CT or MRI, epidemiologic evaluation, PCR

∗PMNs may be found early in viral disease †<500 WBCs may be found in severe pneumococcal meningitis or in early disease caused by any organism ‡Low glucose levels may be found in patients with HSV or mumps infections §Listeria spp. less likely to have a positive smear ¶GBS, E. coli, S. pneumococcus, N. meningitides (B and ACYW-135), Hib, although low sensitivity and speciﬁ city ∗∗Better isolation rates for Candida spp. compared with Histoplasma and Cryptococcus

• Management • Bacterial Meningitis • Fluid resuscitation, scheduled pain control, antiemetic medications. Infectious Disease 245

• Antimicrobial therapy: If index of suspicion is high, do not delay antimicrobial therapy if LP cannot be performed at presentation or if neuroimaging needed before LP; after antibiotic administration, CSF cultures will remain positive for 15 min–2 h for N. meningitides, 4–10 h for S. pneumoniae, and 8 h for GBS (Pediatrics 2001;108(5):1169). • Adjunctive corticosteroids: Dexamethasone is recommended in children with Hib meningitis ≤1 h after the ﬁ rst dose of antimicrobial therapy (to minimize neurologic complications, particularly hearing loss) (2009 AAP Red Book). • Narrow therapy to causative organism based on culture and sensitivity results. • Electrolyte monitoring: Monitor for SIADH. • Serial neurologic examinations, FOC measurements in infants. • Repeat CSF evaluation in 24–48 h indicated in patients with poor response to therapy after 24–36 h, in all patients with GNR or resistant gram-positive infections, and children treated with steroids. • Neuroimaging in patients with (1) focal neurologic ﬁ ndings, increasing FOC, seizures >72 h after initiating therapy, or prolonged altered mental status; (2) persistently positive CSF cultures, (3) recurrent meningitis, and (4) all infants with GNR infections (especially Citrobacter spp. or Enterobacter sakazakii). • Aseptic Meningitis • Supportive care: Fluids and electrolytes, nutrition, scheduled pain control and antiemetic medications, PT and OT as needed. • Patient can be observed off antimicrobial therapy. However, antimicrobial therapy is often initiated while awaiting bacterial cultures of CSF. • Acyclovir therapy is initiated if HSV is considered (if HSV PCR of CSF performed).

EMPIRIC THERAPY FOR SUSPECTED BACTERIAL MENINGITIS ACCORDING TO AGE AND RISK FACTORS

Age or Risk Factor Treatment Regimen Neonatal Ampicillin + cefotaxime or ampicillin + gentamicin (0–2 mo) • Add vancomycin for infants >1 mo or if Gram stain is consistent with S. pneumoniae • Add acyclovir if HSV is on diﬀ erential diagnosis (or if HSV PCR pending) • Consider broader spectrum of coverage for former NICU infants: Vancomy- PEDIATRICS cin + cefotaxime (or ceftazidime if anti-pseudomonal coverage is needed) 2 mo–18 yr Cefotaxime (300 mg/kg/day IV divided Q6h; max, 12 g/day) or ceftriaxone (100 mg/kg/day IV daily or divided BID; max, 4 g/day) + vancomycin (60 mg/kg/day IV divided Q6h; max, 2 g/day) Immunocompro- Cefotaxime or ceftriaxone + vancomycin (dosages as above) mised • Add an aminoglycoside (gentamicin or amikacin) if GNR on Gram stain or patient has neutropenia or is receiving chemotherapy • Add high-dose ampicillin if patient has a T-cell defect (Listeria spp. infection) Neurosurgery Cefotaxime or ceftriaxone + vancomycin (dosages as above) or VPS • Add an aminoglycoside (gentamicin or amikacin) if GNR seen on Gram stain • Alternative regimens: Vancomycin + cefepime or ceftazidime or meropenem Direct extension Cefotaxime or ceftriaxone + vancomycin (dosages as above) Add an aminoglycoside (gentamicin or amikacin) if GNR seen on Gram stain Trauma related Vancomycin + gentamicin + cefepime or ceftazidime or meropenem Brain abscess Vancomycin + cefotaxime + metronidazole (15 mg/kg/dose IV x 1 then 7.5 mg/kg/dose Q6h; max 2g/day) 246 Pediatrics

• Isolation and Prophylaxis • All patients with suspected meningitis should be on droplet precautions until 24 h of effective therapy • Appropriate chemoprophylaxis is required for close contacts of patients with Hib and meningococcal disease (rifampin, ceftriaxone, or ciproﬂ oxacin) • Prognosis • Overall mortality: 5% in developed countries; 8% in developing countries • Neurologic sequelae: Hearing loss (11%), mental retardation (4%), seizures (4%), pare- sis or spasticity (4%) • Poor outcome associated with lower GCS at presentation, etiologic agent (pneumococcal disease has ↑ hearing loss and neurologic sequelae), seizures after 72 h of therapy, CSF glucose concentration <20 mg/dl, and delayed sterilization of the CSF • Follow-up • All children with bacterial meningitis require follow-up hearing evaluation and developmental assessment

INTRAVASCULAR CATHETER-RELATED INFECTION Etiology • Overall: Gram-positive organisms (65%), gram-negative organisms (24%), fungi (11%) anaerobes (<0.5%) • Most common organisms: Skin ﬂ ora (CONS 40%–45%) >gram-negative aerobic bacilli > S. aureus (10%) > enterococci (9%)

CAUSATIVE PATHOGENS OF CATHETER-RELATED BLOODSTREAM INFECTIONS

Causative Pathogens of Catheter-Related Bacteremia Estimated %

Coagulase-negative staphylococci (CONS) 40–45

S. aureus 10

Enterococcus spp. 9

Candida spp. 9

Enterobacter spp. 5

E. coli 5

Klebsiella spp. 6

P. aeruginosa 3

Other gram-negative bacilli (Acinetobacter spp., Citrobacter spp.)1

Other fungi 1

Corynebacterium spp. <1

Bacillus spp. <1

Nontuberculous mycobacteria <1 Infectious Disease 247

• Diagnosis and Management • History and physical exam: Fever, catheter malfunction (↓ or unidirectional ﬂ ow), sepsis ± erythema, pain, and discharge at catheter exit site; subcutaneous tract or subcutaneous pocket. Findings suggestive of disseminated infection, including septic emboli to retina, skin, bone, viscera, and organ dysfunction caused by immune complex deposition (nephritis). In neonates, nonspeciﬁ c signs (apnea, bradycardia, hypotension) may be the only clinical symptoms.

TYPES OF CENTRAL VENOUS CATHETER RELATED INFECTIONS

Term Defi nition

Exit-site infection Erythema, induration, or tenderness within 2 cm of the catheter exit site; may be associated with other signs and symptoms of infection

Tunnel infection Erythema, induration, or tenderness along the subcutaneous tract of a tunneled catheter and >2 cm from the catheter exit site

Pocket infection Purulent ﬂ uid in the subcutaneous pocket of a totally implanted venous access device with or without overlying erythema, induration, tenderness, drainage

Catheter-related ≥1 positive blood culture (bacteremia or fungemia) drawn from an bloodstream intravascular catheter or a peripheral venipuncture in the presence infection of an intravascular catheter, signs and symptoms consistent with infection (ie, fever, apnea or bradycardia, hypotension, inﬂ ammation at the catheter site) and exclusion of other possible sources of the bacteremia or Positive simultaneous blood culture from CVC and peripheral vein yielding the same microorganism and at least one of the following: • Simultaneous quantitative blood culture with >ﬁ vefold CFU isolated from the blood drawn from CVC than from blood drawn

peripherally PEDIATRICS • Positive semiquantitative (>15 CFU/catheter segment) or quantitative (>100 CFU/catheter segment) catheter tip cultures • Growth of microorganisms >2 h earlier from CVC blood culture than from peripheral when both obtained simultaneously

Adapted from Principles and Practices of Pediatric Infectious Diseases, 3rd ed. (p. 87-599) 2008, and CID 2009;49(1):1.

• Empirical antibiotic therapy for CRBSI: Consider the prevalence of resistant organisms in the institution and etiology of patient’s prior CVC infection or colonization. • Neonates: Vancomycin + gentamicin or third-generation cephalosporin • Children: Nafcillin or vancomycin + anti-pseudomonal penicillin or cephalosporin ± gentamicin (gentamicin in severely ill, neutropenic, short gut, or immunocompromised patients) • Duration of therapy: ID consultation to guide antibiotic choice and length of therapy. In general, demonstration of blood cx sterility is important to determine the duration of therapy and likelihood of complications. 248 Pediatrics

Patient with CVC and fever, apnea, bradycardia or exit site cellulitis

Obtain 2 blood cultures (1 peripheral)* Gram stain & culture of any exudate Exclude other sources of fever Start empirical antibiotic therapy

+ blood culture &/or site or tunnel infection Exclude other sources of bacteremia

Persistent bacteremia Symptoms>48–72 h

Evaluate for complications Doppler US Echocardiogram Fundoscopic exam

Complicated Uncomplicated

Tunnel infection Septic thrombosis Candida spp, CONS Other microorganism Port abscess Endocarditis P.aeruginosa, †,‡ Thrombophlebitis S.aureus, etc§

ID consult, may retain ID consult, catheter CVC and treat with removal and antibiotics, consider treat with antibiotics antibiotic lock therapy

ID consult, remove CVC and treat with If clinical deterioration, antibiotics or persistent or relapsing antifungals bacteremia

Figure 20-8 Management of central venous catheter–related infection. ∗At least two blood cultures should be obtained before starting initial antibiotic therapy (through the catheter(s)—all lumens and peripheral venipuncture). Semiquantitative and differential time to blood culture positivity between samples obtained from a peripheral venipuncture site and the catheter or the catheter tip is important (but not done in every institution). Blood culture volume in the culture bottle is more important than the total number of blood cultures obtained. Pathogen recovery rate at 24 h varies from 72% (6-mL single culture) to 47% (combined yield of two separated 2-mL samples). Multiple cultures aid determination of “contami- nants” vs. true pathogens as number of positive blood cultures increased the positive predictive value (PPV). †Exclude metastatic seeding of infection and other sources of bacteremia. ‡Catheters should be removed if severe sepsis, suppurative thrombophlebitis, endocarditis, or presence of bacteremia >72 h on antimicrobial therapy to which the infecting microbes are susceptible. §Remove long- or short-term catheters in patients with infections caused by S. aureus, P. aeruginosa, fungi, or mycobacteria and short term also for gram-negative bacilli and enterococci. See duration of therapy. Adapted from CID 2009;49:1.

GENERAL RECOMMENDATIONS FOR TREATMENT OF CENTRAL VENOUS CATHETER RELATED INFECTIONS∗

Type of Infection or Pathogen Proposed Treatment Regimen Tunnel infection, port abscess Remove CVC†‡ and IV antibiotics for 5–7 days Bacteremia 7 days–8 wk depending on the causative microorganism and the development of complications

(continued on next page) Infectious Disease 249

Type of Infection or Pathogen Proposed Treatment Regimen CONS Remove CVC and treat IV antibiotics for 5–7 days If catheter is retained, use antibiotic lock therapy and IV antibiotics for 10–14 days S. aureus Remove CVC and IV antibiotics for ≥14 days; if it is a long-term CVC, treatment might need to be extended for 4–6 wk for infective endocarditis Enterococcus spp. Remove CVC and IV antibiotics for 7–14 days; if long-term CVC and catheter retained, add antibiotic lock therapy for the same duration Gram-negative bacilli Remove CVC and IV antibiotics for 7–14 days; for long-term CVC salvage, IV antibiotics and antibiotic lock therapy for 10–14 days Candida spp. Remove CVC and IV antibiotics with antifungal therapy for 14 days after the ﬁ rst negative blood culture result ∗ID consultation is important to guide individualized management. †May not be always feasible to remove the CVC. When feasible, catheters should generally be removed after blood culture contamination is ruled out. ‡ General guidelines include removal of the catheter if CVC is no longer required; alternate site exists; patient is critically ill; sx persist for >48–72 h or failure to resolve bacteremia despite appropriate therapy when catheter salvage is attempted; patient has underlying cardiac valve disease; complications (eg, endocarditis, metastatic infection, septic thrombophlebitis); or infections caused by Candida spp., Staphylococcus aureus, P. aeruginosa or mycobacteria, Bacillus spp., Micrococcus spp., or Propionibacteria spp., Nocardia spp., Burkholderia cepacia, Stenotro- phomonas spp., and Acinetobacter baumannii.

• Complications • Death: Fatality rates from 10%–50%; higher in chronically ill patients, neonates, presence of malignancy, immunodeﬁ ciency. • Sepsis syndrome. • Thrombosis and septic thrombophlebitis (9%–69%). • Metastatic seeding of infection or deep-seated abscess (6%–13%). • Endocarditis: ↑ Risk with fungal and S. aureus infections. PEDIATRICS • Recurrence is uncommon. When caused by the same organism, it is associated with failure to remove the catheter and colonization with the causative pathogen. Re-infection with new organism is more common in previously infected catheters.

Available at www.AccessPediatrics.com • Antiviral Guide • Deep Neck Infections • Tuberculosis • HIV and AIDS • Parasitic Diseases • Tick-borne Illnesses • Prevention of recurrent S. aureus SSTI and eradication of S. aureus in household contacts • Osteomyelitis and Septic Arthritis • Endocarditis • Encephalitis • Fever of Unknown Origin • Infections After Transplantation CHAPTER 21 Nephrology

BLOOD PRESSURE LEVELS FOR BOYS BY AGE AND HEIGHT PERCENTILE∗

GFR ESTIMATION METHODS Estimation of GFR based on Creatinine Clearance: 24-hour urine collection

• Endogenous creatinine clearance (Ccr) in mL/min estimates the GFR; this requires collection of a 24-h urine sample. • Creatinine is actively secreted by renal tubules in very small amounts; thus, this technique may overestimate GFR by 10%–20%. • Procedure for 24-h urine collection: Empty bladder fully and discard urine before start of 24-h period. Collect all urine for 24 h. At conclusion, draw serum plasma creatinine value and verify compliance and accuracy of collection by total creatinine excretion in sample (expected amounts: neonates, 7.9–10.2 mg/kg/d; 1 mo–1 yr, 11.9–14.7 mg/kg/d; girls and prepubertal boys, 15.3–19.8 mg/kg/d, pubertal boys, 19.2–24.2 mg/kg/d).

• Calculation of Ccr based on 24-h urine collection: U × V cr Ccr = Pcr

C cr = creatinine clearance (mL/min)

Ucr = urine creatinine (mg/mL) V = urine ﬂ ow rate (mL/min, obtained by dividing total urine volume by total collection time in minutes)

P cr = plasma creatinine (mg/mL)

• The resulting Ccr (~GFR) is standardized to BSA: C × 1.73 Standardized C = cr cr BSA

2 Standardized Ccr = creatinine clearance (mL/min/1.73 m )

Ccr = calculated creatinine clearance (mL/min) BSA = patient’s calculated BSA

Estimation of GFR Based on Schwartz Formula (Pediatrics 1976;58(2):259) • Based on the age, height (length), serum creatinine, and predeﬁ ned constant based on age; resulting value is mL/min/1.73 m2, and no further standardization is necessary. • Provides an acceptable estimate of the GFR except in situations where the patient’s serum creatinine is increasing or decreasing rapidly or when the patient is markedly emaciated. k × Height (cm) GFR (mL/min/1.73 m2) = Pcr (mg/mL) • Values for k: Low birth weight ≤1 yr , 0.33; full-term infant ≤1 yr, 0.45; 2–12 yr, 0.55; 13–21 yr girls, 0.55; 13–21 yr boys, 0.70 • Potentially more accurate formula published by Schwartz et al ( J Am Soc Nephrol 2009;20(3):629).

250 Nephrology 251

Normal Serum Creatinine Estimate

Boys: PCr (mg/dL) = 0.35 + (0.025 × Age in yr) Girls: PCr (mg/dL) = 0.35 + (0.018 × Age in yr)

NORMAL SERUM CREATININE VALUES BY AGE

Age Serum Creatinine (mg/dL)

≤28 wk gestation∗ 0.66–1.31∗

29–32 wk gestation∗ 0.59–1.18∗

33–36 wk gestation∗ 0.40–1.05∗

37–42 wk gestation∗ 0.34–0.85∗

1 mo–1 yr∗ 0.10–0.30

1–5 yr 0.30–0.50

5–9 yr 0.40–0.60

9–13 yr 0.50–0.70

13–18 yr 0.60–0.90

∗In neonates, values are generally slightly lower in girls and tend to decline with advancing postnatal age. Data from J Pediatr 1976;88(5):828. Arch Dis Child 1983;58(3):212.

NORMAL GFR VALUES BY AGE

Age Normal GFR (mL/min/1.73 m2) ± 1 SD

1 wk 41 ± 15

2–8 wk 66 ± 25 PEDIATRICS 8 wk–2 yr 96 ± 22

2–12 yr 133 ± 27

Girls 13–21 yr 126 ± 22

Boys 13–21 yr 140 ± 30

Data from Pediatrics 2003;111(6):1416.

HYPERTENSION For extended evaluation and treatment recommendations, refer to the National Heart, Lung, and Blood Institute’s The Fourth Report On The Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. Available at www.nhlbi.nih.gov/health/prof/ heart/hbp/hbp_ped.pdf or Pediatrics 2004;114(2):555. • Normal: SBP and DBP both <90% for age, gender, height. • White-coat hypertension: BP >95% in ofﬁ ce or clinic but normotensive outside clinical setting; ambulatory BP monitoring is helpful to conﬁ rm. • Prehypertension: Average SBP or DBP value ≥90% but <95%; for adolescents, SBP ≥120 mm Hg or DBP ≥80 mm Hg is prehypertensive. • Hypertension, stage I: average SBP or DBP values over 3+ encounters ≥95%. (Children with known renal or cardiac disease or diabetes are considered hypertensive >90th percentile.) • Hypertension, stage II: Average SBP or DBP values ≥99% + 5 mm Hg • Hypertensive urgency and emergency: See chapter 9. 252 Pediatrics

Sustained BP >95% for sex, age, height∗

Complete History Complete Physical Exam • Neonatal history • 4-ext BP • Family history • HT,WT,BMI • Dietary history • Diagnostic clues: Skin • Risk factors: Smoking, EtOH lesions,cardiac murmurs or use, drug use∗ gallops, abdominal masses, • Symptomatology∗ vascular bruits, retinal exam • ROS: Sleep, exercise, • ± Ambulatory BP stress, daily activities monitoring

First-Line Workup Biochemical: CBC, UA and Cx, chemistry panel, Ca, uric acid, lipid panel, thyroid screen, plasma renin, urine tox screen (if warranted by history), ± plasma/urine catechols, ± plasma/urine steroids

Imaging: Echocardiogram, renal US with Doppler, ± polysomnography

Figure 21-1 Initial workup of hypertension. ∗Severe hypertension, hypertensive emergencies, or hypertension with headache, epistaxis, diplopia, seizures, encephalopathy, hemiplegia, lethargy, or somnolence require hospitalization, a more aggressive evaluation, and IV antihypertensive therapy (see critical care chapter). (Data from Pediatr Rev. 2007;28(8):283 and Pediatr Clin North Am. 1999(46):2:235.)

EVALUATION OF RED URINE AND HEMATURIA • Gross hematuria: RBCs in urine visible to naked eye • Microscopic hematuria: 5+ RBCs per HPF microscopy (present on 3+ dipsticks over 2–3 d in a well-hydrated patient) Differential Diagnosis Upper Tract • Glomerular (brown, tea, or cola color) • Benign: Sporadic, familial, exercise, fever • AGN • Goodpasture syndrome, SLE • Tubulointerstitial • Cystic diseases: PKD, medullary cystic kidney • Nephrocalcinosis or hypercalciuria, RTA, cystinosis, oxalosis, nephrolithiasis • Transplant rejection (most common UA ﬁ nding in transplant rejection: normal UA) • Trauma • Papillary necrosis: Sickle cell trait, aspirin • Medication toxicity: Aminoglycoside, cyclosporin, cisplatin, analgesics • Medication hypersensitivity: PCN, sulfa, NSAIDs, diuretics • Toxins: Radiocontrast, heavy metals, radiation (often microscopic) Nephrology 253

EVALUATION OF RED URINE

UA dipstick for hemoglobin (blood) Urine microscopy for RBCs, casts

(-) Dipstick (+) Dipstick (+) Dipstick

(-) RBCs (-) RBCs (+) RBCs

Foods (blackberries, beets, rhubarb), Myoglobinuria, Hematuria red food coloring, medications hemoglobinuria (levodopa, rifampin), metabolites (porphyrins†, urates or uric acid (-) RBC (+) RBC crystals‡, urobilin) casts casts

Glomerular or Glomerulo- lower urinary nephritis tract pathology

Figure 21-2 Evaluation of red urine. ∗Colorless when ﬁ rst voided, may turn red upon standing in urine. †May present as pink or red paste in infant’s diaper.

MICROSCOPIC HEMATURIA*

FHx progressive renal disease, or urine FHx (-) for progressive renal disease, urine with casts or protein, or UProt/UCr > 0.2 (-) for casts or protein, and UProt/UCr < 0.2

BP, hearing test, serum creatinine Check U /U ratio and All WNL Prot Cr and C3/C4†, renal US with Doppler serum creatinine PEDIATRICS

Any of above abnormal Abnormal Normal creatinine creatinine

Pediatric nephrology consult, ± renal biopsy‡

U /U U /U , U /U Ca Cr Ca Cr Ca Cr (+) FHx of MH (–) FH of MH

24-hr urine for calcium and Familial Isolated creatinine, renal US, microscopic microscopic consider evaluation for stone hematuria hematuria

Possible hypercalciuria Reevaluate Q6–12 mo§

Figure 21-3 Workup of persistent, asymptomatic microscopic hematuria. ∗Assumes that UTI, GI or GU trauma, and bleeding diatheses have been ruled out. †C3 levels low in postinfectious GN, C3/C4 low in MPGN, SLE kidney disease, and endocarditis with atheroemboli. ‡See “Renal Biopsy: Indications and Con- traindications” at www.AccessPediatrics.com. §May consider obtaining UA of family in evaluation of familial microscopic hematuria. (Pediatrics 1998;102(4);e42.) 254 Pediatrics

• Infection: Bacterial, viral, TB • Tumors: Wilms, leukemia, lymphoma • Reﬂ ex nephropathy, obstructive uropathy • Vascular • Renal vein thrombosis, renal artery thrombosis (often gross hematuria) • Arteriovenous malformation (normal UA unless acute hemorrhage) Lower Tract (Red or Pink Color) • UTI, cystitis (eg, cyclophosphamide), urethritis, prostatitis • Calculi, trauma, foreign body • Obstructive uropathy Bleeding Diathesis • Hemophilia, thrombocytopenia, anticoagulation • Life-threatening urinary bleeding: Sickle cell, tuberous sclerosis (hemorrhage into angiolipoma), AVM, trauma

COMPONENTS OF URINALYSIS

Diff erential Normal Diagnosis of Notes and Component Value Abnormalities Limitations

Color Clear Red to brown: see hematuria section White: pyuria, phosphate crystals, chyluria, propofol Black: Alkaptonuria (excretion of homogentisic acid) Green: Methylene blue, propofol, amitriptyline Blue: Tryptophan malabsorption Purple: Purple urine bag syndrome in patients with indwelling catheters (risk of UTI)

pH 4.5–8.5 Excessively or constantly • Useful in w/u of stones (alka- acidic: RTA, excess acid load line → Proteus spp.) and RTAs (TPN) • Unreliable if excess urine is run over UA strip

Speciﬁ c 1.010–1.025 Low: Diabetes insipidus, • Each thousandth of SG above gravity water intoxication 1.000 ~30 points of osmoles (eg, High: Dehydration, SIADH SG 1.020 ~ Uosm 600) • Large molecules (eg, glucose, proteins, radiocontrast dye, may elevate speciﬁ c gravity falsely) • Infants <3 mo cannot concentrate urine well → SG unreliable

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Diff erential Normal Diagnosis of Notes and Component Value Abnormalities Limitations

Protein Negative Glomerular dysfunction • Dipstick detects albumin only (GN, nephrotic syndrome, (eg, does not detect immuno- nephritic syndrome), diabetic globulins) nephropathy (see proteinuria • Positive for values >300–500 in this chapter) mg/dL; not sensitive for microal- buminuria • Dilute urine will underestimate proteinuria; concentrated urine will overestimate • False-positive results: Iodinated radiocontrast media (must wait 24 h), overlong immersion, alkaline pH (>8.0), ammonium compounds or detergents, gross hematuria or pyuria • False-negative results: Very dilute and acidic (pH <4.5) urine, nonalbumin proteinuria

Glucose Negative Spillage from hyperglycemia: • Occurs at plasma levels DM, HHNS >180 mg/dL in patients with Renal glucosuria: Proximal normal renal function tubular dysfunction • False-negative results: Ketones, high SG, elevated ascorbic acid • False-positive results: Oxidiz- ing agents (bleach)

Hematuria Negative GN, nephrolithiasis, urinary • Detects intact RBCs, hemoglo- tract malignancy or trauma bin, myoglobin PEDIATRICS • Dipstick detects 5–10 RBC per μL or 1–2 RBC per hpf (as sensitive as microscopy) • False-positive results: Alkaline urine, oxidizing agents used to clean perineum, semen, ascorbic acid • False negative: excess nitrites, high SG, captopril

Leukocyte Negative Infectious pyuria • False-positive results: Drugs or esterase Noninfectious (sterile) pyuria: foods rendering urine red Interstitial nephritis, renal • False-negative results: Antibi- TB, nephrolithiasis (see table otics (gentamicin, cephalexin, below) tetracycline), proteinuria, glucosuria

(continued on next page) 256 Pediatrics

Diff erential Normal Diagnosis of Notes and Component Value Abnormalities Limitations

Nitrite Negative Infection with Enterobac- • False-positive results: Vaginal teriaceae (convert nitrate secretions, phenazopyridine, to nitrite) red dyes or other chromo- gens, prolonged air exposure • False-negative results: Increased urine SG, increased urobilinogen, urine pH <6.0, vitamin C supplementation, low-nitrate diet, retention of urine in bladder <4 hr

Crystals Negative PRECIPITATE IN ACIDIC URINE: Uric acid: Acidic urine, tumor lysis syndrome (in setting of ARF), hyperuricosuria Calcium oxalate: Hyperoxaluria, hyperglycinuria, ethylene glycol ingestion (in setting of ARF) Cysteine: Cystinuria

PRECIPITATE IN ALKALINE URINE: Magnesium ammonium phosphate (struvite): UTI with urease-positive organisms Calcium phosphate

Bacteria Negative UTI, asymptomatic bacteriuria, contamination

RBC Negative See hematuria in this chapter

WBC Negative Neutrophils: UTI, PKD, • Clinical signiﬁ cance of Kawasaki’s disease (culture- eosinophils in urine unclear negative pyuria), urethritis, (Clin Nephrol 1994;41:163) renal TB, renal calculi, acute appendicitis, prostatitis Eosinophils: Classically associated with AIN but also seen in transplant rejection, pyelonephritis, prostatitis, cystitis, atheroembolic disease, and RPGN Lymphocytes: Inﬁ ltrative diseases (eg, chronic tubulointerstitial disease)

Epithelial cells Negative Tubular (ATN) or transitional • No signiﬁ cance in isolation; (bladder, ureters) epithelial cells noted on a aspirated or catheterized urine sample my indicate contamination

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Diff erential Normal Diagnosis of Notes and Component Value Abnormalities Limitations

Casts Negative Hyaline casts: Normal; may see ≤10 per hpf RBCcasts: Glomerulonephritis, vasculitis WBCcasts: Tubulointerstitial disease, acute pyelonephritis, glomerular disorders Epithelial cell casts: ATN, acute glomerulonephritis Fatty casts: Nephrotic syndrome Granular, waxy, and broad casts: Degenerating cellular casts (in order of advancing degeneration); broad casts generally an indicator of renal failure

PROTEINURIA • Normal protein excretion: <100 mg/m2/d • Proteinuria: >100 mg/m2/d • Nephrotic range proteinuria: >1000 mg/m2/d

ETIOLOGIES OF PROTEINURIA

Category Description Etiologies Glomerular Filtration barrier disruption → loss Nephritic syndrome, nephrotic of albumin syndrome, HTN, DM, HUS

Tubulointer- ↓ Resorption of fi ltered proteins Inherited: Cystinosis, Lowe syndrome PEDIATRICS → stitial loss of globulins Acquired: ATN, AIN, heavy metal poisoning, antibiotic induced Overfl ow ↑ Production of fi ltered proteins Myoglobinuria, AML Isolated Benign by defi nition: Mild proteinu- Functional (fever, exercise, stress) ria, nl renal fx, nl urine sediment, nl Orthostatic (only when upright) C3/C4 levels, no h/o renal disease Idiopathic (transient or persistent)

Quantiﬁ cation Urinalysis Dipstick • Negative, trace (10–20 mg/dL), 1+ (30 mg/dL), 2+ (100 mg/dL), 3+ (300 mg/dL), 4+ (1000–2000 mg/dL). • False-positive results: Gross hematuria, pH >8.0, chlorhexidine or benzalkonium contamination, concentrated urine (if SG >1.025, dipstick should be 2+); false-negative results: very dilute urine. • Dipstick testing detects albumin only (proteinuria on dipstick testing = albuminuria); glycoproteins, immunoglobulins, Tamm-Horsfall protein, are also excreted by the kidney but not detected by UA. 24-h Urine Collection for Protein • Gold standard; must verify reliability of collection based on expected creatinine in sample 258 Pediatrics

Spot Urine Collection (J Pediatr 1990;116:243) • Ratio of urinary protein (mg/dL):creatinine (mg/dL) in random specimen • Directly correlates to 24-h collection sample; often much more practical • Reference ranges: <0.5 for 6 mo–2 yr; <0.2 for ≥ 2 yr; >3 is nephrotic range Causes of Benign Proteinuria • Febrile proteinuria: Fever >38.3°; mechanism unknown; UA dipstick ≤2+, resolves with defervescence • Exercise-induced proteinuria: ± Hematuria after vigorous exercise; UA dipstick ≤2+; resolves in 48 h • Orthostatic (postural) proteinuria: Most common cause of persistent asymptomatic proteinuria in school-aged children and adolescents; <1g/d; conﬁ rmed with bedtime vs. ﬁ rst morning void

PROTEINURIA DETECTED ON URINALYSIS

Negative Repeat U/A Positive • False-positive • Benign isolated proteinuria (fever, stress, exercise)

Trace 1+ to 3+ 4+

Both Repeat UA • UPr: UCr ratio (compare first AM Evaluate for WNL (first morning void with previous PM void to r/o nephrotic void) in 1 yr Orthostatic orthostatic proteinuria) syndrome proteinuria • UA and microscopy

Either is abnormal

Idiopathic proteinuria • Lytes, BUN, creatinine, albumin, cholesterol, (consider (<1 g/d and all other tests hepatitis B/C serologies, HIV, ANA, C3/C4 levels) WNL): Close follow-up and • Urine culture reevaluation over next • Renal US 1–2 mo • 24-h urine collection for protein

RENAL BIOPSY* IF: • Hematuria • HTN • Decreased GFR • Decreased C3/C4 • Proteinuria >1 g/d • Hypoalbuminemia†

Figure 21-4 Evaluation of proteinuria. ∗See “Renal Biopsy: Indications and Contraindications” section this chapter. †May elect to empirically treat for nephrotic syndrome with steroids prior to biopsy for ages 1–8 yr. (Data from J Pediatr 1990;116:243; Pediatr Nephrol 1999;13:697; and Pediatrics 2000;105:1242.)

GLOMERULAR DISEASE • Nephritic syndrome: HTN, edema, hematuria, ± renal insufﬁ ciency, ± proteinuria • Nephrotic syndrome: Nephrotic range proteinuria, hypoalbuminemia, edema, hyperlipidemia, ± hematuria Nephrology 259

OVERVIEW OF NEPHRITIC AND NEPHROTIC SYNDROMES

Nephritic Syndromes Age Labs Biopsy

Acute Postinfectious GN 5–12 yr ↓ C3 (nl by 8 wk) LM: Mesangial • 1–2 wk after streptococcal pharyngitis Normal C4 proliferation (serotype 19) or 3–6 wk after skin infec- ⊕ ASO IF: Granular pat- tion (serotype 49) UA: RBC casts, PMNs, tern of diﬀ use • 90% nephritic; 70% HTN proteinuria IgG/C3 deposits • HTN/proteinuria resolves by 6 wk, in subepithelial microhematuria by 2 yr part of GBM and mesangium • Complications: ARF, HTN (60%), HTN encephalopathy (10%) Biopsy if: EM: Glomeruli “lumpy-bumpy” • Tx: Supportive ARF, nephrotic presentation, normal C3, and enlarged • Px: 95% recovery, 5% RPGN or any of following with subepithe- beyond 2 months: lial deposits of gross hematuria, Ig and C3) proteinuria, ↓ C3, renal dysfunction

IgA Nephropathy (Berger Nephropathy) 15–35 yr Normal C3 IF: IgA mesan- • Hematuria ± proteinuria 1–2 d after viral ↑ Serum IgA (50%) gial deposits infection → nephritic syndrome, HTN → resolves ~1 wk • Tx: Supportive • Px: 20%–40% → ESRD (all patients need adult follow-up)

Henoch Schonlein Purpura 5–15 yr Normal C3 IF: Similar to IgA • 1–3 wk post-URI → abdominal pain, ↑ Serum IgA nephropathy but deposits palpable purpura, arthralgias, gross ↑ ESR hematuria ± nephritic syndrome also found in capillaries of • Px: <1% develop persistent renal disease skin, intestines • Tx: Supportive, NSAIDs for arthralgia, PEDIATRICS steroids for severe abdominal pain ± GI bleed • Best prognosis: Isolated hematuria • Poor prognosis: HTN, ARF, RPGN • Ureteritis (rare): Child <5 yr, loin pain, renal colic → ureteral stenosis

Nephrotic Syndromes

Minimal Change Disease 2–6 yr Nl C3/C4 EM: Fusion of • HTN <10%; hematuria 10%–20% (75%– UA: Oval fat bodies, foot processes ± • Prognosis: Very good, relapse common 80%) hematuria and ↓ with age • Tx: 85%–90% steroid responsive (see below) • Presumptive MCD if age >1 yr and <10 yr, no gross hematuria, no HTN, nl C3/C4 and renal function → steroid responsive (J Pediatr. 1981;4:561)

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Nephritic Syndromes Age Labs Biopsy

Focal Segmental Glomerulosclerosis 2–10 yr Nl C3/C4 LM: Mesangial • HTN 20%; hematuria 60%–80% (10%– UA: Oval fat bodies, proliferation and segmental • Px: CKD in 50%–80% at 10 yr 15%) hematuria scarring • Tx: Only 1/3 respond to steroids

Membranoproliferative GN 5–15 yr ↓ C3/C4 EM: Thickened, • HTN frequent; hematuria 80% (10%) split “tram track- ing” of basement • Prognosis: ESRD common at 10 yr membrane, • Tx: Variable steroid response subendothelial C3 deposits

PRIMARY AND SECONDARY NEPHRITIC AND NEPHROTIC SYNDROMES

Primary Etiology Nephritic Presentations Nephrotic Presentations

Renal RPGN MCD (Primary IgA nephropathy FSGS Diseases) Immune complex (ANCA- Membranous GN (NSAIDS) associated, anti-GBM) MPGN (phenytoin) MPGN Mesangioproliferative GN IgA nephropathy Congenital nephrotic syndrome

Systemic PIGN SLE (Secondary HSP HSP Diseases) SLE Heavy metal toxicity (lead, mercury) Endocarditis (chronic bacteremia) Infection: Syphilis, HIV, Chronic HBV/ Cryoglobulinemia HCV, malaria Goodpasture’s syndrome Diabetes mellitus ANCA-associated (Wegener’s, Lymphoma, myeloma Churg Strauss, microscopic Sickle cell disease polyangiitis)

Approach to Workup Nephritic Syndrome • History, UA w/micro, blood culture, ASO, ANCA, C3/C4, AntiDNAse B, ANA, anti-GBM, renal biopsy with immunoﬂ uorescence. (If renal function is normal or nearly normal → consider only history, UA w/ micro, blood cultures, ASO, C3/C4, ASOT and pursue additional w/u only if C3/C4 normal.) • PIGN most common hypocomplementemic GN; SLE, shunt nephritis, cryoglobulinemia often diagnosed in conjunction with history. MPGN is often diagnosed by biopsy if there is signiﬁ cant renal failure or complement levels do not normalize in a timely fashion. Nephrotic Syndrome • History, UA w/ micro, albumin, cholesterol, lytes, C3/C4, coagulation panel (consider: HBV/HCV serology, HIV, ANA, cryoglobulins, serum and urine protein electrophoresis). • Empiric MCD diagnosis: Presumptive dx of MCD if age >1 yr and <10 yr, no gross hematuria, no hypertension, normal complement levels and renal function, and steroid responsive (J Pediatr 1981;98(4):561). Nephrology 261

• Biopsy: Hematuria, HTN, renal insufﬁ ciency, low C3/C4, age <1 yr or >8 yr, failure of empiric steroid therapy, frequent relapses (>4/yr) or inability to maintain remission off steroids. Hypocomplementemia in Renal Disease • ↓ C3/C4: MPGN, SLE, atheroemboli, cryoglobulinemia • ↓ C3: PIGN

Treatment and Prognosis • Nephritic syndrome: diuresis and sodium restriction, control HTN, ACE inhibitor or ARB for persistent proteinuria → ± immunosuppression • Nephrotic syndrome (Pediatrics 2000;105(6):1242) General Management • Outpatient (mild to moderate edema): School/PE as tolerated, restricted Na intake, judicious oral diuretics (increased risk of DVT in nephrotic syndrome) • Inpatient (severe edema or presence of pleural effusion, ascites, genital edema) • Fluid restriction: ~ 600–700 mL/m2 BSA/d. • Diet: Low-sodium; restrict sodium intake to 2 meq/kg/d (max, 2 g). • Check PPD before giving steroids or immunosuppressive agents. • Vaccination concerns: Check varicella antibody titer if no documented vaccine or disease; if exposed and susceptible, VZV IVIG within 72 h; no live virus vaccines; 23-valent pneumococcal vaccination when steroid course complete and disease in remission. Diuresis • Use caution because aggressive diuresis confers increased risk of DVT. • IV Lasix: 1 mg/kg/dose Q12h • IV albumin: 25% at 0.5–1.0 g/kg/12 h followed by IV Lasix if not responding to lasix alone • Metolazone: 0.1 mg/kg/dose BID if not lasix/albumin responsive ACEI/ARB • Used in persistent proteinuria; reduces proteinuria by 50%, monitor for increased Cr, hyperkalemia Steroid Responsive 2

• Prednisone 60 mg/m /d or 2 mg/kg/d divided Qday/BID (max, 80 mg/d) for 4–6 wk PEDIATRICS or until remission; then decrease to 40 mg/m2 or 2 mg/kg every other morning and taper over 4–6 wk. • Check UA daily; remission deﬁ ned as negative or trace protein for 3 consecutive days. • 80%–90% will respond. Median time to remission 10 days. 60%–80% will have ≥1 relapse (30%–40% if initially given 6 weeks high-dose steroid course). • Monitor for steroid side effects: Gastric ulcers, endocrine (osteoporosis, DM, short stature), ﬂ uid retention, HTN, mood lability, cataracts, HPA suppression. Steroid Resistant • Cyclophosphamide, pulse IV methylprednisolone, cyclosporine, levamisole Congenital Nephrotic Syndrome • ACEIs, indomethacin, daily IV albumin, dialysis, nutrition optimization, bilateral nephrectomy, and transplant; no role for steroids or immunosuppressive agents Prognosis • Majority have repeated relapses • Steroid responsive: No risk of future CRI, not hereditary, fertility preserved (unless cyclophosphamide used) • Steroid resistant: May develop FSGS → progression to ESRD

Complications of Nephrotic Syndrome • Edema • Malnutrition (protein loss) • Electrolyte disturbances 262 Pediatrics

• Hypercoagulable: Arterial and venous thromboembolism (renal vein thrombosis, PE, sagittal sinus thrombosis, thrombosis of indwelling central lines) • Infection • Hypertriglyceridemia, hypercholesterolemia

VESICOURETERAL REFLUX (VUR) • Retrograde ﬂ ow of urine from the bladder to upper urinary tract. • Occurs in 1% newborns ~ 1/3 of healthy children with h/o UTI (white girls age <2 yr are more likely to have VUR associated with UTI; more often to have prenatal diagnosis in boys.

Types • Primary: Intravesicular ureter is shortened (may be genetic) and fails to compress fully during bladder contraction → failure of one-way valve. Lengthens with growth of infant, sometimes resulting in spontaneous resolution. • Secondary: Competent, normal intravesicular ureter associated with anatomic (PUV) or functional (dysfunctional voiding, neurogenic bladder) abnormalities → high bladder pressure → failure of one-way valve

Severity and Grades (Figure 21-5) I II III IV V

Figure 21-5 Grades of VUR based on VCUG. (Reproduced with permission from Brunicardi FC, Andersen DK, Billiar TR, et al: Schwartz’s Principles of Surgery, 8th ed. New York: McGraw-Hill. Copyright © The McGraw-Hill Companies.)

• Mild • Grade I: Refl uxes into ureter only; no dilation • Grade II: Refl uxes into ureter and pelvis; no dilation • Moderate • Grade III: Refl uxes into ureter and pelvis; mild hydronephrosis (ureteral and calyceal dilation) • Grade IV: Refl uxes into ureter and pelvis; moderate hydronephrosis • Severe • Grade V: Refl uxes into ureter and pelvis; severe hydronephrosis with calyceal blunting, ± ureter tortuosity

Diagnostic Modalities • Renal US: Provides anatomic evaluation (to detect hydronephrosis, dilatation of ureters, bladder wall hypertrophy, ureterocele). A normal renal US does not rule out VUR. • Radionuclide cystogram (RNC): Less radiation, may be used for f/u of conﬁ rmed VUR. • VCUG: Provides functional evaluation of ureterovesicular junction (evaluation of reﬂ ux). A normal VCUG does not rule out anatomic abnormalities. A VCUG should be performed in the following patients to r/o VUR: Nephrology 263

• Any boy with a ﬁ rst UTI • Girls younger than age 3 yr with a ﬁ rst UTI • Any child younger than age 5 yr with a febrile UTI • Children with recurrent UTIs • Children with a prenatal renal anomaly

Medical Management (grades I–IV; consider for grade V when age 1–5 yr) • Prevention and treatment of constipation, normalization of voiding patterns, antibiotic prophylaxis of UTI, yearly f/u with renal US (ensure normal kidney growth) and VCUG/ RNC • Spontaneous resolution of reﬂ ux by age 4 yr: 90% for grade I, 80% for grade II, 50% for grade III, 30% for grade IV, 12% for grade V • Antibiotic prophylaxis • Pediatric patients: Trimethoprim–sulfamethoxazole (2 mg of TMP/kg once daily) or nitrofurantoin (1–2 mg/kg once daily) • Infants <2 mo: Amoxicillin (5–10 mg/kg once daily)

Surgical correction (ages 1–5 yr: consider for grade V; age 6+ yr: consider if grades III–V) • Endoscopic subureteral injection of bulking agents; open surgical repair • Indications: Multiple breakthrough infections, poor compliance with medical management, evidence of renal scarring or loss of function, prolonged observation without resolution (longer observation preferred and reasonable if normal voiding pattern, no intercurrent UTI)

ACUTE KIDNEY INJURY (ACUTE RENAL INJURY, ACUTE RENAL FAILURE) • Sudden deterioration in renal function (GFR) over hours to days leading to the inability to maintain electrolyte and ﬂ uid homeostasis, and excrete nitrogenous waste. • Associated laboratory changes: ≥100% ↑ serum Cr, ≥75%↓ eCCl, or eCCl <35 mL/min/1.73m2. • Subtypes based on UOP (diuresis to induce UOP in anuric state does not change

prognosis) PEDIATRICS • Anuric: Total cessation of UOP. • Oliguric: UOP <0.5 mL/kg/h in infants; <500 mL/1.73/m2 in older children; worse prognosis and more common than anuric in pediatric population. • Increased Cr may occur without decreased GFR: Cimetidine, trimethoprim, cefoxitin, ketoacidosis. • Increased BUN may occur without decreased GFR: steroids, GI bleed, high protein intake (TPN), severe cardiomyopathy, catabolic states (burns, sepsis). • Mortality generally low in AKI restricted to primary renal etiology, high in AKI associated with multiorgan failure. • pRIFLE classifi cation of AKI (Pediatric modifi cation of adult RIFLE criteria to standardize defi nition of acute kidney injury) (Kidney Int 2007;71:1028). • Risk: ↑ in serum creatinine (SCr) by 1.5X or ↓ glomerular fi ltration rate (GFR) by 25% or urine output (UO) <0.5 mL/kg/h for 6 h • Injury: ↑ in SCr by 2X or ↓ GFR by 50%, OR UO <0.5 mL/kg/h for 12 h • Failure: ↑ in SCr by 3X or ↓ GFR by 75%, OR SCr ≥4 mg/dL with acute increase of >0.5 mg/dL or UO <0.3 mL/kg/h for 24 h or anuria for 12 h • Loss: Persistent ARF, complete loss of kidney function >4 wk • End-stage renal disease: Loss of kidney function >3 mo 264 Pediatrics

ETIOLOGIES OF ACUTE KIDNEY INJURY

Etiology Urine Characteristics Prerenal

Decreased intravascular volume: Dehydration, sepsis or Bland sediment, hyaline casts, systemic vasodilation, GI losses, nephrotic syndrome ﬁ ne granular casts

Decreased cardiac output: CHF, arrhythmias

Renal vasoconstriction: ACEI, ARBs, NSAIDs, hepatorenal syndrome

Renovascular (large vessel): Bilateral renal artery stenosis + ACEI use, thrombosis, embolism, dissection, vasculitis Intrinsic

Renovascular (small vessel): HUS/TTP, DIC, endocarditis (emboli), HTN crisis

Tubular disease (ATN): Ischemia/reperfusion injury, toxins Pigmented (brown) granular (aminoglycosides, amphotericin, myoglobinuria, hemo- casts, RBCs or protein in UA globinuria, ethylene glycol, contrast media)

Interstitial Disease (interstitial nephritis): WBCs, WBC casts Drugs (penicillins, cephalosporins, sulfas, NSAIDS), (urine eosinophils, rash, arthral- pyelonephritis, protein deposition disorders gias speciﬁ c to drug allergy)

Glomerulonephritis RBC casts, RBCs, protein Postrenal

Urinary tract obstruction: UPJ obstruction, ureteral Bland sediment, hyaline obstruction (nephrolithiasis), PUV, severe bladder neck casts dysfunction (neurogenic bladder, anticholinergics)

CHARACTERISTICS OF PRIMARY CATEGORIES OF AKI

Prerenal Intrinsic Postrenal

Urine SG >1.020 <1.015 Varies

Urine osm >500 <300 300–400

Urine:plasma Cr >40 <20 <20

Urine:plasma osm >1.3 <1.3 Varies

Urine Na (mEq/L) <20 >40 >40

FENa <1% >2% >3%

Evaluation • All oliguria is considered obstructive until proven otherwise. • Postrenal and prerenal causes must be ruled out before pursuing renal parenchymal etiologies. • UA with microscopy is critical in the workup of AKI. • History: Prior renal disease, renal osteodystrophy (suggests possibility of AKI on CRI), growth and development, previous urinary tract pathology, recent ﬂ uid losses or drug or toxin exposure. Nephrology 265

• Laboratory (before ﬂ uid challenge or diuretics): Renal US (including Doppler and lower urinary tract), ECG (if hypocalcemic or hyperkalemic), UA with microscopy, BMP, serum albumin, urinary chemistries (spot sodium, creatinine, osmolarity, urea → calculate → UPr/Cr, urine/plasma osmolarity, FENa); consider: C3/C4, ASO, ANA, ANCA radionuclide scan, renal biopsy. × × × • Calculation of FENa: (Urine Na Serum Cr) 100/(Serum Na Urine Cr). Only applicable in presence of oliguria and absence of diuretics. [FE = (U Urea × Serum Cr) × × urea 100/(BUN Urine Cr) may be calculated in patients on diuretics; FEurea <35% suggests prerenal etiology in adults (Kidney Int 2002;62(6):2223).] Neonates have decreased

capacity for sodium resorption, so FENa must be interpreted with caution in these patients.

Management and Initial Approach Empiric Treatment • Hypovolemic (oliguric, no CHF) → r/o urethral or bladder outlet obstruction via catheterization → isotonic saline volume repletion (colloid if hypoproteinemia or blood loss). • Euvolemic or hypervolemic and no response → furosemide 2–4 mg/kg IV × 1 (converts oliguric to non-oliguric but no change in prognosis) → fl uid restriction if no response (see below). • Strict I/O, daily weights. • Treat underlying cause (urgent bladder catheterization ± surgical intervention for outlet obstruction). • Vigilant normalization of fl uid status (volume challenge if prerenal). Fluid restriction if hypervolemic = 400–600 mL/m2/d (insensibles) + renal and extrarenal losses (1:1). • Monitor or treat: Hyperkalemia, hypernatremia or hyponatremia, hyperphosphatemia, hypocalcemia, fl uid overload, CHF, hypertension, acidosis, uremia, infection. • Diet: Low protein, potassium, phosphate; provide ≥ 25% daily calorie requirement. • Dosage adjustment of medication with renal excretion; avoid nephrotoxic medication, contrast media.

General Indications for Dialysis: AEIOU • A (acidosis): Acidosis unresponsive to conservative measures (generally when <7.20) • E (electrolyte imbalances): Hyperkalemia >7.0 or <7.0 with ECG changes; seizures caused by hyperphosphatemia (very poorly cleared by dialysis); severe hypernatremia or hypona- PEDIATRICS tremia in oliguric or anuric patient • I (intoxication, inborn errors): Salicylates, theophylline, isopropanol, methanol, boric acid, barbiturates, lithium, ethylene glycol, valproate, carbamazepine, paraquat; hyperammonemia 2/2 IEM crisis • O (volume overload): Hypervolemia with diuretic-refractory HTN or pulmonary edema, or volume reduction for provision of additional therapies • U (uremia): Symptomatic uremia (eg, encephalopathy, bleeding, pericarditis; most often occurs when BUN >150 or rapid increase)

Prognosis for Recovery of Renal Function • Good for prerenal etiology, typical HUS, ATN, AIN, tumor lysis; poor for RPGN, renal vein thrombosis renal, cortical necrosis. • 60% of patients have some form of renal injury 3–5 yr later (hyperﬁ ltration, microalbu- minuria) (Kidney Int 2006;69(1):184).

CHRONIC KIDNEY DISEASE • Deﬁ nition: Chronic (≥3 mo) irreversible loss of kidney function manifested as (1) nl or ↓ GFR and abnormalities in blood/urine composition, renal imaging, or renal biopsy, or (2) GFR <60 (Pediatrics 2003;111(6):1416). 266 Pediatrics

CLASSIFICATION OF CKD

Stage GFR (mL/min/1.73 m2) Notes 1 ≥90 Kidney damage associated with nl or ↑ GFR 2 60–89 Mild 3 30–59 Moderate 4 15–29 Severe 5 <15 (or dialysis) ESRD

Pediatrics 2003;111(6):1416.

CAUSES OF ESRD IN PEDIATRIC PATIENTS

Age <5 yr Age > 5 yr (Congenital Causes) (Acquired or Inherited Causes) Obstructive uropathy Chronic GN Nephrotoxins Renal hypoplasia or dysplasia Renovascular disease PKD Severe VUR Bilateral Wilms tumor IEM (cystinosis, hyperoxaluria) Cystinosis HUS Alport’s syndrome Interstitial nephritis

• Clinical features: Growth failure, HTN, nocturia, polyuria, pruritus, nausea, vomiting, anorexia, peripheral neuropathy, encephalopathy, teeth and bone abnormalities (osteodystrophy, delayed bone age, rickets), anemia

Management • General • Avoid IVs and lab draws in nondominant arm for future dialysis access. • Immunizations according to normal schedule; no live vaccines on immunosuppressive medications (give before transplant if possible). • Renal replacement therapy • Dialysis or transplantation in ESRD. • Fluids • Insensibles (400–600 mL/m2/d) + 1:1 replacement of UOP. • Maximum ﬁ xed daily intake once in ﬂ uid homeostasis. • Nutrition • ↓ Phos, ↓ K diet, no-salt-added diet with 1–2 mEq/kg/d sodium goal (although patients with tubular dysfunction may lose Na and require supplementation), multivitamin (Dia- lyvite, Nephrocaps). • Infants: Similac PM 60/40 formula (whey:casein 60:40; low protein, low Na, low Phos); may require Na, K, Phos supplementation. • Protein: Lower limit of RDA (~1 g/kg/d); sources of high-biologic value (dairy, meat). • Prevention of renal osteodystrophy • GFR <75: phosphate restriction (dairy, meats, carbonated beverages), calcium supplementation (100–300 mg/kg/d), phosphate-binding agents (calcium carbonate, calcium acetate, sevelamer, lanthanum HCl). • GFR <50: Above, plus 1,25-OH vitamin D supplementation (calcitriol). • Monitoring for hyperkalemia and metabolic acidosis • Hyperkalemia: Acute treatment when K >7.0 or with any associated ECG changes → • Metabolic acidosis: Sodium bicarbonate or sodium citrate (goal serum HCO3, 22–24) dialysis. Nephrology 267

• Other • Anemia: Iron supplementation, recombinant erythropoietin when Hb <10 (goal, 12). • HTN: Proteinuria: nifedipine, hydralazine; ¢ proteinuria: ACE-I. • Short stature: If GH resistant (↑ GH, ↓ IGF-1) and height ≥ 2 SD below normal → recombinant human growth hormone.

RENAL BIOPSY: INDICATIONS AND CONTRAINDICATIONS Indications for Percutaneous Biopsy • Normal renal function : • Microscopic hematuria with proteinuria (chronic) • Persistent nonorthostatic proteinuria (>500–700 mg/d without known cause) • Any GN other than postinfectious • Acute renal failure : • No cause identifi ed after ruling out prerenal and postrenal causes • Associated with nephritis, vasculitis, nephritic syndrome, or systemic disease • Diffi culty differentiating ATN from glomerular or vascular lesions or CRF • ATN suspected but anuria prolonged (>3 wk) • Chronic renal failure: • Uncertain etiology, or standard follow-up after therapy • Hematuria: • Persistent microscopic hematuria >1 yr duration • Signifi cant proteinuria • Persistently low C3 levels and suspected SLE or MPGN • FH of nephritis • Hearing defi cit • Any associated renal insuffi ciency • HTN (after excluding anatomic and vascular etiologies) • Recurrent gross hematuria, with negative nonglomerular workup • Proteinuria : • Persistent hematuria • Nephrotic syndrome: Steroid resistant or with hematuria, HTN, azotemia

• HTN (after excluding anatomic/vascular etiologies) PEDIATRICS • Persistently low C3 levels • Systemic disease (HSP, DM, SLE), HSP and nephrotic range proteinuria or decreased renal function, DM and high-grade proteinuria or non-response to ACEI • Persistent, nonorthostatic, isolated proteinuria for >1 yr (>500-700 mg/d w/o etiology) • FH of chronic CH or CKD • Any associated renal insufﬁ ciency • Renal allograft : • Delayed autograft function • Recurrence of disease • Suspected rejection • Complication of therapy Contraindications to Percutaneous Biopsy • Absolute: Solitary native kidney • Relative: Small hyperechoic kidneys (higher risk of bleeding, indicative of chronic irreversible disease), multiple bilateral cysts, presence of renal tumor, uncorrectable bleeding diathesis, uncontrolled severe HTN, hydronephrosis, active renal/perirenal infection, anatomic kidney abnormalities, skin infection over both biopsy sites, uncooperative patient

Available at www.AccessPediatrics.com • Hypertension • Renal replacement therapies (modes of dialysis) CHAPTER 22 Neurology

NEUROLOGIC EXAM Observation • Developmental stage, social interaction • Gross and ﬁ ne motor movements, abnormal movements

Vital Signs and Anthropometrics • Growth charts, including FOC

Mental Status • LOC, ± GCS, ± Mini Mental Status Exam

Cranial Nerves

CRANIAL NERVES AND EXAMINATION METHODS

Cranial Nerve Nerve Exam

I Olfactory Test sense of smell

II Optic Perform funduscopic exam, visual acuity, visual ﬁ elds, pupillary response

III Oculomotor Assess medial, superior, and inferior recti muscles, inferior oblique, and levator palpebra superioris muscles; cover/uncover test (Figure 22-1)

IV Trochlear Assess superior oblique muscle, cover/uncover test (Figure 22-1)

V Trigeminal Assess muscles of mastication, sensation to face and anterior scalp, corneal reﬂ ex

VI Abducens Assess lateral rectus muscle, cover/uncover test (Figure 22-1)

VII Facial Assess facial muscles, taste (anterior 2/3 of tongue), parasympathetics to lacrimal and salivary gland

VIII Auditory Test hearing to ﬁ nger rub, vestibular function

IX Glossopharyngeal Test gag and palate elevation

X Vagus Test gag and palate elevation

XI Spinal accessory Assess strength of trapezius and sternocleidomastoid

XII Hypoglossal Assess tongue bulk and atrophy, symmetry

268 Neurology 269

SR(R3) SR(R3) IO(R3) IO(L3) SR(L3) SR(L3)

LR(R6) MR(R3) Nose MR(L3) LR(L6)

IR(R3) IR(R3) SO(R4) SO(L4) IR(L3) IR(L3) RIGHT LEFT Figure 22-1 Innervation of the extraocular muscles. Cranial nerves are represented in parentheses next to the muscle of innervations (eg, R4 is right fourth cranial nerve). IO, inferior oblique; IR, inferior rectus; LR, lateral rectus; MR, medial rectus; SO, superior oblique; SR, superior rectus.

Deep Tendon Refl exes • 4+: Hyperrefl exia with clonus • 1+: Hyporefl exia • 3+: Hyperrefl exia with spread across joint • 0: No movement • 2+: Normal

Motor • Muscle bulk and tone • 3/5: Full ROM against gravity only • Assess pronator drift for subtle weakness • 2/5: Full ROM in horizontal plane • Muscle strength: (gravity eliminated) • 5/5: Full strength • 1/5: Trace (“ﬂ icker”) of movement • 4/5: Full ROM against light resistance • 0/5: No movement

Coordination • Cerebellum and basal ganglia testing • Finger to nose, heel to shin, rapid alternating movements • Assess for head tilt or tremor, ﬂ uidity of movement • Assess for abnormal movements • Assess gait in the forward and backward directions; heel, toe and tandem gait • Romberg test : Assess patient standing with feet together and eyes closed; if patient steps to the side or falls → positive test result (may indicate a disturbance in vestibular apparatus or proprioception) PEDIATRICS

Sensory • Test in all extremities (Figure 22-2) • Pin prick, temperature sensation (spinothalamic tract in anterior spinal cord) • Vibration, proprioception (posterior columns in posterior spinal cord) • Assess for sensory level on the trunk if concern for spinal cord lesion

Miscellaneous Localizing Signs and Reﬂ exes

Maneuver Description Signifi cance

Babinski sign Upgoing plantar response Localizes to corticospinal tract

Hoﬀ man sign Flicking of patient’s second or third ﬁ nger Localizes to corticospinal tract causes contraction of the ipsilateral thumb at or above cervical spinal cord

Abdominal Stroke abdomen toward umbilicus; lack Localizes to the corti- reﬂ ex of brisk contraction of abdominal muscles cospinal tract at or above toward stroke is a ⊕ test thoracic spinal cord

Cremasteric Stroke inner thigh caudal to rostral, result- Localizes to the corticospi- reﬂ ex ing in contraction of cremasteric muscle nal tract at or above lumbar spinal cord

(continued on next page) 270 Pediatrics

Maneuver Description Signifi cance

Primitive Suggest frontal lobe dam- reﬂ exes age (except in neonates or • Glabellar Percuss forehead, and eye blink does not infants) extinguish • Snout Percuss lips in the midline, and lips pucker • Palmomental Stroke thenar eminence of hand, and mentalis muscle moves

Peripheral nerve Nerve root

Ophthalmic branch

Trigeminal Maxillary branch Mandibular branch Anterior cutaneous nerve of neck C3 Supraclavicular nerves P ost. Mid. Ant. C4 T2 C5 Axillary nerve T3 T4

i T5 T2 Medial cutaneous nerve of arm m T6

T7 cic ra cic

Lateral cutaneous nerve of arm ra T8 o

(branch of radial nerve) th T9 l l T1

ra T10 te

Medial cutaneous nerve of forearm a T11 C6 L

Anterior thoracic rami T12 Lateral cutaneous nerve of forearm X L1 L1

* C6 Radial † Median L2 C8 Ulnar C7 Lateral femoral cutaneous Obturator L3

Anterior femoral cutaneous

Lateral cutaneous nerve of calf

Saphenous L4 L5 X = Iliohypogastric † = Ilioinguinal = Genitofemoral Superficial peroneal * Dorsal nerve of penis Perineal nerve of penis

Sural S1 Lateral and medial plantar Deep peroneal A Figure 22-2 Cutaneous innervation (anterior and posterior views). (Reproduced with permission from Simon RP, Greenberg DA, Aminoff MJ: Clinical Neurology, 7th ed. Available at http://www.accessmedicine.com. New York: McGraw-Hill. Copyright © The McGraw-Hill Companies. All rights reserved.) Neurology 271

Nerve root Peripheral nerve

Great occipital

C2 Lesser occipital Great auricular

Posterior rami of cervical nerves C4 Supraclavicular T2 T3 Axillary T4 T5 C5 Lateral cutaneous nerve of arm T2 T6 T7 Posterior cutaneous nerve of arm T8 Medial cutaneous nerve of arm T9 T10 Lateral cutaneous nerve of forearm T1 Lateral thoracic rami

T11 Posterior thoracic rami Posterior cutaneous nerve of forearm C6 T12 L1 Medial cutaneous nerve of forearm X L2 Posterior lumbar rami

S3 Posterior sacral rami C6 S4 S5 Radial Median Ulnar C7 C8 Lateral femoral cutaneous Obturator L 3 Anterior femoral cutaneous S2 Posterior femoral cutaneous Lateral cutaneous nerve of calf PEDIATRICS X = Iliohypogastric L5 Superficial peroneal

L4 Saphenous

Sural

Calcaneal S1 Lateral plantar Medial plantar B Figure 22-2 (Continued )

Primitive Reﬂ exes NORMAL INFANT REFLEXES THAT APPEAR AT BIRTH

Refl ex Description Disappearance

Moro Lift head 30 degrees and allow to fall to neutral 1–3 mo (startle) Positive: Arm extension and abduction → arm adduction

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Refl ex Description Disappearance

Palmar grasp Flexion of hand when object placed against palm 4 mo

Root Stroking cheek causes mouth to turn toward stimulus 3–4 mo

Tonic neck Head is turned to side while the child is supine. 5–6 mo Positive: Ipsilateral arm/leg extension, contralateral arm and leg ﬂ exion (“fencing posture”); normal infant tries to break reﬂ ex

Babinski Stroke lateral border of sole from heel to great toe 1–2 yr Positive: Great toe dorsiﬂ exion, fanning of other toes

CLINICAL DISCRIMINATION OF UPPER AND LOWER MOTOR NEURON LESIONS

UMN Lesion LMN Lesion

Hyperrefl exia (± Hoff man, Babinski signs) Hyporefl exia

Hypertonia Hypotonia

Spasticity Flaccidity

Normal muscle bulk ± Muscle atrophy

No fasciculations Fasciculations

ACTIONS OF THE PRINCIPAL MUSCLES AND THEIR NERVE ROOT SUPPLY

Action tested Roots∗ Nerves Muscles

Brachial

Adduction of extended arm C5, C6 Brachial plexus Pectoralis major

Initiation of abduction of arm C5, C6 Brachial plexus Supraspinatus

Abduction and elevation of C5, C6 Axillary nerve Deltoid arm up to 90°

Flexion of supinated forearm C5, C6 Musculocutaneous Biceps, brachialis

Extension of forearm C6, C7, Radial Triceps C8

Extension (radial) of wrist C6 Radial Extensor carpi radialis longus

Adduction of ﬂ exed arm C6, C7, Brachial plexus Latissimus dorsi C8

Supination of forearm C6, C7 Posterior interosseous Supinator

(continued on next page) PEDIATRICS ensor carpi ulnaris magnus, brevis magnus, semitendinosus, semitendinosus, semimembranosus longus and brevis soleus cial) longus Peroneus osseous Ext Nerves Muscles Median nerve Opponens pollicis Ulnar Interossei ∗ L4 Femoral femoris Quadriceps S2 gluteal Inferior maximus Gluteus L3 Femoral Iliopsoas S1 Superior gluteal medius Gluteus S2 Sciatic femoris, Biceps Tibialposterior Tibialis C8 inter Posterior T1 T1 L3, S1, L5 C8interosseous Posterior Extensor digitorum S2 Tibial Gastrocnemius,

L5 S1 (deep) Peroneal (deep) Peroneal tibial Anterior Extensor hallucis L1, L2, L2, L3 FemoralL2, L4, L5, Sartorius L5, S1, C7, C7, C8, L4, L5, C8, S1, exed exed exion of foot exion of wrist C6, C7 Median nerve carpi radialis Flexor toe exion of great (medial) exion of foot nger externally exion from semifl exion from fth fi fth ngers Extension of knee knee of Flexion L5, position Hip fl position rotated Adduction of thighAbduction rota- and internal tion of thigh L4 L2, L3, Extension of thigh Obturator longus, Adductor Crural Hip fl Extension of proximal Extension proximal of phalanges Action testedExtension wrist (ulnar side) of Roots Pronation of forearmPronation Radial fl Opposition of thumb against C6, C7fi Median nerve teres Pronator Dorsifl Dorsifl Abduction and adduction of fi Eversion of footEversion L5, S1 (superfi Peroneal Plantar fl Inversion of footInversion L4, Contraction of anal sphincter S2, S3, S4 Pudendal muscles Perineal Predominant root(s) supplying a particular in bold italic type. root(s) indicated muscle are Predominant ∗ 274 Pediatrics

NEUROIMAGING BASICS

Modality Best For Examining Advantages Disadvantages US Ventricles and gross brain Can be done at bedside Poor resolution structure of neonates Quick with open fontanelles No radiation TCD for sickle cell disease Relatively inexpensive CT Intracranial blood or Quick Poorly defi nes soft tissues calcifi cations Able to be used if implant- Poor visualization of poste- Cranial bone integrity able device is present and rior fossa MRI is contraindicated Radiation exposure Relatively inexpensive CTA Intracranial arterial Quick Radiation exposure system Inexpensive May cause renal injury from contrast Possible iodine allergy MRI Brain parenchyma Best defi nition of soft Requires time to obtain tissues images Better resolution of Slight risk of irreversible renal structures scarring (primarily in those Best for evaluating with preexisting renal disease) posterior fossa May require sedation No radiation More expensive than CT MRA Intracranial arterial No contrast necessary Requires more time to system, carotids, basilar No radiation obtain images arterial system More expensive than CT Vascular malformations MRV Intracranial venous No radiation Requires more time to system (eg, r/o sinous obtain images venous thrombosis) More expensive than CT Vascular malformations MRS Suspected metabolic d/o No radiation Requires specialized neuro- Evaluation of neonatal HIE radiologist interpretation Noninvasive biochemical tumor typing (via assessment of molecular composition and biochemical changes in brain tissue)

CT SIGNAL DENSITY

Darker (black) ←⎯⎯⎯⎯⎯ Isodense ⎯⎯⎯⎯⎯→ Lighter (white) Air Fat CSF Brain tissue Blood Contrast Bone

MRI SIGNAL INTENSITY

Fat CSF Gray Matter White Matter Bone Blood T1 Very bright Dark Intermediate Bright Very dark See below; depends on T2 Dark Very Intermediate Dark Very dark chronicity bright PEDIATRICS

Microhe- morrhages (blood is dark) Pediatrics Chronic Chronic (months–years) GRE/FFE SWI Blood (blood is dark) (continued on next page) 2003;60:166 c area of brain involved. of brain involved. c area contralateral eye deviation, rapid eye contralateral 2000;55:616 e deviation as seizure generalizes e deviation as seizure : Neurology Acute Acute ischemia is dark (ADC DWI is where bright if true ischemia is and present not artifact) rst simple febrile seizure: Late Subacute Late (1 wk–1 mo) Neurology med visual phenomenon, ipsilateral eye deviation eye med visual phenomenon, ipsilateral Acute Acute ischemia (ischemia is bright within 30 min) Consciousness preserved (unlike complex partial). complex preserved (unlike Consciousness baseline to return postictal obtundation secondary by and facial clonic activity arrest followed generalization head and ey Contralateral seizure rst unprovoked Early Subacute 3–day 7) (day Pathology (pathology causing any parenchymal edema is bright) FrontalTemporal bizarre, brief, Hypermotor, Olfactory automatisms, oromotor staring, aura, quiet, ParietalOccipitalmanifestations Sensory phenomenon with or without motor Rolandic for Poorly Initial sensory then speech face; changes in mouth, tongue, rst nonfebrile seizure in a child: Pathology Pathology (white ismatter darker, gray ismatter brighter) Acute Acute (6 h–day 3) 1996;97(5):769 Treatment of a child with a fi Evaluating a fi The neurodiagnostic evaluation of a child with a fi Type (Partial) Seizures Focal Simple partial Subtype (Variable) Semiology Typical Complex depend on specifi Manifestations partial Secondarily generalized T1 Isodense or darkT2 Bright dark Very Dark Bright Bright Dark Dark T1Structure and anat- (gray T2omy is matter darker, white Flair is matter brighter) DWI ADC SEIZURES Practice Parameters • • • CLINICAL SEIZURE CLASSIFICATION EVALUATION OF INTRACRANIAL HEMORRHAGE USING MRI EVALUATION OF INTRACRANIAL COMMON MRI SEQUENCES AND POTENTIAL APPLICATIONS POTENTIAL AND MRI SEQUENCES COMMON 276 Pediatrics

Type Subtype Typical Semiology Generalized Seizures Generalized Absence Behavioral arrest, staring, rhythmic or semi-rhythmic automatisms (blinking, lip smacking); immediate return to baseline upon cessation of seizure Clonic Brief rhythmic jerking of extremities with minimal postictal change Atonic Brief loss of postural tone, which may result in only a drop of the head or a fall; minimal postictal change Tonic Brief tonic extension, fl exion, or mixed posturing with minimal postictal change Tonic-clonic Tonic extension followed by increasingly coarse and slow clonic jerking with postictal obtundation Myoclonic Very rapid, nonrhythmic contractions of proximal or axial muscles Infantile Flexion, extension, or mixed fl exion and extension of axial spasm and proximal muscles, which is briefl y sustained and then recurs in clusters

Simple Febrile Seizures • Criteria for diagnosis: • Age: 6 mo–5 yr; Peak age of incidence: 18 months • Temperature: >101.5°F not caused by CNS infection • Duration: <15 min • Character: Generalized • If >15 min or focal, then considered a complex febrile seizure • Evaluation: • 6–12 mo: Needs LP (CNS infections difﬁ cult to clinically ascertain at this age) • 12–18 mo: Consider LP if any clinical concern for a CNS infection • 18 mo–5 yr: no LP unless clinical signs for CNS infection • All ages: Evaluation for source of fever • EEG, CT, and MRI not routinely indicated • Treatment • Reassurance and education • Rectal diazepam (for seizures lasting >5–10 min) • No anticonvulsants indicated • Recurrence • Risk of subsequent simple febrile seizure • ~30% after ﬁ rst • ~50% after second • Higher if a complex febrile seizure • Risk of subsequent epilepsy • ~2% • Risk in general is ~1% • Higher if a complex febrile seizure Evaluation of a First Nonfebrile Seizure • History: Prior seizure or events concerning for seizures (new onset bedwetting, loss of consciousness, episodes of lost time), recent head trauma, signs of illness, birth history • Neurologic exam: Look for evidence of focality • Mental status: Postictally obtunded, unresponsive • Cranial nerves: Funduscopic exam, dysconjugate gaze, hemifacial weakness, any motor or sensory asymmetry Neurology 277

• Motor and DTRs: Asymmetries of tone, movement, and refl exes • Coordination: Any involuntary movements • Gait: Assess for asymmetric arm swing • Laboratory evaluation: sodium, calcium, glucose; other labs as indicated (urine toxicology screen, extended serum toxicology screen, CBC) • Ancillary studies • CT: In the ED if there is a history of trauma, the patient has focal neurologic fi ndings, or the patient will undergo an LP and has a depressed sensorium • No contrast needed when evaluating for intraparenchymal blood; contrast necessary for evaluation of mass lesion or abscess • If an outpatient imaging study will be obtained: MRI preferred • MRI with contrast: Useful for patients with a fi rst seizure that did not sound like absence epilepsy, benign rolandic epilepsy, or other idiopathic epilepsy • EEG • A postictal EEG is indicated to rule out nonconvulsive (subclinical) seizure activity; otherwise of little utility • An interictal EEG is useful in helping to consider the likelihood of seizure recurrence (30% if EEG, neurological exam, and MRI are normal; 90% if all three are abnormal); should be obtained 1–2 wk after event • Disposition • If truly a fi rst-time seizure and the patient has returned to baseline: Discharge home, seizure precautions (including no driving for teens), seizure fi rst aid, rectal diazepam prescription and teaching • If a recurrence of previous events: Consider an anticonvulsant or proceed with an outpatient workup if events are infrequent and not prolonged • If patient is not returning to baseline or is continuing to have recurrent seizures in the ER: Admit for observation and expedited workup and to ensure control of seizures Evaluation of Patient with Known Epilepsy with a Breakthrough Seizure • History: Type of seizures, usual frequency, anticonvulsant medication, last dose taken, last dose alteration, precipitating factors (illness, lack of sleep, medication nonadherence)

• Laboratory tests: Drug levels (not necessary to get calcium, magnesium, glucose unless PEDIATRICS clinically indicated) • Ancillary tests (EEG, CT, MRI): Rarely indicated unless it is a new or different event and there is clinical concern for an underlying structural process • Disposition: Discharge if the patient experienced typical postictal changes and has returned to baseline

EPILEPSY CLASSIFICATION SCHEME

MRI/Labs Symptomatic EEG (known cause) Idiopathic Cryptogenic

Generalized Abnormal MRI or Juvenile myoclo- Normal MRI and labs labs (genetic abnor- nic epilepsy Usually have devel- mality, metabolic Absence opmental delay, MR, disease) epilepsy abnormal exam Diﬃ cult to control Eg, lissencephaly

Localization-related Abnormal MRI Rolandic Normal MRI and labs May be surgically epilepsy Localizable Focus curable on EEG Eg, mesial temporal sclerosis 278 Pediatrics

Epilepsy Classifi cation Scheme • Based on etiology and seizure type • Etiology • Symptomatic: Confi rmed underlying structural abnormality visible on imaging • Idiopathic: Presumed or confi rmed genetic cause (ion channelopathy, or familial epilepsy syndrome) • Cryptogenic: No confi rmed structural or genetic etiology (including chromosomal disorder or IEM) • Seizure type • Localization related (focal or partial seizures) • Generalized • Classifi cation: Symptomatic localization related epilepsy, idiopathic generalized epilepsy, cryptogenic localization related epilepsy, etc.

COMMON EPILEPSY SYNDROMES

Epilepsy Age of Onset Clinical Treatment Syndrome and Prognosis Characteristics EEG Pattern Options

West Peak, 4–6 mo; Triad of: infantile Hypsarrhythmia• ACTH Syndrome 90% before spasms, devel- • Lamotrigine, leveti- 12 mo opmental delay, racetam, felbamate, Prognosis: hypsarrhythmia tiagabine, VPA, and Generally poor on EEG topiramate have (cryptogenic been tried with generally better some evidence than symptom- • Vigabatrin, especial- atic) ly in patients with tuberous sclerosis

Benign Typical is 5–10 yr Nocturnal tonic Spikes and • Oxcarbazepine childhood clonic seizures aris- sharp waves in often ﬁ rst choice epilepsy ing from the lower mid temporal Prognosis: Major- • May use any with cen- rolandic area of and central ity fully resolved drug used in trotemporal cortex, region and may by adolescence partial onset spikes Daytime with be unilateral or epilepsy (benign bilateral facial twitching, • Benign course, Rolandic preservation of and not all epilepsy, consciousness, physicians treat BRE) excessive pooling of with AED saliva, and tonic or tonic-clonic activity of face Absence Childhood form: Absence seizures; 3-Hz spike and • Ethosuximide epilepsy 5–12 yr up to several wave activ- • Lamotrigine hundred per day ity that may be Juvenile form: • VPA Adolescence induced with hyperventila- Prognosis: tion Majority remit by adulthood Juvenile 12–18 yr Myoclonic jerks, Diﬀ use, bilateral, • VPA myoclonic Prognosis: generalized tonic- and symmetric • Lamotrigine epilepsy clonic seizures, spike and poly Majority lifelong; • Levetiracetam good response to and absence spike and wave medications seizures 4–6 Hz activity

(continued on next page) Neurology 279

Epilepsy Age of Onset Clinical Treatment Syndrome and Prognosis Characteristics EEG Pattern Options Lennox- Childhood Mixed seizure dis- Slow spike and • Very refractory to Gastaut Prognosis: poor order with tonic, wave pattern treatment syndrome tonic-clonic, myo- (1.5–2.5 Hz) • Most common clonic, atypical on a slow AEDs used are absence, and/or background VPA, phenytoin, head drops; often felbamate, accompanied by lamotrigine, mental retardation topiramate, and benzodiazepines • Ketogenic diet

Landau- <10 yr Acquired aphasia No speciﬁ c pat- • VPA and lam- Kleﬀ ner Prognosis: and epileptiform tern; may have otrigine syndrome Variable (earlier discharges from spikes, sharp • High-dose onset better) temporal and waves, and spike diazepam parietal regions and wave activity • Steroids are in temporal and sometimes used parietal regions

Treatment of Status Epilepticus • See Chapter 9 (critical care).

Treatment of Epilepsy ANTIEPILEPTIC MEDICATIONS

Adverse Eff ects† Starting Typical Pharmacokinetics Dosage Therapeutic (metabolism, Common Serious (mg/kg/ Range half-life in hours, But ∗ Drug Target Use day) mcg/mL other) Rare PEDIATRICS

Carbam- Na LRE 5–10 8–12 Hepatic, 8–24, Hypona- Leuko- azepine auto induction tremia penia, hepatitis

Phenytoin/ Na LRE 5 10–20 Hepatic, 10–30, Gingival Bone fosphenytoin nonlinear elimi- hyper- marrow nation plasia suppression

Ethosux- Ca ABS 10–15 40–100 Hepatic, 30–40 GI upset, None imide headache

Felbamate Na, LRE, 15 20–100 Hepatic, 20–23 Anorexia, Hepatic GABAR GE insomnia failure, aplastic anemia

Gabapentin Ca, LRE 10 1-2 Renal, 5–7, ab- Sedation, None sorbed in carrier- weight dependant way gain

(continued on next page) 280 Pediatrics

Adverse Eff ects† Starting Typical Pharmacokinetics Dosage Therapeutic (metabolism, Common Serious (mg/kg/ Range half-life in hours, But Drug∗ Target Use day) mcg/mL other) Rare Lamotrigine Na, Ca LRE, 0.6 (not on 4–20 Hepatic, 15–30 Insomnia Stevens- GE VPA) Johnson 0.15 (on syn- VPA) drome ↑ slowly! Levetirac- SV2 LRE 20 20–40 Renal, 6–8 Sleepi- None etam ness, psychiatric disturbance Lorazepam GABAR LRE, 0.1 N/A Hepatic Sedation Respira- GE tory depression Oxcarba- Na LRE 10 20–50 Hepatic, 8–15 Hypona- Symp- zepine tremia, tomatic ataxia, hypona- diplopia tremia Phenobar- GABAR LRE, 5 20–40 Hepatic, 100 Sedation Respira- bital GE (adults); tory hyper- depres- activity sion (children) Pregabalin Ca LRE ‡ ‡ Renal, 5–7 Sedation, None weight gain Topiramate Na, LRE, 5–10 5–25 Hepatic/renal, Cognitive Renal GABAR GE 20–30 slowing, stones, paresthe- glau- sias, coma, weight oligo- loss hidrosis Valproic Na, Ca LRE, 15 50–150 Hepatic, 10–20 Tremor, Hepa- acid GE hair loss, titis, weight pancrea- gain, titis thrombocytopenia Zonisamide Na, Ca, LRE, 1–2 10–40 Hepatic, 50–70, Weight Renal GABAR GE no eﬀ ect on P450 loss, stones, paresthe- glau- sias coma, oligo- hidrosis

∗ Bold, italicized drugs are considered ﬁ rst-line therapies for the bold, italicized type of epilepsy. † Adverse eff ects: Virtually all anticonvulsants have been associated with severe dermatologic reactions such as Stevens-Johnson syndrome. Also, no anticonvulsant has been shown to be safe in pregnancy, and many have been associated with an increased risk of fetal malformations. Mechanism: Ca = decreased voltage-gated calcium channel conductance, GABAR = increase conductance of GABA-A receptor, Na = decreased voltage-gated sodium channel conductance, SV2 = acts on synaptic vesicle protein SV2. Indication: ABS = absence; GE = generalized epilepsy, LRE= localization-related epilepsy. Pharmacokinetics: Primary metabolic pathway (hepatic or renal or both), adult half-life (h). ‡ No range established for pediatric population. Neurology 281

HEADACHES (Cephalalgia 2004;24(suppl 1):1 or www.ihs-classifi cation.org/en) Neuroimaging in Headache Evaluation • Obtaining a neuroimaging study on a routine basis is not indicated in children with recurrent headaches and a normal neurologic exam. • Neuroimaging should be considered in children with the following: • Recent onset of severe headache • Change in the type of headache • Neurologic dysfunction • Neuroimaging should be considered in children with an abnormal neurologic examination (eg, focal fi ndings, signs of increased intracranial pressure, signifi cant alteration of consciousness) and those with the coexistence of seizures and headaches. IHS HEADACHE CLASSIFICATION SCHEME

Primary Headache Disorders Secondary Headaches Migraine Headache attributed to head or neck trauma Tension type Headache attributed to cranial or cervical vascular disorder Cluster Headache attributed to nonvascular intracranial disorder Other primary headache Headache attributed to substance or withdrawal from substances disorders Headache attributed to infection (see http://www.ihs- classiﬁ cation.org/en) Headache attributed to disorders of homeostasis Headache attributed to disorders of the cranium, neck, eyes, ears, nose, sinuses, teeth, or other facial or cranial structures Other headache, cranial neuralgia, central or primary facial pain Adapted from http://www.ihs-classiﬁ cation.org/en.

Migraine Headaches

DIAGNOSTIC CRITERIA FOR MIGRAINE HEADACHE PEDIATRICS

Migraine without Aura Migraine with Aura A. At least fi ve attacks fulfi lling A. At least two attacks fulfi lling criteria B–D criteria B–D B. Aura consisting of at least one of the following but B. Headache attacks lasting 4–72 h no motor weakness: C. Headache has at least two of 1. Fully reversible visual symptoms including posi- the following: tive features (eg, fl ickering lights, spots or lines) 1. Unilateral location or negative features (eg, loss of vision) 2. Pulsating quality 2. Fully reversible sensory symptoms including 3. Moderate or severe pain positive features (eg, pins and needles) or nega- intensity tive features (eg, numbness) 4. Aggravation by or causing 3. Fully reversible dysphasic speech disturbance avoidance of routine physical C. At least two of the following: activity 1. Homonymous visual symptoms or unilateral D. During headache, at least one sensory symptoms of the following: 2. At least one aura symptom develops gradually 1. Nausea or vomiting over ≥5 min or diff erent aura symptoms occur in 2. Photophobia and phono- succession over ≥5 min ≤60 min phobia D. Headache fulfi lling criteria B–D for migraine E. Not attributed to another without aura begins during the aura or follows the disorder aura within 60 min E. Not attributable to another disorder Note: Other migraine variants include retinal, basilar, hemiplegic, confusional, abdominal migraines and cyclic vomiting. Adapted from http://www.ihs-classifi cation.org/en. 282 Pediatrics

Complications of Migraine • Chronic migraine : >15 d/mo for >3 mo (not caused by analgesic overuse) • Status migrainosus: Deﬁ ned as headache lasting >72 h • Persistent aura without infarction >1 wk • Migraine-triggered seizure

TREATMENT OF MIGRAINE HEADACHES

Medication Route Dose Maximum Abortive therapy NSAIDS Ibuprofen PO 7.5–10 mg/kg Q6–8h 2.4 g/day Acetaminophen PO 10–15mg/kg Q4–6h 15 mg/kg/dose, 75 mg/kg/ day, or 2.6 g/day Triptans Sumatriptan PO 25, 50, 100 mg Two doses in 24-h period Nasal 5, 20 mg Sub-Q 6 mg Zolmitriptan PO 2.5, 5 mg Nasal 5 mg Prophylactic Therapy AED PO 500–1000 mg/day Valproic acid (9–17 yr) IV 15–45 mg/kg/day Topiramate PO See “Status Migrainosus” Start at 12.5–25 mg Qhs and increase by 25 mg Levetiracetam PO/IV weekly to 100 mg/day 250–500 mg BID (consider starting at 10–20 mg/kg/day Antidepressant Amitriptyline PO 0.25 mg/kg Qhs (<3 yr), 1 mg/kg/day or 10 mg/day or (children) 10 mg Qhs (3–12 yr) Antihistamine Cyproheptadine PO 0.25 mg/kg/day divided 2–6 y: 12 mg/day TID, or 7–14 y: 16 mg/day 2–8 mg/day divided TID adults: 0.5 mg/kg/day Antihypertensive Propranolol PO 20-35 kg: 10–20 mg/ 4 mg/kg/day (children), or dose TID 160-240 mg/day (adults) >35 kg: 20–40 mg/dose 3 TID Neurology 283

Management of Status Migrainosus (institutional practice based on expert consensus) • DHE is contraindicated in patients with hypertension or cardiac disease. • Need to wait 24 hours between using a triptan and initiating DHE. • In younger or smaller children, may need to adjust all doses below. • Begin IV ﬂ uids (100%–200% maintenance rate). • Begin IV ketorolac 7.5–15 mg IV Q6h. • Begin IV valproic acid 500 mg to run over 30 min; repeat Q8h. • If headache persists, give promethazine IV (12.5–25 mg), metoclopramide IV, or ondansetron IV to premedicate for DHE. • If headache persists, administer DHE. • DHE may be diluted in 250 cc of normal saline and given over 1 h. • DHE starting doses: 6–9yr, 0.1 mg/dose; 9–12 yr, 0.15 mg/dose; 12+ yr, 0.2 mg/dose. • May be given Q6h for a maximum of eight doses. • Dose may be increased by 0.05 mg/dose unless the patient is having side effects (eg, nausea, vomiting, GI upset).

CHRONIC DAILY HEADACHES

Tension Type HA

A. ≥10 episodes occurring on <1 d/mo on average (<12 d/yr) B. Headache lasting from 30 min–7 d C. Headache has at least two of the following characteristics 1. Bilateral location 2. Pressing or tightening (nonpulsating quality)

3. Mild or moderate intensity 4. Not aggravated by routine physical activity D. Both of the following: 1. No nausea or vomiting (anorexia may occur)

2. No more than one of photophobia or phonophobia PEDIATRICS E. Not attributed to another disorder

Chronic Daily Headache∗

>15 headaches/mo for >4 mo with HA lasting >4 hours/day

∗May include chronic migraine (transformed), chronic tension type, new daily persistent headache, or hemicranium continuum Adapted from http://www.ihs-classiﬁ cation.org/en 284 Pediatrics

DEMYELINATING DISEASES

Defi nition Gender Course Symptoms MRI Lesions Lab Studies

CIS First episode Mono- Monofocal Correspond CSF: Cell count, of acute phasic or polyfocal with present- protein, IgG inﬂ ammatory without ing symptoms synthesis and demyelina- encephal- May include index, oligo- tion opathy optic neuritis clonal bands, or transverse myelin basic myelitis protein, EBV/ CMV/ Mycoplasma PCR Serum: NMO antibody (when optic neuritis or transverse myelitis present), EBV and CMV titers, EBV nuclear antigen, Myco- plasma titers or PCR

ADEM Encephalopa- F:M ratio: Typically Monofocal Gray and Same workup thy with acute 0.4–0.8:1 monopha- or polyfo- white matter as CIS multifocal sic, but cal with involved Typically do inﬂ ammatory there are encephal- Lesions of the not see oligo- demyelinating recurrent opathy same age clonal bands process typi- and mul- cally follows a tiphasic Lesions are viral illness forms more poorly deﬁ ned than in MS Spinal lesions usually encompass the entire diameter of the cord at a given level

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Defi nition Gender Course Symptoms MRI Lesions Lab Studies MS Episodes of F:M ratio: In children, Polyfocal White matter Same workup infl ammatory <6 yr most often and deep gray as CIS demyelination 0.8:1; relapsing nuclei Oligoclonal disseminated in 6–10 yr, and Lesions of vari- bands present space and time 1.6:1; remitting, ous ages in 90% of (in children, >10 yr, may be children with must have two 2.1:1 secondary Brain lesions are typically MS but may additional non- progres- not be present ADEM events if sive located perpendicularly to when fi rst initial attack was diagnosed diagnosed as the long axis ADEM) of the corpus CSF WBC callosum usually 0–30, Progression: and are often although may Primary progres- periventricular be as high sive course: Spinal lesions as 60 2%–7% typically span Relapsing and only a portion remitting course: of the diameter 90% (~15% of the cord and progress to are not as long secondary as in NMO progressive course) NMO Chronic F:M ratio: Relapsing Polyfocal May see evi- CSF: Oligoclo- infl ammatory 3.2:1 dence of optic nal bands may demyelinat- neuritis be present ing condition Brain lesions May have characterized may be pres- higher CSF by the major ent but do not WBC than criteria of optic fulfi ll the crite- in MS neuritis and ria for MS acute myelitis NMO-IgG may Typically be present Minor criteria spinal lesions PEDIATRICS (need 2/3 for dx) should span are spinal MRI at least three lesion spanning levels longitu- at least three dinally levels, serum NMO-IgG, brain MRI not meeting criteria for MS

Management Acute Therapy • First-line therapy: Corticosteroids 30 mg/kg/dose (max 1 g/dose) IV daily × 3–5 d, may taper oral prednisone for 4–6 wk if indicated. • Second-line therapy: IVIG 2 g/kg divided into daily doses (usually 400 mg/kg/dose × 5 d) in patients in whom corticosteroids are contraindicated or for whom there was no response to corticosteroid treatment. In severe disease, consider plasmapheresis before IVIG. Chronic Therapy Pediatric relapsing and remitting MS: • First-line therapy: IFN-β and glatiramer are thought to decrease relapse rate; may be associated with depression, generalized edema, or transaminitis. • Second-line therapy: Azathioprine (treatment failure or inability to tolerate ﬁ rst line). 286 Pediatrics

• Monthly IVIG has been used if children are unable to tolerate other therapy. • Alternative therapeutic options: Methylprednisolone pulses, mitoxantrone, cyclophosphamide, methotrexate, natalizumab. NMO: • Azathioprine, and/or corticosteroids (alone or in combination); mitoxantrone, rituximab, or cyclophosphamide. • IFN therapy is less effective in patients with NMO and is not typically used

OVERVIEW OF CAUSES OF CHILDHOOD WEAKNESS

CNS and Spinal Motor Peripheral Cord∗ Neuron Nerve NMJ Muscle Hereditary Degenera- SMA 1,2,3 CMT 1, 2 Muscular dystrophies tive ALS Dejerine Sottas • Dystrophinopathies Friedrich’s ataxia (Duchenne, Becker MD) Hereditary • Sarcoglycanopathies neuropathy with (limb-girdle MD) liability to pres- • Myotonic dystrophy sure palsy • FSH MD Giant axonal • Congenital MD neuropathy Mitochondrial myopathies Metabolic GM2 Refsum’s disease Metabolic myopathies gangliosi- Abetalipopro- • Acid maltase defi ciency dosis teinemia • Carnitine defi ciency Metachromatic • Myophosphorylase leukodystrophy defi ciency Krabbe’s disease • Phosphofructokinase Porphyria defi ciency Tangier disease Mitochondrial myo- Fabry’s disease pathies Congenital Congenital Congenital Congeni- Congenital myopathies malforma- hypomyelinating tal myas- • Central core disease tion neuropathy thenia • Nemaline rod myopathy • Centronuclear myopathy Myotonic disorders • Myotonia congenital • Paramyotonia congenital Periodic paralysis • Hypokalemia • Hyperkalemic

(continued on next page) Neurology 287

CNS and Spinal Motor Peripheral Cord∗ Neuron Nerve NMJ Muscle Acquired Disorders Inﬂ amma- MS AIDP/Guillain- Transient Dermatomyositis tory NMO Barré syndrome neonatal Polymyositis myasthe- Immuno- Transverse Miller Fisher vari- nia Inclusion body logic myelitis ant GBS myositis Autoim- ADEM CIDP mune Parasitic myositis Vasculitis myasthe- Sarcoidosis nia gravis Toxic Environmental Botulism Myotoxic drugs toxins Tick Steroid myopathy Lead paralysis Mercury Organophos- phates n-Hexene Neurotoxic drugs Infectious Abscess Polio Herpes zoster Viral myositis Herpes simplex Parasitic myositis Bell’s palsy Mycoplasma TB Lyme disease Leprosy Other Stroke Seizure (eg, Todd’s PEDIATRICS paralysis) Mass lesion Migraine

∗ If any combination of hyperreﬂ exia, bilateral lower extremity weakness, bowel or bladder dysfunction, or sensory level are present, consider spinal cord compression, which is a neurologic emergency.

DETERMINATION OF BRAIN DEATH (institutional practice based on expert consensus) 1. Clinical criteria a. The patient is in a coma as manifested by a complete loss of consciousness, vocaliza- tion, and volitional activity. b. The patient has a body temperature >32°C. c. There is no spontaneous respiratory effort. d. There is an absence of brainstem function as deﬁ ned by: (1) Midposition or fully dilated pupils that do not respond to light. (2) Absence of eye movements by oculocephalic and caloric testing. (3) Absence of movement of bulbar musculature including facial and oropharyngeal muscles. The corneal, gag, cough, sucking, and rooting reﬂ exes are absent. 288 Pediatrics

2. The clinical criteria identiﬁ ed above must be present for the following minimum periods of time depending on the patient’s age: a. Birth–1 mo postterm: 48 h b. 1 mo postterm–1 yr: 24 h c. 1–16 yr: 12 h d. >16 yr: 6 h 3. In any situation in which there is a possible drug effect or a reversible metabolic condition involving the patient’s altered state of consciousness and when there is doubt as to the nature of the pathological process responsible for the cessation of neurologic function, the condition of brain death may be established by studies of cerebral perfusion that document the absence of intracranial circulation. 4. The performance of an EEG is not a prerequisite for a clinical determination of brain death.

EVALUATION OF GLOBAL DEVELOPMENTAL DELAY (Neurology 2003;60:367) Criteria • Typically applied to children >5 yr • Social and personal • Delays in two or more of the following areas • Activities of daily living (Figure 22-4): • Fine gross motor delays • Speech and language • Cognition

First-Line Evaluation • History and physical exam: Important components include assessing for regression in development, consanguinity, miscarriages in other pregnancies, family history of developmental delay, dysmorphic features. • Hearing and vision screening exams. • Obtain results of newborn screen or send initial screen if not previously completed. • EEG (if seizures present). • Screen for autism spectrum disorders (see Neurology 2000;55:468). Second-Line Evaluation • MRI brain without contrast in all patients with global developmental delay (with contrast if seizures present). • Genetic testing • Chromosomes and CMA in all patients • Fragile X testing • Rett testing • Metabolic testing should be completed in the context of historical or physical exam fi ndings suggestive of a specifi c etiology, including serum amino acids, urine organic acids, acylcarnitine profi le, mucopolysaccharides, serum glucose, bicarbonate, lactate, pyruvate, ammonia, and creatine kinase. • Serum lead level.

Available at www.AccessPediatrics.com • Ataxia • Stroke • Weakness PEDIATRICS

) do not 40% to ; typically occurs 2+ → 10 2002; 34:730). Ca ↓ 38.0°C (100.4°F) on two ≥ Clin Infect Dis. renal failure, 1993;19:129) → 289 release of intracellular contents into ciency). → 2008;26(16):2767) /day (200 mL/kg/day if wt <10 kg) with D5 ¼ NS + 2 . 3 Cancer Treatment Rev 38.3°C (101°F) or a temperature 38.3°C (101°F) or a temperature (

HR (tachycardia) and/or BP (hypotension), mental status HR (tachycardia) and/or BP ≥ J Clin Oncol (

mortality from gram-negative infections (80% mortality from gram-negative ↓ Urine culture (only if UA abnormal; do not catheterize immunosup- Urine culture (only if UA abnormal; Rapid lysis of tumor cells Will phosphorus, potassium, uric acid therapy starts (may occur at presentation). → CBC, blood cultures (all lumens of CVL), UA (no catheterization), CBC, blood cultures (all lumens Aggressive hydration with or without diuresis is fundamental sign of serious infection. It should be evaluated immediately. rst and only Sarcomas, NBL, germ cell tumors, lymphoma, leukemia, leptomeningeal spread Sarcomas, NBL, germ cell tumors, lymphoma, leukemia, leptomeningeal Local or radicular pain in 80%, lower extremity weakness or numbness, bowel or Local or radicular pain in 80%, lower extremity weakness or cations to empiric therapy: Consider adding antifungal coverage if fever persists >5 d. nition rasburicase (contraindicated in G6PD defi (AMS) are ominous signs; examine sites for infection (oropharynx, respiratory tract, (AMS) are ominous signs; examine of recent procedures, skin and soft tissues), abdomen perianal area, CVL sites, locations (eg, typhlitis). pressed patients), CXR (based on signs and symptoms), abdominal US, other cultures pressed patients), CXR (based CSF, CVL site, wound). based on clinical suspicion (stool, imipenem/cilastatin, or meropenem (often dependent on institutional practice and/or imipenem/cilastatin, or meropenem (often dependent on institutional previous infections/sensitivities). + antipseudomonal cern for sepsis: Triple therapy with vancomycin + amynoglycoside penicillin (ceftazidime, cefepime, or carbapenem) ( I & D skin lesions. occasions 1 h apart. (Note: The temperature should not be taken rectally for immuno- occasions 1 h apart. (Note: The compromised patients!) Hyperphosphatemia: Aluminum hydroxide, dialysis (severe case). Hyperphosphatemia: Aluminum hydroxide, dialysis (severe High risk (ANC <100, infant ALL, AML, induction therapy) and/or patient with con- High risk (ANC <100, infant ALL, AML, induction therapy) Intermediate risk: Allopurinol Low risk: Watch and wait Alkalinization is currently not recommended Hyperuricemia: Hydration 2–3L/m Hyperkalemia and hypocalcemia: See Chapter 15. High risk: Rasburicase (recombinant urate oxidase) Fever: Single temperature Neutropenia: ANC <500/mm Low risk and patient appears well: Monotherapy with ceftazidime, piperacillin/tazobactam,Low risk and patient appears well: Monotherapy with ceftazidime, Modifi Evaluation: History and physical exam: Optional studies: (drop metastases) from CNS tumors bladder incontinence chemotherapy (NHL, ALL, AML, especially acute monocytic leukemia) chemotherapy (NHL, ALL, AML, especially acute monocytic 12–72 h after bloodstream More common in tumors with high proliferative rate, large volume, or sensitive to More common in tumors with high proliferative rate, large Often the fi • • • • • • • • • • • • • • • Tumors: Prevention: Empiric therapy: Management Defi Diagnosis Pathophysiology: History: • • • Spinal Cord Compression Tumor Lysis Syndrome • • • • • Oncology EMERGENCIES ONCOLOGIC Fever and Neutropenia • • CHAPTER 23 290 Pediatrics

• Evaluation: Emergent MRI of the spine (CT myelography if MRI is unavailable) • Management • Rapidly progressing or exam with anatomic level of dysfunction: Dexamethasone 1–2 mg/kg IV once • Child with or possible dx of cancer: Dexamethasone 0.25–0.5 mg/kg PO Q6h • Deﬁ nitive therapy: Emergent spinal decompression (laminectomy), radiation, chemotherapy (see ﬁ gure below)

Acute onset paraplegia?

Yes No

1. Admit 1. Admit 2. Laminectomy 2. Dexamethasone 3. ±Dexamethasone (0.5–2mg/kg/day) (0.5–2mg/kg/day) 3. Biopsy

Laminectomy 1. Chemotherapy Positive 2. Radiation No effect? (Continue to desired outcome)

Yes

Figure 23-1 Algorithm for the management of spinal cord compression.

Anaphylaxis with Chemotherapy CLASSIFICATION AND TREATMENT OF HYPERSENSITIVITY REACTIONS TO INFUSIONS∗

Hypersensitivity Acute infusion reaction Grade (allergic reaction) (cytokine release syndrome)

1 Transient ﬂ ushing or rash; Mild drug fever <38°C (<100.4°F) Tx: Infusion interruption or intervention may not be indicated

2 Rash Moderate Flushing Tx: Requires infusion interruption and respond Urticaria promptly to symptomatic tx (eg, antihistamines, bronchodilator, NSAIDs); prophylactic Dyspnea medication indicated for ≥24 h Drug fever ≥38°C (≥100.4°F)

3 Symptomatic bronchospasm Severe (ie, prolonged or recurrent sx) ± urticaria Tx: Interrupt infusion; parenteral tx indicated Allergy-related edema or as per symptoms (eg, antihistamines, broncho- angioedema dilator, NSAIDs, epinephrine IM, steroids, IVF); Hypotension hospitalization is indicated for other clinical sequelae (eg, renal impairment, pulmonary inﬁ ltrates)

(continued on next page) Oncology 291

Hypersensitivity Acute infusion reaction Grade (allergic reaction) (cytokine release syndrome)

4 Anaphylaxis Life threatening Tx: ABCs; intubate if concerned about airway compromise; albuterol for wheezing; IM or IV epinephrine for acute respiratory distress; NS bolus as necessary for hypotension; H1 blocker (diphenhydramine), H2 blocker (ranitidine), corticosteroid (methylprednisolone) ± pressor or ventilator support as indicated

5 Death Death

∗Common agents are platinum drugs (eg, cisplatin, carboplatin), etoposide and L-asparaginase, but anaphylaxis can occur with any chemotherapy agent. Adapted from Common Toxicity Criteria for Adverse Events, Vol. 4; 2009. Available at http://ctep.cancer.gov

Hyperleukocytosis • Deﬁ nition: WBC >100,000 (risk of clinical complications increases with ↑ WBC) • Pathogenesis: ↑ Blood viscosity → leukostasis caused by ↑adherence → causes CNS hemorrhage or thrombosis, pulmonary leukostasis, tumor lysis → sx depend on location of leukostasis • Management: Hydration, monitor WBC, monitor and tx for tumor lysis; initiate deﬁ nitive tx for tumor; consider exchange transfusion or leukapheresis for the following groups: • Age < 2yr: WBC >100,000 cells/mm3 • Child with ALL: WBC >200,000 cells/mm3 with symptoms or >400,000 cells/mm3 without symptoms • Child with AML (M4/M5): WBC >150,000 cells/mm3 • Child with all other AML: WBC >200,000 cells/mm3 with symptoms or >300,000 cells/mm3 without symptoms

NAUSEA MANAGEMENT

• Etiology: Chemotherapy induced (anticipatory also common), radiation induced, PEDIATRICS disease induced (eg, brain tumors, CNS leukemia, constipation), drug induced (Cancer J 2008;14(2):85)

EMETOGENIC POTENTIAL OF CHEMOTHERAPY AGENTS

Level Agents

High Actinomycin-D, cisplatin (>40 mg/m2), cyclophosphamide (>1 g/m2), cytarabine (>1 g/m2), ifosfamide

Moderate Anthracyclines (daunorubicin, doxorubicin), carboplatin (<40 mg/m2), cyclophosphamide (<1 g/m2), methotrexate (IV >1 g/m2)

Mild Bleomycin, epipodophyllotoxins (etoposide), paclitaxel, topotecan, vinblastine

Low or non- Asparaginase, mercaptopurine (PO), methotrexate (low dose, PO, IT), emetogenic steroids, vincristine

Adapted from Principles and Practice of Pediatric Oncology, 5th ed. 2005. 292 Pediatrics

• Treatment: Antiemetic drugs and nonpharmacologic approach (see table below)

ANTIEMETIC AGENTS

Agent Effi cacy Routes Side eff ects

5-HT3 antagonists Marked PO, IV Headache, constipation with prolonged (ondansetron) administration

Aprepitant Marked PO Fatigue, weakness, nausea, constipation

Dexamethasone Moderate PO, IV Hyperglycemia

Dronabinol (tetrahy- Moderate PO Dry mouth drocannabinol)

Metoclopramide Marked PO, IV Extrapyramidal symtoms, sedation

Promethazine∗ Marked PO, IV Extrapyramidal symtoms, sedation

∗Not for use in children under 2 yr. Adapted from Principles and Practice of Pediatric Oncology, 5th ed. 2005.

MUCOSITIS • Etiology: r/o viral stomatitis; cytotoxic damage by chemotherapy or radiation of oral mucosa or GI tract; local immune activity and bacterial colonization may be associated. • Clinical presentation: Pain and ulceration, which lead to infection and ↓ oral intake.

GRADING THE SEVERITY OF MUCOSITIS

Grade Symptom

0 No symptom

1 Soreness and erythema

2 Erythema, ulcers; can eat solid food

3 Ulcers, tolerates liquid diet only

4 No possible alimentation

• Prevention and treatment (Cancer 2007; 109:820) • If untreated, mucositis may lead to signiﬁ cant malnutrition and overwhelming infection • Early detection by regular assessment of oral pain and hygiene • Use of soft toothbrush • Various mouthwashes have been used traditionally (without strong evidence) (eg, chlorhexidine, topical anesthetics [benadryl:maalox:lidocaine mixture ratio for swish and spit], carafate) • Aggressive pain management (eg, morphine PCA) • Consider nutrition support based on grade of mucositis and nourishment status (eg, TPN). • Consider antimicrobials when infection is suspected

SPECIFIC MALIGNANCIES Acute Lymphoblastic Leukemia (ALL) • Deﬁ nition: Uncontrolled proliferation of immature lymphocytes; by convention >25% lymphoblasts on BMA • Epidemiology: 30% of childhood cancers; ~2500–3500 cases/yr; peak incidence 2–5 yr of age; Risk is ↑ 14-fold in children with Down syndrome; minor risk ↑ in siblings with ALL and in children with immunodeﬁ ciencies Oncology 293

• Diagnosis • History and physical exam: ↓ Energy, fever (60%), bone pain (25%), night sweats, weight loss, pallor, petechiae or bruising (50%), HSM (66%), lymphadenopathy (50%; defi nition: epitrochlear or supraclavicular LN >5 mm, inguinal LN >15 mm, and >10 mm for all other LN; malignant LN are typically rubbery, fi rm, and nontender). May also have headache, nausea or vomiting, AMS, testicular enlargement (2%–5%). Older children may have wheezing, cough, or SVC syndrome caused by a mediastinal mass. • Labs/evaluation: • CBC (hyperleukocytosis; ~50% with a WBC >10,000 and ~20% >50,000); 95% present with ≥1 cell line down (~90% with a Hb <11 g/dL, ~45% <7 g/dL), ~75% with platelets <100,000/mm3 • Chem 10: May be normal or ↓ Ca2+, but with tumor lysis ↑ Ca2+, ↑ K+, ↑PO4– • PT, PTT, liver panel (↑ PT/PTT, ↑ transaminases), ↑ LDH, ↑ uric acid if tumor lysis • CXR: Evaluate for mediastinal mass • BMA (>25% lymphoblasts) and LP (~5% with CNS involvement) for defi nitive dx • Differential dx: JRA, osteomyelitis, ITP, pertussis, EBV, aplastic anemia, other malignancies (eg, neuroblastoma, EWS, RMS). • Classifi cation: Multiple systems exist for describing ALL variants: morphologic, immunologic, cytogenetic (see tables below). • Cytogenetic: Karyotype and FISH; results are taken into account with other factors and used to confer a designation of low, standard, high, or very high risk.

MORPHOLOGIC CLASSIFICATION OF ALL

Frequency of FAB Classifi cation Description ALL Cases (%)

L1 Premature B-cell morphology ~85

L2 Intermediate morphology, (ie, ↑cytoplasm ~14 and dispersed chromatin); similar prognosis to FAB L1

L3 Mature undiﬀ erentiated morphology <1 PEDIATRICS

IMMUNOLOGIC CLASSIFICATION OF ALL

B-Cell T-Cell

CD markers Pre–B cell, (most common) = 19, 20, ± CALLA 2, 3, 4, 5, 7, 8 Mature B cell (L3) = (10, 19, 20) + 22, 25, and surface Ig

Distribution 70%–80% of ALL cases 15%–17% of ALL cases

Prognosis Favorable prognosis associated with pre–B Poorer prognosis in some cell ALL studies

Features May rarely present with a primary mass; usually (>&, older age, higher presents with bone marrow disease incidence of mediastinal mass

CALLA: Common ALL antigen (CD 10) found on 70% of leukemic cells with a B-precursor phenotype.

• Treatment: Consists of four or ﬁ ve phases; total duration of therapy ~2 yr for girls and 3 yr for boys. The drug regimen and duration of therapy are based on risk designation as shown in tables below (Pediatr Clin North Am 2008;55:1). 294 Pediatrics

DESCRIPTION OF TREATMENT PHASES OF ALL

Treatment Phase Description

Induction Induce remission (ie, M1 marrow: <5% blasts and trilineage recovery of normal bone marrow elements); Ara-C and IT MTX regardless of known CNS disease; remission achieved in 95% by ﬁ rst 4-6 weeks

Consolidation Consolidate remission and prevent CNS involvement (ie, IT chemo); commonly uses multiple agents with diﬀ ering mechanisms of action; 1–2 mo

Interim maintenance Give child and bone marrow rest while still receiving chemotherapy (usually antimetabolite type); generally a less intense phase of ~2 mo

Delayed intensiﬁ ca- Similar to induction and consolidation periods; the goal is to ↓ tion (re-induction or overall leukemia burden to undetectable or to deﬁ ned level of reconsolidation) minimal residual disease (MRD); usually 2 mo

Maintenance Maintain the child in a disease-free state, (eg, oral 6-MP daily, MTX weekly, monthly infusions of VCR, steroids & periodic LP with IT MTX)

TREATMENT BY ALL RISK GROUP (Blood 2007;109:926)

Approximate Risk Recommended 4-yr Event-Free Group Features Cases (%) Therapy Survival (%) Low Hyperdiploidy∗ or 20 Conventional 92 trisomy 4, 10, 17 antimetabolite- based therapy t(12,21) 20

Standard WBC <50,000/mm3 Intensiﬁ ed antime- 82 15 tabolite therapy Age 1–9.9 yr No favorable cytogenetics High T-cell phenotype 15 Intensive multi- 73 agent therapy Age ≥10 yr or 15 WBC>50,000/mm3 6 Very high t(9;22) 3 Intensive multi- 46 agent therapy + tyrosine kinase inhibitor (eg, imatinib) t(4;11); age <1 yr 4 Consider alloge- neic HSCT after Hypodiploidy 2 ﬁ rst remission (≤44); induction failures and slow responders

∗Hyperdiploidy: Leukemic cells having 54 to 58 chromosomes per cell instead of 46. Oncology 295

• Prognosis • Event free survival: Overall 5-yr survival of 78%; as high as 90% with favorable features • Favorable features: WBC at presentation <50,000, age 1–9 yr, hyperdiploidy (versus extreme hyperdiploidy or hypoploidy), CALLA/CD10+, no organ involvement, no chromosomal translocations, speciﬁ c low-risk translocations (ie, t(12;21)), rapid response to initial chemotherapy, female, caucasian. • Sites of relapse: Bone marrow > CNS > testicles; however, multiple sites of relapse common; boys experience relapse more often than girls.

Hemophagocytic-Lymphohistiocytosis (HLH) • Defi nition: ↑ Proliferation of macrophages and T cells; macrophage engulfment of lymphoid or myeloid precursors (Leukemia 1996;10:197). Two types: sporadic (associated with malignancies, infections, and disease of immune system; Am J Pediatr Hematol Oncol 1988;10:196) or familial (eg, Griscelli syndrome, Chediak Higashi syndrome) • Epidemiology: Estimated incidence of 2-3 cases per 1,000,000 children; boys and girls are affected equally • Diagnosis • Diagnosis is diffi cult and usually made late in dz. Nonspecifi c symptoms, including fever (91%), hepatomegaly (90%), splenomegaly (84%), neurologic symptoms (47%), rash (43%), lymphadenopathy (42%), abdominal pain. May mimic child abuse (Pediatrics. 2003;111:e636). • Five of seven criteria need to be present: (1) fever (>38.5°C for ≥7 d); (2) splenomegaly; (3) cytopenias (meets criteria if two of three of the following are present: ANC <1,000/ mm3, thrombocytopenia < 100,000/mm3, Hb <9g/dL); (4) hypertriglyceridemia (fasting >2 mmol/L or >3 SD normal value for age) or fi brinogen (<1.5 g/L or >3 SD below normal for age); (5) hemophagocytosis in bone marrow, lymph node, or spleen (may need repeated biopsy to demonstrate, not always able to demonstrate); 6) low or absent NK cell activity; and 7) ↑ soluble IL2-receptor and ↑ ferritin (> 500 mcg/L). Typically, ferritin is > 4000 mcg/L (Semin Oncol 1991;18:29). • Treatment • Early hematology/oncology consultation • Current treatment protocols: Dexamethasone, etoposide, cyclosporine (Med Pediatr Oncol 2003;41:103), and IT MTX/VP-16 if there is CNS involvement (Br J Haematol 2005;129:622). • HSCT is the best chance for a defi nitive cure. Indicated for patients with poor response to chemotherapy, familial HLH with homozygous mutations, or in CNS dz. PEDIATRICS • Prognosis • Aggressive life threatening HLH may be seen at any age, although it is especially common in familial disease and children <18 mo (Leukemia 1996;10:197). • Current survival ranges from 50% to 70% depending on the disease severity and the presence of HLH matched donor for HSCT (Br J Haematol 2005;129:622).

Neuroblastoma • Deﬁ nition: Includes a variety of neuroblastic tumors derived from neural crest cells (eg, ganglioneuroblastomas, ganglioneuromas, and neuroblastomas [97% of neuroblastic tumors]). • Epidemiology: Third most common pediatric malignancy (after leukemia → brain), ~10% of all pediatric cancer; ~650 cases /yr in US. Age at dx: 40% <1 yo, 35% 1–2 yo, 25% ≥2 yo; incidence ↓ until age 10 yr (rare after that). • Diagnosis • Either one of the following criteria needs to be met: 1. Unequivocal histologic dx from tumor tissue by light microscopy ± immunohistochemistry, electron microscopy, or increased urine (or serum) catecholamines or their metabolites 2. Evidence of metastases to bone marrow on an aspirate or trephine biopsy with concomitant elevation of urinary or serum catecholamines or their metabolites • History and physical exam: Presenting symptoms are attributable to the local effects of tumor growth (adrenal, 40%; paraspinal ganglia, 25%; thoracic, 15%; pelvic, 5%; and 296 Pediatrics

cervical, 3%). Abdominal pain, vomiting, weight loss, anorexia, bone pain, limping, periorbital ecchymoses, abdominal mass, Horner’s syndrome, sx and signs of cord compression (paralysis, bowel or bladder dysfunction, weakness). Also, 2-4% of patients may have paraneoplastic syndromes (Pediatr Clin North Am. 2002;49:1369): • ↑ Vasoactive intestinal peptide→ “VIP syndrome” → diarrhea, fl ushing • Opsoclonus-myoclonus syndrome (“dancing eyes and dancing feet”): horizontal nystagmus and spasms of the lower extremities • Catecholamine effects: Flushing, HTN, headache, sweating, testicular pain, anxiety • Labs • CBC (60% have anemia), chem 10, ↑ ferritin, ↑ LDH, uric acid, liver panel, PT/PTT, serum and urine catecholamine metabolites (ie, vanillylmandelic acid (VMA) and homovanillic acid (HVA)) (in >90% of cases, VMA or HVA is >3 SD above age-specifi c norms) • If suspicion is high, then tissue biopsy (see below), skeletal survey, MIBG scan or bone scan, CT or MRI of the abdomen, CXR ± chest CT (if suspect extraabdominal metasta- sis), head CT if clinically indicated • Tissue biopsy (small, round, blue cells on histology; immunohistochemical staining; and test for MYCN amplifi cation, hyperdiploidy, CD44 expression, specifi c translocations for other cancers) and bilateral BMA • Treatment • Surgery: Improved prognosis. Patients with low-risk disease: (stage 1–2b) are treated with surgery alone (J Clin Oncol 1988;6:1271). • Chemotherapy: Cyclophosphamide, carboplatin or cisplatin, etoposide, and adriamycin. The goal is to reduce tumor size. Intermediate risk dz is tx with chemotherapy followed by resection if possible (NEJM 1999;341:1165). For patients with high risk disease high- dose chemotherapy with autologous transplant is indicated. • Radiation therapy: For tumors that are unresectable or unresponsive to chemotherapy. • Prognosis • Prognosis is worse compared with other pediatric malignancies (eg, ALL). NB accounts for ~15% of all pediatric cancer fatalities. Five-year EFS varies greatly according to risk group (low risk, 90%–95%; intermediate risk, 85%–90%; high risk, 30%) (Lancet 2007;369:2106). • Favorable features: Age <1 yr (survival as high as 83%); female gender; hyperdiploidy; ↓ ferritin; stages 1, 2, or 4S; no MYCN amplifi cation. • Unfavorable features: Age >2 yr, male gender, ↑ ferritin, advanced stage euploidy, MYCN amplifi cation. Malignant CNS Tumors

CHARACTERISTICS OF CENTRAL NERVOUS SYSTEM TUMORS IN CHILDREN YOUNGER THAN 20 YEARS OF AGE

International classifi cation of childhood cancer (ICCC) group Brainstem Astrocytoma Medulloblastoma Glioma Ependymoma

Site Cerebrum, Cerebellum Midbrain, Ventricles or cerebellum pons, spinal cord; medulla fourth ventricle most common in <3 yr

Incidence (%)∗ 52 21 15 9

Peak age (yr)∗ 5, 13 3 8, 17 2

M:F ratio∗ 1:1 2:1 1:1 1:1

(continued on next page) Oncology 297

International classifi cation of childhood cancer (ICCC) group Brainstem Astrocytoma Medulloblastoma Glioma Ependymoma

Workup Brain CT and Brain CT (hyperdense Brain CT and Brain CT (hyper- (fi ndings) MRI; glial mass), MRI of the MRI (grade I: dense mass with fi brillary acidic brain and spine with welldemar- homogenous protein (GFAP) contrast (heteroge- cated lesion enhancement, tumor marker neous contrast-en- ± calcifi ca- calcifi cation or hancing lesion with tion; grade cyst common), areas of necrosis or II: infi ltrating MRI of the hemorrhage, cysts); lesion) brain and spine LP after surgery with contrast (≥33% are positive) (hypointense T1, hyperintense T2 and prominent enhancing)

Histology and Glial cell origin; Embryologic origin; Biopsy to Ependymal genetics none small blue cell tumor, identify rosettes Homer-Wright ro- type except (diagnostic); settes (40%); look for for GBM; monosomy 22 in neuroepithelial cell incidence ↑ sporadic cases markers;↑ in those in those with with PTCH-1, APC NF-1 gene mutation, N- myc dysregulation

Patient Grade I or II: Stage M0: >3yr, Grade I: Grade I: stratifi cation Diff use <1.5 cm2 residual Focal Myxopapillary Grade III: Stage M1: <3yr, Grade II: Grade II: Anaplastic >1.5 cm2 residual Diff use Low grade, Grade IV: GBM Grade III: diff erentiated High-grade Grade III:

anaplastic anaplastic PEDIATRICS Grade IV: GBM

Treatment Surgery + Maximal surgical Grade I: Maximal surgery radiation+ resection + cranio- Observe if + radiation chemotherapy spinal irradiation + asymp- chemotherapy tomatic ± surgery Grade II–IV: Supportive care, including steroids to ↓ edema, radiation; no surgery or chemotherapy

Survival rate∗ 74% at 5 yr M0: >80% at 5 yr Grade I: 66%–75% at 5 yr M1: 55%–76% at 5 yr 100% at 5 yr if total resection Grade II–IV: <1-yr survival

∗http://seer.cancer.gov/publications/childhood/cns.pdf 298 Pediatrics

COMMONLY USED CHEMOTHERAPY AGENTS, TOXICITIES AND ANTITUMOR SPECTRUM

Drug Class Antitumor (Mechanism) Examples Toxicities Spectrum

Alkylating agents Cyclophosphamide Myelosuppression, Leukemia, lym- (cross-link DNA by nausea and vomiting, phoma, sarcoma, covalent bonding, alopecia, cystitis, water neuroblastoma preventing replication retention and transcription) Ifosfamide Myelosuppression, Sarcoma, GCT, nausea and vomiting, leukemia, alopecia, cystitis, lymphoma neurotoxicity

Cisplatin Myelosuppression, GCT, brain nausea and vomiting, tumors, osteosar- alopecia, ototoxicity, coma, neuroblas- neurotoxicity toma, HD

Busulfan Myelosuppression, Leukemia (BMT) nausea and vomiting, alopecia, pulmonary, neurotoxicity, hepatic

Antimetabolites Methotrexate Myelosuppression, mu- Leukemia, (structural analogs cositis, rash, hepatic, lymphoma, of vital cofactors or renal, neurotoxicity osteosarcoma intermediates in DNA or RNA synthesis) Mercaptopurine Myelosuppression, Leukemia hepatic, mucositis

Thioguanine Myelosuppression, Leukemia nausea and vomiting, mucositis, hepatic veno-occlusive disease

Cytarabine Myelosuppression, Leukemia, nausea and vomiting, lymphoma, LCH mucositis, neurotoxicity, ocular, skin

Antitumor antibiotics Doxorubicin Myelosuppression, Leukemia, (DNA intercalation nausea and vomiting, lymphoma, most leading to inhibition alopecia, mucositis, solid tumors of topoisomerases, diarrhea, cardiac strand breaks, and free radical Dactinomycin Myelosuppression, Wilms, sarcoma formation) nausea and vomiting, alopecia, mucositis, vesicant, hepatic veno- occlusive disease

Bleomycin Nausea and vomiting, Lymphoma, alopecia, lung, skin, testicular and fever, mucositis, vesicant, GCT Raynaud’s disease

(continued on next page) Oncology 299

Drug Class Antitumor (Mechanism) Examples Toxicities Spectrum

Plant products Vincristine (vinca Neurotoxicity, alopecia, Leukemia, Vinca alkaloids alkaloid) SIADH, hypotension, lymphoma, most (inhibits mitosis by vesicant solid tumors binding to tubulin) Vinblastine (vinca Myelosuppression, Histocytosis, alkaloid) alopecia, mucositis, Hodgkin’s dis- mild neurotoxicity, ease, testicular vesicant

Epidopophyllotoxins Etoposide (epi- Myelosuppression, Leukemia, (inhibit podophyllotoxin) nausea and vomiting, lymphoma, topoisomerase II) alopecia, mild neuro- neuroblastoma, toxicity, hypotension, sarcoma, brain allergic reaction, tumors, HLH secondary leukemia

Miscellaneous prednisone, dexam- Increased appetite, Leukemia, Corticosteroids ethasone obesity, striae, diabetes, lymphoma, LCH (receptor-mediated immunosuppression, lympholysis) AVN of hip, HTN

Asparaginase Asparaginase (eg, Allergic reaction, coagu- Leukemia, (asparagine I-Asp, PEG-Asp) lopathy, pancreatitis, lymphoma depletion) hepatic, neurotoxicity

Adapted from Principles and Practice of Pediatric Oncology, 5th ed. 2005:300–303.

BONE MARROW TRANSPLANTATION • Overview of HSCT process: Identify appropriate candidate → donor selection → stem cell collection → conditioning regimen (myeloablation vs reduced intensity) → stem cell transplant (SCT) → supportive treatment

ELIGIBLE CONDITIONS FOR BONE MARROW TRANSPLANT PEDIATRICS

Malignant Conditions Nonmalignant Conditions

Leukemia (high risk or relapsed) Bone marrow failure (eg, aplastic anemia) Lymphoma Premalignant disorders (eg, MDS) Solid tumors (eg, neuroblastoma) Inborn errors of metabolism (eg, MPS I) Brain tumors (eg, Immunodeﬁ ciency (eg, SCID, Wiskott-Aldrich syndrome) medulloblastoma) Hemoglobinopathies (eg, sickle cell disease)

REIMMUNIZATION SCHEDULE AFTER BONE MARROW TRANSPLANT*

Months After BMT Titers or Vaccines

12 Draw baseline tetanus titer and give DTaP #1 (Td if >7 yr of age)

13 Repeat tetanus titer to evaluate antibody response; if response is adequate, continue reimmunization; if not, repeat DTaP in 3 mo and follow repeat titer for response

14 DaPT #2, IPV #1, pneumococcal (PCV7) #1, HBV #1

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Months After BMT Titers or Vaccines

15 Meningococcal, HIB #1, HAV #1, HBV #2

16 DaPT #3, IPV #2, pneumococcal (PCV7) #2

18 Pneumococcal (PCV7) #3, HIB #2

20 Pneumococcal (PCV7) #4, HBV 3

22 Pneumococcal (23PS) #1, IPV #3, HAV #2

24 MMR, Hib #3

25 MMR #2 Pneumococcal (23PS) #2 (3–5 yr after #1) Inﬂ uenza vaccine yearly starting ~9 mo after SCT

Adapted from http://www.cdc.gov/vaccines/Pubs/downloads/b_hsct-recs.pdf. ∗For this schedule, HSCT recipients are presumed immunocompetent at ≥24 months after HSCT if they are not on immunosuppressive therapy and do not have GVHD

LATE EFFECTS OF CANCER TREATMENTS

Treatment Important Factors Common Complications

Chemotherapy Drug type and doses Endocrine dysfunction (eg, GH, thyroid deﬁ ciency) Gonadal dysfunction Cardiopulmonary toxicities Obesity Neurocognitive delay Psychiatric disorders

Radiation Total dose and Neurocognitive delay with craniospinal XRT or TBI involved ﬁ eld of (especially if age <6 yr) radiation Poor skeletal growth and organ damage over involved ﬁ eld

Surgery Anatomic area Amputations or extensive surgeries (especially in involved solid tumors)

HSCT Type of conditioning Chronic GVHD regimen and initial Secondary malignancies (eg, EBV-PTLD, solid disease burden tumors, leukemia) Conditioning related (see chemotherapy and radiation eﬀ ects)

Available at www.AccessPediatrics.com • Differential Diagnosis of Malignancies Based on Site and Age • Acute myeloid leukemia • Wilms tumor • Bone marrow transplantation PEDIATRICS infection, sepsis); “return to play criteria.”

Provide Mycoplasma → 301 : Add oblique view of foot, ankle, and elbow (foot (see treatment section) includes the necessary compo- (see treatment section) includes entire bone Anterior movement of one vertebrae in relation to adjacent vertebrae Anterior movement of one vertebrae in relation to adjacent tear of a ligament that connects two or more bones (localized tear of a ligament that connects PRICEMMMS

Minimize swelling and pain, minimize loss of strength and ROM, and Minimize swelling and pain, minimize loss of strength and ROM, under tension at site of tendon ammation of growth plate (epiphysis Stress injury or fracture of pars interarticularis inspection, neurovascular, palpation, range of motion, provocative tests (a inspection, neurovascular, palpation, range of motion, provocative Infl and injury to a muscle or tendon ammation Fever; sweating; age <5 yo; local tenderness/warmth/redness; no history of Fever; sweating; age <5 yo; local tenderness/warmth/redness; Pain greater than 3 mo A force or alignment that results in the joint opening medially A force or alignment that results Stretch or Infl A force or alignment that results in the joint opening laterally (opposite of valgus) A force or alignment that results Pain less than 3 mo ags: evaluated in the ED receive proper discharge –19% of musculoskeletal injuries nitions injuries require weight-bearing views—so that a Lisfranc injury is not missed). injuries require weight-bearing views—so that a Lisfranc injury nents for proper care of acute musculoskeletal pain and swelling. nents for proper care of acute Fructure (if in doubt, splint and order follow-up radiographs in 5–10 d). Fructure (if in doubt, splint and order follow-up radiographs Normal X-ray does not rule out Fructure: Consider other views if exam strongly suggests Normal X-ray does not rule out Fructure: Consider other views The mnemonic Two views minimum of elative Rest: Do not do anything that hurts. Take out of sports or offending activity untilelative Rest: Do not do anything that hurts. Take out of sports rotection: Non–weight-bearing (crutches, cast/splint, knee brace, ankle stirrup, sling), rotection: Non–weight-bearing (crutches, cast/splint, knee ce: Controls pain and decreases swelling. Apply ice daily until pain and swelling ce: Controls pain and decreases swelling. Apply ice daily until tenderness, swelling, ± joint instability over injured ligament) tenderness, swelling, ± joint instability elevated WBC, ESR, or CRP (evaluate for septic arthritis or osteomyelitis). injury; night pain; weight loss; migratory joint pain (SLE, rheumatic fever, HSP, subacute injury; night pain; weight loss; migratory joint pain (SLE, rheumatic endocarditis, Lyme disease, gonococcal arthritis, viral or insertion) ), functionvideo demonstration of each exam is available at http://www.sportsmedkids.com prevent injury instructions for optimal management and rehabilitation. instructions for optimal management shoulder, back injuries, and chronic back pathology injuries, their diagnoses and shoulder, back injuries, and chronic management. as appropriate. If unable to walk without limp Wean crutches when able to crutches. perform normal heel–toe gait. normal strength, stability, mobility, and function return. resolve. Recommendations: Use a bag of crushed ice or frozen peas directly on the resolve. Recommendations: Use a bag of crushed ice or frozen and never sleep with ice. skin for 20 min every hour, avoid refreezing cold gel packs, Goal of section: The reader will understand common causes of acute ankle, knee, Goal of section: The reader will 1% • • • Strain: Acute: Radiographic studies Spondylolysis: Red fl Spondylolisthesis: P I Treatment goals: History Sprain: Chronic: Apophysitis: Valgus: Varus: R Physical exam: • Treatment of Acute Injury: PRICEMMMS • • • • • • • • • • • • • • Evaluation • Defi • • Orthopedics and Sports Medicine and Sports Orthopedics STRAINS SPRAINS AND Introduction • CHAPTER 24 302 Pediatrics

(Contraindications: Raynaud’s disease, impaired sensation, peripheral vascular disease, and cold hypersensitivity) • Compression: ↓swelling. Use ACE compression wrap or hose. • Elevation: ↓ swelling. Elevate injury above the level of the heart. • Medications: Prescribe acetaminophen, NSAIDS, or narcotics, as appropriate. • Modalities: ↓ pain and spasm. PT or athletic trainer (with US, electrical stimulation, iontophorisis, massage, and stretches) to facilitate the home exercise program. • Motion: Start with early ambulation and ROM exercises with a graded return to activity. → Facilitates an earlier return to play. • Strengthening: Exercise and proprioception training prevents reinjury. Identify weakness. → Prescribe PT or home exercise program to address deﬁ cits.

FRACTURES AND SPLINTING Defi nitions • Bone anatomy: Diaphysis (shaft), metaphysis, physis (growth plate), epiphysis • Fructure lines: Transverse, oblique, spiral • Intra-articular Fructure: Extends into the joint space • Comminuted Fructure: Broken into multiple fragments • Segmental Fructure: Comminuted Fructure with well-defi ned large fragments • Buckle (torus) Fructure: Incomplete Fructure with a small fold in the cortex • Greenstick Fructure: Incomplete, angulated Fructure of a long bone • Avulsion Fructure: Tendon or ligament pulls off a piece of bone from the tendon insertion site • Impaction Fructure: Direct force down the length of bone results in telescoping • Apophysitis: Infl ammation ± separation of 2° growth center such as a tuberosity or tubercle

Type I Type II Type III Type IV Figure 24-1 Salter-Harris Fructure classiﬁ cation involving the physeal growth plate.

• Salter-Harris Type I—Separation of the epiphysis from metaphysis • Salter-Harris Type II—Fructure line extends through the physis and metaphysis • Salter-Harris Type III—Fructure line extends through the physis and epiphysis to the articular surface • Salter-Harris Type IV—Fructure line extends from the articular surface through the epiphysis, physis, and metaphysis • Salter-Harris Type V—Compression or crush injury of epiphyseal plate Evaluation • Inspect for swelling, ecchymoses, deformity, and pallor. • Document pulses and determine sensation. • Determine need for immediate orthopedic referral (see below). • Radiographic studies: • Two views minimum of entire bone → Add oblique view of foot, ankle, (foot injuries require weight-bearing views so that a Lisfranc injury is not missed) and elbow • Normal X-ray does not rule out Fructure → Consider other views if exam strongly suggests Fructure (if in doubt, splint and order follow-up radiographs in 5–10 d). Note: talus, scaphoid, and stress Fructure → initial X-rays are usually negative. Orthopedics and Sports Medicine 303

Management Principles • Complications and indications for immediate orthopedic consultation: • Life-threatening conditions: Hemorrhage, fat embolism, major trauma. • Open Fructure: High risk of infection (ie, osteomyelitis) → Start IV antibiotics. • Arterial injury: Increased risk with displaced or supracondylar Fructure and dislocations of elbow and knee. Document vascular exam → If distal pulses are absent and orthopedic assistance is not readily available, an attempt at reduction should be made promptly. • Nerve injury: Increased risk with shoulder, hip, and knee dislocations. Document neurologic exam (ie, distal sensation). • Compartment syndrome: Remember the fi ve P’s—pain, pallor, paresthesia, paralysis, and pulseless (late fi nding). • Tenting of the skin: Prompt reduction is usually necessary to prevent ischemic injury and skin breakdown. • Three fractures that always require prompt orthopedic consult: (1) supracondylar Fruc- ture, type II or higher, (2) pelvis Fructure, (3) femur Fructure. • Immobilization: To avoid iatrogenic compartment syndrome and pressure ulcers, splinting is the preferred form of immobilization. Casting is usually reserved for clinic follow-up. However, acute casting may be appropriate for unstable Fructure (ie, dislocated Fructure ± reduction, involving two adjacent bones, segmental Fructure, spiral Fructure). • Pain control: Analgesics are usually needed for the fi rst 2–5 d. If considerable pain is present despite treatment, consider compartment syndrome, vascular injury, or infection. High-pressure areas due to casting can lead to skin breakdown → ulcers. • Control swelling: (1) elevation above level of heart, (2) cryotherapy applied for 20 min every 2 h until both pain and swelling resolve. UPPER-EXTREMITY ACUTE FRACTURE MANAGEMENT

Considerations and management Clavicular fracture • Distal or middle 1/3rd clavicular fracture: • Most require sling for 4-6 wk; pain control; ROM exercises to start within 3-5 days and no contact sports for 3 mo • Consider surgery for: 1. >1 bone width displacement, 2. comminuted fracture, 3. shorten- PEDIATRICS ing (>18 mm for boys; >14 mm for girls), 4. open fracture, 5. neurovascular compromise, 6. respiratory compromise, 7. skin tenting, 8. type 2 distal clavicle fracture • Proximal 1/3rd fracture: • Most occur due to high energy impact ie, MVA • Must exclude mediastinal injury (mimics sternoclavicular dislocation) • Consider orthopedic consult for all these types of fracture especially if 1. due to high energy impact, 2. signiﬁ cant displacement >1 cm, 3. posterior diplacement, 4. posterior sternoclavicular dislocation Scapular fracture

SHOULDER • Majority are secondary to high energy impact ie, MVA 75% associated with other serious injuries (ie, head, neck, or chest injury) • Orthopedic consult and sling Shoulder dislocation • Anterior → reduction • Suspect Hill-Sachs and Bankart fracture in acute anterior • Posterior → Orthopedic shoulder dislocation → shoulder X-ray series with AP, consult prior to reduction lateral axillary, and Y views Traction apophysitis of proximal humerus (“little league • Rest and ice daily shoulder”) • Sling if needed • X-ray may show normal or wide physis • No throwing 4–6 wk and no pitching 3–6 mo

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Considerations and management

Proximal fracture Splinting: • Complete displacement, ≤3 cm overriding and <60° • Swathe and sling immo- angulation → splint bilization or coaptation • Open fracture, skin tenting, neurovascular injury, or unac- with double sugar tong ceptable displacement → ortho consult, ORIF Casting: • Note: Proximal humeral ossiﬁ cation not until age 6 mo, • Long arm hanging cast greater tuberosity at 1–3 yr, lesser tuberosity at 4–5 yr → fracture may be missed on X-ray

Shaft fracture • At risk for radial nerve injury → Most children recover function (80% of growth occurs at proximal humerus and will remodel) • <3 yo and <45° (acceptable angulation) → splint • Completely displaced fracture, unstable oblique/spiral fracture, fracture angulated >20° in children and 10° in adolescents, or radial nerve injury → ortho consult

Supracondylar fracture Splinting: • At risk for radial or medial nerve and brachial artery • Posterior elbow splint at injury. 30° until X-ray • Three types: • For type I only → long • Type I—Nondisplaced with preserved Baumann angle arm splint with elbow (<4 ° of varus is accepted) → splint + orthopedic clinic ﬂ exed 90° and forearm f/u in 1 wk neutral

ELBOW • Type II—Displaced with intact posterior cortex → ortho Casting: Long arm consult for closed reduction and pinning • Type III—Displaced with no contact with cortex → ortho consult for ORIF and pinning

Transphyseal fracture → Ortho consult for closed reduction and pinning

Lateral condylar fracture Splinting: • Nondisplaced → splint, no surgery • Posterior elbow splint at • Displaced >2–4 mm → ortho consult for reduction and 90° and forearm in neutral pinning • Ortho consult for any fracture that extends to articular surface, capitellum, or trochlea

Medial epicondylar fracture • Potential ulnar nerve injury • Displaced <5 mm → splint • Displaced >5 mm → ortho consult for ORIF

Medial epicondyle traction apophysitis (“little league • Rest and ice daily elbow”) • Sling if needed • Often due to repetitive throwing and valgus stress • No pitching for 3–6 mo • X-ray may show normal or wide physis

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Considerations and management

Radial head subluxation (“nursemaid’s elbow”) • Usually occurs ages 6 mo to 5 yr when an adult pulls arm • Reduce by hyperpronation of wrist and forearm followed by simultaneous forearm supination and elbow ﬂ exion

Radial head fracture Splinting: • Ossiﬁ cation at 5 yr • Sling or posterior splint • <30° angulation, nondisplaced → splint/sling with elbow 90° and forearm neutral • >30° → closed reduction/splint • >45° → closed reduction and pinning • If still >40° s/p closed reduction, translation >3 mm, or completely displaced → ORIF

Radial neck fracture Splinting: • 50% of radial neck fracture have other associated fracture/ • Posterior splint with injury elbow 90° and forearm • Most Salter-Harris type I and II injuries neutral • Age <10 yo: <30° of residual angulation → splint (if able to supinate and pronate >70°, then up to 45° acceptable) • Age >11 yo: <30° of angulation and <3 mm of transloca- tion acceptable → splint • If not within above guidelines → closed reduction or ORIF

Proximal and mid-radius fracture Splinting (in general): • Greenstick, buckle, or Galeazzi fracture → splint • Proximal radius → long arm cast or sugar tong with forearm supinated RADIUS Distal radius fracture • Middle radius → long • Physeal (if nondisplaced) → splint arm cast or sugar tong → • Physeal (if displaced) ortho consult and closed reduc- with forearm neutral

tion and pinning PEDIATRICS • Distal radius → sugar • Note: If Salter-Harris type III/IV, open fracture, nonreduc- tong with forearm → ible, neurovascular injury ORIF pronated → short arm • Metaphyseal (nondisplaced buckle fracture) → splint cast after elbow immobi- • If displaced, refer to acceptable fracture angulations and lized for 2 wk reduction goals below: • Age 4–8 yr: Sagittal angulation 20° male, 15° female, frontal 15° (both) • Age 9–10 yr: Sagittal angulation 15° male, 10° female, frontal 5° (both) • Age 11–13 yr: Sagittal angulation 10° male, 10° female, frontal 0° (both) • Age >13 yr: Sagittal angulation 5° male, 0° female, frontal 0° (both) • Note: If failed reduction → ORIF (reverse sugar tong splint shown) • Galeazzi fracture—Radial shaft (mid- and distal) fracture with distal radioulnar disruption • Type I - Dorsal displacement of distal radius • Type II - Volar displacement of distal radius • Tx - Closed reduction and elbow cast (noted above) in full supination

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Considerations and management

Olecranon fracture Splinting: • Nondisplaced → splint • Posterior splint with • Displaced >3 mm + extra-articular → closed reduction elbow ﬂ exed at 75°–80° with immobilization/splint (leave partially extended) • Displaced >3 mm + intra-articular and/or comminuted F/U: → ORIF • PCP or ortho consult

Both radius and ulna fracture Splinting (long arm cast • Nondisplaced → splint + orthopedic clinic f/u or splint): • Plastic deformation (bowing fracture): If >20° angulation or • Proximal one-third → unable to fully rotate → reduction under general anesthe- forearm pronated sia → ortho consult • Middle one-third → • Greenstick fracture + rotation and angular deformity pres- forearm neutral ent → closed reduction by reversing deforming forces → • Distal one-third → sugar tong splint or bivalved long arm cast → ortho consult forearm supinated • Complete shaft fracture → closed reduction→ ortho consult if parameters are greater than age appropriate limits (below) • Age <9 yr: <15° of proximal/mid-shaft angulation and ULNA 30°–45° malrotation acceptable • Age ≥9 yr: <10° proximal/mid-shaft angulation acceptable, ages 9-14yr <20°–30° malrotation acceptable

Monteggia fracture → Ortho consult • Fractured ulnar diaphysis with dislocation of radial head. Splinting s/p reduction: Types I– IV radiographically defi ned. Can only r/o with • Place in long arm splint three-view (AP, oblique, lateral) X-ray with elbow fl exed up to • Axis of radius should point toward center of capitellum 110°–120° and forearm in on all X-ray views. If disrupted, then consider radial neck midsupination or neutral fracture, elbow dislocation, or lateral condyle fracture • Note: Radial head disloca- • Management primarily determined by ulnar fracture type: tion may be easily missed • If ulnar plastic deformation or incomplete ulnar fracture (even with radiology); (greenstick/buckle) → closed reduction with up to 10° always review your own angulation acceptable followed by radial head reduction fi lms • If complete transverse, oblique or comminuted fracture of ulna or unable to reduce radial head → ORIF

HAND FRACTURE MANAGEMENT

Considerations Management Scaphoid fracture Splinting: • “Snuﬀ box” tenderness. • Short arm thumb spica → cast for 4–8 wk or 6–12 wk

WRIST • Nondisplaced Splint for 6–12 wk. if scaphoid fracture • Displacement ≥1 mm is diagnostic of instability → ORIF. • Partial gamekeeper’s will Thumb MCP fracture then require hand-based • Non–intra-articular or complex head/shaft fracture → thumb spica for an closed reduction and splinting. additional 4 wk • Base fracture (metaphyseal ± Salter-Harris type II with fracture on medial side, lateral angulation) → reduction

THUMB and cast. • Base fracture (metaphyseal ± Salter-Harris type II with fracture on lateral side, medial angulation or Salter-Harris type III [Bennett’s fracture] or Salter-Harris type IV) → ORIF.

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Considerations Management

Gamekeepers thumb (± fracture) • Involves injury to ulnar collateral ligament of thumb MCP joint → instability of joint → cast • If presence of palpable torn ligament ends (Stener lesion) lodged between adductor pollicis aponeu- THUMB rosis and its normal position → ortho consult for surgery. Best results if repair occurs within 7–14 d of injury

Epiphyseal/Physeal fracture → pinning or ORIF Splinting: • 2nd and 3rd MCP fracture → Neck fracture closed reduction/splint → teardrop splint → • 2nd and 3rd MCP <10° angulation tolerated • 4th and 5th MCP fracture • 4th and 5th MCP → 45°–60° angulation tolerated → boxer splint • Note: When positioning, MCP must be in maximum • In both, the wrist should ﬂ exion and all IP joints fully extended to prevent be extended 10°–15° with ﬂ exion contraction. thumb aligned to forearm

→

METACARPAL Shaft fracture closed reduction/splint • Note: When positioning, MCP ﬂ exed 70° and IP joints extended (“beer can” position).

Base fracture • Usually high energy with tissue disruption → ORIF ± pinning.

Proximal and middle phalanx fracture Splinting: • Most common fractures of the proximal phalangeal • Mallet ﬁ nger → apply base volar or dorsal splint to • Acceptable shaft fracture <30° angulation for <10 yr; keep ﬁ nger extended <10°–15° angulation for >10 yr • Unacceptable reduction • Phalangeal neck fracture—Often unstable and of mallet or open fracture

→ PEDIATRICS displaced due to persistent attached collaterals to the surgery distal fragment → ORIF • Jersey ﬁ nger and reverse → • lntra-articular (displaced or >= 30 % of articular mallet surgery surface) fracture → ORIF ± pinning • Open, spiral, oblique, unacceptable angulation, or →

PHALANX irreducible ORIF

Distal phalanx fracture • Extraphyseal fracture → splint • Proximal or comminuted → Evacuate hematoma that is >50% of nail plate and nail bed repair • Physeal fracture may cause mallet deformity with DIP in fl exed position. Avulsion of fl exor digitorum pro- fundus at the DIP may cause “Jersey fi nger” or reverse mallet with inability to fl ex fi nger at DIP 308 Pediatrics

LOWER-EXTREMITY FRACTURE MANAGEMENT

Considerations Management

Avulsion fracture—At apophysis, describe sudden “pop” • Rest and no weight- → • Ischial tuberosity—Hamstring, forceful jumping bearing for 1 wk gradual weight- • Anterior superior iliac spine—Sartorius, forceful kicking bearing with crutches or sprint → limited activity for • Anterior inferior iliac spine—Rectus femoris, forceful 1–2 mo kicking • Holster ACE wrap • Lesser trochanter—Psoas, forceful sprint, jump, kick • Daily ice until pain • Iliac crest—Abdomen/obliques, repetitive contraction and swelling resolved • Pubic symphysis—Leg adductors, swim, kick, jump HIP • If displaced >2 cm or painful >6 mo → Consider surgical repair

Pelvic fracture → Ortho consult • Suspect if tender, swelling, high-energy trauma, GCS <15, or distracting injury • Type I avulsion fracture → manage as above • All other fracture (including femoral head and neck) → ortho consult for reduction, ORIF, or spica casting

Femur shaft fracture → Ortho consult • Middle third of shaft most common site • One-half of femur • Suspect tumor from femoral shaft fracture occurring from fracture in infants low-energy trauma and young children related to non- • Ortho consult required for all fracture accidental trauma • Management may consist of reduction, traction, Pavlik harness, spica casting, or ORIF → FEMUR Distal femur fracture Ortho consult • Salter-Harris classiﬁ cation Splinting: • Nondisplaced fracture → splint • Long leg cast with • Displaced type II or metaphysis fracture → closed reduc- knee ﬂ exed at 15°, tion under general anesthesia molded against opposite side of impact • All others including irreducible type II and displaced types III, IV, and V fracture → ORIF

Patellar fracture Splinting: • Nondisplaced → splint • Long leg splint with • >4 mm displaced or >3 mm stepoﬀ → ORIF knee fully extended (see ﬁ gure below) Sleeve fracture • Avulsion of distal pole of patella • Not obvious on X-ray → MRI to evaluation → ORIF

Sinding-Larsen-Johansson • Single or double Cho- KNEE • Apophysitis at inferior pole of patella Pat knee straps • Rest and ice daily Osgood-Schlatter • PT for hamstring • Apophysitis of tibial tubercle and eccentric quad • Seen in early adolescents strengthening • Acute onset of pain should be distinguished from fracture → activity as pain allows

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Considerations Management

Tibial tuberosity fracture → Ortho consult • X-ray with knee extended Splinting: • Type I: avulsion of tuberosity without involvement of • Long leg splint, knee physis, minimal displacement immobilizer, or cast • Type II: avulsion with displacement, no intra-articular with knee mostly extension extended for 6 wk • Type III: avulsion with displacement and intra-articular extension ± meniscal disruption • <5 mm of displacement → Treat in cylinder cast w/knee extended for 6 wk • >5 mm of displacement or type II/III → ORIF

KNEE Tibial spine fracture (mimics ACL tear) • Minimally displaced at distal junction of proximal tibia and tuberosity → splint • All other fracture → surgery

Osteochondritis dissecans of femur • Non–weight-bearing • Classically at medial femoral condyle, AVN of a piece of crutches osteochondral bone, which can then separate • ± Casting • Progressive pain, locking, and intermittent swelling → • Serial F/U X-ray to non–weight-bearing and immobilize in knee brace/cast ensure OCD place- • If fragment loose, or pain lasts >6 mo → surgery ment

Proximal tibial physis fracture Splinting: • Risk of compartment syndrome and popliteal artery injury • Long leg splint/ • Nondisplaced → splint cast with knee fully extended • Displaced (requires reduction) → ORIF

Proximal shaft fracture Splinting:

• Risk of compartment syndrome and anterior tibial artery injury • Long leg splint/cast PEDIATRICS • Nondisplaced → splint with knee mostly extended + varus • Displaced → ORIF molding

Diaphysis fracture Splinting: • Nondisplaced → splint • Long leg splint/cast • Displaced → attempt closed reduction with knee ﬂ exed at 45° • If failed reduction, unstable, or shortening → ORIF

Toddler fracture • Distal tibia fracture in child age <5 yr, history of minimal trauma

TIBIA AND FIBULA • X-ray series needs to include oblique views to see nondisplaced spiral fracture

Distal fracture → Ortho consult • Minor Salter-Harris types I and II or avulsion fracture → Splinting: closed reduction and splinting • Long leg splint or cast • All other fracture (ie, intra-articular and joint instability) are with knee ﬂ exed no high risk → ORIF more than 5° • Ankle neutral 310 Pediatrics

ANKLE AND FOOT FRACTURE MANAGEMENT

Considerations Management

Ankle sprain Splinting: • Classically graded I (mild), II (moderate), III (severe) • Ankle stirrup splint or air cast • To determine if needs X-ray: (1) unable to bear weight • Non–weight-bearing immediately, (2) unable to walk four steps in emergency initially for grade II/III room, (3) lateral or medial malleolus tenderness, (4) high ankle sprain, (5) navicular tenderness, (6) base 5th metatarsal tenderness • High ankle sprain—if ⊕ syndesmosis squeeze, which indicates tear and potential unstable ankle joint, may see mortise widening on X-ray → ankle stirrup with compressive wrap for 4–6 wk

ANKLE Talus fracture Splinting: • Neck fracture most commonly seen • Non–weight-bearing • If nondisplaced → splint • Long leg splint/cast with • If displaced >3 mm or varus rotation >5° → ORIF knee ﬂ exed • Ankle at 90° Calcaneous fracture • Most immobilize with splint • If severely displaced or intra-articular → ORIF

Sever’s disease (calcaneal apophysitis) • Tuli’s heel cups 4–6 wk • ⊕ heel squeeze on exam and pain at Achilles insertion • Ice daily • Resolves as growth plate closes → symptomatic treatment • Calf stretch

Kohler’s disease • Rest and ice daily • Self-limiting AVN of the navicular bone from repetitive • Persistent pain treated stress with non–weight-bearing • Ages 5–7 yr and short leg cast • Symptomatic treatment

Metatarsal fracture • Most shaft/neck Fracture → short leg walking cast • Base of 5th metatarsal: (1) avulsion fracture of tuberosity → walking boot; (2) “Jones” fracture of proximal metaphyseal–diaphyseal → ORIF if displaced (poor healing) FOOT

Lisfranc fracture Splinting: • Fracture at base of 2nd MT with ligament injury • Non–weight-bearing • Frequently missed in ER and on X-ray, especially without • Short leg cast for 6 wk fracture • Consider casting even • Poor prognosis if no treatment when no fracture seen • Late midfoot collapse a common sequelae • Obtain three-view with oblique X-ray series (weight- bearing) • If >2 mm displacement or MT dislocated → ORIF

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Considerations Management

Freiberg’s infarction Splinting: • Self-limiting AVN of 2nd MT head → MT pad • Short leg cast • Typically females age >13 yr • Persistent pain → surgery

FOOT Proximal and distal phalanx fracture Splinting: • Attempt reduction using digital block for anesthesia • Buddy tape to adjacent toe • Walking boot if necessary

Prognosis • Children’s fractures remodel and heal quickly. The younger the patient and the closer the fracture is located to a growth center, the greater the amount of angulation is tolerated. • Children tolerate casting better than adults and develop less stiffness. Often, they are most likely to regain normal ROM and strength, requiring very little to no physical therapy. • Complex regional pain syndrome (late complication) often follows an acute injury and is characterized by hypersensitivity (allodynia), altered blood ﬂ ow (mottled skin appearance), temperature changes (typically cooler), and swelling.

Available at www.AccessPediatrics.com • Ankle Examination • Knee Examination • Shoulder Examination • Elbow Examination PEDIATRICS CHAPTER 25 Pulmonology

WHEEZING AND ASTHMA Wheezing • Defi nition: Continuous high-pitched sound with musical quality emitting from the chest during expiration. • Differential diagnosis: Modifi ed asthma predictive index (API; J Allergy Clin Immunol 2004;114(6):1282): Identifi es children with wheezing who are at risk for persistent asthma; requires h/o four or more episodes of childhood wheezing and one major and two minor criteria

DIFFERENTIAL DIAGNOSIS FOR A CHILD WITH WHEEZING

Age <5 Years Age >5 Years

• Asthma • Asthma • Infection (viral upper or lower respiratory infections, bronchiolitis, • Vocal cord dysfunction tuberculosis, pertussis) • GERD • Bronchopulmonary dysplasia • CF • Sinusitis • Foreign body aspiration • Anatomic abnormality (vascular ring, mediastinal mass) • Tracheobronchomalacia • Aspiration due to swallow dysfunction or GERD • Cardiac disease with congestive heart failure • Immunodeﬁ ciency, immotile cilia • CF

MODIFIED ASTHMA PREDICTIVE INDEX

Major Criteria Minor Criteria

Parental history of asthma Allergic sensitization to eggs, milk, or peanuts Physician-diagnosed atopic dermatitis Wheezing apart from viral illness Allergic sensitization to at least one Blood eosinophilia >4% aeroallergen

Asthma • Defi nition: Chronic infl ammatory disorder of the airways associated with airway hyperresponsiveness that leads to recurrent episodes of combinations of wheezing, breathlessness, chest tightness, or coughing. Usually associated with diffuse but variable airfl ow obstruction within the lung that is often reversible spontaneously or with treatment. • Pathophysiology: Combination of bronchial smooth muscle constriction and obstruction of the lumen (by infl ammatory exudates and airway wall edema).

312 Pulmonology 313

Diagnosis

CLINICAL HISTORY AND PHYSICAL EXAM FOR DIAGNOSING ASTHMA

History Physical Exam

• Age at onset of wheezing • Respiratory: Evaluate degree of • Frequency, timing (day or night) air entry; evaluate for prolonged expiratory phase, tachypnea, • H/o prematurity, BPD retractions (subcostal, sternal, • Use of urgent care ED visits, hospitalizations, need for intercostal), wheezing vs stridor O or intubation 2 • Signs of atopy: Eczema, rhinor- • Comorbid conditions: Eczema, allergies, chronic rhea, transverse nasal crease rhinitis, sinusitis, GERD (allergic salute), Dennie’s lines • FHx of asthma and allergic conditions (folds inferior to the lower eyelid), • Triggers for wheezing: URI or infection, exercise, cold allergic shiners (periorbital air, allergens (eg, dust mite, animal dander, grass or darkening), conjunctivitis, pale or tree pollen, molds, cockroach), irritant exposures (eg, edematous nasal turbinates tobacco smoke, air pollution), emotional stress • Absence of clubbing • Environmental exposures: Pets, tobacco smoke, • Normal growth carpet, dust, cockroaches, central air or heat, use of pillow or mattress covers (dust mite exposure) • Positive response to short-acting bronchodilator • Current medications (check adherence and drug delivery technique)

• Diagnostic studies • CXR: May be normal or may show hyperinfl ation (fl attened diaphragm ↑ chest A/P diameter) or peribronchial thickening. • Peak fl ow monitors: May be useful in children ≥6 yr, especially those with poor symptom perception. Used to assess the severity of exacerbations, monitor response to therapy (compare with personal best at baseline or can estimate goal PEF using predicted table by gender, height, age). Limitations include that it is effort dependent and requires training (can have false high and low values).

↓ ↓ PEDIATRICS • Spirometry: Obstructive pattern with FEV1 and FEV1/FVC ratio; scooped or concave pattern on expiratory ﬂ ow–volume loop. ↑ ≥ • Positive bronchodilator (BD) response = of 12% in FEV1 after inhaled short-acting -agonist. • Bronchial provocation tests: May use exercise, histamine, or methacholine to provoke airway hyperresponsiveness with recovery post-BD. • Management: There are four components to asthma management (NAEPP EPR-3, 2007, http://www.nhlbi.nih.gov/guidelines/asthma): • Component 1: Asthma assessment (see table below) and objective monitoring (see table “Assessing control and adjusting therapy”) • Component 2: Education for a partnership in asthma care • Train families in self-management skills, including monitoring, treatment, and communication. • Deﬁ ne goals for good asthma control. Goals should include (1) control symptoms, allowing normal levels of activity and undisturbed sleep; (2) prevent exacerbations; (3) maintain normal lung function; and (4) use minimal therapy necessary to minimize side effects. • Provide a written asthma action (management) plan and emergency information. • Printable asthma action plan template: NHLBI EPR3, page 402(http://www.nhlbi.nih. gov/guidelines/asthma/asthgdln.pdf) • Printable MDI instructions: NHLBI EPR3, page 403(http://www.nhlbi.nih.gov/ guidelines/asthma/asthgdln.pdf) 314 Pediatrics

• Component 3: Control of environmental factors and comorbid conditions that affect asthma • Defi ne specifi c allergy sensitization (skin testing or RAST/ImmunoCap) and avoid exposure; consider immunotherapy. • Eliminate exposure to active or passive tobacco smoke; limit exposure to air pollutants. • Manage comorbid conditions (GERD, allergic rhinitis). • Annual infl uenza vaccine, good handwashing. • Component 4: Pharmacologic therapy β • All patients need access to quick-relief bronchodilator (short-acting 2-agonist). • Daily controller therapy based on severity and control; consider both impairment and risk (See tables “Medications commonly used for treating Asthma” and “Stepwise approach to management of Asthma” below). • Inhaled drug delivery technique is important to avoid frequent errors; check regularly. • MDI with a spacer has similar or better effi cacy, more portability and a shorter administration time compared to a nebulizer. • Spacer (valved holding chamber) with MDI improves lower airway delivery at all ages (including adults) and reduces side effects (thrush with ICS).

CLASSIFYING ASTHMA SEVERITY AND INITIATING THERAPY∗

Persistent Components of severity Intermittent Mild Moderate Severe

Symptoms ≤ 2 days/wk >2 days/ wk Daily Throughout the day

Nighttime 0-4 yr: 0 0-4 yr: 1-2x/mo 0-4 yr: 3-4x/mo 0-4: >1x/wk awakenings ≥5 yr: ≤ 2x/mo ≥5 yr: 3-4x/mo ≥5 yr: >1x/wk ≥5 yr: Often, 7x/wk

SABA use for ≤2 days/wk >2 days/wk Daily Several symptoms times per day

Interference None Minor Some Extreme with normal activity Impairment

Lung function Normal FEV1 FEV1 >80% FEV1: 60%-80% FEV1 < 60% between exacer- predicted predicted predicted bations 5-12 yr: FEV1/ 5-12 yr: FEV1/ 5-12 yr:

FEV1 >80% FVC >80% FVC 75%-80% FEV1/FVC< predicted 75% ≥12 yr: FEV1/ ≥12 yr: FEV1/

5-12 yr: FEV1/FVC FVC normal FVC reduced ≥12 yr: FEV1/ >85% 5% FVC reduced >5% ≥12 yr: FEV1/FVC normal

Exacerbations 0-1/yr 0-4 yr: ≥2 in 6 mo OR ≥4 wheezing episodes per requiring oral 1 year lasting >1 day Risk corticosteroid ≥5 yr: ≥2/yr

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Persistent Components of severity Intermittent Mild Moderate Severe

Recommended Step 1 Step 2 Step 3 0-4 yr: Step 3 Initial Therapy 5-12 yr: Step (see table “Stepwise 3 or 4 approach to man- ≥12 yr: Step agement of asthma” 4 or 5 below) and consider short course of oral systemic steroids

In 2-6 weeks, evaluate level of asthma control and adjust therapy accordingly.

∗ Some criteria vary by age. Adapted from NHLBI, EPR 3, 2007:41

ASSESSING CONTROL AND ADJUSTING THERAPY∗

Components of Not Well Very Poorly Severity Well Controlled Controlled Controlled

Symptoms ≤2 d/wk >2 d/wk Throughout the day

Nighttime 0–11 yr: ≤1x/mo 0–11 yr: ≥2x/mo 0–11 yr: ≥2x/wk awakenings ≥12 yr: ≤2x/mo ≥12 yr: 1–3x/wk ≥12 yr: ≥4x/wk

Interference with None Some limitation Extremely limited normal activity

SABA use for ≤2 days/wk >2 days/wk Several times symptoms per day Impairment PEDIATRICS Lung function

• FEV1 or peak ﬂ ow >80% predicted or 60%–80% predicted <60% predicted or personal best or personal best personal best

• FEV1/FVC (> = 5 yr) >80% 75%–80% <75% Exacerbations 0–1x/yr <5yr: 2–3x/yr <5 yr: >3x/yr requiring oral ≥5yr: ≥2x/yr ≥5 yr: ≥2x/yr corticosteroids

Risk Treatment-related Medication side eﬀ ects do not correlate with speciﬁ c levels of adverse eff ects control but should be considered in the overall assessment of risk

Recommended Action for • Maintain current Step up 1 step • Consider short Treatment step and reevaluate course of oral • Regular follow-up in 2–6 wk corticosteroid q 1-6 mo • Step up 1–2 steps • Consider and reevaluate stepdown if well in 2 wk controlled for For side eﬀ ects, consider alternative ≥3 mo treatment options

Adapted from NHLBI, EPR 3, 2007:40,43 316 Pediatrics

MEDICATIONS COMMONLY USED FOR TREATING ASTHMA

Medication Class Examples Adverse Eff ects Comments

Short-acting Albuterol Tachycardia, ner- Short-term symptom β -agonist (SABA) Levalbuterol vousness, tremors relief and pre-exercise

Systemic Prednisolone Altered behavior, Short courses are eﬀ ec- corticosteroid Prednisone nausea or vomiting, tive for exacerbations or pituitary adrenal establishing control at Methylprednisolone axis suppression initiation of therapy Dexamethasone (long-term therapy) High-dose or extended therapy should be weaned as tolerated

Inhaled MDI: Fluticasone, Thrush Mainstay of preventive corticosteroid (ICS) beclomethasone, Decreased height therapy fl unisolide, triamci- velocity∗ Diff erent ICS have nolone (temporary) similar effi cacy but DPI: Budesonide, Adrenal suppression diff erent potency mometasone (high dose) High-dose therapy Nebulized: Budes- should be weaned onide

ICS + long-acting Fluticasone + As above for ICS, FDA alert: LABAs β 2-agonist (LABAs) salmeterol Headache should not be used for Budesonide + symptom relief or with- formoterol out concomitant ICS

Leukotriene receptor Montelukast Headache, nausea, FDA alert: Rarely neu- antagonist Zaﬁ rlukast cough ropsychiatric events have been reported. Also used for allergic rhinitis

Anti-IgE monoclonal Omalizumab Injection site For use in persistent antibody reaction allergic asthma refrac- Anaphylaxis tory to high-dose ICS

∗For further discussion see NHLBI EPR3 page 222 (http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf)

STEPWISE APPROACH TO MANAGEMENT OF ASTHMA∗†

Preferred Treatment Step 1 SABA PRN Step 2 Low-dose inhaled corticosteroid (ICS)

Step 3‡ 0–4 yr: Medium-dose ICS 5–11 yr: Low-dose ICS + either LABA, LTRA, or theophylline; OR medium-dose ICS ≥12 yr: Low-dose ICS + LABA; or medium-dose ICS

Step 4‡ 0–4 yr: Medium-dose ICS + either LABA or montelukast ≥5 yr: Medium-dose ICS + LABA

Step 5‡ 0–4 yr: High-dose ICS + either LABA or montelukast ≥5 yr: High-dose ICS + LABA (consider omalizumab for patients ≥12 yr with allergies)

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Preferred Treatment Step 6‡ 0–4 yr: High-dose ICS + either LABA or montelukast + oral systemic steroid ≥5 yr: High-dose ICS + LABA + oral systemic steroid (consider omalizumab for patients ≥12 yr with allergies)

∗ Refer to NHLBI EPR3 (http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf) for alternative treatments. † The stepwise approach is meant to assist, not replace, clinical decision making. If clear beneﬁ t is not observed within 4–6 wk when patient technique and adherence is satisfactory, consider adjusting therapy or consider alternative diagnoses. Before stepping up, review adherence, inhaler technique, environmental control, and comorbid conditions. ‡ Consult with asthma specialist if Step 3 care or higher is required. Adapted from NHLBI, EPR-3, 2007:305, 306.

CYSTIC FIBROSIS • Epidemiology: 30,000 patients in the US; incidence of CF in US by racial or ethnic group: Caucasians, one in 2500; Hispanics, one in 8500; African Americans, one in 15,000; Asian Americans, one in 31,000. • Genetics • AR transmission; defect in a single gene on chromosome 7 that encodes a chloride channel called the cystic ﬁ brosis transmembrane regulator (CFTR). • The ΔF508 mutation is the most common mutation, present in ~70% of CF alleles in the US; however, >1500 CFTR mutations have been identiﬁ ed. • Diagnosis: CF is a clinical diagnosis that requires laboratory corroboration.

CRITERIA FOR THE DIAGNOSIS OF CYSTIC FIBROSIS

• ≥1 characteristic Evidence of abnormal CFTR function as demonstrated by phenotypic feature or one of the following: ∗ • Positive family history Plus • Elevated sweat chloride ≥60 mmol/L on ≥2 occasions of CF or • Identiﬁ cation of two disease-causing CFTR gene mutations • Positive CF newborn • Abnormal nasal transepithelial ion transport screen result

∗Should be performed at CF center or experienced laboratory. Adapted from J Pediatr 1998;132(4):589. PEDIATRICS

• Sweat chloride test: Pilocarpine iontophoresis is the gold standard for CF diagnosis but is not always conclusive (see table “Reference values for sweat chloride test” below). Sweat test can be done starting at age 2 weeks. • Sequencing of all known CFTR DNA mutations can identify 90% of CF mutations. • Sweat chloride levels and genotype analysis cannot be used to predict prognosis. • Newborn screen (NBS) can identify newborns at risk for CF. NBS protocols for screening vary by state, but all NBS identify ↑ blood level of immunoreactive trypsinogen (IRT). • First NBS ⊕ → Refer to a CF center for repeat testing. Testing is based on your state’s NBS program (IRT testing repeat, sweat test, CF DNA mutation analysis or a combination of these tests). • The panel of CF DNA mutations analyzed varies by state, therefore this test can miss rare mutations. If a patient has borderline sweat test and/or clinical suspicion for CF then sequencing of all known CFTR DNA mutations should be performed.

REFERENCE VALUES FOR QUALITATIVE PILOCARPINE IONTOPHORESIS SWEAT CHLORIDE TEST∗

Normal (CF Unlikely) Indeterminate∗∗ Abnormal (CF Likely) Infants <6 mo ≤29 mmol/L 30–59 mmol/L ≥60 mmol/L ≥6 mo ≤39 mmol/L 40–59 mmol/L ≥60 mmol/L ∗Sweat test can be performed starting at 2 weeks of age. ∗∗ Sweat chloride values in indeterminate range and clinical concern → full sequence CFTR DNA sequencing to establish the diagnosis. 318 Pediatrics

COMMON SYMPTOMS AND SIGNS OF CYSTIC FIBROSIS IN VARIOUS AGE GROUPS

Adolescence and Infancy Childhood Adulthood

Meconium ileus Failure to thrive Delayed sexual develop- Obstructive jaundice Steatorrhea ment Failure to thrive Distal intestinal obstruction Obstructive azoospermia or infertility Hyponatremic dehydration Chronic sinopulmonary disease Congenital absence of the or metabolic alkalosis Recurrent pneumonia vas deferens Edema with hypoproteine- Chronic cough and sputum mia and anemia Chronic bronchitis with “Atypical” asthma with bron- Pseudomonas aeruginosa Rectal prolapse chiectasis, clubbing Bronchiectasis or clubbing Recurrent pneumonia or Persistent CXR abnormalities bronchiolitis Pansinusitis Pansinusitis Salty-tasting skin Chronic abdominal pain Nasal polyps Acute salt depletion Idiopathic pancreatitis Symptoms of vitamin A, D, E, Cirrhosis Chronic metabolic alkalosis or K deﬁ ciency Distal intestinal obstruction Heat prostration with hypo- electrolytemia Diabetes mellitus Hemoptysis Pneumothorax

Adapted from Pulmonary Disease and Disorders 1997:803.

INCIDENCE, DIAGNOSTIC TESTS, AND TREATMENT FOR COMMON MANIFESTATIONS OF CYSTIC FIBROSIS

Overall Manifestation of CF Incidence Diagnostic Tests Treatment

Pulmonary Infection Double gag or Oral, inhaled, or IV anti- Haemophilus infl uenzae 16% sputum culture biotics (see Antibiotics section) Staphylococcus aureus 51% Bronchoalveolar MSSA lavage MRSA 21% CXR and/or Chest CT P. aeruginosa 54% Stenotrophomonas 13% maltophilia Nontuberculous no data mycobacteria Burkholderia cepacia 3% complex

Pancreatic insuffi ciency 91% Fecal elastase Pancreatic enzyme 72-hr fecal fat study replacement therapy

(continued on next page) Pulmonology 319

Overall Manifestation of CF Incidence Diagnostic Tests Treatment

Malnutrition 57%∗ Serial height, High-calorie, high- weight, and BMI protein diet measurements Oral supplements Serum vitamin Acid blockers ADEK levels Appetite stimulants Enteral feeds via gastrostomy tube

Chronic sinusitis Consider sinus Antibiotics with polyps 10-25% X-rays or CT scan Nasal steroids without polyps 75-90% Nasal sinus washes Endoscopic sinus surgery

CF-related diabetes 21% Annual random Subcutaneous insulin (do not see ketosis) blood glucose Carbohydrate counting screening OGTT: Every other year for 10-16 yo, then annually when >16 yo.

Infertility Males: >95% Semen analysis Genetic counseling Females: ≤20% Testicular or pelvic Microsurgical epididymal US sperm aspiration

CF-Related Liver Disease

Focal biliary cirrhosis 2%–5% Abdominal US, LFT, Ursodeoxycholic acid liver biopsy Liver transplantation

Cholelithiasis ≤12% Abdominal US Ursodeoxycholic acid Cholecystectomy PEDIATRICS for recurrent severe symptoms

∗Goal BMI percentile for patients 2-20 yr is ≥ 50th percentile for age. Data obtained from Am J Clin Nutrition, 2008;88(1):161. CF Patient Registry Annual Data Report 2008. Available at http://www.cﬀ .org.

• Complications • Pulmonary exacerbation: Typically caused by lower respiratory infection. • Systemic signs and symptoms: Anorexia, weight loss or poor gain, ↓ exercise tolerance, fever (atypical). • Symptoms: ↑ Cough, ↑ sputum production (wet cough), change in sputum color/ viscosity, shortness of breath. • Signs: New or ↑ crackles or wheezing, hemoptysis (infrequent). • Objective measures: ↓ in lung function from baseline (FEV >10% decrease), new CXR ↓ 1 ﬁ ndings, O2 saturation (infrequent).

• Acute treatment: 10–21 d of antibiotics (oral/inhaled or IV/inhaled), supplemental O2 if required, increased airway clearance ± hospitalization. Consider hospitalization with IV antibiotics for multiply resistant bacteria or severe or refractory exacerbations. (If hospitalized, provide contact isolation for MRSA and multiresistant P. aeruginosa and B. cepacia complex.) • Noninvasive positive pressure ventilation has been used for patients with advanced CF lung disease and hypercapnia (≥50 mmHg). 320 Pediatrics

• Lung transplantation: Indications for lung transplant referral include progressive

pulmonary function impairment (FEV1 <30% predicted), severe hypoxemia or hypercapnia, increasing functional impairment, or major life-threatening pulmonary complications. Five-year survival posttransplant is ~50%. • Nutritional deﬁ ciency: Risk for malnutrition high because of fat malabsorption, ↑ energy requirements, and poor appetite. Nutritional status is correlated with pulmonary health and lung function. Enteral (gastrostomy) feeding indications: weight has fallen two percentiles; no weight gain for 6 months, BMI <10%.

INCIDENCE, RISK FACTORS, AND TREATMENT OF COMPLICATIONS OF CYSTIC FIBROSIS

Complication Incidence Risk Factors Treatment Meconium ileus 10%–20% of Surgery infants at birth PEG electrolyte solution (laxative bowel prep) DIOS ~15% of older Pancreatic Aggressive bowel regimen patients insuﬃ ciency (ie, PEG electrolyte solu- Advanced lung tion bowel prep, laxatives, disease gastrograﬃ n enemas) Laparotomy (rarely) ABPA 1%–10% Systemic steroids ± antifungal therapy (ie, itraconazole) Hemoptysis

Minor Infrequent Pulmonary exac- Treat infection erbations Observation Vitamin K deﬁ - Vitamin K: Check PT/PTT ciency Liver dysfunction with abnormal PT/PTT

Major ~1% of patients Age Acutely: O2, ABC each year Advanced bron- Consider holding chiectasis Pulmozyme and airway clearance Bronchial artery embolization

Arthritis ~1% of older Pulmonary exac- NSAIDs (CF-associated children erbations Occasionally, short course arthritis, Severe pulmonary of steroids Hypertrophic disease osteoarthropathy) Spontaneous 3%–4% of patients Older age Standard therapy for pneumothorax during their Advanced bron- pneumothorax caused (poor prognostic lifetime chiectasis by other conditions (eg, sign) chest tube) Previous episode (50% recurrence) Pleurodesis for persistent air leaks should be performed in a manner to not preclude possible future lung transplantation Pulmonology 321

Chronic Management Airway Clearance Therapies • Purpose: Loosen and clear airway mucus; may be preceded by bronchodilator therapy. • All methods should be done with huffi ng and coughing to expectorate mucus. • Methods: Postural drainage and percussion (PD&P), high-frequency chest wall oscillation (percussive vest), PEP, Flutter™, Acapella™, IPV, cough-assist device • Frequency: One to two times a day when well; three to four times a day when ill Nutrition • Risk for malnutrition is high because of fat malabsorption, ↑ energy requirements, and poor appetite. • All patients should be on a high-calorie, high-protein diet. • Monitoring: Height, weight, and BMI or weight for length trend and % predicted reviewed at every encounter. Goal: BMI or weight and length ≥50% predicted for age. • Salt supplement: 1/8 tsp/day for <6mo age and 1/4 tsp/day for infants >6mo age. Older children get suffi cient salt from their diet. • Oral supplements: Vitamin and enzyme supplementation, high-calorie milkshakes, fortifi ed milk, or juice-based drinks in addition to regular meals; may also use Polycose powder. Antibiotics • Selected based on sputum or a deep throat swab culture SABA with sensitivities. • Higher doses are often required because of altered pharmacokinetics in these patients. • Goal: Suppression of the organism to levels at which symptoms and signs are minimized (eradication is unlikely once mucoid phenotype is present). • At least two antibiotics of different classes are generally recommended to avoid resistance, particularly for P. aeruginosa.

PHARMACOLOGIC THERAPY FOR CYSTIC FIBROSIS

Dosage Adverse Eff ects Comments Pancreatic Enzyme Replacement Therapy (PERT) Pancrelipase Infants: 2000–4000 lipase Fibrosing Dose titrated according (Creon, ZenPep, U/120 mL milk colonopathy to clinical malabsorption PEDIATRICS Pancreaze) 1–4 yr: 1000 lipase U/kg/ (at high doses) Average dose, 1800 meal + ½ dose with snacks Diaper dermatitis lipase U/kg/meal >4 yr: 1000–2000 lipase Oral lesions (if the Max dose: 2500 lipase U/kg/meal + ½ dose with patient chews the U/kg/meal or 10,000 snacks beads) U/kg/d Constipation Fat-Soluble Vitamin Replacement (ADEKs, <1 yr: 1 mL/day Hypervitaminosis Supplementation AquADEKs, 1–3 yr: 2 mL/day required because of Source CF, malabsorption of fat- 4–10 yr: 1 tablet/day Vitamax) soluble vitamins even >10 yr: 2 tablets/day with enzymes Vitamin K 2.5–5.0 mg twice weekly Use in conjunction with (daily with liver disease) oral or IV antibiotics Mucolytics rhDNase 2.5 mg nebulized once Chest pain, May use twice daily in (Pulmozyme) daily pharyngitis acute illness

(continued on next page) 322 Pediatrics

Dosage Adverse Eff ects Comments Hypertonic 4 mL nebulized twice daily Bronchospasm, sore Give SABA 15 min prior (7%) saline throat, chest tightness (Hyper-Sal) N-acetylcysteine 1 mL of 10% or 20% Bronchospasm, Bad odor ↓ with (Mucomyst) nebulized three or four cough refrigeration times a day Give SABA 15 min prior Antiinfl ammatory Therapy Azithromycin <25 kg: 10 mg/kg 3 X a wk Diarrhea, nausea + P. aeruginosa 25–40 kg: 250 mg 3 X a wk Monitor LFT, renal AFB negative >40 kg: 500 mg 3 X a wk function Ibuprofen: High 20–30mg/kg/dose Q12h GI bleeding Requires periodic phar- dose (max, 1.2 g/dose; 3.2 g/d) Renal insuﬃ ciency macokinetic testing to Do not change brands ensure correct dosing (kinetics can diﬀ er)

ORAL, INHALED, AND INTRAVENOUS ANTIBIOTIC OPTIONS FOR PATIENTS WITH CYSTIC FIBROSIS

Organism Drug Dosage∗ Adverse Eff ects Oral

P. aeruginosa Ciproﬂ oxacin 40 mg/kg/d divided May cause hypoglycemia, Q12h (max, 2 g/d) avoid in patients with prolonged QT

S. aureus Doxycycline >8 yr: 2–4 mg/kg/d Tissue hyperpigmenta- divided Q12–24h; max, tion, enamel hypoplasia, 100 mg/dose or 200 or permanent tooth mg/d discoloration

S. aureus (MRSA) Trimethoprim/ 10–20 mg/kg/d TMP GI upset, rash, urticaria, H. infl uenzae sulfamethoxazole component divided myelosuppression Q6–8h S. maltophilia

A. fumigatus Itraconazole 2–5mg/kg/dose Liver dysfunction (ABPA) Q12–24h

S. aureus (MRSA) Linezolid 10 mg/kg Q8–12h; max, Headache, myelosup- 600 mg Q12h pression Second-line; very expensive Inhaled

P. aeruginosa Tobramycin (TOBI) 300 mg BID in Dysphonia, broncho- 28-day cycles spasm

P. aeruginosa Aztreonam 75mg once/day x 28days Bronchospasm, cough (Cayston) using Altera e-ﬂ ow device

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Organism Drug Dosage∗ Adverse Eff ects Intravenous

P. aeruginosa Aztreonam 50 mg/kg/dose Q6–8h; Rash, diarrhea, nausea, max, 50 mg/kg/dose or vomiting (1%–10%) 2 g/dose

P. aeruginosa Ceftazidime 50 mg/kg/dose Q8h; Diarrhea, may ↑ INR in nu- max, 50 mg/kg/dose tritionally deﬁ cient children, or 6 g/d hepatic or renal disease

P. aeruginosa Colistimethate 5 mg/kg/dose divided Nephrotoxicity sodium Q6–8h, increase 1 mg/ Neurologic abnormalities kg/dose until 8 mg/kg/ (primarily paresthesias, dose (max, 160 mg/dose) may also see dizziness, is reached or side eﬀ ects slurred speech, vertigo, noted headache, fever)

P. aeruginosa Gentamicin/ 3 mg/kg/dose Q8h (titrate Nephrotoxicity μ tobramycin to peak of 10–12 g/L Ototoxicity and trough <2 μg/L)

P. aeruginosa Meropenem 40 mg/kg/dose Q8h; Headache, nausea, vomit- B. cepacia max, 2 g/dose or 6 g/d ing, diarrhea, hypoglycemia

P. aeruginosa Ticarcillin/ 400 mg/kg/d ticarcillin Headache, nausea, vomit- S. aureus (MSSA) clavulanic acid component divided ing, diarrhea, hepatotox- Q4–6h; max, 24 g of icity, hypoglycemia S. maltophilia ticarcillin component/d

S. aureus (MRSA) Clindamycin 10 mg/kg/dose Q8h; Abdominal pain, nausea, max, 900 mg/dose or vomiting, diarrhea, ↑ LFT, 2.7 g/d renal dysfunction

S. aureus (MRSA) Vancomycin 13–15 mg/kg/dose Q8h; “Red-man” syndrome max, 1.5 g/dose or 4 g/d Nephrotoxicity PEDIATRICS

∗ These are recommended starting doses for commonly used antibiotics. Exact dosing for a particular antibiotic or class should be conﬁ rmed for each individual patient.

APPARENT LIFE-THREATENING EVENT (ALTE) • Defi nitions • ALTE: “An episode that is frightening to the observer and that is characterized by some combination of apnea, color change, a marked change in muscle tone, choking, or gagging.” (Pediatrics 1987;9:292). The presenting symptoms in descending order of frequency are apnea, cyanosis, hypotonia, unresponsiveness, labored breathing, and lethargy. • Apnea: Cessation of airfl ow of at least 20 seconds. May be central (lack of output from brain, or neuromuscular etiology) or obstructive (paradoxical inverse movement of the chest wall or abdomen). Sometimes confused with periodic breathing (≥3 respiratory pauses of ≥3 sec each, separated by intervals no longer than 20 s (Pediatrics 1979;63:355). • Central cyanosis: Arterial circulation of unsaturated blood. Identifi ed by blue oral mucous membranes, especially the lips and tongue. Peripheral cyanosis suggests increased extraction of oxygen by tissues. • Acrocyanosis: Blue discoloration of the hands and feet (normal neonate/infant fi nding). • Circumoral cyanosis: Bluish “moustache” or purple perioral region (normal neonate/ infant fi nding). 324 Pediatrics

DIFFERENTIAL DIAGNOSIS OF ALTE

Causes Frequency (%)

GI: GERD, gastroenteritis, esophageal dysfunction, colic 33

Idiopathic or apnea of infancy 23

Neurologic: Seizure, central apnea, hypoventilation, intracra- 15 nial bleed, meningitis, encephalitis, hydrocephalus, brain tumor, neuromuscular disorders, vasovagal reaction, malformation of the brainstem

Respiratory: RSV bronchiolitis, pertussis, aspiration, pneumonia, URI 11 or LRTI, wheezing, foreign body

Otolaryngologic: Laryngomalacia, subglottic or laryngeal stenosis, 4 OSA

Cardiovascular: Congenital heart disease, cardiomyopathy, arrhyth- 1 mia, myocarditis

Metabolic or endocrine: Electrolyte abnormality, hypoglycemia, IEM <1

Infection: UTI, sepsis

Nonaccidental trauma (NAT): Shaken baby syndrome, intentional suﬀ ocation, ﬁ ctitious disorder by proxy (Munchausen)

Other: Breathholding, choking, drug or toxin ingestion, botulism, unintentional smothering, anemia, hypothermia

• Diagnosis • History: • Very detailed history about the event with speciﬁ c focus on relationship to feeding, reﬂ ux symptoms, choking, gagging, coughing, vomiting, medications taken by the child or mother, presence of apnea, duration of pause in respirations, color change and distribution, change in tone, shaking of the body, eye deviation, loss of consciousness, coryza, fever, trauma, witnesses, type of resuscitation (and who performed it), mental and physical status at present and EMS record review. (See the table above for a differential diagnosis of ALTE. • Other routine perinatal and neonatal history, including FHx of infant deaths. • Physical exam: Very detailed exam with special focus on vital signs; signs of trauma (ROM of all joints, bruising, hemotympanum, retinal exam); and exam of the nasopharynx for congestion, milk, or blood. • Evaluation: Very focused. Tests should be guided by history and physical exam. Consid- erations include inpatient observation, labs (CBC, chem 10, CBG, lactate, liver panel, amylase/lipase, PT/PTT), noncontrast head CT, EKG, four-extremity blood pressure,

pre- and post-ductal SpO2, CXR, barium swallow, pH probe, OCRG, isotope-labeled milk scan, or sleep study. Pulmonology 325

PULMONARY FUNCTION TESTING (SPIROMETRY)

Inspiratory Vital Inspiratory Reserve Capacity Capacity Volume (VC) (IC) Total (IRV) Lung Capacity (TLC) Tidal Volume (TV) Volume Expiratory Reserve Volume (ERV)

Residual Functional Residual Volume (RV) Capacity (FRC)

Time Figure 25-3 Volume–time graph of air movement during breathing. Note TLC volume at the end of maximal inspiration; FRC is the volume remaining at the end of quiet expiration; RV is volume in the lung at the end of maximal expiration; VC = TLC minus RV; FVC is VC performed with maximal effort. 10

8 FEF25 6 FEF50 ∗

FEV½ PEDIATRICS 4 ∗ Expiration FEV1 2 FVC FEF75

(L/sec) 0

2 46

Flow 2 Volume (L)

4 Inspiration FIF25

FIF75 6

FIF50 8

10 Figure 25-4 Normal fl ow–volume loop from spirometry. Note: FEV is the volume of gas exhaled in the fi rst ∗ 1 second of forced expiration. FEV1 and FEV½ values vary, but are depicted here as 4L and 2L, respectively, for illustration purposes. FEF between 25% and 75% (FEF25%–75%) is the average fl ow rate (Forced Expiratory Flow rate) between 25% and 75% of FVC. FIF, Forced Inspiratory Flow; FVC, Forced Vital Capacity. 326 Pediatrics

INTERPRETATION OF ABNORMAL SPIROMETRY TEST RESULTS

Lung Disease Pattern Spirometry Findings Diseases

Obstructive ↓ or normal FVC Small airway obstruction: Asthma, CF, ↑ ↓ FEV production of or 1 ↓ clearance of mucus ↓ FEV /FVC ratio 1 Central airway obstruction: Subglottic ↓ FEF 25%–75% and tracheal stenosis, tracheomalacia, Concave expiratory loop vascular ring, vocal cord paralysis Loss of parenchymal elastic recoil: Emphysema, interstitial ﬁ brosis

Restrictive ↓ or normal FVC Interstitial lung disease (eg, ﬁ brosis) ↓ FEV1 Scoliosis ↑ FEV1/FVC ratio Neuromuscular disorders ↑ Normal/ FEF25%–75% ↓ Inspiratory VC

Available at www.AccessPediatrics.com • Chronic cough • Hemoptysis PEDIATRICS ex glucose, glucose, bacteria present Miscellaneous Miscellaneous Findings PMN PMN (%) bromyalgia ) 3 serum sickness, septicemia, brosis, WBC (cells/mm 50,000–300,000 >75 Low 327 high <200 <25 Joint hypermobility, benign joint hypermobility joint hypermobility benign Joint hypermobility, High <2,000 <25 Debris Decreased 15,000–20,000 75 Decreased 20,000Decreased 80 25,000Decreased 50–60 bacteria Acid-fast Nocturnal idiopathic pain syndrome (growing pains), refl Nocturnal (growing syndrome idiopathic pain JIA, JRA, spondyloarthritis, psoriatic arthritis, SLE (lupus), juvenile Transient synovitis, rheumatic fever, septic arthritis, osteoarticular fever, rheumatic synovitis, Transient Sickle cell disease, other hemoglobinopathies, hemophilia other hemoglobinopathies, Sickle disease, cell and clear Very Gout, mucopolysaccharidoses, mucolipidosis type III, Fabry’s disease, disease, type mucolipidosis III, Fabry’s Gout, mucopolysaccharidoses, Color and Color Clarity Viscosity Xanthochromic Xanthochromic and turbid Yellow and Yellow cloudy Yellow-white and cloudy Yellow and Yellow opaque Serosanguinous and turbid drug induced ciency related, Leukemia, neuroblastoma, metastatic disease, primary metastatic disease, bone tumors neuroblastoma, Leukemia, ammatory Sarcoidosis, immune complex deposition, cystic complex immune fi Sarcoidosis, ammatory ammatory disorders: ammatory dermatomyositis, IBD, MCTD, linear scleroderma, progressive systemic sclerosis, panniculitis, panniculitis, sclerosis, systemic progressive linear scleroderma, MCTD, IBD, dermatomyositis, HSP KD, vasculitis, CRMO/SAPHO syndromes, Infection/postinfective: tuberculosis, brucella/lyme/fungal arthritis brucella/lyme/fungal tuberculosis, problems: Hematologic Neoplasia: pain syndromes: Idiopathic Traumatic Traumatic arthritis Infl Chronic arthritis Pyogenic Tuberculous arthritis Normal Yellow Reactive arthritis Septic arthritis syndrome, localized hypermobility, Marfan syndrome, Ehlers–Danlos syndrome, irritable hip Marfan syndrome, Ehlers–Danlos syndrome, hypermobility, localized syndrome, epiphysis, slipped upper femoral other osteochondritis, disease, Perthes’ (transient synovitis), pain back syndrome, patella anterior patella, chondromalacia Infl Mechanical/orthopedic problems: sympathetic dystrophy, widespread idiopathic pain syndrome, fi idiopathic pain syndrome, widespread sympathetic dystrophy, alkaptonuria, syndrome Lesch–Nyhan Other: Metabolic disorders: immunodefi Noninfl EVALUATION OF SYNOVIAL FLUID Rheumatology COMPLAINTS DIAGNOSES OF MUSCULOSKELETAL DIFFERENTIAL IN CHILDREN CHAPTER 26 • Rheumatic (JIA, JAS, SLE) • Rheumatic (JIA, JAS, IBD, cell disease, • Other (sickle vasculitis) Fever Multiple joints YES NO • Infection/sepsis (gonococcal) • Infection/sepsis systemic • Other (malignancy, JIA, SLE) ACUTE ARTHRITIS • Trauma synovitis • Transient arthritis• Lyme SLE) • Rheumatic (JIA, JAS, (HSP) • Vasculitis fungal) (TB, • Infection IBD) • Other (malignancy, Fever Single/few joints Single/few YES NO Differential diagnosis of a child presenting with signs/symptoms acute arthritis. • Transient synovitis (low grade fever) grade (low synovitis Transient • (septic arthritis,• Infection osteomyelitis) (serum • Vasculitis sickness, KD) hypersensitivity, SLE) • Rheumatic (JIA, JAS, IBD) • Other (malignancy, Figure 26-1 328 Rheumatology 329

LABORATORY EVALUATION OF RHEUMATIC DISEASES

Specifi city/ Disease Test Sensitivity PPV Systemic lupus ANA 57%/93% Moderate erythematosus (SLE) Anti-dsDNA 97%/57% 95% Anticardiolipin Ab Yes/No Low (lupus anticoagulant) Anti-Smith Ab High/25%–30% 97% Drug-induced lupus Antihistone Ab1 High/95% High Scleroderma ANA 54%/85% High Anticentromere 99.9%/65% High Anti–Scl-70 100%/20% High MCTD ANA No/93% High Anti-U1 ribonucleoprotein High/Moderate High (RNP)1 Polymyositis, CK No/High Low Dermatomyositis Anti–Jo-1 Ab Yes/30%–50% High Muscle biopsy Yes/Moderate High Sjögren’s syndrome ANA 52%/48% Moderate Anti-SSA/Ro (type A)2 87%/8%–70% 40% Anti-SSB/La (type B) 94%/16%–40% 40% Wegner’s Anti-proteinase 3 Ab High/moderate High granulomatosus c-ANCA Ab 50%/95% High

1False positive in SLE. 2False positive in cutaneous lupus. CREST, calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias; MCTD, mixed connective tissue disease; PPV, positive predictive value.

Data from S Medical J 2005;98:185. PEDIATRICS

JUVENILE IDIOPATHIC ARTHRITIS (JIA) • Deﬁ nition: Onset of arthritis prior to 16 years of age that lasts ≥6 wk; previously known as juvenile rheumatoid arthritis (JRA) and juvenile chronic arthritis (JCA) • JIA classiﬁ cation system: • Systemic • Oligoarthritis • Persistent (no more than four joints involved during course of disease) • Extended (more than four joints involved after 6 mo of disease) • Polyarthritis (RF−) • Polyarthritis (RF+) • Psoriatic arthritis • Enthesitis-related arthritis • Undifferentiated arthritis • Epidemiology: Most common childhood rheumatic disease with incidence of 2–20/100,000 and prevalence of 16–150/100,000; male>female; frequently presents during the toddler years (1–3 yo) • Diagnostic evaluation • Diagnosis is primarily clinical. • Supportive laboratories: CBC (anemia of chronic disease, thrombocytosis, leukocytosis), α ↑ ESR, CRP, 1 antitrypsin (serum), serum amyloid A (SAA) protein, Ig ( or normal), ANA, RF, HLA-B27. 330 Pediatrics

• Arthrocentesis: Not performed unless a septic joint is suspected. • Slit-lamp eye exam: r/o uveitis. • Characteristics and treatment

CHARACTERISTICS OF POLYARTICULAR, OLIGOARTICULAR, AND SYSTEMIC TYPES OF JIA

Oligoarthritis Polyarthritis Systemic Disease1

Percent of cases 60 30 10

Clinical ≤4 joints >4 joints involved; Variable number/types of presentation involved; large and small joints; joints involved; concomi- predominantly tant arthritis, quotidian knees, ankles, fever, and salmon-colored ﬁ ngers, wrists, evanescent rash that is and elbows in sometimes pruritic; rash an asymmetric appears as fever subsides; fashion HSM, LAD, serositis; ↓ H/H, ↑ plt, ↑ WBC; elevated inﬂ ammatory markers; ↑ transaminases

Age of onset Peak 1–2 yo; Peak 1–3 yo; all ages No peak; throughout early childhood childhood

Sex ratio (♀:♂) 5:1 3:1 1:1

Systemic Absent; major Generally mild; Often self-limited; 50% involvement morbidity is possible unremitting with chronic and destruc- uveitis articular involvement tive arthritis

Occurrence of 5%–15% 5% Rare chronic uveitis

⊕RF Rare 10%2 Rare ⊕ANA 75%–85%3 40%–50% 10%

Prognosis Excellent except Guarded to moder- Moderate to poor eyesight ately good

Treatment • NSAIDS • NSAIDS + therapies below • ± intra- • Corticosteroids articular steroid • MTX, sulfasalazine, azathioprine injections • Biologic agents: TNF-α inhibitors (inﬂ ix- • MTX imab, etanercept, adalimumab; IL-1 receptor antagonists), IL-1 inhibitor (anakinra)

Additional Other biologic Anti–IL-6 monoclonal, options for agents: abatacept antibody tozilizumab, cur- treatment (FDA approved for rently under investigation adults); rituximab (FDA approved for adults)

1Still’s disease: acute complication is development of macrophage activation syndrome (MAS) with considerable morbidity/mortality. 2RF-positive disease usually has a more severe course; also usually persists into adulthood. 3↑ risk of uveitis in these patients. Adapted from Textbook of Pediatric Rheumatology. 5th ed. 2005, p 225. Rheumatology 331

PEDIATRIC SYSTEMIC LUPUS ERYTHEMATOSUS (pSLE) • Defi nition: Multisystem autoimmune disease characterized by immune complex deposition and infl ammation within organs and blood vessels. Epidemiology • pSLE is more common in male than female (prepubertal ♀:♂ ratio 4:1; postpubertal ♀:♂ ratio 5–8:1). • More common in African-Americans, Hispanics, and Asians compared to Caucasians. • Diagnosis • Clinical manifestations: Variable presentations ranges from being an insidious process to a rapidly fatal disease → most often with fevers, weight loss, anorexia, and fatigue + multisystem involvement. pSLE may be a more aggressive disease compared to that in adults. • Diagnostic criteria based on the American College of Rheumatology 1982 revised criteria for the classifi cation of pSLE (Arthritis Rheum 1997;40:1725).

DIAGNOSTIC CRITERIA FOR PEDIATRIC SYSTEMIC LUPUS ERYTHEMATOUS (PSLE)

Need 4 out of 11 criteria to be serially present at the time of presentation

1. Malar rash (also known as a “butterﬂ y” rash—ﬂ at or raised erythematous rash that spares the nasolabial folds) 2. Discoid rash (erythematous raised patches with keratotic scaling and follicular plugging) 3. Photosensitive rash (sun-exposed areas) 4. Oral ulcers (oral or nasopharyngeal painless ulcerations) 5. Nonerosive arthritis ≥2 peripheral joints 6. Blood abnormalities (cytopenia, including Coomb’s positive hemolytic anemia, leukopenia [<4000 cells/mm3], lymphopenia [<1500 cells/mm3], and/or thombocytope- nia [<100,000/mm3]) 7. Serositis (pleuritis, pericarditis) 8. Renal involvement (proteinuria >0.5 g/day or >3+ protein, cellular casts) 9. Positive ANA (in the absence of a drug exposure that can cause a false-positive ANA: hy-

dralazine, procainamide, minocycline, INH, penicillin, sulfonamides, and anticonvulsants) PEDIATRICS 10. Immunologic manifestation (any of the following: anti-dsDNA, anti-Smith, antiphospholipid antibodies, or anticardiolipin antibodies, lupus anticoagulant, or a false-positive syphilis serologic test for 6 mo, conﬁ rmed negative by Treponema pallidum immobilization/ﬂ uorescent treponemal antibody absorption test) 11. Neurologic disease (psychosis or seizures in the absence of drugs or metabolic derangements)

Adapted from Arthritis Rheum 1997;40:1725.

• Diagnostic Evaluation • Clinical diagnosis of SLE is supported by laboratory fi ndings. • Laboratory test: CBC, Chem 10, liver panel, ESR, CRP, D-dimer, UA with micro, C3, C4, lupus anti-anticoagulant, anti-B2 glycoprotein-1, anti-cardiolipin IgG/IgM, PT/ PTT, ANA, anti-dsDNA or, anti-Smith, anti-RNP, anti-ENA with and without DNAse, RPR, direct Coomb’s. • C3 and C4 are not part of diagnostic criteria but may be ↓ during disease fl are. • An ANA test is not specifi c for SLE in the absence of other laboratory or clinical fi ndings. Note that 5%–20% of healthy children can have a positive ANA. • High-titer dsDNA levels may be of utility in serving as a marker of nephropathy severity. • CXR: Evaluate for cardiomegaly and pleural effusions. Echocardiography if cardiomegaly present to r/o pericardial effusion. • Treatment • Goal of therapy: Treat active disease aggressively while minimizing side effects and toxicity of drugs. The decision to utilize immunosuppressive agents (alone or in combination therapy) is dictated by the disease severity. 332 Pediatrics

• Approximately 85% of pSLE cases develop renal involvement within 2 yr of diagnosis → A 24-hr urine for total protein, creatinine, and volume q6mo for surveillance of lupus nephritis. If proteinuria >0.5 g/day → renal biopsy to assess disease severity. • Monitor for neuropsychiatric manifestations (recent literature suggests majority of children/adolescents develop neuropsychiatric manifestations). • Caveats (no RCT of therapies has been performed for children with SLE): • Corticosteroids: cornerstone of therapy at disease onset for active disease. Disease fl are: IV methylprednisolone (30 g/kg/dose daily, maximum dose of 1 gm), followed with oral prednisone (1–2 g/kg/day) and weaned as clinical/laboratory parameters improve • NSAIDs: symptomatic relief of arthritis (if kidney function normal) • Hydroxychloroquinine: cutaneous disease and arthritic symptoms (requires twice-yearly dilated eye exam) • Low-dose ASA: preventive therapy for those with high-titer antiphospholipid antibodies (no data proving effi cacy). • Steroid sparing agents (eg, cyclophosphamide, mycophenylate mofetil, methotrexate, azathioprine, cyclosporine): chronic maintenance therapy • Biologic modulation (IVIG) • Biologic modulation (rituximab): refractory thrombocytopenia, treatment-resistant hemolytic anemia, combination therapy for severe SLE organ disease involvement (varying degrees of improvement in case series/reports) • Plasmapheresis: possible utility in settings where removal of clinically signifi cant pathogenic antibodies is merited (pulmonary hemorrhage, severe CNS disease). Does not inhibit ongoing pathogenic antibody production. Risks of plasmapheresis: hypogammo- globulinemia, coagulopathy, etc. • Regimens: No standard treatment regimens exist. • Mild SLE—combination of NSAIDs, low-dose oral corticosteroids, and hydroxychloroquinine • Moderate SLE—NSAIDs, corticosteroids, hydroxychloroquine, ± additional immunosup- pressant to facilitate corticosteroid wean (eg, MTX, mycophenylate mofetil, azathioprine, cyclosporine) • Severe SLE—NSAIDS, hydroxychloroquinine, and corticosteroids (higher doses) • Class III or IV SLE nephritis or cerebritis: cyclophosphamide 6+ mo (based on response) → transition to maintenance mycophenylate mofetil after cyclophosphamide induction course completed

CLINICAL FEATURES CORRESPONDING TO SPECIFIC VASCULITIDES

Clinical Features Type of Vasculitis

Pulmonary and renal symptoms Wegener granulomatosis, microscopic polyangiitis, Goodpasture syndrome

Pulmonary–dermal symptoms Cryoglobulinemia

Asthma and eosinophilia Churg–Strauss syndrome

Upper respiratory tract involve- Wegener granulomatosis ment (ie, sinusitis, OM)

Mucocutaneous ﬁ ndings Kawasaki disease (KD) Behçet syndrome

Abnormal pulses Takayasu arteritis, KD, polyarteritis nodosa Rheumatology 333

Henoch–Schönlein Purpura (HSP) • Deﬁ nition: HSP is characterized by the tetrad of palpable purpura, arthritis, abdominal pain/GI bleeding, and renal involvement. HSP predominantly affects small vessels by depositing IgA immune complexes leading to leaky blood vessels, inﬂ ammation, and swelling. • Epidemiology • HSP is the most common systemic vasculitis in children and is rare in adults • Incidence 10–20/100,000 children • Affects 3–15 yo but can involve other age groups • Frequently occurs during winter and spring and is often preceded by a URI or pharyngitis • ♂ > ♀ ratio 1.5:1 • Diagnosis • Clinical diagnosis Based on history and physical exam

CLINICAL MANIFESTATION OF HENOCH–SCHÖNLEIN PURPURA

Organ Clinical Manifestation

Skin• Nonthrombocytopenic, nonblanching, palpable purpura located over gravity-dependent areas (lower extremities and buttocks ); can involve additional areas (face, ears, and arms), especially in young children • Urticaria may precede purpura • Rash may be pruritic, ecchymotic, or hemorrhagic • Rash occurs in cyclic waves (or crops) every 3–4 d, and new rash may appear prior to resolution of previously occurring rash

Musculoskeletal• Transient arthritis of larger joints in a symmetric fashion (primarily knees, ankles, and feet)

GI• Colicky, intermittent abdominal pain secondary to subserosal purpuric lesions • ~1/3 of cases: pain precedes rash by days, raising suspicion for an acute abdominal process • Vomiting and GI bleeding (microscopic or macroscopic) • Chylous ascites, pancreatitis (very rare) PEDIATRICS • Intussusception

Renal• Typically within 4 wk of onset of disease: microscopic or macroscopic hematuria, mild to nephrotic range proteinuria, peripheral edema, hypertension, renal insuﬃ ciency • ESRD very rare in childhood

Other (very rare)• Orchitis, testicular torsion, epididymitis, carditis, cerebral vasculitis, pulmonary hemorrhage

• Laboratory studies/evaluation: CBC may reveal leukocytosis, normal platelet count or thrombocytosis (thrombocytopenia should be absent), ± mild anemia secondary to GI losses, UA with micro to evaluate for hematuria and proteinuria, chem 7 to evaluate renal function, stool guaiac for evidence of microscopic GI losses. Other labs that may be considered: albumin (↓), infl ammatory markers (ESR, CRP)are frequently elevated, endothelial markers (such as vWF antigen), D-dimer. • Imaging: No routine imaging is required. However, abdominal US should be done if suspecting intussusception (an air/contrast enema is diagnostic and therapeutic if performed early). • Biopsy • Skin: Rarely done. Perform for unusual presentations in which the diagnosis is unclear; immunofl uorescence (IF) confi rms predominance of IgA and fi brinogen deposition VASCULITIS

Large vessel Medium Small vessel vasculitis vessel vasculitis vasculitis

• Childhood systemic polyarteritis nodosa • Giant cell arteritis • Cutaneous polyarteritis nodosa ANCA • Takayasu arteritis • Kawasaki disease positive? NO YES 334

Immune-complex • Wegener granulomatosis mediated small • Microscopic polyangitis vessel vasculitis • Churg-Strauss syndrome • Drug-induced

• Henoch-Schönlein purpura • Cryoglobuliinemic vasculitis • Lupus vasculitis • Goodpasture syndrome • Sjogren disease • Drug-induced immune- complex vasculitis • Behcet syndrome • Infection-induced immune- complex vasculitis

Figure 26-2 Classiﬁ cation of vasculitides by vessel size. Rheumatology 335

• Renal: Reserved for signifi cant renal involvement, declining kidney status, or chronic proteinuria; biopsy reveals IgA and fi brinogen deposition on IF, GN with focal and segmental lesions to crescentic disease • Disease course and prognosis • Disease duration • 4 wk from disease onset to resolution in two-thirds of children • Expect recurrence within 6 wk with a milder disease course • Isolated microscopic and/or macroscopic hematuria; may have persistent microscopic hematuria lasting months or years, especially following an URI • Risk factors for chronic renal failure are related to initial clinical presentation: • Nephrotic syndrome with or without nephritis, renal insuffi ciency, and HTN • Crescentic disease (high propensity for ESRD within 1 year) • Prognosis overall is excellent, as HSP is a relatively, benign, self-limiting condition. • Morbidity and mortality is associated with GI complications in the short term and renal disease over the long term. • Recovery within 2 years in >75% • Progression to ESRD in 1%–5%, with its development occurring in days up to 20 yr after disease onset • Treatment • Most patients who are clinically well appearing, tolerating PO, and have suffi cient pain control can be sent home with close follow-up with their PCP. Recommend checking UA with micro q2 weeks and then space out to q month over a period of 6 months to year. Also annual BP monitoring ± BUN/Cr. • Supportive care with bland diet and outpatient management for mild GI involvement; bowel rest and TPN for moderate to severe GI involvement (severe abdominal pain, bloody stools) • Consider gastric protection with H2 blocker or PPI and H1 blocker if pruritis is present. • Acetaminophen for joint manifestations (NSAID therapy may exacerbate GI symptoms and potentially affect kidneys, although they can be used). • Corticosteroids • Controversial for the prevention of persistent renal disease • Possible benefi t in severe GI involvement

• Severe renal involvement, CNS disease, or signiﬁ cant pulmonary disease may require PEDIATRICS stronger immunosuppressive therapy, such as cyclophosphamide.

Kawasaki Disease (Pediatrics 2004;114(6):1708) • Defi nition: KD is a systemic vasculitis of unclear etiology primarily affecting medium-sized vessels with a predilection for coronary arteries. • Epidemiology • 1 cause of acquired heart disease in children worldwide. • 85% of cases occur in children <5 yo • Incidence is 9–19/100,000 children <5 yo in the US according to CDC (exceeds 100/100,000 in some Asian countries) • Americans of Asian and Pacifi c Island descent > Hispanics > Caucasians • ♂ > ♀ • Ratio ♂:♀1.5–1.7:1 • Diagnosis • Diagnosis of “complete KD” based on history and physical exam. Signs of KD can appear and resolve prior to presentation to a healthcare professional; therefore, a detailed timeline of signs/symptoms should be documented. • Requires exclusion of other disease with similar fi ndings (see table below). 336 Pediatrics

DISEASES AND DISORDERS WITH SIMILAR CLINICAL FINDINGS TO KAWASAKI DISEASE

Viral infections (eg, measles, adenovirus, enterovirus, EBV, CMV) Scarlet fever Staphylococcal scalded skin syndrome Toxic shock syndrome Bacterial cervical lymphadenitis Drug hypersensitivity reactions Stevens–Johnson syndrome Juvenile idiopathic arthritis Rocky Mountain spotted fever Leptospirosis Mercury hypersensitivity reaction (acrodynia)

DIAGNOSTIC CRITERIA FOR COMPLETE KAWASAKI DISEASE

≥5 d of fever1, plus four of the ﬁ ve principal features

1. Changes in extremities • Acute: Erythema and edema of hands and feet • Convalescent: Membranous desquamation of ﬁ ngertips 2. Polymorphous rash 3. Bilateral, painless bulbar conjunctival injection without exudate 4. Changes in lips and oral cavity (ie, erythema and cracking of lips, strawberry tongue, diffuse injection of oral and pharyngeal mucosa 5. Cervical lymphadenopathy (≥1.5 cm in diameter), typically unilateral Other clinical fi ndings Cardiovascular ﬁ ndings• Congestive heart failure, myocarditis, pericarditis, valvular regurgitation, and myocardial infarction • Coronary artery abnormalities • Aneurysms of medium-sized noncoronary arteries • Raynaud’s phenomenon • Peripheral gangrene (usually under 1 year of age)

Musculoskeletal• Arthritis, arthralgia (15%; usually less than 2-mo duration)

GI tract• Paralytic ileus • Diarrhea, vomiting, abdominal pain (61%) • Hepatic dysfunction, obstructive jaundice caused by hydrops of the gallbladder

Central nervous system• Extreme irritability (50%; usually responsive to IVIG therapy) • Aseptic meningitis (related to KD or combination of disease and IVIG therapy) • Sensorineural hearing loss, facial palsy • Anterior uveitis (mild)

Genitourinary system• Urethritis/meatitis

(continued on next page) Rheumatology 337

Other clinical fi ndings Other ﬁ ndings• Perineal rash and desquamation • Erythema, induration at previous BCG inoculation site • Beau lines: transverse furrows of ﬁ ngernails in convales- cence phase • Macrophage activation syndrome

1A diagnosis of KD can be made on the fourth day of fever when four out of ﬁ ve criteria are present, or if coronary abnormalities are present in the absence of full criteria. Experienced clinicians who have treated many KD patients may establish diagnosis before day 4. Adapted from Pediatrics 2004;114(6):1708.

• Incomplete Kawasaki Disease: If diagnostic criteria for complete KD are not met, incomplete KD should be strongly considered in the appropriate clinical scenario (see table and “Evaluation of suspected incomplete KD” algorithm below.)

LABORATORY FINDINGS SUGGESTIVE OF INCOMPLETE KD

Elevated acute-phase reactants (CRP ≥3.0 mg/dL or ESR ≥40 mm/hr) White cell count ≥15,000/cells/mm3 Normocytic, normochromic anemia for age (see Hematology chapter) Pyuria: ≥10 WBCs/high-power ﬁ eld (obtained by bag or clean-catch method, not catheterization, since cells are of urethral origin) Serum alanine aminotransferase level >50 U/L Serum albumin ≤3.0 g/dL After 7 d of illness, platelet cell count ≥450,000/μL CSF pleocytosis (LP is not part of the routine KD evaluation)

Adapted from: Pediatrics 2004;114(6):1708.

• Treatment

• IVIG, 2 g/kg given as a single infusion over 10–12 hr. PEDIATRICS • Note: Infants with cardiac compromise may not tolerate volumes, and dividing dose over several days is an appropriate consideration. • Repeat IVIG dose (2 g/kg) if fever does not abate 48 hr from completion of initial IVIG infusion. • If after second dose of IVIG, patient continues with fever, consider corticosteroid therapy with 1–3 days of pulsed IV methylprednisolone (30 mg/kg). • Limited data suggest benefi t from anti-TNF agents (infl iximab or etanercept) for KD refractory to IVIG and corticosteroids. • Aspirin 80–100 mg/kg/day in four divided doses until afebrile for 48 hr → then aspirin 3–5 mg/kg/day once daily until repeat negative echo at 6–8 wk into illness, then stop aspirin. • Caveats • Therapy prior to day 5 of illness may be associated with an increased need for IVIG retreatment, but this should not dissuade the physician from prompt therapy, as this usually indicates ongoing vasculitis/infl ammatory response. • Administration of IVIG should occur for those presenting after the 10th day of illness (ie, earlier missed diagnosis of KD) if persistent signs of infl ammation (ie, fever, ↑ ESR or CRP) or of evolving CAD. • Follow-up imaging • For uncomplicated cases of KD (negative echocardiogram at presentation, adequate response to treatment), obtain repeat echocardiogram at 1–2 wk from 1st day of fever and 6–8 wk from the fi rst day of fever. Consider other modalities of imaging (eg, cardiac MRI) if quality of echocardiogram is suboptimal. 338 Pediatrics

Fever ≥ 5 days and 2 or 3 clinical KD criteria1

Assess Patient Characteristics2

Consistent Inconsistent Persistent with KD with KD Fever

KD Assess Laboratory Tests Unlikely

CRP < 3.0 mg/DL CRP ≥ 3.0 mg/DL and ESR < 40 mm/hr and/or ESR ≥ 40 mm/hr

Follow Daily < 3 Supplemental ≥ 3 Supplemental Laboratory Criteria3 Laboratory Criteria3

Fever Fever Echo Treat and 4 continues resolves Echo for 2 days

No Typical Echo + Echo + 5 Peeling Peeling7

Fever Fever No f/u Echo5 6 Persists Abates Treat

Repeat Echo, KD Consult Unlikely KD Expert

Figure 26-3 Evaluation of suspected incomplete KD. (Reprinted with permission from Pediatrics 2004;114(6):1708.) 1Infants ≤6 mo on day ≥7 of fever without other explanation should undergo laboratory testing; if evidence of systemic infl ammation is found, obtain echocardiogram (even if infant has no other clinical criteria). 2Characteristics suggesting KD are listed in the table “Diagnostic Criteria for Complete Kawasaki Disease”. Characteristics suggesting disease other than KD include exudative conjunctivitis, exudative pharyngitis, discrete intraoral lesions, bullous or vesicular rash, or generalized adenopathy → Consider alternative diagnoses (see the table, “Diseases and Disorders with Similar Clinical Findings to Kawasaki Disease”). 3See the table LABORATORY FINDINGS SUGGESTIVE OF INCOMPLETE KD. 4Do not delay treatment for echocardiogram. 5Echocardiogram is considered positive for purposes of this algorithm if any of the following three conditions are met: (1) z score of LAD or RCA ≥2.5, (2) coronary arteries meet Japanese Ministry of Health criteria for aneurysms, or (3) ≥3 other suggestive features (perivascular brightness, lack of tapering, decreased LV function, mitral regurgitation, pericardial effusion, or z scores in LAD or RCA of 2–2.5) exist. 6If the echocardiogram is positive, treatment should be given to children within 10 d of fever onset and those beyond day 10 with clinical or laboratory signs (CRP, ESR) of ongoing infl ammation. 7Typical peeling begins around nail bed of fi ngers and then nail bed of toes. Rheumatology 339

Coronary Thrombosis Treatment (see Pediatrics 2004;114(6):1708) • Coronary thrombosis management in Kawasaki Disease (see Pediatrics 2004;114(6):1708) • Cardiology consult • Acute therapy includes ﬁ brinolytic therapy (streptokinase, urokinase, or tPA) in a tertiary care center under the supervision of a cardiologist. • Chronic therapy for coronary artery aneurysm (CAA): • Aspirin 3–5 mg/kg/day once daily • Some add dipyridamole or clopidogrel to ASA in those considered high risk. • Some add anticoagulant therapy with warfarin or heparin in combination with antiplatelet therapy for children with severe coronary involvement or past coronary thrombosis.

BENIGN HYPERMOBILITY SYNDROMES • Epidemiology • 10%–25% of the population has hyperﬂ exible joints, not necessarily indicative of congenital syndrome or connective tissue disorders • Age affected: 3–10 yr • ♀:♂ ratio 2:1 • Familial tendency • Diagnosis • Clinical manifestations • Varying degrees of joint laxity without instability or disability • Arthralgia and/or transient mild swelling during the afternoon or night or after activities • Commonly involves lower extremities and larger joints but can involve any joint • Frequent ankle or wrist sprains • Absence of underlying systemic or rheumatic disease

COMMON GENETIC CONDITIONS ASSOCIATED WITH HYPERMOBILITY

• Marfan syndrome • Osteogenesis Imperfecta • Homocystinuria • Williams syndrome

• Stickler syndrome • Trisomy 21 (Down syndrome) PEDIATRICS • Ehlers–Danlos syndrome

• Treatment • Reassurance (symptoms diminish during musculoskeletal maturation occuring in puberty) • Supportive footwear • Strength training and guided exercise • Bracing • Avoidance of hyperextension of joints, but physical activity should not be discouraged • ± NSAIDs or acetaminophen

Available at www.AccessPediatrics.com • Approach to the child with suspected rheumatic disease • Seronegative spondyloarthropathies • Childhood ﬁ bromyalgia • Complex regional pain syndrome • Juvenile dermatomyositis CHAPTER 27 Toxicology

• One to two tablets or 1 to 2 tsp (standard pediatric “swallow” ~5–10 cc) of the standard- strength preparations of the following medications are potentially fatal to a 10-kg child: • Antiarrhythmics, antimalarials (chloroquine, hydroxychloroquine), benzocaine, β-blockers, CCBs, camphor, clonidine, Lomotil (diphenoxylate/atropine), lindane, methyl salicylate, opioids (codeine, morphine, pentazocine), phenothiazines (thioridazine, chlorpromazine), quinine, theophylline, TCAs (imipramine, desipramine) • Nontoxic pharmaceuticals: Antacids, antibiotics, corticosteroids, contraceptives, laxatives, mineral oil, ACE inhibitors • Nontoxic household products: Cosmetics, deodorants, dehumidifying (silica gel) packets, matches, candles

COMMONLY INGESTED AGENTS IN POISONINGS IN CHILDREN YOUNGER THAN 6 YEARS (2005)

Cosmetics or personal care substances 13.4% Cleaning products 9.8% Analgesics 8.2% Foreign bodies 7.4% Topicals 7.2% Cough and cold medicines 5.7% Plants 4.0% Pesticides 4.0% Vitamins 3.9% Antihistamines 2.9%

Data from Clin Toxicol. 2006;44:803.

INITIAL INGESTION EVALUATION (Emerg Med Clin North Am 2007;25:249)

Poisoned patient

Treatment Diagnosis Airway History Breathing Physical examination Circulation Toxidrome recognition Decontamination Diagnostic testing Enhanced elimination Focused therapy Get tox help: Call poison control (800-222-1222)

Figure 27-1 Simultaneous diagnostic and treatment approach to a poisoned patient. (Adapted from Emerg Med Clin North Am 2007;25:249) 340 Toxicology 341

• History: Should address the questions what?, when?, how?, how much?, what symptoms?, and why?: Timing of ingestion, substance(s) taken, amount taken (pill count or volume quantiﬁ cation, if bottle available), location of ingestion (kitchen vs bedroom vs other), reason or circumstances of exposure or ingestion, symptoms before arrival, other substances in the home (possible co-ingestions), concomitant illness or trauma (possible supratherapeutic or chronic dosing of acetaminophen or aspirin), history of depression or prior suicide attempts (in adolescents), history of street drug use.

STREET NAMES OF COMMON DRUGS OF ABUSE

Marijuana: Acapulco gold, bhang, doobie, PCP: Angel dust, goon, horse tranquilizer, hog, ganja, grass, joint, Mary Jane, pot, rope, Sherman, tank, wickie stick (with marijuana) reefer δ-hydroxybutyrate (GHB): Bioski, Georgia Amphetamines: Black beauties, crank, crys- home boy, grievous bodily harm, liquid G, tals, cat (methcathinone), ice, ecstasy, meth, liquid ecstasy, somatomax, cow growth pep pills, smart drug (Ritalin), speed, uppers hormone Ecstasy: Adam, E, lollies, love drug, smarties, Cocaine: All-American drug, coke, crack, vitamin E, XTC girl, mother of pearl, nose candy, Peruvian Heroin: Boy, China white, dust, Harry, horse, powder, snow, toot, white lady junk, monkey, smack, speed ball (with LSD: Acid, blotters, microdots, paper acid, cocaine), atom bomb (with marijuana) pyramids, window pane, Zen

• Anticipate: Seizures, altered mental status, multi-organ dysfunction, respiratory failure, cardiac failure, arrhythmias, or unexplained metabolic acidosis. • Primary survey: See Figure 27-1. • Secondary survey, laboratory investigation: More detailed history and physical exam (including possible abnormal odors), including pulse oximetry and cardiac monitoring, laboratory testing (glucose, electrolytes, anion gap, osmolar gap, baseline CBC and liver panel, urinalysis for hemoglobinuria or myoglobinuria, urine pregnancy test), blood gas (with carboxyhemoglobin if carbon monoxide toxicity is possible), urine drug screen (detects limited number of agents; rarely, color of urine may be helpful), serum drug levels (only to guide therapy or predict toxicity, eg, acetaminophen, salicylates, theophylline, lithium, lead, iron, methemoglobin, toxic alcohols, anticonvulsants, digoxin), chest radiography (if respiratory symptoms present, may identify selected

radiopaque objects), baseline ECG (evaluate QRS duration for TCA, β-blocker, CCB PEDIATRICS toxicity).

AGENTS OF INTOXICATION WITH UNIQUE ODORS

Odor Agent

Wintergreen Methyl salicylate

Garlic Arsenic, DMSO, organophosphate insecticides, selenium

Rotten eggs Hydrogen sulﬁ de, sulfur dioxide

Fresh hay Phosgene

Mothballs Camphor, naphthalene, paradichlorobenzene

Bitter almond† Cyanide

Pears Chloral hydrate, paraldehyde

Fruity Isopropyl alcohol, ketones (diabetic ketoacidosis), phenol

Carrots Water hemlock (cicutoxin)

†30% of the population is unable to detect; Bitter almonds are not readily available in the United States 342 Pediatrics

RAPID URINE TESTING FOR DRUGS OF ABUSE

Duration of Urine Drugs Causing False-Positive Drug Detectability Preliminary Results

Amphetamines 2–3 d Amantadine, bupropion, chlorpromazine, desipramine, ephedrine, phenylephrine, pseudoephedrine, ranitidine, selegiline, trazodone

Cocaine 2–3 d Topical anesthetics containing cocaine-like structure

Marijuana 1–7 d (light use); 1 mo Dronabinol, efavirenz, hemp seed oil, ibupro- with chronic moderate fen, naproxen to heavy use

Opiates 1–3 d Fluoroquinolones, poppy seeds, quinine (tonic water), rifampin

Phencyclidine 7–14 d Dextromethorphan, ketamine

Data from Med Lett 2002;44 (1137):71

URINE COLOR CHANGE ASSOCIATED WITH POISONINGS

Color Substance Responsible

Orange to red-orange Deferoxamine, hydroxocobalamin, lead (chronic poisoning), mercury, phenazopyridine, rifampin

Pink Ampicillin, cephalosporins

Brown Carbon tetrachloride, chloroquine

Blue-green Copper sulfate, methylene blue

ITEMS OF INGESTION DETECTABLE WITH CONVENTIONAL RADIOGRAPHY (CXR, KUB)

Chloral hydrate Iron and other heavy metals Calcium Neuroleptic agents Opiate or cocaine packets Sustained-release or enteric-coated agents

PHYSICAL EXAM FINDINGS OF SELECTED TOXINS*

Symptoms Intoxications Withdrawals

Tachycardia Anticholinergics, sympathomimetics, theophyl- Barbiturates, line, levothyroxine, TCAs benzodiazepines, ethanol

Bradycardia β-blockers, CCBs, cholinergics, cholinesterase inhibitors, clonidine, digoxin, ethanol,∗ opiates

Tachypnea Alcohols, hydrocarbons (chemical pneumonitis), nerve agents, PCP, phosgene, salicylates

Bradypnea Barbiturates, benzodiazepines, ethanol,∗ marijuana, opioids

(continued on next page) Toxicology 343

Symptoms Intoxications Withdrawals

Pulmonary edema Meprobamate, methadone, opioids, paraquat, (noncardiogenic) phenobarbital, phosgene, propoxyphene, salicylates

Hypoxia Benzocaine (secondary to methemoglobinemia), carbon monoxide, opioids, sedative–hypnotics

Hypertension Anticholinergics, caﬀ eine, nicotine, PCP, sym- Ethanol pathomimetics, levothyroxine

Hypotension Antihypertensives, barbiturates, benzodiaz- Barbiturates, epines, ethanol,∗ iron, opioids, rodenticides benzodiazepines, (containing arsenic, cyanide), TCAs ethanol

Miosis Cholinergics, clonidine, organophosphates, opioids, oxymetazoline, phenothiazines, pilocarpine

Mydriasis Anticholinergics, antihistamines, marijuana, Opioid sympathomimetics, TCAs

Hyperthermia Amphetamines, anticholinergics, cocaine, Ethanol MAOIs, neuroleptic malignant syndrome, PCP, salicylates, serotonin syndrome

Hypothermia Barbiturates, benzodiazepines, carbon monoxide, clonidine, ethanol, opioids, oral hypoglycemics, phenothiazines, TCAs

Seizures Amphetamines, anticholinergics, atropine, bu- Barbiturates, propion, caﬀ eine, camphor, carbon monoxide, benzodiazepines, chlorinated hydrocarbons (lindane), cocaine, ethanol cyanide, INH, inhalants, insulin, lead, lidocaine, lithium, methanol∗, mushrooms, nicotine, oral hypoglycemics, organophosphates, PCP, salicylates, strychnine, TCAs, theophylline

Anion gap meta- Alcohols∗ (ethanol,∗ ethylene glycol,∗ metha- PEDIATRICS bolic acidosis (see nol∗), carbon monoxide, cyanide, ibuprofen, Fluid, Electrolyte, INH, iron, metformin, salicylates and Acid–Base Balance, Chapter 15, for more detail)

Hypoglycemia Alcohols,∗ β-blockers, insulin, oral hypoglycemics, salicylates

Acute ataxia or Alcohols,∗ anticonvulsants, (especially pheny- nystagmus toin) antihistamines, barbiturates, carbon monoxide, organic solvents, PCP (rotary nystagmus, versus vertical nystagmus of brainstem lesion)

Emesis, severe Boric acid, corrosives, ﬂ uoride, iron, salicylates, Opioids theophylline

Renal failure Carbon tetrachloride, ethylene glycol,∗ methanol,∗ mushrooms, oxalates

Skin Color Red: Anticholinergics, boric acid, carbon monoxide, cyanide Blue: Methemoglobinemia

(continued on next page) 344 Pediatrics

Symptoms Intoxications Withdrawals

Diaphoresis Organophosphates, PCP, salicylates, sympath- Opioids omimetics

Altered mental Anticonvulsants, antihistamines, antipsychot- Ethanol status ics (risperdone), benzodiazepines (Rohypnol), carbon monoxide, clonidine, cyanide, GHB, ethanol,∗ ethylene glycol,∗ heavy metals (lead), hemlock, INH, insulin, lithium, opioids, oral hypoglycemics, TCAs, thallium, toluene, toxin- induced hepatic encephalopathy

∗ Associated with an increased osmolar gap.

TOXIDROMES

Other Skin and Neurologic Symptoms Mucous or Mental or HR RR Pupils Membranes Status Mnemonic Agents

Adrenergic ↑↑Dilated, Diaphoretic Agitated, ± Hyper- Amphet- reactive psychosis, thermia, amine, delirium tremors, hy- caﬀ eine, pertension, cocaine, hyperreﬂ exia ephedrine, sympathomimetics, theophylline

Anticho- ↑↔Dilated, Dry, ﬂ ushed Depressed, HOT as a Antihis- linergic slug- skin; dry confused, hare, MAD as tamines, gishly mucous hallucina- a hatter, RED atropine, reactive membranes tions, EPS as a beet, belladonna DRY as a alkaloids, bone, BLIND benztro- as a bat: Hy- pine, mush- perthermia; rooms, delirium or phenothi- hallucina- azines, sco- tions; polamine, ﬂ ushed, dry TCAs skin; dilated pupils

Cholin- ↓ Con- Diaphoretic Depressed, DUMBBELLS: Black ergic stricted skin; saliva- confused Diarrhea and widow spi- tion, tearing GI upset, der bites, urination, mush- miosis, rooms, bradycardia, pesticides bronchoc- (carbam- onstriction, ates, or- emesis, ganophos- lethargy, phates), lacrimation, pilocarpine secretions or salivation

(continued on next page) Toxicology 345

Other Skin and Neurologic Symptoms Mucous or Mental or HR RR Pupils Membranes Status Mnemonic Agents

Opioid ↓/↑↓ Con- Dry or no Depressed, Constipation Narcotics stricted change confused or urinary retention, ± hyporeﬂ exia, pulmonary edema

Salicylism ± ↑↑Normal No change Confusion, Nausea, Aspirin, oil seizures, metabolic of winter- tinnitus acidosis green

Sedative– ↔/↓↓ Normal No change Depressed, ± urinary Benzodiaz- hypnotics or con- confused retention, epines stricted constipation, hypotonia

TCAs ↑↑Normal No change Confusion, Ventricular Imipramine, coma, arrhythmia, amitrip- seizures ↓ BP, anti- tyline cholinergic eﬀ ects

OVERVIEW OF ANTIDOTES AND RECOMMENDED INITIAL DOSING IN PEDIATRICS

Toxin Antidote Acetaminophen NAC PO: 140 mg/kg loading dose Then 70 mg/kg Q4h x 17 doses; see acetaminophen toxicity treatment section for IV dosing PEDIATRICS Arsenic, mercury, lead, Dimercaprol: 3–5 mg/kg/dose Q4h (duration depends on degree other heavy metals of intoxication) Benzodiazepines Flumazenil 0.01 mg/kg IV over 30 sec; may repeat q1 min (max dose 0.2 mg or 0.05 mg/kg, maximum of 5 dose series q 30 min; lack of response after ﬁ rst 5-dose series suggests alternate etiology) β-blockers Glucagon 0.05 mg/kg bolus followed by infusion of 0.05 mg/kg/h with vasopressors as needed ∗ Carbon monoxide Mild to moderate (COHb <20%): 100% O2 via nonrebreather mask Moderate to severe (COHb >20%): Hyperbaric oxygen chamber therapy Carbon tetrachloride NAC: Generally same dosing schedule as acetaminophen overdose Digoxin Anti-digoxin antibody: Estimate digoxin antibody vials (each vial is 38 mg) to administer once digoxin reaches steady state (~8h postingestion): (Serum digoxin [ng/mL] × Body weight [kg])/100 Ethylene glycol, Fomepizole: No dosage data in pediatrics, may use: 15 mg/kg methanol IV load; maintenance dose 10 mg/kg Q12h × 4 doses Iron Deferoxamine 15 mg/kg/h infusion Lithium Sodium replacement as needed; low-dose dopamine; hemodialysis

(continued on next page) 346 Pediatrics

Toxin Antidote

Methemoglobinemia Methylene blue: 1–2 mg/kg

Neuroleptics (result- Diphenhydramine: 5 mg/kg divided Q6–8h or benztropine 1–2 mg ing in acute dystonia) IV/IM (adults), 0.02 mg/kg IV/IM (children >3 yrs, max 1 mg; use in children <3 yrs only in life threatening emergencies)

Opioids Naloxone: 0.01 mg/kg upto adult dose of 2 mg IV; may be repeated†

Organophosphates Atropine: 0.05 mg/kg repeated Q5–10 min Pralidoxime: 15–25 mg/kg over 5–10 min; may be repeated after 1–2 h (maximum 1g/dose)

TCAs Sodium bicarbonate: 1–2 mEq/kg repeated to keep pH between 7.45 and 7.55; see table below for other treatments

∗Dissolved serum CO correlates better with neurologic outcomes and candidacy for hyperbaric oxygen therapy, although dissolved serum CO testing is not standard practice. † Half-life of reversal agent is less than the half-life of many opiates; must be monitored and repeated or continuously infused as needed to prevent relapse of intoxication. For opiates with half-lives longer than that of naloxone, the hourly infusion rate is generally two-thirds of the bolus dose required to awaken the patient. Data from Arch Dis Child 2002;87(5):392.

ANTIARRYTHMIC THERAPY USED IN CASES OF POISONING

Contraindicated First-Line Additional Medications Toxin Measures∗ Measures and Measures

Antihistamines Sodium bicarbonate Magnesium sulfate, Class Ia and III propranolol, isoproterenol, ﬂ ecainide, magnesium sulfate

Class I Sodium bicarbonate, Atropine, phenytoin Class I (although antiarrhythmics run mildly alkalotic, lidocaine can be and keep potassium used for arrhythmias low normal caused by Ia and Ic)

Class II Atropine, glucagon, Adrenaline, isopro- Isoproterenol may antiarrhythmics cardiac pacing terenol, dopamine, result in tachyar- dobutamine rhythmias

Class III Amiodarone: Toxicity is Lidocaine for sotalol, antiarrhythmics generally low magnesium sulfate Sotalol: Initial treatment as for other β-blockers

Class IV Calcium gluconate, Atropine, glucagon, antiarrhythmics cardiac pacing dopamine

Cocaine Sodium bicarbonate Diazepam, NTG, cal- β-blockers cium antagonists

Digoxin Correct hyperkalemia Atropine, lidocaine, Class Ia, Ic, DC car- (avoid calcium), amiodarone, phe- dioversion, calcium, digoxin antibodies, nytoin inotropes cardiac pacing

(continued on next page) Toxicology 347

Contraindicated First-Line Additional Medications Toxin Measures∗ Measures and Measures

TCAs Sodium bicarbonate; Phenytoin, atenolol, Class Ia try to avoid other glucagon, lidocaine agents as much as for ventricular ar- possible rhythmias, magnesium sulfate

∗ In all cases, ﬁ rst-line measures include adequate resuscitation, correction of hypoxia or hypercarbia, and evaluation and correction of acid–base or electrolyte disturbances. Data from Arch Dis Child. 2002;87(5):392–399.

TOXIC AMOUNTS OF SELECTED MEDICATIONS

Medication Toxic Amount Acetaminophen Children: Single ingestion of 200 mg/kg or 150–175 mg/kg/day over 2–4 days Adults: Single ingestion of 7.5–10 g or 4 g/d for >2 d Ibuprofen 400 mg/kg Iron 50–60 mg/kg elemental iron; >500 μg/dL serum value at 6 h postingestion Salicylates 150 mg/kg

(SI units) μM/L μg/mL 1000 6000 5000 4000 500 3000

2000

1300 200 1000 900 150 800 700 600 100 500 Probable hepatic toxicity

400 PEDIATRICS 50 300 Possible hepatic toxici 250 200

No hepatic toxicity 100 90 80 ty 70 60 10

Acetaminophen plasma concentration 50 40 25% 30 5

04812 16 20 24 Hours after ingestion Figure 27-2 Nomogram for prediction of acetaminophen hepatotoxicity after acute overdose. Note: The upper line deﬁ nes serum acetaminophen concentrations likely to be associated with hepatotoxicity; the lower line deﬁ nes serum levels 25% below those expected to cause hepatotoxicity. (Reprinted with permission from Olson KR: Poisoning & Drug Overdose, 5th ed. New York: McGraw-Hill. Copyright © The McGraw-Hill Compa- nies, Inc. All rights reserved.)

Available at www.AccessPediatrics.com • Acetaminophen toxicity • GI decontamination, including activated charcoal, orogastric lavage, whole-bowel irrigation Section 4: Neonatology

CHAPTER 28 Newborn Nursery

Neuromuscular maturity

-1012345

Posture

Square window (wrist) >90° 90° 60° 45° 45° 30°

140° 110° 90° Arm recoil to to to 0° 180° 180° 140° 110°

Popliteal angle 90° <90° 180° 160° 140° 120° 100°

Scarf sign <90°

Heel to ear

Total Neuromuscular Maturity Score

Physical maturity -1012345

Skin Stickey, friable, Gelatinous, Smooth, pink, Superficial Cracking, pale Parchment, Leathery, transparent red, visible veins peeling &/or areas; rare deep cracking; cracked, translucent rash; few veins veins no vessels wrinkled Lanugo None Sparse Abundant Thinning Bald areas Mostly bald Plantar Heel toe 40–50 > 50 mm: no Faint red marks Anterior Creases Creases over surface mm: −1 < 40 crease transverse anterior 2/3 entire sole mm: −2 crease only Breast ImperceptibIe Barely Flat areola; no Stippled areola; Raised areola; Full areola; 5- to perceptible bud 1- to 2-mm 3- to 4-mm 10-mm bud bud bud Eye/Ear Lids fused Lids open; Slightly curved Well-curved Formed & firm Thick cartilage; loosely: −1 pinna flat; pinna; soft; slow pinna; soft but instant recoil ear stiff tightly: −2 stays folded recoil ready recoil Genitals Scrotum flat, Scrotum empty; Testes in upper Testes Testes down; Testes (male) smooth faint rugae canal; rare descending; few good rugae pendulous; deep rugae rugae rugae Genitals Clitoris Prominent Prominent clitoris Majora & Majora large; Majora cover (female) prominent & clitoris & small & enlarging minora equally minora small clitoris & minora labia flat labia minora minora prominent Total physical maturity score Figure 28-1 New Ballard score for assessment of fetal maturation of newly born infants. (Reproduced with permission from Ballard JL, et al: New Ballard score, expanded to include extremely premature infants. J Pediatr 1991;119:417. New York: McGraw-Hill. Copyright © The McGraw-Hill Companies. All rights reserved.)

ROUTINE NEWBORN CARE Hearing Screen • Mandated ABER or OAE testing prior to 3 months. Bathing • Sponge bath until cord stump falls off. Feeding • Encourage breastfeeding within 1 hr of birth and formula within 3 hr if baby is alert, has no abdominal distension or respiratory distress, and has a good cry. Newborn Nursery 349

APGAR SCOREa 0 12 Heart rate Absent Slow (< 100) >100 Respiratory effort Absent Slow, irregular Good, crying Muscle tone Limp Some flexion Active motion Response to catheter No Grimace Cough or in nostrilb response sneeze

Color Blue or pale Body pink; extremities Completely pink blue

Figure 28-2 Infant evaluation at birth—Apgar score. (Reproduced with permission from Hay WW Jr, Levin MJ, Sondheimer JM, Deterding RR: Current Diagnosis & Treatment: Pediatrics, 19th ed. New York: McGraw-Hill. Copyright © The McGraw-Hill Companies. All rights reserved.) aOne minute and 5 minutes after complete birth of the infant (disregarding the cord and the placenta), the following objective signs should be observed and recorded. bTested after the oropharynx is clear.

• Term babies take 0.5–1 oz q2–4hr initially. • Breastfeeding should occur q1-3hr (see Chapter 4).

Eyes • 0.5% erythromycin ointment to both eyes within 2 hr after birth for prophylaxis against ophthalmia neonatorum.

Vitamin K • 0.5–1 mg IM within 6 hr of life to prevent hemorrhagic disease of the newborn.

Stool • Meconium within 48 hr of life.

Urine • Void within 30 hr of life.

Umbilical cord • Triple dye, then keep cord clean and dry until stump falls off (average 6–14 DOL).

Nails • Keep short with emery board or baby nail clippers.

Sleep • Back to sleep to reduce the risk of SIDS. NEONATOLOGY EARLY DISCHARGE CRITERIA (<48 H OF LIFE) (institutional practice; adapted from Pediatrics 2010;125(2):405) • 37-41 completed weeks’ gestation • No ﬁ ndings that require continued hospitalization. • Vital signs documented as normal (see “Newborn Exam” above). 350 Neonatology

• Infant has urinated regularly and passed at least one stool spontaneously. • Infant has completed at least 2 successful, consecutive feeds • No signiﬁ cant bleeding at circumcision site • Risk of development of hyperbilirubinemia has been assessed and appropriate follow up arranged. • Infant has been appropriately screened for sepsis on the basis of maternal risk factors (including GBS status and adequacy of antepartum prophylaxis). • Maternal labs have been reviewed and found to be normal/negative (RPR, Hepatitis B surface antigen, HIV and GBS). • Infant blood work, such as blood type, Coombs, have been reviewed (as clinically indicated) • Initial hepatitis B vaccine administered • Newborn metabolic and hearing screens have been completed per state regulations. • Mother is able to provide adequate newborn care upon discharge (including feeding, normal urination/stooling patterns, cord, skin, and genital care, able to identify signs of illness, identify jaundice, and understands basic infant safety (eg, car seat safety, supine positioning for sleep) • Maternal social and environmental risk factors are assessed (substance abuse, homelessness, abuse or neglect, domestic violence, etc.) • A medical home for the infant is established (infants discharged <48 hours of age will follow up within 48-72 hours of discharge). • Any potential barriers to follow up have been identiﬁ ed and addressed (lack of transportation, no access to telephone services, language barriers, etc.) CIRCUMCISION Circumcision Care • Clean routinely with mild soap and water. • Apply petroleum jelly to the site following circumcision for 3–5 d to prevent adhesions. • Observe frequently for signs of bleeding. • Infant should void within 8–12 hr after circumcision. Care of the Uncircumcised Penis • Clean externally with mild soap and water. • Forceful retraction of the foreskin should not be attempted. • Parents should be advised that for several months to years, the foreskin will adhere to the glans penis. • Once the foreskin is easily retractable, it should be retracted during bath time to clean the glans. (Pediatr Rev 2006;27:477.)

THE NEWBORN NURSERY The Newborn Exam ROUTINE NEWBORN EXAM

Physical Exam Component Look for…

Observation Signs of respiratory distress, abnormalities in tone and/or color

Palpate anterior and posterior Large or bulging fontanelles fontanelles

Palpate skull and sutures Overlapping/separated sutures, craniotabes

Face Dysmorphisms, asymmetry

Eyes Set and position, red reﬂ ex, pupillary reﬂ exes

(continued on next page) Newborn Nursery 351

Physical Exam Component Look for…

Ears Set and position, pits, tags, malformations, patent ear canals

Nose Nasal ﬂ aring, asymmetry, obstruction, dislocation

Mouth, including buccal mucosa, Rooting refl ex, suck refl ex, natal teeth, Epstein pearls, tongue, palate and posterior pharynx cleft lip and/or palate, gag refl ex

Neck Redundant skin folds, masses, branchial cleft cysts/ remnants

Skin Birthmarks, hemangiomas, jaundice, plethora/pallor, meconium staining, rashes, bruising

Inspect and palpate precordium Active or quiet precordium

Palpate for PMI Displaced PMI or dextrocardia

Auscultate with bell and diaphragm; Cardiac murmurs, arrhythmias, clicks, rubs count HR for 1 min

Observe respirations; auscultate Equality of breath sounds, crackles, stridor, wheezes; lungs; count RR for 1 min screen for bowel sounds in the chest

Inspect thorax and clavicles Asymmetry, accessory nipples; palpate clavicles for crepitus

Palpate breast tissue Gynecomastia, masses, asymmetry

Auscultate abdomen in four Bowel sounds in all areas quadrants

Palpate abdomen—light and deep Organomegaly, masses, enlarged kidneys, diastasis rectus, umbilical hernias

Examine umbilical cord and count Odor, edema, erythema, discharge, bleeding vessels

Palpate axillary and inguinal regions Lymphadenopathy

Palpate brachial and femoral pulses Discrepancy or asymmetry in pulses, brachial-femoral delay

Inspect genitalia—female Hymenal tags, imperforate hymen, masses, bleeding, discharge, clitoromegaly

Inspect genitalia—male Undescended testes, masses, hydroceles, hernias, hypospadius, microphallus

Barlow and Ortolani maneuvers Hip clicks or clunks, hip dislocations

Inspect buttocks and posterior legs Asymmetric skin folds, leg length discrepancies, while infant is prone imperforate anus

Inspect spine while infant is prone Sacral dimples or defects, scoliosis, kyphosis, bony abnormalities, hair tufts

Extremities and digits Range of motion, malformations, count digits, NEONATOLOGY examine palmar creases

Reﬂ exes Rooting, Moro, clonus, Babinski, plantar and palmar grasps 352 Neonatology

Caput Succedaneum Cephalohematoma Subgaleal hemorrhage Extradural Skin hemorrhage Epicranial aponeurosis Periosteum Skull Dura

Figure 28-3 Sites of extracranial bleeding in the newborn. (Reproduced with permission from Hay WW Jr, Levin MJ, Sondheimer JM, Deterding RR: Current Diagnosis & Treatment: Pediatrics, 19th ed. Available at http://www. accessmedicine.com. New York: McGraw-Hill. Copyright © The McGraw-Hill Companies. All rights reserved.)

Common Problems Encountered in the Newborn Nursery STRIDOR

Diﬀ erential• Tracheomalacia, laryngomalacia, foreign body, airway edema, airway obstruction, subglottic stenosis, craniofacial dysmorphisms, vocal cord paralysis, esophageal abnormalities, compression by vascular ring/sling

Evaluation• Pulse oximetry, CXR, lateral neck ﬁ lms; consider direct laryngoscopy, airway ﬂ uoroscopy, and/or barium swallow

Management• Consider otolaryngology consult; prepare for intubation if patient in distress

VOMITING∗

Diﬀ erential• GER • Overfeeding (more common with bottle feeding) • Obstruction: malrotation with volvulus, duodenal atresia, esophageal atresia • NEC • Inborn error of metabolism

Evaluation • Review feeding notes/documentation, serial abdominal exams, abdominal radiograph series; consider upper GI series and/or abdominal ultrasound; consider chemistry panel and/or blood gas

Management• If vomiting is mild and no pathology is seen on imaging, may observe • If obstruction diagnosed: place PIV, start maintenance IV ﬂ uids NPO, place NG tube, obtain surgery consult • If NEC diagnosed: place PIV, start MIVF, NPO, place NG, draw cultures, start broad-spectrum antibiotics, obtain surgical consult, order serial abdominal radiographs

∗Bilious emesis in an infant is malrotation until proven otherwise Newborn Nursery 353

RESPIRATORY DISTRESS

Diﬀ erential• Pulmonary pathology: TTN, pulmonary edema, HMD/surfactant deﬁ - ciency, persistent pulmonary hypertension, meconium aspiration, airway obstruction, pneumothorax • Infection: pneumonia, sepsis • Congenital malformation: CHD, CDH, malformation of lung parenchyma, chest wall deformities • Inborn errors of metabolism: compensatory respiratory alkalosis from primary metabolic acidosis Evaluation• Auscultation, CXR, pulse oximetry and cardiopulmonary monitors, ABG • Consider sepsis evaluation • Consider ECG/ECHO Management• Suction, NPO, and MIVF; consider oxyhood, NCPAP, or intubation and PPV • Endotracheal surfactant replacement as necessary (especially in HMD or meconium aspiration) • Needle decompression and/or chest tube for pneumothorax • Treatment for sepsis; correction of metabolic acidosis • If CDH antenatally diagnosed: avoid BMV, intubate, and start PPV; prepare for ECMO

CYANOSIS∗

Diﬀ erential• Pulmonary disorder: hypoxemia from respiratory insuﬃ ciency or failure, apnea, pneumothorax • Airway obstruction, choanal atresia • Cardiovascular disorder: cyanotic CHD, persistence of the fetal circulation • Infection: sepsis, shock, circulatory collapse • Severe hypoglycemia Evaluation• Auscultation, inspect nares, CXR, cardiopulmonary monitoring, pre- and postductal pulse oximetry, CBC, WBG, ABG, ECG, ECHO, hyperoxia test Management• Oxygen, NPO, place PIV, start MIVF; consider NCPAP/intubation and PPV; consider sepsis evaluation

∗Peripheral cyanosis (acrocyanosis) is a common occurrence in the newborn, especially in the hours following delivery, and may persist for several days.

Nonsterile Delivery • A nonsterile delivery with nonsterile umbilical cord care may put the infant at risk for neonatal tetanus, although the risk is low in the United States. Most mothers with adequate tetanus vaccination status have adequate tetanus antibodies that provide passive immunization to the newborn. • Management: If the umbilical cord was cut in a nonsterile fashion, then wound prophylaxis with 250 U of human tetanus immune globulin (TIG) is recommended, to be given as soon as possible following delivery (IVIG should be given if TIG is unavailable). In addition, the baby should receive tetanus toxoid vaccine (Td). NEONATOLOGY

Available at www.AccessPediatrics.com • Circumcision • Newborn exam abnormalities CHAPTER 29 Fetal Assessment and Prenatal Diagnosis

ROUTINE PRENATAL CARE Screening US • First trimester: Routine screening of an unselected population allows for better estimation of GA, leading to reduced frequency of labor induction for postterm labor and use of tocolysis for suspected preterm labor; detection of multifetal pregnancies, and anatomic “markers” suggestive of increased risk for chromosomal abnormalities or fetal malformations (see below). • Second trimester (anatomy scan): Allows detection of 50%–60% of all congenital anomalies with experienced users. Ideally performed between 18–20 wk gestation. • Third trimester: Current data do not support the routine use of US in the third trimester.

Aneuploidy Screening • : Routinely offered to all pregnant women (see screening for fetal chromosomal anomalies below).

Assessment of Gestational Age • Initial assessment of GA is made based on a careful menstrual history. • The estimated date of conﬁ nement (EDC) or estimated date of delivery (EDD) is calculated by adding 7 d to the ﬁ rst day of the LMP and then counting back 3 mo. • Note that conceptual age is not equivalent to GA. For an idealized 28-d menstrual cycle, ovulation occurs approximately 2 wk after the LMP. • This leads to frequent confusion in terminology both before and after delivery.

Postmenstrual age

Chronological age Gestational age Date of assessment Birth Conception day of LMP day of delivery st Expected date 1 Corrected age

Figure 29-1 Summary of age terminology in the perinatal period.

354 Fetal Assessment and Prenatal Diagnosis 355

Assessment of Fetal Lung Maturity • Fetal lung maturity should be assessed before elective delivery at less than 39 wk unless lung maturity can be inferred from any of the following: • Fetal heart tones have been documented for at least 20 wk by non-electronic fetoscope or at least 30 wk by Doppler. • 36 wk have elapsed since a serum or urine hCG pregnancy test result was reported to be positive. • US dating during ﬁ rst or second trimester supports a GA of 39 wk or greater.

EVALUATION OF FETAL LUNG MATURITY

Predictive Predictive Value for Value for Maturity Immaturity Can Threshold When Test When Test Pooled Value to Shows Shows Aff ected by Vaginal Indicate Maturity Immaturity Relative Blood or Specimen Test Maturity (%) (%) Cost Meconium? Be Used?

L:S ratio >2.0 95–100 33–50 High Yes No

PG If present, 95–100 23–53 High No Yes (bac- indicates teria may maturity cause false- positive)

FSI >47–48 95 51 Low Yes No

FLM-TDx >55 mg/g 96–100 47–61 Moderate Yes Yes

Lamellar ≥50,000 97–98 29–35 Low Blood only Unknown body count

Adapted from ACOG Practice Bulletin No. 97: Fetal Lung Maturity. Obstet Gynecol 2008;112:717.

THE FETAL ENVIRONMENT: MATERNAL MEDICAL CONDITIONS Diabetes Mellitus During Pregnancy • Fetal complications of maternal DM • Congenital anomalies • Incidence, 5%–10%; two to four times the control population • Caudal dysplasia (sacral agenesis): 200- to 400-fold increase • Neural tube defects: 10-fold increase; anencephaly, myelomeningocele • Congenital heart disease: Fivefold increase; hypertrophic cardiomyopathy, VSD, transposition of the great arteries • Macrosomia: Increased risk of cephalopelvic disproportion, traumatic delivery, Erb’s palsy • Polyhydramnios: 15% incidence • IUGR: Only in mothers with very poorly controlled diabetes, with a diabetic vasculopathy of the placental vessels, leading to poor placental growth NEONATOLOGY • Hypoxia • Intrauterine fetal demise: Stillbirth rate increases when postprandial glucose level is >120 mg/dL • Perinatal mortality • Increased risk of developing type II DM later in life 356 Neonatology

Hypertension in Pregnancy • Deﬁ nitions • Preeclampsia: New-onset hypertension (BP >140/90 mm Hg or MAP >105) with proteinuria (>30 mg/dL or +1 in a random specimen or 300 mg in a 24-h specimen) ± edema • Eclampsia: Development of convulsions or coma in the setting of preeclampsia • Gestational hypertension: Hypertension occurring after the 20th week of pregnancy or during the ﬁ rst 24 hours postpartum without evidence of preeclampsia • Chronic hypertension: Hypertension diagnosed before pregnancy or before the 20th week of pregnancy; or hypertension diagnosed during pregnancy but persisting beyond the 42nd postpartum day • Superimposed preeclampsia: Worsening of hypertension (increase in SBP >30 mm Hg or DPB >15mm Hg) or increase in the degree of proteinuria in a pregnant patient with chronic hypertension

SEQUELAE OF MATERNAL HYPERTENSION IN NEONATES

System Findings Clinical Manifestations

Cardiovascular Increased cardiac output, systemic Systemic hypertension, intravas- vasoconstriction, and hypertension cular hemolysis Increased hydrostatic pressure Generalized edema

Uteroplacental Uteroplacental insuﬃ ciency Fetal somatic growth deﬁ ciency; fetal hypoxemia and distress Decidual ischemia Abruptio placentae; placental infarcts Decidual thrombosis Thrombocytopenia

Renal Decreased renal blood ﬂ ow and GFR; Proteinuria; elevated Cr, de- endothelial damage creased Cr clearance; oliguria High AT-II responsiveness of tubular Elevated uric acid vasculature All of the above ATN, renal failure

Cerebrovascular Cerebral motor ischemia Eclampsia (seizures) High CPP with regional ischemia Cerebral hemorrhage Cerebral edema Coma Regional ischemia Central blindness; loss of speech

Hepatic Ischemia; hepatocellular injury Elevated LFTs Mitochondrial injury Intracellular fatty deposits

Hematologic Intravascular hemolysis Schistocyte burr cells; elevated free hemoglobin and iron; decreased haptoglobin levels Decidual thrombosis, release of ﬁ brin Thrombocytopenia; antiplatelet degradation products antibodies

• Fetal and neonatal complications • Prematurity (often caused by medical intervention) • Uteroplacental insufﬁ ciency → fetal somatic growth deﬁ ciency, fetal hypoxemia or distress • Abruptio placentae Fetal Assessment and Prenatal Diagnosis 357

FETAL AND NEONATAL COMPLICATIONS OF MATERNAL MEDICAL CONDITIONS

Maternal Medical Maternal Complications Fetal and Neonatal Condition During Pregnancy Complications DM Hypoglycemia; DKA; hyperten- Hypoglycemia, macrosomia, sion; progression of diabetic birth trauma, IUGR, hypoxia, retinopathy; polyhydramnios; caudal dysplasia, congenital cephalopelvic disproportion; heart defects, neural tube increased risk of malpresenta- defects, intrauterine fetal tion, cesarean section, and demise operative vaginal delivery Hypertension Generalized edema, intravascular IUGR, fetal hypoxemia and hemolysis, thrombocytopenia, distress, prematurity renal insuﬃ ciency, proteinuria, seizures, cerebral hemorrhage, coma, central blindness, elevated liver enzymes, abruption placentae, preterm labor Hypothyroidism First trimester miscarriage, IUGR, suboptimal neurodevel- preeclampsia, placental opmental outcome abruption, preterm delivery, postpartum hemorrhage Substance abuse Tobacco: Perinatal death, Tobacco: Growth restriction, spontaneous abortion, stillbirth, increased risk of SIDS and abruption placentae, placenta respiratory diﬃ culties previa, premature delivery Cocaine: Abruption placentae, Cocaine: IUGR, adverse neu- spontaneous abortion, prema- rodevelopmental outcomes ture rupture of membranes

SONOGRAPHIC AND FETAL ECHOCARDIOGRAPHIC ASSESSMENT Antenatal Ultrasonography • Indications: • Dating pregnancy: If no reliable dating is available, discrepancy between uterine size and date (suspected IUGR; suspected large-for-dates pregnancies) • Fetal and placental location: Conﬁ rm pregnancy, suspected missed abortion, suspected ectopic pregnancy, suspected placenta previa, before prenatal diagnostic or interventional procedures • Survey of fetal anatomy: History of malformation, advanced maternal age, diabetic pregnancy, polyhydramnios and oligohydramnios, abnormal presentation, exposure to teratogens, abnormal maternal serum screen • Fetal anomalies detected by antenatal US • CNS: Fetal ventriculomegaly, meningomyelocele and type II Chiari malformation, anencephaly, encephalocele, Dandy-Walker cyst, choroid plexus cyst, holoprosencephaly • Spine: Diastematomyelia, sacrococcygeal teratoma • Head and neck: Gross craniofacial abnormalities, cystic hygroma, increased nuchal translucency, teratoma and lymphangioma NEONATOLOGY • Thorax and heart: Intrathoracic mass (cystic adenomatoid malformation, pulmonary sequestration and diaphragmatic eventration), diaphragm hernia, laryngeal atresia, CHAOS, cardiac malformations and tumors • GI tract: Esophageal atresia and tracheoesophageal ﬁ stula, bowel obstruction, anterior abdominal wall defects, diaphragmatic hernia, choledochal cyst, heterotaxy • GU tract: Pelviectasis, hydronephrosis, renal agenesis, multicystic kidneys, renal dysplasia or duplication, lower urinary tract obstructions, ambiguous genitalia • Musculoskeletal system: Skeletal dysplasias, arthrogryposis, phocomelia 358 Neonatology

Fetal Echocardiography • Speciﬁ c familial, fetal, and maternal indications for prenatal fetal echocardiograms exist (J Am Soc Echocardiogr 2004;17(7):803).

SERUM SCREENING FOR FETAL CHROMOSOMAL ABNORMALITIES CHANGES OBSERVED IN ANEUPLOIDIES AND OTHER FETAL ANOMALIES

Neural Tube Serum Marker Trisomy 21 Trisomy 13 Trisomy 18 Defects Second Trimester

AFP ↓ Normal ↓↑

hCG ↑ Normal ↓∗

Unconjugated estriol ↓ Normal ↓∗

Inhibin-A ↑ Normal ∗∗ First Trimester

PAPP-A ↓∗ ↓∗

hCG ↑∗ ↓∗

∗Value not typically used for estimating the risk of this disorder. D, decreased; I, increased; N, no change; N/A, not applicable.

• US fi nding of aneuploidy • Nuchal measurements: Nuchal translucency at 11–14 wk (sagittal view) and nuchal fold at 15–20 wk (axial view); the size of fl uid collection at the back of a fetus’s neck is increased in several chromosomal abnormalities. • Short femur and/or humerus. • Absent nasal bone. • Congenital heart defects. • Other fi ndings are more commonly seen in aneuploidy but are neither sensitive or specifi c: Hydrops, major malformation (omphalocele, holoprosencephaly, CDH, ONTD), echogenic bowel, intracardiac echogenic focus, dilated renal pelvis.

PRENATAL GENETIC DIAGNOSIS Amniocentesis • Typically performed at 16–18 wk GA. • Success rate of single procedure, >95%; success rate of establishing cell cultures from amniotic ﬂ uid cells, >99%. • Cytogenetic analysis can be completed 7–12 d after procedure. • Complications: Chorioamnionitis (<1 in 1000 procedures), leakage of amniotic ﬂ uid (1 in 300–500 procedures), bleeding, fetal injury, fetal loss. The risk of fetal loss is <1 in 200–400 or ~0.25%–0.5% above pregnancy losses in control studies matched for maternal age.

Chorionic Villus Sampling (CVS) • Biopsy of the villa of the developing placenta. • Usually performed at 10–14 wk GA. • Approaches • Transcervical: Fine catheter passed through vagina and cervical os to biopsy the chorion frondosum Fetal Assessment and Prenatal Diagnosis 359

• Transabdominal: Patient perception of procedure similar to that of amniocentesis • Cytogenetic analysis can be performed directly on tissues obtained (cytotrophoblastic layer of villi); no cell culture is necessary. • Higher rate of maternal cell contamination and mosaicism than amniocentesis (0.6% vs 0.3%). • Complications resulting in fetal loss after CVS: Infection, PROM, placental disruption. • Pregnancy losses attributable to CVS occur at 0.5–2.0% above the background rate of 2.5–3.0% of pregnancies. • Risks of CVS: in experienced hands, the loss rates have been found to be no higher than that seen after mid-trimester amniocentesis. • Limb reduction defects were initially reported as a complication of CVS; these defects are rare and seem to be limited to CVS performed before 66 days GA, use of a large catheter or recovery of a large sample of villi, and inexperienced operators. Fetal Blood Sampling (Percutaneous Umbilical Blood Sampling, Cordocentesis) • Limited to pregnancies >19 wk GA. • 20- to 22-gauge needle inserted into umbilical vein under US guidance • Indications • Need for rapid cytogenetic analysis (within 48–72 h); rarely performed • Measurement of factor VIII levels when other prenatal diagnostic tests of hemophilia A are inconclusive • Measurement of serum enzyme levels in various metabolic disorders • Measurement of hemoglobin and possible RBC transfusion in cases of fetal anemia or hydrops Fetal MRI • Fetal MRI is now being used to better characterize structural anomalies noted on screening US or to more carefully evaluate a fetus at higher risk of such anomalies. PRENATAL DIAGNOSIS OF SPECIFIC DISORDERS • A wide variety of genetic and metabolic disorders can be tested for prenatally using one or more of the above mentioned approaches or technologies. • A comprehensive, up-to-date catalog of tests available for many conditions and the labs that conduct these tests may be found at http://www.genetests.org. ANTEPARTUM FETAL SURVEILLANCE • Aimed at reducing rate of intrauterine fetal death from 28 wk onward. • <1% of these deaths result from sudden catastrophic events (eg, cord prolapse, abruptio placentae), which will not be predicted or prevented by antenatal surveillance. • Other conditions, however, place the fetus at increased risk of death from chronic uteroplacental insufﬁ ciency. Surveillance in these cases may allow early detection of fetal distress and intervention to prevent adverse outcomes. INDICATIONS FOR ANTENATAL SURVEILLANCE

Maternal

Antiphospholipid antibody syndrome Oligohydramnios

Hyperthyroidism (poorly controlled) Polyhydramnios

IDDM IUGR NEONATOLOGY

Cyanotic heart disease Multiple gestations

SLE Postterm pregnancy

(continued on next page) 360 Neonatology

Maternal

Hypertension Previous fetal demise (unexplained or recurrent)

Chronic kidney disease Isoimmunization (moderate to severe)

Hemoglobinopathies PPROM

Pregnancy-induced hypertension Unexplained third trimester bleeding

Decreased fetal movement Fetal Gastroschisis S/p fetal shunting procedures

Intrathoracic chest mass or CDH Monochorionic twins

Selective heart defects, arrhythmias

Non-stress Test • First-line assessment of fetal well-being in nonlaboring patients. • Reactive test: At least two accelerations of fetal HR >15 bpm above baseline and last at least 15 seconds in a 20 minute period of monitoring. • Nonreactive NST: During a 20-min time period, two such accelerations do not occur or are <15 sec. • High false-positive rate. • Combination of the NST with a measurement of amniotic fl uid volume (amniotic fl uid index; see below) reduces the false-positive rate (referred to as the modifi ed biophysical profi le [modifi ed BPP]). Contraction Stress Test • Evaluates response to maternal uterine contractions. • Contractions may be occurring spontaneously or may be induced mechanically (eg, nipple stimulation) or pharmacologically (eg, IV oxytocin). • Performed by observing at least three contractions lasting 40 seconds within a 10-min period • Negative CST result: No late decelerations observed, or signifi cant variable decelerations noted. • Positive CST result: Late decelerations present after ≥50% of the contractions. • Equivocal CST result: Late variable decelerations are present but after <50% of contractions, or signifi cant variable decelerations are noted. Biophysical Profi le • Combines NST with four observations made by US over a 30-min period. • A score of 2 is given for each component that is present and 0 for each that is absent. • BPP can be done without NST; in this circumstance, max score would be 8/8.

BIOPHYSICAL PROFILE SCORE

Component Observation (2 points if present, 0 points if absent)

Fetal breathing ≥1 episode of at least 30 sec

Fetal movement ≥3 discrete body or limb movements

Fetal tone ≥1 episode of active extension with return to ﬂ exion of a limb or trunk, or the opening or closing of a fetal hand

Amniotic ﬂ uid volume Single vertical pocket at least 2 cm deep

NST Reactive test Fetal Assessment and Prenatal Diagnosis 361

INTERPRETATION OF BIOPHYSICAL PROFILE SCORE

Score Interpretation Intervention

8–10 Reassuring No special action needed

6 Equivocal Repeat testing in 24 h if preterm; delivery if term

0–4 Abnormal Delivery, except under extenuating circumstances

INTRAPARTUM FETAL MONITORING Fetal Heart Rate (FHR) Monitoring • Primary method of assessment of fetal well-being. • A non-reassuring FHR tracing is highly sensitive for the detection fetal distress but is quite nonspeciﬁ c. • No proven beneﬁ t in outcome from use of FHR monitoring. • Interpretation of FHR • Baseline fetal HR • Usually 120–160 bpm • Fetal tachycardia: Hypoxia, maternal fever, intra-amniotic infection, thyroid disease, drugs, fetal cardiac arrhythmia • FHR variability (variation in successive beats of HR): The result of CNS input and is an indicator of fetal CNS integrity • FHR reactivity: Compared with FHR variability, these are larger amplitude changes in FHR that occur over longer periods of time (accelerations; early, variable, and late decelerations)

SUMMARY OF FETAL HEART RATE PATTERNS AND IMPLICATIONS

FHR Finding Description Mechanism Interpretation

Accelerations Increase in the Physiologic fetal re- Reassuring fetal HR sponse to movement

Early Shallow and sym- Fetal head compres- Uncommon; generally not decelerations metric; occur at time sion during labor concerning of contraction

Variable Slowing of the FHR Umbilical cord com- Nonreassuring features in- decelerations with abrupt onset pression clude deceleration to <70 and return bpm, duration >60 sec, associated with change in baseline or decreased variability

Late Decrease in FHR Transient fetal hypoxia Occasional or intermittent decelerations below baseline after caused by decreased late decelerations are com- contraction placental perfusion mon; when persistent, are with contractions nonreassuring

Sinusoidal HR Sinusoidal pattern Unknown Rare; associated with

lasting ≥10 min; severe chronic fetal NEONATOLOGY relatively ﬁ xed pe- anemia, medications (eg, riod of three to ﬁ ve alphaprodine), severe cycles/min and an hypoxia, and acidosis amplitude of 5–15 bpm above and below baseline 362 Neonatology

Management of Nonreassuring Fetal Heart Tones (NRFHT) • Maternal position: Lateral recumbent (either side). • Fetal stimulation: Directly with digital examination (intrapartum) or acoustic (antepartum). • Oxygen therapy: Administration of supplemental oxygen to the mother. • Amnioinfusion: After ruling out prolapsed cord or rapid fetal descent by pelvic exam, replacement of amniotic ﬂ uid with normal saline may be considered for signiﬁ cant variable or prolonged decelerations. • Tocolytic agents: Excessive uterine contractions resulting in a NRFHT may be managed with terbutaline or magnesium sulfate.

Available at www.AccessPediatrics.com • Estimating fetal age with sonography • Fetal interventions • Multiple gestation pregnancies NEONATOLOGY ow ow ensure must rm endotra- rm Remember that volutrauma ating the lungs; you should → hemorrhage Acute fetal/placental Poly/oligohydramnios Preeclampsia Intrauterine growth restriction Emergent cesarean delivery detector to confi 2 • • • • • 363 cant lung injury. Fetal arrhythmia Evidence of fetal distress Thick meconium Hydrops fetalis Maternal diabetes Multiple gestation • • • • • • The catheter should be placed only as far as necessary to obtain free The catheter should be placed only as far as necessary to obtain → and appropriately sized facemasks for the anticipated delivery: ating bag ow of blood. Preterm delivery Narcotics in labor Maternal infection Postterm delivery Fetal malformation Uterine tetany cheal intubation). and barotrauma can cause signifi an adequate seal is formed around the infant’s mouth to ensure the pressure being an adequate seal is formed around the infant’s mouth to ensure delivered is transmitted to the airway. fl venous access available. provide enough pressure to achieve adequate chest rise VLBW or EBLW infants Flow infl and the bag is connected to an oxygen source. A fl Be sure PEEP is set correctly internal diameters], appropriate sizes of endotracheal tubes [with 2.5-, 3.0-, and 3.5-mm stethoscope, suction catheters with suction source, CO meter, adequate tubing length, and oxygen blender may be necessary, as well as a and oxygen blender may be necessary, as well as a meter, adequate tubing length, important in the pulse oximeter to monitor oxygen saturation. This is particularly congenital cardiac resuscitation of ELBW/VLBW infants and infants with known may need to be disease (both scenarios in which excessive oxygen administration avoided). Bulb suction. An emergent umbilical venous catheter can be placed as indicated to provide immediate An emergent umbilical venous catheter can be placed as indicated Use extreme caution when providing PPV to avoid overinfl access is not readily Epinephrine can be administered via endotracheal tube if venous Materials for endotracheal intubation (laryngoscope with Miller 00, 0, and 1 blades; Materials for endotracheal intubation (laryngoscope with Miller Transport incubator with transport monitors. or mask, you When providing positive-pressure ventilation (PPV) with a bag Radiant warmer: Should be turned on and pre-warmed to prevent rapid heat loss in Radiant warmer: Should be turned • • • • • • Caveats: Situations in which resuscitation may be expected: Situations in which resuscitation in advance of known high-risk deliveries. Equipment should be prepared • • • • • • • • • • • • Stabilization, Delivery Room Care, and Initial Room Care, and Delivery Stabilization, Infant of the VLBW Treatment DELIVERY ROOM STABILIZATION IN THE Delivery Anticipation of High-Risk CHAPTER 30 364 Neonatology

Figure 30-1 Algorithm for resuscitation of the newborn. (Reprinted with permission from DeCherney AH, Nathan L: Current Diagnosis & Treatment: Obstetrics & Gynecology, 10th ed. New York: McGraw-Hill. Available at http://www.accessmedicine.com. Copyright © The McGraw-Hill Companies. All rights reserved.)

MEDICATIONS COMMONLY USED DURING NEONATAL RESUSCITATION

Medications Dose/Route Precautions

Epinephrine (1:10,000 0.1–0.3 mL/kg IV or via ETT* • Give rapidly dilution), 0.1 mg/mL • Repeat q3–5 min as needed

Volume expanders 10 mL/kg IV or IO• Give over 5–10 min, slower for (normal saline, blood) premature infants • Continue to reassess after each bolus

(continued on next page) Stabilization, Delivery Room Care, and Initial Treatment of the VLBW Infant 365

Medications Dose/Route Precautions

Sodium bicarbonate 2 mEq/kg IV or IO• Give slow push over at least 2 min (0.5 mEq/mL) • Must ensure adequate ventilation prior to dosing • Can repeat q5–10 min as needed

Naloxone 0.25–0.5 mL/kg IV, IM, IO, SQ, • Give rapidly (0.4 mg/mL) or via ETT • Repeat q3–5 min as needed

10% dextrose 2 mL/kg IV, IO• Check bedside glucose

* IV route is the preferred route and should be repeated as soon as IV access is established if the ﬁ rst dose was via ETT.

COMMONLY USED INOTROPES IN THE NICU

Infusion rate Medication (μg/kg/min) Indication Dopamine 2.5 – 20 • 1st line for hypotension in neonates • Has been shown to increase cerebral blood ﬂ ow in neonates • Cochrane review showed dopamine to be superior to dobutamine, with no increased eﬃ cacy with combining the two drugs Epinephrine 0.1 – 1• Added if maximal dopamine is not adequate • Some centers will use hydrocortisone at 1 mg/kg q8h for 3–5 d for refractory hypotension Milrinone 0.125 – 0.750• Very limited data exist on the use of milrinone in the premature infant • Has been used as an adjunct therapy in older infants with pulmonary hypertension as a pulmonary vasodilator

ENDOTRACHEAL TUBE SIZES

ETT size (internal Depth of insertion Laryngoscope diameter in mm; all (cm; as measured at Weight Blade uncuff ed tubes) the lips) <1000 g 00 2.5 6–7 1000–2000 g 0 3.0 7–8 2000–4000 g 1 3.5 8–10 >4000 g 1 3.5–4.0 10

Placement of Umbilical Catheters

Umbilical Arterial Catheter NEONATOLOGY • Sizes are 3.5 Fr (for <1500 g) and 5.0 Fr (>1500 g); both are single-lumen catheters. • Ideal position when verifying by X-ray is between T7 and T10 (above origin of celiac trunk). • Depth of insertion (in centimeters) is estimated as follows: (weight (kg) × 3) + 9 Umbilical Venous Catheter • Sizes are 3.5 Fr (double lumen, for <1500 g) and 5 Fr (triple lumen, for >1500 g). • Ideal position is at the junction of the inferior vena cava and the right atrium. 366 Neonatology

• If unable to advance UVC to this position, pull back so that the tip is proximal to the liver. • If UVC must be used in this “low lying” position, alternative vascular access must be established as soon as possible and this line removed. • Depth of insertion (in centimeters) is estimated as follows: (Depth of UAC insertion ÷ 2) + 1 Triage • Will be institution speciﬁ c, so check with your hospital’s guidelines.

TCH INSTITUTIONAL PRACTICE: DELIVERY ROOM TRIAGE

Level 1 Level 2 Level 3 Gestational age ≥35 wk by date 32–34 6/7 wk by date <32 wk by date Birth weight >2000 g 1800-2000 g <1800 g 5-minute APGAR >7 4–6 0–3 score Maternal Type A1 and A2 All other classifi cations All other classifi ca- diabetes tions Meconium Asymptomatic with N/A Symptomatic with or without meconium meconium below below the cords cords Respiratory N/A If no oxygen require- All with oxygen distress ment, but still needs to requirement be evaluated Sepsis risk Maternal fever or PROM Maternal fever and/or All infants with factors without chorioamnioni- chorioamnionitis with signifi cant tis and asymptomatic mild symptoms symptoms term baby

MECONIUM ASPIRATION • Acute and chronic hypoxia can result in passage of meconium in utero, and gasping by fetus or newborn can cause aspiration of ﬂ uid contaminated by meconium. • Passage of meconium occurs in 12% of deliveries. • Presence may be associated with persistent pulmonary hypertension with or without superimposed aspiration.

Meconium-stained infant

Vigorous? Not vigorous? (HR >100 bpm, and (HR < 100 bpm, or poor strong respiratory effort, respiratory effort, or poor and good muscle tone) muscle tone)

• Intubate and suction • Observe trachea • Resuscitate as needed • Resuscitate as needed

Figure 30-2 Algorithm for immediate postdelivery care of the meconium-stained infant. Stabilization, Delivery Room Care, and Initial Treatment of the VLBW Infant 367

• During resuscitation if thick meconium is obtained and: • HR >100→ Repeat intubation if needed to remove remaining meconium. • HR <100 → If severely depressed, intubate and use PPV. • Triage after meconium aspiration resuscitation. • No meconium and no distress → level 1 • Meconium in airway and pink in room air → observation for 6 h if possible; level 1 or level 2 • Meconium in airway with respiratory distress and/or oxygen is required → level 3

RISK MANAGEMENT OF MATERNAL GBS

Maternal Intrapartum Antibiotic Prophylaxis (IAP) for Infants At Risk for Early-Onset GBS Disease Vaginal and rectal GBS screening cultures at 35–37 weeks’ gestation for ALL pregnant women (unless patient had GBS bacteriuria during the current pregnancy or a previous infant with invasive GBS disease)

Intrapartum prophylaxis indicated Intrapartum prophylaxis • Previous infant with invasive GBS disease not indicated • GBS bacteriuria during current pregnancy • Previous pregnancy with a • Positive GBS screening culture during positive GBS screening current pregnancy (unless a planned culture (unless a culture was cesarean delivery in the absence of labor also positive during the or amniotic membrane rupture is current pregnancy) performed) • Planned cesarean delivery • Unknown GBS status (culture not done, performed in the absence of incomplete, or results unknown) and any labor or membrane rupture of the following: (regardless of maternal GBS • Delivery at <37 weeks’ gestation culture status) • Amniotic membrane rupture ≥18 • Negative vaginal and rectal hours GBS screening culture in late • Intrapartum temperature ≥100.4°F gestation during the current (≥38.0°C) pregnancy, regardless of intrapartum risk factors

Figure 30-3 Maternal indications for intrapartum antibiotic prophylaxis. (Reprinted with permission from Cunningham FG, Leveno KJ, Bloom SL, et al: Williams Obstetrics, 22nd ed. New York: McGraw-Hill. Available at http://www.accessmedicine.com. Copyright © The McGraw-Hill Companies. All rights reserved.)

Onset of labor or ROM at < 37 weeks’ gestation with significant risk for imminent preterm delivery

No GBS culture GBS positive GBS negative

Obtain vaginal and IV antimicrobials rectal GBS culture GBS No GBS for ≥ 48 hours and initiate IV positive prophylaxis (during tocolysis) antimicrobials NEONATOLOGY No growth at 48 hours Intrapartum antimicrobial prophylaxis at Stop antimicrobials delivery

Figure 30-4 Algorithm for prophylaxis for women with GBS disease and threatened preterm delivery. (Reprinted with permission from Cunningham FG, Leveno KJ, Bloom SL, et al: Williams Obstetrics, 22nd ed. New York: McGraw-Hill. Available at http://www.accessmedicine.com. Copyright © The McGraw-Hill Compa- nies. All rights reserved.) 368 Neonatology

MANAGEMENT OF THE INFANT AT RISK FOR EARLY-ONSET GBS DISEASE

Maternal antibiotics for Maternal IAP suspected for GBS?a chorioamnionitis? Ye s Ye s

Signs of Ye s Full diagnostic evaluationb neonatal sepsis? Empiric therapyc

Gestational age Ye s < 35 weeks? Limited evaluation Observe ≥ 48 h No If sepsis is suspected, full diagnostic evaluation Duration of IAP Ye s and empiric therapyb < 4 h before delivery?d No No evaluation No therapy Observe ≥ 48 he a If no maternal intrapartum prophylaxis for GBS was administered despite an indication (see previous page), data are insufficient on which management strategy to follow. b Includes CBC, blood culture, and CXR if respiratory symptoms are present. When sepsis is suspected, a lumbar puncture should be performed, if possible (CSF for cell count and differential, Gram's stain, protein, glucose, bacterial culture). c Usually ampicillin + gentamicin; duration of therapy varies depending on results of blood culture, CSF analysis (if obtained) and the clinical course of the infant. If laboratory results are not suggestive of bacterial infection and infant is clinically well, antibiotics may be stopped after 48 h. d Applies only to penicillin, ampicillin, or cefazolin and assumes recommended dosing regimens. e A healthy-appearing infant who was 38 weeks’ gestation at delivery and whose mother received 4 h of intrapartum prophylaxis before delivery may be discharged home after 24 h if other discharge criteria have been met and a person able to comply fully with instructions for home observation will be present. If any of these conditions is not met, the infant should be observed in the hospital for at least 48 h and until criteria for discharge are achieved. Figure 30-5 Algorithm for treatment of a newborn whose mother received IAP for prevention of GBS. (Reprinted with permission from Hay WW Jr, Levin MJ, Sondheimer JM, Deterding RR: Current Diagnosis & Treatment: Pediatrics, 19th ed. New York: McGraw-Hill. Available at http://www.accessmedicine.com. Copyright © The McGraw-Hill Companies. All rights reserved.) Stabilization, Delivery Room Care, and Initial Treatment of the VLBW Infant 369

Ter m infant

Maternal fever Infant with clinical PROM (≥ 18 hr) ≥ 100.4°F within signs/symptoms of prior to delivery 24 hours before or sepsis (regardless after delivery of maternal fever) and/or OB is considering maternal chorioamnionitis or systemic infection and infant is asymptomatic

Limited sepsis Infant Infant workup, empiric symptomatic asymptomatic antibiotics

Observe for 24 hrs, Symptomatic infants: consider limited sepsis Respiratory distress, workup and empiric hypotension, lethargy, antibiotics, outpatient apnea, temp instability, Full sepsis workup, followup 2-5 d after seizures, tachycardia, empiric antibiotics discharge vomiting, diarrhea, poor feeding Figure 30-6 Term infant: evaluation and empiric treatment for sepsis.

• Evaluation should include full sepsis workup evaluation of blood and CSF, initiation of empiric ampicillin/gentamicin

INITIAL CARE OF THE VLBW INFANT General Principles • Low birth weight is <2500 g. • Very low birth weight is <1500 g. • Extremely low birth weight is <1000 g. • The early management of these infants is crucial in determining long-term outcomes. NEONATOLOGY 370 Neonatology

Preterm infant

Maternal fever Infant with clinical PROM (≥ 18 hr) ≥100.4°F prior to or signs/symptoms of prior to delivery within 24 hours sepsis (regardless before or after of maternal fever) delivery and/or OB is considering chorioamnionitis or systemic infection and infant is asymptomatic

Symptomatic infants: Same Asymptomatic Symptomatic manifestations as term infants

Limited sepsis Full sepsis Limited sepsis Full sepsis evaluation, evaluation, evaluation, evaluation, empiric empiric empiric empiric antibiotics antibiotics antibiotics antibiotics

Figure 30-7 Preterm infant: evaluation and empiric treatment for sepsis.

MANAGEMENT GOALS

System Points to Remember Respiratory• Synchronized ventilation is the preferred mode of ventilation. • Use the smallest possible tidal volumes (4–6 mL/kg) to achieve adequate oxygenation and ventilation.

• In general, goal PaO2 is 50–80 mm Hg, and goal PaCO2 is 50–60 mm Hg. • The potential beneﬁ ts of “minimal ventilation” remain a matter of debate. • Surfactant therapy is administered as soon after delivery as possible, preferably within 1 h. • Surfactant candidate: infant ventilated for respiratory distress syndrome

requiring > 6-7 cm H2O mean airway pressure and an FiO2 of >30%.

• If peak infl ation pressures >30 cm H2O are required, consider high- frequency oscillatory ventilation (HFOV). • All infants <1000 g birth weight should be on vitamin A (5000 IU intramuscularly three times weekly for a total of 12 doses). • All infants <1250 g birth weight should receive caff eine citrate (20 mg/kg loading dose, followed by 5 mg/kg daily). • Both of the above have shown some benefi t in the reduction of chronic lung disease of prematurity. Cardiovascular• Maintaining adequate tissue perfusion is the ultimate goal. • Limited data suggest adverse eff ects on cerebral perfusion for mean arterial pressures <30 mm Hg, but long-term data on neurodevelopment are lacking. • Generally, accept mean arterial pressures >25 mm Hg for infants 24–26 wk gestation (as long as adequate perfusion is present).

(continued on next page) Stabilization, Delivery Room Care, and Initial Treatment of the VLBW Infant 371

System Points to Remember

• Dopamine is fi rst line for treatment of hypotension (rare instances where hypotension in this age group is due to hypovolemia, so avoid fl uid boluses as much as possible, unless indicated by history [ie, placental abruption]). • Hydrocortisone can be used (1 mg/kg q8h for 2–3 days) in cases of refractory hypotension • Symptomatic PDA is common (up to 80% in infants with birth weight <1000 g). For more information refer to Chapter 32. • Symptoms related to a signifi cant PDA may include need for increased ventilatory support, increased oxygen requirement, ± murmur, and metabolic acidosis. • PDA is associated with, but not been shown to be causative of, most of the comorbidities that occur with prematurity. • Prophylactic indomethacin is not used as standard of practice, due to lack of evidence for improved long-term outcomes. • One to two courses of indomethacin can be used (prudent to evaluate PDA with echocardiography prior to treatment). → additional courses associated with development of severe ROP and renal insuffi ciency. • If symptomatic PDA persists, consider surgical ligation.

Fluids/ • The lower the gestational age, the higher the fl uid requirements will be, Electrolytes secondary to tremendous insensible losses through immature, noncorni- fi ed skin and an increased body surface area–to-weight ratio. • Total fl uid requirements for preterm infants (in mL/kg/d):

Birth Weight (g) Day 1–2 Day 3 ≥Day 5

<1000 100 140 150

1000–1500 80–100 100–120 150

>1500 65–80 100 150

• Maintain glucose infusion rate (GIR) of 4–8 mg/kg/min. • If hyperglycemia (>220 mg/dL) results, decrease the dextrose concentration of IVF no lower than a minimum concentration of 5% and a minimum GIR of 4 mg/kg/min. • If weaning the GIR to 4 mg/kg/min does not resolve the problem of hyperglycemia, administer insulin bolus of 0.025–0.1 units/kg, followed by an infusion of 0.01 units/kg/h; titrate infusion to achieve blood glucose level of 150–220 mg/dL (ensure IV tubing is properly primed with insulin- containing fl uid to prevent adsorption of insulin within tubing). • TPN should be started as soon after birth as possible to avoid entering a negative nitrogen balance (our “starter” TPN, which is used only for infants in the fi rst 24 h of life, contains only dextrose at 5% or 10% [see above], and amino acids [provide 1.5–2 g/kg/d of protein on the fi rst day of life]). • Generally, serum sodium can be monitored at q6–8h intervals in infants <1000 g birth weight as an indirect marker of total body free water balance. NEONATOLOGY • If serum sodium decreases, this may indicate excessive fl uid administration. • If serum sodium increases, this may indicate restricted fl uid administration. 372 Neonatology

System Points to Remember

Nutrition• All infants with birth weight <1500 g are started on TPN as soon as feasible. • Goals are to provide 1.5–2 g/kg/d of protein on DOL advancing daily by 0.5–1 g/kg/d to a maximum of 3.5–4 g/kg/d. • Lipid emulsion is started on DOL 1 or 2 at 1 g/kg/d (=5 mL/kg/d) and advanced daily to a maximum of 3 g/kg/d (=15 mL/kg/d) as tolerated. • Enteral feeds are started as soon as the infant’s clinical condition allows (no pressor support, not receiving indomethacin) with 10–20 mL/kg/d of trophic feeding. • Preference is to start with maternal milk, but preterm formula may also be used. • For infants <1500 g birth weight, trophic feeds are continued for a total of 3 d before advancing. • Feeds are advanced by 10–20 mL/kg/d as the patient tolerates. • The caloric density is increased to 24 cal/oz when the infant reaches feed volumes of 100–120 mL/kg/d, either by adding human milk fortiﬁ er to the expressed breast milk or by changing to an appropriate preterm formula.

Infection • Premature infants are susceptible to infectious complications for several control reasons: • Immaturity of the immune system • Immaturity of protective skin barriers • Need for vascular catheterization in the NICU • Methods to prevent nosocomial infection include: • Meticulous attention to hand hygiene (waterless alcohol gel or foam, or traditional antimicrobial soaps) • Early introduction of enteral feeds, preferably with human milk • Judicious ordering of laboratory work, thereby minimizing blood draws (skin pricks as well as accessing vascular catheters) and allowing for clustering of care

Sample Admission Orders • Respiratory: If infant intubated, order ventilator settings. • Appropriate ventilator settings for infants with acute lung injury: • SIMV 20–40 breaths/min, PIP as needed to achieve adequate chest rise and tidal

volume of 4–6 mL/kg, PEEP 5 cm H2O, Ti 0.20–0.30 sec, FiO2 as needed to achieve targeted oxygen saturations: • For infants with birth weight <1250 g or postmenstrual age (PMA) <29 wk who require oxygen, oximeter alarms should be set at 85%–93%. • For infants with >1250 g or PMA >29 wk who require oxygen, oximeter alarms should be set at 85%–97%. • Order chest X-ray to evaluate position of endotracheal tube (ETT); may also need abdominal plain ﬁ lm to evaluate position of umbilical catheters. • Order blood gas (arterial, venous, or capillary). • Cardiovascular: If infant is hypotensive, order dopamine to start at 5 μg/kg/min. • Order heparinized saline to run at 0.5 mL/h through the umbilical or peripheral arterial catheter, and for each dormant port in the umbilical venous catheter. • Central nervous system • Routine cranial US for infants with BW <1500 g, to be done at 7–10 d of age. • Please see Chapter 31 for recommendations on follow-up. • Ophthalmologic screen for ROP for all infants born <32 wk gestation or <1500 g birth weight. Stabilization, Delivery Room Care, and Initial Treatment of the VLBW Infant 373

• Fluids/Electrolytes/Nutrition • Fluid/TPN orders as required (outlined in the table above). • Order electrolytes at 6–8 h of life in infants <1000 g, then q6–12h as indicated. • Order ionized calcium level at 24 and 48 h of life. • Serum triglycerides can be followed once the infant has been on lipid emusion infusion for >4 h. • Hematologic • Order total serum bilirubin (TSB) at 12–24 h of age, depending on presence of jaundice, extensive bruising, or ABO/Rh incompatibility. • Follow serial TSB as indicated. • Document mother’s blood type and Rh status. • Infectious • Order CBC with differential and platelet count at baseline. • Decision to start antibiotics will depend on whether risk factors for infection are present, and is at the discretion of the attending physician. • Document results of maternal HIV, RPR, hepatitis B, and GBS screens. • Nursing • Strictly record all fl uid intake and output. • Order humidifi ed Giraffe Omnibed (or other humidifi ed isolette) to servo-control mode. • Humidifi cation protocol as per NICU nursing policy. • If a humidifi ed isolette is not available, an open warmer may be used → Use of a plastic wrap blanket will help reduce evaporative water loss and convective heat loss from the skin. • Continuous cardiorespiratory monitoring • Medications • Vitamin K (0.5 mg IM × 1) • Eye prophylaxis (erythromycin ophthalmic ointment) • Survanta 4 mL/kg (if needed; see below for indications). Check with your institution for dosing amount and interval of other synthetic surfactant preparations. • Antibiotics as indicated (start with ampicillin/gentamicin for empiric coverage) • For infants <1000 g birth weight, vitamin A (5000 IU intramuscularly three times weekly for a total of 12 doses) • For infants <1250 g birth weight, caffeine citrate (20 mg/kg loading dose, followed by 5 mg/kg daily), even if infant is intubated (used in the prevention of chronic lung disease of prematurity)

Use of Nitric Oxide • Currently, use of inhaled nitric oxide (iNO) is indicated for the treatment of term and late preterm (≥34 wk gestation) neonates with hypoxic respiratory failure associated with clinical or echocardiographic evidence of pulmonary hypertension.

ADMINISTRATION OF EXOGENOUS SURFACTANT

Prophylactic Treatment Rescue Treatment

• Most infants <28 wk gestation are • Rescue treatment by single- or multiple-dose intubated in delivery room and given surfactant replacement reduces mortality from surfactant, preferably within the ﬁ rst RDS as well as pneumothorax. 15 min of life. • Outborn infants <28 wk and between 2 and 48 h • Data suggests two doses are better of age who require >30% oxygen should receive NEONATOLOGY than one. rescue surfactant, with repeat dosing as above. • Repeat surfactant dose q6h (up to a • Spontaneously breathing infants >28 wk with * total of four doses ) if infant requires respiratory distress who require >40% FiO2 ventilation with mean airway pressure on nasal CPAP are also candidates for rescue

>6–7 cm H2O and FiO2 >30%. surfactant.

(continued on next page) 374 Neonatology

Prophylactic Treatment Rescue Treatment

Dosage and Administration • 4 mL/kg administered via ETT*. • Careful observation during administration: Lung compliance may change rapidly and necessitate rapid weaning of inﬂ ation pressures to prevent air leak and volutrauma. • Consider up to four doses as indicated.

*This dosing speciﬁ cally applies to Survanta™; check label insert for dosing amount, interval and total doses for other synthetic surfactant preparations.

MODES OF VENTILATION IN THE NICU • Key is to limit lung injury associated with mechanical ventilation.

• In general, goal pH is >7.20, PaO2 is 50–80 mm Hg, and PaCO2 is 50–60 mm Hg.

Synchronized • Most frequently used in newborns with respiratory failure to Intermittent improve consistency of oxygenation and reduce patient Mandatory discomfort Ventilation • Values to be set (pressure-control SIMV): Rate (breaths/min), peak (SIMV) inﬂ ation pressure (PIP), positive end-expiratory pressure (PEEP), inspiratory time (Ti) • Weaning: Can wean rate, PIP to prevent overventilation Pressure • Potential indications: Support • Infants >10 kg Ventilation (PS) • Need for volume-controlled ventilation • Assistance of spontaneous breaths in older, chronically ventilated infants (>40 wk PMA or >2500 g weight) • Due to ET tube and ventilator tubing characteristics, patient is burdened with increased work of breathing

• Remedied by adding additional pressure (10–15 cm H2O) above PEEP for each spontaneous breath • Be cognizant of potential for breath stacking on this mode of ventilation; also, PS ventilation provides no back-up rate, so monitor closely for apnea • Scant data to support use of this mode as a weaning tool

• Weaning: Wean PIP as tolerated until within 2 cm H2O of PEEP + PS,

then begin PS trials (PS, PEEP, and FiO2 values are set on vent, without PIP or backup rate; start with 1–2 h/day, advancing as tolerated) • Once infant reaches full-time PS, begin weaning total PS down to

goal 10 cm H2O

Volume • In time-cycled, pressure limited ventilation, tidal volume (Vt) can vary Guarantee from breath to breath depending on the compliance of the lungs (VG) (similar and whether the baby is at rest or awake and “ﬁ ghting” the ventilator • more consistent breath-to-breath, VG mode to Pressure To make the delivered Vt Regulated can be used • Values to be set: Rate, V (4–6 mL/kg), maximal PIP allowable to reach Volume Control, t preset V , Ti, and PEEP PRVC) t

• Weaning: To prevent overventilation, wean the Vt or rate (the maximal PIP setting is meant to be a safety mode to prevent barotrauma) • Due to lack of data on long-term beneﬁ t, use is limited to special circumstances

(continued on next page) Stabilization, Delivery Room Care, and Initial Treatment of the VLBW Infant 375

Assist Control • All spontaneous breaths are supported by the ventilator (AC) • Values to be set: PIP, Ti, PEEP, and a backup rate of 20–40 breaths/ min (in the event that the infant becomes apneic) • Weaning: To prevent overventilation, wean PIP (not the rate, as this is only a backup rate in case of apnea) • Due to lack of data on long-term beneﬁ t, use is limited to special circumstances (ie, diaphragmatic hernia) High-Frequency • Potential indications: Oscillatory • Infants ≥34 wk gestation with severe respiratory failure who are at Ventilation risk for requiring ECMO (HFOV) • Management of severe, acute lung disease requiring PIP >30 cm

H2O • Infants with air-leak syndrome • HFOV + iNO has been reported to reduce the need for ECMO in patients with hypoxic respiratory failure • Complications: pulmonary hyperinﬂ ation and air leak

• Values to be set: Paw (mean airway pressure; generally 1–2 cm H2O Δ above the last Paw used on conventional IPPV), P (just high enough to produce perceptible chest wall motion; generally start at two times

the Paw), frequency (start 10–15 Hz; generally, the smaller the infant,

the higher the starting Hz), % inspiratory time (start at 33%), FiO2 (start 100%, wean as tolerated)

• Increase Paw until adequate lung recruitment is achieved and you are

able to begin weaning FiO2 • Monitoring: CXR within 2–4 hours of initiating HFOV to follow for hyperinﬂ ation, then q8–12h as indicated ↓ Δ ↑ • Weaning: To prevent overventilation, P or Hz; when FiO2 is <60%,

begin judicious weaning of Paw by 1–2 cm H2O decrements • Can change to conventional mechanical ventilation when: • Air leak resolves

• Paw is weaned to 10–12 cm H2O • ΔP is ≤30 NEONATOLOGY CHAPTER 31 Discharge Planning

CRITERIA FOR DISCHARGE 1. Able to maintain normothermia in an open crib. 2. Normal saturations in room air or completed arrangements and parental teaching for any supplemental oxygen or equipment needed 3. No apnea/bradycardia for 5 days before discharge 4. Tolerating feeds by mouth or other means without respiratory distress 5. Appropriate weight gain for gestational age 6. Home health service in place if needed 7. Parental comfort with routine care, medications, any equipment needed, and any procedures needed 8. Parental infant CPR instruction 9. Appropriate follow-up arranged, including a primary physician comfortable with managing the level of care required and able to see patient within 2 days of discharge Discharge Planning • Discharge planning should be started early, especially for infants with complex medical needs. DISCHARGE PLANNING CONSIDERATIONS FOR THE HIGH-RISK NEONATE

Planning Criteria Timing Follow-up State All infants Each state is diﬀ erent Some states only newborn in terms of timing of require one screening screen screening and which test, and others require disorders are screened two; check with your for; check with your state state on the number on the timing and sample and timing of state preparation screenings required In Texas, two screens are done: First at 24–48 h of life; second at 7–14 d of life Some states only require one screen Second screen is usually to evaluate for false-negative results on the ﬁ rst screen Cranial US Infants born at <32 wk PMA At 7 to 10 d of age or ear- No hemorrhage on or birthweight <1500 g lier at the discretion of initial screen: the attending physician • If GA <28 wk, repeat at 4 wk chronological age and 36 wk PMA (or sooner if discharged <36 wk PMA) • If GA >28 wk, repeat at 4 wk chronological age or 36 wk PMA (or sooner if discharged earlier than 36 wk PMA)

(continued on next page) 376 Discharge Planning 377

Planning Criteria Timing Follow-up

If grade II IVH or greater: • Weekly cranial US to follow for development of post-hemorrhagic hydrocephalus; more frequently if clinically indicated

Ophthal- All infants <30 wk PMA or 31–33 wk PMA Based on ﬁ ndings of mologic <1500 g birthweight initial screen (may be screen or within a few days for pre-threshold disease Infants 1500–2000g birth- to every 1–3 wk for im- weight if the infant is at high mature retinas at risk of risk for developing ROP progressing to ROP)

Audiology All newborns ≥34 wk PMA As needed for failed screen Infants admitted to the level initial screen II nursery or NICU for ≥5 d require screening with an ABR

Car seat All infants born <37 wk Can be tested immedi- testing PMA or older infants with ately before discharge disorders that may impact home the airway (eg, hypotonia)

Vaccinations See Chapter 19 (Infectious Diseases) for vaccination guidelines

Occu- Infants who meet one of the As soon as possible dur- As recommended by pational following: ing the hospitalization consulting therapist therapy or • Birth at ≤28 wk PMA physical • Birthweight <1000 g therapy • Neurologic injury (IVH, PVL) • Any disorder that impacts movement • Orthopedic impairment

Early Child- All infants <1500g birth- Initial screen is usu- hood In- weight or <32 wk PMA ally after discharge from tervention All infants who are believed hospital, but referral (programs to be at risk for abnormal should be made before are state- neurodevelopment or abnor- discharge speciﬁ c) mal physical development All infants who are believed to be discharged to a high-risk home situation (eg, multiple other children, young mother) NEONATOLOGY Women, All premature infants Referral should be made Infant, and All infants that are to be before discharge Children discharged on special medi- Program cal formulas (programs are state- speciﬁ c) 378 Neonatology

PALIVIZUMAB PROPHYLAXIS Criteria (Red Book: 2009 Report of the Committee on Infectious Diseases) • Infants born at ≤28 wk who are <12 mo of age at start of RSV season (maximum, 5 monthly doses) • Infants born between 29 and 31 6/7 wk of gestation who are <6 mo of age at start of RSV season (maximum, 5 monthly doses) • Neonates born between 32 and 34 6/7 wk gestation without CLD who are <3 mo of age at the start of RSV season, or born during RSV season, with either of the following risk factors (maximum, 3 monthly doses; discontinue after infant reaches 3 mo of age): • Child care attendance (private or commercial facility) • Sibling age <5 yr • Infants <24 mo of age at the start of RSV season who have required any medical therapy for CLD within the previous 6 mo: • Oxygen • Bronchodilator • Diuretics • Corticosteroids • Infants with hemodynamically signiﬁ cant cyanotic or acyanotic heart disease* who are: • ≤24 mo of age and • Receive medication to control congestive heart failure, have moderate to severe pulmonary hypertension, or have cyanotic heart disease • Infants born <35 wk with congenital abnormalities of the airway or neuromuscular disease that compromises handling of respiratory secretions (maximum, 5 monthly doses).

∗Cardiac conditions that do not require palivizumab prophylaxis: Secundum ASD, small VSD, pulmonary stenosis, uncomplicated aortic stenosis, mild coarctation of the aorta, PDA, cardiomyopathy (not receiving medical therapy), lesions adequately corrected by surgery (unless on medical therapy for heart failure) (maximum, 5 doses)

Dosage • 15 mg/kg IM monthly during RSV season (varies by region; see www.cdc.gov/Features/ dsRSV)

Other considerations: • Hospitalized infants who qualify for prophylaxis during the RSV season should receive the ﬁ rst dose 48 to 72 hr before discharge or promptly after discharge • If an infant currently receiving prophylaxis experiences a breakthrough infection, continue prophylaxis as recommended after recovery • No data exist to support prophylaxis of hospitalized patients for the prevention of hospital-acquired RSV infection. • Palivizumab does not interfere with response to vaccines.

DEVELOPMENTAL FOLLOW-UP (Institutional Practice) • The following infants are referred to a Developmental Pediatrician for followup within 6 months from discharge: • All infants <1500g birth weight. • All infants of any gestational age/birth weight discharged from the Level III NICU or the Level II NICU. • All infants with in utero substance exposure. • All infants with chromosomal or congenital anomalies. • All infants discharged home with complicated medical needs (i.e., ventilator dependent, tube feedings, etc.) NEONATOLOGY

is ts established ts lms serially) lms be ndings may ndings. uid administration uid high altitude, CHD, ciency, asphyxia, cant PDA include: 379 ts established with medical or surgical treatment, ndings exist for PDA) c ﬁ c ow in postductal aorta state and de- cant anemia present, may reduce high-output ow in MPA (alone does not cause ductal closure, but excess ﬂ

uid administration uid [ie, indomethacin vs ligation]) nitive management (medical versus surgical Left atrial/left ventricular enlargement Ductal diameter >1.5 mm Predominantly left-to-right shunt Disturbed diastolic fl Reversal of end-diastolic fl associated with increased incidence of PDA) crease pulmonary overcirculation) increased fl membranes Ventilatory support (may increase PEEP to control pulmonary edema) Ventilatory support (may increase PEEP to control pulmonary PRBC transfusion (if signifi Defi Decreased in: antenatal steroids, intrauterine growth restriction, prolonged rupture of Decreased in: antenatal steroids, Fluid restriction May be normal, or may see LVH, BVH, or LAE May be normal, or may see pulmonary edema or cardiomegaly (compare fi May be normal, or may see pulmonary Findings associated with hemodynamically signifi Increased in: prematurity, hyaline membrane defi Increased in: prematurity, hyaline • • • • • with medical or surgical treatment; may continue to feed these infants with medical or surgical treatment; may continue to feed these prevents but treatment reduces the need for ventilator support and theoretically emboli progression to heart failure, pulmonary hypertension, and septic those <1000 g. sepsis. similar to pulmonary disease or Symptomatic PDA: No long-term benefi Asymptomatic PDA without need for ventilator support: No long-term benefi Asymptomatic PDA without need for ventilator support: No Electrocardiography (no specifi Pulmonary edema Heart failure Pulmonary hypertension of PDA) Septic emboli (from vegetations located on the pulmonary side CXR Echocardiography with Doppler Large PDA can be diagnosed relatively accurately based on clinical fi Large PDA can be diagnosed relatively echocardiogram with Doppler, because fi Small PDA usually requires an DA closed in 50% of full-term infants by 24 h, 90% by 48 h, >99% by 96 h. of full-term infants by 24 h, DA closed in 50% (10% of all CHD in term infants). Incidence in term infants: ~0.02%–0.04% ~45% of infants <1750 g, ~80% of infants <1000 g. Incidence in preterm infants: Spontaneous closure of PDA occurs in 38%–85% of babies <1500 g and in 25%–34% of Spontaneous closure of PDA occurs • • • • • • • • • Management • • • Complications • • • • Diagnosis • • • Clinical Manifestations • • Cardiology ARTERIOSUS PATENT DUCTUS • • • CHAPTER 32 380 Neonatology

Indomethacin • Effectiveness diminishes above 1500 g and beyond 3–4 wk of life • Two approaches: • Prophylactic administration (not standard practice at TCH) • Dose: 0.1 mg/kg indomethacin IV q24h for three doses • Who: All infants <1000 g with RDS necessitating surfactant • Rationale: Administering prophylactic doses during the ﬁ rst 3 DOL results in a greater rate of permanent ductus closure (J Pediatr 2000;136:330.) • Treatment of the symptomatic PDA • Dose: Administration is q12–24h, following urine output closely, and is dependent on when indomethacin is begun postnatally (see the table below)

INDOMETHACIN DOSING REGIMEN

Age at First Dose Dose 1 (mg/kg) Dose 2 (mg/kg) Dose 3 (mg/kg) <48 h 0.2 0.1 0.1

2–7 d 0.2 0.2 0.2 >7 d 0.2 0.25 0.25

Adapted with permission from Drug Monographs: Indomethacin (accessed July 31, 2009). Available at http://www. accessmedicine.com. New York: McGraw-Hill. Copyright © The McGraw-Hill Companies. All rights reserved.

• Who: Infant with evidence of signifi cant symptoms of PDA (eg, murmur, ↑ ventilator support, signs of heart failure); must rule out a ductal dependent lesion prior to initiation of indomethacin therapy • Rationale: Treat a slightly more targeted population; risk treating those who would spontaneously close • Treatment failure: 30%–50% of PDAs will either reopen or fail to close after treatment; if the PDA either fails to close or reopens and remains symptomatic/hemodynamically signifi cant, options include: • Repeat: Administer one to two more 0.2 mg/kg IV doses q12–24h of indomethacin (although extended dosing has been shown to be associated with more moderate to severe retinopathy of prematurity and renal impairment in one study [ J Pediatr 2008;153:183]). • Surgical ligation: Infants <28 wk gestation with Doppler evidence of ductus fl ow after the initial indomethacin course are unlikely to respond to a subsequent course (Pediatrics 2003;112(3 pt 1):583). Given the long-term neurodevelopmental concerns with surgical closure, many continue to favor a second course of indomethacin prior to surgical ligation. The decision to pursue further dosing of indomethacin versus surgical ligation is made on a case-by-case basis after weighing the risk:benefi t ratio for each. PDA in the full-term infant is a distinct clinical entity. Older full-term infants are less likely to respond to cyclooxygenase inhibitors and are more likely to need a surgical correction (traditional thoracotomy, transcatheter closure, or thoracoscopic ligation).

EVALUATION OF SUSPECTED CONGENITAL HEART DISEASE EMPIRIC APPROACH TO EVALUATION

Asymptomatic Murmur Cyanosis/Heart Failure

History History

O O Vitals (four-extremity BP, Sp 2) Vitals (four-extremity BP, Sp 2) Physical examination Physical examination EKG EKG CXR CXR Arterial blood gas Hyperoxia test Echocardiogram Cardiology 381

History Family History • Risk for CHD increases if a parent or sibling has CHD and triples if two close relatives are affected. Genetic testing is available for some forms of CHD. Prenatal Testing • If possible, obtain fetal ultrasound reports, which may identify structural malformations, CCAM, or CDH. • Speciﬁ c familial, fetal, and maternal indications for prenatal fetal ultrasounds exist (J Am Soc Echocardiogr 2004;17:803). Perinatal History • Sepsis may result in myocardial dysfunction and poor cardiac output. • Consider meconium aspiration, infection, and PPHN.

SYMPTOMS ASSOCIATED WITH ABNORMAL PULMONARY BLOOD FLOW

↓ Pulmonary Blood Flow ↑ Pulmonary Blood Flow

Cyanosis Tachypnea (at rest or with activity) Squatting Diaphoresis (at rest or with activity) Loss of consciousness Poor weight gain

Vital Signs, Oximetry, and Four-Extremity Blood Pressures • Normal vital signs do not rule out CHD. • Four-extremity BP: >10 mm Hg gradient between upper and lower body suggests aortic coarctation, arch interruption, or arch hypoplasia (this fi nding is specifi c, not sensitive). A widely patent, nonrestrictive PDA may mask this fi nding, even if severe obstruction is present. • Pre/postductal sats: Preductal sats (right hand) versus postductal sats (either foot) (note: in cases of right aortic arch, the preductal sat is measured at the left hand).

Diff erential Cyanosis Reverse Diff erential Cyanosis (Preductal > Postductal) (Postductal > Preductal)

PPHN d-TGA with either PPHN or systemic outﬂ ow Left sided-obstructive lesions: obstruction • Critical aortic stenosis • Aortic arch hypoplasia • Aortic arch interruption • Aortic coarctation

EKG • Many are normal in CHD. EKG FINDINGS AND ASSOCIATED CARDIAC DISEASE NEONATOLOGY Superior Axis (“Northwest” or Right Axis Deviation Indeterminate)

TOF AVCD d-TGA Tricuspid atresia TAPVR Pulmonary atresia with intact ventricular septum

(continued on next page) 382 Neonatology

Large QRS Complexes Small QRS Complexes

All leads: Pompe’s disease Myocarditis Specifi c leads: Pericardial eff usion (pericarditis) • Right or left ventricular hypertrophy Hypothyroidism • Right or left bundle branch block Thick chest wall (adults) • Pre-excitation Normal newborn infants • Intraventricular block • Artifi cial pacemaker

AO AO SVC PA PA LA APP LA

RA LV RV RA LV RV

IVC Posteroanterior Left lateral Figure 32-1 Chest X-ray. (Reprinted with permission from Hay WW Jr, Levin MJ, Sondheimer JM, Deterding RR: Current Diagnosis & Treatment: Pediatrics, 19th ed. New York: McGraw-Hill. Available at http://www.accessmedicine.com. Copyright © The McGraw-Hill Companies. All rights reserved.)

CHEST X-RAY FINDINGS IN CONGENITAL HEART DISEASE

Lesion “Classic” CXR Finding Increased pulmo- PDA nary blood fl ow d-TGA “Egg on a string” Tricuspid atresia with large VSD TAPVR “Snowman” (unobstructed TAPVR) Decreased pulmo- Pulmonic stenosis nary blood fl ow Tricuspid atresia with small VSD TOF “Boot-shaped heart” Hypoplastic left heart syndrome Pulmonary atresia with intact ventricular septum Normal pulmonary Aortic coarctation “Figure 3 sign” or rib notching blood fl ow

Arterial Blood Gases

CO • P 2 may be increased in pulmonary disease or heart failure. • Metabolic acidosis raises concerns about poor cardiac output and heart failure. O • P 2 is lower at any given oxygen saturation for neonates compared to non-neonates due to

an increased afﬁ nity of O2 by fetal hemoglobin. Cardiology 383

Hyperoxia Test • Most sensitive and speciﬁ c portion of initial workup of suspected CHD. O • Empiric PGE1 should be started for any baby with Sp 2 <85% on both room air and 100%

FiO2. Note that the infant can experience further deterioration of oxygenation after

empiric treatment with PGE1 (see “Initial Stabilization of Congenital Heart Disease”).

• To perform the test, preductal SpO2 and PaO2 are measured on room air and 100% FiO2 (after 10 min).

INTERPRETATION OF THE HYPEROXIA TEST

Room Air FiO 100% PaCO2 Condition PaO2 (mm Hg)/SpO2 PaO2 (mm Hg)/SpO2 (mm Hg) Normal 70 / 95% >300 / 100% 35

Pulmonary disease 50 / 85% >150 / 100% 50

Methemoglobinemia 70 / 95% >200 / 100% 35

Cardiac disease: • Parallel circulation1 <40 / <75% <50 / <85% 35 • Mixing with restricted PBF2 <40 / <75% <50 / <85% 35 • Mixing without 40–60 / 75%–93% <150 / <100% 35 restricted PBF3 • Diﬀ erential cyanosis4 Pre: 70 / 95% Post: <40 / <75% Varies 35-50 • Reverse diﬀ erential Pre: <40 / <75% Post: >50 / >90% Varies 35-50 cyanosis4

1d-TGA. 2Tricuspid atresia with pulmonary stenosis/atresia, pulmonary atresia, critical pulmonary stenosis with intact ventricular septum, TOF. 3Truncus arteriosus, TAPVR, hypoplastic left heart syndrome. 4d-TGA with PPHN or systemic outﬂ ow obstruction. (Reprinted with permission from Clin Perinatol 2001;28:91)

PATHOPHYSIOLOGY AND AGE AT PRESENTATION OF VARIOUS TYPES OF CONGENITAL HEART DISEASE

Pathophysiology: Transition from fetal to transitional circulation is profoundly unfavorable

Symptoms Severe cyanosis Shock Pulmonary edema

Diﬀ erential Dx• PA / IVS • Critical AS • Obstructed • Critical PS • Interrupted aortic arch TAPVR

0–3 d • Ebstein’s malformation • Coarctation of aorta • HLHS • d-TGA with IVS • Obstructed TAPVR • HLHS Pathophysiology: PDA closure (causing cardiovascular collapse) or PVR falls (causing pulmonary overcirculation)

Symptoms Cardiovascular collapse Severe pulmonary overcirculation NEONATOLOGY

Diﬀ erential Dx• Severe AS • Truncus arteriosus • Severe aortic coarctation • PDA 4–10 d • TOF with severe PS • AVM • Single ventricle with PS

(continued on next page) 384 Neonatology

Pathophysiology: Heart unable to meet systemic O2 demand as PVR continues to fall

Symptoms Heart failure and pulmonary edema

Diﬀ erential Dx• Complete AV canal defect • TOF with mild PS • Unobstructed TAPVR

2–18 wk • d-TGA with VSD • Single ventricle lesions without PS • ALCAPA (only one in this group that may present with shock) Pathophysiology: Left-to-right shunting with mild pulmonary overcirculation

Symptoms Tachypnea, poor feeding, incidental murmur

Diﬀ erential Dx• VSD • ASD • PDA Pathophysiology: Mild outfl ow tract obstruction

4–12 mo Symptoms Poor feeding, incidental murmur

Diﬀ erential Dx• Aortic stenosis • Pulmonary Stenosis • Aortic coarctation

Initial Stabilization of Congenital Heart Disease • Severe CHD may present with cyanosis, heart failure, or shock. • For an unstable neonate with suspected CHD, begin with ABCs of resuscitation, attempt central access (UVC and/or UAC), rule out other causes (see “Evaluation of Suspected Congenital Heart Disease”), and begin empiric management as follows.

Empiric Management Airway Management (Clin Perinatol 2001;28:91) • Sedation and neuromuscular blockade are options for endotracheal intubation to avoid vagally mediated bradycardia and catecholamine-induced dysrhythmia.

• Goal SpO2 prior to deﬁ nitive diagnosis 80%–85% to prevent potential pulmonary overcirculation.

Prostaglandin E1 • Infants without other identiﬁ ed causes of cyanosis (and hyperoxia test suggestive of CHD), and infants in heart failure or shock (especially within the ﬁ rst 3 wk of life) are presumed to have ductal-dependent CHD until proven otherwise. • If metabolic acidosis is present or echocardiography is not readily available, start empiric

treatment with PGE1. • Relaxes smooth muscle, resulting in dilation of pulmonary vasculature, DA, and systemic vasculature.

• Start: 0.05–0.1 mcg/kg/min; titrate down while monitoring perfusion and SpO2. • Maintenance: Often can decrease dose to 0.0125–0.0250 μg/kg/min once infant is stable. • Second IV access should be obtained for ﬂ uid infusion in case of hypotension. • Patient should be mechanically ventilated if higher doses are anticipated or prior to interfacility transport. • Monitor for pulmonary overcirculation at higher doses in patients with left-to-right

shunt (PGE1 is also a pulmonary vasodilator). Cardiology 385

• Side effects of PGE1: • Apnea • Gastric antral hyperplasia • Hypotension • Tachycardia/bradycardia • Fever • Seizure • Response: Expect a clinical response in 15–30 min for cyanotic CHD (smooth muscle of ductus is particularly sensitive) and 1–3 h for acyanotic CHD (relaxation of pulmonary vasculature not as rapid); response may be delayed or absent in older infants. Titrate as low as possible after stabilization. If decompensation is noted after starting, a lesion with impaired left-heart return may exist (see below); stop infusion immediately. • Contraindications (processes obstructing left heart return): • Infradiaphragmatic (obstructive) TAPVR • Conditions with impaired left heart return (HLHS/cor triatriatum/TGA/mitral stenosis) and restrictive atrial septum Cardiac Catheterization • Temporizing measures (balloon atrial septostomy) are possible in cases with impaired left-

heart return and restrictive atrial septum. Once interatrial ﬂ ow is obtained, PGE1 can be stopped in some cases. Vasopressors • May be necessary if acidosis/heart failure does not resolve with the above measures.

• Ensure adequate intravascular volume after initiation of PGE1. • See Chapter 30 for further information.

Available at www.AccessPediatrics.com • Transitional (Neonatal) Circulation NEONATOLOGY CHAPTER 33 Dermatology

BENIGN NEONATAL RASHES

Disease Description Course Treatment Other

Erythema Erythematous macules, 24–48 h after birth, None Aﬀ ects 50% toxicum papules, pustules, may be seen ≤2 wk of full-term vesicles, or wheals of age neonates on the face, torso, Resolve spontane- Eosinophils on proximal limbs, and ously and heal Wright’s stain buttocks without sequelae of pustules Spares palms and soles

Transient Fragile, superﬁ cial pus- Present at birth None Aﬀ ects darker- neonatal tules; no erythema Hyperpigmentation skinned, pustular After rupture → may last several full-term melanosis collarette of scale and months neonates hyperpigmentation Sterile Widespread, including subcorneal the palms and soles neutrophilic pustules

Miliaria Small, ﬂ accid vesicles Sometimes present Avoid over- Caused by crystalline on the forehead, neck, at birth heating and obstruction of upper trunk, and oc- overswad- eccrine sweat cluded areas dling ducts near the surface of the skin

Miliaria Small erythematous Usually after ﬁ rst wk Avoid over- Caused by rubra papules and pustules of life heating and obstruction on the forehead, neck, overswad- of eccrine upper trunk, and oc- dling sweat ducts cluded areas in the deeper layer of the epidermis

Milia 1- to 2-mm white or Usually resolve by None If seen on yellow epidermoid age 1 mo palate, known cysts usually on the as Epstein’s face Pearls.

Neonatal Discrete, noncome- Onset during ﬁ rst None neces- May be caused cephalic donal papules or 2–3 wk of life; spon- sary; may be by Malassezia pustulosis pustules on an taneously resolves improved spp. (neonatal erythematous base within weeks with topical acne) Usually on the cheeks; clotrimazole also on the forehead, chin, eyelids, neck, upper chest, and scalp

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386 Dermatology 387

Disease Description Course Treatment Other

Acropus- Crops of acral, pruritic May present in the Topical corti- Must exclude tulosis of vesicles and pustules neonatal period but costeroids or scabies (bur- infancy on the hands, wrists, usually at 3–6 mo oral antihista- rows, genital feet, and ankles of age mines involvement); Last 1–2 wk and If severe, microscopic recur in 3–4 wk consider exam of scraping Less frequent dapsone relapses with age; Some pts complete resolution respond to usually by age 3 yr oral erythromycin

Nevus Hairless, thin, orange Progressive thicken- Observation; <1% develop sebaceous plaque on the scalp or ing and a verrucous complete secondary face; may be seen on appearance excision for basal cell the neck or trunk cosmesis carcinoma

Congenital Tan or brown, oval Commensurate Yearly skin Giant nevi with melanocyt- plaques; sometimes growth with age; check for greater risk ic nevus hairy occasionally regress changes of melanoma May become verru- Consider bx progression cous with pigment and excision Neurocutane- changes based on ous melano- clinical cytosis with changes, some larger melanoma scalp or axial risk, location, lesions age, and FH

Nevus Salmon pink, vascular Most fade or resolve None neces- simplex or patch commonly on spontaneously, but sary; pulsed- macular the forehead, upper neck lesions usually dye laser for (vascular) eyelids, or nape of persist cosmesis stain the neck (salmon May become more patch, prominent with crying; angel kiss, blanches with pressure stork bite)

Mongolian Bluish patches often Most fade with time None Document in spot (dermal on the lumbosacral or newborn skin melanocy- buttock areas exam to avoid tosis) Seen more commonly misdiagnosis in patients with darker of bruising or skin and Asians child abuse Diﬀ use or unusual distribution may suggest systemic involvement (eg, storage NEONATOLOGY disease, phakomatosis pigmentovas- cularis) 388 Neonatology

ABNORMAL NEONATAL RASHES

Disease Description Clinical Course Treatment Other

Neonatal Annular plaques Typically resolve Evaluate for inter- Almost all have lupus with raised, red without scarring nal manifesta- anti-Ro antibod- erythema- borders and Dyspigmentation tions: Congenital ies; may also see tosus central clearing may persist for heart block (ECG), anti-La or U1RNP Predilection for months hepatobiliary antibodies disease (LFTs), the face (espe- May have residual Cardiac NLE: thrombocytope- cially periorbital telangiectasias 20% mortal- area) nia (CBC), CNS ity; two-thirds Photosensitivity require pacemakers

Lamellar Collodion baby: First few weeks: Neonatal period: After birth, ichthyosis Taut, shiny ery- Collodion mem- Humidifi ed in- monitor in ICU thematous skin brane replaced cubator, bland for temperature → scaling, fi s- with large platelike emollients, and instability, fl uid sures, superfi cial scales, superfi cial nonadherent and electrolyte desquamation fi ssures dressings for imbalances, and Ectropion Scalp scaling erosions signs of sepsis Eclabion ± scarring alopecia Long-term: PO Genetics referral and topical retin- for counseling, Hypoplastic nasal ± nail dystrophy oids, lactic acid or possible muta- and auricular Ear canals occluded propylene glycol tional analysis cartilage with scales → creams; may recurrent ear infec- need fl uid, calo- tions rie, iron, protein Obstructed sweat supplementation ducts → heat intolerance

Bullous At birth: Erythro- Blistering episodes, congenital derma, erosions, secondary bacterial ichthyosi- peeling, denuded infections, disﬁ g- form eryth- skin urement, malodor roderma or Later: Severe ± scarring alopecia epidermo- hyperkeratosis lytic hyperkeratosis (EHK)

Non- Collodion mem- Collodion mem- bullous brane at birth brane replaced congenital Ectropion by generalized ichthyosi- erythroderma with Eclabion form eryth- persistent scaling roderma (variable severity) Nail dystrophy Obstructed sweat ducts → heat intolerance

(continued on next page) Dermatology 389

Disease Description Clinical Course Treatment Other

Harlequin Thick, platelike Usually premature ichthyosis scale with ex- and may die within treme ectropion, days to weeks eclabion because of compli- May see autoam- cations putation of distal Delayed growth digits and development if the patient survives past infancy

Netherton Generalized Failure to thrive Emollients, kera- syndrome erythroderma, Atopic diathesis tolytics, retinoids, scaling corticosteroids Ichthyosis linearis May have sparse circumﬂ exa: Increased caloric abnormal hair Serpiginous and protein re- migratory annular quirements or polycyclic rash Antibiotics for with double-edged infection scale (usually after age 2 yr) Improves with age; intermittent ﬂ ares

Epidermol- Ranges from mild Onset at birth or Gentle cleansing Increased caloric ysis bullosa blistering to gen- early infancy Nonadherent and protein re- (EB) eralized ﬂ accid Secondary infec- dressings and quirements bullae or erosions tions common topical antibiotics Varied muta- → scarring, for erosions tions contractures, pig- High incidence ment changes of squamous cell Loose-ﬁ tting carcinoma → death clothing ± eye, oral (RDEB) mucosa, GI, GU Cool environ- involvement Upper airway ment obstruction (JEB > RDEB)

Ectodermal May see Hair, nail, teeth, Gentle cleansing Secondary infec- dysplasias desquamation, sweat gland abnor- Bland emollients tions of erosions erythroderma, malities common hyperkeratosis, Nonadherent Hyperthermia dressings and Genetics referral erosions as for counseling neonate Ear anomalies topical antibiotics for erosions Abnormal hair, ± Cleft lip or palate teeth, nails (par- ± Limb anomalies tial or complete)

Staphy- Superﬁ cial bulla Prodrome: Fever, Parenteral Frequently seen lococcal with desquama- malaise, irritability antibiotics in diaper area in scalded tion Scaling or Bland emollients infants skin Perioral crusting desquamation for for denuded skin syndrome Diﬀ use tender 3–5 d after bullae NEONATOLOGY Erythema formation No mucous Reepithelialization membrane in 10–14 d involvement

JEB, junctional epidermolysis bullosa; RDEB, recessive dystrophic epidermolysis bullosa 390 Neonatology

DIAPER RASHES

Clinical Type Description course Treatment Other

Irritant: See Erythematous Exacerbated See below Complication: below for plaques or by scrubbing Secondary additional patches sparing and use of com- bacterial or treatment the inguinal folds mercial wipes or yeast infec- recommenda- Caused by strong detergents tion tions exposure to urine Usually lasts <3 d or stool after treatment is May be perianal if initiated diarrhea is present

Treatment for Irritant Diaper Dermatitis • Frequent diaper changes to reduce urine and stool exposure; rinse with warm water only (avoid using baby wipes/chemical cleansers). • Topical barriers (generous application to clean skin with each diaper change) • First line: Petrolatum (Vaseline), zinc oxide (Desitin), Triple Paste • Second line: Topical sucralfate, Questran in 10%–20% petrolatum (bile acid seques- trant; possibly benefi cial if the infant has diarrhea) • Avoid: All powders and all agents containing fragrance, preservatives, camphor, phenol, benzocaine, salicylates • Topical antifungals (nystatin, miconazole, clotrimazole, ketoconazole): Indicated when dermatitis appears to be candidal or after rash present for 3+ d (increased risk of superinfection with increased duration of rash). Consider culturing affected areas before starting antifungals if diagnosis is uncertain. Apply before barrier three to four times daily until resolved. • Topical steroids (1% or 2.5% hydrocortisone or desonide): For 3–5 d applied before barrier for severe infl ammation; may use along with topical antibiotics or antifungals • Daytime: Increase air exposure time by leaving off a diaper for short time between changes and during nap time; loosen diaper to increase air fl ow • Nighttime: Diaper change at least once during the night Refractory Diaper Dermatitis • Always consider histiocytosis, nutritional defi ciencies (zinc, biotin), child abuse, immunodefi ciency syndromes, seborrhea, psoriasis, bacterial infection, and IBD

Candidal Beefy, red plaques May cause Topical nystatin Suspect diaper involving the discomfort with or imidazole, when irritant dermatitis inguinal folds urination or barrier creams, dermatitis Satellite red pap- defecation frequent diaper does not ules or pustules changes (see improve above) within several Desquamation at days border Rarely, low- potency topical corticosteroid

Perianal Bright red, sharply Itching, rectal 1 wk course of Rapid strep streptococcal demarcated pain; may have cephalosporin; test or skin dermatitis plaques blood-streaked or 10–14 d cx of aﬀ ected May involve vulvar stools if skin is course of PCN, area positive or penile area eroded amoxicillin, or for GABHS erythromycin; May have ﬁ ssur- Often misdi- ± topical ing, mucoid dis- agnosed and antibiotics charge, crusting treated for other causes before dx is made

(continued on next page) Dermatology 391

Clinical Type Description course Treatment Other

Psoriasis Shiny, bright red, May have Barrier creams, well-demarcated satellite spread TCI, low- plaques involving of psoriasiform potency TCS for the skin folds papules to the no longer than Lacks the yellow trunk, limbs, 2 wk intervals (if scale often seen face, and scalp symptomatic) with seborrheic dermatitis

Seborrheic Greasy, scaly, Usually begins Bathing Linked with dermatitis crusted, 1 wk after birth Frequent mois- sebum erythematous May persist for turization overproduc- plaques tion and months Ketoconazole Malassezia Involves skin folds, 2% cream if spp. diaper area, scalp extensive or No satellite lesions persistent May be psorias- Short course iform of low-potency topical corticosteroids if inﬂ amed

Acroder- Perioral and Usually appears Zinc supple- If no tx → FTT matitis perianal and acral within 1–2 wk mentation: Low serum enteropathica erythematous after breast 3 mg/kg/d zinc with low (AR defect patches and milk weaned alk phos in intestinal plaques with 2° or at 4–10 wk if absorption of scale and crust, bottle fed zinc) erosions, vesicles, Secondary or bullae infections with Chronic: Licheni- Staphylococcus ﬁ ed psoriasiform and Candida plaques spp. are com- ± other mucocu- mon taneous ﬁ ndings: Blepharitis, conjunctivitis, cheilitis, stomatitis

Langerhans Tender, coalescent May become Skin: TCS, topi- Multiorgan cell pink papules, impetiginized cal antibiotics, disease with histiocytosis pustules and Congenital form PUVA high mortal- vesicles on the often limited to Systemic: Che- ity rate, scalp, neck folds, the skin and is motherapy may appear axillae, perineum, self-healing like severe and trunk → ery- seborrheic Other forms thematous eroded dermatitis, often assoc with plaques, scaling, with erosions, multisystem crusting hemorrhagic disease NEONATOLOGY ± plaques on crusts. Can gingivae see erosions in body creases. CHAPTER 34 Endocrinology

ADRENAL AND PITUTARY INSUFFICIENCY IN NEONATES PRIMARY ADRENAL INSUFFICIENCY

Inherited Causes Adrenocortical Impaired Steroid Disorders of Steroid Dysgenesis Responsiveness Biosynthesis Acquired Causes

• Caused by Pseudohypoaldos- StAR (acute steroid regula- Exogenous mutations in teronism: tory protein) defi ciency: glucocorticoid DAX1 and SF1 • Mutation of • Mediates transfer of choles- administration: genes aldosterone terol across mitochondrial • Infants receiv- • These genes receptor gene or of membrane ing high-dose encode a epithelial sodium • Adrenals are large and lipid glucocorticoids for nuclear tran- channel genes laden >10–14 d are at scription factor high risk • Clinical presenta- • Decreased levels of all expressed in tion with salt wast- adrenal steroids • May require both gonads ing, hyperkalemia, hydrocortisone • 46 XY males appear female and the adrenal shock, dehydration for unexplained cortex or only minimally virilized Familial unrespon- hypotension or 3-β-Hydroxysteroid dehydro- • Results in siveness to ACTH: hypoglycemia or defi ciency of all genase defi ciency: in preparation for • Results in normal adrenal steroids surgery mineralocorticoid • Catalyzes the conversion of pregnenolone, 17-OH- activity, with Bilateral adrenal pregnenolone, DHEA, and diminished gluco- hemorrhage: androstenedione corticoid activity • Can be seen in • Clinical manifestations: • Clinical presenta- LGA infants with tion with profound • Salt-wasting adrenal crisis diffi cult delivery/ hypoglycemia and • 46, XX female may be coagulopathy hypotension mildly virilized • Asymptomatic • 46, XY male is undervirilized infants can have • Elevated substrates: DHEA suprarenal calci- and 17-OH-pregnenolone fi cations on plain • Elevated 17-OH- fi lm of abdomen progesterone 21-Hydroxylase defi ciency: • Most common cause of CAH • Classic salt-wasting CAH: • Adrenal crisis with shock, hyperkalemia, and hyponatremia • Polyuria • Presentation at 1–4 wk of life • 46, XX infants are virilized

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392 Endocrinology 393

Inherited Causes Adrenocortical Impaired Steroid Disorders of Steroid Dysgenesis Responsiveness Biosynthesis Acquired Causes

• 46, XY infants have large phallus and hyperpigmented scrotum • Markedly elevated levels of 17-OH-progesterone Aldosterone synthase deﬁ ciency: • Rare condition • Hyponatremia and hyperkalemia

Diagnosis of Adrenal Insuffi ciency • ACTH or glucagon stimulation • Cortisol concentration should exceed 15–20 mcg/dL (413.8–551.8 nmol/L) 1 h after IV administration of cosyntropin (ACTH) 100 mcg/m2 or 2–3 h after IV administration of glucagon 50 mcg/kg • Markedly elevated enzyme substrates • DHEA and 17-hydroxypregnenolone concentrations in 3-β-hydroxysteroid dehydrogenase defi ciency • 17-Hydroxyprogesterone in 21-hydroxylase defi ciency • All C19 and C21 steroids are low in StAR defi ciency

Treatment of Acute Adrenal Insufﬁ ciency • IV glucose and normal saline for hypoglycemia and hypotension, respectively • IV hydrocortisone 50 mg/m2 to be given immediately, followed by maintenance dose of 50–100 mg/m2/day in four to six divided doses or by continuous infusion • Oral ﬂ udrocortisone 0.05–0.1 mg once daily for hyperkalemia or salt-wasting

SECONDARY ADRENAL INSUFFICIENCY

Etiologies Clinical Presentation Diagnosis Treatment

• Secondary to • Unexplained hypoglycemia • Random • Fluid resuscita- single gene after 4–5 postnatal days of age growth hor- tion in acutely mutations • Unexplained hypotension mone is hypotensive <5 ng/mL (nl is infant • Malforma- • Findings associated with 8–15 ng/mL) tions or injury hypopituitarism: • Hydrocortisone to the sella • Low random 50–100 mg/m2 IV • Lack of onset or abnormal turcica or and stimulated as a single dose, progression of labor hypothalamus cortisol levels then to 10 mg/ • Midline craniofacial or CNS m2/day in three deﬁ cit • Low random free T and TSH divided doses • Nystagmus, optic nerve 4 levels daily

hypoplasia, and other ocular NEONATOLOGY • Growth hormone abnormalities at 40 mcg/kg/day • Hypoplastic genitalia in boys SQ once daily • Prolonged jaundice; elevated • Oral levothyroxine hepatic transaminases 15 mcg/kg/day

(continued on next page) 394 Neonatology

Etiologies Clinical Presentation Diagnosis Treatment

• Hypernatremia, polyuria

• Low TT4 and inappropriately normal TSH values on newborn screen • MRI ﬁ ndings: ectopic posterior pituitary “bright spot,” small anterior pituitary, and attenuated or interrupted pituitary stalk

HYPOTHYROXINEMIA AND PREMATURITY See below for an algorithm for the workup of an abnormal-state newborn screen as far as thyroid function screen.

Abnormal thyroid screen on state Newborn Screen (NBS) in an asymptomatic infant

Check Send serum repeat TSH, FT4 NBS

Repeat NBS TSH and TSH and/or Repeat NBS with abnormal T4 normal T4 abnormal normal thyroid screen

No follow No follow up needed up needed

• Send FT4 by equilibrium dialysis (from a non-heparinized line in a non-heparinized tube) • Consider endocrinology consult

Figure 34-1 Algorithm for workup of an infant with abnormal newborn thyroid screen.

Other Considerations • VLBW infants (<1500 g) have an eightfold risk of developing transient primary hypothyroidism. • The prevalence of primary or secondary hypothyroidism in preterm infants is similar to that seen in term infants (approximately 1:4000); there are no estimations on the prevalence of hypothyroxinemia of prematurity. • It is important, but very difﬁ cult, to distinguish central hypothyroidism from hypothyroxinemia of prematurity, and additional clinical ﬁ ndings should raise suspicion of central hypothyroidism: • Microphallus • Cleft lip/palate Endocrinology 395

• Midline facial hypoplasia • Nystagmus • Hypoglycemia • Prolonged unconjugated hyperbilirubinemia • Cortisol, growth hormone, prolactin, or gonadotropin deﬁ ciency • Radiologic evidence of structural brain abnormalities (including intraventricular hemorrhage)

Neurodevelopmental Outcome and Hypothyroxinemia in the Preterm Infant • Neurologic dysfunction at 5 yo and school failure at 9 yo were signiﬁ cantly related to

lower neonatal T4 values, even after adjustment for other perinatal factors. • Severe hypothyroxinemia had an 11-fold increased risk of disabling cerebral palsy compared with infants who did not have hypothyroxinemia. • However, no causal relationship has been established between neurodevelopmental outcome and hypothyroxinemia. Thyroid Hormone Supplementation for Preterm Infants with Hypothyroxinemia • Cochrane systematic review concluded that available data do not support the use of prophylactic thyroid hormones in preterm infants to reduce neonatal mortality or morbidity or to improve neurodevelopmental outcomes. (Cochrane Database of Systematic Reviews 2007(1), CD005948)

HYPERKALEMIA Deﬁ nition • Serum potassium > 6.5 mEq/L Etiology • Decreased excretion • Increased load • Redistribution • Factitious CAUSES OF HYPERKALEMIA IN THE NEONATE

Etiology Examples

Decreased • Acute kidney injury excretion • Positive potassium balance in the VLBW infant in the ﬁ rst few days of life • Adrenal failure (eg, congenital adrenal hyperplasia, bilateral adrenal hemorrhage) • Medications • Potassium-sparing diuretic • Propranolol • Indomethacin • ACE inhibitors NEONATOLOGY Increased • Hemolysis potassium load • Intraventricular hemorrhage • Hematoma • Excess potassium administration • Tissue necrosis

(continued on next page) 396 Neonatology

Etiology Examples Redistribution of • Secondary to metabolic or respiratory acidosis potassium • Sepsis • Necrotizing enterocolitis • Renal tubular acidosis • Medications • Digoxin Factitious reasons• Hemolysis due to heel-stick specimen • Thrombocytosis

Evaluation • Laboratory studies • Electrolytes • BUN, creatinine • Platelet count • Blood gas, ionized calcium • Total calcium and magnesium • Serum glucose (as a baseline before further interventions, see below) • Adjunct studies • ECG to assess for progressive changes associated with hyperkalemia (peaked T waves, prolonged PR interval, loss of P wave, widening of the QRS complex, sine wave QRS-T, ventricular dysrhythmia, asystole) Treatment • Ensure continuous cardiac monitoring. • Without electrocardiographic changes • Stop any potassium-containing IV ﬂ uids and/or enteral potassium supplements. • Monitor potassium levels frequently. • If potassium levels continue to rise or ECG changes develop, then proceed as below. • With electrocardiographic changes • Administer 100 mg/kg of 10% calcium gluconate or 20 mg/kg of 10% calcium chloride over 30–60 min (goal: stabilize the conducting tissues of the heart). • If acidosis is present, administer sodium bicarbonate (1–2 mEq/kg) over 10–20 min (goal: induce redistribution of potassium from the extracellular space to the intracellular space in exchange for hydrogen). • If the infant is normoglycemic, administer insulin concomitantly with glucose to prevent hypoglycemia (Goal: induce redistribution of potassium from the extracellular space to the intracellular space).

• Dose is 0.1 unit/kg of regular insulin in 2 mL/kg of D25W to be given IV over 15–60 min. • This may be repeated in 30–60 min as needed. • Follow serum glucose levels every 30–60 min until stable. • An adequate glucose source is critical and GIR may need to be ≥8–10 mg/kg/min to assist in stimulating endogenous insulin secretion and provide adequate glucose to administer the insulin infusion so as not to cause hypoglycemia. • If hyperkalemia is refractory, peritoneal dialysis or a double-volume exchange transfusion may be necessary. HYPOKALEMIA General Principles • Serum levels generally do not reﬂ ect total body potassium content to shifts to and from different body compartments in relation to pH. • Balance is maintained by regulation of intake (IV ﬂ uids and enteral) and excretion (renal and GI). Endocrinology 397

• Hypokalemia can lead to arrhythmias (prolongation of the QT segment on ECG), ileus, renal concentration defects, and alteration in mental status.

ETIOLOGY AND MANAGEMENT

Possible Etiologies Evaulation Treatment

• GI losses • Serum and urine pH • If possible, reduce potassium • Nasogastric suction and electrolytes losses. • Ileostomy drainage • ECG to evaluate for QT • Supplement potassium as needed. • Chronic diuretics prolongation • Renal tubular defects

NEONATAL HYPERCALCEMIA Deﬁ nition • Hypercalcemia is deﬁ ned as serum total calcium level >11 mg/dL (iCa >1.36 mmol/L). Investigations • Blood: Total and ionized calcium, pH, phosphorus, alkaline phosphatase, creatinine, intact PTH level, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, serum total protein • Urine: Calcium/creatinine ratio, tubular absorption of phosphate • Imaging: Renal ultrasonography, long-bone radiographs • Other tests: PTHrP, vitamin A levels, parents’ serum and urine calcium

ä Serum Total Calcium

↑ iCa Normal iCa • Increased binding to albumin or globulin Check PTH

↑ PTH Normal PTH ↓ PTH • Primary (NSHPT) or • Familial secondary hypocalciuric hyperparathyroidism hypercalecemia

Check Vit D1

↑ Vit D metabolites Normal Vit D ↓ Vit D metabolites • Subcutaneous metabolites • Iatrogenic fat necrosis • Idiopathic • Malignancy (PTHrP) • Granulomatous • Hypervitaminosis A infantile NEONATOLOGY disease hypercalcemia • Hypophosphatasia • Jansen's metaphyseal • Williams chondrodysplasia Syndrome • Hypophosphatemia • Vitamin D intoxication

Figure 34-2 Workup of Neonatal Hypercalcemia. NSHPT, neonatal severe hyperparathyroidism; PTHrP, parathyroid hormone-related peptide 1 Serum 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 levels 398 Neonatology

Management • Depends on cause of hypercalcemia • Asymptomatic hypercalcemia requires no speciﬁ c treatment, although adjusting calcium intake and vitamin D supplementation may be considered. • Mild hypercalcemia (1.45–1.60 mmol/L) • No speciﬁ c therapy is needed. • If persistent, a change in Ca:Phos ratio in TPN by no more than 20% will correct hypercalcemia in 48 h. • Do not remove calcium in TPN if iCa is lower than 1.6 mmol/L. • Moderate hypercalcemia (>1.6 mmol/L) • Decrease Ca:Phos to 0.5:1–0.8:1. • If iCa is >1.8 mmol/L, remove Ca from TPN, and discontinue or decrease phosphorus intake by 50%. • Measure iCa every 12 h until levels are back to normal. • Resume IV calcium when iCa is below 1.45 mmol/L. • Symptomatic hypercalcemia • Volume expansion if cardiac function is normal (can give 10–20 mL/kg of normal saline over 15–30 min). • Furosemide may be given to promote calciuria. • Discontinue thiazide diuretics (if applicable). • Inorganic phosphate may lower serum calcium in hypophosphatemic patients. • Glucocorticoids are effective in hypervitaminosis A and D and in subcutaneous fat necrosis; they are ineffective in hyperparathyroidism. • In older children and adults, calcitonin has been used as an adjunctive therapy; very little data on the use of calcitonin in neonates exist. • In severe cases, parathyroidectomy with autologous reimplantation may be helpful.

NEONATAL HYPOCALCEMIA Deﬁ nition • In infants >1500 g, hypocalcemia is deﬁ ned as iCa concentration <1.0 mmol/L (normal range is 1.0–1.4 mmol/L). • In VLBW infants, iCa levels as low as 0.8 mmol/L are usually well tolerated, without development of symptoms.

Early Hypocalcemia • Deﬁ nition • Usually occurs in the ﬁ rst 4 DOL • An exaggeration of the fall in serum calcium concentration

CAUSES OF EARLY HYPOCALCEMIA IN THE NEONATE

Cause Mechanism

Prematurity• Abrupt interruption of the placental supply • Low intake provided by oral and parenteral nutrition • Insuﬃ cient release of PTH by the immature parathyroid glands • Inadequate responsiveness of the renal tubular cells to PTH • Exaggerated rise in calcitonin secretion • High renal sodium excretion aggravates calciuric losses

• End-organ resistance to 1,25 (OH)2D3

(continued on next page) Endocrinology 399

Cause Mechanism

Maternal diabetes• Related to hypomagnesemia caused by maternal hypomagnesemia secondary to urinary losses of magnesium → degree of hypocalcemia in proportion to severity of maternal diabetes • Functional hypoparathyroidism

Perinatal asphyxia• Delayed enteral feedings • Increased phosphorus load secondary to decreased GFR • Increased calcitonin concentration • Correction of acidosis with alkali

Maternal anticonvulsants • Increased catabolism of vitamin D → relative vitamin D deﬁ ciency

Late Hypocalcemia • Deﬁ nition • Occurs after the ﬁ rst 4 DOL

CAUSES OF LATE HYPOCALCEMIA IN THE NEONATE

Cause Mechanism

Phosphate loading• The renal tubules in the immature kidneys of the neonate are unable to respond to PTH, leading to inability to excrete phosphorus • Low GFR in neonates also contributes to decreased phosphorus excretion • Also seen in infants fed with cow’s milk or evaporated milk that is high in phosphorus • High phosphate load causes calcium bone deposition; however, the neonate appears to have “transient hypoparathyroidism” and is unable to respond appropriately

Hypomagnesemia• Magnesium deﬁ ciency inhibits the secretion of PTH and reduces responsiveness to its action • Primary hypomagnesemia with secondary hypocalcemia • Autosomal recessive disorder • Primary defect in intestinal transport of magnesium • Serum magnesium level is usually <0.8 mg/dL; low PTH • Transient neonatal hypomagnesemia • Associated with hypocalcemia • Renal magnesium wasting results from administration of loop diuretics, aminoglycosides, amphotericin B, urinary tract obstruction, or diuretic phase of renal failure • Low serum magnesium associated with inappropriately high urinary magnesium excretion NEONATOLOGY Primary neonatal • PTH deﬁ ciency hypoparathyroidism

Secondary neonatal • Maternal hypercalcemia → fetal hypercalcemia → fetal hypoparathyroidism hypoparathyroidism • As the increased placental delivery of calcium is abruptly interrupted at delivery, infant is at high risk for developing hypocalcemia

(continued on next page) 400 Neonatology

Cause Mechanism

Congenital • Inherited as X-linked or autosomal recessive abnormalities of • Rearrangement or microdeletions aﬀ ecting the short arm of chromo- parathyroid glands some 22q11 • Seen in DiGeorge and velocardiofacial syndromes • Incomplete development of the branchial arches, resulting in varying degrees of parathyroid and thymic hypoplasia

Abnormalities • Mutation in the gene for PTH, leading to defective PTH of PTH

Defective • Mutation of the parathyroid and renal CaSR, leading to excessive regulation of PTH calcium-induced inhibition of PTH secretion secretion

Vitamin D • Can result from maternal vitamin D deﬁ ciency deﬁ ciency • Decreased intestinal and renal absorption of calcium

Infantile osteo- • Inherited as autosomal recessive petrosis • Failure of osteoclasts to resorb immature bone, leading to abnormal bone cavity formation • Classic features are fractures, visual impairment, and bone marrow failure

Bicarbonate • Decreases ionized calcium levels and bone resorption of calcium therapy

Blood or blood • Citrated blood can form nonionized calcium complexes product transfusion

Diuretic and • Promotes calciuresis and nephrocalcinosis/nephrolithiasis xanthine therapy

Lipid infusion (TPN)• Serum free fatty acids form insoluble complexes with calcium

Clinical Manifestations of Hypocalcemia • Asymptomatic • Agitation • Generalized seizures (focal seizures have been reported) • Nonspeciﬁ c signs, such as lethargy, vomiting, and abdominal distention

Evalutation

WORKUP FOR NEONATAL HYPOCALCEMIA

Early Hypocalcemia Late Hypocalcemia

• Serum ionized calcium: • Total and ionized serum calcium Measure at 24 h of life • Serum phosphorus and magnesium and every 12 h thereafter • CXR (thymic shadow, aortic arch position) until the infant is receiving Ca either from TPN or • Intact PTH level a milk source and has a • Genetic studies: FISH or CMA for chromosome 22q deletion stable, normal ionized Ca. • Consider sepsis/meningitis workup • Serum magnesium • Endocrine consult is optional if history is typical and thymus is • Serum phosphorus seen on CXR • Consider EEG and CT scans if history and presentation are atypical Endocrinology 401

TREATMENT

Early Hypocalcemia Late Hypocalcemia Symptomatic infant of any IV therapy gestation • Bolus infusion of Ca gluconate 100 mg/kg (10 mg/kg • IV administration of 100 mg/kg of elemental calcium) over 30–60 min 10% calcium gluconate 30–60 min • If central line is in place, begin calcium gluconate infusion or 20 mg/kg of calcium chloride at 1000 mg/kg/day (~100 mg/kg/day elemental calcium) over 10–20 min, then start main- • If central line is not available, limit calcium gluconate tenance therapy with IV calcium infusion to 600 mg/kg/day ( ~60 mg/kg/day elemen- gluconate at 500 mg/kg/d; patients tal calcium) regardless of iCa value receiving calcium boluses should be placed on cardiorespiratory monitors • Measure iCa 1 h after the bolus, then every 4 h. When iCa is >1.0 mmol/L and symptoms have been controlled, • If concomitant hypomagnesemia, start IV maintenance therapy using decrease frequency of monitoring to every 6–8 h magnesium sulfate 25–50 mg/kg/ • If iCa remains <1.0 mmol/L after initial bolus, repeat dose over 1–2 h twice daily until infusion of Ca gluconate 100 mg/kg while continuing levels normalize current rate of IV Ca infusion • If iCa is 1.0–1.20 mmol/L, no additional IV boluses of Asymptomatic infants <1500 g calcium needed, but maintain infusion rate • Start TPN with calcium as soon as • Consider oral feeds and start oral supplement with possible Ca glubionate (Neo-Calglucon; see below) • If TPN is not available, add Ca glu- • If iCa is 1.21–1.30 mmol/L, decrease Ca gluconate infu- conate 500 mg/kg/d to IV infusion sion to 250 mg/kg/d (~ 25 mg/kg/d elemental Ca) • If calcium will be used in TPN for • Start oral feeds and oral supplement with Ca glubi- more than 48 h, add phosphorus to onate (Neo-Calglucon; see below) avoid hypercalcemia • Discontinue IV Ca infusion if iCa is >1.21 mmol/L on Asymptomatic infants >1500 g two measurements and patient is tolerating feeds with oral Ca glubionate • Treat if iCa is <1.0 mmol/L • If iCa is ≥1.3 mmol/L and feeds and oral Ca supple- • For infants requiring IV therapy, ments have been started, discontinue IV Ca infusion begin IV Ca gluconate 500 mg/kg/d • If serum Mg is <1.6 mg/dL, give magnesium sulfate infusion 25 mg/kg IV over 1–2 h • For infants on enteral feeds, intravenous Ca may not be needed, • Measure serum Mg after completing infusion, and repeat bolus every 12 h until Mg level is ≥1.6 mg/dL but monitor serum ionized Ca and phosphorus regularly • Use of calcitriol at the discretion of the endocrine service

Oral Therapy • Applies when asymptomatic and iCa ≥1.0 mmol/L • Start oral feeds with breast milk, Similac PM 60/40 (Abbott Laboratories), or Gerber Good Start (Nestlé) • Start oral Ca supplement with Ca glubionate (Neo-Calglucon) 720 mg/kg/d divided four times daily (0.5 mL/kg PO q6h). This will provide ~50 mg/kg/d of elemental Ca. • Maximum oral calcium glubionate that can be given is 1200 mg/kg/d or ~75 mg/kg/d elemental Ca. This product is hyperosmolar and can cause diarrhea. Each mL of Neo-Calglucon provides 360 mg of Ca glubion-

ate or 23 mg of elemental Ca NEONATOLOGY

OSTEOPENIA OF PREMATURITY Deﬁ nition • Osteopenia of prematurity is deﬁ ned as postnatal bone mineralization that is inadequate to fully mineralize bones. 402 Neonatology

ETIOLOGY

Cause Examples

Deﬁ ciency of • Unfortiﬁ ed breast milk calcium and • Long-term TPN phosphorus • Use of inappropriate formula to feed preterm infants (principal cause) • Furosemide therapy • Long-term corticosteroid use • Renal phosphorus wasting

Vitamin D • Maternal deﬁ ciency → congenital rickets deﬁ ciency • Inadequate postnatal supplementation → nutritional rickets • Vitamin D malabsorption → hepatobiliary rickets • Chronic renal failure (renal osteodystrophy) • Chronic use of phenytoin or phenobarbital → increased 25(OH)D metabolism • Hereditary • Decreased 1-α-hydroxylase activity

• Tissue resistance to 1,25(OH)2D3

Clinical Features • VLBW infant with a history of fl uid restriction and on prolonged TPN and/or corticosteroids • “Washed out” or undermineralized bones—signs develop during the fi rst few weeks of life • Signs of rickets will develop after 6 wk of age • Incidental fi nding of healing fractures on routine X-rays is common • Respiratory insuffi ciency/inability to wean from mechanical ventilation • Pain on movement due to pathologic fractures • Decreased linear growth with sustained head growth • Acquired skull abnormalities (frontal bossing, craniotabes) • “Rachitic rosary” (enlargement of costochondral junctions) when overt rickets is present

Evaluation of Osteopenia of Prematurity WORKUP OF OSTEOPENIA OF PREMATURITY

Laboratory Studies Imaging Studies

• Serum phosphorus • Wrist or knee ﬁ lms and/or CXR • Usually low, typically <4 mg/dL (<1.3 mmol/L) • Epiphyseal growth plate widening • Serum calcium • Cupping or fraying of metaphyses • Can be low, normal, or elevated • Subperiosteal bone formation • Not a good indicator of metabolic bone disease • Osteopenia (especially of skull, • Serum alkaline phosphatase spine, scapulae, and ribs) • Pathologic fractures (new or • Often, but not always, correlates with degree of dis- healing) ease severity (>1000–1200 IU/L in severe rickets) • Up to 40% of bone mineralization • Normal VLBW infant without osteopenia can have can be lost before radiographic alkaline phosphatase in the 400–600 IU/L range changes occur • Alkaline phosphatase can also be elevated due to obstructive hepatobiliary disease; correlation with • Bone mineral content measurements remain investigational clinical course and radiographic studies is warranted • Vitamin D and PTH levels • Should be reserved for complicated cases or cases not responding to routine therapy Endocrinology 403

Prevention and Treatment • Early initiation of enteral feedings, as clinical condition allows • Use of human milk fortiﬁ ers if receiving breast milk or use of premature formulas for infants with birth weight <1800–2000 g, regardless of gestational age (caloric intake on these feeding regimens should be approximately 120 kcal/kg/d); this will ensure adequate calcium and phosphorus intake • Discontinue use of medical formulas in VLBW infants as soon as possible • Vitamin D intake should be approximately 400 IU/d • Avoidance of furosemide to decrease calcium wasting; consider adding or changing to thiazide diuretic • Avoidance of unnecessary handling of infants with known osteopenia to prevent pathologic fractures • Gently daily passive ROM may enhance growth and bone mineralization • Monitor serum calcium, phosphorus, and alkaline phosphatase periodically

Outcome • At 6 mo of corrected age, spine and total bone mineral densities, corrected for anthropometric values, are in the range of normal-term newborn infants. • At 8–12 yo, formerly preterm infants were shorter and lighter and had lower bone mineral concentration than controls.

NEONATAL HYPERGLYCEMIA Deﬁ nition • Plasma glucose >145 mg/dL or whole blood glucose >125 mg/dL. Values up to 250 mg/dL have not been associated with speciﬁ c morbidity.

Etiology • Excessive exogenous parenteral glucose • Drugs (steroids, caffeine, phenytoin, diazoxide) • VLBW infants (birth weight <1500g): insulin resistance, dysregulated gluconeogenesis • Sepsis • Physiologic stress (mediated by catechols and regulatory/counterregulatory hormone balance) • Hypoxia • Transient neonatal diabetes mellitus (a very rare condition, usually resolved by 3–6 mo of age, but has a signiﬁ cant risk of recurrence in the 2nd and 3rd decades of life • Postsubtotal pancreatectomy for insulin-producing tumors • Aplastic pancreas or islet cell hypoplasia • Ingestion of hyperosmolar formula • Dysregulated gluconeogenesis • Immaturity of glucose transport proteins

Management • Insulin therapy is reserved for infants already receiving low glucose infusion rates (4–6 mg/kg/min) with persistent blood glucose values >220 mg/dL. If insulin therapy is required (note that all doses are expressed in terms of regular insulin): • Give an initial insulin bolus (0.025–0.1 units/kg, depending on the infant’s weight and NEONATOLOGY blood glucose level). • Follow bolus with insulin infusion at 0.01 units/kg/h. Care should be taken to ensure that IV tubing is ﬂ ushed with the insulin solution in order to saturate the binding sites on the tubing. This prevents the insulin from sticking to the plastic tubing. • Check glucose levels hourly until stable. • Titrate insulin infusion rate by 0.01 units/kg/h until goal blood glucose values of 150–220 mg/dL are obtained. 404 Neonatology

• If blood glucose value falls below 100 mg/dL, discontinue insulin infusion, and continue to follow serial blood glucose measurements until stable. • Adjust insulin dose with increasing caloric intake. • Goal is to maintain blood glucose concentration at a level between 100 and 150 mg/dL.

NEONATAL HYPOGLYCEMIA Defi nition • Defi nition is controversial, but generally accepted as a plasma glucose <40 mg/dL in any infant, regardless of gestational age. Goal is to maintain a glucose level of >45 mg/dL in the fi rst 24 h, then >50 mg/dL beyond the fi rst 24 h. • Plasma glucose concentration in all neonates reaches a nadir between 30 and 90 min after birth, and then stabilizes between 45 mg/dL and 80 mg/dL by 3–6 h. • Glucose levels <40 mg/dL warrant intervention as described below.

MECHANISMS OF HYPOGLYCEMIA IN HIGH-RISK POPULATIONS

Mechanism of Hypoglycemia Examples Increased glucose utilization • LGA infants (hyperinsulinism) • IDM • Islet cell hyperplasia or neoplasia (adenoma, nesidioblastoma) • Beckwith–Wiedemann syndrome • Abrupt cessation of high glucose infusion (such as in infants born to mothers with poorly controlled DM) • Post-exchange transfusion with blood containing high glucose concentration (ie, exchange with CPD) blood • Erythroblastosis fetalis

Decreased carbohydrate stores/ • Prematurity production • IUGR • SGA infants • Postmature infants • Severe maternal preeclampsia • Delayed initiation of feeds/inadequate glucose infusion

Mixed cause (combination of • Perinatal stress (sepsis, shock, hypothermia, increased utilization and decreased asphyxia, postresuscitation) production) • Post-exchange transfusion with heparinized blood low in glucose concentration • Polycythemia • Maternal therapy with β blockers

Inborn errors of metabolism• Defects in carbohydrate metabolism (eg, glycogen storage disease, hereditary fructose intolerance, galactosemia) • Amino acidopathies (eg, MSUD, propionic academia, methylmalonic academia, tyrosinemia, HMG-CoA lyase deﬁ ciency, glutaric acidemia type II) • Defects in fatty acid metabolism (eg, medium- and long-chain fatty acid deﬁ ciencies)

(continued on next page) Endocrinology 405

Mechanism of Hypoglycemia Examples Impaired glucose mobilization • Growth hormone defi ciency (hormone defi ciencies) • Glucagon defi ciency • Cortisol defi ciency • Panhypopituitarism • Resistance to ACTH • Epinephrine defi ciency • Thyroid hormone defi ciency • Hypothalamic hormone defi ciencies

Clinical Features

• Some infants may be asymptomatic until • Grunting, tachypnea severely hypoglycemic • Seizures • Weak or high-pitched cry • Hypothermia • Irritability, jitteriness, tremors • Sweating • Apnea, cyanotic spells • Hypotonia, limpness • Feeding difﬁ culties • Tachycardia • Lethargy or stupor

Diagnosis • Bedside testing using colorimetric assay should not be used, as this method requires user interpretation and hence inter-user differences. • POC devices are acceptable, as they eliminate the need for user interpretation. • If the POC device shows persistent hypoglycemia, a stat conﬁ rmatory test should be sent to the laboratory. • Treatment should not be delayed while waiting for results of a conﬁ rmatory test.

Treatment Asymptomatic Infants • All infants at risk for hypoglycemia should have serial glucose levels documented (ie, Q2h for 8 hours after delivery). • Infants who are asymptomatic should have feeds initiated as soon as the infant’s condition allows (breastfeeding or formula, as per the mother’s request), with a repeat glucose level 20 min after feed. • Feeds of glucose water will transiently raise glucose level but will often trigger a rebound hypoglycemia and should therefore be avoided. • If blood glucose level does not normalize after fi rst feed, more aggressive measures may be required (see below). Symptomatic Infants • All symptomatic infants, regardless of age or cause, should be treated with parenteral glucose infusion emergently because long-term complications are signifi cant. • Bolus should be given at 2 mL/kg of D10W over 1 min followed by a continuous glucose infusion providing GIR 6–8 mg/kg/min. NEONATOLOGY (% dextrose concentration) × (mL/kg/day of fl uids) GIR (mg/kg/min) = 144

For example, if an infant is receiving D12.5W at 100 mL/kg/day, the GIR would be (12.5 × 100)/ 144 = 8.7 mg/kg/min 406 Neonatology

• The goal is to maintain plasma glucose concentration >50 mg/dL.

• If repeat blood glucose is <50 mg/dL, give another bolus of 2 mL/kg D10W, and increase GIR by 10%–20%. Check blood glucose after 20 min. • Blood glucose measurement should be done 20 min after therapy is initiated and should be regularly monitored q1–2h until stable, then q4–6h. • Weaning from parenteral glucose may be done when the plasma glucose has stabilized to >60 mg/dL for 3–4 h. Glucose infusion can be decreased every 1–2 h by 10%–20% while continuing to follow serial blood glucose levels. • In situations where the infant must be given dextrose concentrations >12.5%, central venous access must be obtained (eg, UVC or PICC). • Feeding can be continued once the blood glucose levels are stable and within an acceptable range (as long as a metabolic defect is not suspected). • Continue to monitor preprandial blood glucose levels until infant has been completely weaned off IV ﬂ uids. • Infants who require continuous IV infusion of glucose for >5–7 d to maintain normoglycemia will require more extensive evaluation and may require pharmacologic interventions. An endocrine consult should be considered at that time. The following laboratory studies should be considered (see the table below).

WORKUP OF PERSISTENT NEONATAL HYPOGLYCEMIA

When to Obtain Test Laboratory Study

During period of hypoglycemia• Insulin • Glucose (to calculate insulin:glucose ratio; a value >0.30 indicates a nonhyperinsulinemic cause) • Cortisol • Glucagon • Growth hormone • Serum and/or urine ketones (should be absent in cases of hyperinsulinism) • Lactate

At any time• Fatty acid proﬁ le

• Thyroid function studies (TSH, T4) • Uric acid • Plasma amino acids • Urine organic acids • Urine-reducing substances • Abdominal imaging

• Pharmacologic therapy may be required for persistent hypoglycemia: intramuscular glucagon (assumes the infant has adequate glycogen stores), diazoxide (for hyperinsulinism). • Surgical intervention with subtotal pancreatectomy may be required for infants with insulin-producing tumors.

HYPERNATREMIA Deﬁ nition • Serum sodium >150 mmol/L

Etiology • Increased insensible water losses • Inadequate water intake Endocrinology 407

• Excess sodium administration • Following administration of sodium bicarbonate during resuscitation • Increased free water losses from the urinary tract

APPROACH TO THE NEONATE WITH HYPERNATREMIA BASED ON VOLUME STATUS

ECF Volume Possible Status Etiologies Findings Treatment

Hypovolemia • Increased renal • Weight loss • Increase free water admin- or and insensible • Tachycardia istration to decrease serum Euvolemia free water loss sodium at a rate no greater • Hypotension • Diabetes insipi- than 1 mEq/kg/h. • Metabolic acidosis dus (DI; central or • May need to use intranasal nephrogenic) • Polyuria if DI; desmopressin for central DI. eventual ↓ in UOP • Note: Correction of hyperna- if not DI tremia should be done over 48 h to decrease the propensity of cerebral edema.

Hypervolemia• Excessive isotonic • Weight gain with • Restrict sodium intake or hypertonic edema ﬂ uid • Normal heart rate, blood pressure, and urine output, with

an elevated FENa

HYPONATREMIA Deﬁ nition • Serum sodium <130 mmol/L

APPROACH TO THE NEONATE WITH HYPONATREMIA BASED ON VOLUME STATUS

ECF Volume Status Possible Etiologies Findings Treatment

Hypovolemia• Renal water and salt • Findings consistent • Administer sodium and wasting (especially in with dehydration free water to replace VLBW infants) • Decreased weight losses and make up • Diuretic use • Rising BUN deﬁ cits • Osmotic diuresis • Metabolic aci- • Salt-wasting disorders dosis (adrenal and renal—see • Tachycardia below) • Poor skin turgor • GI losses • Third-space losses (necrotizing enterocolitis NEONATOLOGY and losses from skin sloughing)

(continued on next page) 408 Neonatology

ECF Volume Status Possible Etiologies Findings Treatment

Euvolemic• SIADH from: • Weight gain w/o • Restriction of free water • Pain edema if sodium is >120 mEq/L • Opiate administration • With SIADH: • If neurologic symptoms • IVH decreased UOP and are present: • Asphyxia increased urine • Furosemide (1 mg/ osmolarity • Meningitis kg q6h) with replace- • Pneumothorax • NOTE: Diagnosis ment of urinary of SIADH assumes sodium losses with • Positive-pressure no volume-related hypertonic saline (3%) ventilation reason for ADH • Return to simple free Excess free water • release. water restriction once administration serum sodium >120 mEq/L and neurologic signs improve

Hypervolemic• Sepsis with decreased • Weight gain with • Treatment of underlying cardiac output edema disorder • Necrotizing enterocolitis • Decreased UOP • Restrict free water as • Heart failure • For infants with clinically allowed with some degree of sodium • Impaired lymphatic mature renal func- ↑ ↑ restriction drainage tion, BUN, urine SG, and ↓ FENa • Neuromuscular blockade

Available at www.AccessPediatrics.com • Disorders of sexual differentiation • Congenital hypothyroidism • Infant of diabetic mother • Disorders of magnesium NEONATOLOGY ected (continued on next page) uids uids uids uids Surgical consult Surgical suction intermittent low Repogle to IV fl may Remember that high anal atresias with GU abnormalities be associated Enema is usually therapeutic If continues, abnormal stooling of Hirschsprung’s diagnosis consider disease and rectal biopsy Enema can be therapeutic but may intervention need surgical consult Surgical suction intermittent low Repogle to IV fl is standard; Diverting colostomy end-to-end if aff anastomosis is verysegment short consult Surgical suction intermittent low Repogle to IV fl consult Surgical suction intermittent low Repogle to IV fl before the investigation rst be stabilized 409 nitive nitive the into ux of contrast Imperforate anus should be evident on physical examination be may Anal stenosis evident on physical examination plug with a the meconium normal-caliber colon ileal from a microcolon obstruction with stool a enema shows Contrast segment distally narrowed a (aganglionic) leading to segment proximal dilated (normal colon) If rectal suspected, biopsy the defi will provide diagnosis refl ileum terminal bilious emesis enema Upper GI or contrast a malpositioned shows cecum thorough physical examination and history. thorough physical examination stooling. begins as to the cause of delayed obstruction. For infants who are unstable, the infant must fi For infants who are unstable, the Virtually all infants, term and preterm, will have passed meconium by 48 h of age. Virtually all infants, term and The delayed passage of meconium may be the result of a mechanical or functional bowel result of a mechanical or functional of meconium may be the The delayed passage delayed passage of meconium should begin with a The evaluation of any infant with CauseAnorectal abnormality (imperforate anal stenosis) anus, DiagnosisMeconium plug enema shows Contrast Management Meconium ileus enema reveals Contrast Hirschsprung’s disease Ileal atresia no enema shows Contrast Malrotation Infants with usually present • EVALUATION, AND MANAGEMENT DIFFERENTIAL DIAGNOSIS, OF MECONIUM OF DELAYED PASSAGE Gastroenterology OF MECONIUM DELAYED PASSAGE • • • CHAPTER 35 410 Neonatology

Cause Diagnosis Management

Volvulus Surgical emergency because Emergent surgical consult the ischemic gut may prog- Repogle to low intermittent suction ress to frank necrosis IV ﬂ uids Plain ﬁ lm of the abdomen reveals a massively dilated proximal colon Contrast enema reveals a midtransverse colon obstruction

Ileus May be secondary to a Bowel rest number of factors: IV ﬂ uids • Sepsis Treatment of underlying condition • NEC causing the ileus • Hypokalemia • Hypothyroidism • Hypermagnesemia • Narcotic analgesia therapy

GASTROESOPHAGEAL REFLUX DISEASE (GERD) • GER is defi ned as passage of gastric contents into the esophagus. • GER is very common in term and preterm neonates. • A very large majority of infants exhibit no signs of clinical compromise and hence do not warrant specifi c treatment(GER) vs. infants who experience feeding diffi culties, poor weight gain, failure to thrive, etc as a direct result of refl ux (GERD). • For infants who have persistent “spitting up,” care must be taken to ensure that there is no true underlying pathology as a cause. • Apnea and GER are common occurrences in premature infants, but studies have shown no temporal relationship between the two. Risk Factors • Congenital diaphragmatic hernia • Short bowel syndrome (SBS) • Esophageal atresia repair • Bronchopulmonary dysplasia • Gastroschisis • Neurologic defi cits • Omphalocele

Differential Diagnosis • Differential diagnosis for GER should include: • Inborn errors of metabolism • GI tract anatomic abnormalities: Esophageal • Renal dysfunction webs or stenosis, duodenal web or stenosis, • Neurologic deﬁ cits malrotation, gastric outlet obstruction • Bronchopulmonary dysplasia

Clinical Presentation • Dysphagia • Irritability • Odynophagia • Failure to thrive • Arching of the back with feeds • Hematemesis

Management • Initial management should be aimed at nonpharmacologic maneuvers (eg, GERD precautions): • Positioning of the infant with the head of the bed elevated. • Changing the rate of feeding (slow rate of bolus feeds to 60-90 minutes, feed less volume more frequently). Gastroenterology 411

• Consider thickening feeds with commercially available thickeners. • Discontinuation of caffeine for apnea of prematurity may ameliorate symptoms of GER. • Pharmacologic therapy can be used if the above measures fail, but data on efﬁ cacy in this patient population are very limited. • Use of H2 blockers or PPIs to decrease gastric acid release have been reported with mixed results • Use of promotility agents is not advocated because of potentially serious side effects (eg, Parkinsonian reaction and tardive dyskinesia with the use of metoclopramide, may not be reversible). • Infants with severe symptoms as above have GERD. • Infants with GERD often have true esophagitis or gastritis and have been shown to ben- eﬁ t from gastric acid reduction. • Surgical intervention with fundoplication may be considered for infants who fail to respond to pharmacologic therapy and continue to display signs of GERD.

INDIRECT (UNCONJUGATED) HYPERBILIRUBINEMIA • 25%–50% of term neonates and a larger percentage of preterm neonates will develop clinical jaundice. • Clinical exam is not a reliable tool to estimate serum bilirubin level. • The major source of bilirubin is from the breakdown of hemoglobin in the RES. • Bilirubin is also produced from other heme-containing proteins in the peripheral tissues (eg, cytochromes, myoglobin) • The majority of fetal unconjugated bilirubin is cleared via the placenta to the maternal circulation.

RISK FACTORS FOR INDIRECT (UNCONJUGATED) HYPERBILIRUBINEMIA

Factors that Major Risk Factors Minor Risk Factors Decrease Risk

• Predischarge TSB or TcB in high-risk • Predischarge TSB or TcB • Predischarge TSB or zone in high-intermediate- TcB in the low-risk • Jaundice in the ﬁ rst 24 h risk zone zone • Known hemolytic disease • GA 37–38 wk • GA ≥41 wk • GA 35–36 wk • Jaundice observed • Exclusive bottle before discharge feeding • Older sibling received phototherapy • Older sibling with h/o • African American • Cephalhematoma or signiﬁ cant jaundice race bruising • Macrosomic IDM • Hospital discharge • Exclusive breastfeeding (especially >72 h with poor feeding or excessive • Maternal age <25 yr weight loss) • Male gender • East Asian race

Physiologic Unconjugated Hyperbilirubinemia • Generally, whereas bilirubin peaks in term neonates at 3–4 d, it peaks at 4–5 d in preterm neonates.

• Physiologic hyperbilirubinemia occurs for several reasons: NEONATOLOGY • Increased bilirubin production caused by decreased RBC survival in the neonate compared with adults • Increased enterohepatic recirculation caused by ↑ levels of β-glucuronidase and decreased gut motility • Decreased hepatic ligandin leading to decreased bilirubin uptake in the liver • Decreased UDPG-T activity leading to decreased conjugation of bilirubin • Decreased hepatic excretion 412 Neonatology

NONPHYSIOLOGIC (PATHOLOGIC) UNCONJUGATED HYPERBILIRUBINEMIA CAUSES OF NONPHYSIOLOGIC (PATHOLOGIC) UNCONJUGATED HYPERBILIRUBINEMIA

Cause Examples and Points to Consider Hemolysis• Intrinsic RBC membrane defects (elliptocytosis, spherocytosis) • ABO, Rh, or minor blood group incompatibility • Increased production of bilirubin caused by accelerated breakdown of RBCs Polycythemia• Increased bilirubin load caused by increased RBC mass • See Chapter 37 chapter for further details Bleeding into body • Sequestered blood turnover contributes to bilirubin load cavity • May be seen with bleeding into any body cavity (cephalhematoma, GI bleeding, pulmonary hemorrhage) Conjugation • Crigler-Najjar syndrome (types I and II; caused by relative defi ciencies defects in UDP glucuronyl transferase) • Gilbert syndrome (caused by mild form of UDP glucuronyl transferase defi ciency) • Lucey-Driscoll syndrome (caused by an undefi ned maternal hormone that interferes with bilirubin conjugation) Breast milk • Jaundice that appears around 5–7 d of life, peaks later at 10–15 d, and jaundice declines over several weeks • Caused by an undefi ned factor in breast milk that promotes intestinal re-absorption of bilirubin • Cessation of breast milk for 24–48 h causes a rapid decrease in serum bilirubin level Breastfeeding • Early onset jaundice caused by poor caloric intake and relative dehydration jaundice • Resolves as breastfeeding improves and milk supply increases Metabolic disorders• Galactosemia, hypothyroidism, maternal DM Increased enterohe- • From any cause that delays transit through the gut (bowel obstruction patic recirculation at any level, CF, ileus from any cause) Displacement • Drugs (aspirin, sulfonamides, ceftriaxone) of bilirubin from • Increased fatty acid concentration albumin • Acidosis • Hypothermia

Evaluation • Do not delay therapy while awaiting results of laboratory tests. • Obtain total and direct bilirubin levels (most data correlating TSB with incidence of kernicterus are based on capillary samples of TSB). • CBC with reticulocyte count. • Blood type and Rh of mother and infant with direct Coombs test. • Peripheral blood smear. • Serum albumin. • Adjunct tests such as urine for reducing substances, metabolic tests, thyroid function, blood and urine cultures, imaging studies (cranial US for bleeding, abdominal radiographs for evidence of obstruction) if the index of suspicion is high. Management • See nomograms below for the American Academy of Pediatrics’ guidelines for phototherapy and for exchange transfusion in infants (≥35 wk gestation). • Standard phototherapy for infants whose TSB is not approaching exchange transfusion level may be used as a ﬁ rst-line therapy. Gastroenterology 413

25 428

20 342

High risk zone 95th percentile

one 15 isk z 257

k zone High intermediate r mol/L

ermediate ris μ int 10 Low 171

Low risk zone Total Serum Bilirubin (mg/dL) Total 5 85

0 0 0 12 24 36 48 60 72 84 96 108 120 132 144 Postnatal Age (hours) Figure 35-2 Bhutani Nomogram: Nomogram for designation of risk (likelihood) of a subsequent bilirubin level exceeding the 95th percentile, based on the hour-speciﬁ c serum bilirubin value, for well newborns at least 36 wk gestation and 2000 g at birth, or 35 wk gestation and 2500 g at birth. Note: These values are NOT to be used to represent the natural history of unconjugated neonatal hyperbilirubinemia. (Reproduced with permission from Hay WW JR, Levin MJ, Sodheimer JM, Deterding RR: Current Diagnosis & Treatment: Pediatrics, 19th ed. New York: McGraw-Hill. Available at http://www.accessmedicine.com. Copyright © The McGraw-Hill Compa- nies, Inc. All rights reserved.) For more information: Pediatrics 2004;114(1):297 and Pediatrics 1999;103:6.

• Irradiance should be >18 μW/cm2 per nm. • As much of the infant’s skin surface area as possible should be exposed to the phototherapy light. • Intensive phototherapy should be used for infants whose TSB is approaching exchange transfusion level. • This involves overhead bili-lights combined with a bili-blanket. • Overhead lights should be positioned to deliver an irradiance of >30 μW/cm2 per nm.

25 428

20 342

15 257 mol/L 10 171 μ

5 Infants at lower risk (≥38 wk and well) 85 Total Serum Bilirubin (mg/dL) Total Infants at medium risk (≥38 wk + risk factors or 35–37 6/7 wk and well) Infants at higher risk (35–37 6/7 wk + risk factors) 0 0 Birth 24 h 24 h 72 h 96 h 5 days 6 days 7 days Age

• Use total bilirubin, do not subtract direct reacting or conjugated bilirubin. • Risk factors = isoimmune hemolytic disease, G6PD deficiency, asphyxia, significant lethargy, temperature instability, sepsis, acidosis, or albumin < 3.0 g/dL (if measured). NEONATOLOGY • For well infants 35–37 6/7 wk can adjust TSB levels for intervention around the medium risk line. It is an option to intervene at lower TSB levels for intants closer to 35 wks and at higher TSB levels for those closer to 37 6/7 wk. • It is an option to provide conventional phototherapy in hospital or at home at TSB levels 2–3 mg/dL (35–50 mmol/L) below those shown but home phototherapy should not be used in any infant with risk factors. Figure 35-3 Guidelines for phototherapy in hospitalized infants ≥ 35 weeks’ gestation. (Reproduced with permission from Hay WW JR, Levin MJ, Sodheimer JM, Deterding RR: Current Diagnosis & Treatment: Pediatrics, 19th ed. New York: McGraw-Hill. Available at http://www.accessmedicine.com. Copyright © The McGraw-Hill Companies, Inc. All rights reserved.) For more information: Pediatrics 2004;114(1):297. 414 Neonatology

• As much of the infant’s skin surface area as possible should be exposed to the phototherapy light. • IVIG administered to infants with isoimmune hemolysis leading to hyperbilirubinemia has been shown to decrease the need for exchange transfusion. • Administer IVIG if TSB continues to increase in the presence of known isoimmune hemolysis despite intensive phototherapy or if TSB is within 2–3 mg/dL of the exchange transfusion level. • The dose is 0.5–1 g/kg over 2 h; the dose may be repeated in 12 h if needed. • Exchange transfusion is pursued for infants according to the ﬁ gure below. (See Chapter 37 for guidelines on how to perform an exchange transfusion.) • Scant data exist to provide guidelines for the treatment of indirect hyperbilirubinemia in premature infants <35 wk of gestation and infants with LBW (<2500 g). The best guidelines that are used extensively come from expert consensus and are roughly as shown in the table below. 30 513 Infants at lower risk (≥38 wk and well) Infants at medium risk (≥38 wk + risk factors or 35–37 6/7 wk and well) Infants at higher risk (35–37 6/7 wk + risk factors) 25 428

20 342 mol/L μ

15 257 Total Serum Bilirubin (mg/dL) Total

0 171 Birth 24 h 24 h 72 h 96 h 5 days 6 days 7 days Age • The dashed lines for the first 24 hours indicate uncertainty due a wide range of clinical circumstances and a range of responses to phototherapy. • Immediate exchange transfusion is recommended if infant shows signs of acute bilirubin encephalopathy (hypertonia, arching, retrocollis, opisthotonos, fever, high pitched cry) or if TSB is ≥ 5 mg/dL (85 μmol/L) above these lines. • Risk factors—isoimmune hemolytic disease, G6PD deficiency, asphyxia, significant lethargy, temperature instability, sepsis, acidosis. • Measure serum albumin and calculate B/A ratio. • Use total bilirubin. Do not subtract direct reading or conjugated bilirubin. • If infant is well and 35–37 6/7 wk (medium risk) can individualize TSB levels for exchange based on actual gestational age. Figure 35-4 Guidelines for exchange transfusion in infants ≥ 35 weeks’ gestation. (Reproduced with permission from Hay WW JR, Levin MJ, Sodheimer JM, Deterding RR: Current Diagnosis & Treatment: Pediatrics, 19th ed. New York: McGraw-Hill. Available at http://www.accessmedicine.com. Copyright © The McGraw-Hill Companies, Inc. All rights reserved.) For more information: Pediatrics 2004;114(1):297.

GUIDELINES FOR PHOTOTHERAPY AND EXCHANGE TRANSFUSION IN LOW-BIRTHWEIGHT INFANTS

Total Serum Bilirubin [mg/dL (μmol/L)] Consider Exchange Birth Weight (g) Consider Phototherapy at: Transfusion at: <1500 5–8 (85–140) 13–16 (220–275) 1500–1999 8–12 (140–200) 16–18 (275–300) 2000–2499 11–14 (190–240) 18–20 (300–340) Adapted from Maisels MJ: Jaundice. In Avery GB, Fletcher MA, MacDonald MG (eds). Neonatology: Pathophysiol- ogy and Management of the Newborn. Philadelphia: JB Lippincott; 1999:765–819. Gastroenterology 415

LARGE OR INCREASED GASTRIC ASPIRATES (“RESIDUALS”) • In general, residuals that are either >50% of the feeding volume or are accompanied by changes in the clinical examination of the infant warrant further investigation. • In addition to the volume of the residual and the clinical examination, the characteristics of the residuals are helpful in forming a differential diagnosis.

DIFFERENTIAL DIAGNOSIS OF LARGE OR INCREASED GASTRIC ASPIRATES

Bilious Residual Nonbilious Residual Bloody Residual • Bowel obstruction • Advancing of feeds too rapidly • Traumatic nasogastric insertion • NEC • NEC • NEC • Intestinal malrotation • Stricture after episode of NEC • Swallowed maternal blood • Volvulus • Gastric outlet obstruction • Coagulopathy • Meconium plug or ileus • Ileus • Stress gastritis • Ileus • Infection • Volvulus • Transpyloric passage • Inborn error of metabolism • Medications (corticosteroids, of the feeding tube • Constipation indomethacin) • Formula intolerance

Evaluation • Physical examination, as above • Plain radiograph of the abdomen with left lateral decubitus view to evaluate for evidence of obstruction, pneumatosis intestinalis, and pneumoperitoneum • CBC, blood culture, serum electrolytes, coagulation proﬁ le

MANAGEMENT OF LARGE OR INCREASED GASTRIC ASPIRATES

Bilious Residual Nonbilious Residual Bloody Residual

For surgical abdomen or NEC: Assuming the clinical exam remains For NEC: • NPO entirely benign: • See management • Decompression of stomach by • For aspirates containing undi- under “Bilious placement of Repogle tube to gested milk in which the volume is Residual” low intermittent suction not >50%: May need to decrease For suspected coagu- volume of feeds • Consult pediatric surgery lopathy: service • For aspirates with partially • NPO digested milk: May discard residual • Initiation of IV ﬂ uids as • Decompress stom- and resume feeds as prescribed appropriate ach with Repogle • For concerns of surgical cause (NEC, to low intermittent • Obtain blood, urine and CSF stricture post-NEC): See manage- cx and start broad-spectrum suction ment under “Bilious Residual” antibiotics (ampicillin, vanco- • Check PT, PTT, mycin, and gentamicin; add For suspected infection: ﬁ brinogen, CBC, clindamycin if bowel necrosis • Make NPO and decompress D-dimer or perforation is suspected) stomach with Repogle to low • If evidence of DIC, For ileus: intermittent suction treat underlying NEONATOLOGY • NPO • Obtain appropriate cx cause • Decompress stomach by • Obtain CBC • Replenish platelets placement of Repogle to low • Initiate broad-spectrum antibiotics and coagulation intermittent suction (ampicillin, vancomycin, and factors as needed • Investigate cause of ileus gentamicin) (infection, NEC, electrolyte disturbances) 416 Neonatology

NECROTIZING ENTEROCOLITIS Risk Factors • Prematurity • Generally, the lower the GA, the higher the risk of NEC. • ~10% of infants who develop NEC are full term. • Cocaine-exposed infants have a 2.5-fold higher risk of developing NEC. • Enteral feeding • >90% of infants who develop NEC have received at least one enteral feeding. • Hyperosmolar formula or medications alter mucosal permeability and cause direct injury. • Breast milk signiﬁ cantly lowers the risk of NEC. Breast milk has been shown to decrease the incidence of NEC. • Immunoprotective factors are lacking in commercial formula. • All other interventions at this time remain experimental (use of immunoglobulins, prophylactic enteral antibiotics, probiotics). • Asphyxia or hypotension: Lead to low perfusion of mesenteric bed, causing intestinal ischemia and mucosal injury. • Hyperviscosity syndromes. • Exchange transfusions. • Use of H2 blockers. • PAF and other inﬂ ammatory mediators. • Clinical evidence for feeding volume and timing of initiation of enteral feeding remain controversial.

CLINICAL PRESENTATION OF NECROTIZING ENTEROCOLITIS

Systemic Signs and Symptoms

Lethargy Poor perfusion Apnea Bloody stools Bradycardia Abdominal distension Respiratory distress Abdominal tenderness Irritability Gastric residuals Feeding intolerance Ileus Hypotension Abdominal wall erythema Temperature instability Localized abdominal mass Acidosis Ascites Oliguria Vomiting (bloody or bilious) Coagulopathy

STAGING OF NECROTIZING ENTEROCOLITIS

Stage Systemic Signs Abdominal Signs Radiographic Signs

Stage 1: • Apnea • Gastric residuals • Normal or nonspeciﬁ c Suspected NEC • Lethargy • Feeding intolerance • Bradycardia • Guaiac-positive stools • Temp instability

(continued on next page) Gastroenterology 417

Stage Systemic Signs Abdominal Signs Radiographic Signs

Stage IIA: • As in Stage 1 • Abdominal distension • Ileus Mild NEC • Abdominal tenderness • Dilated loops of bowel • Absent bowel sounds • Focal pneumatosis • Bloody stools intestinalis

Stage IIB: As in Stage 1, plus: • Further abdominal • Extensive pneumatosis Moderate NEC • Mild acidosis distension intestinalis • Thrombocytopenia • Abdominal tenderness • Ascites • Abdominal wall edema • ± Portal venous gas • Abdominal mass

Stage IIIA: • Mixed acidosis • Worsening abdominal • Prominent ascites Advanced NEC • Need for mechani- wall edema • Paucity of bowel gas cal ventilation • Worsening abdominal • Sentinel loop of bowel • Hypotension wall tenderness • Oliguria • Worsening abdominal wall discoloration (ery- • Neutropenia thema or ecchymotic • Coagulopathy changes)

Stage IIIB: • Generalized • Tight abdominal • Absent bowel gas Advanced NEC edema distension • Pneumoperitoneum • Intractable • Signiﬁ cant discolor- hypotension ation of abdomen • Shock • DIC • Electrolyte abnormalities

Differential Diagnosis • Ileus associated with infection (sepsis) • Malrotation with obstruction or midgut volvulus • Intussusception • Perforation (gastric or isolated small bowel) • Mesenteric vessel malformations leading to hypoperfusion or thrombosis • Infectious or allergic enterocolitis • Severe forms of metabolic disease (eg, galactosemia may produce vomiting, abdominal distension, hypotension, shock)

Diagnosis • Clinical examination: Systemic and abdominal signs/symptoms as outlined above • Laboratory studies: • CBC • Culture of blood, urine, CSF, ± stool

• Blood gas measurement (preferably arterial) NEONATOLOGY • Serum electrolytes • BUN/creatinine • Radiographic studies • Flat plate radiograph of abdomen • Add a left-lateral decubitus (ie, left side down) ﬁ lm of abdomen if pneumoperitoneum is suspected (bowel perforation commonly occurs within 48-72 h of symptom onset) 418 Neonatology

MANAGEMENT OF INFANTS WITH NECROTIZING ENTEROCOLITIS

Stage I Stages IIA and IIB Stages IIIA and IIIB

• Make NPO • All stage I management • All stage I and II man- • Decompress bowel (place repogle tube plus: agement plus: to low intermittent suction) • Constitute TPN to deliver • Refractory hypoten- • Continuous cardiorespiratory 100–120 kcal/kg/d sion may become monitoring • Adjust fl uids to allow an issue; will need support with pressors, • Controversial: Removal of umbilical for possible frequent intravascular volume catheters and placement of peripher- transfusion of blood expansion with blood ally inserted venous and arterial lines products, third-space losses, and renal failure products or crystalloid • Broad-spectrum antibiotics (gentamicin, solutions and ampicillin or vancomycin; clin- • Respiratory support as required • Common fi ndings in damycin may be added if perforation or this stage include se- • Cardiovascular support bowel necrosis is suspected) vere thrombocytope- as required with pres- • Monitor for pathologic bleeding nia, DIC, leukopenia or sors (eg, dopamine) • Strict monitoring of “ins and outs” neutropenia • Strongly consider • Surgical intervention • Remove potassium from all fl uids obtaining a surgical • Cultures as outlined above may be necessary at consultation this stage • Other labs listed above can be followed serially as indicated • Serial abdominal plain fi lms ± decubitus views to evaluate for free air Q6–12 h for the fi rst 48–72 h; then as needed

Surgical Management • Surgical options include exploratory laparotomy (with resection of nonviable bowel and creation of an enterostomy) or placement of peritoneal drains. • Relative indications for surgical intervention: • Bowel perforation and pneumoperitoneum • Intractable metabolic acidosis • Severe abdominal distension leading to inability to ventilate • Abdominal wall erythema • Fixed, sentinel loop on abdominal radiographs (suggesting a segment of gangrenous bowel)

Prognosis • Infants with NEC who sustain an intestinal perforation have mortality rates of ≤40%. • Stenoses or strictures of the small or large bowel may develop, leading to symptoms of obstruction; contrast enema is usually diagnostic. • Infants who develop NEC that requires surgical intervention have higher risk of serious sequelae, including increased morbidity and mortality, hepatic disease associated with prolonged parenteral nutrition, and developmental delay

DIRECT (CONJUGATED) HYPERBILIRUBINEMIA • DH is a sign of hepatobiliary dysfunction. • An absolute level of >2.0 mg/dL or a value that is >20% of total serum bilirubin (TSB) warrants further investigation. • Consulting the GI or liver service would be appropriate at any point during the workup. Gastroenterology 419

ETIOLOGIES OF DIRECT (CONJUGATED) HYPERBILIRUBINEMIA

Pathophysiology Examples

Extrahepatic biliary disease• Biliary atresia • Choledochal cyst

Intrahepatic biliary disease• Paucity of bile ducts (syndromic form is Alagille’s syndrome) • Progressive intrahepatic cholestasis • Inspissated bile α Hepatocellular disease • 1-Antitrypsin (A1AT) deﬁ ciency • CF • Tyrosinemia • Hereditary fructose intolerance (HFI) • Galactosemia • Rotor and Dubin-Johnson syndromes • TPN-associated cholestasis (TPNAC) • Other metabolic or genetic causes of conjugated hyperbilirubinemia • Infectious causes • Neonatal hemochromatosis • Hypoperfusion state • Infants on ECMO

Diagnosis • Infants who present with cholestasis may be evaluated according to the guidelines shown in the following table. The workup can be tailored to speciﬁ c diagnoses based on clinical presentation and history.

EVALUATION OF DIRECT (CONJUGATED) HYPERBILIRUBINEMIA

Rationale for Study Diagnostic Studies

Evaluate for anatomic causes US of liver or biliary tree

Evaluate liver function ALT, AST, Alk Phos, GGT, unconjugated and conjugated bilirubin, albumin

Evaluate liver synthetic capacity Glucose, PT, PTT

Evaluate for viral hepatitis Hepatitis panel, EBV, CMV, adenovirus, enteroviruses, parvovirus

Evaluate for genetic or metabolic A1AT with Pi phenotype, serum and urine amino acid causes proﬁ le, urine organic acid proﬁ le, ammonia, urine suc- cinylacetone, urine ketones, serum lactate and pyruvate, serum ferritin, urine reducing substances, urinalysis, echocardiography (suspicious for cardiac disease) NEONATOLOGY Evaluate for CF Genetic testing or sweat testing

Evaluate for hemolytic diseases Peripheral blood smear, blood typing of infant and mother, Coombs test

Evaluate for hepatic excretory HIDA scan capacity Liver biopsy 420 Neonatology

Management • The primary treatment should be aimed at the underlying cause of cholestasis. Adjunctive therapies are listed in the table below.

ADJUNCTIVE THERAPIES FOR DIRECT (CONJUGATED) HYPERBILIRUBINEMIA

Adjunct Therapy Purpose

Enteral feeding• Establishment of enteral feeds to the maximum that the patient will tolerate may help ameliorate cholestasis related to TPNAC. • Fortiﬁ ed human milk or standard premature formula is appropriate for premature neonates with cholestasis. • In infants with signiﬁ cant cholestasis, fat absorption may be impaired, and formulas (eg, Pregestimil or equivalent) containing a majority of fats as MCTs may be helpful in aiding fat absorption.

Ursodeoxycholic acid • UDCA is a potent choleretic, increasing bile ﬂ ow and hence help- (UDCA) ing to improve cholestasis. • Its eﬃ cacy in neonatal cholestasis is not proven. • If a bile acid synthetic defect is suspected, UDCA should be held until that workup is completed.

Fat-soluble vitamins• TPN should provide adequate amounts of vitamins A, D, and E. • Vitamin K should be supplemented if bleeding occurs or PT is prolonged. • When full enteral feeds are achieved, consider giving vitamin E supplement plus BID doses of Poly-Vi-Sol ± PO vitamin K supplement. • If infant is on full enteral feeds but still with cholestasis, consider measuring serum levels of vitamins A, D, and E every 2–3 mo.

Copper and • Cu and Mn are excreted in bile. manganese • In infants with cholestasis, Cu and Mn may accumulate in the liver and cause further hepatocellular injury. • As such, infants with conjugated bilirubin ≥4 mg/dL should have Cu and Mn limited in the TPN (eg, should be given “trace elements” twice weekly to prevent subsequent deﬁ ciencies of these nutrients).

Unproven therapies• These include: changing the amino acid mixture, reducing or withholding lipid infusion, TPN “cycling”, or injection of cholecystokinin.

Available at www.AccessPediatrics.com • Upper GI bleeding • Lower GI bleeding • Short bowel syndrome NEONATOLOGY usions able usions. uid shifts. uid intravascularly, intravascularly, May need emergent need emergent May (continued on next page) → euvolemic aluate for structural for abnormali- aluate Avoid large fl large Avoid Polyhydramnios (AFI >24) Placentomegaly → • Should ideally be done under US guidance. → 421 at least two fetal compartments (ascites, pleural uid in culties/Management usion is suspected edema of head/neck/oropharynx. severe intubation due to cult Consider ENT or anesthesia support Consider intubation as needed. for usions. thoracentesis in delivery area to alleviate lung compression from large large from lung compression alleviate in delivery to thoracentesis area eff dial eff ties as a cause of hydrops. → of lungs compression or other extrinsic in utero often with depressed cardiac function cardiac often with depressed Arterial access is helpful to follow invasive blood pressures. invasive Arterial follow is helpful to access Remember that most hydropic infants are infants are Remember that most hydropic ev should be obtained to Echocardiogram Varying degrees of pulmonary hypoplasia due to large pleural eff of pulmonary large due to degrees Varying hypoplasia Pericardiocentesis may be necessary if cardiac tamponade from pericar- be necessary may tamponade from if cardiac Pericardiocentesis Chest tube placement for rapidly reaccumulating pleural eff rapidly reaccumulating for Chest tube placement • • • • • • • • nition for fetal tachyarrhythmias); if this is not possible, the risks of intrauterine death versus for fetal tachyarrhythmias); if premature delivery have to be weighed. circulating antibody to red-cell antigens. circulating antibody to red-cell effusion, pericardial effusion, skin edema, polyhydramnios) without any identifi effusion, pericardial effusion, By organ system (see table below). For a discussion on immune-mediated disease, see Chapter 37. For a discussion on immune-mediated Decreased fetal movements (mirror syndrome) Generalized maternal edema Infants with nonimmune hydrops are at very high risk for fetal demise. Infants with nonimmune hydrops at treating underlying causes (maternal digitalis therapy Intrauterine therapy is aimed Prevalence is estimated at 1:1500-4000. Asian population. Highest prevalence in Southeast Increased uterine size for dates Presence of excess extracellular fl Presence of excess extracellular Pulmonary Diffi Cardiovascular support. inotropic with appropriate Hypotension be treated should System Diffi Potential Management • • • BY ORGAN SYSTEM MANAGEMENT OF NONIMMUNE FETAL HYDROPS • • • Diagnosis • • • • Genetics FETAL HYDROPS NONIMMUNE Defi • CHAPTER 36 422 Neonatology

System Potential Diffi culties/Management

Fluids and • Infants are total body fl uid overloaded but are usually euvolemic (intra- electrolytes vascular status). • Fluid intake should be based on a “dry” weight (ie, the 50th percentile for gestational age). • Fluids should be restricted (40–60 mL/kg/d) to avoid further fl uid overload and to allow diuresis. • Vigilant attention to all fl uid intake and output to maintain an adequate circulating volume. • Electrolyte losses should be replaced accordingly in the IV fl uids. • Diuretics should be used very judiciously. • Abdominal US should be obtained to evaluate for an intra-abdominal mass/process that is compressing the IVC and other vascular structures.

Hematology• For infants who are very anemic (hematocrit <30%), an isovolumetric partial volume exchange transfusion should be done to raise the hematocrit to ~40%–50% (see Chapter 37). • For management of immune-mediated disease, please refer to Chapter 37 for further discussion.

Infectious • Workup should proceed as indicated to ﬁ nd infectious etiologies for the disease infant’s hydrops. • Serum PCR can be sent to ﬁ nd evidence of a multitude of viral pathogens (enteroviruses, parvovirus, adenovirus, rubella). • Blood sample for viral cultures (for herpes simplex virus, CMV antigenemia). • Urine for CMV culture. • Serologies for bacterial or other pathogens as indicated.

Renal• Renal US to evaluate for intrinsic renal disease/obstructive uropathy as a cause of hydrops. • The role of ultrafi ltration has not been established in the treatment of fl uid overload found in hydropic infants, especially as the edema is known to improve with very careful monitoring of total fl uid intake and output.

• Examination of the placenta by Pathology is recommended. • Genetic counseling as warranted for the family.

CLINICAL FINDINGS OF TRISOMY 13, 18, 21

Clinical Presentation Trisomy 21 Trisomy 18 Trisomy 13 Craniofacial Flat facial profi le Prominent occiput Microcephaly Slanted palpebral Short palpebral Sloping forehead fi ssures fi ssures Wide fontanels Anomalous auricles Low-set “tulip Microphthalmia shaped” ears Cleft lip Cleft palate Abnormal helices Cutis aplasia of scalp

(continued on next page) Genetics 423

Clinical Presentation Trisomy 21 Trisomy 18 Trisomy 13 Extremities Dysplasia of midphalanx Clenched hand Polydactyly of ﬁ fth ﬁ nger Short hallux Single palmar crease Single palmar crease Posterior prominence Sandal crease of heel Cardiac Endocardial cushion VSD, PDA, ASD VSD, PDA, ASD defect, VSD, PDA Neurologic Hypotonia Weak fetal activity Holoprosencephaly Deafness Seizures Other Excess skin on back Polyhydramnios Single umbilical artery and neck Small placenta Single umbilical artery Muscle hypoplasia Adipose tissue hypoplasia

MAJOR TERATOGENIC AGENTS AND PRENATAL EXPOSURE EFFECTS

Teratogen Clinical Presentation Ethanol Growth defi ciency (prenatal onset) Microcephaly Dysmorphic facial features (short palpebral fi ssures, short nose, smooth philtrum, thin and smooth upper lip) Irritability Phenytoin Growth defi ciency Dysmorphic facial features (wide anterior fontanel, hypertelorism, short nose, broad nasal bridge) Cleft lip/palate Short neck Widely spread, small nipples Hypoplasia of distal phalanges Valproic acid High forehead and narrow bifrontal diameter Dysmorphic facial features (midface hypoplasia, broad, low nasal bridge, long philtrum, small mouth) Cardiac defects (HLHS, aortic coarctation, AS) Long, thin fi ngers and toes Warfarin Nasal hypoplasia and depressed nasal bridge Stippling and uncalcifi ed epiphyses Shortened fi ngers with mild nail hypoplasia NEONATOLOGY Methotrexate Growth defi ciency Microcephaly with hypoplasia of cranial bones Wide fontanels, prominent eyes, and micrognathia Mesomelia

(continued on next page) 424 Neonatology

Teratogen Clinical Presentation Retinoic acid Microcephaly with narrow forehead Microtia/anotia Depressed nasal bridge Hypertelorism Conotruncal malformations (TGA, TOF)

CLINICAL FEATURES OF VACTERL AND CHARGE SYNDROMES

Association Etiology Clinical Presentation

VACTERL Unknown; more Vertebral anomalies frequently seen in Anal atresia children born to mothers with DM Cardiac anomalies (conotruncal anomalies, CAVC) Tracheoesophageal ﬁ stula with esophageal atresia Renal anomalies Limb anomalies (radial dysplasia, polydactyly, syndactyly) Single umbilical artery

CHARGE CHARGE is caused Coloboma by coding region Heart defect (TOF, PDA, CAVC) mutations and large tresia choanae deletions of the CHD7 A gene (8q12) Retarded growth and development Genital anomalies (genital hypoplasia in males) Ear anomalies and/or hearing loss (sensorineural or mixed)

Available at www.AccessPediatrics.com • Etiologies of nonimmune fetal hydrops NEONATOLOGY rm with periph-

↓ PT, PTT count ↑ ); severe thrombocytopenia 3 Mother’s platelet • DIC (Sepsis) • Hypoxia • Acidosis • Cold stress • Severe liver disease • Maternal ITP • Maternal drug exposure • Familial ∗ ∗ 425 infant infant Ill-appearing Well-appearing ) occurs in 0.1%–0.5%. 3 count normal Brief differential diagnosis for thrombocytopenia in neonates. Normal PT, PTT Mother’s platelet • NAIT (Neonatal Alloimmune Thrombocytopenia) • Neonatal drug exposure • Hemangioma • Congenital thrombocytopenia (see below) • Maternal ITP in remission • Congenital Infection (eg, CMV, toxoplasmosis, rubella) • Hypersplenism • Marrow infiltration • NEC (<50,000/mm Sick newborns have an incidence as high as 22%–50%. Sick newborns have an incidence See Chapter 35 (Gastroenterology). See Chapter 35 (platelet count <150,000/mm Occurs in 1%–5% of newborns eral smear to exclude laboratory error *One of the most common causes of thrombocytopenia is improper specimen collection; conﬁ *One of the most common causes of thrombocytopenia is improper specimen Figure 37-1 • Hematology HYPERBILIRUBINEMIA INDIRECT (UNCONJUGATED) • THROMBOCYTOPENIA • CHAPTER 37 426 Neonatology

Immune Thrombocytopenias: Decreased Platelet Survival COMPARISON OF IMMUNE-MEDIATED CAUSES OF THROMBOCYTOPENIA IN NEONATES

Autoimmune Alloimmune Thrombocytopenia Thrombocytopenia

Deﬁ nition• Antibody made against maternal • Antibody made against pater- platelet antigen; antigen is also nal platelet antigen; antigen is found on fetal platelets also found on fetal platelets

Clinical ﬁ ndings• Mild to moderate thrombocytope- • May lead to severe thrombo- nia (20,000–50,000/mm3) cytopenia (<20,000/mm3) and • Petechiae and bruising are common in utero hemorrhagic complications (~20% of infants • Mother usually has thrombocytope- with NAIT have intracranial nia or history of ITP hemorrhages) • Maternal platelets may be normal • Infant appears healthy but because she may have adequate may have petechiae and production of platelets to compen- bruising sate for increased destruction • Maternal platelet count is usually normal • Most common antigen is HPA-1

Pathophysiology• Maternal autoantibodies cross the • Maternal alloantibodies cross placenta and bind to neonatal plate- the placenta and bind to lets, causing increased destruction neonatal platelets, causing increased destruction

Diagnosis• Identiﬁ cation of autoantibody in • Identiﬁ cation of alloantibody maternal serum against antigens on using paternal platelets and her own platelets maternal serum

Prenatal • Use of steroids to prevent fetal • Use of steroids, immune management thrombocytopenia is controversial; globulin, PUBS, fetal scalp not shown to be of benefi t platelet counts during labor, • Use of immune globulin to prevent and elective cesarean delivery fetal thrombocytopenia is contro- can be used on a case-by-case versial; not shown to be of benefi t basis • PUBS (Percutaneous Umbilical cord Blood Sampling) seems to be safe but is invasive, and its use is controversial; not shown to be of benefi t • Mode of delivery (cesarean section vs vaginal) does not change maternal or fetal outcomes; cesarean section is not shown to be of benefi t

Postnatal • May include platelet transfusions • If diagnosis is made before management (pooled donor), steroids, immune delivery, maternal platelets are globulin or exchange transfusion collected 24 h before delivery • Transfuse platelets for levels • If infant requires platelet <20,000/mm3 or for clinical bleeding transfusions postnatally, use collected maternal platelets that have been washed and resuspended in plasma

(continued on next page) Hematology 427

Autoimmune Alloimmune Thrombocytopenia Thrombocytopenia

• If emergent transfusion is required and maternal platelets are not available, either maternal whole blood or HPA-1–negative donor platelets may be used • Immune globulin at a dose of 1–2 g/kg total given over 2–3 h for 2–5 d has been reported with some success • Steroids can be considered for persistent thrombocytopenia

Other Causes of Thrombocytopenia with Decreased Platelet Survival Mechanism Condition Therapy Platelet consumption• DIC • Treat underlying disorder (remember that DIC is a secondary phenomenon) • Replenish clotting factors and supplement with vitamin K as needed • Giant heman- • Transfuse platelets as necessary gioma (Kasa- • Replenish clotting factors as needed bach-Merritt • Treatment of hemangioma may involve corti- syndrome) costeroid administration, surgical removal, or embolization of hemangioma • NEC • Treatment of underlying disease • Transfuse platelets and replenish clotting factors as needed

Platelet destruction• Immune • See table immediately prior thrombocy- • Drug-induced thrombocytopenia is treated topenias with removal of the oﬀ ending agent

• Hypersplenism • Associated with viremic illnesses, portal hypertension • Transfuse platelets as needed • Splenectomy in severe cases

Intrinsic platelet • Wiskott-Aldrich • Transfuse platelets as needed dysfunction syndrome • May-Hegglin anomaly • Bernard-Soulier syndrome NEONATOLOGY

Thrombocytopenia with Decreased Production • Injury to megakaryocytes • Marrow failure or inﬁ ltration 428 Neonatology

• Congenital thrombocytopenia • Thrombocytopenia-absent radii (TAR) syndrome • Fanconi anemia • Familial thrombocytopenia • Recall that thrombocytopenia may also be seen in infants with erythroblastosis fetalis (likely caused by hepatic and splenic platelet trapping or consumption caused by DIC) and after exchange transfusion with platelet-poor blood.

POLYCYTHEMIA • Deﬁ ned as a central hematrocrit >65% (free-ﬂ owing venous or arterial hematocrit) • Heelstick hematocrit can be as much as 5%–20% above the true, central hematocrit. • Warming the heel before specimen collection decreases this discrepancy. • Pathologic symptoms of polycythemia are attributable to hyperviscosity (locally, tissue hypoxia, acidosis, hypoglycemia, and microvascular thrombosis). Hyperviscosity may be caused by conditions other than polycythemia. • Blood viscosity increases exponentially with hematocrit >65%.

BRIEF DIFFERENTIAL DIAGNOSIS OF POLYCYTHEMIA IN NEONATES

Category Possible Mechanism Examples

Hypertransfusion Increased transfer of Delayed cord clamping RBC mass from placenta Cord stripping to infant at the time of delivery Positioning the infant below the placental vascular bed Maternal–fetal hemorrhage Intrapartum asphyxia or acidosis Twin-to-twin transfusion Forceful uterine contractions

Increased fetal Stimulus for increased Placental insuﬃ ciency related: erythropoiesis fetal erythropoiesis from • Maternal hypertension fetal hypoxia • Chronic placental abruption • Postmaturity • Cyanotic heart disease • IUGR • Maternal cigarette smoking Stimulus for increased Infant of a diabetic (chronic or gestational) fetal erythropoiesis mother from increased oxygen Congenital hyperthyroidism consumption Beckwith-Wiedemann syndrome Congenital adrenal hyperplasia Unknown Trisomies 13, 18 and 21

Decreased Concentration of RBC Dehydration relative plasma mass in smaller volume volume of plasma (hemoconcen- tration)

Clinical Presentation • Multiple organ systems may be affected. • The clinical presentation depends on the extent of involvement of each system. Hematology 429

POSSIBLE MANIFESTATIONS OF POLYCYTHEMIA IN NEONATES BY ORGAN SYSTEM

Organ System Symptoms CNS Lethargy Vomiting Venous thrombosis Poor feeding Hypotonia Cerebral infarction Hyperirritability Tremors or jitteriness Vasomotor instability Seizures Cardiorespiratory Respiratory distress Tachycardia CHF Pulmonary hypertension GI Feeding intolerance NEC (association) GU Decreased GFR Hematuria Proteinuria ARF Renal vein thrombosis Priapism Metabolic Hypoglycemia Hypocalcemia Hypomagnesemia Hematologic Thrombocytopenia Hyperbilirubinemia Other thromboses

Management • Partial exchange transfusion (see below) can be done to lower hematocrit and decrease blood viscosity, but this treatment is controversial because data do not suggest an improvement in long-term neurologic outcomes over infants not subjected to partial exchange transfusion. • Use of partial exchange transfusion should be done in accordance with the institution’s guidelines and policies. MANAGEMENT OF POLYCYTHEMIA NEONATOLOGY Central Hematocrit 65%–70% Central Hematocrit >70%

Asymptomatic Expectant management Partial exchange transfusion Increase ﬂ uid administration by 20–30 mL/ kg/day and repeat HCT within 4–6 h

Symptomatic Partial exchange transfusion Partial exchange transfusion 430 Neonatology

• To calculate the volume of blood to be exchanged to bring the hematocrit to 50%–60%, the following equation may be used: − × × [HCTinitial HCTdesired] Weight (kg) 90 mg/kg

HCTinitial EXCHANGE TRANSFUSION INDICATIONS FOR PERFORMING AN EXCHANGE TRANSFUSION

Indication Type Hyperbilirubinemia Double volume over 60–90 min. Hemolytic disease of the newborn Double volume over 60–90 min. Metabolic disorders causing se- Partial exchange (40–70 mL/kg) may be suﬃ cient to vere acidosis or hyperammonemia decrease metabolite levels until dialysis can be started. Severe hyperkalemia or other Partial exchange (40–70 mL/kg) may be suﬃ cient to severe electrolyte abnormality decrease metabolite levels until dialysis can be started. Polycythemia Partial exchange (40–70 mL/kg) is done; for calculation of exact volume for exchange, see Polycythemia in this chapter. Severe anemia (in the presence of Partial exchange (40–70 mL/kg) hypervolemia or in normovolemia in which large-volume transfusions may not be tolerated)

Preparation • Equipment • Radiant warmer. • Means for continuous cardiorespiratory monitoring. • All necessary equipment for resuscitation if required. • Exchange transfusion kit (which should include an 8-Fr umbilical venous catheter); alternatively, exchange transfusion can be performed via umbilical artery or vein catheterization if absolutely needed. Positioning of the venous catheter should be at the level of the diaphragm; if this cannot be achieved, insert catheter just until free ﬂ ow of blood is seen with gentle aspiration. • Blood warmer. • Type and cross-match blood (for exchange transfusion being performed for hyperbilirubinemia, hemolytic disease of the newborn, metabolic and electrolyte disturbances, or severe anemia; in cases of exchange transfusion for polycythemia, removed blood will be replaced with normal saline). • Ask for the blood bank to mix PRBCs and plasma to a ﬁ nal hematocrit of 40%–45%. • Ask for 30–50 mL of extra blood to prime the tubing system before beginning the exchange (not applicable in exchange with NS being performed for polycythemia).

GUIDELINES FOR TYPING AND CROSS-MATCHING BLOOD FOR VARIOUS INDICATIONS

Indication Blood Typing and Cross-Matching Hyperbilirubinemia Type and cross-match against infant plasma and RBCs Hemolytic disease of the newborn • Rh incompatibility Type O, Rh-negative, low anti-A and anti-B titers; cross-match to maternal plasma and RBCs • ABO incompatibility Type O, Rh-compatible

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Indication Blood Typing and Cross-Matching

• Minor blood group incompatibilities Type O, Rh-compatible

Metabolic disorders causing severe Type and cross-match against infant plasma and acidosis or hyperammonemia RBCs

Severe hyperkalemia or other severe Type and cross-match against infant plasma and electrolyte abnormality RBCs

Severe anemia (in presence of hyper- Type and cross-match against infant plasma and volemia or in normovolemia when RBCs large volume transfusions may not be tolerated)

• Laboratory work to be sent before starting: Total and ionized calcium, electrolytes, pH, glucose, CBC

Procedure • Points to remember • Completely prime the system with donor blood (or saline in the case of exchange for polycythemia). • Remember to turn the stopcock in the clockwise direction only. • Exchange in aliquots of 5–20 mL depending on size of patient and clinical status. • Have someone present at bedside while you are performing exchange to document the amount of blood exchanged and to record vitals Q15–30 min (or as outlined by your NICU guidelines). • Procedure steps 1. Using the master stopcock, remove an aliquot of blood from the infant. 2. Turn the stopcock clockwise one step to waste bag and ﬂ ush. 3. Turn the stopcock clockwise one step to the donor blood port (or to the saline port in exchange for polycythemia) and draw up a volume identical to the volume removed in Step 1. 4. Turn the stopcock clockwise one step and infuse donor blood or saline into the infant. 5. Wait 2–5 min. 6. Repeat from Step 1 to complete the predetermined volume of exchange. 7. After the exchange is completed, send off the same lab studies that were performed before starting.

Complications • Infectious: Viral infections transmitted via blood transfusion (HBV, HCV, CMV, HIV) as well as Staphylococcus spp. • Vascular accidents • Bleeding complications • Electrolyte or metabolic abnormalities • Hypoglycemia • Necrotizing enterocolitis

ANEMIA NEONATOLOGY • Physiologic nadir occurs at 6–12 wk for term infants, 5–10 wk for premature infants (1200 g– 2500 g birthweight), and 4–8 wk for infants with birth weight <1200 g. 432 Neonatology

BRIEF DIFFERENTIAL DIAGNOSIS OF ANEMIA IN NEONATES

Etiology Mechanism Examples Blood Loss Obstetric causes Placental abruption • ↓ or normal Placenta previa hematocrit Placental trauma ↑ • or normal Rupture of anomalous vessels (vasa previa, velamen- reticulocyte tous insertion) count Cord hematoma • Normal bilirubin (unless Cord rupture blood is Occult loss Fetomaternal hemorrhage (chronic or acute) from pla- retained) cental malformations (eg, chorioangioma), obstetrical procedures (amniocentesis, version), spontaneous Fetoplacental hemorrhage (from chorioangioma, tight nuchal cord, or occult cord prolapse) Twin-to-twin transfusion syndrome Neonatal causes Intracranial bleeding Cephalohematoma Subgaleal hemorrhage Hemorrhagic caput succedaneum Retroperitoneal bleeding Splenic or hepatic rupture Adrenal or renal hemorrhage GI bleeding (should rule out swallowed maternal blood with Apt test if suspicion is high) Iatrogenic (frequent blood draws) Hemolysis Immune-mediated Rh incompatibility • ↓ Hemat- ABO incompatibility ocrit Minor blood group incompatibility ↑ • Retic Maternal autoimmune disease (eg, SLE) ↑ • Bilirubin Maternal or neonatal drug exposure (eg, penicillin) Hereditary Membrane defects (spherocytosis, elliptocytosis) disorders of RBC Metabolic defects (G6PD defi ciency, pyruvate kinase defi ciency) Hemoglobinopathies (α and β thalassemia syndromes) Acquired Infection hemolysis DIC Nutritional defi ciencies (eg, vitamin E defi ciency) Microangiopathic hemolytic anemia Hemangioma Renal artery stenosis Severe aortic coarctation Diminished Diamond-Blackfan syndrome production Congenital leukemia ↓ • Hemat- Neoplasms ocrit Osteopetrosis • ↓ Retic Drug exposure (eg, penicillin) • Normal bilirubin Physiologic anemia Anemia of prematurity Hematology 433

Workup and Diagnosis • Review FHx. • Review obstetric and peripartum history. • Perform physical examination. • Labs and studies: • CBC • Reticulocyte count • Blood smear • Total and fractionated bilirubin levels • Apt test (to test for swallowed maternal blood an infant GI tract) • Kleihauer-Betke preparation (to assess for the presence and degree of fetomaternal hemorrhage) • Workup for congenital infection (so-called TORCH infections) based on history and physical examination • US of head and abdomen • Some of the genetic causes of anemia can be worked up in the parents to minimize blood draw from the infant • Bone marrow evaluation is reserved only for very select cases

Therapy • Therapy should be guided by the infant’s physiologic status and hemodynamic stability. • See “Transfusions” section for guidelines on transfusion of PRBCs in the neonatal population • The use of erythropoietin in premature infants is controversial and is currently reserved for consideration on a case-by-case basis.

BLOOD PRODUCT TRANSFUSION OPTIONS IN ANEMIA

Type of Transfusion Considerations

PRBCs• Calculate the volume of transfusion to be given (see below) • Irradiated cells should be used for neonates • Leukocyte reduced units reduce the risk of exposure to foreign lymphocytes and CMV • Families can be oﬀ ered the option of donor-directed blood (irradiation of this blood is of particular importance because of the HLA compatibility among ﬁ rst-degree relatives and the risk of foreign lymphocyte engraftment)

Whole blood• Indicated for large acute blood loss

Partial exchange • Indicated for infants with severe anemia in whom transfusion of transfusion (isovolemic regular PRBC units would present a signiﬁ cant volume overload transfusion) (eg, hydropic infants)

• Calculation of the volume of PRBC or whole blood transfusion: ∗ × − NEONATOLOGY TBV [(HCTdesired HCTobserved) / HCTblood to be given∗∗]

(∗): TBV (Total Blood Volume): Preterm neonate = 100 mL/kg; term neonate = 85 mL/kg; 4 mo = 75 mL/ kg; >4 mo = 70 mL/kg. (∗∗): AS-1 and AS-3 PRBC unit hematocrits range from 55-65% (mean 57%); CPDA-1 PRBC unit hematocrit ranges from 60-80%. (CPDA-1 is not used at TCH; check with your institution.) 434 Neonatology

TREATMENT OF ABNORMAL BLEEDING IN NEONATES

Treatment Considerations Vitamin K IM dose of vitamin K (1 mg) is given at birth for prophylaxis Consider prophylaxis with vitamin K for infants on prolonged courses of antibiotics or with cholestasis to prevent secondary defi ciencies FFP Used for immediate replacement of clotting factors See “Transfusion” section for indications and methods of transfusion Platelets Usually transfused for platelet level <20,000/mm3 or active bleeding Fresh whole blood Can be given for large, acute blood loss Clotting factor Given for known, specifi c factor defi ciencies to avoid overload of concentrates nondefi cient factors Cryoprecipitate Best source of concentrated fi brinogen and factor VIII

BLOOD PRODUCT TRANSFUSIONS • Blood products that are transfused include PRBCs, platelets, FFP, cryoprecipitate, and granulocytes. • As with all medical therapy, transfusion of any blood product has potential side effects, the most notable of which is transmission of bloodborne infectious diseases (HIV, hepatitis viruses [A, B, or C], CMV, as well as a multitude of others; see Chapter 18 for speciﬁ c risks). • Documentation in the chart as to the indication for transfusion should be completed. • Informed consent must be obtained before transfusion of any blood products.

GUIDELINES FOR TRANSFUSION OF BLOOD PRODUCTS IN NEONATES

Blood General Indications and Dosing and Product Principles Contraindications Administration Side Eff ects

PRBCs • RBCs provide For hematocrit • Usual transfu- • Acute hemolytic increased <35%–40%: sion, 5–15 mL/ transfusion reaction oxygen- carrying • Mechanical ven- kg at ~5 mL/ • Usually caused capacity kg/h tilation with FiO2 by antibodies in • Preservative >35% or mean • Adjust dose and patient plasma solutions are airway pressure time of transfu- reacting to donor

used to extend >6 cm H2O sion depending RBCs the storage life • Hypotension on the infant’s • Rare in neonates of PRBCs (shelf- ability to handle • Chronic or recur- unless there is life, 21–35 d volume expan- rent bleeding high titer maternal depending on sion isohemagglutinins which solution (anti-A, anti-B) is used; check For hematocrit • Allergic reactions with your blood <25%–30%: • Usually caused by bank to deter- • HR >180 bpm antibodies in pa- mine the shelf for 24 h tient plasma react- life of PRBCs ing with proteins used at your • Apnea >9–12/h in donor plasma institution) requiring b-m ventilation • Rare in neonates • Average hematocrit, 70%–80% • Wt gain <10 g/kg/ • Volume overload day w/ full caloric • Hypocalcemia intake • Hypothermia

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Blood General Indications and Dosing and Product Principles Contraindications Administration Side Eff ects

• PRBC units • Unexplained • TRALI undergo lethargy • Caused by anti- changes during • Plan for major bodies in donor storage as the surgery plasma reacting unit approaches with patient’s HLA its expiration antigens For hematocrit date • <20%–25%: More likely with • pH ↓ from components with ~7.40–~6.50 • May consider high plasma con- transfusion in- • Potassium tent (platelets, FFP) dependent of concentration • Hyperkalemia symptoms increased from • Febrile nonhemolytic ~4.2 mM to transfusion reactions ~50–75 mM • Caused by cytokines • 2,3-DPG levels released in donor decrease over unit; occurs less the ﬁ rst 14 d often in leukocyte but are replen- reduced units ished within • Bacterial contamina- hours of being tion transfused • Transfusion associated GVHD • May be prevented with irradiation of blood products before transfusion

Platelets• Each unit • No data exist • 5–10 mL/kg • More likely to be of platelets on minimum over 30–60 contaminated with contains >5 platelet level in min bacteria 10 x10 platelets patients at risk • Should • ABO-incompatible in 50 mL of an- for intraventricu- increase plasma in platelet ticoagulated lar hemorrhage, the platelet transfusion may plasma but levels of count (in a cause hemo- • Stored at 50,000–100,000 nonconsump- lytic transfusion 3 room tem- platelets/mm tive clinical reaction perature for are generally situation) by ≤5 d accepted 30,000– • In all other 60,000/mm3 neonates, trans- • If alloimmune fuse for levels thrombocy- <20,000 topenia, may • Transfuse when need to use there is active washed mater- bleeding nal platelets • Adjust dose and time of transfusion NEONATOLOGY depending on the infant’s ability to handle volume expansion

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Blood General Indications and Dosing and Product Principles Contraindications Administration Side Eff ects

Fresh • ~1 U/mL of • To correct • 10–20 mL/kg • Hyperkalemia does Frozen each coagula- coagulopathies over 30–60 not occur Plasma tion factor caused by factor min • TRALI (FFP) (may have deﬁ ciencies • Adjust the • Acute hemolytic lower levels dose and time reactions are ex- of unstable of transfusion tremely unlikely factors V and depending • Hypocalcemia VIII) on the infant’s (caused by sodium • Sodium ability to citrate in FFP) content is handle volume 160–170 expansion mEq/L • Potassium content is 3.5–5.5 mEq/L • Contains all plasma proteins (including albumin and antibodies)

Granu- • Therapy is • In septic • 10–15 mL/kg • All of the potential locytes controversial neonates not over 2–4 h adverse reactions responding to • Adjust the seen with PRBC antimicrobial dose and time transfusion therapy of transfusion • Pulmonary compli- • If used, can depending cations only be used as on the infant’s • Transmission of a temporizing ability to CMV measure until handle volume the infant is able expansion to produce his or her own neutrophils

Available at www.AccessPediatrics.com • Neonatal thrombosis • Abnormal bleeding NEONATOLOGY monitor monitor monitor monitor → → monitor CBC monitor LFTs on treatment LFTs cause interstitial Can nephritis functionrenal weekly on treatment cause bone Can suppression marrow → weekly on therapy Moderate CSF penetration primarily by Cleared the liver (continued on next page) 437 7 d postnatal age: 450,000 ≤7 d: 25 mg/kg/dose q12h >7 d: 25 mg/kg/dose q8h ≤7 d: 25 mg/kg/dose q12h >7 d: 25 mg/kg/dose q8h ≤7 d: 25 mg/kg/dose q12h >7 d: 25 mg/kg/dose q6h ≤ • • • • • • interval above as listed 75 mg/kg/dose IV q6h 75 mg/kg/dose IV q12h units/kg/d divided every 8 h 500,000 units/kg/d divided every 4 h IV q12h ≤7 d old: 150 mg/kg/dose 30–37 wk PMA: 30–37 wk PMA: >37 wk PMA: 50 mg/kg/dose at same Use Meningitis or no CSF obtained: Sepsis without meningitis: >7 d: 50 mg/kg/dose q6h >7 d postnatal age: 450,000– ≤7 d: 50 mg/kg/dose q8h >7 d old: 75 mg/kg/dose IV q6h <30 wk postmenstrual age (PMA): <30 wk postmenstrual age (PMA): Empiric treatment for early- or for Empiric treatment late-onset >72 hrs) sepsis: (age GBS meningitis: GBS meningitis: • • • Meningitis: • Treatment >48 h: Treatment • • • • • • Other GBS infections: 200,000 units/kg/d divided every 6 h Non-CNS infections: • • spp. spp. Escheri- Strepto- Entero-

spp. spp.) Organisms Organisms Covered ( organisms coccus Dose Susceptible chia coli Listeria monocytogenes Notes Treponema pallidum Treponema Pseudomonas Pseudomonas aeruginosa Staphylococcus aureus coccus coccus Other Gram- and enteric negative anaerobes PCN-susceptible Staphylococcus Streptococcus Ampicillin Gram-positive Antibiotic Penicillin GKPenicillin GBS Piperacillin Nafcillin Methicillin-sensitive Infectious Diseases Infectious IN NEONATES COMMON ANTIBIOTICS CHAPTER 38 438 Neonatology

Organisms Antibiotic Covered Dose Notes

Vancomycin Aerobic and anaero- • <30 wk PMA: Only 10%–15% of bic Gram-positive • ≤7 d: 20 mg/kg/dose IV q24h serum concentration cocci and bacilli • >7 d: 20 mg/kg/dose IV q18h enters CSF. Methicillin-resistant • 30–37 wk PMA: Optimal serum S. aureus (MRSA) concentration: • ≤7 d: 20 mg/kg/dose IV q18h Coagulase-negative • >7 d: 15 mg/kg/dose IV q12h • Trough: 15–20 staphylococci mcg/mL • >37 wk PMA: Clostridium diffi cile • ≤7 d: 15 mg/kg/dose IV q12h Bacillus spp. • >7 d: 15 mg/kg/dose IV q8h Ampicillin-resistant • >44 wk PMA (meningitis): Enterococcus • 15 mg/kg/dose IV q6h

Gentamicin, Broad Gram- Gentamicin CSF penetration amikacin, negative bacillus • Indications: early- or late-onset depends on menin- tobramycin coverage sepsis (age >72 h); covers geal inﬂ ammation. Synergistic against Gram-negative rods; use for Monitor peak and S. aureus, GBS, L. synergy trough levels, as monocytogenes, • <35 wk PMA: 3 mg/kg/dose these antibiotics can enterococci IV q24h cause nephrotoxic- • ≥35wk PMA: 4 mg/kg/dose ity and ototoxicity. IV q24h • If given >48 h (>2 doses), draw gentamicin trough before and peak level after the third dose. Monitor BUN/Cr: • Optimum levels: peak= 5–10 mcg/mL, trough = <1.5 mcg/mL • For SYNERGY (against S. aureus, Enterococcus): • 1–1.5 mg/kg/dose IV q24h Tobramycin • <30 wk PMA: • ≤7 d: 3 mg/kg/dose q24h • >7 d: 3 mg/kg/dose q18h • 30–37 wk PMA: • ≤7 d: 3 mg/kg/dose q18h • >7 d: 2.5 mg/kg/dose q12h • >37 wk PMA: • ≤7 d: 2.5 mg/kg/dose q12h • >7 d: 2.5 mg/kg/dose q8h • Optimum levels: peak = 8–10 mcg/mL; trough = <2 mcg/mL Amikacin • <30 wk PMA: • ≤7 d: 15 mg/kg/dose q24h • >7 d: 15 mg/kg/dose q18h • 30–37 wk PMA: • ≤7 d: 15 mg/kg/dose q18h • >7 d: 15 mg/kg/dose q12h

(continued on next page) Infectious Diseases 439

Organisms Antibiotic Covered Dose Notes

• >37 wk PMA: • ≤7 d: 15 mg/kg/dose q12h • >7 d: 15 mg/kg/dose q8h • Optimum levels: peak = 15–40 mcg/mL; trough = <10 mcg/mL

Clindamycin Gram-positive cocci • ≤37 wk PMA: Poor CSF penetra- Anaerobes (includ- • ≤7 d: 5 mg/kg/dose q8h tion ing Bacteroides • >7 d: 10 mg/kg/dose q8h Cleared by the → fragilis) • >37 wk PMA: liver monitor LFTs while on therapy • 13 mg/kg/dose q8h

First-gener- Susceptible Cefazolin: Poor CSF penetra- ation cepha- Staphylococcus, • ≤7 d postnatal age: tion losporins Streptococcus, and • 20 mg/kg/dose q12h (cefazolin, pneumococci cephalexin) • >7 d postnatal age: • <2000 g: 20 mg/kg/dose q12h • >2000 g: 20 mg/kg/dose q8h

Second- Same as ﬁ rst Improved generation ce- generation activity over ﬁ rst- phalosporins plus generation against (cefuroxime, β-lactamase– cefoxitin, Haemophilus producing organ- cefotetan, infl uenzae isms cefprozil) E. coli Little data in Citrobacter neonates, so use is Klebsiella limited Enterobacter cloacae

Third- Gram-negative Cefotaxime: Ceftazidime generation ce- enterics • <1200 g, 0–4 wk: 50 mg/kg/ can be used for phalosporins H. infl uenzae dose q12h adequate coverage (ceftriaxone, of Pseudomonas • ≤7 d postnatal age: cefdinir, Neisseria gonorrheae aeruginosa. • 1200–2000 g: 50 mg/kg/ ceftazidime, Neisseria menin- Ceftazidime, cefo- dose q12h cefotaxime, gitidis taxime, and ceftriax- ceﬁ xime) • >2000 g: 50 mg/kg/dose one all achieve good q8–12h CSF penetration. • >7 d postnatal age: Ceftriaxone displaces • 1200–2000 g: 50 mg/kg/ bilirubin from albu- dose q8h min, raising serum • >2000 g: 150–200 mg/kg/d levels of free uncon- divided q6–8h jugated bilirubin → Ceftazidime: not recommended NEONATOLOGY • <7 d postnatal age: for use in neonates except in treating • 50 mg/kg/dose q12h gonococcal infection • 1–4 wk postnatal age: in nonjaundiced • 30–50 mg/kg/dose q8h neonates. In jaun- diced neonates, use cefotaxime.

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Organisms Antibiotic Covered Dose Notes

Ceftriaxone • ≤7 d postnatal age: • 50 mg/kg/d q24h • >7 d postnatal age: • ≤2000 g: 50 mg/kg/d q24h • >2000 g: 50–75 mg/kg/d q24h • Gonococcal prophylaxis: • 25–50 mg/kg as a single dose (maximum: 125 mg/dose) • Gonococcal infection: • 25–50 mg/kg/d (maximum: 125 mg/dose) q24h for 7 d, up to 10–14 d if meningitis is documented

Macrolides Gram-positive Infants <6 mo: (azithromycin) bacteria • Pertussis (IV, oral): 10 mg/kg MRSA daily for 5 d Neisseria spp. T. pallidum Chlamydia trachomatis Bordetella pertussis

Oxazolidinone Resistant Enterococ- Neonates: Use must be ap- (linezolid) cus faecium, S. au- • 10 mg/kg/dose q8h proved by infectious reus, Streptococcus disease service Preterm infants: pneumoniae • 10 mg/kg/dose q12h

Carbapenems Aerobic and anaero- 0–7 d postnatal age: Use must be ap- (meropenem) bic Gram-positive • Non-meningitis: 20 mg/kg/ proved by infectious and Gram-negative dose q12h disease service bacteria • Meningitis: 40 mg/kg/dose Good CSF penetra- q12h tion >7 d postnatal age: Resistant organisms: Burkholderia • Weight 1200–2000 g: cepacia, E. faecium, • Non-meningitis: 20 mg/kg/ Stenotrophomonas dose q12h maltophilia • Meningitis: 40 mg/kg/dose q12h • Weight >2000 g: • Non-meningitis: 20 mg/kg/ dose q8h • Meningitis: 40 mg/kg/ dose q8h Infectious Diseases 441

NEONATAL MENINGITIS OVERVIEW OF ETIOLOGY AND TREATMENT OF NEONATAL MENINGITIS

Age of Most Common Infant Etiologies Empiric Therapy Length of Therapy

<1 mo L. monocytogenes, Ampicillin and cefo- 14–21 d: GBS, GBS, Enterobacteri- taxime OR ampicillin and L. monocytogenes aceae (E. coli) gentamicin 21 d: Enterobacteriaceae If Gram-negative bacilli, (cefotaxime + aminogly- use cefotaxime instead coside) of gentamicin, as gentamicin has poor CSF penetration.

1–3 mo GBS, S. pneumoniae, Ampicillin and 10–14 d: S. pneumoniae N. meningitidis, H. cefotaxime 7 d: N. meningitidis infl uenzae,Enter- obacteriaceae 7–10 d: H. infl uenzae

>3 mo S. pneumoniae, Cefotaxime or ceftri- Same as above N. meningitidis, axone H. infl uenzae, above Add vancomycin if neonatal pathogens possible PCN-resistant S. pneumoniae until susceptibilities return

Consider less common forms of neonatal meningitis if index of suspicion is high based on history or physical examination ﬁ ndings: viral (HSV (meningoencephalitis), enterovirus, VZV), tuberculosis, fungal, and noninfectious causes (eg, leukemic inﬁ ltrates).

Clinical Features • Neurologic: seizures, lethargy, irritability, decreased tone; full fontanelle • Fever (>38°C) or hypothermia (more common in preterms) • Respiratory distress: grunting, tachypnea, nasal ﬂ aring • Poor feeding • Diarrhea, vomiting • Apnea

Risk Factors • Premature rupture membranes, maternal fever/infection, fetal hypoxia, birth trauma, galactosemia (E. coli sepsis), low birth weight, preterm infants (<37 wk)

Workup • CBC, blood culture, UA with microscopy/culture, LP (cell count, protein, glucose, Gram stain/culture), PCR studies if indicated (HSV, enterovirus, VZV, LCMV) • Viral surveillance cultures, if indicated: conjunctiva, nasopharynx, rectum • Culture any cutaneous lesions concerning for HSV, VZV: NEONATOLOGY • Classic ﬁ nding of ↓ CSF glucose, ↑ CSF protein, and pleocytosis: seen more with early GBS meningitis, Gram-negative meningitis and late Gram-positive meningitis; may also be suggestive of viral meningitis (eg, enterovirus). • Only if all three parameters are normal does LP provide evidence against infection; no single CSF parameter can exclude the presence or absence of meningitis in neonates. • Bacterial meningitis commonly causes CSF pleocytosis >100 WBC/μL, predominantly polymophonuclear cells evolving to lymphocytes. 442 Neonatology

• Viral meningitis in neonates: picture may be similar but with a less dramatic pleocytosis. • Maternal investigation: If possible, send placenta for pathology and, if indicated, cultures/PCR. • MRI/CT: to identify focal areas of infection, infarction, hemorrhage, edema, hydrocephalus, or abscess formation. Consider with focal neurologic abnormalities, persistent infection, or clinical deterioration. • Eye exam may be helpful to evaluate for chorioretinitis.

CSF PROFILES FOR INFANTS WITH BIRTH WEIGHT <1500 GRAMS

Postnatal Age (days) Weight CSF Component (grams) 0-7 8-28 29-84

†Erythrocytes/mm3 ≤1000 335 (0–1780) 1465 (0–19,050) 808 (0–6850) 1001–1500 407 (0–2450) 1101 (0–9750) 661 (0–3800)

Leukocytes/mm3 ≤1000 3 (1–8) 4 (0–14) 4 (0–11) 1001–1500 4 (1–10) 7 (0–44) 8 (0–23)

Neutrophils (% of ≤1000 11 (0–50) 8 (0–66) 2 (0–36) total leukocytes) 1001–1500 4 (0–28) 10 (0–60) 11 (0–48)

‡Glucose (mg/dL) ≤1000 70 (41–89) 68 (33–217) 49 (29–90) 1001–1500 74 (50–96) 59 (39–109) 47 (37–76)

*Protein (mg/dL) ≤1000 162 (115–222) 159 (95–370) 137 (76–260) 1001–1500 136 (85–176) 137 (54–227) 122 (45–187)

The values represent means (range). Normal CSF values vary depending on the study from which the information was obtained. The above values are representative of the cited study. For normal CSF values for broader term and preterm infant populations, refer to Chapter 20. Adapted from J Peds 1990;116:971. † The wide variability in the CSF erythrocyte count likely represents trauma from the procedure. ‡ Compare CSF to serum glucose ratios (normal should be approximately 0.5-0.8). * CSF protein levels may be “normally” elevated in preterm infants for the ﬁ rst week of life.

GROUP B STREPTOCOCCAL INFECTIONS CLASSIFICATION OF GROUP B STREPTOCOCCAL DISEASE

Early-Onset Late, Late-Onset Disease* Late-Onset Disease Disease

Time of 0–7 DOL >7 d–3 mo of life >3 mo of life onset Mean time: 8 h Mean time: 36 d

Commonly • All infants • Predominantly term • Predominantly neonates aﬀ ected infants <32 wk gestation or im- population munocompromised patients

Symptoms• Respiratory • Fever • Fever distress • Lethargy • Irritability • Apnea • Irritability • Nonspeciﬁ c signs • Hypotension • Nonspeciﬁ c signs • Respiratory distress → cardiovascular collapse

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Early-Onset Late, Late-Onset Disease* Late-Onset Disease Disease

Infectious • Bacteremia • Bacteremia without • Bacteremia without focus foci (40%–55%) focus (55%) • Rarely focal infections • Pneumonia • Meningitis (35%) • Can aﬀ ect any organ system (30%–45%) • Osteoarthritis (~5%) • Meningitis • Cellulitis/adenitis (~2%) (6%–15%)

Serotypes AII (Ia, II, III, V Type III predominates Type III most common)

∗Maternal risk factors speciﬁ c for early neonatal GBS infection: previous fetal loss, UTI or bacteruria with GBS, primiparity

Treatment • Usual duration of treatment (see the table below)

DURATION OF THERAPY FOR GBS INFECTION BASED ON CLINICAL SCENARIO

Uncomplicated bacteremia without focus 10 d (sterile)

Uncomplicated meningitis 14 d (for Gram positive), 21 d (for Gram negative)

Complicated meningitis As dictated by serial LPs, imaging studies

Septic arthritis/osteomyelitis 3–4 wk (or longer as indicated by clinical course)

Endocarditis/ventriculitis Minimum of 4 wk

OPHTHALMIA NEONATORUM Ophthalmia neonatorum or conjunctivitis in the newborn is due to chemical exposure, infections, or anatomic obstruction.

SUMMARY OF VARIOUS CAUSES OF OPHTHALMIA NEONATORUM

Chemical Chlamydial Gonococcal Dacryostenosis

Age at pre- First 48 h 1–2 wk of life 2–5 DOL Usually by 2–4 wk sentation of life of life

Symptoms Mild to Varies: Intense puru- Tearing and mu- moderate Mild conjunctivitis lent discharge, coid discharge conjuncti- with watery/mucopu- chemosis, lid Swelling in the vitis rulent discharge to edema nasal portion of NEONATOLOGY Can have marked swelling of Can progress eye with or without tearing eyelids and inﬂ amed, to corneal mild erythema thickened conjuncti- perforation if vae (chemosis) with left untreated pseudomembrane formation

(continued on next page) 444 Neonatology

Chemical Chlamydial Gonococcal Dacryostenosis

Diagnosis This is a Conjunctival swab Swab culture Clinical → may diagnosis of culture of everted of discharge have unilateral or exclusion eyelids bilateral swelling, Antigen detection discharge is usu- and PCR also ally sterile, or with available common skin fl ora Treatment No specifi c Not prevented IV or IM cef- ~90% of cases re- therapy; dis- by erythromycin triaxone as a solve with lacrimal continue use or silver nitrate single dose sac massage in the of off ending prophylaxis Full SBI evalu- fi rst year of life agent In most patients, ation should If infant appears spontaneous resolu- be done ill, further evalu- tion occurs for invasive ation for invasive Oral erythromycin gonococcal infection should be for 10–14 d disease undertaken

Vaccinating the Term Infant • See Chapter 19.

Vaccinating the Preterm Infant • All vaccines (DTaP, HIB, IPV, inﬂ uenza, PCV7) except Hepatitis B vaccine should be given on time with routine childhood immunizations, at full doses, as recommended in full-term infants (see Chapter 19 for Immunization Guidelines). Anterolateral thigh is the site of choice. • Hepatitis B vaccine in premature and low birth weight infants is dependent on maternal Hepatitis B antigen status and infant weight (see below)

SUMMARY OF HEPATITIS B VACCINATION IN THE PRETERM INFANT

Maternal Hep B Status Infant weight: <2 kg Infant weight >2 kg

HBsAg positive HepB vaccine + HBIG ≤12 h of HepB vaccine + HBIG ≤12 h birth, and immunize with four of birth, and immunize with doses Hep B vaccine: 0, 1, 2–3, three doses Hep B vaccine: 0, and 6–7 mo 1, and 6 mo

Check titers anti-HBsAg at 9–15 mo of age If negative, revaccinate with three more doses at 2-mo intervals, recheck titers

HBsAg unknown HepB vaccine + HBIG ≤12 h Hep B vaccine ≤12 h of birth, of birth HBIG ≤7 d if mom tests HBsAg +

HBsAg negative First HepB vaccine at 30 d if First HepB vaccine at birth clinically stable, or at discharge Immunize at 2, 4, 6–18 mo if ≤30 DOL (three doses) Immunize at 2, 4, 6–18 mo (three doses)

Available at www.AccessPediatrics.com • Torch Infections • Neonatal Hepatitis NEONATOLOGY 100% rior urethral valves) rior urethral syndrome Urethral obstruction (eg, poste- obstructionUrethral (eg, Ureterocele obstruction Ureteropelvic obstruction Ureterovesicular of ureters Extrinsic compression bladder Neurogenic Megacystis or megaureter × • • • • • • • Plasma Na uid challenge of 10–20 mL/kg of normal × Plasma Cr 445 × valid if diuretic is used) not Urine Na rm inadequate urine output and r/o obstruction. indomethacin use Urine Cr Renal agenesis Renal dysplasia Polycystic disease Medications Radiographic contrast Maternal ACE inhibitor or (%)= • • • • • • ATN abnormalities Congenital disease Thromboembolic Nephrotoxins Na • • • • FE (These studies are Na nition calculate FE Serum electrolytes, BUN, creatinine CBC, platelet count Urinalysis with microscopic analysis and creatinine to Urinary sodium and creatinine with simultaneous serum sodium volume Hemorrhage Dehydration CHD Polycythemia Indomethacin use drugs Adrenergic Birth asphyxia Sepsis Reduced intravascular intravascular Reduced abdominal masses and other congenital urogenital abnormalities. evidence of heart failure or volume overload, a fl suggests intrinsic renal or saline can be administered over 30–60 min. Lack of response postrenal failure. associated increase in serum creatinine seen with nephrotoxic medications) Bladder catheterization to confi Laboratory studies Non-oliguric: Increased serum creatinine with normal or increased urine output (usually Non-oliguric: Increased serum Perform history to elicit predisposing factors listed above and physical exam to palpate for Perform history to elicit predisposing factors listed above and exam and there is no If prerenal failure is suspected on the basis of history or physical Oliguric: Anuria or oliguria (<0.5 mL/kg/h in children; <1 mL/kg/h in infants) with an Oliguric: Anuria or oliguria (<0.5 Imaging: US examination of kidneys and urinary system • • • • • • • Prerenal• • Renal Intrinsic Postrenal • • • • • Diagnosis • • • • • INJURY IN NEONATES ETIOLOGY OF ACUTE KIDNEY Nephrology RENAL FAILURE, ACUTE INJURY (ACUTE RENAL ACUTE KIDNEY INJURY) IN NEONATES Defi • CHAPTER 39 446 Neonatology

Prerenal Intrinsic Renal Urine osmolality (mOsm) >400 <400 Urine sodium (mEq/L) 31 ± 19 63 ± 35 Urine/plasma creatinine 29 ± 16 10 ± 4 Fractional excretion of sodium (%) <1.5 >2.5

Management Oliguric Acute Kidney Injury • Discontinue or minimize all fl uids that contain potassium and phosphorus. • Please see chapter 34 for management of hyperkalemia in neonates. • Fluid management should be strict, with administration of fl uids equal to insensible fl uid losses plus urine and other fl uid output (eg, chest tubes). • Monitor serum sodium, potassium, calcium, and phosphorus levels. • Treat hypocalcemia as required (see Chapter 34 [Endocrinology] for treatment of hypocalcemia in neonates). • Protein intake may need to be restricted. • Monitor for metabolic acidosis and correct as appropriate with intermittent administration of sodium bicarbonate or sodium acetate infusions. • Monitor BP and treat hypertension as indicated (See “Hypertension” section in this chapter). • Serum levels of all medications that are excreted by the kidney must be monitored carefully to avoid further nephrotoxic injury. Limit all nephrotoxic agents when clinically feasible. • Dialysis is indicated when conservative measures fail to prevent severe fl uid overload, hyperkalemia, and metabolic acidosis. • Hemodialysis vs peritoneal dialysis vs continuous renal replacement therapy (eg, CVVH) • May be limited by the size of the infant • For postrenal failure, need to bypass the obstruction with a bladder catheter, percutaneous nephrostomy drainage, or surgical correction. Non-oliguric Acute Kidney Injury • Monitor serum sodium, potassium, calcium, and phosphorus levels because patients may require replacement of these electrolytes because of excessive losses. • Monitor urine output closely because patients may be polyuric. • Monitor serum concentrations of all nephrotoxic medications when possible and avoid further exposure when clinically feasible.

HYPERTENSION IN NEONATES Deﬁ nition • Full-term infants: SBP >90 mm Hg; DBP >60 mm Hg • Premature infants: systolic BP >80 mm Hg; DBP >50 mm Hg DIFFERENTIAL DIAGNOSIS OF HYPERTENSION IN NEONATES

System Examples Vascular Renal artery or vein thrombosis Renal artery stenosis Aortic thrombosis Coarctation of aorta

Renal Obstructive uropathy Renal failure Renal neoplasia (Wilms tumor)

(continued on next page) Nephrology 447

System Examples Neurologic Drug withdrawal Pain or agitation Increased ICP (very rare manifestation in neonates) Seizures Endocrine Congenital adrenal hyperplasia Hyperthyroidism Adrenal neoplasia (neuroblastoma, pheochromocytoma) Medications Pancuronium Corticosteroids Dopamine Vitamin D Epinephrine Other Bronchopulmonary dysplasia ECMO Fluid overload Idiopathic Spurious (improper BP cuﬀ size)

Evaluation • Physical exam: Check femoral pulses and examine the abdomen to evaluate for masses or enlarged kidneys. • Laboratory studies: Determine renal function with serum creatinine and BUN levels, urinalysis, serum electrolytes, and plasma renin activity. • Radiologic studies: Abdominal US, head US, echocardiogram. • Adjunct studies may be obtained based on clinical suspicion: Renal vessel angiography to evaluate for renal artery stenosis, renal scan to determine the extent of renal scarring or loss of function, renal biopsy (not routinely done for isolated hypertension), 24-h urine collection to determine catecholamine levels. Management • Treat any underlying cause of hypertension (eg, fl uid overload, pain or agitation, medications). • Management guidelines for hypertension in neonates are controversial. • For hypertension that is symptomatic (nonspecifi c cardiac fi ndings of tachypnea, cardiomegaly, or heart failure or neurologic symptoms such as irritability, lethargy, or seizures), immediate treatment to lower BP is indicated. • Hydralazine has been used for control, titrating to the lowest effective doses. • Labetalol and nicardipine starting with lowest doses (limited use in neonates reported) • For moderate hypertension (asymptomatic) • Diuretics • Vasodilators (hydralazine, nicardipine) or β-blockade (labetalol, propranolol) • ACE inhibitors may be used but with caution because use may lead to oliguria, hyperkalemia, or renal failure. Bilateral renal artery stenosis must be excluded before use. Check serum electrolytes and creatinine within 24 h after initiation and dose escalations.

• For mild hypertension, simple observation may all be that is needed. If hypertension does NEONATOLOGY not improve or worsens, treat as above.

Available at www.AccessPediatrics.com • Congenital syndromes and disorders with renal manifestations CHAPTER 40 Neurology

NEONATAL SEIZURES

ETIOLOGIES OF NEONATAL SEIZURES

Underlying Defect Points to Remember Hypoxic–ischemic • Leading cause of neonatal seizures in full-term infants. encephalopathy • This diagnosis should never be one of exclusion. • Data supporting this diagnosis (history of prolonged labor, perinatal depression, prolonged resuscitation) should be obtained and documented. Focal ischemia/ • Second most common cause of neonatal seizures in full-term infants. infarction • Most common presentation is right-sided clonic seizures due to infarction in the left middle cerebral artery territory. • Cerebral vein thromboses can lead to venous infarcts. Intracranial • In term infants, subarachnoid hemorrhage is more associated with hemorrhage subsequent seizure than subdural hemorrhage. • Infratentorial subdural hemorrhages require urgent evaluation due to risk of brainstem compression. • In preterm infants, intraventricular hemorrhage is the most common type of ICH (see below). Infections of the • Can occur in utero (CMV, toxoplasmosis) or perinatally (herpes simplex, CNS bacterial meningitis with GBS or Escherichia coli being most common). • Prognosis can be very grim. Metabolic • Transient causes (hypoglycemia, hypocalcemia, hyponatremia); see derangement Chapter 34 for further information. • Inborn errors of metabolism (pyridoxine dependency, nonketotic hyperglycinemia, urea cycle defects, glutaric aciduria (type II), maple syrup urine disease, organic acidurias, cofactor deﬁ ciencies, mitochondrial defects , Zellweger Syndrome). Structural defects• Defects of neuronal migration (heterotopias). • Defects of neuronal organization (polymicrogyria). • Cerebral malformation (holoprosencephaly). • Usually will display associated dysmorphic features on physical examination.

COMMON CAUSES OF NEONATAL SEIZURES BY AGE AT PRESENTATION

Day of Life Possible Causes 1 Hypoxic ischemic encephalopathy Maternal drug use Infection Hypoglycemia Hypocalcemia 2–3 All of the above CNS malformation Inborn errors of metabolism Hypernatremia Drug withdrawal Hyponatremia

448 Neurology 449

CLASSIFICATION OF NEONATAL SEIZURES

Seizure Type Clinical Manifestation

Subtle Oral–buccal–lingual or ocular movements Stereotypical stepping/swimming Δ Autonomic dysfunction ( in HR, BP, SpO2) Clonic Rhythmic, slow jerking Focal or generalized Facial, extremity, or axial involvement

Tonic Sustained limb posturing Focal or generalized Asymmetric position of trunk/neck

Myoclonic Rapid isolated jerks Generalized, multifocal, or focal Limb/trunk involvement

NEONATAL SEIZURE MIMICS

Seizure Mimic Clinical Manifestation

Jitteriness Spontaneous or provoked by stimulus Flexion/extension are equivalent Diminished by repositioning Abolished with containment

Benign neonatal Bilateral or unilateral sleep myoclonus Synchronous or asynchronous Occurs during sleep Not due to a stimulus

Stimulus-evoked Focal or generalized myoclonus Severe CNS dysfunction EEG may show cortical spike-wave discharge

Hyperekplexia Generalized stiff ness (stiff -man Autosomal dominant and recessive forms syndrome) Excessive startle responses to unexpected stimuli Excessive stiff ness following startle response Benzodiazepines reduce symptoms

Management • Support respiratory and cardiovascular function (may require endotracheal intubation and mechanical ventilation). • Place on continuous cardiorespiratory monitoring. • Correct any known causes of seizures (see above). • If seizures continue after correction of transient metabolic derangements, load with phenobarbital (20 mg/kg IV); can be followed by repeat doses of 5–10 mg/kg IV to a

total dose of 40 mg/kg IV, if needed. NEONATOLOGY • If seizures continue, load with a benzodiazepine such as midazolam (0.1 mg/kg IV; repeat doses can be given to a total dose of 0.3 mg/kg IV). • If seizures continue, load with fosphenytoin 20 mg/kg. • If seizures continue, can consider loading with pyridoxine (100 mg/kg IV), preferably with EEG monitoring. Maintenance dosing can be 50-100 mg/dose once daily (orally) • Newer agents that are used in older children, adolescents, and adults may sometimes be given (in consultation with the neurology service), but no data exist on the safety and efﬁ cacy of these medications in neonates. 450 Neonatology

INTRAVENTRICULAR HEMORRHAGE • Defi nition: an intracranial hemorrhage that originates in the paraventricular subependymal germinal matrix and may extend into the lateral ventricular system. • 50% of IVH occurs in the fi rst 24 h after birth, and 90% by 7-10 days of life. • Incidence and severity are inversely proportional to gestational age. • Antenatal steroid administration is associated with a lower incidence. • Major risk factors: • Extreme prematurity • Need for assisted ventilation • Pneumothorax • Clinical presentation can be very diverse: • May be asymptomatic • May have nonspecifi c symptoms (bulging fontanelle, sudden drop in hematocrit, apnea/bradycardia, metabolic acidosis, seizures, change in level of consciousness) • May present with a catastrophic constellation of symptoms (profound hypotension, severe neurogenic pulmonary edema, rapid deterioration in neurologic exam, decerebrate posturing) • All infants with birth weight <1500 g and any infant who the attending physician feels is at risk for IVH should receive a screening head US between 7 and 10 DOL. • If abnormalities are noted on the initial screening US, follow-up is recommended at weekly intervals to monitor for the development of posthemorrhagic hydrocephalus. • If no abnormalities are noted on the initial screening US, follow-up cranial imaging can be done at 36–40 wk postmenstrual age to evaluate for evidence of periventricular leukomalacia.

PAPILE’S GRADING OF IVH

Grade I Germinal matrix hemorrhage

Grade II Germinal matrix hemorrhage with intraventricular hemorrhage but without ventricular dilation

Grade III Germinal matrix hemorrhage with intraventricular hemorrhage and dilation

Grade IV Germinal matrix hemorrhage with parenchymal involvement

• Prognosis: • Mortality in severe IVH (grades III/IV) is approximately 20%–50%. • Incidence of posthemorrhagic hydrocephalus in severe IVH (grades III/IV) is approximately 55%–80%. • Long-term major neurologic sequelae are related to the extent of parenchymal injury: • 15%–20% of infants with minor degrees of hemorrhage will have a major neurodevelopmental impairment (slightly higher than those without IVH). • 50%–80% of infants with severe hemorrhage will have major developmental impairment.

NEONATAL ENCEPHALOPATHY • A diagnosis of neonatal encephalopathy can be considered when an infant has both a change in mental status and an abnormal neurologic examination. • The Sarnat classiﬁ cation is most frequently used to describe the severity of encephalopathy and is most appropriate for infants with HIE. Neurology 451

SARNAT STAGES OF HIE

Stage 1 (Mild) Stage 2 (Moderate) Stage 3 (Severe)

Level of con- Hyperalert Lethargic Stuporous, comatose sciousness

Tone Normal Hypotonic Flaccid

Posture Normal Flexed Decerebrate

Reﬂ exes Hyperactive Hypoactive Absent

Pupils Mydriasis Miosis Unequal, poor light reﬂ ex, midline

Oculovestibular Normal Overactive Weak or absent

Seizures None Common Decerebrate

EEG Normal Low voltage with Burst suppression to seizures isoelectric

Duration of <24 h 2–14 d Hours to weeks symptoms

Outcome Nearly 100% 80% normal ~50% die; survivors normal have severe sequelae

• Common causes of encephalopathy include metabolic abnormalities, toxic injury, intracranial hemorrhage, cerebral infarction, CNS developmental anomalies, CNS infection, and HIE.

Hypoxic–Ischemic Encephalopathy (HIE) • Essential points that should be present for diagnosing perinatal asphyxia associated with brain damage include∗: • Profound metabolic or mixed acidosis (with pH <7.00) on umbilical cord arterial sampling • Persistence of Apgar score 0–3 for >5 min • Neurologic manifestations in the immediate neonatal period (seizures, hypotonia, coma, or HIE • Evidence of multisystem organ involvement in the immediate neonatal period

THE MOST COMMON MANIFESTATIONS OF MULTISYSTEM ORGAN INVOLVEMENT

Organ System Manifestations

CNS HIE (see Sarnat classiﬁ cation above)

Pulmonary Persistent pulmonary hypertension RDS

Cardiovascular Hypotension Tricuspid insuﬃ ciency NEONATOLOGY Left ventricular dysfunction Myocardial infarction

GI Hepatic injury

(continued on next page)

∗As deﬁ ned in a joint statement by the American Academy of Pediatrics (AAP) and American College of Obste- tricians and Gynecologists (ACOG). 452 Neonatology

Organ System Manifestations

Renal ATN Acute cortical necrosis Oliguria/anuria

Hematologic Increased nucleated RBC DIC Thrombocytopenia

Metabolic Acidosis Hypoglycemia SIADH Hypocalcemia

• Hypothermia to treat neonatal HIE may be effective in moderate HIE, but long-term efﬁ cacy and safety data are lacking at this time. CAUSES OF NEONATAL HYPOTONIA

Location of Hypotonia Examples

Central Acquired: HIE, electrolyte abnormality, infection, IVH, trauma (upper motor neuron lesion) Congenital: cerebral malformation, chromosomal and metabolic disorders

Peripheral Spinal muscular atrophy, hereditary motor/sensory neuropathy (lower motor neuron Peripheral neuropathy: familial dysautonomia (Riley–Day disease) syndrome) Neuromuscular junction: Mg toxicity, botulism, neonatal myasthenia Muscular: congenital muscular dystrophy, myopathies (metabolic or structural)

NEUROLOGIC SIGNS BY ANATOMIC LOCATION IN THE HYPOTONIC INFANT

Anterior Neuromuscular Central Horn Peripheral junction Muscle

Normal strength Generalized Weakness distal Weakness face, Weakness weakness > proximal eyes, bulbar proximal > distal

Normal or ↑ ↓ or absent ↓ or absent DTRs Normal DTRs ↓ DTRs DTRs DTRs

± Seizures Fasciculations ± Fasciculations No fasciculations

Persistent primi- Sensation loss tive reﬂ exes

• Diagnostic workup may include: • Cranial imaging (US, CT scan, MRI) • EEG • Genetics studies (karyotype, chromosome microarray, speciﬁ c gene tests, or other specialized studies [eg, DNA methylation study for Prader–Willi] after consultation with genetics service) • TORCH screen if clinical suspicion and other stigmata of congenital infection • Metabolic workup • Molecular genetics (CTG repeats, deletions in SMN gene) • CK (levels tend to be high at birth and increase in the ﬁ rst 24 h; false-positive increase with acidosis) Neurology 453

• Nerve conduction studies • Muscle biopsy

NEUROMUSCULAR DISORDERS NEUROMUSCULAR DISORDERS PRESENTING WITH NEONATAL HYPOTONIA

Disorder Genetics Presentation Prognosis

Congenital muscular AR, M=F Diﬃ culties with suck, swal- Normal intellect; dystrophy low, and respirations; joint severe disability contractures

Central core disease AD Generalized weakness Normal life span

Spinal muscular AR; rarely Absent DTRs, weak cry, poor 1–2 yr life atrophy type 1 AD suck; facial muscles spared expectancy (Werdnig–Hoﬀ mann disease)

Hereditary motor and AD; rarely Generalized weakness, delayed Variable disabil- sensory neuropathy AR motor milestones, ataxia, sen- ity; usually live to type III (Dejerine– sory loss, decreased DTRs adulthood Sottas disease)

Nemaline rod AD or AR Generalized weakness, weak Early death due to myopathy respiratory muscles respiratory failure

Riley–Day syndrome AR Sweating with feeds, no Few live beyond response to painful stimuli, adolescence decreased DTRs

Congenital ﬁ ber Unknown Generalized weakness, delayed Nonprogressive type disproportion motor milestones, hip disloca- after 2 yr; normal myopathy tion, contractures life span

HYDROCEPHALUS Deﬁ nition • Progressive dilation of the cerebral ventricular system caused by an imbalance in CSF production/absorption • Obstructive/noncommunicating: ventricles are dilated proximal to site of obstruction • Communicating: excessive secretion or inadequate absorption of CSF

CAUSES OF CONGENITAL AND ACQUIRED HYDROCEPHALUS

Congenital Hydrocephalus Acquired Hydrocephalus

• Aqueductal stenosis • Posthemorrhagic (see “Intraventricular • Neural tube defects (up to 80% of these Hemorrhage” section) infants have hydrocephalus) • Hydrocephalus ex vacuo from cerebral

• Dandy–Walker malformation atrophy after severe insult NEONATOLOGY • Syndromes with vermian agenesis • Postinfectious • Vein of Galen malformation • Neoplasms of the CNS • Arachnoid cysts • Achondroplasia • Osteopetrosis 454 Neonatology

Presentation • Bulging or full fontanelle • Apnea • Split sutures • Bradycardia • Rapid head growth • Irritability • Macrocephaly • Altered level of consciousness • Vomiting

Diagnosis • Many of the congenital causes of hydrocephalus may have accompanying physical ﬁ ndings (ie, cranial bruit for vein of Galen malformations). • Head US, CT, or MRI. MANAGEMENT OF NEONATAL HYDROCEPHALUS

Temporizing Measures Permanent Measure

• Placement of a temporary reservoir or ventriculo-subgaleal • Ventriculoperitoneal shunt until more deﬁ nitive CSF diversion can be performed shunting (most common therapy) • Serial LPs (can be done for communicating hydrocephalus) • Medications to reduce CSF production (acetazolamide ± furosemide; may lead to signiﬁ cant metabolic derangements)

RETINOPATHY OF PREMATURITY (ROP) Diagnosis • Screening for ROP is by indirect ophthalmoscopic retinal examinations for all infants born at <1500 g or <32 weeks and selected infants with birth weight 1500-2000 g and gestational age >32 weeks with an unstable clinical course, at the discretion of the attending. The timing of initial examination is based on postmenstrual age. • Follow-up examinations are recommended by the examining ophthalmologist every 2 to 3 wk or earlier based on ﬁ ndings. • ROP is described by zone, stage, extent, and absence or presence of plus disease. • The retina is divided into three zones (see Figure 1): • Zone 1 is centered on the optic nerve and has a radius of twice the distance from the optic disk to the macula. • Zone 2 is a concentric circle around zone 1 with a radius from the optic nerve to the nasal ora serrata. • Zone 3 is the rest of the retina that reaches to the temporal ora serrata.

Macula

Zone Zone Zone 1 Optic Nerve 3 2

Right Eye Left Eye Figure 40-1 The zones of the retina. (Adapted with permission from: Committee for the Classiﬁ cation of Retinopathy of Prematurity. An International Classiﬁ cation of Retinopathy of Prematurity. Arch Ophthalmol. 1984;102(8):1130-1134.) Neurology 455

• The ﬁ ve stages of ROP indicate severity. • Stage 1 is a thin white line between the vascular and avascular retina. • Stage 2 consists of a ridge between the vascular and avascular retina. • Stage 3 is neovascularization of the ridge or into the vitreous. • Stage 4 is partial retinal detachment, which can be subdivided depending on involvement of the macula. • Stage 5 is total retinal detachment. • The extent of ROP is described by clock hours, with each being a 30° segment of the retina. • Plus disease connotes retinal vascular dilation and tortuosity.

Management • Treatment of ROP is aimed at the avascular retina anterior to the affected area to preserve central vision. • Laser photocoagulation is the now preferred therapy for ROP and may be associated with decreased postoperative discomfort and chemosis compared to cryotherapy → can be associated with cataract development. • Previously, cryotherapy, or freezing of the peripheral retina through the wall of the eye, was the standard. • Cryotherapy may still have some beneﬁ t in eyes with vitreous haze or a poor view of the peripheral retina. • If the ROP has progressed to stage 4 or 5, treatment is focused on retinal reattachment that may include vitrectomy. • Currently, no preventive measures for ROP can be recommended, although targeted oxygen saturation holds some promise. • This involves targeting oxygen saturations of 88%–92% for infants <29 wk and/or birth weight <1250 g, and targeting oxygen saturations of 88%–95% for infants >29 wk.

Available at www.AccessPediatrics.com • Drug-exposed Infants NEONATOLOGY CHAPTER 41 Pain Management

GENERAL PRINCIPLES • Sensory nerve terminals exist on all body surfaces by 22–29 wk of gestation. • Pain assessment should be performed using validated tools in all patients upon admission and then at regularly defi ned intervals. • Physiologic responses to pain include increased circulating levels of catecholamines, increased HR, and increased BP. • Repeated or long-term painful stimuli result in long-term changes such as a lowered pain threshold. • Response to painful stimuli contribute to physiologic disturbances such as hypoxia, hypercarbia, acidosis, and hyperglycemia; this may lead to alterations in oxygen delivery and cerebral blood fl ow. • Infants have long-term disturbances in pain perception that persist well into childhood. • An absence of behavioral or physiologic cues that might indicate pain does not indicate an absence of pain. NONPHARMACOLOGIC MANAGEMENT Behavioral Measures • Swaddling: Keeping the extremities fl exed and close to the trunk • Pacifi ers: Used for non-nutritive sucking • “Kangaroo care” • Developmentally appropriate care • Minimize noise and light stimuli Sucrose • 24% oral sucrose solution used with minor procedures of relatively limited duration • Dosages: • Infants <35 wk CGA: 0.2 mL per dose every 2 min up to recommended maximum of three doses per procedure • Infants ≥35 wk CGA: 1 mL per dose every 2 min up to recommended maximum of three doses per procedure • Give the fi rst dose 2 min prior to anticipated painful event (peak effect after ~ 2 min). If procedure is anticipated to take longer than 5-10 min, give a second dose immediately before the start of the procedure. Give third dose when the procedure is complete if the infant shows signs of pain. • No dose should ever be given during a painful event due to possible aspiration at the time of acute pain when there may be rapid inhalation of air. • After sucrose is administered, a pacifi er should be offered as a secondary source of pacifi cation.

PHARMACOLOGIC MANAGEMENT NOTE: See chapter 2 for additional information on side effects, dosing, and precautions. Nonopioid Analgesic • Acetaminophen • 1.5–1.9 kg: 20 mg PO Q12h • 2.0–2.9 kg: 30 mg PO Q8h • 3.0–3.9 kg: 40 mg PO Q8h • 4.0–5.2 kg: 60 mg PO Q6h • 5.3–7.9 kg: 80 mg PO Q4h (do not exceed 5 doses per day) 456 Pain Management 457

Opioid Analgesics • Morphine • Intermittent IV dosing: 0.05–0.1 mg/kg/dose Q3–4h • Intermittent PO dosing: 0.2–0.5 mg/kg/dose Q4–6h • IV continuous infusion: Initial: 0.01–0.02 mg/kg/h • All dosing should be titrated to effect • Fentanyl • Intermittent IV dosing: 1–2 mcg/kg/dose Q2h • IV continuous infusion: 1–5 mcg/kg/h • All dosing should be titrated to effect

Topical Anesthetics • See chapter 2.

INDICATIONS • For minimally invasive procedures, combinations of a paciﬁ er, swaddling, or sucrose can be used. • Arterial or venous puncture, or heelstick • Peripheral IV placement • Umbilical arterial or venous catheter placement • Endotracheal suctioning • The above measures plus topical anesthetic (see chapter 2 for listing and precautions of topical anesthetics in neonates), local anesthetic, or both should be considered for more invasive procedures. • Lumbar puncture • Administration of immunizations • Circumcision • Opioids should be considered in addition to all appropriate nonpharmacologic measures for: • Percutaneous central venous line placement • Wound dressing change • Chest tube (on insertion, as well as while the chest tube is in place and at the time of removal) • Nonemergent endotracheal intubation • Arterial or venous cutdown NEONATOLOGY CHAPTER 42 Pulmonology

TRANSIENT TACHYPNEA OF THE NEWBORN (TTN) • TTN is a self-limited disorder characterized by tachypnea and other signs of mild respiratory distress such as retractions and cyanosis. • Occurs secondary to a delayed clearance of fetal lung liquid, which leads to airway compression, bronchiolar collapse, and air trapping.

Risk Clinical Mani- Diff erential Factors festation Diagnosis Evaluation Treatment • Prematurity • Presentation • Pneumonia • ABG: may see • Supportive with supple-

• Precipitous within 6 h of • Sepsis mild hypoxemia mental O2, as TTN is a birth and mild respi- self-limited disease delivery • RDS (may ratory acidosis • C-section • Tachypnea, typ- complicate • May need CPAP for delivery ically 60–120 TTN, espe- • CXR: prominent lung recruitment (may without breaths/min + cially if infant perihilar streak- increase the risk of labor mild-to-moder- is premature) ing and mild- air leak) ate respiratory to-moderate • Cyanotic • May off er PO feeding distress cardiomegaly heart disease when RR <70 breaths/ • Physical • May also see min and weaned to • Meconium examination: hyperinfl a- room air aspiration good air entry tion, pleural • Diuretics have not been ± crackles • Persistent eff usions, shown to improve symp- pulmonary • Symptoms tend and widened toms or shorten course hypertension to last 12–72 h fi ssures and are contraindicated

RESPIRATORY DISTRESS SYNDROME (RDS)

Risk Clinical Factors Manifestation Monitoring Treatment • Prematurity Clinical: • Hypotension Surfactant therapy: • Male sex • Tachypnea, (treat as ap- • Many centers start CPAP and do not • Caucasian grunting, and propriate) give “prophylactic” surfactant therapy. race retractions • A PDA can • Many formulations are available. lead to poor • Maternal • O2 requirement Check with your institution to deter- diabetes tends to increase recovery from mine the appropriate dosage/interval/ RDS, and • Perinatal over the fi rst 48 number of doses. h if not treated closure should • Consider prophylactic surfactant asphyxia be considered Laboratory/ therapy as soon as clinically feasible • C-section if patient is radiographic for infants <27 wk gestation who without 3–4 d old with fi ndings: require intubation. labor hemodynamic • • • Thoracic CXR: diff use, fi ne compromise For all other infants, early rescue malforma- granular densi- or continued surfactant (within 1–2 h after birth) is tions ties that develop RDS with poor indicated for worsening respiratory during the fi rst distress on exam or increasing FiO weaning from 2 • Genetic few hours of life requirement above 30%–40%. disorders of mechanical surfactant ventilation production

(continued on next page) 458 Pulmonology 459

Risk Clinical Factors Manifestation Monitoring Treatment • Lack of • ABG: hypoxia, Monitoring/ • Ensure appropriate ETT position and antenatal hypercarbia, supportive equal lung inﬂ ation prior to giving corticoster- mild metabolic therapy: surfactant. oid therapy acidosis, ± • ABG: should • Dosage: 4 mL/kg (Survanta dosing) per in infants elevated lactate be checked ETT q4–6h for up to four doses. 24–34 wk within • Pulmonary hemorrhage can be seen gestation 30–60 min after surfactant therapy; this is thought of surfactant to result from rapid change in lung therapy or compliance. with changes in ventilator Oxygen: settings • O2 saturations alarms should be • Temperature: 85%–97% if ≥1250 g and 85%–93% if O neutral <1250 g to limit exposure to high Fi 2 thermal (these are oximetry alarm limits, not environment targets; targets are ≥88%). should be NCPAP: maintained • Early NCPAP administration may ↓ • Antibiotics: need for mechanical ventilation. RDS is diﬃ cult to distinguish • Indicated in infants with mild respira- O from pneumo- tory distress; Fi 2 requirement <40% nia and sepsis; and PaCO2 <55–60 mm Hg.

consider • Start with 5–6 cm H2O, and increase appropriate as required by 1–2 cm increments to a

cultures and max of 8–10 cm H2O. initiate broad- • Place an NG tube to decompress spectrum gastric air. antibiotics (ie, • Monitor via CXR for lung overdisten- ampicillin and tion leading to decreased tidal volume gentamicin) and hypercarbia. for 48 h Mechanical ventilation: • Indications for mechanical ventilation in-

clude respiratory acidosis (PaCO2 >55–60

mm Hg), FiO2 >40%, or severe apnea. • Initial ventilator settings: SIMV rate 20–40; PIP 20–25; PEEP 4–6; Ti 0.3–0.35;

FiO2 adjusted for desired saturations. • After intubation, rescue surfactant therapy as above. • The ventilator should be weaned (sometimes very rapidly after surfactant administration) as tolerated to avoid lung injury from volutrauma and barotrauma.

PULMONARY AIR LEAK NEONATOLOGY Background Risk Factors • Term infants: mechanical ventilation, meconium aspiration, pneumonia, and congenital lung or chest wall malformation • Preterm infants: mechanical ventilation, RDS, pneumonia, sepsis Pathophysiology • Increased pulmonary pressures can damage the respiratory epithelium → alveolar rupture → allows air to enter the pulmonary interstitium → PIE. 460 Neonatology

• If elevated pressure continues, air can dissect toward the pleura. • Rupture of the pleura leads to pneumothorax and can dissect toward the mediastinum, pericardium, or retroperitoneum. • Retroperitoneal air can rupture into the peritoneum or dissect to the scrotal/labial folds. Pneumothorax • Spontaneous pneumothorax can be found in 0.07%–2% of healthy term infants. • Lung disease increases the rate of pneumothorax to 5%–10%.

PULMONARY AIR-LEAK SYNDROMES: PNEUMOTHORAX, PULMONARY INTERSTITIAL EMPHYSEMA, PNEUMOMEDIASTINUM, PNEUMOPERICARDIUM

Diagnosis Management Complications Pneumothorax

• Physical examination: • Observation: • Ventilatory and • Vitals: tachycardia or bradycar- • If the pneumothorax is found circulatory compro- dia, ↑ blood pressure (can be ↓ incidentally and if patient is in mise can lead to if tension pneumothorax → de- no respiratory distress, has no progressive aci- creased venous return and CO), underlying lung disease, and is dosis (respiratory tachypnea, apnea, desaturation, not mechanically ventilated, the and metabolic) and cyanosis. patient may be closely observed. death if untreated. • Respiratory: grunting, ﬂ aring, • Although some infants may re- • IVH is thought to

retractions, chest asymmetry, quire an increase in their FiO2, result secondary to decreased breath sounds on routine treatment with 100% hypercapnia, hy-

aff ected side. O2is not recommended. poxia, and fl uctuat- • Cardiac: shift in PMI. • Needle aspiration: ing cerebrovascular • GI: abdominal distention from • Should be performed in all pressures. displacement of the diaphragm. patients who are rapidly dete- • SIADH may occur. • CXR: riorating. • AP view—hyperlucent hemitho- • Can be a temporizing measure rax, fl attened diaphragm, in patients who are mechani- mediastinal shift if tension cally ventilated and may be de- pneumothorax. fi nitive treatment for patients • Cross-table lateral—may allow not receiving mechanical for visualization of small collec- ventilation. tions of intrapleural air not seen • Pigtail catheter/chest tube: on AP view. • Often required for patients ↓ ↑ • ABG—may see PaO2 and who develop pneumothorax

PaCO2. who are receiving mechanical • Transillumination: ventilation. • May be able to illuminate • Consider removal of the pneumothorax by placement catheter or chest tube after of a high-intensity light source no air has been drained for directly on the skin. 24–48 h; • ↓ sensitivity if severe PIE, chest Some centers will ﬁ rst place wall edema, full-term, very small the chest tube to water seal infants, or infants with dark skin. and/or clamp, with a follow-up CXR to evaluate for reaccumu- • Needle aspiration: lation before removal. • If the patient is rapidly decom- pensating, needle aspiration can be diagnostic and therapeutic.

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Diagnosis Management Complications Pulmonary Interstitial Emphysema

• PIE can occur in mechanically • Ventilator strategies • PIE can lead to ventilated infants during the fi rst • ↓ mean airway pressure by pneumothorax, 48 h of life. ↓ PEEP and Ti and ↑ respira- pneumoperi- • Risk factors include extreme tory rate. cardium, and air prematurity, RDS, and sepsis. • Consider HFOV to avoid swings embolus. • Vitals: hypotension, bradycardia. in lung volume. • CXR: linear lucencies radiating • Positioning: Place aff ected lung from the hilum and occasionally in a dependent position. cyst-like blebs. • Avoid suctioning and bag • ABG: acidosis, hypercarbia, ventilation. hypoxia. • In very severe cases, selective bronchial intubation or surgical resection may be considered (although no proven benefi t). Pneumomediastinum

• PE: Muffl ed heart sounds. • Pneumomediastinum is usually • Can lead to pneu- • CXR: Air is best seen on the lateral of little clinical signifi cance and mothorax. view. rarely needs treatment. • Rare cardiorespiratory eff ects can occur if the air is under tension and will require medi- astinotomy drainage. Pneumopericardium

• Vitals: initial tachycardia followed • Observation: • Cardiac tamponade by bradycardia, hypotension, • If the patient is asymptomatic • Tension pneumo- cyanosis. and is not receiving mechani- mediastinum • PE: Muﬄ ed and distant heart cal ventilation, the patient can • Mediastinitis (if sounds; may hear a pericardial be observed carefully with resulting from knock or millwheel-like murmur. close monitoring of vital signs. esophageal perfo- • Labs/imaging: • Serial CXRs should be moni- ration) • CXR: AP view demonstrates air tored until the pneumopericar- surrounding the heart. It is most dium resolves. often seen at the inferior aspect • Needle aspiration: of the heart. • Pericardiocentesis should be • EKG: Decreased voltages performed immediately if car- throughout. diac tamponade develops. • Transillumination: Illumination • This is best accomplished may occur in the substernal under US guidance to avoid region. Flickering with cardiac puncturing the myocardium. cycle is sometimes seen and • Continuous pericardial drainage: can help to diﬀ erentiate from • If recurrence of cardiac tam- pneumomediastinum. ponade occurs, a pericardial tube will need to be placed. NEONATOLOGY Procedures • Needle aspiration • See Chapter 3. • Pigtail catheter placement • If a needle aspiration has already been completed in the fourth intercostal space in the midaxillary line, the catheter can be left in place while preparations are being made for pigtail placement. 462 Neonatology

• The entry site is prepped with Betadine prior to starting procedure. • With sterile technique, a guidewire is inserted through the catheter into the pleural space. • Carefully maintaining the position of the wire, the catheter is removed. • A dilator is inserted over the wire to enlarge the opening into the pleural space. • The dilator is removed and replaced by the pigtail catheter (5 or 8 French). • The pigtail is inserted until all ports and the curved portion of the pigtail are within the pleural cavity. • The wire is removed once the pigtail is in place, and the pigtail is attached to a water-

drainage system with a negative pressure of 10–20 cm H2O. • No sutures are needed to secure the pigtail, but it should be covered with a clear occlusive dressing. • Chest tube • See Chapter 3. • Pericardiocentesis • The subxiphoid region should be prepped and draped in a sterile fashion. • A 20–22 gauge IV catheter or angiocatheter should be attached to extension tubing with a three-way stopcock and a syringe. • The catheter should be inserted at a 30°–45° angle in the subxiphoid space toward the left shoulder. • As the catheter is advanced, the syringe should be used to aspirate until air is obtained. • Once air is obtained, the plastic catheter should be advanced only into the pericardial space. • The needle should be removed once the catheter is in place, and air should continue to be aspirated. • Once all the air is removed, the catheter should be withdrawn. • If blood is aspirated, the catheter should be immediately withdrawn to avoid damage to the ventricular wall. • Continuous pericardial drainage: After the pericardial tube is placed, negative pressure

of 5–10 cm H2O is used. PERSISTENT PULMONARY HYPERTENSION Outcomes • PPHN-associated mortality is 10%–15%. • Survivors have a 20%–46% chance of cognitive, neurodevelopmental, or audiologic impairment.

Risk Factors and Diff erential Diagnosis Diagnosis Treatment

Fetal risk factors: PE: Oxygen: • Meconium-stained amniotic • Usually develop • Hypoxia and hypercarbia are fl uid symptoms within the potent pulmonary vasoconstrictors; • Post-term fi rst 12 h of life supplemental oxygen and correction of hypercarbia are important. • Pulmonary parenchymal • Diff erential cyanosis, disease with preductal (right • Continuous pre- and post-ductal upper extremity or saturations should be monitored. • Lung hypoplasia head) > postductal • Goal postductal saturations are • In-utero closure of the (lower extremity or >92%. ductus arteriosus abdomen) • ABGs should be drawn • Pneumonia, sepsis, and postductally. intrauterine or perinatal asphyxia

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Risk Factors and Diff erential Diagnosis Diagnosis Treatment Maternal risk factors: • If gradient is >10% Mechanical ventilation: • Anemia with no structural • If hypoxemic with FiO 100%, heart disease, highly 2 • Fever mechanical ventilation should be suggestive of PPHN initiated. • Pulmonary disease • Cardiac: prominent • Ventilatory strategy depends on • DM precordial impulse, underlying etiology; maintain • UTI during pregnancy single S2 and/or tri- normoxia and normocarbia to cuspid regurgitation • Maternal medication use prevent acidemia. murmur (including SSRIs and NSAIDs) • HFOV is often used in patients with • Skin: cyanosis severe pulmonary parenchymal Diff erential diagnosis: Labs/imaging: disease. • CHD • CXR: • Sepsis iNO: • Normal • iNO is a potent pulmonary • Severe pulmonary parenchy- • Pulmonary parenchymal disease vasodilator. mal disease • Standard dose is 5–20 ppm, and • Secondary pulmonary • “Classic” idiopathic hypertension can be caused it is most eff ective with adequate PPHN hyperlucent alveolar recruitment. by CHD: TAPVR, HLHS, LV lung fi elds, refl ecting • Wean iNO if the infant responds by disease, or obstruction to ↓ pulmonary blood increasing PaO by >10–20 mm Hg, LV outfl ow. It can also be fl ow 2 and FiO is <0.6. caused by LV or RV dysfunc- • ECG: RV predominance 2 tion with right-to-left (normal for age); may • Rebound hypoxemia can occur shunting. rarely have signs of when weaning from 5 ppm, so • Pulmonary hypertension ischemia or infarction wean below 5 ppm gradually. can be caused by hypoxia, • Echocardiogram: • ECMO: hypothermia, hypoglycemia, evaluate shunting, and polycythemia. • ECMO should be considered for ventricular function, patients with a reversible cause of and pulmonary artery PPHN who fail conventional man- pressures agement (including mechanical • Tricuspid jet, if present, ventilation with iNO). can be used to estimate • See ECMO section for additional the RV/pulmonary information. artery pressures • Estimated RV pressure Hemodynamic support: (in mm Hg) = 4 × v2, • Maximize O2 delivery to the tissues where v = velocity of the by maintaining adequate cardiac tricuspid regurgitaton output. jet, in m/sec • In the short term, ↑ systemic BP to • If tricuspid valve is overcome the ↑ PVR (with volume competent, qualitative expansion [normal saline, PRBCs] measures can suggest and/or vasopressors [dopamine, the diagnosis of PPHN, dobutamine, epinephrine]). such as the following: • Avoid polycythemia, which can • Flattened/paradoxi- cause hyperviscosity and ↑ in PVR. cal interventricular septal wall motion Metabolic considerations: (bowing into the • Metabolic alkalosis → ↓ PVR. The left ventricle during NEONATOLOGY use of NaHCO3 is controversial and systole) should be limited to infants with • Dilated or hypertro- signifi cant acidosis. phied right ventricle • Hypoglycemia and hypocalcemia • Dilated right atrium can interfere with myocardial function and should be corrected.

(continued on next page) 464 Neonatology

Risk Factors and Diff erential Diagnosis Diagnosis Treatment Sedation: • Catecholamine release can activate pulmonary receptors and lead to ↑ in PVR. • Narcotic analgesia/sedation is an important part of therapy, and fentanyl infusions are often used at a rate of 2–5 μg/kg/hr. • Handling/stimulation of these infants should be minimized. • Occasionally, neuromuscular blockade is used for patients with continued agitation despite adequate analgesia.

MECONIUM ASPIRATION SYNDROME

Pathophysiology and Clinical Manifestations Management Complications

• Meconium can be passed Meconium-stained fl uid: • Pneumothorax/ in utero with acute • If infant is vigorous—Provide pneumomediastinum: or chronic hypoxia or routine infant care. occurs in 15%–33% of infection. patients • If infant is not vigorous—Intubate, • Meconium staining rare and suction trachea with a 3.0–3.5 • PPHN: occurs in up to <34 wk gestation. ETT. 33% of patients • ~ 5% of infants with • Vigorous: HR >100, spontaneous • Consider echocar- meconium staining will respirations, good tone. diogram to develop meconium determine degree aspiration syndrome. Observation: of PPHN and to • Complete peripheral • Any infant who is depressed and has exclude CHD as airway obstruction → meconium suctioned from the tra- etiology atelectasis and V/Q chea should be observed for signs of mismatch. meconium aspiration syndrome. • Partial obstruction → • CXR: normal or diff use, asymmetric ball-valve eff ect with air patchy infi ltrates ± hyperinfl ation. trapping. • Routine care should be provided; • Clinically, the patient can fl uid restriction may help lessen have acidosis, hypoxemia, pulmonary edema. and hypercapnia. Ventilation and oxygen therapy:

• O2 initiated promptly, as continued hypoxia can lead to further pulmonary vasoconstriction.

• NCPAP can be considered if FiO2 requirements <0.4. • Mechanical ventilation is indicated

with PaCO2 >60 mm Hg or PaO2 <50 mm Hg.

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Pathophysiology and Clinical Manifestations Management Complications

• Ventilation strategies include assuring adequate expiratory time to prevent further air trapping. • Consider HFOV ± iNO or ECMO for inadequate oxygenation/ventilation on conventional ventilator.

Medications: • Surfactant—used in infants with

FiO2 requirement >0.4. • The presence of meconium will inactivate surfactant. • Antibiotics—Meconium aspiration syndrome is diﬃ cult to distinguish from pneumonia on CXR. • iNO—may ↓ need for ECMO in infants with associated PPHN. • iNO in conjunction with HFOV is more eﬀ ective than iNO with conventional ventilation. • Corticosteroids—not currently recommended.

BRONCHOPULMONARY DYSPLASIA (BPD)

Classifi cation, Diagnosis, and Clinical Course Management

Classifi cation/Diagnosis: Oxygen: ↑ • Radiographic changes and treatment • FiO2 contributes to pathogenesis of BPD, and

with supplemental O2 for at least SaO2 should be carefully monitored early in the 28 d, and clinical course of all premature infants. • Mild: breathing RA with saturations • Saturation alarms should be 85%–97% in ≥90% at 36 wk PMA or discharge infants >29 wk PMA and 85%–93% in infants home (infants <32 weeks at birth) or <29 wk PMA or <1250 g. at DOL 56 or discharge home (infants • Periodic blood gas monitoring should be ob- ≥32 weeks at birth) tained, with a goal PaO2 >55 mm Hg. • Moderate: requiring <30% FiO to 2 Mechanical ventilation: keep SaO2 ≥90% at 36 wk PMA or discharge home (infants <32 weeks at • Acute phase

birth) or at DOL 56 or discharge home • Permissive hypercapnia (PaCO2 of 50–55 mm Hg) (infants ≥32 weeks at birth) to minimize airway pressure and lessen further lung injury. • Severe: requiring ≥ 30% FiO2 or positive pressure support to keep • Chronic phase

SaO2 ≥90% at 36 wk PMA or discharge • After the patient is on stable ventilator settings, home (infants <32 weeks at birth) or weaning should be judicious until adequate NEONATOLOGY at DOL 56 or discharge home (infants weight gain is established. ≥32 weeks at birth)

(continued on next page) 466 Neonatology

Classifi cation, Diagnosis, and Clinical Course Management

Clinical course—“classic” BPD: Fluid restriction/nutrition: • Acute course • Fluid restriction is a common strategy to control • Initial improvement in fi rst 1–2 pulmonary edema. wk, then worsening pulmonary • Moderate fl uid restriction to 140–150 mL/kg/d ↑ function ( O2 requirements, tac- of a preterm 24 kcal/oz formula will meet most hypnea, retractions, rales on exam, nutritional needs. and worsening lung opacifi cation • For severe cases, may need to restrict to 110–130 on CXR) mL/kg/d; concentrate feeds to 27–30 kcal/oz to

• O2 requirement fl uctuates; achieve adequate growth. pulmonary edema worsens • Weigh q1–3d; length and FOC measured • Evaluate for PDA and infection as weekly. causes for worsening symptoms • Monitor BUN, calcium, phosphorus, and alkaline Chronic course • phosphatase activity. • Airway obstruction becomes • Nutrition consult warranted in all patients who uneven as hypertrophy of smooth require fl uid restriction. muscle, increased interstitial edema, and bronchiolar metaplasia occur. Prevention: • After 4–6 wk, fi brosis, hyperinfl a- • Vitamin A tion, and pulmonary edema ↑ and • Has been shown to ↓ incidence of BPD in ELBW the patient’s course becomes more infants static. • No long-term data available at this time • Lung remodeling begins over the next 3–9 mo. Weaning from posi- • Dosage: 5000 IU IM three times/wk × 12 doses tive pressure ventilation should be (TCH institutional practice) gradual, as rapid changes may lead • Caff eine to large fl uctuations in oxygenation, • Has been shown to ↓ incidence of BPD in and chronic hypoxemia can lead infants 500–1250 g when started in the fi rst to right-sided heart failure and cor 10 DOL pulmonale. • Also improved survival without neurodevelop- • When discharged home, patients mental disability require close monitoring of SaO2 • Dosage: 20 mg/kg loading dose, then 5 mg/kg/d ↑ → to prevent in PVR right-sided IV or PO heart failure. Diuretics: Clinical course—“new” BPD: ↓ • Diuretics: O2 requirements and improve short- • Since the introduction of surfactant term lung mechanics and use of prenatal steroids, the initial • No long-term benefi ts demonstrated on mortal- course is characterized by a milder ity or duration of O therapy respiratory distress prior to develop- 2 ment of the chronic condition. • Thiazides • The hallmark of this “new BPD” is • Work on the proximal part of the distal renal tubule arrest in alveolar development and • Hydrocholorothiazide simplifi cation of terminal airways. • Neonates and infants <6 mo: 2–3.3 mg/kg/d PO in two divided doses • Chlorothiazide • Neonates and infants <6 mo: • PO: 20–40 mg/kg/d in two divided doses (max dose: 375 mg/d) • IV: 2–8 mg/kg/d in two divided doses • Thiazides are less potent than furosemide and are often used to try to prevent nephrocalcinosis, though evidence for this use is lacking.

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Classifi cation, Diagnosis, and Clinical Course Management

• Furosemide • Potent loop diuretic • Premature neonates • PO: 1–4 mg/kg/dose q12–24 h • IM, IV: 0.5–2 mg/kg/dose q12–24 h • Infants and children • PO: 1–2 mg/kg/dose q6–24 h • Max total daily PO dose: 10 mg/kg/day • IM, IV: 0.5–2 mg/kg/dose q6–12 h • Continuous infusion: 0.1–0.4 mg/kg/h • Chronic diuretic therapy can lead to hypokalemic, hypochloremic, metabolic alkalosis with total body K+ depletion, and nephrocalcinosis. Electrolytes should be followed closely, and supplementation (NaCl, KCl) is often needed. Inhaled medications: • There are currently no data demonstrating long- term beneﬁ ts for inhaled albuterol or corticosteroids in the routine management of BPD or in the prevention of BPD in premature infants. • Infants with BPD can have episodes of severe bronchospasm, for which albuterol or levalbuterol are the rescue agents of choice. • No guidelines as to dosage of these agents are available, though a dose of two puﬀ s MDI with spacer every 6–8 h is frequently used, with weaning over the following 24–48 h. • If the patient has frequent or severe episodes of bronchospasm, use of inhaled corticosteroids for 7–10 d may be helpful. • Use bronchodilators with caution, as they can worsen airway resistance in infants who have (tracheo)bronchomalacia complicating BPD. Further screening: • Echocardiogram • Infants with BPD are at high risk for RV dysfunction from chronic hypoxemia, which can progress to cor pulmonale. • At 36–37 wk, a screening echocardiogram should be obtained to rule out pulmonary hypertension if: • Patient continues to require positive pressure ventilation

• Patient continues to require an FiO2 >30% or >¼ L via nasal cannula to keep oxygen saturation >92% CO NEONATOLOGY • Patient has a P 2 value of >60 mm Hg • Developmental screening • Hearing screens should be completed before 6 mo of age. • Developmental status should be evaluated while hospitalized, with long-term developmental therapies arranged prior to discharge.

NEJM 1967;276:357, Am J Respir Crit Care Med 2001;163:1723, Pediatrics 2004;114:1305 468 Neonatology

APNEA • Apnea is the complete cessation of breathing for 20 sec or longer and tends to be accompanied by bradycardia (HR <100) and hypoxemia. • Apnea can be obstructive (inspiratory efforts present) or central (inspiratory efforts absent). In premature neonates, apnea tends to be mixed, with 40%–65% of episodes central and 10%–35% obstructive. • The incidence of apnea increases with decreasing gestational age, and essentially all infants with a gestational age of <28 wk will have at least one apneic episode. • Apnea tends to begin within 1–2 d of birth and tends to resolve by 37 wk PMA. However, infants <28 wk at birth can have persistent apneic episodes beyond term gestation. • There is no correlation between apnea of prematurity and SIDS.

Monitoring and Evaluation • Monitoring: • Infants <35 wk PMA should be monitored for apneic episodes for at least 1 wk after birth. • Monitoring should continue until no signiﬁ cant apneic episodes are noted for 5–7 d. • Evaluation: • Further evaluation should be strongly considered after the ﬁ rst apneic episode, especially if the patient is term or >7 d old, or if ↑ in apneic episodes from the patient’s baseline. • May include an ABG, CBC, glucose, serum ionized calcium, and electrolytes, ± limited or full sepsis evaluation.

Differential Diagnosis • Infection: • If history of feeding intolerance, temperature instability, or lethargy. • Evaluation: limited or full sepsis evaluation. • Viral cultures and rapid RSV (Respiratory Syncytial Virus)if signs and symptoms are suggestive. • Initiate broad-spectrum antibiotics until culture results are available. • Temperature instability: • If recent changes in the patient’s environment such as weaning to an open crib. • Check temperature probes if applicable. • Metabolic disorders: • Look for accompanying jitteriness, poor feeding, lethargy, or irritability. • Check electrolytes, especially glucose and serum ionized calcium ± ammonia/lactate, if indicated. • Medications: • Maternal history of drug use: check urine drug screen. • Medications given during labor: serum Mg level. • Narcotics administered to patient. • Impaired oxygenation: • If recent change in respiratory support or if patient has accompanying cyanosis, respiratory distress, or tachypnea, consider impaired oxygenation. • Check ABG and CXR. • Place on continuous oximetry monitoring, and consider ↑ respiratory support. • Intracranial pathology: • Neurologic exam should be completed on any patient with apnea. • If abnormal exam or accompanying seizures, obtain head imaging (usually cranial US). • Neurology consult should be strongly considered in any patient with an abnormal neurologic exam or seizures. • Anemia: • Anemia itself does not cause apnea. • Whether PRBC transfusion ↓ frequency of apnea is controversial. Pulmonology 469

• Post-anesthesia: • Premature infants can have ↑ apnea for days after general anesthesia. • Can occur up to 50–60 wk PMA. • Feeding hypoxemia: • Desaturation and bradycardia associated with feeding can occur in infants during nipple feedings. • Tends to resolve by 44–54 wk PMA.

• May use supplemental O2 with feeds, pacing of nipple feeds, and in extreme cases gavage feeding until the infant is more mature. • Congenital hypoventilation syndrome: • Congenital hypoventilation syndrome is an uncommon disorder with hypoventilation and apnea during sleep. • No ↑ effort to breathe even with severe hypoxia and hypercarbia. • Cranial imaging tends to be normal, though hearing screen may be abnormal. • Xanthines (ie, caffeine) not typically effective, and most infants require prolonged mechanical ventilation and tracheostomy.

Management • Initial management: • Most infants respond to tactile stimulation.

• If mechanical ventilation required, use same FiO2 as prior to episode to avoid hyperoxia. • Evaluate for causes of airway obstruction (secretions in ETT or NCPAP prongs, or extreme ﬂ exion/extension of the neck). • Xanthines: → • CNS stimulant to increase the medullary receptor center’s sensitivity to CO2 stimu- lates the central respiratory drive. • Increases resting pharyngeal muscle tone. • Decreases REM sleep. • Strengthens diaphragmatic contractions. • Caffeine citrate is often used. • Neonates: PO, IV: • Loading dose: 20 mg/kg. • Maintenance dose: 5 mg/kg/d. • Consider bolus of 10 mg/kg with an increase in the maintenance dose by 20% if apnea continues. • Currently no evidence for monitoring caffeine levels. • Caffeine generally stopped at 34–36 wk PMA if no apneic spells have occurred for 5–7 d. Keep in mind that caffeine can have an effect for up to 1 wk after discontinuation, and patients should be monitored for further apneic spells until 5–7 d after this period. • NCPAP: • NCPAP ↓ pharyngeal collapse → ↓obstructive apnea.

• Initiate NCPAP at 5–7 cm H2O, and increase in increments of 1–2 cm to a maximum of

8–10 cm H2O. • Pharyngeal muscle control improves at 32–34 wk PMA. • Mechanical ventilation: • Sometimes required if other interventions above are unsuccessful.

• Use the lowest possible settings to avoid lung injury. NEONATOLOGY

EXTRACORPOREAL MEMBRANE OXYGENATION ECMO is an advanced life-support technique that is offered for speciﬁ c indications in infants with cardiac or respiratory failure that have not responded to conventional management. Detailed management of a patient on ECMO is beyond the scope of this book, and all management decisions should be discussed with an experienced clinician. 470 Neonatology

Indications Respiratory Failure • ECMO is indicated for patients who have reversible respiratory failure and their predicted mortality with conventional therapies is high enough to justify the risks of ECMO. • Some of the more common indications include CDH, sepsis/pneumonia, meconium aspiration syndrome, PPHN, and RDS. • OI is a parameter that is commonly followed and is a measure of the severity of respiratory failure. It is measured as: × × OI = [MAP FiO2/PaO2] 100 Cardiac Failure • ECMO can be offered until deﬁ nitive treatment can be provided for some congenital heart defects, including HLHS, coarctation of the aorta, pulmonary atresia, and TAPVR. • ECMO is also indicated for severe pulmonary hypertension not responsive to medical therapy, cardiomyopathies, and failure to wean from cardiopulmonary bypass. ECMO Criteria • ECMO criteria may vary by institution; our criteria include: • Gestational age >34 wk • Birth weight >2,000 g • <10–14 d of mechanical ventilation • Reversible lung disease • Absence of cyanotic heart disease • Normal cranial US (may have grade I IVH) • Failure of maximal medical management • Predictive formula associated with 80%–90% mortality: • Oxygenation index (OI) >40 on two consecutive ABGs → 80% mortality without ECMO → • A-aDO2 >620 for 12 h or for >6 h with evidence of pulmonary barotraumas 90% mortality without ECMO • Exclusion criteria • Coagulopathy, or other contraindication to full anticoagulation • Irreversible pulmonary or cardiac disease • Multiple organ system failure • IVH ≥ grade II • Massive cerebral edema • Multiple congenital anomalies

Available at www.AccessPediatrics.com • ECMO Management • Pulmonary Hemorrhage NEONATOLOGY uid (continued on next page) Central defect; umbilical ring fails defect; umbilical ring fails Central The sac usually remains intact sac usually remains oc- but The genetic defects in 50%–75% association; Beckwith-Wiedemann pentalogy of Cantrell; syndrome; CHD; pulmonary con- hypoplasia; EEC of the colon; genital malrotation trisomies OEIS complex; syndrome; 13, 18, and 21 any evaluation for a thorough have chro- other anomalies and consider mosomal analysis AFP levels to contract and leaves a round defect a round contractto and leaves the membrane that protects enchymal from underlying abdominal organs amniotic ﬂ to exposure during deliverycasionally is ruptured partoccupy of the sac along with variable other abdominal organs births age reproductive and SSRIs in the abdominal wall or failure of in the abdominal wall or failure the abdominal to return midgut to cavity the umbili- after herniation into cal stalk Associated syndromes: VACTERL VACTERL syndromes: Associated elevated not have or may Mother may The liver and small intestine usually and small intestine liver The Seen with mothers at extremes of obesity with maternal Associated with other structuralAssociated or Sporadic; 2–2.5 of 10,000 live Sporadic; 2–2.5 of 10,000 live Most prenatally; diagnosed should Developmental arrest of somites of somites arrest Developmental Defect is covered by a translucent mes- a translucent by Defect is covered • • • • • • • • • • • • 471 further → partialuid and ammation ammatory “peel” ammatory

lies unrelated to the GI tract to lies unrelated without further injury the bowel to with disruption of body wall formation with disruption of body wall formation or weakness at the insertion of the of the after involution umbilical cord right umbilical vein in mes- result of the defect may closure vascular constrictionenteric injurybowel with infl and muscular hypertrophy, blunting, infl serosal vasoconstricting to de-SES; exposure cigarette cocaine, NSAIDs, congestants, smoking, pesticides in atresias with intestinal associated 5%–25% the umbilical stalk through which a por- the umbilical stalk through tion of the GI tract has herniated Exposure to amniotic fl to Exposure and matted be edematous may Bowel with malrotation; be associated Can with anoma- associated Not commonly May be secondaryMay accident vascular to Usually diagnosed antenatally on US antenatally diagnosed Usually Mother AFP levels has elevated vaginally still be delivered Most may Sporadic; 1.5 of 10,000 live birthsSporadic; 1.5 of 10,000 live age; low maternal Young Risk factors: Right-sided defect lateral to the base of the Right-sided to defect lateral Small bowel with villous atrophy and with villous atrophy Small bowel

• • • • • • • • • • Gastroschisis• • Omphalocele

Diagnosis

Epidemiology Pathophysiology Presentation and and Presentation Surgical Disorders Surgical SURGICAL DISORDERS ABDOMINAL ABDOMINAL WALL DEFECTS CHAPTER 43 472 Neonatology

Gastroschisis Omphalocele

• May be delivered vaginally, but consider cesarean section for giant omphalocele because of concern for rupture

• In delivery room, stabilize airway; wrap • In the delivery room, stabilize the intestine with warm, sterile saline airway; wrap the sac with warm, ster- dressings; place-large bore orogastric ile saline dressings; place large-bore tube to continuous suction; and place orogastric tube to continuous suc- peripheral IV for fl uid management and tion; and place peripheral IV for fl uid broad-spectrum antibiotics management and broad-spectrum • Place the infant in clear plastic bowel antibiotics bag to minimize heat and water loss • Do not attempt reduction of the • Inspect bowel for evidence of ischemia, sac because it may rupture, cause torsion, and atresia respiratory compromise, or impair venous return • Place the infant in lateral decubitus position to avoid mesenteric kinking • Same management if the sac is ruptured; small rents in the sac may • Reduce or place the bowel in a sterile be sutured shut silo as soon as possible; delay may lead to bowel swelling and resultant ischemia • Small omphaloceles can often be closed in one-stage surgical repair • If bowel is forced into abdominal cavity, may cause decreased diaphragmatic • Cases associated with signifi cant oth- excursion, requiring increased ventilator er anomalies or large omphaloceles support; may also impair mesenteric, may be managed nonoperatively; the hepatic, and renal perfusion membrane is preserved and treated with silver sulfadiazine to allow • During staged closure, parenteral epithelialization of the amnion over nutrition, gastric decompression, and weeks or months, resulting in durable spontaneous breathing are preferred coverage; if the patient survives other • When reduction of silo contents is com- conditions, he or she can have even- plete, fi nal closure is performed tual closure later in childhood Treatment • Repair of atresias includes primary anas- • Survival rates are 30%–80% because tomosis, or if peel exists, internalization of associated anomalies; with isolated of uncorrected atresia and later reex- omphalocele, survival rates approach ploration and repair after peel resolves those of gastroschisis • Await bowel sounds, passage of meco- • Complications include GER, volvulus nium, and cessation of bilious gastric secondary to nonrotation, and ventral aspirates before starting enteral feeds hernias • Conservative advancement of enteral • Giant omphaloceles can be associ- feeds ated with pulmonary hypoplasia, and • May have return of bowel function in a in severe cases, may cause neonatal few days to weeks death. • Those who fail to demonstrate bowel patency within 3–4 wk of closure should have contrast study to rule out unrecog- nized atresia • Overall survival rate, 90%–95%; increased risk of third trimester fetal demise; most postnatal deaths are caused by perioperative complications (sepsis, NEC, abdominal visceral ischemia, late hepatic failure from TPN-associated cholestasis) Surgical Disorders 473

OBSTRUCTIVE LESIONS OF THE SMALL BOWEL

Malrotation and Duodenal Atresia Jejunoileal Atresia Midgut Volvulus and Stenosis and Stenosis

• Midgut = duodenum to • Complete or partial; • Potential causes: Ischemic transverse colon from intrinsic causes or insult to intestine, internal • Undergoes two 270o external compression herniation of bowel, vol- counterclockwise rota- • Intrinsic: Failure of vulus, bowel perforation, tions during 6–12 wk recanalization of duode- mesenteric thrombosis, of gestation; improper num during 8–10 wk of epithelial plugging, lack rotation or fi xation → gestation → solid from of complete revacuoliza- narrow vascular pedicle epithelial proliferation tion of intestinal lumen with wide mesenteric • External: Annular • Types I–IIIA as in duode- → base obstruction and pancreas; may encircle nal atresia, plus: compromised blood the second portion of the • Type IIIB: “Apple peel” or supply duodenum and cause “Christmas tree” deformity • Ladd bands form obstruction (distal small bowel seg- between ectopic • Type I atresia: Luminal ment forms a corkscrew cecum and right lateral web or membrane, may around the terminus of abdominal wall and tra- be fenestrated; marked the ileocecal artery) verse the duodenum → Pathophysiology size discrepancy with • Type IV: Multiple atresias intermittent, incomplete mural continuity; often (“string of sausages” duodenal obstruction associated with anomalies appearance); most often • If fi xation has not of the common bile duct involve the proximal occurred normally, the • Type II atresia: Dilated jejunum intestine is susceptible proximal segment con- • Dilatation of the bowel at to torsion on the axis of nected to small distal seg- the proximal end always → the SMA gangrene ment by a fi brous cord occurs → large size of the midgut (almost • Type IIIA atresia (most discrepancy between uniformly fatal) common): Complete the proximal and distal discontinuity between ends; dilated bowel has segments impaired peristalsis

• 1 in 100 have some form • 1 in 7000 live births; • 50% in jejunum (30% of improper rotation or intrinsic duodenal atresia proximal; 20% distal) ﬁ xation; clinically signiﬁ - account for 50% of all and 50% in ileum (15% cant disease occurs in small bowel atresias proximal; 35% distal) one in 6000 live births • Associated with other • ~90% of small bowel • Associated with CDH, conditions in 50%–80% atresias are single omphalocele, and of patients; most com- • Associated with malrota- gastroschisis; may be monly trisomy 21 and tion (10%–18%), meco- associated with annular CHD (30% each) nium peritonitis (12%), pancreas and bowel • Other anomalies: meconium ileus (10%) Epidemiology atresias Intestinal malrotation • 15%–30% associated (20%), esophageal atresia with CF or imperforate anus (10%–20%), heterotaxy, biliary atresia, and gallbladder agenesis

• Bilious emesis in any • May have polyhydram- • Antenatally: Polyhydram- child <1 yr is malrotation nios (50%) and “double nios from inability of the NEONATOLOGY until proven otherwise; bubble” on antenatal US fetus to absorb amniotic emesis (bilious or not) ﬂ uid and distended loops is the most common of fetal bowel on US presentation caused by obstruction

(continued on next page) 474 Neonatology

Malrotation and Duodenal Atresia Jejunoileal Atresia Midgut Volvulus and Stenosis and Stenosis

• If intermittent obstruc- • Emesis of bile-stained • Newborns: Abdominal tion is present, the pa- fl uid within hours of distension and bilious tient may have periods birth; 85% of obstruc- vomiting and often failure of normal feeding with tions are distal to the to pass meconium episodes of emesis ampulla of Vater • Usually occur in otherwise • Abdominal distension • Swallowed air cannot normal newborns but rare usually does not occur pass the duodenum → cases are seen with other because the obstruction distended upper abdo- malformations is high in the GI tract men and scaphoid lower • >50% present in the fi rst abdomen month of life; 75% pres- • May pass a small amount ent within the fi rst year of meconium in the fi rst Presentation • Bloody stools and 24 hr and then have no abdominal tenderness further stools are ominous signs of vascular compromise; the patient may subsequently develop sepsis, shock, and luminal perforation

• KUB: Duodenal obstruc- • Abdominal radiography • Abdominal radiography tion, scant gas in rest of with classic “double- shows distended, air-ﬁ lled bowel; gasless abdomen bubble” sign: Two bowel loops and multiple may be seen when bowel distinct gas collections air-ﬂ uid levels infarction has occurred in the upper abdomen • Contrast enema may • Gold standard is Upper representing a dilated show microcolon because GI with small bowel stomach and proximal of little or no material follow through: duodenal bulb passing distal to the right-sided location of • The distal abdomen may obstruction ligament of Treitz, spiral- be gasless or have a small ing or beaking of the amount of air because of duodenum suggesting stenosis or fenestration obstruction of a duodenal web Diagnosis • US: Abnormal position • Diagnosis also suggested of the SMV relative to by aspiration of >30 mL the SMA gastric contents before • Contrast enema: High feeding cecum in the RUQ or failure of contrast to extend past the transverse colon (suggestive, but not conclusive, for malrotation).

• Initial treatment: Airway • Initial treatment: Airway • Initial treatment: Airway stabilization, placement stabilization, placement stabilization, placement of a large-bore nasal or of large-bore nasal or of large-bore nasal or orogastric tube to low- orogastric tube to low orogastric tube to low intermittent suction, intermittent suction, intermittent suction, peripheral IV placement, peripheral IV placement, peripheral IV placement, fl uid resuscitation, fl uid resuscitation, correc- fl uid resuscitation, correction of electrolyte tion of electrolyte abnor- correction of electrolyte abnormalities, and malities, surgical consult, abnormalities, and surgi- surgical consult and thorough evaluation cal consult for other anomalies

(continued on next page) Surgical Disorders 475

Malrotation and Duodenal Atresia Jejunoileal Atresia Midgut Volvulus and Stenosis and Stenosis

• Volvulus → surgical • Surgical treatment: • Operative intervention is emergency; malrotation Primary duodenoduo- based on the type of atre- without signs of torsion denostomy (preferred) sia, presence of comorbid is less urgent or duodenojejunostomy conditions, and condition • Ladd’s procedure: to establish intestinal of the bowel at surgery Manual inspection of continuity • The dilated proximal end the bowel, detorsion • GI function usually is tapered or resected of volvulus, lysis of returns in 5–7 d, at which for end-to-oblique-end bands, passage of tube point enteral feeds can anastamosis through the duodenum be initiated and progres- • Distal lumen of bowel to rule out intraluminal sively advanced is irrigated to ensure no obstruction, widening • Complications: Delayed other atretic segments or of the mesenteric base, transit caused by a webs are present incidental appendec- persistently dilated and • Multiple atresias are man- tomy, and nonrotational dyskinetic proximal aged by multiple resec- return of bowel to the duodenum; GER because tions and anastomoses or abdomen of delayed gastric by intramural stenting • If viability of the intestine emptying • If bowel inﬂ amed or is in question, the bowel • Survival rate, 95%; ischemic, anastomosis is should be detorsed and morbidity and mortality Treatment postponed, and diverting reexploration done in are usually related to ostomy is performed 24–36 h to reassess; associated anomalies infarcted areas should be • Often require paren- resected and enterosto- teral nutrition until bowel mies created function returns; then may require elemental • Mortality, 3%–9%; higher formulas to aid absorp- in patients with volvulus, tion before transitioning necrosis, prematurity, or back to regular formula other abnormalities • Complications: Anasto- • Complications: GI motic leakage, sepsis, motility disturbances, strictures, impaired mobil- recurrent volvulus, DIC, ity, malabsorption sepsis, short gut (if <40 cm small bowel left), reperfusion injury, small bowel obstruction, strictures

PRIMARY PULMONARY DISORDERS ASSOCIATED WITH PULMONARY HYPOPLASIA

Congenital Cystic Congenital Diaphragmatic Hernia Adenomatoid Malformation

• Majority caused by failure of development of • Failure of maturation of bronchiolar posterolateral portion of the diaphragm; results structures or focal pulmonary in persistence of foramen of Bochdalek, allow- dysplasia arising in wk 5–6 ing viscera to enter the thoracic cavity • Pulmonary maldevelopment caus- NEONATOLOGY • Rarely may have anterior retrosternal hernia ing replacement of normal paren- of Morgagni chyma with cystic proliferation

(continued on next page) 476 Neonatology

Congenital Cystic Congenital Diaphragmatic Hernia Adenomatoid Malformation

• Always associated with some degree of pul- • Rapid vascular and epithelial growth, monary hypoplasia; the ipsilateral lung has a accelerated cellular proliferation, decreased airway and alveolar numbers, and and decreased apoptosis suggest the pulmonary artery is small; the contralat- possible benign neoplasm eral lung is often also abnormal secondary • Growth of CCAM is exponential to mediastinal shift with decreased alveolar between 20–25 wk; then reaches a numbers and increased PA muscularization plateau and may decrease in size • Pulmonary hypertension with ﬁ xed com- • Stocker histologic classiﬁ cation: Type ponent (caused by pulmonary hypoplasia) I CCAM with single cyst or small and variable component (caused by PA number of large cysts (50%), type reactivity) II CCAM with multiple small cysts Pathophysiology (40%), type III CCAM with homogenous microcystic tissue (10%) • CCAM volume ratio (CVR) obtained by dividing CCAM volume by head circumference; CVR >1.6 at high risk for development of hydrops

• 90% on the left; 10% on the right • Almost all unilateral; 2% bilateral • One in 3000 live births; male and female equal • Sporadic; males > females • >40% have associated anomalies of the • Associated anomalies (these heart, brain, limbs, GU system, or craniofa- are rare, but can be seen): Renal cial region agenesis or dysgenesis, truncus ar- • Has been associated with trisomies 13 and 18 teriosus, tetralogy of Fallot, jejunal and 45 XO, Goldenhar, Beckwith-Wiedemann, atresia, CDH, hydrocephalus, and Pierre Robin, Goltz-Gorlin, rubella, Fryns, and skeletal anomalies Pallister-Killian syndromes • Poor prognostic indicators: Diagnosis earlier Epidemiology in gestation, presence of liver in thorax, low lung-to-head ratio (LHR) (estimate of contralateral lung size at the level of the atria on transverse US of the fetal thorax, divided by the head circumference at the biparietal level), dilated stomach in the chest, polyhydramnios

• May be seen as early as 15 wk but may not be • Usually found antenatally as a mass detected until after routine 16–20 wk US in the fetal chest using US or MRI • Further delineated with fetal MRI • If microcystic and takes up a large • Presents with cyanosis and severe respirato- portion of the lung, the fetus ry distress immediately after birth, scaphoid may develop hydrops secondary abdomen, diminished breath sounds, bowel to mediastinal shift and IVC or sounds heard in left chest, heart sounds in cardiac compression and has poor right chest prognosis • CXR shows loops of bowel in chest; heart is • Macrocystic lesions may present with respiratory distress and be Presentation and Diagnosis Presentation displaced to the opposite side of the chest mistaken for CDH

• In delivery room: Immediate intubation to • Development of nonimmune prevent herniated bowel from ﬁ lling with hydrops is an indication for prenatal air, positive-pressure ventilation with a bag treatment, including cyst aspiration, and mask should be avoided; large bore thoracoamniotic shunt, and resec- orogastric tube placement to continuous tion of CCAM suction, IV access

(continued on next page) Surgical Disorders 477

Congenital Cystic Congenital Diaphragmatic Hernia Adenomatoid Malformation

• Treatment is aimed at maximizing cardiovas- • If fetal surgery is not an option, cular function and minimizing pulmonary maternal steroids have been hypertension and barotrauma reported to arrest the growth of • Administration of iNO is recommended if fetal CCAMs the patient who is >34 wk GA on mechanical • Those that do not self-resolve are ventilation has an oxygen index (OI) > 25 on resected later to prevent infection two separate measurements and malignant potential within the malformation OI = ([Mean airway pressure x FiO2] / PaO2) x 100 • Consider ECMO for OI >40 on two separate • CXR should be taken after delivery measurements and a CT scan of the chest should be done at 6–8 wk of age, even • ECMO has been used pre-, intra-, and post- if the CXR is normal; any residual operatively to improve survival in patients lesion is surgically resected, as there with poor pulmonary function is a risk for malignancy. • In severe cases, fetal ex utero intrapartum treatment (EXIT) to ECMO may be

Treatment considered • In surgery, hernia is reduced by withdrawing viscera from the chest, and the diaphragm is either repaired primarily or with a patch • LHR <1 associated with poor survival; LHR >1.4 has near complete survival • Survival rates vary from 40%–79%, depending on case selection • Mortality is largely related to pulmonary hypoplasia, pulmonary hypertension, and CHD • Late complications: Recurrence of hernia, small bowel obstruction, GER, and thora- columbar scoliosis

Laryngomalacia Presentation • Most common cause of stridor in neonates and infants. • Intermittent, recurrent inspiratory stridor. • Stridor worsens with crying, feeding, supine positioning, agitation. • Stridor may improve with crying in very mild laryngomalacia. • May be associated with difﬁ culty feeding, failure to thrive, dyspnea, tachypnea, apnea, cyanosis, pectus excavatum, and sleep apnea. If severe cases are untreated, cor pulmonale and pulmonary hypertension may develop. • 50%–100% association with GERD. • ~20% with neurologic compromise or multiple congenital anomalies. • ~20 % with second airway lesion. Course • Typically present within ﬁ rst 2 weeks of life.

• 50% resolve by age 9 mo. NEONATOLOGY • 75% resolve by age 18 mo. Evaluation and Management

• Consider treatment for GERD with a PPI or an H2 receptor blocker. • Lansoprazole 0.3–3.3 mg/kg/day or ranitidine 2 mg/kg/dose PO Q8h. • Note that safety and efﬁ cacy data for use of these medication in neonates is very limited. 478 Neonatology

• Routine referral to pediatric otolaryngologist if the patient has isolated, uncomplicated stridor. • Urgent evaluation to pediatric otolaryngologist for “severe symptoms”: Failure to thrive, recurrent hospitalization for dyspnea, apnea, cyanosis, pectus excavatum, severe refl ux, cor pulmonale, pulmonary hypertension. • Flexible fi beroptic laryngoscopy by pediatric otolaryngologist. • Direct laryngoscopy and bronchoscopy if: • Complicated by “severe symptoms” above • Stridor or symptoms are out of proportion to the fi beroptic exam • History and exam suggest a second airway lesion • Surgical correction: Supraglottoplasty. • 20% of patients require surgical intervention for failure to resolve symptom or severe symptoms” listed above. • Performed with either surgical instruments or lasers. • Division of the aryepiglottic folds. • Trimming or lasering of redundant supraglottic mucosa. • 1–3 d postoperative hospitalization.

Available at www.AccessPediatrics.com • Obstructive lesions of the large bowel Index

Page numbers followed by f or t indicate ﬁ gures or tables, respectively.

A Acute lymphoblastic leukemia (ALL) AAT (α-1-antitrypsin) defi ciency, 171t defi nition, 292 Ab screen, 205 diagnosis, 293 Abbott powder formulas, 46–47t epidemiology, 292 Abdominal pain, acute, 139–140 immunologic classifi cation, 293t Abdominal refl ex, 269t morphologic classifi cation, 293t Abdominal wall defects, 471–472t prognosis, 295 Abducens nerve, 268t treatment, 293–294 ABPA (allergic bronchopulmonary aspergillosis), Acute otitis media (AOM), 125–126 320t Acute postinfectious glomerulonephritis, 259t Abscess Acyclovir, 55t brain, 245t Acylcarnitine analysis, 193 retropharyngeal, 136–137t ADEM (acute disseminated encephalomyelitis), skin 284t characteristics, 114t, 233t Admission orders (ADC VANDALISM), 1 incision and drainage, 32–33, 33t Adolescents treatment, 114t eating disorders in, 56–59, 57–58t Absence epilepsy, 278t emergency contraception for, 59 AC (assist-control) ventilation, 87t, 375t gynecologic examination, 51–52, 51t ACE (angiotensin-converting enzyme) human papillomavirus infection in, 56 inhibitors, 73 pediculosis pubis in, 56 Acetaminophen pelvic infl ammatory disease in, 55–56t antidote, 345t scabies in, 56 dosing, 8–9t, 12t, 456 sexually transmitted infections in, 53–54t for migraine headache, 282t vulvovaginal disorders in, 52–53t in neonates, 456 Adrenal hemorrhage, bilateral, 392t Acid–base disorders Adrenal insuffi ciency differential diagnosis, 164–165t, 166–167t, 166f primary, 392–393 in inborn errors of metabolism, 189f, 191t secondary, 393–294t mixed, 168 Adrenergic toxidrome, 344t neonatal, 189, 189f Adrenocortical dysgenesis, 392t nomogram, 166f AGEP (acute generalized exanthematous with partial compensation, 166–167t pustulosis), 121t Acne, neonatal, 386t Albumin 5%, 158t Acrodermatitis enteropathica, 391t Albuterol Acropustulosis of infancy, 387t adverse effects, 316t Acute chest crisis, in sickle cell disease, 200t for anaphylaxis, 61t Acute disseminated encephalomyelitis (ADEM), for asthma, 316t 284t for status asthmaticus, 91t Acute generalized exanthematous pustulosis Alclometasone dipropionate, 124t (AGEP), 121t Aldosterone synthase defi ciency, 393t Acute infusion reaction, 290–291t Alkylating agents, 298t Acute kidney injury (acute renal injury, acute renal ALL. See Acute lymphoblastic leukemia (ALL) failure) Allergic bronchopulmonary aspergillosis (ABPA), categories, 264 320t classifi cation, 263 Allergic contact dermatitis, 111t defi nition, 263 Allergic rhinitis, 62–63t, 127 etiologies, 264 Allergic salute, 62 evaluation, 264–265 Allergic shiners, 62 management, 265 Allergy testing, 60 in neonates, 445–446 Alloimmune thrombocytopenia, 426–427t prognosis, 265 α-1-antitrypsin (AAT) defi ciency, 171t

479 480 Index

α-thalassemia, 199t Antibiotics (cont.) ALTE (apparent life-threatening event), in cystic fi brosis, 322–323t 323–324 empiric choices Altered mental status, 141 for bacterial meningitis, 245t Ambulatory care based on organism, 228f health supervision overview, 209–211t for community-acquired pneumonia, screening recommendations, 212t 237t, 238t Amcinonide, 123t for epiglottitis, 136t American Society of Anesthesiologists (ASA), for fever without localizing signs, physical status classifi cation, 15t 130f, 131f Amikacin, 224t, 438–439t fl uoroquinolones, 224–225t Amino acid analysis, 193t lincosamides, 223t Amino acid metabolic disorders, 191t lipopeptides, 226t Amino acid transport disorders, 191t macrolides, 222t Aminoglycosides, 224t for mastoiditis, 127t Aminopenicillins, 218t monobactams, 221t Aminophylline, 92t for neonatal infections, 437–440t Amitriptyline, 282t nitroimidazoles, 226t Amniocentesis, 358 oxazolidinones, 223t Amoxicillin, 218t penicillins, 218–219t for acute otitis media, 126t for retropharyngeal abscess, 136t for community-acquired pneumonia, 237t rifamycins, 226t for infective endocarditis prophylaxis, 80t for septic arthritis, 134t Amoxicillin–clavulanate, 219t for sinusitis, 128 for acute otitis media, 126t for skin and soft tissue infections, 234 for community-acquired pneumonia, 237t sulfonamides, 225t Amphetamines, 341t, 342t tetracyclines, 223t Ampicillin, 218t, 437t vancomycin, 222t Ampicillin–sulbactam, 219t Anticholinergic toxidrome, 344t AMPLE history, 15 Anticoagulants, 205t Anal stenosis, 409t Antiemetics, 292t Anaphylaxis, 60–61, 61t, 121t Antiepileptics Anemia in increased intracranial pressure, 101 of chronic disease, 197t for migraine headache prophylaxis, 282t defi nition, 196 in pregnancy, neonatal effects, 399t, 423t diagnosis, 196, 197f, 198f for seizures, 279–280t iron-defi ciency, 197t, 198–199 Antihistamines macrocytic, 197f for allergic rhinitis, 62t microcytic, 197f poisoning/overdose, 346t morphologic classifi cation, 197f Antimetabolites, 298t neonatal, 431–433, 432t Antipseudomonal penicillins, 219t screening, 212t Antithrombin (AT) replacement, 208 Aneuploidy, screening for, 354, 358, 358t α-1-Antitrypsin (AAT) defi ciency, 171t Angioedema, 61–62, 121t Antitumor antibiotics, 298t Angiotensin-converting enzyme (ACE) AOM (acute otitis media), 125–126 inhibitors, 73 Apgar score, 349t Anion gap metabolic acidosis, 168 Aplastic crisis, 200t Ankle fractures, 310t Apnea, neonatal Ankle sprain, 310t defi nition, 465 Annular pancreas, 140 differential diagnosis, 468–469 Anorectal abnormality, 409t evaluation, 468 Anorexia nervosa, 56–57, 57–58t incidence, 465 Antiarrhythmics management, 469–470 overview, 77t monitoring, 468 poisoning/overdose, 346t Apophysitis, 301, 302 Antibiotics Apparent life-threatening event (ALTE), for acute otitis media, 125–126t 323–324 aminoglycosides, 224t Appendicitis, 139 for bacterial tracheitis, 136t Apple juice, 157t for bite wounds, 135t Aprepitant, 292t carbapenems, 221t Argininemia, 194t cephalosporins, 220–221t Argininosuccinic aciduria, 194f, 194t Index 481

Arrhythmias, 75t, 76f, 77t Bacterial tracheitis, 136–137t Arsenic poisoning, antidote, 345t Bacterial vaginosis, 52–53t Arterial blood gases Ballard score, 348t in congenital heart disease, 382 Barbiturates, 18, 18t in mechanical ventilation, 89 Barium enema, pre-procedural diet, 4t normal values, 164t Basal metabolic rate, 41t SI laboratory value conversion table, 8t Behçet syndrome, 332t Arterial switch operation, 81 Benign childhood epilepsy with centrotemporal Arthritis spikes, 278t in cystic fi brosis, 320t Benign neonatal sleep myoclonus, 449t differential diagnosis, 328f Benign Rolandic Epilepsy (BRE), 278t juvenile idiopathic, 329–330 Benzodiazepines. See also specifi c drugs synovial fl uid evaluation in, 327t antidote, 345t Ascites, 174 overview, 17, 17t Asparaginase, 299t Berger (IgA) nephropathy, 259t Aspergillosis, 227 Bernard-Soulier syndrome, 427t Aspiration pneumonia, 235t, 237t, 238t β-blockers Asplenia, secondary immunodefi ciency in, 64t as antiarrhythmics, 77t Assist-control ventilation (AC), 87t, 375t antidote, 345t Asthma for dilated cardiomyopathy, 73 defi nition, 312 for hyperthyroidism, 149 diagnosis, 313 β-lactamase resistant penicillins, 219t exacerbation, 137f β-lactamase susceptible penicillins, 218t history and physical exam, 313t β-thalassemia major, 199t management β-thalassemia minor, 197t, 199t assessment of control, 315t Betamethasone, equivalencies, 10t components, 313–314 Betamethasone dipropionate, 123t initial therapy, 315t Betamethasone valerate, 124t medications, 316t Bicarbonate, in fl uid replacement, 154 stepwise approach, 316–317t Bilevel positive airway pressure (BiPAP), 85t therapy adjustment, 315t Biliary cirrhosis, in cystic fi brosis, 319t modifi ed predictive index, 312 Biophysical profi le, 360–361t pathophysiology, 312 Birth weight, 3 severity classifi cation, 314t Bisacodyl, 179 Astrocytoma, 296–297t Bites, 134–135 Athlete’s foot (tinea pedis), 118t Bitter almond odor, 341t Atopic dermatitis, 110–111 Blalock-Taussig shunt, 81, 81f Atrial septal defect (ASD), 66 Blastomycosis, 227 Atrial switch operation, 82, 82f Bleeding disorders Atrioventricular septal defect, 67, 67f, 81 differential diagnosis, 203t Atrophy, 109 history, 204 Auditory nerve, 268t laboratory evaluation, 204 Augmented betamethasone dipropionate, 123t treatment of acute bleeding in, 204t Autoimmune diseases, secondary immunodefi ciency Bleomycin, 298t in, 65t Blood component transfusion Autoimmune thrombocytopenia, 426t CMV-seronegative, 207 Avulsion fracture, 302, 308t cryoprecipitate, 207 Azalides, 222t defi nitions, 205 Azithromycin, 222t granulocyte, 207 for acute otitis media, 126 irradiated blood, 208 for chancroid, 54t leukocyte-reduced blood, 207 for chlamydia, 54t in neonates, 433t, 434–436t for community-acquired pneumonia, packed red blood cells, 206t, 433t, 434t 237t, 238t plasma, 207, 435t in cystic fi brosis, 322t platelets, 206t, 207, 435t for infective endocarditis prophylaxis, 80t risks, 206 for neonatal infections, 440t Blood gases Aztreonam, 221t, 322t, 323t in mechanical ventilation, 89 normal values, 164t B SI laboratory value conversion table, 8t Babinski sign/refl ex, 269t, 272t Blood pressure screening, 212t. See also Bacterial peritonitis, 174, 175t Hypertension 482 Index

Blood transfusion. See also Blood component Carrot odor, 341t transfusion; Exchange transfusion Casts, in urine, 257t for shock, 98 Cat bites, 135t, 233t typing and cross-matching for, 430–431t Cataracts, 192 Blood type, 205 Cefaclor, 220t Bloodstream infections Cefadroxil, 220t central venous catheter-related, 247–249, 247t, Cefamandole, 220t 248f, 249t Cefazolin, 80t, 220t, 439t intravascular catheter-related, 246–247, 246t Cefdinir, 220t Body mass index (BMI), 49 Cefepime, 221t Body surface area, 4 Cefi xime, 53t, 220t Bone marrow transplantation, 299–300 Cefonicid, 220t Bone scan, pre-procedural diet, 4t Cefotaxime, 220t, 238t, 439t Boost, 156t Cefotetan, 55t, 220t Borrelia burgdorferi, 115t Cefoxitin, 55t, 56t, 220t Brachial muscles, actions and nerve root supply, Cefpodoxime, 220t 272–273t Cefprozil, 220t Bradycardia, 76f Ceftazidime, 323t, 439t Brain abscess, 245t Ceftibuten, 220t Brain death, 287–288 Ceftizoxime, 220t Brainstem glioma, 296–297t Ceftriaxone, 220t Breast milk jaundice, 412t for acute otitis media, 126t Breastfeeding, 35–36. See also Human milk for chancroid, 54t Breastfeeding jaundice, 412t for gonorrhea, 53t Bronchiolitis, 138–139 for infective endocarditis prophylaxis, 80t Bronchopulmonary dysplasia (BPD), 465–468t for neonatal infections, 440t Bronchoscopy, pre-procedural diet, 4t for pelvic infl ammatory disease, 56t Buckle (torus) fracture, 302 Cefuroxime, 220t Bulimia nervosa, 57–58t Cellulitis, 114t, 233t, 234 Bulla, 109 Central core disease, 453t Bullous congenital ichthyosiform erythroderma, Central diabetes insipidus, 150–151t 388t Central nervous system tumors, 296–297t Bupivacaine, 12t Central shunt, 81 Busulfan, 298t Central venous line (CVL) Buttock laceration, 31t access, 25–27, 26t, 27f infections C complications, 249 Caffeine, 466t, 469 management, 247, 248f, 249t Calcium types, 247t conversion, 43t Cephalexin, 80t, 220t daily requirement, 43t Cephalosporins, 220–221t, 439–440t ECG changes and, 77 Cephapirin, 220t for neonatal hypocalcemia, 401t Cephradine, 220t in shock, 98 Cerebral edema, 99, 101 Calcium channel blockers, as antiarrhythmics, 77t Cerebral salt wasting (CSW), 150t Calcium defi ciency, 152t Cerebrospinal fl uid analysis, 244t, 442t Candida infections, 52–53t, 119t, 227, 390t Cerumen, 5–6, 6f Carbamazepine, 279t Ceruminolytic preparations, 6t Carbamoyl-phosphatase synthetase (CPS) Cervical adenitis, 231t defi ciency, 193t, 194f Cervical dysplasia, screening recommendations, Carbapenems, 221t, 440t 212t Carbenicillin, 219t Chancroid, 54t Carbohydrates, in total parenteral nutrition, 42, 43t CHARGE syndrome, 187 Carbon monoxide, antidote, 345t Chemical conjunctivitis, in neonates, 443–444t Carbon tetrachloride, antidote, 345t Chemistry studies Carbuncle, 233t SI laboratory value conversion table, 8t Cardiac ischemia, 75 tube colors, 6, 7t Cardiogenic shock, 94t, 96t, 98 Chemotherapy agents Cardiomyopathy antitumor spectrum, 298–299t dilated, 72–73, 72t emetogenic potential, 291t in inborn errors of metabolism, 192 hypersensitivity reactions to, 290–291t Caries, dental, 106–107 toxicities, 298–299t Index 483

Chest pain Coma, 141 differential diagnosis, 78–79 Comminuted fracture, 302 green fl ags, 78 Common warts, 117t red fl ags, 78 Compensated (warm) shock, 93, 97f, 98. workup, 79 See also Shock Chest tube placement, 22–23, 22f, 22t Complement defi ciency, 63–64, 64t Chest x-ray Complex partial seizure, 275t. See also Seizures in congenital heart disease, 379, 382f, 382t Computed tomographic angiography (CTA), 274t in persistent pulmonary hypertension, 463t Computed tomography (CT) in respiratory distress syndrome, 458t brain, 274t in transient tachypnea of the newborn, 458t pre-procedural diet, 5t Chicken broth, 157t signal density, 274t Chickenpox, 116t Condyloma acuminata (genital warts), 56, 117t Child abuse, 141–142 Congenital fi ber type disproportion myopathy, 453t Childhood weakness, 286–287t Congenital heart disease Chlamydia trachomatis infection, 54t, 212t acyanotic, 66–67 Chlamydial conjunctivitis, in neonates, 443–444t arterial blood gases in, 382 Chloral hydrate, 18, 18t chest x-ray fi ndings in, 382f, 382t Chloride cyanotic, 67–70, 381t conversion, 43t differential diagnosis, 383–384t daily requirement, 43t in Down syndrome, 184 in mechanical ventilation, 89 EKG fi ndings in, 381–382t Chlorothiazide, for bronchopulmonary dysplasia, empiric approach to evaluation, 380t 467t four-extremity blood pressures in, 381 Cholelithiasis, in cystic fi brosis, 319t history, 381 Cholestasis, in total parenteral nutrition, 44 hyperoxia test in, 383, 383t Cholinergic toxidrome, 344t infective endocarditis prophylaxis in, 80, 80t Chorionic villus sampling (CVS), 358–359 initial stabilization, 384 Chronic arthritis, 327t management, 384–385 Chronic kidney disease, 265–267 oximetry in, 381 Churg-Strauss syndrome, 333t pathophysiology and age at presentation, Ciprofl oxacin, 224t 383–384t adverse effects, 322t prenatal testing, 381 for chancroid, 54t surgical procedures, 81–82, 81f, 82f for P. aeruginosa, 322t symptoms, 381t, 383–384t Circumcision, 350 Congenital hypoventilation syndrome, 469 Cisplatin, 298t Congenital melanocytic nevus, 387t Citrullinemia, 193t, 194f Congenital muscular dystrophy, 453t Clarithromycin, 80t, 222t Conjugated (direct) hyperbilirubinemia, 175 Clavicular fracture, 303t Conjunctivitis, in neonates, 443–444 Cleft lip and palate, 128–129 Constipation, 39t, 179–180 Clindamycin, 223t Contact dermatitis, 111t adverse effects, 323t Continuous positive airway pressure (CPAP), 85t for bacterial vaginosis, 53t Contraception, emergency, 59 for infective endocarditis prophylaxis, 80t Contraction stress test, 360 for neonatal infections, 439t Controlled mechanical ventilation (CMV), 86t for pelvic infl ammatory disease, 56t Cooked cabbage odor, 189t for S. aureus, 323t Coordination testing, 269 Clinical Respiratory Score (CRS), 90–91t, 138t Copper, for direct hyperbilirubinemia, 420t Clobetasol propionate, 123t Cordocentesis, 359 Clotrimazole, 53t Corneal opacifi cations, 192 CMV-seronegative blood components, 207 Corticosteroids Coagulation studies, tube colors for, 6, 7t adrenal insuffi ciency and, 392t Coagulopathies. See Bleeding disorders as chemotherapy agents, 299t Coca Cola Classic, 157t immunizations in patients receiving, 217t Cocaine, 341t, 342t, 346t inhaled, 316t Coccidioidomycosis, 227 intranasal, 61t Codeine, 13t, 14t systemic, 9–10t, 137f Colistimethate sodium, 323t topical, 110t, 123–124t Colitis, indeterminate, 180. See also Crohn disease; Cortisone, equivalencies, 9t Ulcerative colitis Cow’s milk, 156t Collection tubes, 7t Cow’s milk–based formulas, 46 484 Index

Coxsackie A16, 116t Daptomycin, 226t CPS (carbamoyl-phosphatase synthetase) defi ciency, De Quervain thyroiditis, 149 193t, 194f Decompensated (cold) shock, 93, 97f, 98. Cradle cap, 111t See also Shock Cranial nerves, examination methods, 268t Deep tendon refl exes, 269 Creatinine, serum, 251 Deferoxamine, 345t Creatinine clearance, 250–251 Dehydration Cremasteric refl ex, 269t classifi cation, 55 Crigler-Najjar syndrome, 412t intravenous rehydration, 157, 158t Crohn disease oral rehydration, 155–157 clinical features, 180t symptom-based determination, 154t defi nition, 179 weight-based determination, 154 endoscopic features, 181t Dejerine–Sottas disease, 453t epidemiology, 180t Delayed puberty, 151 radiographic features, 181t Demyelinating diseases, 284–286 treatment, 181–182, 182t Dennie’s lines, 62 Cromolyn sodium, 63t Dental caries, 106–107 Cross-match, 205 Dental procedures, infective endocarditis Croup, 136–137t prophylaxis for, 80t CRS (Clinical Respiratory Score), 90–91t, 138t Dermal melanocytosis, 387t Crural muscles, actions and nerve root supply, 273t Dermatomyositis, 329t Crust, 109 Desonide, 124t Cryoglobulinemia, 332t Desoximetasone, 123t Cryoprecipitate, 207, 208 Developmental observations, 209–211t Cryptococcosis, 227 Dexamethasone Crystals, in urine, 256t adverse effects, 316t CSW (cerebral salt wasting), 150t as antiemetic, 292t CT. See Computed tomography (CT) for asthma, 316t CTA (computed tomographic angiography), 274t as chemotherapy agent, 299t Cutaneous innervation, 270–271f equivalencies, 10t CVL. See Central venous line (CVL) for spinal cord compression, 290 CVS (chorionic villus sampling), 358–359 Dexmedetomidine, 18, 19t Cyanosis, 353t, 380t, 381t Diabetes insipidus, 150–151t Cyclophosphamide, 298t Diabetes mellitus Cyproheptadine, 282t blood glucose goals, 146t Cystic adenomatoid malformation, congenital, cystic fi brosis and, 319t 475–477t diagnosis, 143t Cystic fi brosis HbA1c goals, 146t complications, 319–320, 320t hyperglycemic emergencies in, 98–99, 99t, 100f diagnosis, 317 hypoglycemia management in, 147, 148f epidemiology, 317 inpatient management of, 145 genetics, 317 insulin for, 145–147 management in NPO patients, 146 airway clearance therapies, 321 in pregnancy, 355, 357t, 399t antibiotic options, 321, 322–323t secondary causes, 144 nutrition, 321 secondary immunodefi ciency in, 64t pharmacologic, 321–322t type 1, 143, 143t manifestations, 318–319t type 2, 143–144, 143t pneumonia in, 235t, 318t, 319 Diabetic ketoacidosis (DKA), 98–99, 99t, 100f symptoms and signs, 318t Dialysis, indications for, 265 treatment, 318–319t Diaper dermatitis, 119t, 390, 390t Cytarabine, 298t Diaphragmatic hernia, congenital, 475–477t Cytokine release syndrome, 290–291t Diarrhea, with enteral feeding, 39t Diazepam, 17t D Dicloxacillin, 219t D5 1/2 NS, 158t Diet, pre-procedural guidelines, 4–5t D5 1/4 NS, 158t Difl orasone diacetate, 123t D5W, 158t Digoxin Dacryostenosis, 443–444t as antiarrhythmic, 77t Dactinomycin, 298t antidote, 345t Dactylitis (hand-foot syndrome), 199t for dilated cardiomyopathy, 73 Damus-Kaye-Stansel procedure, 81 poisoning/overdose, 346t Index 485

Dilated cardiomyopathy, 72–73, 72t Eczematous/papulosquamous eruptions, 111–113t Dimercaprol, 345t Edema, cerebral, 99, 101 Diphenhydramine, 61t ELA-Max, 11t Diphtheria, tetanus, pertussis vaccine Elbow fractures, 304t catch-up schedule, 214t, 215t Electrocardiogram (ECG; EKG) contraindications, 216t in congenital heart disease, 381–382t regular schedule, 213t drugs and changes in, 77 Direct Coombs test, 206 electrolytes and changes in, 76–77 Discharge criteria in hypertrophy, 74–75 neonates, 376 intervals, 74 post-sedation, 20t in ischemia and infarction, 75 Discharge orders, 1 low voltage, 75 Discharge summary, 2 normal values, 73t Disseminated intravascular coagulation (DIC), in pericarditis, 71, 71f 427t QRS depolarization axis, 74, 74f Dissociative shock, 95t rate, 74 Distal intestinal obstruction syndrome (DIOS), rhythm, 74 320t Electrolytes, 43t, 153 Distributive shock, 94t, 95t EM (erythema multiforme), 122t Diuretics Embryology, 186t, 187 for bronchopulmonary dysplasia, 467t Emergency contraception, 59 for dilated cardiomyopathy, 73 EMLA, 11t in mechanical ventilation, 89 Encephalopathy, neonatal, 450–452 DMSA scan, 242t End-stage liver disease (ESLD) Dobutamine, 96, 96t ascites in, 174 Dog bites, 135t, 233t bacterial peritonitis in, 174, 175t Dopamine clinical presentation, 172 in neonatal resuscitation, 365t diagnosis, 172 for shock, 96, 96t etiology, 172 Down syndrome (trisomy 21), 64t, 183, 184–185t, hepatic encephalopathy in, 173, 173t 422–423t hepatorenal syndrome in, 173, 174–175t Doxorubicin, 298t portal hypertension in, 172 Doxycycline, 223t treatment, 172 adverse effects, 322t varices in, 173 for chlamydia, 54t End-stage renal disease (ESRD), 266 for lymphogranuloma venereum, 54t Endotracheal tubes, 16t, 365t for pelvic infl ammatory disease, 55t, 56t Energy, DRI by age, 40t for S. aureus, 322t Enfalyte, 156t Dronabinol, 292t Enfamil HMF, 48t Drug hypersensitivity syndrome (DHS), 122t Enfamil Lipil, 156t Drug monitoring Ensure, 156t collection tube colors, 7t Enteral feeding SI laboratory value conversion table, 8t bolus or intermittent, 38t urine testing for substances of abuse, 342t complications, 38t, 39t Drug reaction with eosinophilia and systemic continuous, 38t symptoms (DRESS), 122t delivery routes, 38t Drug reactions, 120–123t in direct hyperbilirubinemia, 420t Drugs of abuse. See Substance abuse indications, 37, 38t Duodenal atresia and stenosis, 473–475t preterm infants, 39t Dyslipidemia, screening recommendations, 212t principles, 36, 37f Enterovirus 71, 116t E Eosinophilia, 202t Ear wax (cerumen), 5–6, 6f Eosinophils, 201t Eating disorders, 56–59, 57–58t Ependymoma, 296–297t ECF (extracellular fl uid), 158t Epidermolysis bullosa (EB), 389t Echocardiography, pre-procedural diet, 5t Epidermolytic hyperkeratosis, 388t Eclampsia, 356 Epididymitis, 131–132t ECMO (extracorporeal membrane oxygenation), Epiglottitis, 136–137t 463t, 470 Epilepsy Ecstasy, 341t classifi cation scheme, 277–278t Ectodermal dysplasias, 389t syndromes, 278–279t Eczema, 110–111 treatment, 279–280t 486 Index

Epinephrine Felbamate, 279t for anaphylaxis, 61t, 97f Femoral vein, 26, 27f in neonatal resuscitation, 264t, 365t Femur fractures, 308t for shock, 96, 96t Fentanyl warnings, 11, 12t dosing, 13t, 14t, 457 Equianalgesic doses, 14, 14t in neonates, 457 Erosion, 109 onset and duration, 13t Erysipelas, 114t in patient-controlled analgesia, 14t Erythema infectiosum (fi fth disease), 116t weaning from, 20 Erythema multiforme (EM), 122t Fetal heart rate (FHR) monitoring, Erythema toxicum, 386t 361–362, 361t Erythromycin, 222t Fetal hydrops, nonimmune, 421–422t for chancroid, 54t Fetus for lymphogranuloma venereum, 54t antepartum surveillance ESLD. See End-stage liver disease (ESLD) biophysical profi le, 360–361t ESRD (end-stage renal disease), 266 contraction stress test, 360 Ethanol, prenatal exposure effects, 423t indications, 359–360t Ethosuximide, 279t non-stress test, 360 Ethyl chloride topical spray, 12t complications of maternal medical conditions, Ethylene glycol, antidote, 345t 354, 355, 357t Etomidate complications of maternal substance abuse, 357t adverse effects, 19t genetic diagnosis techniques, 358–359 dosing, 19t intrapartum heart rate monitoring, onset and duration, 19t 361–362, 361t pharmacologic properties, 18 lung maturity evaluation, 355, 355t in septic shock, 98 serum screening for chromosomal abnormalities, Etoposide, 299t 358t Exanthem subitum (roseola), 116t sonographic assessment, 357, 358 Exanthematous drug reaction, 120t Fever, as oncologic emergency, 289 Exchange transfusion Fever without localizing signs complications, 431 in patients 2 months and younger, 130f for hyperbilirubinemia, 414f, 414t, 430t in patients 2 months to 36 months old, 131f indications, 430t FFP (fresh frozen plasma), 435t partial, 433t Fifth disease (erythema infectiosum), 116t for polycythemia, 430t Finger fractures, 307t preparation, 430t Fissure, 109 procedure, 431 Fixed drug eruption, 121t typing and cross-matching for, 430–431t FLM-TDx, 355t Excoriation, 109 Fluconazole, 53t, 119t Extracellular fl uid (ECF), 158t Fludrocortisone, 10t Extracorporeal membrane oxygenation (ECMO), Fluid requirements, 153–154 463t, 470 Flumazenil, 17, 345t Extraocular muscles, innervation, 269 Fluocinolone acetonide, 124t Extremely low birth weight infants, 369. See also Fluocinonide, 123t Preterm infants Fluoride consumption, 106 Extremity laceration, 31t Fluoroquinolones, 224–225t Eyelid laceration, 31t Fluoroscopy, pre-procedural diet, 5t Fluorosis, 106 F Flurandrenolide, 123t

Face masks, for O2 delivery, 84–85t Fluticasone acetonide, 124t FACES pain scale, 11f Fluticasone propionate, 123t, 124t Facial laceration, 31t FOC. See Head circumference (FOC) Facial nerve, 268t Focal segmental glomerulosclerosis, 260t Factor 8 replacement, 204t Folliculitis, 113t, 233t Factor 9 replacement, 204t Fomepizole, 345t Factor H deﬁ ciency, 64t Fontan procedure, 81, 81f Failure to thrive, 182–183, 191t Fontanelles, 4 Famciclovir, 55t Foot Fanconi syndrome, 152t, 428 fractures, 310–311t Fatty acid oxidation disorders, 191t laceration, 31t Febrile seizures, 276 Formulas, infant, 46–47t Feeding hypoxemia, 469 Fosphenytoin, 104f Index 487

Fractures Glioma, brainstem, 296–297t ankle, 310t Glomerular fi ltration rate (GFR), 250, 251t in child abuse, 141 Glossopharyngeal nerve, 268t elbow, 304t Glucagon, 245t evaluation, 302 Glucose femur, 308t for neonatal hypoglycemia, 405–406 foot, 310–311t requirements, 153 hand, 306–307t in urine, 255t hip, 308t Glycogen storage diseases, 191t knee, 308–309t Glycopeptides, 222t management principles, 303 Glycosylation disorders, 191t radius, 305t Gonococcal conjunctivitis, in neonates, 443–444t shoulder, 303t Gonorrhea, 53t, 212t tibia and fi bula, 309t Goodpasture syndrome, 332t types, 302, 302f Gram-negative organisms ulna, 306t algorithm for identifi cation, 230f Free amino acid formulas, 46 empiric antibiotic choices, 228f Free water defi cit, 161 Gram-positive organisms Freiberg’s infarction, 311t algorithm for identifi cation, 229f Fresh frozen plasma (FFP), 435t empiric antibiotic choices, 228f Fresh hay odor, 341t Granulocyte transfusion, 436t Fruity odor, 341t Graves disease, 149 FSI, 355t Greenstick fracture, 302 Fungal infections, 118–119t, 227 Griseofulvin, 118t Furosemide, for bronchopulmonary dysplasia, 467t Group A β-hemolytic streptococcus (GABHS), Furuncle, 233t 114t, 125 Group B streptococcus (GBS) infections G classifi cation, 442–443t Gabapentin, 279t intrapartum prophylaxis, 367f, 368f GABHS (group A β-hemolytic streptococcus), treatment, 443t 114t, 125 Growth charts, 49, 50f Galeazzi fracture, 305t Gynecologic examination, 51–52, 51t Gallstones, 140 Gamekeepers thumb, 307t H γ-hydroxybutyrate (GHB), 341t H2R antagonists, 169 Garlic odor, 341t Haemophilus ducreyi, 54t Gastric aspirates, large or increased, 414–415 Haemophilus infl uenza Gastric emptying study, pre-procedural diet, 5t in acute otitis media, 125 Gastroesophageal refl ux, 169–170 in cystic fi brosis, 318t, 322t Gastroesophageal refl ux disease (GERD), 169–170, immunization schedule, 213t, 214t 410–411 in sinusitis, 128 Gastrojejunal feeding, 38t. See also Enteral feeding Hair, abnormal, 189 Gastroschisis, 471–472t Halcinonide, 123t Gastrostomy, 38t. See also Enteral feeding Halobetasol propionate, 123t Gatifl oxacin, 225t Hand Gatorade, 157t fractures, 306–307t GBS. See Group B streptococcus (GBS) infections laceration, 31t Gell and Coombs classifi cation, hypersensitivity Hand-foot-mouth disease, 116t immune responses, 60t Harlequin ichthyosis, 389t Generalized seizures, 276t. See also Seizures Hashimoto’s thyroiditis, 147 Genital warts, 56, 117t HbA1c, 146t Gentamicin, 56t, 224t, 438t Head circumference (FOC) Gentamicin/tobramycin, 323t by age for boys, 2t, 3 German measles (rubella), 116t by age for girls, 3t Gestational age assessment, 354, 354f by gestational age, 50f Gestational hypertension, 356 rate of gain, 3, 4 GHB (γ-hydroxybutyrate), 341t Headaches Gianotti-Crosti syndrome, 117t chronic daily, 283 Giant hemangioma, 427t classifi cation scheme, 281t Gilbert syndrome, 412t migraine. See Migraine headaches Glabellar refl ex, 270t neuroimaging in, 281 Glenn anastomosis, 81, 81f tension type, 283 488 Index

Health supervision, 209–211t Herpes simplex virus (HSV) (cont.) Hearing screening, 212t oral infection, 117t Heart disease superinfection in eczema, 110t arrhythmias, 75t, 76f, 77t treatment, 55t, 117t athletic restrictions in, 80–81 Herpes zoster (shingles), 117t congenital. See Congenital heart disease HHV-6, 116t dilated cardiomyopathy, 72–73, 72t HIDA scan, pre-procedural diet, 5t infective endocarditis prophylaxis in, HIE (hypoxic-ischemic encephalopathy), 448t, 80, 80t 451–452t myocarditis, 70–71, 70t High-frequency oscillatory ventilation (HFOV), pacemakers for, 77 87t, 375t pericardial, 71–72, 71f Hip fracture, 308t Heavy metal poisoning, antidote, 345t Hirschsprung’s disease, 140, 409t Height/length Histoplasmosis, 227 by age for boys, 2t HIV by age for girls, 3t immunizations in, 217t by gestational age, 50f screening recommendations, 212t rate of gain, 3 HLHS (hypoplastic left heart syndrome), 69, 69f, Heliox 81, 81f for respiratory failure, 85t Hoffman sign, 269t for status asthmaticus, 92t HSV. See Herpes simplex virus (HSV) Hematology studies Human bites, 135t, 233t SI laboratory value conversion table, 8t Human milk tube colors, 6, 7t characteristics, 45 Hematuria, differential diagnosis, 252–254, composition, 45, 156t 253f, 255t contraindications, 45 Hemoglobin, 196t fortifi ers, 48t Hemolysis with infant formula powder, 47t effect on lab values, 7t storage durations, 36t hyperbilirubinemia and, 412t vitamin and mineral supplementation, 35t Hemolytic disease of the newborn, 430t Human papillomavirus (HPV), 56, 117t, Hemophagocytic-lymphohistiocytosis (HLH), 295 212t, 215t Hemophilia, 204, 204t Hybrid Norwood procedure, 81–82 Hemoptysis, in cystic fi brosis, 320t Hydrocephalus, 453–454 Henoch Schönlein purpura, 333, 335 Hydrocodone, 13t, 14t Hepatic encephalopathy, 173, 173t Hydrocortisone, 124t Hepatitis for anaphylaxis, 61t infectious, 170 equivalencies, 9t noninfectious, 171 Hydrocortisone butyrate, 124t Hepatitis A, 170t Hydrocortisone valerate, 124t Hepatitis A immunization, 212t, 215t Hydromorphone, 13t, 14t Hepatitis B, 170t 21-Hydroxylase defi ciency, 392t Hepatitis B immunization 3-β-Hydroxysteroid dehydrogenase defi ciency, in preterm infants, 444 392t schedule, 213t, 214t, 215t Hyperammonemia, 194–195, 195f Hepatitis C, 170t Hyperbilirubinemia Hepatomegaly, 192 direct (conjugated) Hepatorenal syndrome, 173–174t defi nition, 175, 418 Hepatosplenomegaly, 192 diagnosis, 175, 419, 419t Hereditary angioedema, 62 etiologies, 419t Hereditary hemochromatosis (HH), 171t management, 420t Hereditary hypophosphatemic rickets with in inborn errors of metabolism, 189 hypercalciuria (HHRN), 152t indirect (unconjugated), 175–176, 411 Hereditary motor and sensory neuropathy type nonphysiologic III, 453t causes, 412t Hernia evaluation, 412 congenital diaphragmatic, 475–477t management, 412–414, 413f, 414f incarcerated, 140 physiologic, 411 Heroin, 341t Hypercalcemia Herpes simplex virus (HSV) ECG changes in, 76 diagnosis, 54t neonatal, 397–398, 397f genital infection, 54t, 55t, 117t Hyperekplexia, 449t Index 489

Hyperglycemia Hypoparathyroidism, neonatal, 399t with enteral feeding, 39t Hypophosphatemia, 152t neonatal, 403–404 Hypopituitarism, 393t in total parenteral nutrition, 44 Hypoplastic left heart syndrome (HLHS), 69, 69f, Hyperglycemic hyperosmolar state (HHS), 98–99, 81, 81f 99t, 100f Hyposplenism, secondary immunodefi ciency in, 64t Hyperkalemia Hypotension, 94, 357t. See also Shock causes, 158–159 Hypothermia, induced, 102 ECG changes in, 76 Hypothyroidism, 147, 149 exchange transfusion for, 430t Hypothyroxinemia, in preterm infants, 394–395, neonatal, 395–396 394f signs and symptoms, 158 Hypotonia treatment, 159 in inborn errors of metabolism, 188 workup, 159 neonatal, 452 Hyperleukocytosis, 291 Hypovolemic shock, 94t, 95t Hypermagnesemia, ECG changes in, 77 Hypoxic-ischemic encephalopathy (HIE), 448t, Hypernatremia 451–452t dehydration in, 155t neonatal, 406–407 I signs and symptoms, 160 Ibuprofen treatment, 161–162 in cystic fi brosis, 322t workup, 161, 161f dosing, 9t, 12t Hyperoxia test, 383, 383t for migraine headache, 282t Hypersensitivity immune responses, 60t, 290–291t ICP (increased intracranial pressure), 101–102 Hypersplenism, 427t Idiopathic thrombocytopenic purpura (ITP), 202 Hypertension Ifosfamide, 298t defi nition, 251 IgA (Berger) nephropathy, 259t initial workup, 252f Ileal atresia, 409t in neonates, 446–447 Ileus, 410t in pregnancy, 356, 356t, 357t Imipenem, 221t Hyperthyroidism, 149 Immediate hypersensitivity skin test (IHST), 60 Hypertonic saline, 158t Immunizations Hypertriglyceridemia, in total parenteral after bone marrow transplantation, 299–300 nutrition, 44 catch-up schedule, 214–215t Hyperventilation, 165t contraindications, 216t Hypocalcemia in preterm infants, 444, 444t early neonatal, 398–399, 400t, 401t recommended schedule, 213t ECG changes in, 76 for special populations, 217t late neonatal, 399–401, 400t, 401t Immunodefi ciency disorders Hypoglossal nerve, 268t immunizations in, 217t Hypoglycemia primary, 63, 63t in inborn errors of metabolism, 188, 188f, 191t, secondary, 64–65t 192, 404t Immunotherapy, for allergic rhinitis, 63t neonatal, 188f, 404–406 Imperforate anus, 409t in type 1 diabetes mellitus, 147, 148f Impetigo, 113t, 233t Hypokalemia IMV (intermittent mandatory ventilation), 87t causes, 160 Inborn errors of metabolism ECG changes in, 76 acute and recurrent attacks, 192 neonatal, 396–397 chronic and progressive symptoms, 192 signs and symptoms, 159–160 classes, 188t treatment, 160 clinical and laboratory fi ndings, 191t workup, 160 hypoglycemia in, 188f, 404t Hypomagnesemia laboratory tests, 192–193 ECG changes in, 77 management, 194–195 neonatal, 399t metabolic acidosis in, 189f Hyponatremia signs and symptoms, 188–189, 188f, 189f causes, 163f urine and body odors in, 189–190t dehydration in, 155t urine discoloration in, 190t neonatal, 407–408 Incision and drainage (I&D), abscess, signs and symptoms, 162 32–33, 33t treatment, 162–164 Increased intracranial pressure (ICP), workup, 163f 101–102 490 Index

Indirect Coombs test, 205 Intussusception, 140 Indomethacin, 12t, 380, 380t Ionizing radiation, secondary immunodefi ciency Infants and, 65t bacterial meningitis in, 245t Ipratropium bromide, 92t, 137f feeding Iron-defi ciency anemia, 197t, 198–199 bottle weaning, 106 Iron overload, 171t enteral. See Enteral feeding Iron poisoning, antidote, 345t formula mixing, 46–47t Irradiated blood, 208 formula selection, 45–46 Irritant contact dermatitis, 111t vitamin and mineral supplementation, 35t Isolyte M, 158t fever without localizing signs in, 130f, 131f Isolyte P, 158t preterm. See Preterm infants Isonatremic dehydration, 155t refl exes, 271–272t ITP (idiopathic thrombocytopenic purpura), 202 skin and soft tissue infections in, 234 Itraconazole, 322t total parenteral nutrition. See Total parental Ivermectin, 120t nutrition (TPN) Infections J central venous catheter-related, 247–249, 247t, Jejunoileal atresia and stenosis, 473–475t 248f, 249t Jejunostomy, 38t. See also Enteral feeding fungal, 118–119t, 227 Jevity, 156t intravascular catheter-related, 246–247, 246t Jock itch (tinea cruris), 118t in neonates, 437–440t Joint pain, non-traumatic causes, 132–133t odontogenic, 108 Juvenile idiopathic arthritis (JIA), 329–330 pneumonia. See Pneumonia Juvenile myoclonic epilepsy, 278t skin, 233–234 urinary tract. See Urinary tract infections K Infectious rhinitis, 127 Kasabach-Merritt syndrome, 427t Infective endocarditis, prophylaxis, 80, 80t Kawasaki disease Infertility, in cystic fi brosis, 319t clinical fi ndings, 332t, 336–337t Infl ammatory bowel disease, 180, 180t, 181t. See also defi nition, 335 Crohn disease; Ulcerative colitis diagnosis, 335, 336t, 338f Infl uenza vaccine, 212t differential diagnosis, 336t Infuvite, 44t epidemiology, 335 Inhaled nitric oxide (iNO) incomplete, 337t for persistent pulmonary hypertension, 463t treatment, 337 for preterm infants, 373 Keppra, 103t Insulin Keratosis pilaris, 112t for diabetes mellitus Ketamine dose adjustment, 147 adverse effects, 18t regimens, 145–146, 146t dosing, 18t sliding scale, 146–147 onset and duration, 18t types, 145t pharmacologic properties, 18 for neonatal hyperglycemia, 403 for status asthmaticus, 92t Insulin aspart, 145t Ketoconazole Insulin detemir, 145t for seborrheic dermatitis, 111t Insulin glargine, 145t for tinea versicolor, 120t Insulin glulisine, 145t Ketogenesis disorders, 191t Insulin lispro, 145t Ketorolac, 12t Insulin NPH, 145t Kleihauer-Betke preparation, 433 Insulin pump, 146 Knee fractures, 308–309t Insulin regular, 145t Kohler’s disease, 310t Intermittent mandatory ventilation (IMV), 87t Konno-Rastan procedure, 81 Internal jugular vein (IJ), 26 Interventional radiology, pre-procedural diet, 5t L Intestinal lymphangiectasia, secondary Laceration repair, 30–31t, 30–32 immunodefi ciency in, 65t Lactated Ringer’s solution (LR), 158t Intracranial hemorrhage Lactic acidosis, in inborn errors of metabolism, 191t intraventricular, 450, 450t Lactose-free formulas, 46 MRI evaluation, 275t Lamellar body count, 355t neonatal seizures and, 448t Lamellar ichthyosis, 388t Intraosseous (IO) access, 24–25, 25t Lamotrigine, 280t Intraventricular hemorrhage, 450, 450t Landau-Kleffner syndrome, 279t Index 491

Langerhans cell histiocytosis, 391t Lymphadenitis Laryngomalacia, 477–478 clinical presentation, 231t Laryngoscope tube, 16t defi nition, 231 Lead poisoning differential diagnosis and management, 232f antidote, 345t infectious causes, 228t, 231 screening recommendations, 212t noninfectious causes, 228t Left ventricular hypertrophy (LVH), 74 Lymphadenopathy Length. See Height/length defi nition, 231 Lennox-Gastaut syndrome, 279t differential diagnosis and management, 232f LET (lidocaine, epinephrine, tetracaine) infectious causes, 228t solution, 11t noninfectious causes, 228t, 231 Leukocyte esterase, in urine, 255t Lymphocytes, 201t Leukocyte-reduced blood, 207 Lymphocytosis, 202t Leukocytes, total, 201t Lymphogranuloma venereum, 54t Leukocytosis, 202, 202t Lysosomal metabolism disorders, 191t Leukotriene receptor antagonist, 63t, 316t Levalbuterol, 91t, 316t M Levetiracetam, 280t, 282t Macrocephaly, 191t, 192 Levofl oxacin, 224t Macrocytic anemia, 197 Levonorgestrel, 59 Macrolides, 222t, 440t Levothyroxine, 147 Macular stain, 387t Lice, 120t Macule, 109 Lichenifi cation, 109 Magnesium, 43t, 77 Lidocaine, 12t Magnesium sulfate, 92t Limp, 132–134 Magnetic resonance angiography (MRA), 274t Lincosamides, 223t Magnetic resonance imaging (MRI) Linezolid, 223t, 322t, 440t brain, 274t Lip laceration, 31t fetal, 359 Lipids, in total parenteral nutrition, 42 in intracranial hemorrhage, 275t Lipopeptides, 226t sedated, pre-procedural diet, 5t Lisfranc fracture, 310t sequences and potential applications, 275t Lithium, antidote, 345t signal intensity, 274t Little league elbow, 304t Magnetic resonance spectroscopy (MRS), 274t Little league shoulder, 303t Magnetic resonance venogram (MRV), 274t Liver failure. See also End-stage liver disease (ESLD) Malabsorptive syndromes, 179 in cystic fi brosis, 319t Malassezia furfur, 119t fulminant, 171–172, 172f Mallampati classifi cation, 15, 16t in inborn errors of metabolism, Mallet fi nger, 307t 189, 191t, 192 Malnutrition in secondary immunodefi ciency, 64t in cystic fi brosis, 319t, 320 L.M.X. 4%, 11t defi nition, 49 Local anesthetics secondary immunodefi ciency in, 65t injectable, 12t severity determination, 183t for laceration repair, 30–31t Waterlow criteria, 49 topical, 11–12t Malrotation Lorazepam clinical presentation, 140, 473–474t adverse effects, 17t diagnosis, 409t dosing, 17t epidemiology, 473t onset and duration, 17t management, 409t, 474–475t for seizures, 280t pathophysiology, 140, 473t for status epilepticus, 104f Manganese, for direct hyperbilirubinemia, 420t Low birth weight infants, 369. See also Mannitol, 101, 102 Preterm infants Maple syrup odor, 189t Low-carbohydrate formulas, 46 Marijuana, 341t, 342t Low-molecular-weight heparin (LMWH), 205t Mast cell stabilizer, 63t Low T3 syndrome, 149 Mastoiditis, 126–127 Lower motor neuron lesions, 272t, 452t May-Hegglin anomaly, 427t L:S ratio, 355t McBurney’s point, 139 LSD, 341t Mead Johnson powder formulas, 46–47t Lucey-Driscoll syndrome, 412t Mean cell hemoglobin (MCH), 196t Lumbar puncture, 23–24, 23t, 24f Mean cell volume (MCV), 196t Lyme disease, 115t Measles (rubeola), 116t 492 Index

Measles, mumps, rubella vaccine, Methylprednisolone 212t, 215t adverse effects, 316t Mechanical ventilation for anaphylaxis, 61t adjustments affecting oxygenation and for asthma, 316t ventilation, 88t equivalencies, 9t blood gases and clinical parameters in, 89 for status asthmaticus, 91t for bronchopulmonary dysplasia, 466t Metoclopramide, 292t complications, 89 Metronidazole, 226t diuresis and metabolic alkalosis in, 89 for bacterial vaginosis, 53t fl uids in, 88 for pelvic infl ammatory disease, 56t modalities, 86–87t, 87–88, 88t for T. vaginalis infection, 53t in neonates, 374–375t Miconazole, 53t for respiratory distress syndrome, 459t Microcephaly, 191t, 192 sedation and analgesia in, 88 Microcytic anemia, 197f, 197t stepwise approach, 86–90 Midazolam weaning and extubation, 89–90, 90t adverse effects, 17t Meckel’s diverticulum, 140 dosing, 17t Meconium, delayed passage of, 409–410 onset and duration, 17t Meconium aspiration, 366–367, 366f, 464–465t for status epilepticus, 103t Meconium ileus, 320t, 409t weaning from, 20 Meconium plug, 409t Midgut volvulus, 140, 473–475t Medial epicondyle traction apophysitis, 304t Migraine headaches Medulloblastoma, 296–297t complications, 282 Melanocytic nevus, congenital, 387t diagnostic criteria, 281t Membranoproliferative glomerulonephritis, 260t prophylaxis, 282t Menarche, 151 status migrainosus, 283 Meningitis treatment, 282t aseptic, 243, 245 Milia, 386t defi nitions, 242 Miliaria crystalline, 386t diagnosis, 243–244, 244t Miliaria rubra, 386t etiology, 243t Milk of Magnesia, 179 follow-up, 246 Milk scan, pre-procedural diet, 5t isolation and prophylaxis, 246 Milrinone management, 244–245, 245t in neonatal resuscitation, 365t neonatal, 441–442 for shock, 96, 96t prognosis, 246 Minerals, in total parenteral nutrition, 44t risk factors, 243t Minimal change disease, 259t Meningococcal vaccine, 212t Minocycline, 223t Meningococcemia, 115t Mite infestations, 119–120t Mercaptopurine, 298t Mitochondrial disorders, 191t Mercury poisoning, antidote, 345t Mixed connective tissue disease (MCTD), 329t Meropenem, 221t, 323t, 440t Molluscum contagiosum, 118t Metabolic acidosis Mometasone furoate, 123t, 124t additional testing, 164–165t Mongolian spot, 387t differential diagnosis, 164–165t Monobactams, 221t general approach, 166f, 167–168 Monocytes, 201t in inborn errors of metabolism, Monocytosis, 202t 189f, 191t Monteggia fracture, 306t neonatal, 189, 189f Montelukast sodium, 63t, 316t with partial compensation, 167–168t Moraxella, 125, 128 Metabolic alkalosis Morbilliform drug reaction, 120t differential diagnosis, 165t Moro refl ex, 271t general approach, 166f, 167–168 Morphine in mechanical ventilation, 89 dosing, 13t, 14t, 457 with partial compensation, 167–168t in neonates, 457 Metacarpal fracture, 307t in patient-controlled analgesia, 14t Metatarsal fracture, 310t Mosteller’s formula, body surface area, 4 Methadone, 13t, 14t Mothball odor, 341t Methanol, antidote, 345t Motor testing, 269t Methemoglobinemia, 346t Mousy odor, 189t Methimazole, 149 Moxifl oxacin, 225t Methotrexate, 298t, 423t MRA (magnetic resonance angiography), 274t Index 493

MRI. See Magnetic resonance imaging (MRI) Neonatal resuscitation (cont.) MRS (magnetic resonance spectroscopy), 274t risk factors, 363 MRV (magnetic resonance venogram), 274t triage, 366t Mucolytics, 321t umbilical catheter placement, 365–366 Mucositis, 292 Neonatal tooth, 108 Multiple sclerosis (MS), 285t Neonates Murmur, asymptomatic, 380t abnormal rashes in, 388–391t Muscles, principal, 272–273t acute kidney injury in, 445–446 Muscular dystrophy, congenital, 453t anemia in, 431–433 Musculoskeletal complaints, differential diagnosis, 37 antibiotic use in, 437–440t Mustard procedure, 82, 82f Apgar score, 349t Myocarditis, 70–71, 70t apnea in. See Apnea, neonatal Myoclonus bacterial meningitis in, 245t benign neonatal sleep, 449t benign rashes in, 386–387t stimulus-evoked, 449t blood product transfusion in, 433t, 434–436t bronchopulmonary dysplasia in, 465–468t N circumcision of, 350 N-acetylcysteine, 322t complications of maternal medical conditions, Nafcillin, 219t, 437t 354, 355, 357t Nailbed laceration, 31t complications of maternal substance abuse, 357t Nalidixic acid, 224t congenital cystic adenomatoid malformation Naloxone, 13, 346t, 365t in, 475–477t Naproxen, 12t congenital diaphragmatic hernia in, 475–477t

Nasal cannula, for O2 delivery, 84t conjunctivitis in, 443–444 Nasal continuous positive airway pressure cyanosis in, 353t (NCPAP) delayed passage of meconium in, 409–410 for neonatal apnea, 470 discharge criteria, 376 for respiratory distress syndrome, 459t discharge planning considerations, 376–377t Nasal decongestants, 63t duodenal atresia and stenosis in, 473–475t Nasoduodenal feeding, 38t. See also Enteral feeding early discharge criteria, 349–350 Nasogastric feeding, 38t. See also Enteral feeding encephalopathy in, 450–452 Nasogastric tube insertion, pre-procedural diet, 5t extracranial bleeding sites in, 352f Nasojejunal feeding, 38t. See also Enteral feeding gastric aspirates in, 414–415 Nasojejunal tube insertion, pre-procedural diet, 5t gastroesophageal reﬂ ux disease in, 410–411 Natal tooth, 108 gastroschisis in, 471–472t Nausea. See Vomiting/nausea group B streptococcal disease in. See Group B Neck laceration, 31t streptococcus (GBS) infections Necrotizing enterocolitis (NEC) hydrocephalus in, 453–454 clinical presentation, 416t hyperbilirubinemia in. See Hyperbilirubinemia diagnosis, 417 hypercalcemia in, 397–398, 397f differential diagnosis, 417 hyperglycemia in, 403–404 management, 418 hyperkalemia in, 395–396 platelet consumption in, 427t hypernatremia in, 406–407 prognosis, 418 hypertension in, 446–447 risk factors, 415–416 hypocalcemia in, 398–401 staging, 416–417t hypoglycemia in, 188f, 404–406 Needle aspiration/decompression hyponatremia in, 407–408 of pneumopericardium, 461t hypotonia in, 452 of pneumothorax, 21, 21t, 460t intraventricular hemorrhage in, 450, 450t Neisseria gonorrhea, 53t jejunoileal atresia and stenosis in, 473–475t Neisseria meningitidis, 115t laryngomalacia in, 477–478 Nemaline rod myopathy, 453t malrotation in. See Malrotation Neocate Infant, 157t meconium aspiration in, 366–367, 366f, 464–465t Neocate Jr., 157t meningitis in, 441–442 Neonatal cephalic pustulosis (neonatal acne), necrotizing enterocolitis in. See Necrotizing 386t enterocolitis Neonatal lupus erythematosus, 388t neuromuscular disorders in, 453 Neonatal resuscitation neuromuscular maturity assessment, 348 algorithm, 364f nonsterile delivery, 353 endotracheal tube sizes, 365t omphalocele in, 471–472t medications for, 364–365t pain management in, 456–457 preparation, 363 persistent pulmonary hypertension in, 462–464t 494 Index

Neonates (cont.) Noninvasive positive pressure ventilation, 86t physical exam, 350–351t Nonopioid analgesics, 12, 12t. See also speciﬁ c drugs

physical maturity assessment, 348 Nonrebreather face mask, for O2 delivery, 85t pulmonary air leak syndromes in, 459–462 Norepinephrine, 96t, 97f respiratory distress in, 353t Normal saline (NS), 158t, 264t respiratory distress syndrome in, 458–459t Norwood procedure, 81, 82f resuscitation. See Neonatal resuscitation Notes routine care, 348–349 discharge summary, 2 seizures in, 448–449 on-service, 1 sepsis evaluation and empiric treatment, 369f progress, 1–2 skin and soft tissue infections in, 234 Nursemaid’s elbow, 305t stridor in, 352t Nutramigen Lipil, 157t thrombocytopenia in, 425–428 Nutren 1.0, 156t transient tachypnea in, 458, 458t Nutren 2.0, 156t vomiting in, 352t Nutren Jr., 156t Nephritic syndromes Nystatin, 119t management, 261 overview, 258, 259t O primary, 260t Obstructive lung disease, 326t. See also Asthma; prognosis, 261 Cystic fi brosis secondary, 260t Obstructive shock, 94t, 95t workup, 260 Obstructive sleep apnea, 128, 129f Nephrogenic diabetes insipidus, 150–151t Obturator sign, 139 Nephrotic syndromes Oculomotor nerve, 268t complications, 261–262 Odontogenic infections, 108 management, 261 Odors overview, 258, 259–260t abnormal, 189–190t primary, 260t of agents of intoxication, 341t prognosis, 261 Ofl oxacin, 224t secondary, 260t Old fi sh odor, 189t secondary immunodefi ciency in, 65t Olecranon fracture, 306t workup, 260–261 Olfactory nerve, 268t Nepro, 157t Omalizumab, 316t Nesiritide, 73 Omphalocele, 471–472t Nestle powder formulas, 46–47t On-service notes, 1 Netherton syndrome, 389t Oncologic emergencies Neuroblastoma, 295–296 fever and neutropenia, 289 Neuroimaging modalities, 274t hyperleukocytosis, 291 Neuroleptics, antidote, 346t hypersensitivity reactions to infusions, Neurologic exam, 268–270 290–291t Neuromuscular blockade, in traumatic brain spinal cord compression, 289–290 injury, 102 tumor lysis syndrome, 289 Neuromuscular disorders, 453 Ondansetron, 292t Neuromyelitis optica (NMO), 285t, 286 Ophthalmia neonatorum, 443–444 Neutropenia Opioid analgesics. See also specifi c drugs in inborn errors of metabolism, 189 antidote, 346t as oncologic emergency, 289 conversion between, 14, 14t Neutrophilia, 202t dosing, 13t, 14t Neutrophils, 201t indications, 13 Nevus sebaceous, 387t in patient-controlled analgesia, 13, 14t Nevus simplex, 387t toxidrome, 345t Newborns. See Neonates urine testing, 342t Nitric oxide, inhaled (iNO) weaning from, 14–15 for persistent pulmonary hypertension, 463t Optic nerve, 268t for preterm infants, 373 Oral hygiene, 106, 212t Nitrite, in urine, 256t Oral rehydration Nitroimidazoles, 226t solutions and formulas, 156–157t Nodule, 109 strategies, 155–156 Non-stress test, 360 Orders Nonbullous congenital ichthyosiform admission, 1 erythroderma, 388t discharge, 1 Nonimmune fetal hydrops, 421–422t preoperative, 1 Index 495

Organ systems, embryonic development from Pedialyte, 156t weeks 3 to 7, 186t PediaSure, 156t Organic acidemias, 194f Pediatric Appendicitis Score (PAS), 139t Organic acidurias, 191t Pediatric systemic lupus erythematosus (pSLE), Organophosphates, antidote, 346t 329t, 331–332 Ornithine transcarbamylase (OTC) defi ciency, Pediculosis pubis, 56 193t, 194f Pediculus capitis, 120t Orogastric feeding, 38t. See also Enteral feeding PEG 3550, 179 Osgood-Schlatter disease, 308t PEG-electrolyte solution, 179 Osteochondritis dissecans, femur, 309t Pelvic examination, 51–52, 51t Osteopenia of prematurity, 401–403 Pelvic fracture, 308t Osteopetrosis, infantile, 400t Pelvic infl ammatory disease, 55–56t Ostium primum, 66 Penicillin G, 218t Ostium secundum, 66 Penicillin G benzathine, 54t, 218t Otitis media, acute, 125–126 Penicillin GK, 437t Otitis media with effusion (OME), 126 Penicillin V, 218t Oxacillin, 219t Penicillins, 218–219t Oxazolidinones, 223t, 440t Penis Oxcarbazepine, 280 laceration, 31t Oxycodone, 13t, 14t noncircumcised, care of, 350 Oxygen delivery modes, 84–85t Pentobarbital, 18, 18t, 103t Percutaneous umbilical blood sampling, 359 P Perianal streptococcal dermatitis, 390t P. aeruginosa, in cystic fi brosis, 318t, 322–323t Pericardial disease, 71–72, 71f Pacemakers, 77 Pericardiocentesis, 462 Packed cell volume, 196t Peripheral nerves, 270–271f Packed red blood cells (PRBCs), 206t, Permethrin, 120t 433t, 434t Peroxisomal metabolism disorders, 191t Pain assessment, 11, 11f Persistent pulmonary hypertension, 462–464t Pain management PG, 355t in neonates, 456–457 pH, urine, 254t nonpharmacologic, 11 Phalanx fractures, 307t, 311t pharmacologic. See also specifi c drugs Phencyclidine, 342t nonopioid analgesics, 12, 12t Phenobarbital, 104f, 280t opioid analgesics. See Opioid analgesics Phenotype matching, extended, 206 patient-controlled analgesia, 13, 14t Phenytoin/fosphenytoin, 279t, 423t topical preparations, 11–12t Phosphate defi ciency, 152t Palivizumab, 378 Phosphate enema, 179 Palmar grasp, 272t Phosphorus, daily requirement, 43t Palmomental refl ex, 270t Photodrug reaction, 123t Pancreas, annular, 140 Phototherapy, for hyperbilirubinemia, Pancreatic enzyme replacement therapy, 321t 413f, 414t Pancreatic insuffi ciency, in cystic fi brosis, 318t Physical abuse, 141–142 Pancreatitis, 176–178t Pigtail catheter placement, 460t, Pancrelipase, 321t 461–462 Pancytopenia, 202t Pinna laceration, 31t Papile’s grading, intraventricular hemorrhage, 450t Piperacillin, 219t, 437t Papular acrodermatitis, 117t Piperacillin–tazobactam, 219t Papule, 109 Pityriasis alba, 112t Paracentesis, in ascites, 174 Pityriasis rosea, 112t Paracoccidioidomycosis, 227 Plan B, 59 Paramyxovirus, 116t Plaque, 109

Partial rebreathing face mask, for O2 delivery, 85t Plasma glucose, 143t Parvovirus B19, 116t Plasma transfusion, 207, 435t Patch, 109 Plasma volume (PV), 208 Patellar fracture, 308t Platelet disorders, 203f, 427t Patent ductus arteriosus (PDA), Platelet transfusion, 206t, 207, 435t 67, 379–380 Pleural effusions, 239t Patient-controlled analgesia (PCA), 13, 14t Pleural ﬂ uid analysis, 236t PCP, 341t Pneumococcal vaccine, 213t, 214t Peak ﬂ ow monitors, 313 Pneumococcus, 125, 127 Pear odor, 341t Pneumomediastinum, 461t 496 Index

Pneumonia Preeclampsia, 356 community-acquired Pregabalin, 280t complications, 237 Pregestimil, 157t defi nition, 234 Pregnancy diagnosis, 235–236, 236t diabetes mellitus during, 355, 357t, 399t etiologic agents, 234–235t fetal chromosomal abnormalities screening inpatient management, 237–239 during, 354, 358, 358t outpatient management, 237t fetal lung maturity evaluation during, 355, 355t risk factors, 235t genetic diagnosis during, 358–359 in cystic fi brosis, 235t, 318t, 319 hypertension in, 356, 356t nosocomial or hospital-associated, 239 immunization during, 216t Pneumopericardium, 461t teratogenic agents in, 187, 423–424t Pneumothorax ultrasound screening during, 354 in cystic fi brosis, 320t Prehn’s sign, 132t needle decompression, 21, 21t Prenatal care. See Pregnancy in neonates, 460t Preoperative orders, 1 Poisoning Prescriptions, essential components, 2 antidotes, 345–346t Pressure regulated volume control (PRVC, VC+), 87t commonly ingested substances, 340 Pressure support (PS) ventilation, 374t history, 341 Preterm infants initial evaluation, 340f admission orders, 372–373 physical exam fi ndings, 342–344t cardiovascular care, 370–371t secondary survey, 341 catch-up times, 4 substances detectable with conventional CSF profi les, 442t radiography, 342t developmental follow-up, 378 substances with unique odors, 341t discharge criteria, 376 toxidromes, 344–345t discharge planning considerations, 376–377t urine color changes associated with, 342t feeding urine testing, 342t enteral, 39 Poliovirus vaccine, 212t, 215t formulas, 46 Polyarteritis nodosa, 332t total parenteral nutrition. See Total parental Polycythemia nutrition (TPN) clinical presentation, 428, 429t vitamin and mineral supplementation, 35t defi nition, 428 fl uid/electrolyte management, 371t differential diagnosis, 428t growth chart, 50f exchange transfusion for, 430t. See also Exchange hypothyroxinemia in, 394–395, 394f transfusion infection control, 372t management, 429, 429t nitric oxide administration, 373 in nonphysiologic hyperbilirubinemia, 412t nutrition, 372t Polymyositis, 329t osteopenia in, 401–403 Portal hypertension, 172 respiratory care, 370t Potassium retinopathy of prematurity in, 454–455, 454f conversion, 43t RSV prophylaxis, 378 daily requirement, 43t, 153 secondary immunodefi ciency in, 64t ECG changes and, 76 sepsis evaluation and empiric treatment, 370f Potassium channel blockers, as antiarrhythmics, surfactant administration, 373–374t 77t ventilation modes, 374–375t Potts shunt, 81 PRICEMMMS mnemonic, for treatment of acute Poxvirus, 118t musculoskeletal injury, 301–302 PRBCs (packed red blood cells), 206t, 433t, 434t Primary immunodefi ciency, 63, 63t Precocious puberty, 151 Primitive refl exes, 270t, 271–272t Prednisolone Progress note (SOAP note), 1–2 adverse effects, 316t Promethazine, 292t for asthma, 316t Propofol, 18, 19t, 103t equivalencies, 9t Propranolol, 282t for status asthmaticus, 91t Propylthiouracil, 149

Prednisone Prostaglandin E1, 384–385 adverse effects, 316t Protein, DRI by age, 41–42t for asthma, 316t Protein hydrolysate formulas, 46 as chemotherapy agent, 299t Proteinuria, 255t, 257–258 equivalencies, 9t Proton pump inhibitors (PPIs), 169 for status asthmaticus, 91t Pseudohyperkalemia, 158 Index 497

Pseudohypoaldosteronism, 392t Respiratory syncytial virus (RSV), Pseudohypokalemia, 160 prophylaxis, 378 Pseudomonas, 127 Restrictive lung disease, 326t pSLE (pediatric systemic lupus erythematosus), Resuscitation, neonatal. See Neonatal 329t, 331–332 resuscitation Psoriasis, 113t, 391t Retinitis pigmentosa, 192 Pubarche, 151–152 Retinoic acid, 424t Puberty, 151–152 Retinopathy of prematurity (ROP), Pulmocare, 157t 454–455, 454f Pulmonary air leak, in neonate Retropharyngeal abscess, 136–137t complications, 460–461t rhDNase, 321t management, 460–461t Rhinitis, 127 pathophysiology, 459–460 Rickets, 152t procedures, 461–462 Rickettsia rickettsii, 115t risk factors, 459 Rifampin, 226t syndromes, 460–461t Rifamycins, 226t Pulmonary artery banding, 82 Right ventricular hypertrophy (RVH), 75 Pulmonary atresia with intact ventricular septum Riley–Day syndrome, 453t (PA/IVS), 69–70, 69f RNC (radionuclide cystogram), 242t Pulmonary blood fl ow, abnormal, 381 Rocky Mountain spotted fever, 115t Pulmonary function testing (spirometry), Romberg test, 269 325–326 Root refl ex, 272t Pulmonary hypoplasia, 475–477t Roseola (exanthem subitum), 116t Pulmonary interstitial emphysema, 461t Ross procedure, 82 Pustule, 109 Rotavirus, 213t, 214t PV (plasma volume), 208 Rotten egg odor, 341t Pyloric stenosis, 140 Rovsing’s sign, 139 Rubella (German measles), 116t R Rubeola (measles), 116t Rabies prophylaxis, 135 Rumination, 169 Radial head subluxation, 305 Radionuclide cystogram (RNC), 242t S Radius fractures, 305t Salicylism, 345t Ranitidine, 61t Salter-Harris fracture classifi cation, Rastelli operation, 82 302, 302f Reactive arthritis, 327t Sandifer syndrome, 169 Red blood cells (RBCs) Sarcoptes scabiei, 119–120t normal values, 196t Sarnat stages of hypoxic-ischemic encephalopathy, transfusion, 206, 206t, 208 451t in urine. See Hematuria Scabies, 56, 119–120t Red urine, 252–254, 253f Scale, 109 Refeeding syndrome, 59 Scalp laceration, 30t Rehydralyte, 156t Scapular fracture, 303t Renal fl ow study, pre-procedural diet, 5t Scar, 109 Renal salt wasting (cerebral salt wasting), 150t Scarlet fever, 114t Renal scan, pre-procedural diet, 5t Schwartz formula, for GFR estimate, 250 Renal stones, 140 Scleroderma, 329t Renal ultrasound, 242t Screening recommendations, 209–211t, 212t Respiratory acidosis, 165–168 Scrotum Respiratory alkalosis, 165–168, 191t laceration of, 31t Respiratory distress, in neonates, 353t pain and swelling in, 131–132t Respiratory distress syndrome (RDS), 458–459t Seborrheic dermatitis, 111t, 391t Respiratory failure Secondary immunodefi ciency, 64–65t classifi cation, 83 Sedation clinical predictors, 83 continuum of, 15 management discharge criteria, 19, 20t mechanical ventilation. See Mechanical emergency equipment, 16, 16t ventilation medications, 16–19, 17t, 18–19t noninvasive ventilation modalities, 85–86t monitoring following, 19 oxygen delivery modes, 84–85t patient preparation, 15–16, 15t, 16t pathophysiology, 84f Sedative-hypnotics, toxidrome, 345t workup algorithm, 83f Segmental fracture, 302 498 Index

Seizures. See also Epilepsy SJS (Stevens-Johnson syndrome), 122t breakthrough in known epilepsy, 277 Skin infections, 233–234 classifi cation, 275–276t Skin lesions, 109–110t evaluation of fi rst nonfebrile, 276–277 Sleeve fracture, 308t neonatal, 188, 448–449 Snoring, 129f in poisonings, 343t Snout refl ex, 270t practice parameters, 275 SOAP equipment, for sedation, 16 simple febrile, 276 SOAP note (progress note), 1–2 Selenium sulfi de shampoo, 118t Sodium, 43t, 153 Self-mutilation, 192 Sodium bicarbonate, in neonatal resuscitation, 365t Senna, 179 Sodium channel blockers, 77t Senning procedure, 82 Soft tissue infections, 233–234 Sensory testing, 269 Soy-based formulas, 46 Sepsis, 94t Specifi c gravity, urine, 254t in preterm infant, evaluation and empiric Spinal accessory nerve, 268t treatment, 370f Spinal cord compression, 289–290 in term infant, evaluation and empiric treatment, Spinal muscular atrophy type 1, 453t 369f Spirometry (pulmonary function testing), 325–326 Septic arthritis, 134t, 327t Spironolactone, 174 Septic shock, 94t Splenic sequestration crisis, 199t Serum sickness-like reaction, 121t Spondylolisthesis, 301 Severe sepsis, 94t Spondylolysis, 301 Sever’s disease, 310t Sporotrichosis, 227 Sexual development, 151–152 Sprains, 301–302 Sexually transmitted infections, 53–54t, 212t Staphylococcal scalded skin syndrome, 115t, 389t Shaken baby (shaken impact) syndrome, 142 Staphylococcus aureus Shingles (herpes zoster), 117t in cellulitis, 114t Shock in cystic fi brosis, 318t, 322–323t classifi cations, 95–96t in folliculitis, 113t clinical fi ndings, 94t in impetigo, 113t clinical pearls, 96, 98 in mastoiditis, 127 defi nition, 93 in skin abscess, 114t management, 95–96t, 97f superinfection in eczema, 110t in sepsis, 94 StAR (acute steroid regulatory protein) defi ciency, stages, 93 392t Shoulder dislocation, 303t Startle refl ex, 271t Shoulder fractures, 303t STATS, for intubation preparation, 86 SI units, laboratory value conversion table, 8t Status asthmaticus SIADH (syndrome of inappropriate antidiuretic clinical respiratory score, 90–91t hormone), 150t defi nition, 90 Sick euthyroid syndrome, 149 management Sickle cell disease advanced, 92–93 diagnosis, 199 clinical pearls, 93 health maintenance in, 200t fi rst-line, 91t immunizations in, 217t second-line, 92t pneumonia in, 235t risk factors for ICU admission and sudden secondary immunodefi ciency in, 64t death, 90 signs and symptoms, 199–200t symptoms, 90 treatment, 199–200t Status epilepticus, 102–103 Similac Advance, 156t causes, 103 Similac HMF, 48t clinical pearls, 103 Simple febrile seizure, 276 management algorithm, 104f Simple partial seizure, 275t. See also Seizures medications, 103t SIMV (synchronized intermittent mandatory types, 103 ventilation), 87t, 88t, 374t workup, 105f Sinding-Larsen-Johansson syndrome, 308 Status migrainosus, 283 Sinus tachycardia, 75t Steatohepatitis, 171t Sinus venosus, 66 Stevens-Johnson syndrome (SJS), 122t Sinusitis, 128, 319t Stiff-man syndrome, 449t SIRS (systemic infl ammatory response syndrome), Stimulant laxatives, 179 94t Stimulus-evoked myoclonus, 449t Sjögren’s syndrome, 329t Strains, 301–302 Index 499

Streptococcus pneumonia, 128 β-Thalassemia major, 199t Streptococcus pyogenes, 113t β-Thalassemia minor, 197t, 199t Streptomycin, 224t Thelarche, 151–152 Stress factors, energy expenditure, 41t Thiazides, for bronchopulmonary dysplasia, 467t Stridor, 135–137, 352t Thioguanine, 298t Stroke, in sickle cell disease, 200t Thrombocytopathy, 203f Subclavian vein (SCV), 26 Thrombocytopenia Substance abuse alloimmune, 426–427t in pregnancy, 357t autoimmune, 426–427t street names of drugs of abuse, 341t congenital, 428 urine testing for, 342t with decreased platelet survival, 427t Sucrose, oral, 12, 456 differential diagnosis, 203f, 425f Sulfonamides, 225t idiopathic, 202 Sulphur odor, 190t in inborn errors of metabolism, 189 Sumatriptan, 282t in neonates, 425–428 Superior cavopulmonary anastomosis, 81, 81f Thrombocytopenia-absent radii (TAR) syndrome, Suplena, 157t 428 Supracondylar fracture, elbow, 304t Thromboembolism, 205t Supraventricular tachycardia (SVT), 75t Thrombophilia, 205t Surfactant, for preterm infants, 373–374t Thumb fractures, 306–307t Sutures Thyroid storm, 149 cranial, 4 Thyroiditis, 147, 149 for laceration repair, 30–31t Ticarcillin, 219t Swallow study, pre-procedural diet, 5t Ticarcillin/clavulanic acid, 323t Sweat chloride test, 317, 317t Ticarcillin–clavulanate, 219t Sweaty feet odor, 190t Tinea capitis, 118t Synchronized intermittent mandatory ventilation Tinea corporis, 118t (SIMV), 87t, 88t, 374t Tinea cruris, 118t Syncope, 79 Tinea pedis, 118t Syndrome of inappropriate antidiuretic hormone Tinea versicolor, 119t (SIADH), 150t Tinidazole, 53t Synovial fl uid, evaluation, 327t Tobramycin, 224t, 322t, 438t Syphilis, 54t, 212t Toddler fracture, 309t Systemic infl ammatory response syndrome TOF (tetralogy of Fallot), 67–68, 67f, 81, 81f (SIRS), 94t Tonic neck refl ex, 272t Systemic lupus erythematosus, 329t, 331–332, 388t Topical anesthetics, 11–12t Topiramate, 280t, 282t T Total anomalous pulmonary venous return Tachycardia, 75t, 76f (TAPVR), 68, 68f Takayasu arteritis, 332t Total blood volume (TBV), 208 Tanner stages, 151–152t Total parental nutrition (TPN) TAPVR (total anomalous pulmonary venous carbohydrate/amino acid requirements and return), 68, 68f rate, 42, 43t TAR (thrombocytopenia-absent radii) syndrome, complications, 44 428 electrolyte requirements, 43t TBV (total blood volume), 208 energy requirement, 40–41, 40t, 41t Teeth, 107, 107f, 108 fi nal check, 44–45 Teething, 107 intravenous fl uid requirement, 39–40, 40t Temperature, conversion formulas, 4 laboratory monitoring, 45t TEN (toxic epidermal necrolysis), 122t lipid requirements and rate, 42 Tension type headache, 283 protein requirement, 41–42t Teratogens, 187, 423–424t stress factors, 41t Terbutaline, 92t vitamins, minerals, and trace elements, 44t Terconazole, 53t Toxic epidermal necrolysis (TEN), 122t Testicular torsion, 131–132t Toxic shock syndrome, 115t Tetanus prophylaxis, 32, 32t Toxicology. See also Poisoning Tetracycline, 223t collection tube colors, 7t Tetracyclines, 223t SI laboratory value conversion table, 8t Tetralogy of Fallot (TOF), 67–68, 67f, 81, 81f Toxidromes, 344–345t TGA (transposition of the great arteries), 68, 68f, Trace elements, in total parenteral nutrition, 44t 81, 82, 82f Traction apophysitis of proximal humerus, 303t α-Thalassemia, 199t Transient neonatal pustular melanosis, 386t 500 Index

Transient synovitis, 134t Upper GI series, pre-procedural diet, 5t Transient tachypnea of the newborn (TTN), Upper motor neuron lesions, 272t, 452t 458, 458t Urea cycle, 194f Transposition of the great arteries (TGA), 68, 68f, Urea cycle defects, 191t, 193–194t, 195f 81, 82, 82f Uremia, secondary immunodefi ciency in, 64t Trauma, nonaccidental, 141–142 Urinalysis, 254–256t Traumatic arthritis, 327t Urinary tract infections Traumatic brain injury, 101–102 defi nition, 239 Treponema pallidum, 54t diagnosis, 240, 241t Triamcinolone, 10t etiologic agents, 240 Triamcinolone acetonide, 123t, 124t imaging modalities, 242t Trichomonas vaginalis infection, 52–53t management, 241 Tricuspid atresia, 69, 69f prevention, 241 Tricyclic antidepressants risk factors, 239 antidote, 346t Urine poisoning/overdose, 347t discoloration, 190t, 342t toxidrome, 345t organic acid analysis, 193 Trigeminal nerve, 268t unusual odors, 189–190t Trimethoprim/sulfamethoxazole, 225t, 322t Urine culture, 241t Trisomy 13, 422–423t Ursodeoxycholic acid (UDCA), 420t Trisomy 18, 422–423t Urticaria, 61–62, 120t Trisomy 21 (Down syndrome), 64t, 183, 184–185t, 422–423t V Trochlear nerve, 268t Vaccines/vaccinations. See Immunizations Truncus arteriosus, 68–69, 68f, 82 Vaginitis, 52–53t Trunk laceration, 31t Vagus nerve, 268t Tube colors, for lab samples, 6, 7t Valacyclovir, 55t Tuberculosis screening, 212t Valgus, 301 Tuberculous arthritis, 327t Valproic acid, 280t, 282t, 423t Tumor, 109 Valvotomy, 82 Tumor lysis syndrome, 289 Valvuloplasty, 82 Turner syndrome, 64t Vancomycin, 222t, 323t, 438t Tympanostomy tube, 126 Varicella zoster virus, 116t, 117t Type 1 diabetes mellitus. See Diabetes mellitus Varicella zoster virus immunization, 212t, 215t Type 2 diabetes mellitus. See Diabetes mellitus Varices, 173 Varus, 301 U Vasculitides, 332t, 334f Ulcer, 109 Vasopressin, for shock, 96, 96t Ulcerative colitis VATER/VACTERL association, 187 clinical features, 180t Vaughan-Williams classifi cation, antiarrhythmics, 77t defi nition, 179 Ventricular septal defect (VSD), 66

endoscopic features, 181t Venturi mask, for O2 delivery, 84t epidemiology, 180t Verruca vulgaris, 117t prognosis, 182 Very low birth weight infants, 369. See also Preterm radiographic features, 181t infants treatment, 181–182, 182t Vesicle, 109 Ulna fractures, 306t Vesicoureteral refl ux (VUR), 262–263 Ultrasonography Vinblastine, 299t cranial, 274t, 376t Vincristine, 299t fetal, 354, 357, 358 Vision screening, 212t pre-procedural diet, 5t Vitamin A, for prevention of bronchopulmonary Ultraviolet B exposure, secondary dysplasia, 466t immunodefi ciency and, 65t Vitamin D defi ciency, 152t, 400t, 402t Umbilical artery catheterization (UAC), 27–29, Vitamins, in total parenteral nutrition, 44t 28f, 28t, 365 Voiding cystourethrography (VCUG), 5t, 242t, 262 Umbilical blood sampling, percutaneous, 359 Volume guarantee (VG) ventilation, 374t Umbilical vein catheterization (UVC), 28f, 29–30, Volvulus, 410t 29t, 365–366 Vomiting/nausea Unconjugated (indirect) hyperbilirubinemia, chemotherapy-related, 291–292 175–176 with enteral feeding, 39t Unfractionated heparin (UFH), 205t in neonates, 352t Upper extremity fracture, 303–306t von Willebrand disease, 204t Index 501

W Wintergreen odor, 341t Warfarin, 205t, 423t Wiskott-Aldrich syndrome, 427t Waterlow criteria, malnutrition, 49 Withdrawal, 342–344t Waterston shunt, 81 World Health Organization (WHO), oral Weakness, childhood, 286–287t rehydration solution, 156t Wegener granulomatosis, Wounds 329t, 332t repair, 30–31t, 30–32 Weight tetanus prophylaxis, 32, 32t by age for boys, 2t Wrist fracture, 306t by age for girls, 3t at birth, 3 X conversion, 4 X-linked hypophosphatemia, 152t by gestational age, 50f Xanthines, for neonatal apnea, 469 rate of gain, 3 Werdnig–Hoffmann disease, 453t Y West syndrome, 278t Yeast vaginitis, 52–53t Wheal, 109 Wheezing, 312 Z White blood cells (WBCs) Zaﬁ rlukast, 316t normal values, 201t Zinc, oral, 156 in urine, 256t Zolmitriptan, 282t Wilson’s disease, 171t Zonisamide, 280t