Texas Children's Hospital Handbook of Pediatrics and Neonatology

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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 confirm 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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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 influential 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 unparalleled 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 “baffled the best minds at the university.” A wink and an elbow from Dr. Feigin less than five 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 accelerating jet airliner would require for takeoff, based on the type of aircraft, the number of passengers, the amount of fuel required to fly 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 flew 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 Memorial 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 optimism, 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 finest 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....................................................... 2. Analgesia and Sedation ............................................................... 3. Procedures..................................................................................

1 11 21

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

35 49

Section 3: Pediatrics 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27.

Adolescent Medicine ................................................................... Allergy and Immunology ............................................................. Cardiology .................................................................................. Critical Care................................................................................ Dentistry and Oral Health ........................................................... Dermatology ............................................................................... Ear, Nose, and Throat ................................................................. Emergency Medicine ................................................................... Endocrinology............................................................................. Fluids, Electrolytes, and Acid–Base Balance ................................ Gastroenterology ........................................................................ Genetics ...................................................................................... Hematology ................................................................................ High-Yield Ambulatory Care ....................................................... Infectious Disease ....................................................................... Nephrology ................................................................................. Neurology ................................................................................... Oncology .................................................................................... Orthopedics and Sports Medicine ............................................... Pulmonology ............................................................................... Rheumatology ............................................................................. Toxicology ..................................................................................

51 60 66 83 106 109 125 130 143 153 169 184 196 209 218 250 268 289 301 312 327 340

viii

Contents

Section 4: Neonatology 28. Newborn Nursery........................................................................ 29. Fetal Assessment and Prenatal Diagnosis..................................... 30. Stabilization, Delivery Room Care, and Initial Treatment of the VLBW Infant ......................................... 31. Discharge Planning ..................................................................... 32. Cardiology .................................................................................. 33. Dermatology ............................................................................... 34. Endocrinology............................................................................. 35. Gastroenterology ........................................................................ 36. Genetics ...................................................................................... 37. Hematology ................................................................................ 38. Infectious Diseases ..................................................................... 39. Nephrology ................................................................................. 40. Neurology ................................................................................... 41. Pain Management ....................................................................... 42. Pulmonology ............................................................................... 43. Surgical Disorders .......................................................................

348 354 363 376 379 386 392 409 421 425 437 445 448 456 458 471

Index .................................................................................................. 479

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

Authors Fahd A. Ahmad, MD Resident, Pediatrics G. Todd Alonso, MD Instructor, Pediatric Emergency Medicine Jeffrey Alten, MD Assistant Professor, Pediatrics and Critical Care Medicine University of Alabama at Birmingham Birmingham, Alabama Mary Goodwin Altobelli, MD Resident, Pediatrics Amy S. Arrington, MD, PhD Resident, Pediatrics Ioanna Athanassaki, MD Assistant Professor, Pediatric Endocrinology Claire E. Bocchini, MD Clinical Postdoctoral Fellow, Pediatric Infectious Disease John P. Breinholt, III, MD Assistant Professor, Pediatric Cardiology Indiana University School of Medicine Indianapolis, Indiana Callie Byrd, MD Resident, Pediatrics Waldemar F. Carlo, MD Clinical Postdoctoral Fellow, Pediatric Cardiology

Michael C. Chapman, MD Clinical Postdoctoral Fellow, Pediatric Sports Medicine Daniel C. Chelius, MD Resident, Otolaryngology Catherine Cibulskis, MD Clinical Postdoctoral Fellow, Neonatology Craig A. Coleby, MD Clinical Postdoctoral Fellow, Primary Care Sports Medicine Kendra J. Conkright, MD Resident, Internal Medicine and Pediatrics Christopher Cotroneo, MD Resident, Pediatrics Ashley M. Cox, MD Resident, Pediatrics Shani H. Cunningham, DO Resident, Pediatrics Tamara Cunningham, MD Resident, Pediatrics Natalie J.M. Dailey, MD Resident, Internal Medicine and Pediatrics Carrie A. Danner, MD Resident, Pediatrics

x

Contributors

Jamie A. Decker, MD Assistant Professor, Pediatric Cardiology

Brent D. Kaziny, MD Resident, Pediatrics

Kristin H. Dillard, MD Clinical Postdoctoral Fellow, Pediatric Allergy and Immunology

Jarrod D. Knudson, MD, PhD Clinical Postdoctoral Fellow, Pediatric Cardiology

Ankhi Dutta, MD, MPH Clinical Postdoctoral Fellow, Pediatric Infectious Disease

Kristin C. Koush, MD Chief Resident in Pediatrics

Lisa Ecroyd, MD Resident, Pediatrics Erik G. Ellsworth, MD Clinical Postdoctoral Fellow, Pediatric Cardiology Peter Ermis, MD Resident, Pediatrics Angela Flores, MD Clinical Postdoctoral Fellow, Neonatology Kathleen Blue Fung, MD Resident, Pediatrics Morey W. Haymond, MD Professor, Pediatric Endocrinology Kelly Hicks, MD Resident, Pediatrics Lindsey Hoffman, DO Resident, Pediatrics Zsofia Intody, MD, PhD Resident, Pediatrics Nick A. Jernigan, MD Resident, Internal Medicine and Pediatrics Jamil Joyner, MD Resident, Pediatrics Meena Rao Julapalli, MD Resident, Dermatology

W. Buck Kyle, MD Chief Resident in Pediatrics Jennifer C. Lee, MD Resident, Pediatric Neurology Kathryn Leung, MD Assistant Professor, Pediatric Hematology and Oncology Kim Little, MD Instructor, Pediatrics Charles G. Macias, MD, MPH Associate Professor, Pediatric Emergency Medicine Thaddeus D. May, MD Resident, Pediatrics and Internal Medicine J. Chase McNeil, MD Clinical Postdoctoral Fellow, Pediatric Infectious Disease Mona L. McPherson, MD, MPH Associate Professor, Pediatric Critical Care Suzanne Melancon-Kyle, MD Resident, Pediatrics Barbara A. Montagnino, MS, RN, CNS Clinical Nurse Specialist, Progresssive Care Unit

Contributors Elizabeth H. Muth, MD Resident, Internal Medicine and Pediatrics Duyen K. Nguyen, DO Clinical Postdoctoral Fellow, Pediatric Allergy and Immunology Trung C. Nguyen, MD Assistant Professor, Pediatric Critical Care Medicine Alison E. Niebanck, MD Chief Resident in Pediatrics Kelly Ann Olson, MA, MD Resident, Pediatrics Gloria Oramasionwu, MD, MPH Clinical Postdoctoral Fellow, Pediatric Infectious Disease Michelle Parker, MD Resident, Pediatrics Rod Pellenberg, MD Resident, Pediatrics Britt Peña, MD Chief Resident in Pediatrics Nina Poliak, MD, MPH Clinical Postdoctoral Fellow, Pediatric Allergy and Immunology

Danielle Rios, MD Resident, Pediatrics John M. Robertson, MD Pediatric Pulmonology Houston Pediatric Pulmonary and Sleep Associates Houston, Texas Amber J. Robinett, MD Resident, Pediatrics Christian P. Schaaf, MD, PhD Clinical Postdoctoral Fellow, Molecular and Human Genetics Margaret D. Scheffler, MD Resident, Pediatrics Heidi Schwarzwald, MD, MPH Associate Professor, Pediatric Retrovirology and Global Health Geeta Singhal, MD, MEd Assistant Professor, Pediatrics Justin Smith, MD Resident, Pediatrics Mary Nell Suell, MD Assistant Professor, Pediatric Hematology and Oncology, Pathology

Vandana Raman, MD Clinical Postdoctoral Fellow, Pediatric Endocrinology

Sarat Susarla, MD Pediatric Pulmonology Houston Pediatric Pulmonary and Sleep Associates Houston, Texas

Monica Ramos, MD Clinical Postdoctoral Fellow, Neonatology

Daniel T. Swarr, MD Resident, Pediatrics

Damitra D. Ramos-Patel, MD Chief Resident in Internal Medicine and Pediatrics

Bridget Sweeney Gotsch, MD Resident, Pediatrics

Rebecca Rawalt, MD Clinical Postdoctoral Fellow, Neonatology

xi

Jun Teruya, MD, DSc Associate Professor, Pathology, Pediatrics, and Internal Medicine

xii

Contributors

Ashaunta R. Tumblin, MD Resident, Pediatrics

Katherine J. Weiss, MD Chief Resident in Pediatrics

Irene T. Tung, MD Resident, Pediatrics

Megan A. Westbrook, MD Resident, Pediatrics

Katri V. Typpo, MD Assistant Professor, Pediatric Critical Care Medicine

Angus A. Wilfong, MD Associate Professor, Pediatric Neurology

Jamie Varughese, MD Clinical Postdoctoral Fellow, Adolescent and Sports Medicine

Wojciech Wiszniewski, MD, PhD Clinical Postdoctoral Fellow, Molecular and Human Genetics

Shannon Wai, MBChB Clinical Postdoctoral Fellow, Pediatric Emergency Medicine

Amber E. Young, MD Resident, Pediatrics

Michael F. Wangler, MD Clinical Postdoctoral Fellow, Molecular and Human Genetics

Suyearn Hong Yu, MD Resident, Pediatrics

Consulting Editors Kaashif A. Ahmad, MBBS, MSc Clinical Postdoctoral Fellow, Neonatology

Teresa K. Duryea, MD Associate Professor, Pediatrics

Carlos A. Bacino, MD Associate Professor, Molecular and Human Genetics

Eric C. Eichenwald, MD Associate Professor, Neonatology

Patricia A. Baxter, MD Instructor, Pediatric Hematology and Oncology Maria A. Carrillo-Marquez, MD Clinical Postdoctoral Fellow, Pediatric Infectious Disease Daniel C. Chelius, MD Resident, Otolaryngology Cathrine Constantacos, MD Clinical Postdoctoral Fellow, Pediatric Endocrinology University of North Carolina at Chapel Hill Chapel Hill, North Carolina

Elaine K. Fielder, MD Clinical Postdoctoral Fellow, Pediatric Emergency Medicine Ricardo J. Flores, MD Clinical Postdoctoral Fellow, Pediatric Hematology and Oncology Amy Bennett Good, MD Clinical Postdoctoral Fellow, Neonatology W. Eddie Gordon, MD Clinical Postdoctoral Fellow, Pediatric Critical Care Medicine J. Nina Ham, MD Assistant Professor, Pediatric Endocrinology

Contributors

xiii

Leslie L. Harris, MD Assistant Professor, Neonatology

Siby Moonnumakal, MD Assistant Professor, Pediatric Pulmonology

Lana Hattar, MD Clinical Postdoctoral Fellow, Pediatric Gastroenterology, Hepatology, and Nutrition

James Owens, MD, PhD Assistant Professor, Pediatric Neurology

Ryan W. Himes, MD Clinical Postdoctoral Fellow, Gastroenterology, Hepatology, and Nutrition Emma M. Jones, MD Clinical Postdoctoral Fellow, Pediatric Hematology and Oncology Roshni Kandyil, MD, PhD Clinical Postdoctoral Fellow, Allergy and Immunology Erin C. Kish, MD Clinical Postdoctoral Fellow, Adolescent and Sports Medicine Federico R. Laham, MD Instructor, Pediatric Infectious Disease Fong W. Lam, MD Clinical Postdoctoral Fellow, Pediatric Critical Care Medicine Katherine Leaming-Van Zandt, MD Clinical Postdoctoral Fellow, Pediatric Emergency Medicine Joyce Li, MD, MPH Clinical Instructor, Pediatric Emergency Medicine Harvard Medical School Boston, Massachusetts Charles G. Macias, MD, MPH Associate Professor, Pediatrics Seema Mehta, MD Clinical Postdoctoral Fellow, Gastroenterology, Hepatology, and Nutrition

Faria A. Pereira, MD Assistant Professor, Pediatric Emergency Medicine Muralidhar H. Premkumar, MBBS, DNB, MRCPCH Clinical Postdoctoral Fellow, Neonatology Andrea A. Ramirez, MD Research Postdoctoral Fellow, Pediatric Rheumatology Stefanie P. Rogers, MD Clinical Postdoctoral Fellow, Neonatology Brian R.E. Schultz, MD Clinical Postdoctoral Fellow, Pediatric Emergency Medicine Timothy Slesnick, MD Assistant Professor, Pediatric Cardiology Hannah Fouts Smitherman, MD Pediatric Emergency Medicine Cook Children’s Physician Network Fort Worth, Texas Poyyapakkam Srivaths, MD Assistant Professor, Pediatric Nephrology V. Reid Sutton, MD Associate Professor, Molecular and Human Genetics Carl Tapia, MD, MPH Assistant Professor, Pediatrics Sharonda Alston Taylor, MD Assistant Professor, Adolescent and Sports Medicine

xiv

Contributors

Keita Terashima, MD Clinical Postdoctoral Fellow, Pediatric Hematology and Oncology

Katri V. Typpo, MD Assistant Professor, Pediatric Critical Care Medicine

Ann Thomas, MD Associate Professor, Pediatrics George Washington University Washington, DC

K. Lynette Whitfield, MD Clinical Postdoctoral Fellow, Gastroenterology, Hepatology, and Nutrition

Senior Reviewers James M. Adams, Jr., MD Professor, Neonatology Coburn H. Allen, MD Assistant Professor, Pediatric Emergency Medicine, Pediatric Infectious Disease Diane M. Anderson, PhD Associate Professor, Neonatology Julie A. Boom, MD Associate Professor, Pediatrics Eileen D. Brewer, MD Professor, Pediatric Nephrology K. Dawn Bunting, RD, CSP, LD Assistant Director, Clinical Nutrition Services Gerardo Cabrera-Meza, MD Associate Professor, Neonatology Judith R. Campbell, MD Associate Professor, Pediatric Infectious Disease A. Bruce Carter, DDS Attending Periodontist See Wai Chan, MD, MPH Assistant Professor, Neonatology Binoy Chandy, MD Assistant Professor, Otolaryngology

Lindsay H. Chase, MD Assistant Professor, Pediatric Hospital Medicine Joseph N. Chorley, MD Associate Professor, Adolescent and Sports Medicine Annabelle N. Chua, MD Assistant Professor, Pediatric Nephrology Murali Chintagumpala, MBBS Professor, Pediatric Hematology and Oncology William J. Craigen, MD, PhD Associate Professor, Molecular and Human Genetics Michael C. Distefano, MD Assistant Professor, Pediatric Emergency Medicine Jan E. Drutz, MD Professor, Academic General Pediatrics Daniel I. Feig, MD, PhD Associate Professor, Pediatric Nephrology Caraciolo J. Fernandes, MD, MBBS Associate Professor, Neonatology Ellen M. Friedman, MD Professor, Otolaryngology

Contributors Joseph A. Garcia-Prats, MD Professor, Neonatology Mark A. Gilger, MD Professor, Gastroenterology, Hepatology, and Nutrition Nancy Glass, MD, MBA Professor, Pediatric Anesthesiology Stuart L. Goldstein, MD Professor, Pediatric Nephrology Imelda Celine Hanson, MD Professor, Pediatric Allergy and Immunology Morey W. Haymond, MD Professor, Pediatric Endocrinology Albert C. Hergenroeder, MD Professor, Adolescent and Sports Medicine Anthony Johnson, DO Associate Professor, Obstetrics and Gynecology Karen E. Johnson, MD Associate Professor, Neonatology

xv

Julie P. Katkin, MD Associate Professor, Pediatric Pulmonology Moise L. Levy, MD Clinical Professor, Dermatology and Pediatrics Laura L. Loftis, MD Associate Professor, Pediatric Critical Care Medicine Timothy E. Lotze, MD Assistant Professor, Pediatric Neurology Donald H. Mahoney, Jr., MD Professor, Pediatric Hematology and Oncology Tiffany M. McKee-Garrett, MD Assistant Professor, Neonatology Kenneth J. Moise, MD Professor, Obstetrics and Gynecology Kathleen J. Motil, MD, PhD Associate Professor, Gastroenterology, Hepatology, and Nutrition

Yvette R. Johnson, MD, MPH Assistant Professor, Neonatology

Eyal Muscal, MD, MS Assistant Professor, Pediatric Rheumatology

Juan Juarez, Jr., MD Assistant Professor, Pediatric Emergency Medicine

Barry L. Myones, MD Associate Professor, Pediatric Rheumatology

Henri Justino, MD Assistant Professor, Pediatric Cardiology

Steven R. Neish, MD, SM Associate Professor, Pediatric Cardiology

Arundhati S. Kale, MBBS Associate Professor, Pediatric Nephrology

Oluyinka A. Olutoye, MBChB, PhD Associate Professor, Pediatric Surgery, Obstetrics and Gynecology

Sheldon L. Kaplan, MD Professor, Pediatric Infectious Disease

Lu-Ann Papile, MD Professor, Neonatology

xvi

Contributors

Mary E. Paul, MD Associate Professor, Pediatric Allergy and Immunology Sarah M. Phillips, MD Instructor, Pediatric Gastroenterology, Hepatology, and Nutrition Lori A. Sielski, MD Associate Professor, Neonatology Geeta Singhal Das, MD Assistant Professor, Pediatrics Timothy Slesnick, MD Assistant Professor, Pediatric Cardiology Marianna M. Sockrider, MD, DrPH Associate Professor, Pediatric Pulmonology

Susanne Trout, RD, LD, IBCLC, RLC Clinical Dietitian, Clinical Nutrition Services Mohan Pammi Venkatesh, MD Assistant Professor, Neonatology Lakshmi Venkateswaran, MD Assistant Professor, Pediatric Hematology and Oncology David E. Wesson, MD Professor, Pediatric Surgery Eric A. Williams, MD Assistant Professor, Pediatric Critical Care Medicine

Michael E. Speer, MD Professor, Neonatology and Ethics

Mark L. Winter, PhD, DABAT Assistant Professor, Pharmacology and Toxicology University of Texas Medical Branch Galveston, Texas

C. Philip Steuber, MD Professor, Pediatric Hematology and Oncology

Teresa S. Wright, MD Assistant Professor, Pediatrics, Dermatology

V. Reid Sutton, MD Associate Professor, Molecular and Human Genetics

Parvin Yazdani-Kachooei, MD Assistant Professor, Pediatric Endocrinology

M. Hossein Tcharmtchi, MD Associate Professor, Pediatric Critical Care Medicine

Robert S. Zeller, MD Professor, Pediatric Neurology

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 specifically to serve as an actual point-of-care tool; clinical algorithms, figures, 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 reflects 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 find 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 find 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 references, 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 confident that you will find 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 ↓ → ± ♀ ♂ Δ 1,25(OH)2-D 2/2 2,3-DPG 25(OH) D 5′-NT 6-MP AAA A-aDO2 AAP AAT Ab ABC abd ABER ABG ABNL ABPA ABR abx AC ACEI ACL acL ACOG ACS ACTH AD ADA ADC ADEM ADH ADHD ADL AED AET AFB

normal decreased, decreasing, depressed, down causes, results in, next possibly, consider female male change in 1,25-dihydroxy vitamin D secondary to 2,3-diphosphoglycerol 25-hydroxy vitamin D 5′-nucleotidase 6-mercaptopurine anti-actin antibody alveolar–arterial oxygen tension difference American Academy of Pediatrics α1 antitrypsin antibody airway, breathing, circulation abdominal auditory brainstem-evoked response arterial blood gas abnormal allergic bronchopulmonary aspergillosis auditory brainstem response antibiotics assist control angiotensin-converting enzyme inhibitor anterior cruciate ligament anticardiolipin American College of Obstetricians and Gynecologists acute chest syndrome adrenocorticotropic hormone autosomal dominant adenosine deaminase apparent diffusion coefficient acute disseminated encephalomyelitis antidiuretic hormone attention deficit hyperactivity disorder activity of daily living antiepileptic drug atrial ectopic tachycardia acid-fast bacilli

Abbreviations AFI AFP AG Ag AGE AGEP AHA AHI AI AIDS AIH AIHA AIN AKA AKI Al+++ Ala ALCAPA ALD Alk Phos ALL ALP ALT ALTE AMA AML AMMoL amox amp ampho B AN ANA ANCA ANLL anti-dsDNA Ab anti-GAD Ab anti-LC1 Ab anti-LKM1 Ab anti-LKM-1 anti-SLA/LPAb anti-TPOAb AOM AP APC APTT AR

xix

amniotic fluid index α-fetoprotein anion gap antigen acute gastroenteritis acute generalized erythematous pustulosis American Heart Association apnea-hypopnea index (number of apneas + hypopneas per hour on polysomnography) aortic insufficiency; autoimmune acquired immune deficiency syndrome autoimmune hepatitis autoimmune hemolytic anemia acute interstitial nephritis alcoholic ketoacidosis acute kidney injury aluminum alanine anomalous left coronary artery arising from the pulmonary artery adrenoleukodystrophy alkaline phosphatase acute lymphoblastic leukemia alkaline phosphatase alanine aminotransferase apparent life-threatening episode antimitochondrial antibody acute myelogenous leukemia acute myelomonocytic leukemia amoxicillin ampicillin amphotericin B anorexia nervosa antinuclear antibody antineutrophil cytoplasmic antibody acute nonlymphoblastic leukemia anti-double stranded DNA antibody anti-glutamic acid decarboxylase antibodies anti-liver cytosol-antibody anti-liver/kidney microsome antibody antibodies to liver/kidney microsomes anti-soluble liver/liver pancreas antigen antibody anti-thyroid peroxidase antibodies acute otitis media anterior posterior; aortopulmonary antigen-presenting cell activated partial thromboplastin time aortic regurgitation; autosomal recessive

xx

Abbreviations

ARB ARDS ARF AROM ARR ARVC AS ASA ASD ASMA Asp AST asx ATFL AT-II ATN ATP ATRA AUS AV AVB AVCD AVM AVN AVP AXR BA BAL BAS BCG BCx BDG BE β-HCG BG BID BiPAP B/L BLS BM BMA BMD BMI BMP BMT BN

angiotensin receptor blocker acute respiratory distress syndrome acute renal failure artificial rupture of membranes absolute risk reduction arrhythmogenic right ventricular cardiomyopathy aortic stenosis aminosalicylic acid (aspirin) atrial septal defect anti–smooth muscle antibody aspartate aspartate aminotransferase asymptomatic anterior talofibular ligament angiotensin-II acute tubular necrosis adenosine triphosphate all trans retinoic acid abdominal ultrasound arteriovenous; atrioventricular atrioventricular block atrioventricular canal defect arteriovenous malformation avascular necrosis arginine vasopressin abdominal X-ray bone age British antilewisite; bronchoalveolar lavage balloon atrial septostomy bacillus Calmette-Guérin blood culture bidirectional Glenn barium enema beta human chorionic gonadotropin blood glucose twice daily bilevel positive airway pressure bilateral basic life support bowel movement bone marrow aspirate Becker muscular dystrophy; bone mineral density body mass index basic metabolic panel (see Chem 7) bone marrow transplant bulimia nervosa

Abbreviations BNP BP BPD BPM BPO BSA BTS BUN BV BVH BW Bx C Ca CA CAA CAD CAH CAIS CA-MRSA c-ANCA cap refill CAP CAVC CBC CBD CBG CCAM CCB CCK CD CDC CDH CEA CF CFL CFTR CGA CGD CH50 CHAOS CHB CHD Chem 7

xxi

b-type natriuretic peptide blood pressure bronchopulmonary dysplasia beats per minute benzoyl peroxide body surface area Blalock-Taussig shunt blood urea nitrogen bacterial vaginosis biventricular hypertrophy birthweight biopsy Celsius calcium chronological age coronary artery aneurysm coronary artery disease congenital adrenal hyperplasia complete androgen insensitivity syndrome community-associated methicillin-resistant Staphylococcus aureus cytoplasmic antineutrophil cytoplasmic antibody capillary refill community-acquired pneumonia complete atrioventricular canal complete blood count common bile duct capillary blood gas congenital cystic adenomatoid malformation calcium channel blocker cholecystokinin clusters of differentiation; Crohn’s disease Centers for Disease Control and Prevention congenital diaphragmatic hernia carcinoembryonic antigen complement fixation; cystic fibrosis calcaneofibular ligament cystic fibrosis transmembrane conductance regulator corrected gestational age chronic granulomatous disease total hemolytic complement titer congenital high airway obstruction syndrome complete heart block; congenital heart block congenital heart disease chemistry panel (Na, K, Cl, HCO3, BUN, Cr, glucose)

xxii

Abbreviations

Chem 10 CHF CHO chol CI CK Cl CLD cm CMA CML CMV CN CNS CO CONS COPD CP CPAP CPD CPK CPP CPR CPS Cr CREST CRF CRI CRMO CRP CRPS CRS CRT CS C-section CSF CT CTA CTD CV CVA CVL CVP CVS Cx CXR

chemistry panel including all items of Chem 7 + Ca, Mg, Phos congestive heart failure carbohydrate cholesterol cardiac index; confidence interval creatine kinase chloride chronic lung disease centimeter chromosome microarray analysis chronic myeloid leukemia cytomegalovirus cranial nerve central nervous system carbon monoxide; cardiac output coagulase-negative Staphylococcus chronic obstructive pulmonary disease cerebral palsy continuous positive airway pressure citrate–phosphate–dextrose creatine phosphokinase cerebral perfusion pressure cardiopulmonary resuscitation carbamoylphosphate synthase creatinine calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias corticotropin-releasing factor chronic renal insufficiency chronic recurrent multifocal osteomyelitis C-reactive protein complex regional pain syndrome congenital rubella syndrome capillary refill time coronary sinus caesarean section cerebrospinal fluid computed tomography computed tomographic angiography connective tissue disease cardiovascular costovertebral angle central venous line central venous pressure cardiovascular system culture chest X-ray

Abbreviations cys d d/c d/o D10 D10W D25 DA DBP DC DCM DDAVP DDH DDx DEXA DFA DFS DH DHEA DHEAS DHN DHS DI DIC diff DILV DIOS DIP div DKA DKS dL DLCO DM DMARD DMD DMSA DMSO DNA DOL DORV DRESS DSD DSM-IV DTaP

xxiii

cysteine day discontinue disorder(s) 10% dextrose 10% dextrose in sterile water 25% dextrose ductus arteriosus diastolic blood pressure direct Coombs test dilated cardiomyopathy deamino-8-d-arginine vasopressin (desmopressin) developmental dysplasia of the hip differential diagnosis dual energy x-ray absorptiometry direct fluorescent antibody disease-free survival direct hyperbilirubinemia dehydroepiandrosterone dehydroepiandrosterone sulphate dehydration drug hypersensitivity syndrome diabetes insipidus disseminated intravascular coagulation differential double-inlet left ventricle distal intestinal obstruction syndrome distal interphalangeal divided diabetic ketoacidosis Damus-Kaye-Stansel deciliter diffusing lung capacity diabetes mellitus; dermatomyositis disease-modifying antirheumatic drug Duchenne muscular dystrophy dimercaptosuccinic acid dimethyl sulfoxide deoxyribonucleic acid day of life double-outlet right ventricle drug reaction with eosinophilia and systemic symptoms disorders of sex differentiation Diagnostic and Statistical Manual of Mental Disorders, 4th ed diphtheria toxoid, tetanus toxoid, and acellular pertussis

xxiv

Abbreviations

d-TGA DTR DUB DVT DWI dx dz EB EBM EBV eCCl ECF ECG ECHO ECMO ED EEC EEG EFS eg EGD EHK EIA EKG ELBW ELISA EM EMA EMB EMG endo ENT EOG EPAP EPS ERCP ERV ESR ESRD ETCO2 ETEC ETOH ETT EUS EWS F f/b

d-transposition of the great arteries deep tendon reflex dysfunctional uterine bleeding deep venous thrombosis diffusion weighted imaging diagnosis disease epidermolysis bullosa evidence-based medicine, expressed breast milk Epstein-Barr virus estimated creatinine clearance extracellular fluid electrocardiogram echocardiogram extracorporeal membrane oxygenation emergency department ectodermal dysplasia, ectrodactyly, cleft electroencephalogram event-free survival for example esophagogastroduodenoscopy epidermolytic hyperkeratosis enzyme immunoassay electrocardiogram extremely low birth weight enzyme-linked immunoassay electron microscopy endomysial antibodies ethambutol electromyogram endocrine Ears, nose, and throat electrooculogram expiratory positive airway pressure extrapyramidal symptoms endoscopic retrograde cholangio– pancreatography expiratory reserve volume erythrocyte sedimentation rate end-stage renal disease end-tidal carbon dioxide enterotoxigenic Escherichia coli alcohol (ethanol) endotracheal tube endoscopic ultrasonography Ewing sarcoma Fahrenheit followed by

Abbreviations FB FDA FDP FE FEF25%–75% FENa FEV1 FFP FHx FiO2 FISH fL FLAIR FOB FOC Fr FRC FS FSBG FSGS FSH FT4 FTA-ABS FTT f/u FUO FVC Fx g G6PD GA GABA GABHS GALT GAS GBM GBS GC GCS GCSF GCT GDM GE GER GERD GFR GGT GH

xxv

foreign body Food and Drug Administration fibrin degradation product fractional excretion forced midexpiratory flow rate fractional excretion of sodium forced expiratory volume in 1 second fresh-frozen plasma family history fractional inspired oxygen fluorescent in-situ hybridization femtoliter fluid attenuated inversion recovery fecal occult blood frontal–occipital circumference French functional residual capacity fingerstick fingerstick blood glucose focal segmental glomerulosclerosis follicle-stimulating hormone free thyroxine fluorescent treponemal antibody absorption failure to thrive follow-up fever of unknown origin forced vital capacity fracture gram glucose-6-phosphate dehydrogenase gestational age γ-aminobutyric acid group A β-hemolytic streptococcus galactose-1-phosphate uridyltransferase group A streptococcus glioblastoma multiforme group B streptococcus; Guillain-Barré syndrome glucocorticoid; gonococcus Glasgow Coma Scale granulocyte colony-stimulating factor germ cell tumor gestational diabetes mellitus gastroenteritis gastroesophageal reflux gastroesophageal reflux disease glomerular filtration rate γ-glutamyl transpeptidase growth hormone

xxvi

Abbreviations

GHB GHBP GI GIR Glc Gln Glu Gly GN GNR GnRH GSD GT GU GVHD h H&P HO h/o H+/K+ ATPase H2RA HA HAV Hb HBcAb HBeAg Hb F HBIG HBsAg HCC hCG HCM HCO3− HCV HD HDAg HDL HDV HEENT HELLP Hep B HEV HFOV HbA1C HH

δ-hydroxybutyrate growth hormone binding protein gastrointestinal glucose infusion rate glucose glutamine glutamic acid glycine glomerulonephritis gram-negative rod gonadotrophin-releasing hormone glycogen storage disease genotype genitourinary graft-versus-host disease hour history and physical examination house officer history of hydrogen/potassium adenosine triphosphatase (proton pump) histamine-2-receptor antagonist headache hepatitis A virus hemoglobin hepatitis B core antibody hepatitis B e antigen hemoglobin F hepatitis B immune globulin hepatitis B surface antigen hepatocellular carcinoma human chorionic gonadotropin hypertrophic cardiomyopathy bicarbonate hepatitis C virus hemodialysis; Hirschsprung’s disease; Hodgkin’s disease hepatitis D antigen high-density lipoprotein hepatitis D virus head, eyes, ears, nose, and throat hemolytic anemia, elevated liver enzymes, low platelets hepatitis B hepatitis E virus high-frequency oscillatory ventilation glycosylated hemoglobin A1c hereditary hemochromatosis

Abbreviations HHRH HHS HHV Hib HIDA HIE HIG HIT HIV HLH HLHS HMG-CoA HOCM HPA HPF HPV HR hr HRCT HSCT HSM HSP HSR HSV ht HTN HUS HVA Hx I&D IA IAA IAP IBD IBS IBW I:C IC iCa ICA ICD ICP ICS ICU ID IDDM IDM

xxvii

hereditary hypophosphatemic rickets with hypercalciuria hyperglycemic hyperosmolar state human herpesvirus Haemophilus influenzae type b hepatobiliary iminodiacetic acid hypoxic-ischemic encephalopathy human immune globulin heparin-induced thrombocytopenia human immunodeficiency virus hemophagocytic lymphohistiocytosis hypoplastic left heart syndrome 3-hydroxy-3-methylglutaryl–CoA hypertrophic obstructive cardiomyopathy human platelet antigen high-power field human papillomavirus heart rate hours high-resolution computed tomography hematopoietic stem cell transplant hepatosplenomegaly Henoch-Schonlein purpura hypersensitivity reaction herpes simplex virus height hypertension hemolytic uremic syndrome homovanillic acid history incision and drainage insulin antibodies insulin autoantibody; interrupted aortic arch intrapartum antibiotic prophylaxis inflammatory bowel disease irritable bowel syndrome ideal body weight insulin to carbohydrate inspiratory capacity ionized calcium islet cell antibody implantable cardioverter/defibrillator intracranial pressure inhaled corticosteroids intensive care unit infectious disease insulin-dependent diabetes mellitus infant of a diabetic mother

xxviii

Abbreviations

ie I:E IE IEM IF IFA IGFBP-3 Ig IgA IgE IGF IGF-BP IgG IgM IGT IHA IHS IHST ILD Ile IM INH iNO INR IO IP IPAP IPV IR IRT IRV IT ITP Itra IU IUD IUGR IV IVC IVDU IVF IVH IVIG IVS JAS JCA JDMS

that is ratio of inspiratory time to expiratory time infective endocarditis inborn errors of metabolism immunofluorescence immunofluorescent antibody insulin-like growth factor binding protein 3 immunoglobulin immunoglobulin A immunoglobulin E insulin-like growth factor insulin-like growth factor binding protein immunoglobulin G immunoglobulin M impaired glucose tolerance indirect hemagglutination assay International Headache Society immediate hypersensitivity skin test interstitial lung disease isoleucine intramuscular isoniazide inhaled nitric oxide International Normalized Ratio intraocular; intraosseous interphalangeal inspiratory positive airway pressure intrapulmonary percussive ventilation internal rotation immunoreactive trypsinogen inspiratory reserve volume iliotibial; intrathecal idiopathic thrombocytopenic purpura itraconazole international units intrauterine device intrauterine growth restriction intravenous inferior vena cava IV drug user intravenous fluids; in-vitro fertilization intraventricular hemorrhage intravenous immunoglobulin intact ventricular septum; interventricular septum juvenile ankylosing spondylitis juvenile chronic arthritis juvenile dermatomyositis

Abbreviations JEB JIA JIIM JMML JRA JVD JVP K KCl KD kg KI KOH KUB L LA LABA LCT LAD LAE lb LBBB LBW LCA LCFA LCH LDH LDL LES Leu LFT

LGA LH Li LIP LLSB LM LMP LMWH LOC LP LPA

xxix

junctional epidermolysis bullosa juvenile idiopathic arthritis juvenile idiopathic inflammatory myopathies juvenile myelomonocytic leukemia juvenile rheumatoid arthritis jugular venous distension jugular venous pulse or pulsation potassium potassium chloride Kawasaki disease kilogram potassium iodide potassium hydroxide kidneys, ureters, and bladder x-ray (abdominal x-ray) liter left atrium; lupus anticoagulant long-acting β-agonist long-chain triglycerides lymphadenopathy; left axis deviation; left anterior descending (coronary artery) left atrial enlargement pounds left bundle branch block low birthweight left coronary artery long-chain fatty acids Langerhans cell histiocytosis lactate dehydrogenase low-density lipoprotein lower esophageal sphincter leucine liver function test (liver panel); generally includes at a minimum albumin, total protein, bilirubin (total and direct), alanine and aspartate aminotransferases, alkaline phosphatase large for gestational age luteinizing hormone lithium lymphoid interstitial pneumonia left lower sternal border light microscopy last menstrual period low-molecular-weight heparin level of consciousness lumbar puncture left pulmonary artery

xxx

Abbreviations

LQTS LR LRT LRTI LTBI LUSB LV LVEDP LVH LVNC LVOT LVOTO Lys Lytes m2 MAC MAG-3 MAI MAP MAS MCD mcg MCH MCL MCP MCT MCTD MCV MD MDI MDS MEE MELAS MEN mEq Met Mg mg MGN MH MHA-TP MHC MIBG micro

long QT syndrome lactated Ringer’s solution; likelihood ratio lower respiratory tract lower respiratory tract infection latent tuberculosis infection left upper sternal border left ventricular left ventricular end-diastolic pressure left ventricular hypertrophy left ventricular noncompaction left ventricular outflow tract left ventricular outflow tract obstruction lysine electrolytes (Na, K, Cl, often includes bicarbonate) meter squared Mycobacterium avium complex mercaptoacetyltriglycine Mycobacterium avium intracellulare mean airway pressure macrophage activation syndrome; meconium aspiration syndrome minimal change disease microgram mean corpuscular hemoglobin medial collateral ligament metacarpophalangeal medium-chain triglycerides mixed connective tissue disease mean corpuscular volume myotonic dystrophy metered-dose inhaler myelodysplastic syndrome middle ear effusion mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes multiple endocrine neoplasia milliequivalent methionine magnesium milligram membranous glomerulonephritis microscopic hematuria microhemagglutination assay for antibodies to Treponema pallidum major histocompatibility class methyliodobenzylguanidine microanalysis; microscopic

Abbreviations min MIVF mL MM MMR mo MODY MPA MPGN MPH MPO MPS MR MRA MRCP MRD MRI MRS MRSA MRV MS MSAFP MSG MSM MSSA MSUD MT MTB MTHFR MTP MTX MV MVA MVP Na N/A NAAT NAC NAI NAIT NAS NASH NASPGHAN NAT NB NBL NBS

xxxi

minutes maintenance intravenous fluids milliliter mucous membrane measles, mumps, rubella months maturity onset diabetes of youth main pulmonary artery; milk protein allergy membranoproliferative glomerulonephritis mid-parental height myeloperoxidase mucopolysaccharidosis mitral regurgitation magnetic resonance angiography magnetic resonance cholangiopancreatography minimal residual disease magnetic resonance imaging magnetic resonance spectroscopy methicillin-resistant Staphylococcus aureus magnetic resonance venogram mental status; mitral stenosis maternal serum alpha-fetoprotein monosodium glutamate men who have sex with men methicillin-sensitive Staphylococcus aureus maple syrup urine disease metatarsal Mycobacterium tuberculosis methyltetrahydrofolate reductase metatarsophalangeal methotrexate minute volume; mitral valve motor vehicle accident mitral valve prolapse sodium not applicable nucleic acid amplification test N-acetylcysteine non-accidental injury neonatal alloimmune thrombocytopenia neonatal abstinence scoring nonalcoholic steatohepatitis North American Society for Pediatric Gastroenterology, Hepatology and Nutrition non-accidental trauma nota bene neuroblastoma newborn screen

xxxii

Abbreviations

NC NCPAP NEC NF ng NG NGT NH3 NHL NICU NIH NIV NK nl NLE NMB NMJ NMT NNT NPO NS NSAID NSR NTB NTD N/V O&P O2 OA OAE OCD OCP OCRG OEIS OG OGES OGTT OHV OI OLT OME ONTD OP ophth ORIF Orn

nasal cannula nasal continuous positive airway pressure necrotizing enterocolitis neurofibromatosis nanograms nasogastric nasogastric tube ammonia non-Hodgkin’s lymphoma neonatal intensive care unit National Institutes of Health noninvasive ventilation natural killer normal neonatal lupus erythematosus neuromuscular blockade neuromuscular junction nebulized mask treatment number needed to treat nil per os (nothing by mouth) normal saline nonsteroidal antiinflammatory drug normal sinus rhythm nontuberculous neural tube defect nausea/vomiting ova and parasite oxygen organic acids otoacoustic emissions obsessive–compulsive disorder; osteochondritis dissecans oral contraceptive oxycardiorespirogram omphalocele, cloacal exstrophy, imperforate anus, spinal defects orogastric oral glucose–electrolyte solution oral glucose tolerance test obesity hypoventilation syndrome obesity imperfecta orthotopic liver transplantation otitis media with effusion open neural tube defect organophosphate ophthalmic solution open reduction with internal fixation ornithine

Abbreviations ORS Osm OSAS Osm OT OTC oz Phos P2 PA PAA PAB PaCO2 PAF PAH PA/IVS PALS PAN p-ANCA PaO2 Pap PAPP-A PAPVC PAPVR PAS PB PBF PC PCA PCL PCN PCOS PCP PCR PCV PCV7 PD PDA PDD PDE PE PEEP PEF PEG

xxxiii

oral rehydration solution obstructive sleep apnea obstructive sleep apnea syndrome osmolality occupational therapy ornithine transcarbamylase; over-the-counter ounces phosphorus pulmonic component of second heart sound postero-anterior; pulmonary atresia; pulmonary artery plasma amino acids pulmonary artery band arterial carbon dioxide tension (partial pressure) platelet-activating factor pulmonary artery hypertension pulmonary atresia with intact ventricular septum pediatric advanced life support polyarteritis nodosa perinuclear antineutrophil cytoplasmic antibody partial pressure of oxygen in arterial blood Papanicolaou pregnancy-associated plasma protein A partial anomalous pulmonary venous connection partial anomalous pulmonary venous return periodic acid-Schiff barometric pressure (~760 mm Hg at sea level) pulmonary blood flow platelet count; pressure control patient-controlled analgesia posterior collateral ligament of knee penicillin polycystic ovarian syndrome phencyclidine; primary care provider polymerase chain reaction packed cell volume 7-valent pneumococcal conjugate vaccine peritoneal dialysis patent ductus arteriosus pervasive developmental disorder phosphodiesterase physical exam; pulmonary embolism, pulmonary edema positive end-expiratory pressure peak expiratory flow polyethylene glycol

xxxiv

Abbreviations

PEG 3350 PEP PET PFC PFO PFT PGE1 PHA Phe Phos PI PICC PICU PID PIE PIGN PIP PIV PK PKD PKU PMA PMD PMH PMI PML PMN PNET PNH PO PO2 POC POPE PPD PPHN PPI PPNET PPROM PPS PPV PR PRBC Pro PROM

polyethylene glycol powder (Miralax) positive expiratory pressure positron emission tomography persistent fetal circulation patent foramen ovale pulmonary function testing prostaglandin E1 pseudohypoaldosteronism phenylalanine phosphorous primary immunodeficiency, protease inhibitor percutaneously inserted central catheter pediatric intensive care unit pelvic inflammatory disease pulmonary interstitial emphysema post-infectious glomerulonephritis peak inflation pressure; peak inspiratory pressure; proximal interphalangeal peripheral intravenous (catheter) pyruvate kinase polycystic kidney disease phenylketonuria postmenstrual age primary medical doctor past medical history point of maximal impulse promyelocytic leukemia polymorphonuclear cells primitive neuroectodermal tumor paroxysmal nocturnal hemoglobinuria per os (by mouth) partial pressure of oxygen point of care postobstructive pulmonary edema purified protein derivative persistent pulmonary hypertension of newborn proton pump inhibitor peripheral primitive neuroectodermal tumor preterm prolonged rupture of membranes peripheral pulmonary stenosis positive predictive value; positive pressure ventilation per rectum; pityriasis rosea; pulmonary regurgitation packed red blood cell proline passive range of motion; prolonged rupture of membranes

Abbreviations PS PSC PSG PSH pSLE pt PT PTFL PTH PTHrP PTSD PTT PTX PUBS PUD pulm PUV PUVA PVL PVM PVR PWS Px PZA Q Qhs QID QIg Qp Qs QTc RA RAA RAD RAE RAST RBBB RBC RCA RCM RCT RDEB RDS RDW RES resp retic RF

xxxv

pressure support; pulmonary stenosis primary sclerosing cholangitis polysomnography past surgical history pediatric systemic lupus erythematosus patient physical therapy; prothrombin time posterior talofibular ligament parathyroid hormone persistent parathyroid hormone–related peptide posttraumatic stress disorder partial thromboplastin time pneumothorax percutaneous umbilical blood sampling peptic ulcer disease pulmonary posterior urethral valve psoralen with ultraviolet A periventricular leukomalacia pulmonary vascular markings pulmonary vascular resistance port-wine stain prognosis pyrazinamide every every night four times a day quantitative immunoglobulins pulmonary blood flow systemic blood flow corrected QT interval rheumatoid arthritis, right atrium right atrial appendage right axis deviation right atrial enlargement radioallergosorbent test right bundle branch block red blood cell right coronary artery restrictive cardiomyopathy randomized, controlled trial recessive dystrophic epidermolysis bullosa respiratory distress syndrome red cell distribution width reticuloendothelial system respiratory reticulocyte rheumatoid factor

xxxvi

Abbreviations

RHD RIA RIF RNA RNC RNP r/o ROM ROP ROS RP RPGN RPR rpt RR RRR RSV RTA RUQ RV RVEDP RVH RVOT RVOTO Rx rxn SAA SABA SaO2 SAPHO SBBO SBE SBFT SBI SBP SBS SCD SCFE SCID SCM SCT SD SE SEM SES SG SGA

rheumatic heart disease radioimmunoassays rifampin ribonucleic acid radionuclide cystogram ribonucleoprotein rule out range of motion retinopathy of prematurity review of systems Raynaud’s phenomenon rapidly progressive glomerulonephritis rapid plasma reagin repeat respiratory rate; risk ratio relative risk reduction respiratory syncytial virus renal tubular acidosis right upper quadrant residual volume; right ventricle right ventricular end-diastolic pressure right ventricular hypertrophy right ventricular outflow tract right ventricular outflow tract obstruction prescription; treatment reaction serum amino acids; serum amyloid A short-acting β-agonist systemic arterial oxygen saturation syndrome of synovitis, acne, pustulosis, hyperostosis, and osteitis small bowel bacterial overgrowth subacute bacterial endocarditis small bowel follow-through serious bacterial infection systolic blood pressure short bowel syndrome sickle cell disease; sudden cardiac death slipped capital femoral epiphysis severe combined immunodeficiency sternocleidomastoid stem cell transplant standard deviation side effects systolic ejection murmur socioeconomic status specific gravity small for gestational age

Abbreviations SGS SHBG SI SIADH SIDS SIMV SIRS SJS SLE SMA SMV SOB SPECT SpO2 s/p spp. SSRI SSTI Staph STI STS sub-Q SVC SVCO2 SVR SVT SWI sx T&A T1DM T3 T4 TA TAPVC TAPVR TAR TB TBG TBI TBSA TBW TCA TcB TCH TCI TCS

xxxvii

short gut syndrome steroid hormone–binding globulin sacroiliac syndrome of inappropriate antidiuretic hormone secretion sudden infant death syndrome synchronized intermittent mandatory ventilation systemic inflammatory response syndrome Stevens-Johnson syndrome systemic lupus erythematosus spinal muscular atrophy; superior mesenteric artery superior mesenteric vein shortness of breath single-photon emission computed tomography oxygen saturation status post species selective serotonin reuptake inhibitors skin and soft tissue infections staphylococcus sexually transmitted infection soft tissue sarcoma subcutaneous superior vena cava superior vena cava oxygen saturation systemic vascular resistance supraventricular tachycardia susceptibility weighted imaging symptoms tonsillectomy & adenoidectomy type 1 diabetes mellitus triiodothyronine thyroxine tricuspid atresia; truncus arteriosus total anomalous pulmonary venous connection total anomalous pulmonary venous return thrombocytopenia with absent radius tuberculosis thyroid-binding globulin traumatic brain injury total body surface area total body water tricyclic antidepressant transcutaneous bilirubin Texas Children’s Hospital topical calcineurin inhibitor topical corticosteroid

xxxviii

Abbreviations

Td TDID TDx-FLM Te TEE TEF TEG TEN TFPI TFT TG TGA TH Ti TIBC TID TIPS TLC TLSO TM TMJ TMP TMP/SMX TNF TOA TOF TOF/PA TORCH tox TP tPA TPN TR TRALI TRH TS TSB TSH TSS TST TT4 TTE TTG TTN TTP TV tx

tetanus toxoid, diphtheria toxoid total daily insulin dose (commercial fetal lung maturity assay) expiratory time transesophageal echocardiography tracheoesophageal fistula thromboelastography platelet mapping toxic epidermal necrolysis tissue factor pathway inhibitor thyroid function test triglycerides transposition of the great arteries thyroid hormone inspiratory time total iron-binding capacity three times daily transjugular intrahepatic portosystemic shunt total lung capacity thoracic lumbosacral orthosis tympanic membrane temporomandibular joint trimethoprim trimethoprim/sulfamethoxazole tumor necrosis factor tubo-ovarian abscess tetralogy of Fallot tetralogy of Fallot with pulmonary atresia toxoplasmosis, other (varicella, parvovirus), rubella, cytomegalovirus, herpes, HIV, syphilis toxicology total protein tissue plasminogen activator total parenteral nutrition tricuspid regurgitation transfusion-related acute lung injury thyroid-releasing hormone tricuspid stenosis total serum bilirubin thyroid-stimulating hormone toxic shock syndrome tuberculin skin test total thyroxine transthoracic echocardiography tissue transglutaminase transient tachypnea of newborn thrombotic thrombocytopenic purpura tricuspid valve; tidal volume therapy

Abbreviations Tyr UA UAC UAG UAW UC UCL UDCA UFH UGI UGT U/L UOA UOP UProt:UCr UPJ UPT URAP URI URTI US UTI UV UVB UVC V/D VACTERL

Val VATER

VATS VBG VC VCO2 VCUG VD VDRL VG VHL VIP VLBW VLDL VMA

xxxix

tyrosine urinalysis umbilical arterial catheter urine anion gap upper airway ulcerative colitis ulnar collateral ligament ursodeoxycholic acid unfractionated heparin upper gastrointestinal series uridine diphosphate glucuronosyltransferase upper to lower body segment ratio urine organic acids urine output urinary protein to urinary creatinine ratio ureteropelvic junction urine pregnancy test unidirectional retrograde accessory pathway upper respiratory infection upper respiratory tract infection ultrasonography urinary tract infection ultraviolet ultraviolet B umbilical venous catheter vomiting/diarrhea vertebral anomalies, anal atresia, cardiovascular anomalies, tracheoesophageal fistula, esophageal atresia, renal or radial anomalies, and limb defects valine vertebral anomalies, anal atresia, tracheoesophageal fistula, esophageal atresia, and renal or radial anomalies video-assisted thoracoscopic surgery venous blood gas vital capacity; volume control CO2 production voiding cystourethrography; voiding cystourethrogram dead space Venereal Disease Research Laboratory volume guarantee von Hippel-Lindau vasoactive intestinal polypeptide very low birth weight very low-density lipoprotein vanillylmandelic acid

xl

Abbreviations

VO2 VOD VPA VPS V/Q VRE VS VSD VT VT VTE VU VUR vWD vWF VZIG VZV w/u WBC WBG wk WNL WPW WT wt XLHR XR y yo yr ZES

oxygen uptake veno-occlusive disease valproic acid ventriculoperitoneal shunt ventilation-perfusion vancomycin-resistant Enterococcus volume support ventricular septal defect tidal volume ventricular tachycardia venous thromboembolism vesicoureteral vesicoureteral reflux von Willebrand disease von Willebrand factor varicella zoster immunoglobulin varicella zoster virus work up white blood cell whole-blood glucose week within normal limits Wolff-Parkinson-White syndrome Wilms tumor weight X-linked hypophosphatemic rickets X-ray year years old years Zollinger-Ellison syndrome

CHAPTER 1

Clinical Pearls for the Wards ORDERS Admission Orders (ADC VANDALISM) • Admit to: Floor, service, MD • Diagnoses (prioritized) • Condition: Good, fair, poor, guarded, critical • Vitals and monitoring: Frequency of monitoring (eg, q4, q shift, per routine), type of monitoring (eg, continuous oximetry, telemetry, arterial line, CVP, end-tidal CO2) • Activity: Ad lib, bed rest with or without bathroom privileges, crib with side rails up, restrictions, ambulate TID, and so on • Nursing/respiratory: strict I/O, daily weights, turn patient q shift, dressing care and changes, drain care, NG care, Foley care, suctioning, pulmonary toilet • Diet: Regular, clear liquid, special requirements (ie, ADA, low fat, low calorie), restrictions (ie, 2-g sodium renal diet), NPO • Allergies: Medication and food • Labs • IVF: Type, volume, rate (specify mL/hr for all; for infants, also specify mL/kg/d) • Studies • Medications: Name, dose (also specify mg/kg), frequency, route, duration, reason

Preoperative Orders • Diagnoses (prioritized) • Procedure • Preoperative labs (including blood bank orders)

• Preoperative studies • Diet: NPO/IVF after midnight, and so on • Consent form signed and on chart • H&P reviewed

Discharge Orders • Discharge: When, to where • Diagnoses (prioritized) • Diet • Condition • Activity: Ad lib, bedrest, physical limitations, and so on

• Special needs: Home health needs, monitoring, and so on • Discharge medications • Discharge instructions: When and why to return, where to return, and so on • Follow-up appointments

NOTES On-Service Note • Admit date • Admit diagnoses (prioritized) • Hospital course summary • Physical examination

• Problem list (prioritized) • Assessment or plan (problem based or system based)

Progress Note (SOAP Note) Subjective: Patient comments or complaints, nursing comments, relevant events Objective: • Vitals: Temperature, HR, RR, blood pressure, oxygen saturation, weight (including change from previous) • I/O: Totals and components of IVF, PO intake, emesis, residuals, urine, stool, drains

1

G E N E R A L C L I N I C A L I N F O R M AT I O N

Section 1: General Clinical Information

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 • Admission and discharge diagnoses (prioritized) • Service: Service name, attending physician, resident(s) • Consulting services • Procedures • Physical examination and vitals (admission) • Hospital course (system based or problem based, pertinent labs and studies) • Physical examination and vitals (discharge) • Discharge condition: Improved, good

• Disposition: To outside hospital, home, hospice, and so on • Discharge medications: Name, formulation, dosage, length of treatment, refills • Discharge activity • Discharge diet • Discharge instructions: Dressing or cast care, symptoms to warrant further treatment, where to return for further treatment, and so on • 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, puﬀs, and so on), route, frequency, duration (specify mg/kg when possible) DISP: Number or volume to be dispensed Other: Number of reﬁlls? 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)

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 diﬀerent 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 • 3 mo–6 mo → 20 g/d • 6 mo–1 yr → 10 g/d or 1 lb/mo

• 2 yr–puberty → 0.5 lb/mo or 2 kg/yr∗ (∗Abnormal prepubertal velocity = <1 kg/yr wt 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 influenced 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 first year of life, 4 inches in second year, 3 inches in third year, 3 inches in fourth year, and 2 inches in fifth 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)

G E N E R A L C L I N I C A L I N F O R M AT I O N

Clinical Pearls for the Wards

4

General Clinical Information

FOC (Rate of Gain) • 0–3 mo → 2 cm/mo • 3–6 mo → 1 cm/mo

• 6–12 mo → 0.5 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, ossified 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 6–10 kg 11–20 kg 21–40 kg > 40 kg

BSA = (wt in kg × 0.05) + 0.05 BSA = (wt in kg × 0.04) + 0.1 BSA = (wt in kg × 0.03) + 0.2 BSA = (wt in kg × 0.02) + 0.4 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)

BSA (m2 ) =

height (cm) × weight (kg) 3,600

PRE-PROCEDURAL DIET GUIDELINES Procedure

Diet Recommendations

Barium enema

Normal∗

Bone scan

Normal

Bronchoscopy

NPO: 4–6 h (continued on next page)

Procedure

Diet Recommendations

CT scan with contrast: Abdomen, body

NPO: 6 h, food and formula; 4 h, EBM; 2 h, clears

CT scan with or without contrast: Head

Normal

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 ﬂow 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 small bowel follow-through

NPO: 4 h

VCUG

Normal

5

∗no speciﬁc 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 firstline 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).

G E N E R A L C L I N I C A L I N F O R M AT I O N

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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∗

Water Based (Increase Miscibility)

Oil Based (Lubricate)

Docusate sodium (Colace™ liquid)† Triethanolamine (Cerumenex™)† 3% Hydrogen peroxide 2.5% Acetic acid 10% Sodium bicarbonate Normal saline‡

Almond oil Olive oil Peanut oil Mineral oil 10% oil of turpentine (Cerumol™)

Non oil, Non–Water Based (Increase Miscibility) Carbamide peroxide (Debrox™)† Glycerol

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

Ear Wax Removal Indicated

Manual Removal

Ceruminolytics*

• Metal or plastic loop or spoon (never pointed or sharp) • Difficult if uncooperative patient or if cerumen impacted

• Fill ear canal on affected side, cotton ball in canal • Saline recommended as first line trial • Wait 15–30 min prior to irrigation • Use 2–3 days BID if unsuccessful

Irrigation*

†

• Use body temperature water (35–38°C) with rubber ear syringe, Water-Pik™ on low setting, or improvised device‡ • Irrigate repeatedly until water return is 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 butterfly 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 sufficient. • 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)

COLLECTION TUBE TYPES FOR SELECTED LAB SAMPLES* Red

Blue

Purple

Green

CBC

Chem 7/10

Chem 7/10

Bartonella titer

ESR

Liver panel

Liver Panel

Hepatitis panel

Fibrinogen

ABO/Rh

Amylase

Amylase

HIV Western blot

PTT Hepzyme

Coombs

Lipase

CRP

RPR

D-dimer

Crossmatch

Gentamicin peak, trough, random

Gentamicin (peak, trough, random)

Rubella IgG/IgM

Unfractionated heparin level

Reticulocyte count

CRP

TSH/free T4

Bilirubin (total, direct, indirect)

Antithrombin

HgbA1C

Blood fungus culture

LH/FSH

Monospot

Rubella IgG

Hemoglobin proﬁle

HIV ELISA antibody

EBV titers/EBNA

Drug screen, serum

EBV, CMV, adenovirus: quantitative PCR

Rubella IgG

CMV titers

Osmolality, serum

Amylase

Lipid panel

Iron panel

CK, CKMB

HIV: DNA PCR, RNA, viral load

Bilirubin (total, direct, indirect)

Quantitative immunoglobulins

Vancomycin (random, peak, trough)

Rubella IgG

Osmolality, serum

ANA/ANA proﬁle

Most serum drug levels

CK, CKMB

C3/C4

Vancomycin (random, peak, trough)

HCG

Ammonia (on ice)

ASO titer

PT/INR/PTT

∗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.

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General Clinical Information

SI LAB VALUE CONVERSION TABLE Lab Value

US Unit

SI Unit

Factor* Lab Value

Chemistry

US Unit

SI Unit

Factor*

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

2+

Mg

mEq/L

mmol/L 0.5

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

Hematology

T3

mcg/dL

nmol/L

0.0154

Iron, TIBC

mcg/dL

μmol/L

0.179

Uric acid

mg/dL

μmol/L

59.5

Vit B12

pg/mL

pmol/L

0.738

∗Factor to convert from standard to SI units.

ACETAMINOPHEN DOSING Elixir (160 mg/ 5 mL)

Age∗

Weight

Drops (80 mg/ 0.8 mL)†

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.

Chewable Tablets (80-mg tablets)

9

• Dosages may be repeated every 4 h but should not be given more than five 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 Elixir (100 mg/ 5 mL)

Chewable Tablets (50 mg tablets) —

Age∗

Weight

Drops (40 mg/ 1.5 mL)†

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

Compound

Relative Antiinflammatory Potency

Duration of Action

Relative Sodium Retaining Potency

Approximate Equivalent 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

Methylprednisolone

5

I

0.5

4

(continued on next page)

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General Clinical Information

Compound Triamcinolone

Relative Antiinflammatory Potency

Duration of Action

Relative Sodium Retaining Potency

Approximate Equivalent Dose (mg)∗

5

I

0

Fludrocortisone

10

S

125

4 —

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 diﬀerent 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 • Infiltrations, extravasation, and vesicant injury • Epidemiology and statistics: the basics

Analgesia and Sedation PAIN ASSESSMENT TOOLS • Physiologic parameters: Tachycardia, vasoconstriction, diaphoresis, pupil dilatation, increased minute ventilation, hypertension

0

2

4

6

8

10

No hurt

Hurts little bit

Hurts little more

Hurts even more

Hurts whole lot

Hurts worst

Figure 2-1 FACES pain scale. (From Hockenberry MJ, Wilson D. Wong’s Essentials of Pediatric Nursing, 8th ed. St. Louis: Mosby; 2009. Used with permission. Copyright Mosby.)

NONPHARMACOLOGIC PAIN CONTROL (Emerg Med Clin North Am 2005;23:393) • Cognitive: Music, guided imagery, distraction, positive reinforcement, decentralization, hypnosis • Behavioral: Relaxation techniques, biofeedback exercises, breathing control, distraction, education • Physical: Hot and cold compresses, massage or touch, position and comfort, temperature regulation, transcutaneous electrical nerve stimulation, acupuncture, chiropractic therapy, immobilization • Gate control hypothesis: Close the “pain gates” via nonpainful receptors or excitatory messages from the brain

PHARMACOLOGIC PREPARATION General Principles • Formulations containing epinephrine should NOT be used in terminal capillary circulations (eg, pinna, digits, nose, penis, and other areas of end-capillary circulation).

Category

Drug

Dosage

Warnings

Topical local anesthetic

LET (lidocaine, epinephrine, tetracaine) suturing solution

≤3 mL on gauze or cotton pad in direct contact with wound

• Do not repeat dosing • Laceration should be >5 mm from mucous membranes

ELA-Max, L.M.X. 4% (lidocaine) or EMLA (eutectic mixture of lidocaine and prilocaine)

Maximum dosing to intact skin (30 min for ELA-Max; 60 min for EMLA): Birth–3 mo or <5 kg: 1 g 3–12 mo and >5 kg: 2 g 1–6 yr and >10 kg: 10 g >7 yr and >20 kg: 20 g

• Methemoglobinemia (especially in neonates and infants) • Irregular heart beats • Seizures • Coma • Respiratory depression (continued on next page)

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G E N E R A L C L I N I C A L I N F O R M AT I O N

CHAPTER 2

12

General Clinical Information

Category

Injectable local anesthetic

Drug

Dosage

Warnings

Ethyl chloride topical spray

Spray at target area 3–9 in away for 3–7 s until skin turns just white; immediate onset

• Irritation at site • Pigmentation changes to application site

Lidocaine (with or without epinephrine)

Maximum dose: 4.5 mg/kg Buﬀer 1:10 with sodium bicarbonate (8.4%) to reduce burning sensation at injection site

Bupivacaine

Maximum dose: 2.5 mg/kg Buﬀer with 1:30 with sodium bicarbonate (8.4%) to reduce burning sensation at injection site

• Methemoglobinemia (especially in neonates and infants) • Irregular heart beats • Seizures • Coma • Respiratory depression • If it must be used in neonates and infants, in general, reduce 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 (nonsalicylate)

PO or PR 10–15 mg/kg q 4–6 h Maximum dosage: 1000 mg q6h

• Not anti-inﬂammatory • Caution in patients with liver disease

Ibuprofen (NSAID)

PO 4–10 mg/kg q 6-8 h (not for use in patients younger than 6 mo of age) Maximum dosage: 800 mg q6h

• Caution with renal insuﬃciency • Increased risk of GI ulcers or bleeds

Ketorolac (NSAID)

IV or IM 0.5–1.0 mg/kg q 6 h followed by 0.5 mg/kg q 6 h Maximum dosage, 30 mg q 6 h; no more than 5 days/mo

• Keep patient well hydrated • Caution with renal insuﬃciency • Only parenteral NSAID

Naproxen (NSAID)

PO 5–7 mg/kg q 8–12 h (not for use in patients younger than 2 yr of age) Maximum dosage: 500 mg q8h

• Increased risk of cardiovascular events and GI ulcers or bleeds

Indomethacin (NSAID)

PO 1 mg/kg q 6–8 h Maximum dosage: 50 mg q 6 h

• See comments on other NSAIDS

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 Maximum dose: 60 mg

Commonly combined with acetaminophen

Fentanyl

IV 1–2 mcg/kg/dose < 12 yr IV 0.5–1 mcg/kg/dose ≥ 12 yr

Muscle rigidity and chest 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 Maximum dose: 10 mg

Commonly combined with acetaminophen

Hydromorphone

IV 0.015 mg/kg q 3–4 h PO 0.03–0.08 mg/kg q 3–4 h Maximum dose: 2 mg

High potential for abuse

Methadone

PO 0.1 mg/kg q 4–12 h Maximum dose: 20 mg

Used in narcotic detoxiﬁcation May cause QT prolongation

Morphine

IV 0.05–0.2 mg/kg q 2–4 h PO 0.1–0.5 mg/kg q 4–6 h MS Contin: Can give q 8–12 h Maximum dosage: IV 15 mg, PO 30 mg

Do not crush or chew controlled-release tablets IV onset: 5–10 min Duration: 2–4 h

Oxycodone

PO IR 0.2 mg/kg q 3–4 h PO SR 10–20 mg q 12 h Maximum dose: 30 mg

Do not use sustained-release tablets as a PRN analgesic

∗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.

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14

General Clinical Information

Agent

Loading Dose

Maximum 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

Agent

Interval Dose

PCA Lockout Interval

4 Hours 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 m orphine ⎤ ⎢ 60 mg PO morphine = 90 mg PO morphine ⎥ → × = 15 mg ⎣ ⎦ • Convert to the new opioid. ⎡ 10 mg IV morphine 15 mg IV morphine ⎤ ⎢ 1.5 mg IV hydromorphone = × mg IV hydromorphone ⎥ → × = 2 . 25 mg ⎣ ⎦ • 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.

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 first 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 fluids within 2 h. • Discuss the risks and benefits with the patient and family and outline the plan, including planned medications, before starting. • Assess for risk factors for complications, including significant underlying disease, abnormal airway, age younger than 6 years, active respiratory infection or fever, dehydration, or use of multiple sedation medicines. • ASA Physical Status Classification: Patients classified 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

Modiﬁer added to any classiﬁcation indicating “emergency” status

All ED patients

Adapted from the American Society of Anesthesiologists.

• Physical exam focusing on identifying patients with potentially difficult airways, cardiopulmonary compromise, decreased neurologic baseline, and loose teeth or poor dentition. • Determine Mallampati classification: Visibility of oral cavity used to predict the ease of intubation.

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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 classification. *The original Mallampati classification (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 1000–2500 g

2.5 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

Weight/Age

Laryngoscope 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.

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.

Lorazepam

Diazepam

Dose and Drug Route

Duration

Adverse Effects

Comments

IM or IV 0.04–0.2 mg/kg IM 15 min Maximum single IV 2–3 min dose, 10 mg

Intermediate Blood dyscrasias IM 2–4 h IV 30–90 min Thrombophlebitis

• Active metabolite accumulation may prolong sedation

PO 30–60 min <12 yr IM 10–20 min IM or PO 0.05 mg/kg IV 3–5 min IV 0.01–0.03 mg/kg Maximum dose, 2 mg >12 yr PO 2–4 mg IM or IV: 0.05 mg/kg Maximum dose, 4 mg

Long acting PO 2–8 h IM 2–6 h IV 2–6 h

Blurred vision Hallucinations Restlessness Drowsiness Confusion

• Use with caution in patients with renal or liver disease • Ideal for prolonging sedation or anxiolysis and seizure treatment

PO 10–20 min IM 15 min IV 1–2 min IN: 0.2 mg/kg

Short acting PO 2 h IN 60 min IM or IV 2–6 h

Bitter taste Amnesia Blurred vision Headache Hiccoughs Nausea or vomiting Coughing

• Cardiac arrest and hypotension have occurred after premedication with a narcotic, but fewer cardiac complications • Excellent for muscle relaxation or prolonged sedation • IV injection painful • Only benzodiazepine FDA approved for use in neonates; rapid administration may cause myoclonic activity

<6 mo PO 0.5–1.0 mg/kg Maximum dose, 20 mg IN 0.2 mg/kg Maximum dose, 15 mg IM 0.07–0.08 mg/kg Maximum dose, 10 mg

Midazolam

Onset

>6 mo and <12 yr IV 0.05–0.1 mg/kg Maximum dose, 10 mg >12 yr IV 0.5–2 mg/dose

G E N E R A L C L I N I C A L I N F O R M AT I O N

Analgesia and Sedation

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. • Dexmedetomidine: Sedative, selective α2-adrenoceptor agonist

Onset

Adverse Duration Effects

Pentobarbital

Comments

PO or PR >50–100 mg/kg Maximum dose, 1 g

30–60 min 4–8 h

Unpleasant taste • Contraindicated in myocardial GI irritation depression, Disorientation airway obstrucDelirium tion, apnea, and renal or hepatic Headache impairment Respiratory • 30%–40% failure depression rate

>3 mo only PO 6–10 mg/kg IM 3–7 mg/kg IV 0.5–1 mg/kg; may repeat ≤2 mg/kg in 1-h time period Maximum dose, 100 mg

PO 20–45 min IM 3–4 min IV 1–2 min

PO 1–2 h IM 12–25 min

Increased systemic, intracranial, and intraocular pressures (contraindications) Nystagmus Tachycardia Diplopia Hypersalivation (may pretreat with atropine or glycopyrrolate) Hallucinations Emergence reaction (tx with midazolam) Laryngospasm

IM 2–6 mg/kg IV 1–3 mg/kg; may repeat Maximum dose, 200 mg or 6 mg/kg

IM 10–15 min IV 1 min

Variable

IV 10–15 min

Ketamine

Chloral hydrate

Drug Dose/Route

• Potent analgesia • Rapid sedation • Bronchial smooth muscle relaxation (use in patients with asthma) • Rare respiratory depression, maintains airway well • Eyes may remain open • Movement may occur • Use with caution in patients with head trauma, seizures, WPW, and HTN

Agitation (some- • 3%–7% of patients have sigtimes “rage niﬁcant oxygen phenomenon”) desaturation Confusion • Contraindicated Nausea or in liver impairvomiting ment Apnea or • Provides bradycardia immobility Hypotension (continued on next page)

Drug Dose/Route

Children > 10 yr IV 0.1–0.4 mg/kg For general anesthesia: IV 0.2–0.6 mg/kg followed by an infusion of 5–20 mcg/kg/min

Adverse Duration Effects

Comments

IV <1 min

IV 5–10 min Hypotension Apnea Arrhythmia Pruritus Rash Signiﬁcant respiratory depression

• Good for quick sedation and rapid recovery • Mandatory use of capnography and continuous pulse oximetry

IV 1 min

IV 4–8 min

• Does not cause hypotension or increased ICP • Caution in patients with adrenal insufﬁciency

IV 0.5 – 1 mg/kg Maximum dose, 50 mg followed by an infusion of 50–150 mcg/kg/min Adults and children >50 kg: bolus in 20- to 50-mg increments, followed by infusion as above

Dexmedetomidine

Etomidate

Propofol

Only used for deep sedation in some institutions∗

Onset

19

Apnea Myoclonic jerks Adrenal suppression Nausea or vomiting Hiccups

Bradycardia • Contraindicated in patients with Hypertension (in rapid admin- renal failure, severe hepatic istration) impairment, Hypotension heart block, Nausea hypotension, 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 flumazenil 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 apneafree hours. • Discharge criteria: CV function and airway patency stable, easily arousable and protective reflexes intact, can talk if verbal, can sit if appropriate, and can drink fluids with adequate hydration status.

G E N E R A L C L I N I C A L I N F O R M AT I O N

Analgesia and Sedation

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 reflexes 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

Procedures NEEDLE DECOMPRESSION OF PNEUMOTHORAX • Indications: (1) Tension pneumothorax • Complications: Pneumothorax, bleeding, nerve damage, infection

Setup Equipment Needed for Needle Decompression of Pneumothorax • Personal protection equipment: Gloves, gown, face and eye shield • Pulse oximeter and cardiorespiratory monitor • Oxygen supply via nonrebreather mask • Antiseptic skin prep solution (eg, Povidone-iodine, Chlorhexidine)

• Local anesthetics: 1% lidocaine drawn up • 16- to 20-gauge needle or plastic-over-theneedle catheter (IV catheter) • 50-mL syringe with a stopcock • Occlusive dressing (vaseline gauze, 4 × 4 gauzes and tape)

Procedure • Attach the patient to a cardiorespiratory monitor and apply oxygen per nonrebreather mask. • On the affected side, locate the second intercostal space at the midclavicular line. • Prep the skin using sterile techniques if patient is stable. • If the patient is stable, raise a wheal with 1% lidocaine over the superior edge of the rib below the intercostal space (third rib). • Penetrate the skin over the superior edge of the rib using a 16- to 20-gauge IV catheter. • Advance the IV catheter gradually until a pop is heard or felt on entry of the pleural space. • Remove the needle (a rush of air may be audible as tension is released). • Attach a syringe with a stopcock to the hub of the catheter. • Withdraw desired air, releasing further tension. • Withdraw the needle at the end of the procedure and apply an occlusive dressing to the site (preferably with 3 of 4 sides fixed to skin to create a one-way flap-valve for further decompression). • Obtain a CXR to assess the results of the procedure.

CHEST TUBE PLACEMENT INDICATIONS FOR CHEST TUBE PLACEMENT Emergent

Non-emergent

Pneumothorax • Large pneumothoraces • In all patients on mechanical ventilation • Tension pneumothorax after needle decompression • Recurrent or persistent pneumothorax • Pneumothorax secondary to chest trauma Hemopneumothorax Esophageal rupture with gastric leak into the pleural space

Malignant pleural eﬀusion Recurrent pleural eﬀusion Treatment with sclerosing agents or pleurodesis Parapneumonic eﬀusion or empyema Chylothorax Postoperative care (eg, after coronary bypass, thoracotomy, or lobectomy)

Reproduced with permission from: NEJM 2007;357:e15.

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G E N E R A L C L I N I C A L I N F O R M AT I O N

CHAPTER 3

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, gowns, face and eye shield • Medications for sedation and systemic analgesia • Antiseptic skin prep solution (eg, Povidone-iodine, Chlorhexidine) • 1% lidocaine with epinephrine

• Chest tube tray, including correct size chest tube, a #11 scalpel blade and handle, a curved Kelly clamp, needle driver, and scissors • Chest tube suction unit, including tubing and wall suction hookup • Nonabsorbable 10 silk suture • Occlusive dressing (vaseline gauze, 4 × 4 gauze and tape)

CHEST TUBE SIZE

Age

Chest Tube Size (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 fifth intercostal space in the anterior axillary line at the level of the nipple. • Prep the skin using antiseptic solution; arrange a sterile field 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.)

23

• Use a Kelly clamp to bluntly dissect the sub-Q tissue and intercostal muscles down to the pleura. • Insert your index finger 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 fluid 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 (gown, face and eye shield as indicated) • Topical anesthetic cream • Oral sucrose solution for neonates • Antiseptic skin prep solution (eg, Povidoneiodine, Chlorhexidine)

• A 20 to 22-gauge spinal needle with a stylet (NEEDLE LENGTH < 2yr: 1.5 in; 2-12yr: 2.5 in; >12yr: 3.5 in) • Manometer (if measurement of opening pressure is indicated). • 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.

G E N E R A L C L I N I C A L I N F O R M AT I O N

Procedures

24

General Clinical Information

L4

Dura L4

L5

Subarachnoid space 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 flexed 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 flexion, 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 flowing. (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 fluids, 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

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 fluid extravasation, soft tissue abscess, or osteomyelitis (risk ↓ if IO removed within 3 h of placement)

Setup Equipment Needed for Intraosseous Access • Personal protection equipment: Gloves, (gowns, face and eye shield as needed) • Pillow or rolled towels • Povidone-iodine solutions, alcohol swabs • 1% lidocaine in a 3-cc syringe with a 27-gauge needle for local anesthesia (optional)

• 16- or18-gauge IO needle or EZ-IO (for 3–39 kg use: 15 mm, 15 gauge; ≥40 kg use 25 mm, 15 gauge) or 16- or 18-gauge spinal needle with stylet • Extension tubing with three-way stopcock • 5- or 10-cc syringe • NS ﬂush syringes • 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, infiltrate the skin and down to the periosteum with 1% lidocaine. • Prepare IV tubing with a three-way stopcock and fluids. • Hold the IO needle with the stylet ball in the palm of your hand and place the tip of your index finger 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 firm, 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) flushing with NS to ensure there is no resistance or extravasation of fluid. • 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 fluids to flow. Secure tubing to the leg with tape.

CENTRAL VENOUS LINE (CVL) ACCESS • Indications: (1) peripheral sites are inaccessible, (2) emergent situation requiring largebore IV catheter to deliver rapid fluid 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.

G E N E R A L C L I N I C A L I N F O R M AT I O N

Procedures

26

General Clinical Information

Setup Equipment Needed for Central Venous Line Access • Personal protection equipment: Sterile gloves, gown, face and eye shield • Cardiopulmonary monitor • Sterile drapes • Antiseptic skin prep solution (eg, PovidoneIodine, Chlorhexidine) • Central line kit with appropriate catheter size (2 Fr for neonates; 3 or 4 Fr for children 1-5 years old; 5 Fr for older children)

• 1% lidocaine in a 3-mL syringe with a 25-gauge needle • Sedation and analgesia medications • A rolled-up blanket/towel • IV tubing and IV ﬂuid • Heparinized NS ﬂushes (1 unit heparin per mL NS) • Sterile occlusive dressing (Veni-Gard), Tape • 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 flexed 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 fluid. • 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 flash of blood returns). If CVP is low (eg. hypovolemia), a flash 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.)

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 flushed 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 confirm backflow 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 fluids, 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

G E N E R A L C L I N I C A L I N F O R M AT I O N

Procedures

28

General Clinical Information

Setup Equipment Needed for Umbilical Artery Catheterization • Personal protection equipment: Sterile gloves, gowns, face and eye shield, surgical cap • Radiant warmer with a light source • Cardiopulmonary monitor and pulse oximeter • Sterile drapes • Scalpel (#11 or #15) • Antiseptic skin prep solution (eg, Povidone-iodine, Chlorhexidine) • Curved, nontoothed iris forceps • Small, smooth, curved hemostats • Straight Crile forceps • Iris scissors

Figure 3-4 Course of the UAC and UVC.

• Needle holder • Nonthrombogenic, molded-tip umbilical artery catheters (3.5 Fr for infants <1.2 kg; 5.0 Fr for infants >1.2 kg) • 3-0 or 4-0 silk suture on a curved needle • Linen umbilical tape • Adhesive tape • 10-mL syringe ﬁlled with heparinized NS (1 unit herparin per 1 mL NS) • IVF infusion setup • IV tubing and infusion pump • Three-way stopcock

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. (Significant force should not be used.) • Aspirate the catheter when in position to verify blood return. • Connect the catheter to the fluid and IV tubing. • Remove the umbilical tape. • Obtain abdominal radiograph to confirm the position and make adjustments to the catheter length (catheter may only be advanced under sterile conditions; once sterile field 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 fluids, (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

G E N E R A L C L I N I C A L I N F O R M AT I O N

Procedures

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 floppy 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. (Significant force should not be used.) • Aspirate when the catheter is in position to verify blood return. • Connect the catheter to the fluid and IV tubing. • Obtain an abdominal radiography to confirm 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 gloves (gowns, face and eye shield, surgical cap as needed) • Sterile drapes • Scalpel • Antiseptic skin prep solution such as chlorhexidine or povidone-iodine solution • Laceration repair kit, including a needle holder, tooth forceps, and scissors • Sterile NS

• Sterile gauze • 60-mL syringe with a splash guard or NS spray bottle for irrigation • Towels and bowl • Appropriate bicarbonate buffered anesthesia (see Laceration Management table) in a 3-mL syringe with a 25- or 27-gauge needle • Suture materials appropriate for wound (see Laceration Management table)

LACERATION MANAGEMENT Superficial Suture Special Location Anesthesia* Deep Suture Suture Dressing Removal Note Scalp

1% lidocaine with epinephrine

3–0 or 4–0 Vicryl

4–0 or 5–0 Nylon

Bacitracin, 5–7 days air

Pressure dressing if early hematoma

(continued on next page)

31

Superficial Suture Special Location Anesthesia* Deep Suture Suture Dressing Removal Note Pinna

1% lidocaine

5–0 Vicryl in 6–0 Nylon perichondrium

Bacitracin

Eyelid or eyebrow

1% lidocaine

5–0 Vicryl

5–0 or 6–0 Nylon

Bacitracin, 4–5 days air

Do not shave hair

Lip

1% lidocaine with epinephrine

5–0 Vicryl

6–0 Nylon (rapid)

Air

Care with vermillion border

Face or forehead

1% lidocaine with epinephrine

5–0 Vicryl

6–0 Nylon

Bacitracin, 4–6 days air

Care with facial nerve

Neck

1% lidocaine with epinephrine

4–0 Vicryl

5–0 Nylon

Bacitracin, 4–6 days air

Through Platysma

Trunk

1% lidocaine with epinephrine

4–0 Vicryl

4–0 or 5–0 Nylon

Bacitracin

Extremities or buttocks

1% lidocaine with epinephrine

4–0 or 5–0 Vicryl

4–0/5–0 Nylon 3–0 for over joints

Bacitracin, 7–10 days xeroform 10–14 days if over joints

Hands

1% lidocaine

None

5–0 or 6–0 Nylon

Bacitracin, 7–10 days xeroform 10–14 days if over joints

5–0 rapid if <5 yr old

5 days

NA

Light pressure dressing

7–10 days Rule out abdominal pathology

Nailbeds

1% lidocaine

None

6–0 Vicryl

Bacitracin, NA xeroform

Splint ﬁnger, antibiotics

Feet or sole

1% lidocaine

None

3–0, 4–0, or 5–0 Nylon

Bacitracin, 10–14 xeroform days

Kling wrap

Scrotum

1% lidocaine

None

5–0/6–0 Vicryl 5–0 gut

Bacitracin, NA air, 4 x 4 ﬂuﬀ scrotal support

Penis

1% lidocaine

None

5–0 Nylon

Bacitracin, 6–8 days air

*Use bicarbonate-buﬀered 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, fingers, 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).

G E N E R A L C L I N I C A L I N F O R M AT I O N

Procedures

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 first 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).

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, gown, face and eye shield, surgical cap • Sterile drapes • 1% lidocaine with epinephrine for local anesthesia (in 10-cc syringe with 25-gauge needle) • Sedation medications • Antiseptic skin prep solution (eg, Povidoneiodine, Chlorhexidine)

• #11 scalpel blade with a handle • A curved hemostat and scissors • Wound-packing material, 0.25-inch packing strips (eg “iodoform” gauze ribbon) • NS spray for irrigation • Gauze • Tape • 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 field. • Infiltrate 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 fluid 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 effluent 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

G E N E R A L C L I N I C A L I N F O R M AT I O N

Procedures

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Section 2: Nutrition, Growth and Formula CHAPTER 4

Neonatal and Pediatric Nutrition VITAMIN AND MINERAL SUPPLEMENTATION IN TERM AND PRETERM NEONATES Feeding Regimen

Recommended Supplementation

Human milk fortiﬁed with HMF

BW <2500 g: Iron (2 mg/kg/d) beginning after age 2 weeks until age 1 year BW >2500 g: No recommendation for higher iron needs for this group

Unfortiﬁed human milk

All: Multivitamin (1 mL/d) BW <2500 g: Iron (2 mg/kg/d) beginning after age 2 weeks until age 1 year BW >2500 g: No recommendation for higher iron needs for this group

Premature iron-fortiﬁed formula

None indicated

Premature iron-fortiﬁed transitional formula

None indicated

Term iron-fortiﬁed formula (weight <3 kg)

Multivitamin (1 mL/d) until weight >3 kg

Term Infants Human milk exclusively

Iron (1 mg/kg/d) starting at age 4–6 months Triple vitamin (A, D, C) at 1 mL/d within the ﬁrst few days of life

Term iron-fortiﬁed formula (weight >3kg)

Not indicated

∗HMF is not to be used at discharge. Reproduced with permission from Pediatric Nutrition Reference Guide, 8th ed:57.

BREASTFEEDING Chandran L & Gelfer P. Breastfeeding: the essential principles. Pediatr Rev 2006; 27(11):409. American Academy of Pediatrics Policy Statement. Pediatrics 2005;115(2):496.

Contraindications to Breastfeeding • Galactosemia in an infant • Active maternal illegal drug use • Active, untreated maternal tuberculosis (The mother should be separated from her infant, expressing milk for the baby to be fed via bottle. After treatment has begun and the mother is allowed to be with her infant, she can resume breastfeeding.) • Maternal HIV infection (in developed countries)

35

NUTRITION, GROWTH AND FORMULA

Preterm Infants

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 first week(s) of breastfeeding. • Have no more than one 4-hour sleep period in 24 hours during the first 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)

5d

Store milk in back of refrigerator, where temperature is coolest

Freezer portion of refrigerator

5°F (−15°C)

2 weeks

Store milk in back of freezer; over time, the lipids in milk degrade

Freezer portion of refrigerator with separate doors

0°F (−18°C)

3–6 mo

Upright deep freezer

−4°F (−20°C)

6–12 mo

Freezer

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 benefits of trophic feedings has been well established. • Enteral nutrition helps maintain normal gut flora and immunity. • A wide range of commercially available formulas have made it significantly 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.

GI tract functional?

No

Consider TPN

Yes Normal gut function: • Human milk • Standard infant/ pediatric/ adult formula

Determine appropriate formula

Abnormal gut function: • Protein hydrolysate • Peptide based • Elemental • 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.)

NUTRITION, GROWTH AND FORMULA

Establish need for enteral nutrition support patient unable to take adequate PO due to: • ↑Energy requirement • Physiologic impairment

38

Nutrition, Growth and Formula

Feeding Methods Site

Delivery Route

Indications

Complications

Stomach

Orogastric or nasogastric

• Short term (6–8 wk) nutrition support • Inadequate oral intake • Refusal to eat • Nocturnal feeds • Inability to suck or swallow

• Aspiration • Nasal mucosal ulceration • Tube occlusion • Pneumothorax • Bleeding • Epistaxis

Gastrostomy

• Long-term nutrition support • Congenital anomalies of the GI tract • Esophageal injury or obstruction • Failure to thrive

• Dislodgement • Aspiration • Tube deterioration • Bleeding • Tube occlusion • Pneumoperitoneum • Wound infection • Stoma leakage

Nasoduodenal Nasojejunal Gastrojejunal Jejunostomy

• Congenital upper GI anomalies • Inadequate gastric motility • High aspiration risk • Severe GER • Functioning intestinal tract with proximal obstruction

• Pneumatosis intestinalis • Bleeding • Dislodgement • Tube deterioration • Tube occlusion • Bowel obstruction • Stomal leakage • Wound infection

Transpyloric

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

Method of Enteral Feeding Type

Indications

Advantages

Disadvantages

Bolus or intermittent feeds

• Dysphagia • Anorexia • Supplement to oral intake

• Physiologic method of feeding • Increased patient mobility • May not require a pump • Flexible feeding schedule

• May increase risk of aspiration • Poorly tolerated in patients who cannot tolerate volume (severe GER or delayed gastric emptying)

Continuous feeds

• Delayed gastric emptying • Increased risk of aspiration • Limited absorptive surface area

• Preferred method for small bowel feeding • Slow infusion may improve tolerance • May be given nocturnally to lessen the interruption of daytime schedule and oral intake

• Requires feeding pump • Patient is attached to the pump for the duration of feeding

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

Neonatal And Pediatric Nutrition

39

Monitoring Enteral Feeding Prevention or Intervention

Diarrhea or abdominal cramping

• Decrease delivery rate. • Recognize or avoid drugs that may cause diarrhea. • Consider increasing ﬁber 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. • 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 ﬂuid intake. • Increase free water intake. • Change to ﬁber-containing product.

Gastric retention of formula

• Monitor for correct tube placement. • 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 ﬂushed 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 fortifier 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 fluid 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.

NUTRITION, GROWTH AND FORMULA

Problem

40

Nutrition, Growth and Formula

TPN in Ten: A Step By Step Guide 1. Calculate the IV fluid (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 fluids must be tailored to address individual clinical requirements (eg, children with increased fluid losses from any source; children in renal failure or other fluid 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 fluid (See chapter 1 for BSA calculations). This is the total volume of fluid 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.

Total Energy DRI (kcal/kg/d)∗

Age 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 Schofield method or WHO; they should not be used with the DRIs above. 12% for each degree >37°C 1.15–1.25

Major surgery

1.20–1.30

Sepsis

1.40–1.50

Catch-up growth

1.50–3.00

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 Schofield method:

Basal Metabolic Rate (kcal/d)∗ Male 0–3 yr

Female

(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)

NUTRITION, GROWTH AND FORMULA

Fever Cardiac failure

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 deficiency • 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 final 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 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

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 Reference Guide, 8th ed:81.

NUTRITION, GROWTH AND FORMULA

% Dextrose

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® (adult)

3300 6

Infuvite® 2300 1.2 (pediatric)

3.6

6

5

200

200

10

150

Biotin 60 mcg Folic acid 600 mcg Niacinamide 40 mg Dexpanthenol 15 mg

1.4

1

1

80

400

7

200

Biotin 20 mcg 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 efficacy 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

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 fortifier. • 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.

NUTRITION, GROWTH AND FORMULA

• Does 30% of calories come from fat? Remember that fat should be at least 5% of calories to prevent essential fatty acid deficiency. • 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.

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 profile 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 deficiency (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 deficiency 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 (kcal/oz)

Liquid Mead Johnson Concentrate∗ Powder† All brands

Enfamil Lipil, AR,‡ LactoFree Lipil, ProSobee, Next Step

Nestle Powder†

Abbott Powder†

Nestle Good Start

Similac Advance, Similac Sensitive, Lactose Free, Isomil and Isomil 2, Similac 2, Alimentum or PM 60/40 (continued on next page)

Neonatal And Pediatric Nutrition Caloric Density (kcal/oz)

47

Nestle Powder†

Abbott Powder†

20

1 oz conc. + 1 oz sterile water

1 unpacked scoop + 2 oz sterile water = 2.2 oz (65 mL) formula

1 unpacked scoop + 2 oz sterile water = 2.25 oz (67.5 mL) formula

1 unpacked scoop + 2 oz sterile water = 2 oz (60 mL) formula

24

3 oz conc. + 2 oz sterile water

3 unpacked scoops + 4.8 oz (144 mL) sterile water = 5.6 oz (168 mL) formula

3 unpacked scoops + 4.9 oz (145 mL) sterile water = 5.6 oz (164 mL) formula

3 unpacked scoops + 5 oz (150 mL) sterile water = 6 oz (180 mL) formula

27

2 oz conc. + 1 oz sterile water

2 unpacked scoops + 3 oz (90 mL) sterile water = 3.5 oz (105 mL) formula

3 unpacked scoops + 4.3 oz (127 mL) sterile water = 4.9 oz (146 mL) formula

3 unpacked scoops + 4.25 oz (127.5 mL) sterile water = 5 oz (150 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 and ARA

1.3

2.6

4.6

6.5

2.2

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.

NUTRITION, GROWTH AND FORMULA

Liquid Mead Johnson Concentrate∗ Powder†

48

Nutrition, Growth and Formula

Human Milk Fortifier (HMF) g 4 packets

mg (mEq)/4 packets

Product

CHO

Fat

Prot

Na

K

Ca

P

Fe

VitD (IU / dL)

Enfamil HMF (Mead Johnson)

<0.4

1

1.1

16 (0.7)

29 (0.8)

90 (4.5)

50

1.44

150

Similac HMF (Abbott Nutrition)

1.8

0.4

1

15 (0.7)

63 (1.6)

117 (5.9)

67

0.4

120

Source of Product

CHO

Fat

Prot

Enfamil HMF (Mead Johnson)

Corn syrup solids

High-oleic sunﬂower, soy, MCT and coconut oils

Whey protein hydrolysate, milk protein isolate (whey:casein ratio, 60:40)

Similac HMF (Abbott Nutrition)

Corn syrup solids

MCT oil

Whey protein concentrate, nonfat 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 fortification 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

CHAPTER 5

Assessment of Nutrition and Growth CHARTS OF BODY MASS INDEX FOR AGE • Body mass index (BMI) is calculated as follows: BMI = (Weight in kg)/(Height in m)2

GROWTH CHARTS Standard growth charts are available at www.cdc.gov/growthcharts or www.accesspediatrics.com.

Specialized Growth Charts • Down Syndrome Growth Chart: Pediatrics 1978;61:564. • Cerebral Palsy Growth Chart: J Am Diet Assoc 1996;96:680. • Turner Syndrome Stature Chart: Arch Dis Child 1985;60;932. • Achondroplasia Growth Chart: J Pediatr 1978;93:435. • Noonan Syndrome Growth Chart: Clin Genet 1986;30:150. • Williams Syndrome Growth Chart: Pediatrics 1988;113:318.

MALNUTRITION Waterlow Criteria • These criteria are appropriate for children ages 1 to 3 years. • Changes in weight may be an indicator of acute malnutrition. Actual wt(kg) × 100 Expected wt for ht at 50th %ile • Grade 0: ≥90% (normal) • Grade I: 80%–89% (mild) • Grade II: 70%–79% (moderate) • Grade III: <70% (severe) • Changes in height may be an indicator of chronic malnutrition. Actual ht (cm) × 100 Expected ht for age at 50th %ile • Grade 0: ≥95% (normal) • Grade I: 90%–94% (mild) • Grade II: 85%–89% (moderate) • Grade III: <85% (severe) • Head circumference is influenced by nutritional status until age 36 mo.

49

NUTRITION, GROWTH AND FORMULA

• BMI is an effective screening tool, not a diagnostic one. • For children, BMI is age and gender specific. • Children who are at the 85th to 95th percentiles are considered overweight. • Children who are at or above the 95th percentile are considered obese. • Children who are below the 5th percentile are considered underweight. • BMI charts: www.cdc.gov/growthcharts or www.accesspediatrics.com

50

Nutrition, Growth and Formula Fetal-Infant growth chart for preterm infants* 65

65

60

97% 90%

55

gth Len

55

50% 10% 3%

50

50 45

45

d Hea

35

97% 90% 50% 10% 3%

40 6 5.5

30 97%

25

5

90%

20

4.5 50%

4

4

t gh ei W

3.5

Weight (kilograms)

3.5

10% 3%

3

3

2.5

2.5

2

2

1.5

Plot growth in terms of completed weeks of gestation. Sources: Intrauterine weight - Kramer MS et al (ePediatr 2001); Length and Head circumference Niklasson A et al (Acta Pediatr Scand 1991) and Beeby PJ et al (J Paediatr Child Health 1996); Post term sections the CDC Growth Charts, 2000. The smoothing of the disjunction between the pre and post term sections generally occurs between 36 and 46 weeks.

1 0.5 0 22

Weight (kilograms)

Centimeters

40

nce fere um c r i c

Centimeters

60

24 26

28

30

32

34

36

38 40∗ 42

44

46

1.5 1 0.5

0 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 deficiencies and toxicities • Standard growth charts

Section 3: Pediatrics CHAPTER 6

Adolescent Medicine GYNECOLOGIC EXAM • Examination inspection, speculum exam, and/or, bimanual examination

Indications • For pelvic exam: Symptoms of vaginal or uterine infection, asymptomatic STI screening in sexually active young women, menstrual disorders, undiagnosed lower abdominal pain, sexual assault, suspected pelvic mass, request by the patient. • For Pap smear: Cervical cancer screening should begin at age 21, not sooner, regardless of sexual history (Obstetrics and Gynecology. 2009; 114(6):1409). • Considerations: Patients with physical or mental disability, abnormal anatomy, or physical immaturity with an intact hymen may be difficult to examine; consider exam under general anesthesia.

Equipment EQUIPMENT NEEDED FOR GYNECOLOGIC EXAM • Cotton-tip swabs • pH paper • 10% KOH and saline for wet mounts • Water-soluble lubricant • Disposable nonsterile gloves • Microscope, glass slides, cover slips • Female chaperone, if appropriate

P E D I AT R I C S

• Gown and drape to cover the patient • Exam table with ankle support • Examination light • Speculum • Gonorrhea culture medium or NAAT • Chlamydia screening test– NAAT if available; otherwise culture • Spatula or cytobrush for Pap test, Pap slide containers or ﬁxative; ThinPrep™ kits or other Pap systems

Procedure • 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. • Place the draped patient in the supine position with her feet in ankle supports and have her slide her buttocks to the edge of the exam table and relax her legs into abduction. • Abdomen (inspection, auscultation, palpation, percussion): Examine for skin changes, hernias, organomegaly, masses, tenderness. • External genitalia • Examine hair distribution (note sexual maturity rating), skin changes, labia minora and majora, clitoris, introitus, perineal body, Bartholin glands, Skene’s glands, and urethral meatus. • Palpate for tenderness and adenopathy. • Internal genitalia (speculum exam) • Let the patient know the gel is cold; insert an index finger into the distal vagina and ask the patient to voluntarily contract against the finger (Kegel maneuver). Then insert a second finger (middle) and ask the patient to contract against the finger. • Slowly insert an appropriately sized speculum into the vagina while applying downward pressure. Enter the speculum completely.

51

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 specific 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 fingers 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 flora, 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 nonspecific 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 Vaginitis

Bacterial Vaginosis

Trichomonas vaginalis Infection

Symptoms

Itching and burning

Foul discharge

Itching and burning

Discharge

Thick and white

Watery, positive “whiﬀ ” test result∗

Frothy, ± positive “whiﬀ ” test∗ (continued on next page)

Adolescent Medicine

Microscopy

Yeast Vaginitis

Bacterial Vaginosis

Trichomonas vaginalis Infection

Hyphae seen on KOH prep

Clue cells on saline prep

Trichomonads on saline prep

53

Vaginal pH

<5

5–7

5–7

Treatment

Intravaginal antifungal cream, tablet, or suppository (clotrimazole 1%, miconazole 2%, terconazole 0.4%) used as directed or Fluconazole 150 mg PO x1

Metronidazole 500 mg PO BID × 7 d or Metronidazole gel 0.75%: 1 applicator intravaginally daily ×5d or 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

Metronidazole 2 g PO once or Tinidazole 2 g PO once or Metronidazole 500 mg PO BID × 7 d

∗ A positive "whiﬀ " test occurs when a ﬁshy 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

Disease (Organism) Uncomplicated N. Gonorrhea infection of cervix, urethra or rectum (Neisseria gonorrhea)

Clinical Features

Laboratory Diagnosis

Treatment for Adolescents†

Many are asymptomatic Urethritis‡ is common in young men Rectal infection (usually asymptomatic but may have pruritus, mucopurulent rectal discharge) Mucopurulent cervicitis (yellow-green discharge, friable cervix, >30 PMNs on Gram stain) PID (see below) Perihepatitis (Fitz-Hugh-Curtis syndrome; RUQ pain, liver tenderness) Bartholin or Skene gland abscesses Pharyngitis (usually asymptomatic) Disseminated gonococcal infection in 1%–3%

Positive urine leukocyte esterase result Gram stain demonstrating intracellular gram-negative diplococci Cell culture is gold standard ELISA DNA probes PCR (swab and urine tests available)

Ceﬁxime 400 mg PO once or Ceftriaxone 125 mg IM once Test for reinfection in 3-6mo Note: If chlamydial infection has not been ruled out, treat for both Chlamydia and gonorrhea.

(continued on next page)

P E D I AT R I C S

DIAGNOSIS AND TREATMENT OF SEXUALLY TRANSMITTED INFECTIONS∗

54

Pediatrics

Disease (Organism)

Laboratory Diagnosis

Treatment for Adolescents†

Many are asymptomatic Urethritis is common in young men Mucopurulent cervicitis Epididymitis (gradual onset of red, edematous scrotum in area of epididymis) PID Perihepatitis

Positive urine leukocyte esterase result Cell culture is gold standard

Azithromycin 1 g PO once or Doxycycline 100 mg PO BID × 7–10 d Test for reinfection in 3–6mo

Herpes simplex (Herpes simplex virus)

1- to 2-mm vesicles in clusters that may coalesce with an erythematous base; painful; tender lymphadenopathy

Tzanck prep: multinucleated cells Viral culture HSV PCR

See table: Treatment for Herpes Simplex Virus Infections (see below)

Syphilis (Treponema pallidum)

5- to 15-mm solitary papule with sharp base and induration; nontender; bilateral nontender lymphadenopathy

Dark ﬁeld microscopy RPR, VDRL FTA-ABS, MHA-TP

Treatment for primary, secondary, and early latent disease: Penicillin G benzathine 50,000 U/kg IM, up to adult dose of 2.4 million U in a single dose

Chancroid (Haemophilus ducreyi)

2- to 20-mm multiple papules or pustules that may coalesce; ragged border; purulent; tender; unilateral tender lymphadenopathy

Culture

Azithromycin 1 g PO once or Ceftriaxone 250 mg IM once or Ciproﬂoxacin 500 mg PO BID × 3 d or Erythromycin base 500 mg PO TID × 7 d

Lymphogranuloma Venereum (Chlamydia trachomatis)

2- to 10-mm solitary papule/vesicle; ±painful; unilateral tender lymphadenopathy

Complement ﬁxation Immunoﬂuorescent antibody serologic testing

Doxycycline 100 mg PO BID × 21 d or Erythromycin base 400 mg PO QID × 21 d

Chlamydia (Chlamydia trachomatis)

Clinical Features

ELISA DFA DNA probes PCR (swab and urine tests available)

∗ 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: Inﬂammation 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, conﬁrmed with cell culture or NAAT.

Adolescent Medicine

55

TREATMENT OF HERPES SIMPLEX VIRUS INFECTIONS Primary Outbreak Acyclovir 400 mg PO TID × 7–10 d† or Valacyclovir 1 g PO BID × 7–10 d† or Famciclovir 250 mg PO TID × 7–10 d

Suppressive Therapy

Recurrence∗ Acyclovir 800 mg PO BID × 5 d or Acyclovir 800 mg PO TID × 2 d or Valacyclovir 500 mg PO BID × 3 d or Valacyclovir 1 g/d PO × 5 d†

Acyclovir 400 mg PO BID† or Valacyclovir 500 mg/d PO† or Valacyclovir 1 g/d PO† or Famciclovir 250 mg PO BID

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

Pelvic Inflammatory Disease

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)

P E D I AT R I C S

• Definition: Infection or inflammation 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 Chlamydia or N. gonorrhea infection, WBCs on vaginal wet prep, elevated ESR or CRP. • More specific criteria: Endometrial biopsy with evidence of endometritis, transvaginal ultrasonography or MRI demonstrating thickened tubes, free pelvic fluid, tubo-ovarian abscess. • Complications: Disease recurrence (one episode predisposes to more episodes); chronic abdominal pain; increased risk of ectopic pregnancy; increased risk of infertility; tuboovarian 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.

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, fleshy 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: Podofilox 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

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• Intense fear of gaining weight or being fat, although underweight • Disturbance in the way one’s body weight or shape is experienced, undue influence 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 definitely 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 selfinduced 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 influenced 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 Specified

CLINICAL FEATURES AND POTENTIAL COMPLICATIONS OF EATING DISORDERS

General

Anorexia Nervosa

Bulimia Nervosa

Cold intolerance, weakness, fatigue, dry and hyperkeratotic skin, lanugo, hypothermia, acrocyanosis, edema

Weakness, fatigue, weight ﬂuctuations, calluses on the dorsum of hands, painless parotid gland enlargement, dental enamel erosion and caries, edema (continued on next page)

P E D I AT R I C S

• Patients with disorders of eating who do not fulfill the criteria for AN or BN. • Examples include: • For females, all the criteria for AN are met except that the individual has regular menses. • All the criteria for AN are met except that, despite significant 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.

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Bulimia Nervosa

CNS

Poor concentration, muscle weakness, peripheral neuropathies, seizures, cortical atrophy, cognitive processing diﬃculties

Headaches, muscle cramps, seizures

CV

Postural dizziness and fainting with 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 eﬀusion, CHF

Arrhythmias, cardiomyopathy

Endocrine

Amenorrhea, pubertal delay, poor 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

Irregular menses

GI

Abdominal discomfort, constipation, delayed gastric emptying, SMA syndrome, acute fatty necrosis

Abdominal discomfort, nausea, esophagitis, Mallory-Weiss tears, rupture of esophagus or stomach, acute pancreatitis, paralytic ileus

Hematologic

Leukopenia, anemia, thrombocytopenia, decreased C3 and ESR

Platelet dysfunction

Metabolic

Dehydration; low phosphorus, magnesium, calcium, potassium, sodium, zinc, copper, glucose, vitamin A; high cholesterol, carotene

Dehydration; low phosphorus, potassium, sodium levels

Psychological

Perfectionist, “type A” personality, introverted, poor self-esteem, denial of problem

Impulsive, prone to acting out, outgoing, poor self-esteem, aware of problem and seeks help

Renal

Elevated BUN, decreased GFR, nephrogenic DI, metabolic alkalosis, alkaline urine

Elevated BUN with excessive vomiting, metabolic alkalosis, 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)

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• Interdisciplinary approach with medical provider, mental health provider, and dietician. • Avoid IV fluid 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 first 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 fluid 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 efficacy 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

P E D I AT R I C S

CHAPTER 7

Allergy and Immunology GELL AND COOMBS CLASSIFICATION OF HYPERSENSITIVITY IMMUNE RESPONSES Type

Mechanism

Examples

I: Anaphylactic or immediate hypersensitivity

IgE-mediated mast cell degranulation and activation

Anaphylaxis, allergic rhinitis, allergic asthma, acute urticaria, insect sting allergy

II: Antibodymediated cytolytic reactions

IgM or IgG against antigens bound to cell membrane structures

Autoimmune or drug-induced hemolytic anemia, Goodpasture’s disease, Rh hemolytic disease

III: Immunecomplex mediated

Complexes of IgM or IgG and circulating antigens

Serum sickness, SLE, vasculitis, poststreptococcal glomerulonephritis

IV: Delayed hypersensitivity

T lymphocytes

Tuberculin skin test reactions, GVHD, 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 falsepositive 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-specific IgE assays (eg, RAST) measure circulating Ag-specific IgE and have similar predictive value to skin testing.

Anaphylaxis • Definition: A serious allergic reaction that is rapid in onset and may cause death • Differential Diagnosis: • Vasovagal syncope, panic attack, hyperventilation, systemic mastocytosis, scombroid fish poisoning. Rare causes include carcinoid syndrome, pheochromocytoma, and idiosyncratic 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, shellfish, fish, eggs, milk), insect venom, latex, drugs, immunotherapy • Pathophysiology: Production of IgE in a susceptible individual (sensitization)→ IgEsensitized 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, flushing, 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.

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• 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-specific IgE assays or IHST may be used later to confirm. 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 flushing, 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 Dose

Comments

Epinephrine

0.01 mg/kg (0.01 mL/kg of 1:1000 solution); IM or Sub Q every 3–5 min as needed; 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

Immediate eﬀect, ﬁrst-line therapy

Albuterol

2.5–5 mg nebulized as needed

Airway management

Methylprednisolone or hydrocortisone

2 mg/kg IV 0.5–2.0 mg/kg IV (maximum dose, 250 mg)

No immediate eﬀect, prevention of second wave of symptoms

Diphenhydramine (H1 blocker)

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

Adjunctive therapy

Ranitidine (H2 blocker)

1 mg/kg IV (maximum dose, 50 mg) q6h as needed

Adjunctive therapy

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

Urticaria and Angioedema • Definition: 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 • Classification • Acute: ≤6 to 8 weeks; viral infections, insect stings, foods, drugs (ACEI angioedema) • Chronic: > 8 weeks; physical urticaria (cold, cholinergic, pressure, vibratory, dermographism, exercise); urticarial vasculitis (biopsy for dx); autoimmune urticaria (anti-IgE receptor antibody, anti-thyroglobulin antibody, antimicrosomal antibody); chronic idiopathic urticaria (most likely cause autoimmune)

P E D I AT R I C S

Agent

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• 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 deficiency • 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 danozol with epsilon aminocaproic acid is an option. Recombinant human C1-INH is FDA approved in the United States for prophylaxis.

Allergic Rhinitis • Definition: Allergen-driven inflammation 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 specific than serum assays for allergen-specific 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 steroids

Mometasone furoate, ﬂuticasone

Mainstay of therapy

Antihistamine

Loratadine, fexofenadine, cetirizine

Avoid the use of sedating ﬁrstgeneration antihistamines (continued on next page)

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63

Agents

Example of Medication

Comments

Nasal decongestants

Pseudoephedrine

Use judiciously because of rebound congestion if used >5–7 days

PO and IM steroids

Prednisolone, prednisone

Rarely used due to systemic side eﬀects

Mast cell stabilizer

Cromolyn sodium

Intranasal use

Leukotriene receptor antagonist

Montelukast sodium

Typical use in association with asthma

Immunotherapy (subcutaneous)

Administration of speciﬁc perennial or seasonal allergen(s) identiﬁed as associated with rhinitis in the patient Sublingual immunotherapy not FDA approved

Use when medical management and environmental controls failed Success rate, 80% Discontinue after 3–5 yr for patients with good response

PRIMARY IMMUNODEFICIENCY • Definition: Primary immunodeficiencies (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. • Classification: Classified 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 deficiency (2%). • Diagnosis: Consider work up if two or more warning signs are present (see table below). A genetic defect can often be identified in individuals with PI.

TEN WARNING SIGNS OF PRIMARY IMMUNODEFICIENCY Eight or more new ear infections within 1 year

Two or more months on antibiotics with little eﬀect 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 immunodeﬁciency 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.

P E D I AT R I C S

Two or more serious sinus infections within 1 year

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CLINICAL PRESENTATION OF COMPLEMENT DEFICIENCY Deficiency

Presentation

Early components of the classic Autoimmune inﬂammatory 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 deﬁciency

Recurrent infections and familial relapsing HUS

C1-INH deﬁciency

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 Immunodeficiency • Definition: Acquired defect of the immune system as a result of an extrinsic factor (eg, infections, malnutrition, drugs, malignancy, biochemical abnormalities). More common than primary immunodeficiencies. • Etiologies: See table below.

PATHOPHYSIOLOGY OF EXAMPLES OF SECONDARY IMMUNODEFICIENCIES Causes of Secondary Immunodeficiency

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 influenza, 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 (continued on next page)

Allergy and Immunology Causes of Secondary Immunodeficiency

65

Pathophysiology and Clinical Caveats • Occurs in individuals with protein-calorie malnutrition, vitamin A deﬁciency, pyridoxine deﬁciency, zinc or selenium deﬁciency, 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 aﬀect bone marrow production of B and T cells

Environmental

• Ultraviolet B: Exposure causes ↑ T-cell apoptosis and release 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 deficiencies

P E D I AT R I C S

Malnutrition

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: Deficiency 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 flow). • CXR: Cardiomegaly if the RV is significantly 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 classified 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 flow from the left atrium into the LV, typically indicating Qp:Qs over 2:1); large, unrestrictive VSDs may have only soft pulmonary flow 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 outflow obstruction or increased PVR. • Treatment: • Definitive 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.

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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: Hyperdynamic precordium, holosystolic murmur from AV valve regurgitation, diastolic rumble at apex Figure 8-1 Atrioventricular • Primum ASD: Similar to other ASDs but may have holosyscanal 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, first-degree heart block common • Rx: Medical therapy is the same as for VSD; surgery in the first 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 Tetralogy of Fallot (TOF) (Figure 8-2) • Tetrad: RVH, VSD, overriding aorta, and RVOT obstruction. All four findings are caused by anterior superior deviation of the conotruncal septum. • Most common form of cyanotic heart disease presenting beyond the first 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 flow. • Physiology: Ventricular level shunting (RV blood → aorta), decreased pulmonary blood flow. • Presentation: Murmur, progressive cyanosis (including hypercyanotic spells); degree of cyanosis depends on severity Figure 8-2 Tetralogy of Fallot. of RVOT obstruction; if very severe. RVOT obstruction may be ductal dependent for pulmonary blood flow. • 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 first few months of life. Some severely cyanotic neonates are first treated with a BT shunt.

P E D I AT R I C S

Cyanotic Heart Disease

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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 first week of life; boys are affected more often than girls. • Physiology: Circulations in parallel; requires mixing. • Presentation: Cyanosis in the first hours of life without respiratory distress. • Physical exam: Often nonspecific; typically no murmur; prominent S2 (anterior aorta, closer to the chest wall). • CXR: “Egg on a string” but more commonly nonspecific with increased or normal pulmonary vascular markings. • EKG: RAD and RVH; may be normal. • Treatment: PGE1, balloon atrial septostomy, arterial switch operation early in life.

Figure 8-3 D-Transposition 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. • EKG: RAD, RAE and RVH.

Figure 8-4 Total anomalous pulmonary venous return infracardiac type.

• CXR: Typically in obstructed TAPVC, the heart size is normal early, with pulmonary edema. Classic “snowman” sign is a late finding 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 flow. • 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 flow across a single semilunar valve and truncal valve stenosis (systolic) or regurgitation (diastolic) , wide pulse pressure. • CXR: Cardiomegaly, increased PVM, absence of MPA segment, absent thymus (DiGeorge syndrome), R aortic orch is common.

Figure 8-5 Truncus arteriosus.

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69

• EKG: RVH or BVH; may have ischemic changes if diastolic runoff and systemic “steal” is significant. • Treatment: High risk for NEC preoperatively. so must be cautious with enteral feeding; complete repair is done during the first few weeks of life. Tricuspid Atresia (Figure 8-6)

• The sizes of the TV and RV are crucial in determining the interventional strategy. • RV pressure is suprasystemic. • May have RV to coronary artery fistulae; 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: Nonspecific, decreased PVM, rarely cardiomegaly (RA dilatation). • EKG: RAE, LVH. • Treatment: PGE1, early cardiac catheterization to determine if coronary circulation is RV dependent; if not

Figure 8-8 Pulmonary atresia with an intact ventricular septum.

P E D I AT R I C S

• 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 outflow tract obstruction. • Physical exam: SEM LUSB (from PS; variable, depending on the magnitude of pulmonary blood flow). • EKG: LAD, RAE, possibly LVH. Figure 8-6 Tricuspid atresia. • CXR: RA dilation, ± cardiomegaly, PVM depend on the degree of pulmonary outflow 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. • CXR: Variable cardiomegaly; increased pulmonary vascular Figure 8-7 Hypoplastic left markings. heart syndrome. • EKG: RAD, RAE, RVH. • 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). Singleventricle palliations: Norwood → BDG → Fontan. Pulmonary Atresia with Intact Ventricular Septum (PA/IVS) (Figure 8-8)

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

Figure 8-9 Ebstein anomaly.

Inflammatory infiltrate of the myocardium with necrosis and degeneration of adjacent cardiac myocytes. Most 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 esp. Coxsackie B

Rickettsia

Scorpion venom

Meningococcus

Diphtheria

Adenovirus

Streptococcus

Drugs

Parvovirus B19

Tuberculosis

Others:

Penicillin Sulfonamides

Inﬂuenza A

Protozoans:

Varicella

Toxoplasmosis and others

Amphotericin B 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.

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• Cardiac catheterization: Controversial secondary to risks of the procedure; demonstrates low cardiac output and elevated ventricular end-diastolic pressures. • Endomyocardial biopsy: Mononuclear cell infiltrate with or without evidence of necrosis; classified 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 beneficial 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

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 significant 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 inflow may also be demonstrated. • Cardiac enzymes may be elevated.

P E D I AT R I C S

Acute Pericarditis • Causes: Unknown (one-third of cases); infectious causes (viral: coxsackievirus, echovirus, adenovirus, influenza; bacterial: Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenza, 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 inflammatory disease. Constrictive Pericarditis • Thickened, adherent pericardium impairs ventricular filling. 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 significant pericardial effusion. • Physical exam: Pericardial friction rub = grating sound best heard LSB with patient leaning forward (may be absent with significant 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).

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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 • Definition: Cardiomyopathy with increased ventricular size and reduced contractility in the absence of coronary, valvar, or pericardial disease. • Common associations: Mitral insufficiency, 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 identified 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 eﬀusions

ECG

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

Echocardiogram

Reduced contractility, ventricular dilation, MR, pericardial eﬀusion

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

Specific Studies

Serum

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

Urine

Amino and organic acid proﬁles

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Treatment Outpatient Management • ACE inhibitors and β-blockers (metoprolol/carvedilol): Mainstays of therapy • Diuretics: May be useful for symptomatic edema; no proven long-term benefit • Digoxin: Now used less often, but may improve symptoms in some patients • Vitamins (coenzyme Q10, carnitine, thiamine, riboflavin): 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 Heart Rate (bpm)∗

Frontal Plane QRS PR Vector Interval (degrees)∗ (sec)∗

<1 d

93–154 (123)

+59 to –163

1–2 d 3–6 d

R V1 (mm)∗

S V1 (mm)∗

R V6 (mm)∗

S V6 (mm)∗

0.08–0.16 4.5 (0.11)

2

5–26 (14)

0–23 (8)

0–11 (4)

0–9.5 (3)

107–182 +64 to (148) –161

0.08–0.14 6.5 (0.11)

2.5

5–27 (14)

0–21 (9)

0–12 (4.5)

0–9.5 (3)

107–182 +77 to (148) –163

0.07–0.14 5.5 (0.10)

3

3–24 (13)

0–17 (7)

0.5–12 (5)

0–10 (3.5)

1–3 wk 107–182 +65 to (148) +161

0.07–0.14 6 (0.10)

3

3–21 (11)

0–11 (4)

2.5–16.5 0–10 (7.5) (3.5)

1–2 mo 121–179 +31 to (149) +143

0.07–0.15 7.5 (.11)

3

3–20 (10)

0–12 (5)

5–21.5 (11.5)

3–5 mo 106–186 +7 to (141) +143

0.07–0.15 6.5 (0.11)

3

3–20 (10)

0–17 (6)

6.5–22.5 0–10 (13) (3)

6–11 mo

109–169 +6 to (134) +143

0.07–0.16 6.5 (0.11)

3

1.5–20 (9.5)

0.5–18 (4)

6–22.5 (13)

0–7 (2)

1–2 yr

89–151 (119)

+6 to +143

0.08–0.16 6 (0.12)

3

2.5–17 (9)

0.5–21 (8)

6–22.5 (13)

0–.5 (2)

3–4 yr

73–137 (108)

+6 to +143

0.09–0.16 5 (0.12)

3.5

1–18 (8)

0.2–21 (10)

8–24.5 (15)

0–5 (1.5)

5–7 yr

65–133 (100)

+11 to +143

0.09–0.16 4 (0.12)

4.5

0.5–14 (7)

0.3–24 (12)

8.5–26.5 0–4 (1) (16)

8–11 yr 62–130 (91)

+11 to +114

0.09–0.17 3 (0.13)

4.5

0–12 (5.5)

0.3–25 (0.5)

9–25.5 (16)

0–4 (1)

12–15 yr

+11 to +130

0.09–0.18 3 (.14)

4.5

0–10 (4)

0.3–21 (11)

6.5–23 (14)

0–4 (1)

80–119 (85)

∗2nd to 98th percentile (mean). † th 98 percentile Pediatr Cardiol 1979;1(2):133.

Q III (mm)†

0–6.5 (3)

P E D I AT R I C S

∗∗Q V6 (mm)†

Age Group

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Pediatrics

• Verify: Name, date, reason for study, standardization of leads, confirmation 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 defined 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), originating 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 find 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 –30° • Extreme LAD (Q in I/aVL, not aVF/II/ –150° III): CAVC, tri atresia, primum ASD, left 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 ampliII III 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

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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 maneuvers

Gradual slowing and gradual return

± abrupt termination

Synchronized cardioversion

No response

Usually abrupt termination

P E D I AT R I C S

• 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 • Definition: 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 or pleural effusion), loss of functioning myocardium (CHF, tumor, amyloid)

76

Pediatrics Dysrhythmia Bradycardia

AV conduction block: • Second degree (Mobitz I or II) • Third degree (AV dissociation

Sinus: Normal P wave followed by QRS; QRS after every P

Tachycardia

Blocked atrial ectopy: (atrial rate normal or above normal → blocked at AV node → ventricular bradycardia) usually not hemodynamically significant

Narrow QRS • • • •

Sinus†: Normal P wave followed by QRS; QRS after every P

SVT (increased automaticity; usually not adenosine sensitive) • Atrial tachycardia (focal or chaotic): Abnormal P wave or P wave axis • Atrial flutter • Atrial fibrillation • JET (tachycardia with AV dissociation)

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

SVT (reentry; usually adenosine sensitive) • AVRT: WPW, URAP (or concealed conduction) • AVNRT

Figure 8-12 General approach to pediatric dysrhythmias. *Definition 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.

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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 VaughanWilliams Classification

Mechanism of Action

Example

Target

Arrhythmia to Treat

Sodium channel blockade

Procainamide, quinidine, disopyramide

Atrium and ventricle

AET, AFlutter SVT, VT

Class 1B

Sodium channel blockade

Lidocaine, phenytoin, mexiletine

Ventricle

VT

Class 1C

Sodium channel blockade

Flecainide, propafenone

Atrium

AET, AFlutter, SVT

Class II

β-Blockade

Propranolol, atenolol, nadolol

SA and AV node

SVT, AET, VT

Class III

Potassium channel blocker

Sotalol, amiodarone

Atrium, ventricle

AET, AFlutter, Aﬁb, SVT, VT

Class IV

Blocks L-type calcium channels

Verapamil, diltiazem

SA and AV node

SVT, VT

Class V

Digitalis agents

Digoxin

SA and AV node

Rate control in Aﬁb

Aﬁb, atrial ﬁbrillation; Aﬂ, atrial ﬂutter.

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”).

P E D I AT R I C S

Class I A

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. Inflammatory i. History of preceding viral illness ii. Pericarditis: Fever, friction rub, worse lying flat iii. Myocarditis: Tachycardia, gallop rhythm

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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 sufficient in most cases. Typically, the ECG is the most useful diagnostic test.

SYNCOPE (Cardiol Clin 1997;15(2):277) • Definition: A sudden and transient loss of consciousness and muscle tone that is spontaneously self-terminating • Secondary to insufficiency of nutrients or oxygen to the brain (related to blood flow), most typically from decrease in systemic arterial pressure beyond the limits tolerated by cerebral autoregulation (typically when cerebral blood flow <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

P E D I AT R I C S

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 fluid intake and avoidance 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 difficult to treat. • Cardiac syncope • ↓ Cardiac output → ↓ cerebral blood flow → 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 fibrillation), 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.

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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 first 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

Oral

Amoxicillin

2 g PO

50 mg/kg PO

Unable to take oral medication

Ampicillin or Cefazolin or Ceftriaxone

2 g IM or IV

50 mg/kg IM or IV

1 g IM or IV

50 mg/kg IM or IV

Allergic to penicillins or ampicillin (oral)

Cephalexin∗† or Clindamycin or Azithromycin or clarithromycin

2 g PO

50 mg/kg PO

600 mg PO

20 mg/kg PO

500 mg PO

15 mg/kg PO

Cefazolin or Ceftriaxone† or Clindamycin

1 g IM or IV

50 mg/kg IM or IV

600 mg IM or IV

20 mg/kg IM or IV

Allergic to penicillins or ampicillin (non-oral)

Children

∗Or other ﬁrst- 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

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specific 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

P E D I AT R I C S

• 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 reimplanted 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 “modified” BT shunt involves the interposition of a synthetic graft between the subclavian artery and the PA. This provides or increases pulmonary blood flow (Figure 8-13). • Central shunt (eg, Waterson shunt, Potts shunt): Direct communication between the aorta and a branch PA. Provides or increases pulmonary blood flow. • Damus-Kaye-Stansel: End-to side anastomosis of the main PA to the ascending aorta. Requires reestablishment of pulmonary blood flow via a systemic to PA shunt or a Figure 8-13 BT shunt in TOF. ventricular to PA conduit. Allows unobstructed systemic outflow in the context of single ventricle anatomy and aortic outflow obstruction. • Fontan procedure: Typically the final 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 first (which is the top half of the Fontan) followed at a later surgery by connecting the IVC flow into the PAs (Fontan). • Glenn anastomosis (superior cavopulmonary anastomosis): Direct anastomosis of the SVC to the ipsilateral PA. “Bidirectional” implies flow from the SVC into both PAs. Provides a source of pulmonary blood flow 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 flow via either a BT shunt or a ventricular to PA conduit (“Sano modification”) (Figure 8-16). • Hybrid Norwood: A combined surgical and catheterbased 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.

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the systemic output while controlling excessive pulmonary blood flow. • PA banding: Constrictive band placed around the main PA. Limits excessive pulmonary blood flow, pulmonary artery pressure, or both. • Rastelli operation: Creation of an intracardiac tunnel permitting blood flow 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 flow with an RV–PA conduit. If enlargement of the LVOT is also required, often done in combination with a Konno procedure. • Senning or Mustard procedure (atrial switch): Intraatrial baffle 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 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

Figure 8-16 Norwood palliation with Sano modification.

Figure 8-17 Mustard repair in d-TGA.

CHAPTER 9

Critical Care RESPIRATORY FAILURE Respiratory failure is commonly classified as one or both of the following: • Hypoxic (type 1): Characterized by failure of gas exchange resulting in PaO2 <50 mm Hg breathing a gas mixture of at least 50% oxygen (Figure 9-1) • Hypercapneic (type II): Characterized as failure of ventilatory pump or chronic structural changes (BPD, cystic fibrosis) (Figure 9-2)

↓PaO2 Low inspired O2

↓

FiO2 normal

A-a gradient† ↑

normal Hypoventilation

hypoxemia does not correct

True shunt

administer 100% O2 hypoxemia corrects

V/Q mismatch

Diffusion impairment

airway (asthma, PNA, CHF) vascular (PE)

ILD Pulmonary Edema

Figure 9-1 Workup of hypoxemia.† Alveolar to arterial gradient (A–a) gradient = PaO2 estimated - PaO2 measured. PaO2 estimated = FiO2 × (PB– 47) – PaCO2/R (atmospheric pressure or PB at sea level is 760 mm Hg; respiratory quotient R is a unitless number representing basal metabolic rate; 0.7 is typically used in PICUs.) A normal A–a gradient is ~10 mm Hg. (Adapted from Marino PL: The ICU Book, 2nd ed. Baltimore: Williams & Wilkins; 1990:349.)

Clinical Predictors of Impending Respiratory Failure • Early: Use of accessory muscles of respiration, markedly diminished or absent breath sounds, diaphoresis, inability to speak, AMS, irritability, cyanosis, hypercapnia • Late: Lethargy, apnea, gasping or agonal respiration, bradycardia, hypotension

83

P E D I AT R I C S

alveolar collapse/filling (PNA, CHF) R → L intracardiac shunt intrapulmonary shunt (AVM)

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 obesity kyphosis scoliosis Pleura fibrosis, effusion Lung parenchyma ILD CHF, PNA Airways asthma, CF, bronchiectasis, bronchiolitis, OSA

Neuropathies phrenic nerve damage Guillain-Barré NMJ critical illness polyneuropathy Lambert-Eaton Myopathies diaphragm injury, myositis

Chemoreceptors metab. alkalosis 1° neurologic brainstem stroke tumor hypoventilation 2° neurologic sedatives CNS infection

musc. dystrophies, hypophosphatemia, prolonged paralysis

Figure 9-2 Mechanisms of hypercapnia.

Management of Respiratory Failure OXYGEN DELIVERY MODES AND NONINVASIVE VENTILATION MODALITIES

Modality

Indication

Advantages

Risks and Adverse Effects

O2 via nasal cannula (provides roughly 25%–40% oxygen)∗

For non–lifethreatening conditions, hypoxemia (asthma, pneumonia, bronchiolitis)

100% oxygen†, typically no more than 4 L/min flow

Well tolerated, easy to use, readily available, no associated toxicity

Skin irritation from cannula, drying of nasal passages, nose bleeds

For non–lifethreatening conditions, hypoxemia (asthma, pneumonia, bronchiolitis)

100% oxygen† at no less than 5 L/ min, typically 5–15 L/min

Well tolerated, easy to use, readily available, no associated toxicity, provides more oxygen than nasal cannula

If ﬂow is <5 L/min, “rebreathing” CO2 may occur

Weaning oxygen from high ﬂow rates

The ﬂow of 100% oxygen through the Venturi mask draws in a controlled, adjustable amount of room air (21% oxygen)

Well tolerated, easy to use, no associated toxicity, ﬁxed and accurate concentration of oxygen

Not readily available

(Use humidiﬁcation system) O2 via simple face mask (provides roughly 35%–50% oxygen)∗

O2 via Venturi™ mask (provides 24%–50% oxygen incrementally)

Dose and Administration

(continued on next page)

Critical Care

Dose and Administration

Advantages

85

Risks and Adverse Effects

Indication

O2 via partial rebreathing face mask (provides roughly 50%–100% oxygen)∗

For non–lifethreatening conditions, severe hypoxemia (asthma, pneumonia, bronchiolitis)

100% oxygen, 5–15 L/min Maintain reservoir at least half full on inspiration

High-ﬂow system readily available, provides more oxygen than simple face mask

Nitrogen washout may lead to atelectasis

Severe hypoxemia, hemodynamically stable pneumothorax (nitrogen washout)

100% oxygen 10–15 L/min Maintain reservoir at least 2/3 full on inspiration and allow partial collapse on exhalation

Well tolerated, easy to use, readily available

Nitrogen washout may lead to atelectasis

Heliox∗, 60%–80% He+ 20%–40% O2

Upper airway obstruction (croup, bronchiolitis) May be beneﬁcial in treatment of lower airway disease (asthma)

Can be administered via nasal cannula and face mask Do not use with oxygen tent or hood

Lower density gas decreases turbulent ﬂow → increased O2 and medication delivery to distal airways

Beneﬁcial eﬀects of Helium not seen with <60%; therefore, not helpful if patient requires >40% O2

CPAP‡

Acute: Respiratory distress or failure, poor lung compliance, obstructive airway disease , muscle fatigue, CHF, asthma, acute chest syndrome Chronic: OSA

Typically administer pressures of 5–10 cm H2O May give supplemental oxygen as needed

Overcomes airway resistance to maintain, FRC ↓, muscle fatigue, ↑ lung recruitment, ↓ atelectasis, ↓ V/Q mismatch Reduced risk of infection and local trauma to airway compared with ETT

Constant pressure throughout respiratory cycle; no ↑ with inspiration. Masks may cause skin breakdown with chronic use

(same as above for CPAP)

Administer via nose mask IPAP ( 8-20 cm H2O), EPAP (5-10) cm H2O, supplemental oxygen as needed

Less use of sedatives May prevent intubation

Nasal prongs and masks may cause skin breakdown with chronic use Not well tolerated by some patients Distended stomach caused by swallowed air

O2 via nonrebreather facemask (provides ~80%–100% oxygen)∗

BiPAP‡

(continued on next page)

P E D I AT R I C S

Modality

86

Pediatrics

Modality Noninvasive positive pressure ventilation

Indication Respiratory distress

Dose and Administration Use a ventilator, set parameters (rate, Vt or PIP, PEEP) Supplemental O2 as needed

Advantages As with BiPAP May prevent intubation

Risks and Adverse Effects As with BiPAP

∗The ﬁnal 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 ﬂow 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

Mode Controlled mechanical ventilation (CMV)

Support for PatientGuaranteed Initiated Set Minimum Breaths “Over Rate MV the Vent” Notes Y

Y

N

Vent delivers regular, identical breaths; no spontaneous breaths allowed Rarely used, with the exception of neonatal transport ventilators (continued on next page)

Critical Care

Mode

87

Support for PatientGuaranteed Initiated Set Minimum Breaths “Over Rate MV the Vent” Notes Y

Y

Y

Typically volume control; full 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 mandatory ventilation (IMV)

Y

Y

N

Similar to CMV but allows patient-triggered breaths in 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 intermittent mandatory ventilation (SIMV)

Y

Y

N

Similar to IMV, but internal circuitry manipulates mandatory vent delivered breaths around patient-triggered breaths

Support mode (PS, VS)

N

N

Y

Set pressure or volume is delivered for patient-initiated cycles to support patient-initiated breaths (often combined with other modalities or as a weaning modality, i.e. SIMV + PS)

Pressure regulated volume control (PRVC, VC+)

Y

Y

Y

On some ventilators, these are AC modes, but in others, they are SIMV modes; ask the RT Delivers preset rate and Vt, but ﬂow characteristics are regulated to deliver target volumes at the lowest possible pressure

High-frequency oscillatory ventilation (HFOV)

N/A

N/A

N/A

Escalation of care for patients who require high Paw and have failed conventional ventilators Consider when PEEP is 10 cm H2O or PIP is >35; better separates 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.

P E D I AT R I C S

Assist-control ventilation (AC)

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Pediatrics

• Volume control: Delivers a preset VT during a preset inspiratory time at the preset respiratory rate and constant inspiratory flow. • 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 (Neonates)

SIMV PC (Children)

SIMV VC (Children)

SIMV VC (Adolescents)

Rate (bpm)

20–30

Ti (sec)

0.2–0.5

14–20

14–20

8–14

0.5–0.8

0.5–0.8

V T (cc/kg)∗

0.75–1

N/A†

N/A†

6–8

6–8‡

PEEP (cm H2O)

2–5

2–5

2–5

PIP (cm H2O)

20–25

20–25

2–5 †

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 V with adequate chest rise (lung protective strategy: 6–8 cc/kg). T † 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 oxygenation

Increase Paw (MAP) by ↑ PEEP, PIP, or Ti (PEEP has greater eﬀect); increase FiO2

PEEP maintains FRC and ↓ V/Q mismatch; has >eﬀect than PIP: Paw = K(PIP-PEEP) × [Ti/(Ti + Te)] + PEEP

Overdistension with PEEP will lead to worsening oxygenation Consider HFOV if PEEP >10

Improving ventilation

Increase MV by ↑RR or ↑ V T (in VC modalities) or PIP (in PC modalities)

CO2 directly related to minute ventilation. Rule of thumb: Current PaCO2 × Current respiratory rate = Desired PaCO2 × Desired respiratory rate

Allow for permissive hypercapnia (pCO2 ~60 if pH >7.2) to reduce the potential for barotrauma With obstructive airway diseases, reducing the 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 humidified ventilator circuit) and follow volume status closely.

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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 insufficiency, 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] → Give 1/2 to 2/3 of the calculated dose; then re-evaluate

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)

P E D I AT R I C S

(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 insufficiency.) d. After Cl >90 (or spot urine Cl suggests saline-resistant alkalosis) while pH is >7.50, use acetazolamide (5 mg/kg IV Q8h for 3 doses only; check daily lytes).

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 Deﬁnition 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 • Decrease of arterial pH to <7.32

• Nasal ﬂaring • Increasing respiratory eﬀort • Tachypnea • Tachycardia (increase in HR >20–40 bpm) • Cardiac arrhythmias • Hypotension • Apnea

• Absolute decline in arterial pH >0.07 • PaO2 <60 mm Hg with FIO2 >0.40 (PaO2/FiO2 ratio <150) • SpO2 declines >5%

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

STATUS ASTHMATICUS IN THE INTENSIVE CARE UNIT • Definition: 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, difficulty 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 Score

Assess

Score 0

Score 1

Score 2

Respiratory Rate

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

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

< 2 mos > 60 2-12 mos > 50 > 1-5 yrs > 40 > 5 yrs > 30 (continued on next page)

Critical Care

91

Clinical Respiratory Score (CRS) Patient Score

Assess

Score 0

Score 1

Score 2

Auscultation

Good air movement, scattered expiratory wheezing, loose rales/crackles.

Decreased air movement, inspiratory and expiratory wheezes or rales/ crackles

Diminished or absent breath sounds, severe wheezing or rales/ crackles, or markedly prolonged expiration.

Use of Accessory Muscles

Mild to no use of accessory muscles. Mild to no retractions or nasal ﬂaring on inspiration.

Moderate intercostal retractions, mild to moderate use of accessory muscles, nasal ﬂaring.

Severe intercostal and substernal retractions, nasal ﬂaring.

Mental Status

Normal to mildly irritable

Irritable, agitated, restless.

Lethargic

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 Route

Dose

Albuterol

SABA (airway smooth muscle relaxation)

Inhaled (nebulized or MDI)

Nebulization: 0.15–0.5 mg/kg/h or 10–20 mg/h of continuous therapy; can give sequential nebulization × 3 (≤5 mg each) Max, 20 mg/h MDI: 4–8 puﬀs per dose Q20 min × 3; then Q1h

Levalbuterol

SABA (levorotary enantiomer, airway smooth muscle relaxation)

Inhaled (nebulized or MDI)

MDI: 4–8 puﬀs Q20 min × 3 then Q1h

Methylprednisolone

Steroid∗ (antiinﬂammatory)

IV

2 mg/kg IV once; then 1 mg/kg IV Q6h Max, 60 mg/dose

Prednisone

Steroid∗ (antiinﬂammatory)

PO

2 mg/kg PO once; then 1–2 mg/kg/ day divided Q12h Max, 60 mg/dose

Prednisolone

Steroid∗ (anti inﬂammatory)

PO (tastes better)

2 mg/kg PO once; then 1 mg/kg PO Q6h Max, 60 mg/dose (continued on next page)

P E D I AT R I C S

Type and Mechanism

Medication

92

Pediatrics

Second-Line Treatment Ipratropium bromide

Anticholinergic (airway smooth muscle relaxation)

Inhaled (nebulized or MDI)

<12 yr: Nebulization 250 mcg Q20 min × 3 then Q2–4h prn; MDI 4–8 puﬀs per dose >12 yr: Nebulization 500 mcg Q30 min × 3 then Q2–4h prn; MDI 4–8 puﬀs per dose Can “spike” the albuterol nebulization solution with ipratropium bromide dose and give as one treatment

Magnesium sulfate

Electrolyte (smooth muscle relaxation)

IV

40 mg/kg IV over 20 min; max 2g Although hypotension is exceedingly rare, watch for hypotension and be ready to give a 10–20 cc/kg NS bolus if it develops

Terbutaline†

β-agonist (smooth muscle relaxation)

Sub-Q, IV

IV: 10 mcg/kg IV once; then IV infusion starting at 0.5 mcg/kc/min, 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 anesthetic, bronchodilator

IV

0.5–2.0 mg/kg IV; may be used as a continuous infusion May have bizarre dreams, hallucinations; watch for oversedation 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 eﬀects may include coronary ischemia, chest pain, and arrhythmias. Toxicity will limit the maximum dose for the patient. Closely monitor for side eﬀects. ‡ Aminophylline levels must be monitored closely to avoid toxicity. Obtain the ﬁrst 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 Isoflurane • 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 fluid resuscitation. Do not be afraid to give fluid to patients with asthma. • Status asthmaticus has been associated with metabolic and lactic acidosis.

• Shock Definition: Inadequate delivery of oxygen and nutrients to meet the metabolic needs of the tissues. Shock is not defined 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.

P E D I AT R I C S

SHOCK STATES, SIRS, AND SEPSIS

94

Pediatrics

Defining Shock in Sepsis Fluid-Refractory, Dopamine-Resistant Shock • Shock persists despite ≥60 mL/kg fluid resuscitation in the first 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.

Defining 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

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

Septic shock

Sepsis and cardiovascular organ dysfunction

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

Initial Management

Inadequate intravascular volume relative to the vascular space: Hemorrhage, serum or plasma loss (diarrhea or vomiting, burns, diabetes, nephrotic syndrome), medications, pancreatitis, sepsis

ABCs, O2, IV or IO access, monitors, initial glucose, brief history and PE, neurologic status, Foley catheter Give 20 cc/kg NS rapidly; reassess need for additional ﬂuid Labs: Electrolytes, BUN/Cr, glucose, calcium or ionized calcium (maintain iCa >1.2), Mg, Phos, CBC, blood culture, PT/PTT/INR, ABG with lactate, AST/ALT, albumin, CXR Monitor UOP hourly Additional studies and imaging guided by history and PE Central venous access if given 60 cc/kg and the patient is still in shock; then monitor MVO2, CVP, arterial line; replace blood products for hemorrhage

Distributive

Inappropriate distribution of blood ﬂow: Anaphylaxis, spinal cord injury, drugs (antihypertensive medication ingestion, barbiturate overdose), sepsis, pancreatitis

Same as hypovolemic + identify cause for distributive shock Treat anaphylaxis with sub-Q or IM epinephrine (1:1000) 0.01 mg/kg (max 0.5 mg) or IV or IO epinephrine (1:10,000) 0.01 mg/kg; may need epinephrine infusion, inhaled albuterol or racemic epinephrine, IV/IM corticosteroids (Solumedrol 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 output: Cardiac tamponade, pneumothorax, aortic dissection, critical aortic stenosis, large pulmonary embolus (consider this in trauma patients in addition to hypovolemic or distributive shock)

Same as hypovolemic + rapidly identify tamponade (diminished heart sounds, increased JVD, pulsus paradoxus), or pneumothorax (tracheal deviation, diminished breath sounds, CXR)

Dissociative

Unable to deliver oxygen to the tissues: Carbon monoxide poisoning, methemoglobinemia, heat, cyanide, metabolic (consider this in burn patients in addition to hypovolemic shock)

Same as hypovolemic + rapidly identify the cause; send blood cooximetry and cyanide levels to identify the cause Speciﬁc treatments as appropriate: Place on 100% FiO2; aggressively treat fever Carbon monoxide toxicity patients look cherry red and pulse oximeters read high, but patients are 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)

P E D I AT R I C S

Description

Hypovolemic

96

Pediatrics

Type of Shock Cardiogenic

Description

Initial Management

Myocardial dysfunction: Dysrhythmias, primary or secondary cardiac disease, ductal-dependent congenital cardiac lesions, sepsis, thyrotoxicosis, pheochromocytoma, and in all forms of prolonged shock regardless of etiology; patients with enlarged liver, cardiomegaly, gallop rhythm, rales, cool extremities, poor UOP

ABC’s, O2, IV or IO access, monitors, brief history and PE, neurologic status, Foley catheter In addition to the above labs, BNP level, cardiac enzymes, ECG, echocardiogram Monitor for arrhythmias Identify the cause of cardiogenic shock Normalize preload (diuretics) and afterload reduction Inotropes or vasopressors if BP is low and endorgan is perfusion poor Target BP for end-organ perfusion and UOP >1 cc/kg/h Monitor mixed venous O2 sat, lactate

COMMONLY USED VASOPRESSORS AND INOTROPES IN SHOCK Drug

Infusion Rate

Receptors and Mechanism

Epinephrine

0.1–1 mcg/kg/min

β1 = α1 < β2

Inotrope (at low doses), chronotrope, vasopressor (at high doses)

Norepinephrine

0.05–1 mcg/kg/min

Mainly α1, some β1

Vasopressor

Dopamine

2–20 mcg/kg/min

Mainly β1 at low doses; α1 at high doses (15–20 mcg/kg/min)

Inotrope, chronotrope, vasopressor

Dobutamine

2–20 mcg/kg/min

β1

Inotrope, chronotrope

Vasopressin

0.01–0.06 units/kg/h

Vascular 1 (V1) receptor agonist: Increases intracellular Ca and causes vasoconstriction

Vasopressor

Milrinone

0.125–0.750 mcg/ kg/min

Phosphodiesterase III inhibitor: Blocks the breakdown of cAMP

Inotrope, vasodilator

Effect

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 definitive 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.

0 min

5 min

Initial resuscitation: Push boluses of 20cc/kg isotonic saline or colloid up to and over 60cc/kg until perfusion improves or unless rales or hepatomagaly develop. Correct hypoglycemia and hypocalcemia. Begin antibiotics.

With 2nd PIV start inotrope.

shock not reversed? Fluid refractory shock: Begin inotrope IV/IO, use atropine/ketamine IV/IO/IM to obtain central access and airway if needed. Reverse cold shock by titrating central dopamine or, if resistant, titrate central epinephrine Reverse warm shock by titrating central norepinephrine.

15 min

Dose range: dopamine up to 10 mcg/kg/min, epinephrine 0.05 to 0.3 mcg/kg/min.

shock not reversed?

u n i t

60 min

Catecholamine resistant shock: Begin hydrocortisone if at risk for absolute adrenal insufficiency

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

Cold shock with normal blood pressure:

Cold shock with low blood pressure:

Warm shock with low blood pressure:

1° goals: Titrate epinephrine, MVO2 > 70%, Hgb > 10g/dL

1° goals: Titrate epinephrine, MVO2 > 70%, Hgb > 10g/dL

1° goals: Titrate norepinephrine, MVO2 > 70%,

2° goals: Add vasodilator* (nitrosovasodilators, milrininone, and others) with volume loading, consider levosimendan

2° goals: Add norepinephrine Add dobutamine if MVO2 < 70%, Consider milrinone, enoximone or levosimendan

2° goals: Consider vasopressin, terlipressin or angiotensin Add dobutamine or low dose epinephrine if MVO2 < 70%

P e d i a t r i c

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)

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

P E D I AT R I C S

I n t e n s i v e

c a r e

E m e r g

97

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

e n c y

D e p a r

t m e n t

Critical Care

98

Pediatrics

• Remember after appropriate fluid resuscitation and initial dopamine: • Cold shock: β-adrenergic such as epinephrine (treat the poor cardiac output). • Warm shock” α1 adrenergic such as norepinephrine or vasopressin (vasocontrict the peripheral vessels). • Calcium repletion: Either as bolus dosing or continuous infusion may significantly 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 fluid resuscitation with crystalloids or colloids to improve or maintain BP and perfusion. • Look for signs of fluid overload and myocardial dysfunction on exam as you resuscitate: Crackles on lung exam, S3, hepatomegaly; if any are present, slow down on the fluid 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 H2O in infants; 65 cm H2O for ≥2 yr), MVO2 sat of 70%, CVP 8 to 12, capillary refill 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 increased 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 significant DIC; platelets for clinically significant bleeding. Renal • Fluid requirements: Replace insensible losses only if the patient has oliguria after multiple fluid boluses. • Verify appropriate dosing of medications for renal insufficiency. Endocrine • Consider adrenal insufficiency if the patient is in fluid- 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 Diabetic Ketoacidosis

Hyperglycemic 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 (mEg/L)

15–18

10 to <15

<10

>15

Urine ketones

+

+

+

Small

Serum ketones

+

+

+

Small

Eﬀective serum osmolality (mOsm/kg)

Variable

Variable

Variable

>320

Anion gap

>10

>12

>12

Variable

Alteration in sensorial or mental obtundation

Alert

Alert or drowsy

Stupor or coma

Stupor 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. • Weight loss. • Abdominal pain (DKA only) or vomiting. • Headache, altered mental status.

• May have a illness or infection triggering DKA. • In a patient with known diabetes mellitus, there may be a history of missed insulin doses. • Family history of DM or other autoimmune disorders.

• 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 fluids 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 fluid and electrolyte deficits 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 flags for cerebral edema: Altered mental status, increased vomiting, incontinence, cranial nerve palsies, abnormal pupillary responses, bradycardia, and increasing or decreasing BP.

P E D I AT R I C S

Correction of Acidosis, Dehydration, and Electrolytes

100

Pediatrics

Patient off algorithm, treat as appropriate

Yes

Interventions

Diagnostic Testing

Patient in shock?

For all patients: Β-hydroxybutyrate, glucose, CHEM 7, VBG, Hb A1C. Calculate and follow anion gap, osmolarity, corrected Na.

No

Consider subcutaneous insulin.

Bolus Lactated Ringer's 10ml/kg IV over 1 hour. May repeat once if clinically indicated

New onset diabetes patients Islet cell, insulin, and anti-GAD antibodies, C-peptide, insulin, thyroid peroxidase and thyroglobulin antibodies. Celiac panel

Age <5 or Bicarbonate ≤12, or abnormal mental status?

On Insulin drip Glucose Q1H (goal not greater than 100 mg/dL decrease per hour), electrolytes Q2H, monitor real and corrected Na and anion gap.

No

Yes K <5.0? No

Begin IVF without additional K

LR or NS at 2.5 L/m2/day not to exceed 4 L/m2/day including initial boluses. Add dextrose to IVF when blood glucose <300.

Yes

Begin 2 Bag Fluid system

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

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

Insulin infusion at 0.1units/kg/hour (0.05units/kg/hour if age less than 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 accumulates 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 beneficial 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, constricting 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. Definitive treatment involves relieving the obstruction (ie, with a shunt or EVD).

Determine the Cause

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 reflexes, 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).

P E D I AT R I C S

• 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: Inflicted 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). • If febrile: Workup for causes of fever (CT head before LP to determine safety of LP).

102

Pediatrics

• Aggressive control of fever is present with acetaminophen 10 to 15 mg/kg PR. • Specific 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 beneficial; severe hyperventilation to pCO2 <30 may cause harm through decreased cerebral blood flow. 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 benefit. • Hypothermia has been shown to improve neurologic outcomes for adult patients after cardiac arrest. Glucose • Avoid hypoglycemia and hyperglycemia. • Provide initial fluids without dextrose; monitor serial glucose. • Begin dextrose in IV fluids 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 first seizure of subsequent epilepsy in ~1/3 of patients; another 1/3 occurs in patients with known epilepsy (often low antiepileptic medication levels).

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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 fluttering 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 definition 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 first-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 inflicted neurotrauma, especially in infants • Ingestions • Electrolyte disturbances • Intracranial lesions (tumor, bleeding, stroke) • Increased ICP • Hypoxia or ischemia Clinical Pearls for Status Epilepticus

MEDICATIONS USED FOR REFRACTORY STATUS EPILEPTICUS Medication

Dose

Comments

Keppra™

15–30 mg/kg IV load; then BID not to exceed 60 mg/ kg/day or 1500 mg/dose

Dose adjustment for renal failure

Pentobarbital

5–10 mg/kg IV load over 1–2h, then infuse 1–6 mg/ kg/h titrated to maintain burst suppression on EEG.

May see cardiac and respiratory depression, hypotension, need for inotropes or vasopressors; over time will see immunosuppressive eﬀects and may see liver dysfunction

Midazolam (Versed)™

0.15 mg/kg IV load; then infuse 2–6 mcg/kg/min IV

May see cardiac and respiratory depression, hypotension

Propofol

1–2 mg/kg IV load; then infuse 3–10 mg/kg/h IV

Monitor for propofol infusion syndrome; use caution in children younger than 12 years old

P E D I AT R I C S

• 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 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 first 5 minutes of status epilepticus, you can administer an intranasal, rectal, or buccal benzodiazepine as the first dose of a benzodiazepine (Figure 9-5).

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Pediatrics Medications

Monitoring

Lorazepam 0.1 mg/kg IV (Max dose = 2 mg/dose) If no IV access may give first dose as rectal, intranasal, or buccal benzodiazepine

Cardiac Monitor, Pulse Oximetry, Frequent blood pressure measurements throughout algorithm.

Seizures Stop Seizures continue for 5 minutes

Fosphenytoin 20 PE/kg IV (A,B) (Max dose 1 gram total)

Lorazepam 0.1 mg/kg IV (Max dose = 2 mg/dose) Fosphenytoin 30 PE/kg IV (A,B) (Max dose 1 gram total) (Max rate = 150 PE/minute) Seizures continue for 5 minutes after full dose given Phenobarbital 20 mg/kg IV (C) (Max dose 800 mg) (Max rate 50 mg/minute)

Monitor for adequate chest rise, ventilation, adequate circulation, airway protective reflexes Obtain Phenytoin peak level 30 minutes after last infusion

Obtain Phenobarbital peak level 4 hours after infusion

Seizures continue for 10 minutes after full dose given Obtain Neurology consult for additional recommendations. Patient may need pharmacologic coma to control seizures. Additional medication options include: Keppra 15–30 mg/kg IV Pentobarbital, Propofol, or Versed continuous infusions

Pharmacologic Coma

Order STAT EEG (D)

Central venous pressure monitoring, arterial pressure 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 (Dilantin), 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 efficacy 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.

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105

Decision Tree for Work-up of Status Epilepticus Patients

Known Seizure Disorder

First Seizure

Febrile

Afebrile

Febrile

Afebrile

All Patients Check AED Levels Neurology Consult Electrolytes Glucose d-stick Tracheal Aspirate*

All Patients Check AED Levels Neurology Consult Electrolytes Glucose d-stick

All Patients Brain CT, Lumbar Puncture (Obtain extra CSF), CBC, Glucose d-stick, Chemistry Panel (Including Calcium, Mg, Phosphorus), Chest X-Ray, Tracheal Aspirate*, UA+Urine culture, Blood culture, Viral cultures, Neurology consult

All Patients Brain CT, Glucose d-stick, Chemistry Panel (Including Calcium, Mg, Phosphorus), Tracheal Aspirate*, Toxicology Screen, Neurology consult

Consider Toxicology Screen EEG Vancomycin/Cefotaxime/Ceftriaxone

Consider CBC ECG EEG Workup for IEM

Consider CBC, Cultures (blood, viral), Brain CT, Lumbar puncture, EEG, Chemistry panel (including Calcium, Mg, Phosphorus)

Consider Toxicology Screen EEG, Brain CT in infants < 1 year

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 deficits. If head CT demonstrates intracranial pathology concerning for increased ICP, neurosurgical consultation should be obtained immediately.

‡

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 influenza A or B (seasonal); stool or rectal swab for viral culture; rapid adenovirus screen; and arbovirus studies (seasonal).

P E D I AT R I C S

Brain CT is recommended before performing an LP to determine the presence of intracranial pathology that might be a contraindication to LP.

§

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 first tooth. • Use a pacifier, not a bottle, as the infant’s means of non-nutritive sucking (no dipping in sweetener; goal wean from pacifier 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 refined 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 first tooth. • Flossing should be done daily after contact occurs between adjacent teeth. • Toothbrushing with American Dental Association–approved fluoridated toothpaste (Morbid Mortal Wkly Rep 2001;50(RR-14):1).

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

Fluoride • Children with optimal fluoride consumption through adolescence have 50% to 75% less decay (sources: fluoridated community water, oral supplements, fluoridated toothpaste). • Slightly over half of the U.S. water supply is fluoridated (at varying amounts). • Optimal community water supply fluoridation is 0.7 to 1.2 ppm. • Determine the fluoride level of the local community water (local water utility or see http://apps.nccd.cdc.gov/MWF). • Adequate daily intake of fluoride: 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 fluoride is ingested with each brushing by young children using regular fluoridated toothpaste; a pea-sized drop of regular fluoridated toothpaste contains 0.4 to 0.6 mg of fluoride. • Fluorosis: Excess fluoride 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 fluoride intake).

EARLY CHILDHOOD CARIES • Defined 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.

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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 fluoride exposure, daily flossing, twice-daily brushing with fluoridated toothpaste, limit refined 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, difficulty chewing, poor weight gain, failure to thrive, risk of dental decay in adult teeth, malocclusion. • Treatment of established disease: extraction, fillings, dental crowns and fillings.

NORMAL ERUPTION Teething (Figure 10-1) • Symptoms: Oral (salivation, biting), local (circumoral rash, ear rubbing), systemic (lowgrade 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).

E FG H C D

Shed (years) 6–7 7–8 10–12 9–11 10–12

R M Q PON

1

16

Secondary

Primary T K Lower teeth S L

8 9 10 67 11 5 12 13 4 14 3 Upper teeth 2 15

Second molar First molar Canine (cuspid) Lateral incisor Central incisor

23–31 10–12 14–18 9–11 17–23 9–12 10–16 7–8 6–10 6–7

32 31

17 18

Lower teeth

30 29 28 27 26

19 20 21

25 24 23

22

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 first 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 first secondary eruption is usually the lower central incisor.

P E D I AT R I C S

I B Upper teeth J A

Erupt (months) Central incisor 8–12 Lateral incisor 9–13 Canine (cuspid) 16–22 First molar 13–19 Second molar 25–33

Erupt (years) Central incisor 7–8 Lateral incisor 8–9 Canine (cuspid) 11–12 First premolar 10–11 (first bicuspid) Second premolar 10–12 (second bicuspid) First molar 6–7 Second molar 12–13 Third molar 17–21 (wisdom tooth) Third molar 17–21 (wisdom tooth) Second molar 11–13 First molar 6–7 Second premolar 11–12 (second bicuspid) First premolar 10–12 (first bicuspid) Canine (cuspid) 9–10 Lateral incisor 7–8 Central incisor 6–7

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Pediatrics

ABNORMAL ERUPTION Neonatal or Natal Tooth • Natal tooth: Tooth present at birth • Neonatal tooth: Tooth that emerges during the first 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 specific oral pathology, dysmorphism, growth disturbance, bony abnormalities, or findings suggestive of endocrine or genetic disorder)

Odontogenic Infections • An infected tooth may present with pain and sensitivity or as a superficial 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

C H A P T E R 11

Dermatology TYPES OF LESIONS Primary: Specific changes caused directly by disease process • Macule: Nonpalpable, <1 cm • Patch: Nonpalpable, >1 cm • Papule: Solid, palpable, <1 cm • Nodule: Solid, palpable, 1–2 cm, dermal • Tumor: Solid, palpable, >2 cm • Plaque: Solid, palpable, >1 cm, width > thickness

• Vesicle: Raised, clear, fluid filled, <1 cm • Bulla: Raised, clear, fluid filled, >1 cm • Pustule: Raised, pus filled • Wheal: Transient, palpable edema

Secondary: Nonspecific changes caused by evolution of primary lesions • Scale: Accumulation of loosely adherent keratin • Crust: Accumulation of serum, cellular, bacterial, and squamous debris over damaged epidermis • Fissure: Superficial, often painful break in epidermis • Erosion: Loss of epidermis; heals without scarring • Ulcer: Loss of epidermis and part or all of dermis; heals with scarring

• Excoriation: Linear erosion • Lichenification: Accentuated skin markings caused by thickening of epidermis; usually caused by scratching or rubbing • Scar: Fibrous tissue replacing normal architecture of dermis • Atrophy: Epidermal (thinning of epidermis) or dermal (decrease in the amount of collagen or causing depression of skin)

CHARACTERIZATION OF SKIN LESIONS Distribution

Duration

Exposure

• Primary vs. secondary changes • Color • Consistency and texture • Mobility

• Symmetry

• How long?

• Sick contacts • Local

• Dermatomal • Photodistribution

• Since birth? • Recurrent?

• Recent travel • Medications

• Conﬁguration

• Contact areas

• Shape • Well vs. ill-deﬁned

• Personal care products • Environmental exposures • Occupational exposures • Recreational exposures

• Mucous membrane involvement

• Flexor vs extensor surfaces • Koebner phenomenon: areas of previous trauma

• Arrangement

• Seasonal variation

• Pruritus • Pain and tenderness • Paresthesias

• Bleeding

• Systemic • Fever or chills

• Malaise or fatigue

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109

P E D I AT R I C S

Signs and Symptoms

Description

110

Pediatrics

Description

Distribution

Duration

• Discrete

Exposure • Family history

Signs and Symptoms • Arthritis or 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 → lichenification, hyperpigmentation, fissuring → 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, pustules, weeping, acute increase in erythema

• Topical or oral antibiotic • Obtain culture

Eczema herpeticum (HSV superinfection) • Source of contact often adult caretaker with “cold sore”

• First-degree lesions: Crops of vesicles on inﬂamed base at sites of eczema • Late: “punched-out” erosions • Common associated symptoms: Fever, malaise, irritability, intense itching, eczema ﬂare • Severe: Widespread viral dissemination with multiorgan involvement

• Stop TCS or TCI • Acyclovir or valacyclovir • Treat for secondary bacterial infection if indicated • Treat known contacts • Eye exam for periorbital involvement • Obtain culture &/or DFA

Long-term TCS use

• Skin atrophy, ecchymoses, striae, telangiectasias, poor wound healing, perioral dermatitis or steroid rosacea, hypothalamus–pituitary axis suppression with systemic absorption

• Limit use for ﬂares only (usually <1- 2-wk intervals) • Use lower potency TCS for face, underarms, and groin • If indicated, evaluate for adrenal suppression and treat appropriately

Postinﬂammatory pigment changes

• Hypo- or hyperpigmented macules or patches in areas of previous involvement • Fades over months to years

Sun protection and continued treatment of ﬂares of dermatitis

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)

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111

• Mild flare: 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 flare: 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 flare: 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: Erythema, scaling, edema, vesicles, pustules, erosions • Chronic: Licheniﬁcation, ﬁssures

Results from contact with a substance that chemically or physically damages skin • Urine or feces → diaper rash • Lip licking or thumb sucking • Detergents or solvents • Topical medications • Battery acid

• May occur after single contact with a strong irritant or after repeated contact with milder irritants • Rash minutes to hours after exposure

• Avoidance of irritants • Emollients, barrier creams • May consider TCS if no improvement (controversial)

Allergic (type • Acute: Erythematous, IV cellscaly, vesicular, mediated crusted, immune weeping reaction) • Chronic: Licheniﬁcation, ﬁssuring, excoriations

Data from Dermatol Ther 2004;17:334.

OTHER ECZEMATOUS OR PAPULOSQUAMOUS ERUPTIONS Disease

Description

Course

Treatment

Other

Seborrheic dermatitis (infantile form)

• “Cradle cap”: Greasy scales on scalp • Disseminated: Bilateral, well-demarcated, symmetric pink patches and plaques with scaling in diaper area, retroauricular areas, neck, trunk, and proximal extremities, prominent in skin creases/folds

• Usually begins 1 wk after birth • May persist for months

• Bathing • Frequent moisturization • Ketoconazole 2% cream if extensive or persistent • Short course of lowpotency TCS if inﬂamed

• Linked with sebum overproduction and Malassezia spp. infection

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P E D I AT R I C S

• Poison ivy, oak, sumac • 1° exposure → • May use patch testing rechallenged • Nickel (jewelry, metal to conﬁrm by allergen → clasps, glasses) diagnosis dermatitis • Rubber (shoes, clothing) • Avoidance of • Rhus (poison • Paraphenylenediamine ivy, oak, sumac): allergen (may (hair dyes, leather, take >6 wk patchy or black-dyed henna) for complete linear vesicles • Topical antibiotics (eg, or bullae on ex- clearing of neomycin, bacitracin) rash) posed surfaces 2–7 days after • Emollients • Topical or exposure, lastsystemic cor• TCS ing 3–4wk ticosteroids

112

Pediatrics

Disease

Description

Course

Treatment

Other

Keratosis pilaris∗

• Skin-colored follicular hyperkeratotic or erythematous papules on the upper arms, thighs, cheeks

• May become more pronounced at puberty (some may improve at puberty) • Often improves with age • Improvement in summer; worsening in winter

• No deﬁnitive treatment • May try emollients, lactic acid or glycolic acid creams, urea cream, salicylic acid, short course of TCS for inﬂamed areas

• Can be associated with ichthyosis vulgaris, atopic dermatitis

Pityriasis alba

• Small, ill-deﬁned, symmetric, hypopigmented patches with ﬁne scales, often on cheeks; may be seen on upper extremities

• May become more obvious in summer on tanned skin • May last for months to years • Resolves spontaneously

Emollients, low-potency TCS, sunscreen

Pityriasis rosea

• “Herald” patch: Initial 1- to 10-cm salmoncolored oval patch or plaque with collarette of ﬁne scale, usually on trunk • Within days: “Christmas tree” distribution of oval, hyperpigmented, smaller, thin plaques or papules similar to a herald patch on trunk • Face, palms, soles usually spared • May see oral erosions • Inverse pityriasis rosea: Variant involving axillae and inguinal areas; more common in younger children and darkerskinned patients

• Most common in adolescents and young adults • More common in spring

• Reassurance • TCS ± PO antihistamine PRN for pruritus • Possible beneﬁt of 14day course of erythromycin† (controversial) • UVB light treatment for severe cases

• May have mild prodrome: Fever, HA, malaise • May be pruritic • Lasts 6–8 wk; sometimes months • May be mimicked by syphilis (check RPR if indicated) • Possible association with HHV-6, HHV-7

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Dermatology Disease

Description

Course

Treatment

Other

Psoriasis‡

• Well-demarcated erythematous papules and plaques with thick, silvery scales; often on elbows, knees, scalp, trunk, but can occur anywhere • Diaper area in infants • Scalp - scaling, papules & plaques • Nail dystrophy pitting, other

• Guttate type: Drop-like lesions on trunk, often after streptococcal infections, URI • Localized pustular type: Discrete pustules, scaly plaques on palms or soles • Generalized pustular type: Erythema with sheets of small pustules, migratory annular erythematous plaques on tongue, possible after corticosteroid withdrawal, fever, arthralgias • Koebner phenomenon

• Topical corticosteroids, calcipotriene, coal tars, phototherapy, methotrexate, cyclosporine, acitretin, TNF-α inhibitors, mycophenolate mofetil • Never use systemic steroids because of psoriasis ﬂares when stopped

• Inverse psoriasis: Variant involving ﬂexural areas

113

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

BACTERIAL INFECTIONS Description

Cause

Impetigo

• Honey-crusted erosions, superﬁcial vesicles or bullae at sites of skin breakdown • May be pruritic • Usually on face, hands, genitalia, or scalp

• S. aureus • Usually no • Gentle constitutioncleansing (nonal symptoms • Topical bullous, bullous, or • Bullous form antibiotics pustular) may occur • Systemic • Streptoon intact skin antibiotics coccus for extensive pyogenes cases (usually nonbullous)

Course

Folliculitis

• Pustules or red papules originating from hair follicles • Usually on scalp, face, chest, back, buttocks, extremities

• Usually S. aureus

• Benign • Heals without scarring

Treatment

Other • Ecthyma: Deep impetigo with ulcer formation, often on legs, heals with scarring

• Antibacterial washes • Topical antibiotics if localized • Systemic antibiotics if extensive or recurrent (continued on next page)

P E D I AT R I C S

Type

114

Pediatrics

Type

Description

Cause

Course

Abscess

• Erythematous, tender, purulent masses, fairly wellcircumscribed

• Usually S. aureus or GABHS

• May become • Warm, moist ﬂuctuant and compresses spontane• If ﬂuctuant, ously drain I&D • Systemic antibiotics if indicated

Treatment

Other

Cellulitis

• Acute, ill-deﬁned, suppurative inﬂammation of deeper subcutaneous tissues with erythema, warmth, swelling, tenderness

• S. aureus • Prodrome: Fever, chills, or GABHS malaise through area of skin breakdown or hematogenous spread

• Systemic antibiotics

Erysipelas

• Progressive, superﬁcial, welldemarcated cellulitis (primarily involving the dermis)

• GABHS

• Prodrome: Fever, chills, malaise • May resolve with desquamation and postinﬂammatory pigment changes

• PCN for 10–14 d (erythromycin if PCN allergy) • Rest • Elevation

• Cover for S. aureus if no improvement or atypical (bullous)

Scarlet fever

• Blanching, erythematous “sandpaper” rash starting on central body and spreading • Circumoral pallor, ﬂushed cheeks

• GABHS

• Prodrome (high fever, chills, HA, sore throat, anorexia) → rash develops within 12–48 h → exudative pharyngitis, strawberry tongue within days → 7–10 d: desquamation lasting 2–6 wk

• PCN for 10–14 d (erythromycin if PCN allergy)

• Monitor for other GABHS sequelae: peritonsillar abscess, rheumatic fever, acute glomerulonephritis

• Recurrent: MRSA eradication with intranasal mupirocin TID x 1 wk ± bleach bath Q2-3 d (1/2 cup bleach:20 gallons water) (for patient and contacts) • Other treatments: Daily chlorhexidine washes, rifampin/ doxycycline x 1 wk∗

(continued on next page)

Dermatology Type

Description

Toxic • Diﬀuse maculopapular erythroshock syndrome derma on trunk with centripetal spread • Erythema or edema of palms or soles • Desquamation of hands or feet 1–3 wk after onset of symptoms

Cause

Course

Treatment

• S. aureus or GABHS exotoxin

• Sudden onset of high fever, myalgias, vomiting or diarrhea, headache, pharyngitis → rapid progression to shock

• Removal of foreign body or nidus of infection • Early, aggressive septic shock treatment including early antibiotics (see chapter 9)

115

Other

Staphylococcal scalded skin syndrome

• Generalized Exfoliative erythema, often toxins of tender → suS. aureus perﬁcial, ﬂaccid bullae → moist, crusty skin with desquamation • Mucus membranes not involved

• Prodrome: • Parenteral Fever, malaise, antibiotics irritability • Bland • Scaling or emollients desquamation for denuded for 3–5 d after skin bullae forma- • Aggressive tion pain control • Reepithelialization in 10–14 d

Meningococcemia

• Petechiae or • Neisseria purpura, ecchymeninmoses, ischemic gitidis necrosis, hemorrhagic bullae

• Severe system- • IV third• Treat conic symptoms generation tacts with with rapid cephalosporin, rifampin decompensaPCN, chloram- prophylaxis tion phenicol

Lyme disease†

• Erythema migrans → annular erythematous plaques, centrifugal spread • Usually on trunk, axilla, groin, or popliteal fossa

Rocky Mountain spotted fever

• Erythematous • Rickettsia • Fever, macules on rickettsii headache, wrists or ankles through myalgia → with centripetal tick bite in rash appears spread spring and on day 3–6 summer • Maculopapular • May develop lesions on palms severe sysor soles temic symptoms with • Severe: petechiae, progressive retiform purpura worsening

• Doxycycline (if >8 yo) • Amoxicillin (if <8 yo or pregnant) • Disseminated severe disease: Thirdgeneration cephalosporin • Doxycycline for all ages

∗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.

P E D I AT R I C S

• Borrelia • Rash occurs burgdorferi ~7–15 d after tick detached • Lasts ≤6 wk if untreated

• Nikolsky sign: Mechanical pressure induces dermal– epidermal cleavage • No organisms seen on skin culture or biopsy

116

Pediatrics

VIRAL INFECTIONS Type

Description

Course

Treatment

Other

Rubeola or measles (paramyxovirus)

• Erythematous maculopapular rash starts on face and spreads to trunk or extremities

• Rash appears ~5 days after onset of symptoms • Fades over several days in cephalocaudad direction

• Supportive care

• Prodrome: Malaise, fever, cough, coryza, conjunctivitis, Koplik spots (gray papules on buccal mucosa)

Rubella or German measles (rubella virus)

• Discrete, erythematous, maculopapular eruption on face with spread to body over 24 h

• Rash appears within 5 d after onset of symptoms • Fades over several days in cephalocaudad direction

• Supportive care

• Prodrome: Fever, headache, URI symptoms • Tender posterior cervical and suboccipital LAD • Forscheimer’s spots: Pinpoint rose-colored macules or petechiae on soft palate

Roseola or exanthem subitum (HHV-6)

• Pink macules and papules on trunk, neck, extremities as high fever resolves

• Rash fades over a few days

• Supportive care

• Usually 6 mo to 3 yr age group

Erythema infectiosum or Fifth’s disease (parvovirus B19)

• Facial erythema (“slapped cheeks”) • Erythematous reticular, macular, ± pruritic eruption on extremities, trunk

• Usually asymptomatic • May have mild myalgias, lowgrade fevers • Rash may last a few weeks

• Supportive care

• Rash may recur with heat (eg, showering) during course of illness

Hand-footmouth disease (coxsackie A16; enterovirus 71)

• Erythematous patches and vesicles on hands, feet, buttocks, oral mucosa

• Fever, anorexia, oral pain → oral mucosal ulcers • Most spontaneously resolve over 2–3 wk

• Monitor hydration status • Carafate PO • Aggressive pain control

Chickenpox (primary varicella zoster virus infection)

• Crops of vesicles with surrounding erythema (“dew drops on rose petal”) → pustules → rupturing with crust formation • Lesions in all stages at same time • Most commonly on trunk, face, proximal extremities

• Incubation: • Symptom10–21 d atic relief • Absent or mild • Immunoprodrome compromised or • Resolution in dissemi10–14 d nated: • Spread via respiAcyclovir ratory route therapy, • Possible compliVZIG within cations: Pneumo- 96 h of nia, encephalitis, exposure staphylococcal superinfection

• Contagious from 24 h before onset of rash until all lesions crusted over

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Dermatology

117

Description

Course

Treatment

Herpes zoster or shingles (VZV reactivation)

• Pain, burning, pruritic grouped vesicles on an erythematous base • Usually unilateral, involving one dermatome

• May disseminate in immunocompromised patients • Postherpetic neuralgia: Pain lasting weeks to years after resolution of rash

• Early treatment with antivirals • Aggressive pain control

Other

Herpes simplex virus • HSV1: Mostly oral • HSV2: Mostly genital

• Gingivostomatitis: Vesicles → erosions, regional adenopathy • Herpetic whitlow: Painful, deepseated vesicles on ﬁngertips • Eczema herpeticum: Generalized vesicles or erosions over atopic dermatitis • Genital: Venereal transmission, grouped vesicles on erythematous base; fever, malaise, LAD

• Recurrent: Grouped vesicles on erythematous base, heal without scarring in 10–14 d; pain, burning, tingling, most often found on lips or genitalia; often triggered by fever, trauma, sunlight, menstruation, gastroenteritis, stress

• Acyclovir or valacyclovir at ﬁrst sign of disease may abort or shorten episode • Aggresive pain control • Acyclovir for primary disease in children • Valacyclovir suppressive therapy (daily) for those with frequent recurrences

GianottiCrosti (papular acrodermatitis of childhood)

Symmetric, skincolored or slightly erythematous papules on face, buttocks, extensor (acral) surfaces of extremities

• May be preceded by URI, mild constitutional symptoms • Spontaneous resolution in weeks to months

• Supportive care

Verruca vulgaris or common warts (HPV)

• Verrucous, graypink papules on ﬁngers, dorsal hands, soles of feet, genitals

• May occur at sites of trauma • Autoinoculation may occur by manipulating lesions • May enlarge or multiply in immunocompromised patients

• Salicylic • Genital warts acid, liquid (condyloma nitrogen, acuminata) trichloroa• In <2-3yo: cetic acid, Vertical cantharidin, transmission or podophyllin, from caregivers imiquimod, with warts destructive • Older kids: lasers, other Consider contact sexual abuse immunotherapy∗

• May be associated with viral infections (eg, EBV, HBV, others), bacterial infections (streptococci), or postvaccination

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P E D I AT R I C S

Type

118

Pediatrics

Type

Description

Course

Molluscum contagiosum (poxvirus)

• Small, isolated, dome-shaped, skin-colored papules with central umbilication

• Lesions • As for comcontagious and mon warts, autoinoculable also gentle curettage • May become inflamed • May involute spontaneously over months to years • Persist, multiply, and enlarge in HIV+ patients

Treatment

Other

∗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 course

Treatment

Other

• May be associated with posterior cervical or suboccipital LAD • Kerion may lead to scarring and permanent hair loss if left untreated

• Griseofulvin: 15–20 mg/kg/d for 6–8 wk • Selenium sulﬁde shampoo: 2x/wk for patient and contacts to reduce viable spores and prevent spread

May also consider oral terbinaﬁne, ﬂuconazole, pulse itraconazole tx

Disease

Description

Tinea capitis

• Scaly patches of broken hair or hair loss on scalp • If becomes inﬂammatory → boggy, erythematous mass with follicular pustules (kerion)

Tinea corporis

• Pruritic annular plaque with clear center and scaly, papulovesicular borders (“advancing margin of scale”)

• 2- to 4-wk course of topical antifungal BID (eg, clotrimazole, terbinaﬁne) • Oral treatment if widespread (eg, Griseofulvin)

Tinea pedis (“athlete’s foot”)

• Interdigital maceration; dry, scaly soles; vesicles or erosions over instep

• Colonization • Topical antifunaided by gal BID warmth and humidity of shoes and sweating

Tinea cruris (“jock itch”)

• Pruritic, often symmetric, welldemarcated, scaly, erythematous plaques in inguinal folds, upper thighs • May spread to buttocks and perianal area

• May have raised papular or pustular margin

• Topical antifungal BID

• Moist area aids colonization • Often with concomitant tinea pedis

(continued on next page)

Dermatology Clinical course

Description

Tinea versicolor (Malassezia furfur)

• Hypo- or hyperpigmented macules with ﬁne scales on upper torso or trunk and neck

Candida

• Oral (thrush): superﬁ- • Oral candidiasis cial, sometimes tenin immunocomder, white plaques promised on oral mucosa; patients may reveals denuded, spread to erythematous base esophagus, when scraped oﬀ causing feeding (contrast to oral diﬃculties leukoplakia from EBV • Suspect that doesn’t scrape) candidal • Intertriginous: superinfection Erythematous, scaly, if irritant diaper moist plaques dermatitis does not improve • Diaper area: Beefy, within severythematous plaques involving in- eral days; often painful with uriguinal creases, often with satellite pustules nation, bowel movement or red papules • Vulvovaginal: Thick, • Vulvovaginal: May cause white discharge and white plaques on irri- dysuria and itching tated, erythematous vaginal mucosa

• Skin discoloration may take months to resolve • Often recurs (especially in hot, humid summer months)

Treatment

Other

• Selenium sulﬁde or ketoconazole shampoo, topical azoles for small areas • Single oral ketoconazole 400 mg dose (not FDA approved in children) • Fluconazole and Itraconazole have also been suggested∗ • Oral: Nystatin • Risk factors: solution Prematurity; antibiotic, • Intertrigo: Nystacorticostertin powder oid, or OCP • Diaper dermatiuse; diabetes tis: Topical imidamellitus; zole or nystatin, immunobarrier creams, comprofrequent diaper mised state changes; lowstrength topical corticosteroids if necessary • Vulvovaginal: topical imidazoles, oral antifungals for recurrent or refractory cases (eg, ﬂuconazole 150 mg once in adolescents)†

∗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

Scabies

• Pruritus (worse at night and with hot bath) • Small, erythematous papules with excoriations or crusting on interdigital webs, wrist,

Sarcoptes scabiei

• Permethrin 5% cream: • Secondary bacterial Cover entire body infection common overnight (include • Usually pruritus scalp in infants); resolves within a few repeat in 1 wk days after treatment • Ivermectin: 200 mcg/kg but rash may last once; may repeat in several weeks 7–10 d

Other

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P E D I AT R I C S

Disease

119

120

Pediatrics

Type

Description

Cause

• ankles, feet, axillae, GU area, buttocks, areolae, scalp and face in infants • May see vesicles, burrows (wrists, ankles)

Lice (Head)

• Intense pruritus • Nits and lice seen on scalp • Excoriations, erythema, scaling of scalp and neck

Pediculus capitis

Treatment

Other

• Wash all clothing and bed linens in hot water and dry in high heat • All contacts must be treated at least once (twice if symptomatic)

• May use topical steroids for pruritus relief • Norwegian or crusted type: Highly contagious; seen in immunocompromised patients

• Permethrin 1% rinse or overnight application of 5% cream • Repeat in 1 wk • 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)

• May develop secondary bacterial infection

DRUG REACTIONS Type

Description

Pathogenesis Course

Treatment

Morbilliform or exanthematous

• Symmetric, erythematous macules and papules on trunk and upper extremities that become conﬂuent • May be urticarial on limbs, purpuric on ankles or feet • Spares mucosa

• PCNs, sulfa, cephalosporins anticonvulsants, allopurinol, others

• 4–14 d after initiation • May have pruritus and low-grade fever • Resolves in 1–2 wk without sequelae

• Stop oﬀending agent if possible; desensitization if necessary • TCS or antihistamines for pruritus

Urticaria (immediate IgE-mediated hypersensitivity)

• Pruritic, transient erythematous, edematous papules and plaques • May have central pallor (wheals)

• PCNs, cephalosporins, NSAIDs, monoclonal antibodies, contrast media, others

• Minutes to hours after exposure • Each lesion usually lasts <24 h • Chronic urticaria >6 wk

• Stop oﬀending agent • Antihistamines • Desensitization, if drug necessary

(continued on next page)

Dermatology Type

Description

Pathogenesis Course

121

Treatment

• Minutes to hours after exposure • Often lasts for few days

• Protect airway • Epinephrine • Stop and avoid oﬀending agent • Antihistamines • Chronic: Steroids PO

Anaphylaxis

• Urticarial or angioedema lesions + systemic symptoms (hypotension, tachycardia)

• PCN, latex • Rarely, local anesthetic, topical antiseptic • Anaphylactoid: Contrast media

• Minutes after exposure

• Immediately stop oﬀending agent • Protect airway • Systemic corticosteroids • Epinephrine • Avoid drug in future; desensitize if necessary

Serum sickness-like reaction

• Urticarial, morbilliform, “purple urticaria” • Fever • Joint pain

• Cefaclor, bupropion, minocycline, PCNs, propranolol, others

• 1–3 wk after exposure

• Stop oﬀending agent • Supportive and symptomatic care

Fixed drug eruption

• One or few annular, erythematous or edematous plaques • May have dusky hue or central blister • Favors face, acral sites, genitalia

TMP-SMX, NSAIDs, barbiturates, tetracyclines, pseudoephedrine, others

• First exposure: 1–2 wk • Reexposure: within 24–48 h • Fades over several days with postinﬂammatory pigment changes • Recurs in same location upon reexposure

• Stop oﬀending agent • Topical corticosteroid

Acute generalized exanthematous pustulosis (AGEP)

• Erythematous edematous plaques with small, nonfollicular, sterile pustules favoring intertriginous areas, trunk, and extremities • May have burning, pruritus

• β-lactam antibiotics, macrolides, CCBs, antimalarials

• <4 days after exposure, lasts 1–2 wk, then superﬁcial desquamation

• Stop causative drug • Topical corticosteroids • Antipyretics

P E D I AT R I C S

Drug-induced • Pale or pink sub• ACEIs, PCNs, cutaneous edema NSAIDs, angioedema of face, extremicontrast media, ties, genitalia monoclonal • May extend to lar- antibodies ynx, oropharynx, intestinal wall

(continued on next page)

122

Pediatrics

Type

Description

Pathogenesis Course

Drug reaction • Starts morbil• Antiepilepliform on face, tics, sulfa, with eosinoupper trunk, allopurinol, miphilia and extremities → nocycline, gold systemic edema with salts, dapsone, symptoms antiretrovirals, (DRESS), drug follicular accentuation others hypersensitivity • May have pustules, syndrome blisters, erythro(DHS) derma, purpura • Often with edema of face

Treatment

• 2–6 wk after drug initiation • Prominent eosinophilia and atypical lymphocytes • Often with lymphadenopathy, arthralgia or arthritis, liver involvement, myocarditis, interstitial pneumonitis, interstitial nephritis, thyroiditis, GI bleeding if allopurinol induced

• Stop oﬀending agent • Systemic corticosteroids • Check serial liver enzymes if elevated • Check thyroid function tests at onset of reaction and 2–3 mo later • May require steroid maintenance treatment for weeks to months because of relapses when tapered

Erythema multiforme (EM)

• Acrofacial, grouped or coalescent target lesions, erythematous rings with dusky or crusted centers, or urticarial • Minimal (only one site) or no mucosal involvement or systemic symptoms

• Most common: Infection (especially HSV, Mycoplasma spp.) • More rarely: Drugs

• Abrupt onset within 24–72 h, last ≥7 days • Most heal without sequelae • Occasional postinﬂammatory pigment changes • HSV-associated EM may recur

• Symptomatic: Antihistamines; bland emollients for erosions; diphenhydramine, lidocaine and Maalox in 1:1:1 mix mouthwash for mouth pain • Recurrent HSVassociated EM: Acyclovir 10 mg/ kg/d in divided doses for ≥6 mo

StevensJohnsonSyndrome (SJS) (<10% BSA)

• Irregular, coales• NSAIDs cent, erythema(especially tous or dusky oxicams), antimacules, mucosal biotics (sulfa), (lips, oral, ocular, antiepileptics, genital) erosions antiretrovirals (two or more sites • Infections required) and ten- (eg, HSV, derness → hours Mycoplasma), to days later, neimmunizations crotic epidermal detachment and ﬂaccid blisters, hemorrhagic crusting

• Prodrome: URI, fever, skin pain, arthralgias • Usually occurs 7–10 d after initiation of drug • May develop LAD, hepatitis, cytopenias, respiratory or GI involvement, photophobia, odynophagia • Risk of infection, electrolyte and ﬂuid imbalance, insulin resistance, multiorgan failure

• Immediately stop causative drug • Supportive care: Wound care, gentle cleansing, bland emollients with nonadherent dressings for erosions, eye care • Diphenhydramine, lidocaine, and Maalox in 1:1:1 mix mouthwash for mouth pain • Monitor ﬂuids, electrolytes, and vitals • IVIG: 0.5–1g/kg/d for 3–4 d

SJS– TEN overlap (10-30% BSA)

TEN (>30% BSA)

(continued on next page)

Dermatology Type

Description

Photodrug

• Erythematous • Tetracyclines, patches, papules, quinolones, vesicles or bullae NSAIDs, over sun-exposed antiepileptics, areas amiodarone, • Localized burning, thiazides, voriconazole itching

Pathogenesis Course

123

Treatment

• After variable amount of sun exposure • May cause scarring

• Stop causative drug, sun protection, TCS, antihistamines

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

TOPICAL CORTICOSTEROID GUIDE* Generic Name

Brand Names

Vehicles

I (superpotent)

Augmented betamethasone dipropionate 0.05%

Diprolene

Gel, ointment

Clobetasol propionate 0.05%

Clobex, Olux, Temovate, Cormax

Shampoo, foam, spray, solution, gel, lotion, cream, ointment

Diﬂorasone diacetate 0.05%

Apexicon, Psorcon

Ointment

Fluocinonide 0.1%

Vanos

Cream

Flurandrenolide 4 mcg/cm2

Cordran

Tape

Halobetasol propionate 0.05%

Ultravate

Cream, ointment

Cyclocort

Ointment

Augmented betamethasone dipropionate 0.05%

Diprolene

Lotion, cream

Betamethasone dipropionate 0.05%

Diprosone

Ointment

Desoximetasone 0.25%

Topicort

Cream, ointment

Diﬂorasone diacetate 0.05%

Apexicon, Psorcon

Cream

Fluocinonide 0.05%

Lidex

Solution, gel, cream, ointment

Halcinonide 0.1%

Halog

Solution, cream, ointment

II Amcinonide 0.1% (high potency)

III (medium to high potency)

Mometasone furoate 0.1%

Elocon

Ointment

Amcinonide 0.1%

Cyclocort

Lotion, cream

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 (continued on next page)

P E D I AT R I C S

Class

124

Pediatrics

Class

Generic Name

Brand Names

Vehicles

IV (medium potency)

Betamethasone valerate

Luxiq, Beta-Val

Foam, lotion, cream

V (medium to low potency)

VI (low potency)

VII (least potent)

Hydrocortisone valerate 0.2%

Westcort

Ointment

Hydrocortisone butyrate 0.1%

Locoid

Ointment

Mometasone furoate 0.1%

Elocon

Cream

Triamcinolone acetonide 0.1%

Kenalog, Aristocort

Ointment

Fluticasone propionate 0.05%

Cutivate

Lotion, cream

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, Aristocort

Lotion, cream

Aclometasone dipropionate 0.05%

Aclovate

Cream, ointment

Desonide 0.05%

Desonate, Desowen, Locara, Verdeso

Lotion, foam, gel, cream, ointment

Fluocinolone acetonide 0.01%

Capex, Synalar

Solution, shampoo, cream

Hydrocortisone butyrate 0.1%

Locoid

Cream

Triamcinolone acetonide 0.025%

Kenalog, Aristocort

Lotion, cream, ointment

Hydrocortisone 2.5%

Hytone, Nutracort, Synacort

Lotion, cream, ointment

Hydrocortisone 1%

Many over-thecounter brands

Spray, lotion, cream, 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 eﬀects. 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

C H A P T E R 12

Ear, Nose, and Throat ACUTE OTITIS MEDIA (AOM) • Epidemiology: 33% of all pediatric office visits; by 3 yo, 80% have ≥ 1 AOM • Pathophysiology: URI or inflammation → Eustachian tube dysfunction or occlusion → effusion → infection • Etiologic agents: Respiratory viruses >> Haemophilus influenzae (Post PCV7 52%, Pre PCV7 15-30%) > Pneumococcus spp. (Post PCV7 34%, Pre PCV7 25-50%) > Moraxella spp. (Pre PCV7 3%–20%) > GABHS > other (Pediatrics 2004;113:1451) • Diagnosis • History: Fever (especially increasing fever curve), URI, ear pain or fullness, hearing loss, vomiting, ear drainage or diarrhea. • Physical exam: Bulging tympanic membrane (TM), purulent material, air-fluid level, ↓ or no movement of TM, otorrhea, ± redness, ± bullae. • Best predictors are position (ie, bulging), mobility of TM (↓ or no movement of TM), and color (PIDJ 1998;17(6):540). Consider tympanocentesis and bacterial culture for children with recurrent or chronic disease. • Treatment • Pain and fever control are the most important interventions. • Within 24 hours, 61% of patients have resolution of symptoms without antibiotics. • Antibiotics (see table below) often do not change the duration of illness of AOM.

CRITERIA FOR INITIATION OF ANTIBIOTICS IN CHILDREN WITH AOM Diagnosis of AOM is Certain

Diagnosis of AOM is Uncertain

<6 mo

Start antibiotic treatment

Start antibiotic treatment

6–24 mo

Start antibiotic treatment

Observe with follow-up assured if the patient’s condition is non-severe (temperature <39°C [102.2°F] and mild otalgia); Start antibiotics if the patient’s condition is severe (moderate to severe otalgia and temperature >39°C)

≥ 24 mo

Observe with follow-up assured if the patient’s condition is non-severe (temperature <39°C [102.2°F] and mild otalgia); Start antibiotics if the patient’s condition is severe (moderate to severe otalgia and temperature >39°C)

Observe with follow-up assured

125

P E D I AT R I C S

Age

126

Pediatrics

ANTIBIOTIC CHOICES FOR TREATMENT OF AOM Temperature >39°C (102.2°F)

Initial antibiotic choice

Treatment failure at 48–72 h after initial management

No

Amoxicillin, 80–90 mg/kg/day (If penicillin allergic: Non– type I: cefdinir, cefuroxime, or cefpodoxime; type I: azithromycin, clarithromycin)

Amoxicillin–clavulanate, 90 mg/kg/ day of amoxicillin with 6.4 mg/kg/ day of clavulanate (If penicillin allergic: Non–type I: ceftriaxone for 3 days; type I: clindamycin)

Yes

Amoxicillin–clavulanate, 90 mg/kg/ day of amoxicillin with 6.4 mg/kg/ day of clavulanate (If penicillin allergic, ceftriaxone for 3 days)

Ceftriaxone for 3 days (If penicillin allergic, tympanocentesis, clindamycin)

• Single high-dose azithromycin (30 mg/kg/dose) is equal to amoxicillin in efficacy. (PIDJ 2005;24:153) • Add topical agents as well for AOM with perforation or if the patient has tympanostomy tubes (eg, Ciprofloxacin; Ofloxacin). • 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. influenzae > 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 fluid level, TM retraction or bulging, serous middle ear fluid, ↓ 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 → definite 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 • Definition: 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 inflammation. However, when inflammation

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 Agents

Diagnosis

Diagnosis

Acute mastoiditis

Fever (often <2 yrs of age), recent AOM with temporary improvement followed by clinical decline Exam: Postauricular swelling, erythema ± ﬂuctuance, TM suggestive of infection, pinna anteriorly displaced Test: CT temporal bone with contrast

Pneumococcus spp. (serotype 19A is associated with high rates of β-lactam resistance) > GABHS > Staphylococcus aureus > others

ENT consultation;† Start, vancomycin/ clindamycin (oxacillin/ nafcillin depending on local prevalence of MRSA) and cefotaxime

Treatment*

Chronic mastoiditis

Usually with persistent ear drainage ± fever ± postauricular swelling Test: CT temporal bone with contrast

S. aureus, Pseudomonas spp., other GNRs, mycobacteria, fungal; 80% of chronic cases demonstrate coinfection with anaerobes

Would also include ticarcillin–clavulanate + gentamicin and topical ear drops (Ciproﬂoxacin or Cortisporin)

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

RHINITIS • Inflammation 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 shiners; other atopic disease (asthma, eczema); red, itchy eyes

Low grade fever; rhinorrhea or congestion; cough; sore throat; possible GI symptoms (diarrhea, vomiting)

Etiologic agents

Dust mites, ragweed, grass, dust, animal dander

Any respiratory virus

Treatment

Antihistamines, nasal steroids, nasal saline, leukotriene antagonists

Frequent nasal saline, encourage ﬂuid intake, supportive care

P E D I AT R I C S

* If the patient has an acute onset of symptoms with minimal ﬂuctuance 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 signiﬁcant ﬂuctuance, vertigo, neurologic symptoms, vomiting, hearing loss, or any other signs/symptoms of intracranial involvement.

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SINUSITIS • Pathophysiology: Usually result of bacterial superinfection of viral URI or inflamed 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. influenzae (~20%), Moraxella catarrhalis (~20%) and GABHS. After PCV 7 vaccine ↓ incidence of pneumococci and ↑ rates of H. influenzae (≤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 floor 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: ↑ Difficulty 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 complications?

Tonsils grade IV?

YES

NO

Expedited sleep study & referral to specialist

YES

NO

Sleep study

Continue screening at subsequent visits

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

NO

Sleep study and referral to specialist

Sleep study

• 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 difficulty, dental anomalies, hearing loss, poor weight gain

Available at www.AccessPediatrics.com • Pharyngitis • Adenotonsillar hypertrophy • Obstructive sleep apnea • Branchial anomalies

P E D I AT R I C S

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

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 count, Gram stain, glucose, protein) & CSF cx (hold CSF for viral studies) Consider: • Rapid viral testing (RSV/Influenza/adenovirus) • HSV workup2

YES Treat as clinically appropriate

Laboratory workup CBC, blood cx, UA1 with micro & cx

Febrile ê 48h

NO

NO

Toxic? (Lethargy, poor perfusion, hypo/hyperventilation, cyanosis, irritable)

NO

Admit to hospital on antibiotics 0–28d Ampicillin & gentamicin ê29d Ampicillin & cefotaxime (meningitis dosing if CSF pleocytosis/gram stain abnormal)

Any culture (+)

NO

YES

YES

CSF cx/studies, consider rapid viral testing → ceftriaxone IM → Admit to Observation unit or inpatient admit

YES

High risk?3 (see Box 1)

NO

Clinically well & Inpatient: Cx (–) ≥ 48h Observation: Cx (–) @23h

Send home without antibiotics if: • Adequate caregiver education • Reliable follow up in 12–24h • PCP & caregiver agree with plan

YES

Send home if: • Reliable f/u in 12–24h • Adequate caregiver education • PCP & caregiver agree with plan

OR Admit ± empiric antibiotics (Do LP prior to antibiotics)

Box 1 1 Urine 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).

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131

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

Toxic? (Ill-appearing, lethargy, poor perfusion, hypo/hyperventilation, cyanosis, irritable)

YES

Laboratory workup CBC blood cx, UA with micro & cx, CSF (cell count, Gram stain, glucose, protein) & CSF cx WBC >20,000 or if clinically indicated → CXR

YES

NO

Identified bacterial source for fever: AOM, sinusitis, pneumonia, cellulitis, abscess, osteomyelitis, septic arthritis

Treat source for fever as clinically appropriate

Admit to hospital on antibiotics Vancomycin and cefotaxime ± other indicated antibiotics YES

NO

Viral syndrome? Bronchiolitis, varicella, croup, 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: 1. Female ≤ 2 year, 2. Males circumcised ≤6 mo OR uncircumcised ≤12 mo

NO

YES

Received 3 doses of PCV7

U/A with micro and cx if: 1. Female ≤ 2 year, 2. Males circumcised + ≤6mo or uncircumcised + ≤12mo, 3. History of UTI, GU defect Send home without antibiotics if: tolerating PO, reliable follow up arranged, caregiver education complete (OR monitor patient in Observation unit/inpatient admit)

NO

NO

CBC d/p, draw and hold blood cx, UA with micro and cx

CBC or UA abnormal?

YES

3

• If WBC > 15,000/mm or ANC >10,000 → Send blood cx, ceftriaxone IM, & f/u in ≤24h • If WBC > 20,000/mm3 → CXR → If + treat for pneumonia; if – blood cx, ceftriaxone IM, & f/u in 24h • 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 Appendage

Testicular Torsion

Epididymitis

Age group

Neonatal, 12–28 yo (66%)

Sexually active adolescents

Onset

Sudden

Gradual

Gradual/sudden

Testicular lie

High

Low

Low

7–14 yo

(continued on next page)

P E D I AT R I C S

Send home if: tolerating PO, reliable follow up arranged, caregiver education complete (or monitor patient in observation unit/inpatient admit)

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Pediatrics

Testicular Torsion

Epididymitis

Torsion of Testicular Appendage

Cremasteric reﬂex

Usually not present

Present

Present

Prehn’s sign∗

Negative

Positive

Variable

Urinalysis

Normal

+WBCs on UA

Normal

Presentation

Acute onset of pain, nausea/vomiting, purple, swollen, painful testes

Fever, chills, urethral discharge, nausea, neonatal, 12–28 yo (66%), edematous and tender epididymis

Pain located in the superior pole of testicle; mild erythema or edema; blue dot sign (21%)

Doppler ultrasonography

↓ or absent ﬂow

Normal or ↑ ﬂow in epididymis

Torsed appendage with ↓ ﬂow but normal ﬂow to testes

Treatment

Emergency surgery: Bilateral ﬁxation of testes (irreversible damage possible in 5–6 h) Manual detorsion (open book technique) if timely surgical intervention not available

Scrotal support (briefs), NSAIDs Antibiotics† • Prepubertal: Most commonly no antibiotics required; may consider Trimethoprim– sulfamethoxazole • Sexually active: Ceftriaxone + azithromycin/ doxycycline

Scrotal support (briefs), NSAID Resolves within 2–12 days

∗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 • Definition: 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 nontraumatic causes Fracture

2%

Overuse (soft tissue injury, muscular strain, Osgood-Schlatter’s disese, hematoma of the thigh)

18%

Osteomyelitis Other (appendicitis, PID, torsion constipation, etc.)

2%

Transient synovitis

40%

Legg-Calve-Perthes syndrome (avascular necrosis of the femoral head)

2% (continued on next page)

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% of nontraumatic causes Inﬂammation (rheumatologic: JRA, SLE, reactive arthritis or HSP) Infection (skin, soft tissue, joint, septic arthritis)

3% 4%

Foreign body Tumor “Toddler’s fracture” (nondisplaced spiral fracture of the tibial shaft) Trauma

1% 1% —

SCFE Sickle cell pain crisis

<1%

*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, inflammation, 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 Laboratory Studies

High–impact fall

Localized pain, swelling, loss or ↓ ROM

None unless infection is suspected

X-rays

Infectious

Fever, chills, erythema, induration, pain

Guarding, warmth, erythema, induration, discharge

CBC, ESR, CRP, blood cx, joint aspirate, skin or abscess culture

X-rays, MRI (deep infection or onset <1-2 weeks prior), bone scan (unclear site)

Inﬂammatory

Acute onset

Guarding, can bear weight, allows passive ROM ± swelling, ± erythema

CBC, ESR, CRP

X-rays

Chronic: Pain >6 mo ± FHx of RA

Warmth or erythema, CBC, ESR, CRP, one or more joints joint aspiration

Night pain, pain unrelated to activity, not relieved by OTC meds, ± fever

Mass, local tenderness

History

Traumatic

Neoplastic

Radiology

CBC, ESR, CRP, Alk X-rays, MRI or Phos, calcium, CT, bone scan, electrolytes; staging workup joint aspirate (continued on next page)

P E D I AT R I C S

Physical Examination May Reveal

Category

134

Pediatrics Physical Examination May Reveal

Laboratory Studies

Radiology

Problem since birth

Deformity, leg length discrepancy, loss of ROM

None

X-rays

Neurologic

Ataxia, loss of balance, disorganized gait

↑ or ↓ muscle tone, ↑ or ↓ DTR, cavus foot or claw toes

CK (if DMD is in diﬀerential diagnosis)

X-rays

Developmental

Painless limp (LCP disease), knee pain (LCP disease, SCFE)

Loss of ROM in joints, asymmetric ROM, pain with ROM

None

X-rays

Category

History

Congenital

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 physical exam

Fever (usually >101.3°F) ; refusal to bear weight*; warm red, swollen joint; ↓ ROM (may be rigid); if septic hip (hip ﬂexed and abducted); most sxs ~3 days duration; recent URI (53%) trauma (31%)

Recent URI, low grade to normal temperature, allows passive ROM, can bear some weight

Laboratory studies

CBC∗ (↑ WBC, usually >12,000/mm3), ↑ ESR∗ (usually >40), ↑ CRP (>2)

None required; CBC usually normal, ESR or CRP mild elevation

Radiologic studies

US of joint (85% show eﬀusion), MRI ⊕ in 88%, radiography (20% reveal joint space widening)

U/S or Ultrasound, MRI not needed unless need to help distinguish from septic arthritis. Consider X-rays to rule out femoral neck fractures.

Etiology

Staphylococcus aureus (MRSA) > Kingella > Streptococcus pneumoniae > Salmonella; consider GBS in neonates

Postinfectious reactive ﬂuid in joint (joint ﬂuid cx results negative)

Treatment

Orthopedic emergency (needs immediate drainage), joint aspiration (send for 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

NSAIDS scheduled until symptomatically improved

∗Positive predictive value of septic arthritis using ﬁndings 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

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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 verified for all patients and prophylaxis provided as indicated. • Rabies prophylaxis: • Consider when exposure to saliva is sufficient 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 infiltrated 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 Prevention 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 2–3%

Percentage

5–10%

80–90%

Appearance

Puncture wounds

Tears and punctures

Moon shaped

Suture?

Do not close punctures

Can close if <12h old

Can close if <8h old

Infection rate

50%

30%

Organisms

Pasteurella multocida, Streptococcus spp., Staphylococcus spp.

Treat with prophylactic antibiotics

Prophylaxis for all high risk wounds (deep puncture wounds (e.g cat bites), moderate to severe wounds with associated crush injury, wound in area of 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

60%

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

P E D I AT R I C S

Streptococcus spp., Staphylococcus spp., Eikenella corrodens, anaerobes

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COMMON CHARACTERISTICS AND TREATMENT RECOMMENDATIONS FOR INFECTIOUS CAUSES OF STRIDOR Feature

Epiglottitis

Bacterial Tracheitis

Croup

Retropharyngeal Abscess 4–10 yr (median, 3.5 yr)

Age

3–7 yr

5–10 yr

6 mo–3 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 biphasic

Inspiratory

Comments

Sore throat (50%); respiratory distress; neck hyperextended; patient prefers sitting in “tripod” position

Sore throat; thick, purulent secretions; patient prefers being supine

Croup usually preceded by URI symptoms ± respiratory distress; sore throat

Sore throat, ↓ PO, neck stiﬀness (59%, ↓ ROM of neck), retropharyngeal bulge (43%), neck mass (91%), agitation (43%)

X-ray of neck (AP & Lat)

“Thumbprint sign”

Tracheal narrowing

Subglottic narrowing (50%) “steeple sign”

Retropharyngeal soft tissue swelling

Etiology

S. pneumoniae , GABHS, S. aureus, Moraxella catarrhalis, Haemophilus influenzae∗ Inhalation or caustic injury, blind ﬁnger sweep

S. aureus, H. influenzae (nontypeable; type B common before vaccination)

Parainﬂuenza type I (60%), II, III, IV; inﬂuenza; adenovirus; RSV; measles (unimmunized host)

S. aureus (MSSA or MRSA), Haemophilus spp., GABHS, anaerobes

Management

ABC (anticipate diﬃcult intubation), CBC, blood cx Admit to ICU; ENT consult

ABC (anticipate diﬃcult intubation), airway humidiﬁcation, hydration. Admit patient; ENT consult for possible bronchoscopy for suctioning

Dexamethasone (0.6 mg/kg PO or IM; maximum 10 mg), racemic epinephrine only if stridor at rest; Other: Heliox, inhaled budesonide (2 mg) ± Discharge home†

ABC (rarely requires intubation), CT neck; ENT consult for possible drainage; Admit patient on IV antibiotics, ± IVF and pain control

Antibiotic

Third-generation cephalosporin (eg, ceftriaxone)

Third-generation cephalosporin + MRSA coverage‡

No

MRSA coverage‡ ± third-generation cephalosporin (continued on next page)

Emergency Medicine

Feature

Epiglottitis

Morbidity and mortality

6%–10% without intubation (1% with intubation)

Bacterial Tracheitis

Croup

~4%–20%

Rare mortality

137

Retropharyngeal Abscess High mortality (50%) if associated with mediastinitis or other complications

∗H. influenzae 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 (CRS Ä3; PEF ê60%)

Moderate (CRS 4–6; PEF ê40%)

Management O2 to keep SpO2 ≥ 92% Yes Yes <2yr: 5mg/6puffs, SABA neb/MDI with spacer <2yr: 2.5mg/4puffs, ≥2yr: 5mg/6puffs ≥2y: 5mg/6–8puffs x 1 dose → reassess Frequency of SABA q20min PRN x 3doses then q1–3h

Yes 5mg/8puffs q20min PRN x 3doses → if no improvement start continuous SABA

Ipratropium bromide

No

Consider

st If no response after1 SABA ADD Ipratropium x 3 doses

Corticosteroid

Yes (PO)

Yes (PO)

Yes (PO/IV)

CRS Ä3 or PEF ê60% tolerating q3–4h SABA Vital signs stable on room air

• • •

Discharge home Continue SABA tx per action plan Compete PO steroid Initiate/continue long term control medications (if applicable) Patient education 1. Review medications 2. Drug delivery teaching 3. Review action plan 4. Recommend follow-up

CRS >3 & <6 or PEF ê40% and NOT improving

CRS ê6 or PEF <40% and NOT improving

Admit to hospital • O2 to keep SpO2 ≥92% • Continue SABA tx at frequency required by patient • Continue PO steroid • Consider initiation/ continue long term control medications (if applicable) • Initiate asthma education & action plan

Admit to hospital (special care unit) • • • •

O2 to keep SpO2 ≥ 92% Place on continuous SABA IV route for steroid Consider adjunct tx 1. IV Terbutaline 2. NPPV 3. Heliox • Consider initiation/ continue long term control medications • Initiate asthma education & action plan

Admit to ICU O2 to keep SpO2 ≥ 92% Continuous SABA Add ipratropium x 3 doses IV corticosteroid Consider IV magnesium Consider adjunct tx 1. IV Terbutaline 2. NPPV 3. Heliox • ABG, VBG, or CBG • Mechanical ventilation as needed

• • • • • •

Impending/actual respiratory arrest (CRS 8–12; 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

P E D I AT R I C S

Frequent reassessment

•

Impending/actual respiratory arrest (CRS 8–12; PEF Ä25%)

Severe (CRS 6–8; PEF <40%)

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CLINICAL RESPIRATORY SCORE (CRS) Assess

Score 0

Score 1

Score 2

Respiratory rate/min <2 mo 2–12 mo 1-5 yr >5 yr

<50 <40 <30 <20

50–60 40–50 30–40 20–30

>60 >50 >40 >30

Auscultation

Good AE, ↓ AE, inspiratory and expirascattered tory wheezes expiratory wheeze

Use of accessory muscles

Mild to no use of accessory muscles

↓↓ or absent AE, severe wheezing, marked prolonged expiration

Moderate intercostal retracSevere intercostal tions, mild to moderate use of and substernal retracaccessory muscles, nasal ﬂaring tions, nasal ﬂaring

Mental status

Normal

Irritable, agitated, restless

SpO2 on room air

>95%

90%–95%

Lethargic <90%

Color

Normal

Normal to pale

Cyanotic, dusky

AE, air entry. Adapted from Texas Children’s Hospital evidence based clinical guidelines for asthma.

BRONCHIOLITIS • Definition: An inflammatory 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%; Parainfluenza viruses (second most common cause), adenovirus, human metapneumovirus, influenza 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, immunodeficiency as these patients may require closer monitoring. Physical exam should include vital signs, pulse oximetry, respiratory assessment (tachypnea, nasal flaring, 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 figure: FWLS 0-60 days). • Consider RSV or influenza 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 significant 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 • Discharge criteria: (1) RR ≤70 breaths/min; (2) SpO2 ≥90% while awake; (3) parent able to do nasal saline + bulb suction; (4) PO feedings tolerated to maintain hydration,

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(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

Differential 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, abnormal menses

Tubo-ovarian abscess, PID, ovarian cyst, ovarian torsion, 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

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.

P E D I AT R I C S

• 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 internal rotation of the right leg while the patient is lying on back with hip and knee flexed 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 (calcified fecalith, sentinel loop; neither is sensitive), ultrasonography (⊕ if >6 mm noncompressible appendix, wall thickening (>2 mm), free fluid, mesenteric thickening, localized tenderness with graded compression, calcified fecalith; sensitivity and specificity varies by institution), abdominal CT (dilated non-opacified appendix with adjacent inflammatory changes, appendicolith, target sign, wall thickening (>2 mm), fat stranding, free fluid; 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).

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Intussusception • Definition: 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 significant 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, significant 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 • Definition: 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 → fluid resuscitation with NS based on level of dehydration then D5 ½ NS at 1.5 maintenance (add K after confirming UOP).

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ALTERED MENTAL STATUS AND COMA • Definition: ↓ 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%; difficult 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

P E D I AT R I C S

• 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 injuries and forensic photography. • Laboratory: Test for bruising or bleeding diathesis, anemia (CBC, PT/PTT), evaluate for dehydration or malnutrition (chem 10), screen for bone pathology (Ca2+, 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 nonambulatory), 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 significant 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

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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

C H A P T E R 14

Endocrinology DIABETES MELLITUS (DM) • Definition: Plasma glucose level that meets ADA criteria for DM (see table below)

DIAGNOSING DIABETES MELLITUS AND IMPAIRED GLUCOSE REGULATION Normal mg/dL (mmol/L)

Impaired∗ mg/dL (mmol/L)

Diabetes Mellitus mg/dL (mmol/L)

Fasting plasma glucose

<100 (5.6)

100–125 (5.6–6.9)

≥126† (7)

2-h OGTT

<140 (7.8)

140–199 (7.8–11)

≥200† (11.1)

Random glucose

<200 (11.1)

≥200 (11.1)

≥200 (11.1) + classic symptoms‡

∗Impaired glucose tolerance = prediabetes. † Asymptomatic criteria require conﬁrmation on another day. ‡ Classic symptoms include weight loss, polyuria, polydipsia ± polyphagia, lethargy, and vaginal yeast infection. Adapted from Diabetes Care 2003;26(suppl):S1.

CHARACTERISTICS SUGGESTING TYPE 1 VERSUS TYPE 2 DIABETES MELLITUS Type I

Type 2

Variable

Pubertal

Classic symptoms

Days or weeks

Subacute or absent

Physical exam

Weight loss

Obese, acanthosis nigricans, features of PCOS

Predominant race

Caucasian

Non-caucasian

C-peptide level

Low

High

Autoantibodies

Positive

Negative

Ketoacidosis

Common, recurrent

Less common (~1/3), very rarely recurrent

Adapted from Oski’s Pediatrics: Principles & Practice, 4th ed. 2006:2115.

• Categories • Type 1 DM: ~65% of pediatric patients with DM; 5% to 10% of adults with DM. • Mechanism: Absolute insulin deficiency caused by autoimmune β-cell destruction (~90% of cases); idiopathic (~10% of cases). • Presentation: Acute onset (<1 mo) of classic symptoms (weight loss, polyuria, polydipsia ± polyphagia, lethargy, or vaginal yeast infection); 25% present with DKA. • Diagnosis: See table “Diagnosing Diabetes Mellitus and Impaired Glucose Regulation.” • Screening: Not recommended (short asymptomatic period; no effective prevention). • Type 2 DM: ~35% of pediatric patients with DM; 90% to 95% of adults with DM. • Mechanism: Insulin resistance and relative insulin deficiency. • Presentation: Usually subacute; many are asymptomatic, overweight (BMI >85%) or obese; absent or mild polyuria; acanthosis nigricans; glucosuria; usually no ketonuria. • Diagnosis: Establish hyperglycemia and then differentiate from type 1 (see table ” Characteristics Suggesting Type 1 versus Type 2 Diabetes Mellitus”). • Screening: See table “Recommendations For Type 2 Diabetes Mellitus Screening”.

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Age of onset

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• 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 ﬁrst- 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, druginduced (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 deficiency 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, ﬁnger stick ketones or urine ketones, administer insulin and glucagon injections, and count carbohydrates. ∗Insulin level is only useful if drawn before the ﬁrst dose of insulin is given; this is usually done in the ED.

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PHARMACOKINETICS OF DIFFERENT TYPES OF INSULIN Onset (h)

Peak Glycemic Effect (h)

Duration (h)

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

0.5

2.5–5

4–12

1–2

4–12

18–24

3–4

3–14

6–23

3–4

∗

≥24

Insulin aspart protamine suspension and insulin aspart (Novolog® Mix 70/30)

0.2

1–4

18–24

Insulin lispro protamine and insulin lispro (Humalog® Mix 75/25™)

0.2–0.5

2–12

18–24

Insulin NPH suspension and insulin regular solution (Novolin® 70/30)

0.5

2–12

18–24

Types of Insulin Rapid Acting

Short Acting Insulin regular (Humulin® R, Novolin® R)

Intermediate Acting Insulin NPH (isophane suspension) (Humulin® N, Novolin® N)

Intermediate to Long Acting Insulin detemir (Levemir®)

Long Acting Insulin glargine (Lantus®)

Combinations

P E D I AT R I C S

∗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 ﬂexible (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)

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• Disadvantages: Less ﬂexibility (ﬁxed 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, ﬂexibility (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 beneﬁt–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 first 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 fluids; 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 fluids 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).

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• 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 figure “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 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 deficiency; iodide excess (amiodarone), other goitrogens (lithium, cobalt) • Secondary: Thyrotropin (TSH) deficiency (isolated or associated with other anterior pituitary hormone deficiencies); thyrotropin-releasing hormone deficiency (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, galactorrhea, 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)

P E D I AT R I C S

Hypothyroidism

Check FSBG to see if <80 mg/dL (4.4 mmol/L)

Hypoglycemia Clinical presentation: Headache, hunger, sweating, tachycardia, blurred vision, somnolence, seizures, loss of consciousness

Tolerating PO?

YES NO

YES

Give “Mini dose glucagon” Mix glucagon according to full dose instructions. Give dose IM using a regular insulin syringe. Dose based on age: Child ≤ 2 yr: 2 units [20 mcg] 2-15 yr: 1 unit [10 mcg]/yr of age >15 yr: 15 units [150 mcg]

FSBG 50-80 mg/dL (2.8-4.4 mmol/L) Give 4 oz juice + 15 g complex CHO (eg, small sandwich)

148

FSBG <40 mg/dL (2.2 mmol/L) More aggressive treatment (eg 11/2 tubes concentrated glucose, or cake frosting between gums and lips) Recheck FSBG in 15 minutes

YES

Figure 14-1

NO

Monitor FSBG as clinically appropriate until FSBG ≥ 100 mg/dL consistently (5.6 mmol/L)

Management of hypoglycemia.

FSBG ≥ 80 mg/dL (4.4 mmol/L)?

YES

IV access: Give D50 (1 mL/kg) or D25 (2 mL/kg) OR No IV access: Give glucagon SubQ: Child ≤ 20 kg, 0.5 mg; >20 kg, 1 mg (Note: glucagon effect lasts 1 hr; can cause emesis) Recheck FSBG in 30 minutes FSBG ≥ 80 mg/dL (4.4 mmol/L)?

NO

Recheck FSBG in 30 minutes

FSBG ≥ 80 mg/dL (4.4 mmol/L)?

NO

Conscious?

NO

Give double of initial glucagon dose & establish IV (Repeat glucagon q30 min till IV or taking PO)

YES Start IV D5W or D10W water at maintenance

Check FSBG q15 min till FSBG >100 mg/dL (5.6 mmol/L) → once stable check FSBG as clinically appropriate

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• 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

Other Thyroid Diseases Acute thyroiditis • Incidence/etiology: Rare; common causes GABHS, S. pneumoniae, S. aureus and anaerobes. • Clinical findings: The patient is always toxic with fever and chills. The thyroid gland is large, erythematous, and very tender ± fluctuance. May have hoarseness or dysphagia. TFT are usually normal. • Treatment: Specific 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, influenza, echovirus, coxsackievirus, EBV, or adenovirus • Clinical findings: Onset is generally insidious. Similar to acute thyroiditis, and thyroid is firm 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.

P E D I AT R I C S

• 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, fine 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 specific 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 first 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, tachycardia, restlessness; may progress to delirium, coma, or death if untreated. • Evaluation: Diagnose based on clinical findings and scored using the Burch-Wartofsky criteria (Endocrinol Metab Clin North Am 1993;22:263) • Management: Propanolol (or esmolol), propylthiouracil (PTU), iodine, steroids, cooling.

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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 normal or increased plasma volume, which results in hyponatremic euvolemia or hypervolemia

Increased urine Na loss, which leads to hyponatremic dehydration

Etiology

CNS: Tumor or injury, surgery, meningitis, encephalitis, subarachnoid hemorrhage, hydrocephalus Lung: Pneumonia, TB Other: HIV/AIDS, neoplasm, thoracic surgery, drug use

CNS injury, tumor, meningitis (eg, bacterial, TB), subarachnoid or intracerebral hemorrhage, stroke, craniosynostosis repair

Clinical manifestation

Symptoms: Headache, blurred vision, nausea and vomiting, muscle cramps, weakness, irritability, change in mental status Signs: Not dehydrated; normal skin turgor; normal or ↑ BP; ± edema, ↓ DTR, asymmetric pupils, low GCS, pseudobulbar palsy

Symptoms: Polyuria, nausea, vomiting, headache, weight loss, ↑ thirst, altered mental status, seizures if severe hyponatremia, coma Signs: Moderate to severe dehydration (dry mucus membranes, sunken eye, sunken fontanel), orthostatic hypotension and ↑ HR, delayed capillary reﬁll

Diagnostic evaluation

Euvolemic or hypervolemic on exam ↓ Na (< 135 mmol/L), ↓ serum osmolality (<280 mOsm/kg), ↓ serum uric acid, ↑ urine osmolality, ↓ UNa, ↓ urine volume

Hypovolemic on exam ↓ Na, ↑ serum osmolality, ↓ serum uric acid, ↓ urine osmolality, ↑ UNa, ↑ urine volume

Management

Fluid restriction (start with <75% of maintenance, ie, 1000 mL/m2/d); if no improvement, decrease to 50%, and so on Demeclocyline or AVP receptor antagonist 3% hypertonic saline only if Na <120 meq/L and child seizing

Correct intravascular volume and provide sodium replacement with IVF

∗Also known as Renal salt wasting (RSW)

DIABETES INSIPIDUS

Etiology

Central Diabetes Insipidus

Nephrogenic Diabetes Insipidus

CNS injury, tumor, meningitis, subarachnoid hemorrhage, stroke, DIDMOAD (Wolfram) syndrome

Familial: X-linked recessive inheritance (V2 receptor gene defect); AR inheritance (aquaporin 2 gene defect). Others: Hypercalcemia, hypokalemia, drugs (eg, lithium), chronic renal disease (continued on next page)

Endocrinology

151

Central Diabetes Insipidus

Nephrogenic Diabetes Insipidus

Clinical manifestation

Polyuria, polydipsia, nocturia, hypernatremia, dehydration, seizure (if severe hypernatremia)

Dehydration; infants exhibit irritability, poor feeding, growth failure, vomiting

Diagnostic evaluation

Low urine osmolality (50–300 mOSm/L) High serum osmolality (>300 mOsm/L ) Low urine speciﬁc gravity <1.010 Water deprivation test may be needed for deﬁnitive diagnosis Central DI responds to vasopressin

Water deprivation test may be needed for deﬁnitive diagnosis Nephrogenic DI is resistant to vasopressin

Management

Management of hypernatremia Vasopressin IV for acute DI, coma, post-surgery DDAVP: PO, subcutaneous, or intranasal

Provision of free water Salt-restricted diet Drugs: Thiazide diuretics, 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

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 Breast

B1 : Prepubertal B2 : Breast bud

Boys Gonadal

G1 : Prepubertal <2.5 cm length G2: Testes >2.5 cm length or ≥4 cc vol

B3: Breast elevation

G3: Testes >3-3.5 cm length

B4: Areolar mound (“mound on a mound”)

G4: Testes >3.5-4 cm length

B5: Adult

G5: Adult testicular length >4 cm (continued on next page)

P E D I AT R I C S

• 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 • Pubertal arrest = No progress in puberty over two years.

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Pediatrics Girls

Pubic hair

Boys

PH1: Prepubertal

Pubic hair

PH1: Prepubertal

PH2: Sparse hair on medial labia

PH2: At base of penis

PH3: Coarse, curly hair, spread over mons pubis

PH3: Spread to mons pubis

PH4: Increasing distribution over labia majora

PH4: Not on thighs

PH5: Adult (on inner thighs)

PH5: On thighs

RICKETS LABORATORY DATA IN RICKETS Calcium

Phosphate

Alk Phos Calcidiol Calcitriol PTH

N, ↓ N, ↓ ↓

N, ↓ ↓ ↓

↑ ↑↑ ↑↑

↓ ↓ ↓↓

N ↓, N, ↑ ↓

N ↑ ↑↑

Deﬁcient 25hydroxylase

↓

↓

↑

↓

↓

↑

Deﬁcient 1-αhydroxylase

↓↓

↓↓

↑↑↑

N

↓↓↓

↑↑↑

Vitamin D end organ resistance

↓↓

↓↓

↑↑↑

N

↑↑↑

↑↑↑

X-linked hypophosphatemia

N

↓↓

↑

N

N, ↓

N

HHRH∗

N

↓↓

↑

N

↑

↓

Fanconi syndrome

N

↓↓

↑

N

↑

↑

Vitamin D deﬁciency Mild Moderate Severe

Tumor Induced

N

↓

↑

N

↑

N

Phosphate deﬁciency

N, ↑

↓↓

↑↑

N

↑

↑

Ca deﬁciency

↓↓

↓

↑↑

N

↑

N, ↑

Hypophosphatasia

N, ↑

N,↑

↓

N

N

N

∗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 insufficiency • Hypothyroidism

C H A P T E R 15

Fluids, Electrolytes, and Acid–Base Balance MAINTENANCE IV FLUID (MIVF) AND ELECTROLYTE REQUIREMENTS Daily Fluid Requirements Kilograms of Body Weight–Based Method (Pediatrics. 1957;19:823) • 1–10 kg: 100 mL/kg/d and • 10–20 kg: 50 mL/kg/d and • >20 kg: 20 mL/kg/d BSA-Based Method (Pediatrics. 1960;25:496) • See “BSA Nomogram and Calculations” in Chapter 1 for BSA calculation. BSA (m2) × 1500–1600 mL/m2/d = Daily requirement • Examples (22-kg child): Daily (body weight–based method): (100 mL/kg/d × 10 kg) + (50 mL/kg/d × 10 kg) + 20 mL/kg/d × 2 kg) = 1540 mL/d (divide by 24 for hourly rate = 64 mL/h) • Daily (BSA-based method): 0.84 m2 × 1600 mL/m2/d = 1344 mL/d (divide by 24 for hourly rate = 56 mL/h) Glucose • Included in IV fluids to prevent protein catabolism, 3–4 mg/kg/min (not calorically adequate; see TPN section in Chapter 4 for parenteral nutrition). D5W = 5% glucose solution = 5 g glucose/dL = 5 g glucose/100 mL = 50 mg/mL water Sodium (Na) • Maintenance: 2–3 mEq/kg/d

• For 1x MIVF, the following saline concentrations approximate maintenance Na: D1/4NS for 0–20 kg and D1/2NS for >20 kg Potassium (K) • Maintenance is age dependant. • Infant; 2–3 mEq/kg/d • Child: 1–2 mEq/kg/d • Adolescent: 1 mEq/kg/d • Adult: 0.5–1.0 mEq/kg/d

• K should always be added if anticipated duration of IVF greater than 24 h • When providing 1x MIVF, adding KCl 20 mEq/L to IVF will approximate daily maintenance for all ages

Modifications to Maintenance Daily Fluid Requirements: • Calculations above are for 1x MIVF, assuming an average, hospitalized patient with caloric demands 20% to 30% above resting energy expenditure. • Any perturbation affecting fluid intake or output or energy demand or /utilization directly affects daily MIVF needs Increased MIVF Needs • ↑ Fluid losses: Renal (renal tubular injury, hyperglycemia, diuretic administration, mannitol administration, diabetes insipidus), GI (vomiting, diarrhea, NG suction, burns (see Critical Care chapter) • ↑ Energy expenditure: Fever (↑ 12% for each °C over 37°C), radiant warmer, hyperthyroidism, hypermetabolic states

153

P E D I AT R I C S

Normal saline (NS) = 0.9% saline = 154 mEq/L; ½ NS = 0.45% saline = 77 mEq/L; ¼ NS = 0.225% saline = 38 mEq/L

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Pediatrics

Decreased MIVF Needs • ↓ Fluid losses: Anuric or oliguric renal failure, SIADH, ventilation with humidified 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 fluids; 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 fluid 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 fluid 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, restless, or irritable

Apathetic, lethargic, unconscious

Thirst

Normal or may refuse liquids

Thirsty, eager to drink

Poor or absent 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 tongue

Moist

Dry

Parched

Skin fold

Instant recoil

Recoil in <2 sec

Recoil in >2 sec

Capillary reﬁll

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 Classification of Dehydration • Clinical parameters determine the degree of dehydration, and biochemical parameters (primarily serum sodium) guide the choice of rehydration fluids.

TYPES OF DEHYDRATION WITH ASSOCIATED FLUID AND SODIUM DEFICITS Biochemical Characteristics

Deficits*

Type

Serum Sodium (mEq/L)

Serum Osmolality Fluid (mOsm/L) (mL/kg)

Isonatremic

130–150

280–300

100–120

8–10

Hypernatremic

>150

>300

100–120

2–4

Hyponatremic

<130

<280

100–120

10–12

Na (mEq/kg)

∗Deﬁcits shown are averages to demonstrate the relationship of ﬂuid (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 efficacious 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 (Deficit Replacement)

Replacement of Ongoing Losses

Nutrition

Minimal dehydration or prevention of dehydration

Not applicable

Normal daily maintenance ﬂuid (eg, 100 mL/ kg for <10 kg) plus 60–120 mL (<10 kg) or 120–240 mL (≥10 kg) ORS for each diarrheal stool or vomiting episode

If possible, continue with breastfeeding or age-appropriate normal diet after initial hydration, including adequate caloric intake (do not restrict diet and do not discontinue breastfeeding)

Mild to moderate dehydration

ORS 50 mL/kg (mild) to100 mL/kg (moderate) over 4 h in small, frequent aliquots (5–10 mL every 5–10 min)

Same as above

Same as above

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).

P E D I AT R I C S

Degree of Dehydration

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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 Solution

kcal/oz

CHO (g/dL)

Na (mEq/dL)

K (mEq/dL)

Ca (mg/dL)

P (mg/dL)

Approximate Osmolality

Oral Rehydration Solutions Enfalyte

—

3

5

2.5

0

0

200

Pedialyte (ﬂavored)

—

2.5

4.5

2

0

0

250

Rehydralyte

—

2.5

7.5

2

0

0

310

WHO oral rehydration solution 1975∗

—

2.0

9.0

2

0

0

311

1.35

7.5

2

0

0

245

WHO oral -— rehydration solution 2006 General Formulas Boost

30

17

2.4

4.3

64

131

610–670

Human breast milk

20

7.1

0.7

1.3

17

14

260

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 (1%, cow)

12.8

5.3

1.8

3.9

38

95

280

Milk (whole, 18 cow)

4.6

1.8

3.7

58

93

280

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 Advance

20

7.3

0.7

1.8

26

28

300

(continued on next page)

Fluids, Electrolytes, and Acid–Base Balance Enteral Solution

kcal/oz

CHO (g/dL)

Na (mEq/dL)

K (mEq/dL)

Ca (mg/dL)

157

P (mg/dL)

Approximate Osmolality

Special Formulas Neocate infant

20

7.9

1.1

2.7

42

63

375

Neocate Jr

30

10.4

1.8

3.5

50

94

610

Nepro

54

17

4.6

2.7

53

70

665

Nutramigen 20 Lipil

7

1.4

1.9

32

43

270

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

10

11.7

0.1

1

—

—

650–750

Colas and 12.1 sodas (CocaCola Classic)

11.3

0.2

0

—

5.1

390–750

Chicken broth

—

25

0.8

—

—

500

5.8

2

0.3

—

—

330

Other fluids Apple juice (Minute Maid)

~1–5

Gatorade: 6.3 Lemon-lime ﬂavor

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 fluid 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 benefit of using colloid over crystalloid fluids for resuscitation (Cochrane Database Syst Rev 2000(2):CD000567). • Second phase of rehydration • Administration of maintenance fluid needs (based on weight), replacement of any additional deficits 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 fluids 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 deficits. • 1/2 NS or NS for maintenance fluids and continued loss replacement. NS is not usually maintenance fluid; however, it may be beneficial in preventing hyponatremia from hypotonic fluids in hospitalized dehydrated pts (due to ↑ ADH in this population).

P E D I AT R I C S

∗Monitor for hypernatremia given the high sodium content; developed for rehydration (not maintenance) in areas without IV capability. — = no information. MMWR 2003;52(RR–16):1–16.

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Pediatrics

COMPOSITION OF COMMONLY USED IV FLUIDS Na (mEq/L)

Cl Lactate∗ (mEq/L) (mmol/L)

K (mEq/L)

Ca (mg/dL)

Total 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 saline (3%)‡

513

513

0

0

0

1026

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)

D5W

0

0

0

0

0

278

340

∗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 fibrillation → 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 fist during antecubital draw) • Hemolysis during blood draw or capillary sample (fingerstick, 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, fluoride, 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 deficiency, 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 fingerstick to prevent pseudohyperkalemia). • Stat ECG. • Clinical history: Oral intake; medications; FH; recent major surgery, burns, or muscle injury. • Blood draw history: Difficulty of blood draw, site (fingerstick, 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

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

P E D I AT R I C S

• 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 • 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 (flush IV first 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

160

Pediatrics

• Renal: Nephrogenic diabetes insipidus • Cardiac: Arrhythmias, ECG changes (U waves, T-wave flattening, ST-segment changes, QT prolongation → VT → VF)

Causes • Pseudohypokalemia (artifactual): Marked leukocytosis (>100,000/μL) and delayed analysis • Transcellular shift (redistribution hypokalemia) • Alkalosis • Insulin administration before sample (small effect), insulinoma • Drugs or toxins (barium, theophylline, toluene, CCB, chloroquine) • β-Agonists • Hypokalemic periodic paralysis • Extrarenal losses (random urine K <20 mEq/L) • Diarrhea • Sweat • Laxative abuse • Villous adenoma of rectosigmoid colon • Fasting or inadequate intake • Renal losses (random urine K >20 mEq/L) With metabolic acidosis • Distal (type I) or proximal (type II) RTA • Ureterosigmoidostomy • DKA • Carbonic anhydrase inhibitors

With normal acid–base status • Diuretic phase of acute tubular necrosis, postobstructive diuresis, osmotic diuresis • Tubular toxins: Amphotericin, cisplatin, aminoglycosides • Hypomagnesemia • Interstitial nephritis With metabolic alkalosis • ↓ UCl(<10–20 mEq/L): Emesis, NG suction, chloride-losing diarrhea, CF, posthypercapneic state, prior loop or thiazide diuretic use • ↑ UCl(>20 mEq/L): nl BP: Bartter’s syndrome, Gitelman’s syndrome, current loop or thiazide diuretic use • ↑ UCl(>20 mEq/L): ↑ BP: adrenal adenoma or hyperplasia, reninsecreting tumor, licorice ingestion, Liddle syndrome, renovascular disease, Cushing syndrome

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 reflects inappropriate renal loss of K; <3 reflects appropriate renal K retention

Treatment • Treatment should be determined by the cause. • Serum K levels >3 mmol/L rarely cause significant 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 reflection 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 reflexes

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161

Hypernatremia Hypovolemic

Hypovolemic hypernatremia ↓UOSM UNa>20

Hypervolemic

Euvolemic hypernatremia

↑UOSM UNa< 20

Renal Losses • ATN, diuretic phase • Osmotic diuresis • Postobstructive diuresis

Euvolemic

↓UOSM

Extrarenal • Diabetes Losses insipidus • Diarrhea • Increased insensible losses • Incorrectly mixed formula (diluted)

↑UOSM

Hypervolemic hypernatremia ↑FENa

• Transient • Exogenous Na hypernatremia† administration

nl FENa

• Mineralocorticoid excess • Hyperaldosteronism

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

Method 1 (Calculation Method) 1. Calculate the free water deficit. 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 deficit 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 fluid 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 fluid type, volume and rate: Concentration of Na (mEq/L) in D5W = [Maintenance Na]/[1/3 or ½ of free water deficit volume + Daily maintenance fluid volume] • Round to standard IV fluid solution if possible (see table above, “Composition of Commonly Used IV Fluids”)

P E D I AT R I C S

• Hypervolemic hypernatremia: Correct underlying cause • Euvolemic hypernatremia: Correct underlying cause • Hypovolemic hypernatremia (dehydration): Results from relative loss of free water compared with Na (rarely Na excess); two methods of correction (described in the following sections).

162

Pediatrics

Example: (22 kg child, serum Na 165 mEq/L, 10% dehydration = 2.2 L total fluid deficit)

Deficit

Fluid

Na

Free water deﬁcit∗

1800 mL (free water)

0 mEq

Remaining deﬁcit†

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 deﬁcit formula above. † based on estimation of percent dehydration (see beginning of chapter)—free water deﬁcit.

Total Fluid: ½ free water deficit (900 mL) + remaining deficit (400 mL) + maintenance fluid (1540 mL) = Total fluid 2840 mL/day = 118 mL/h Total Sodium: Na in isotonic remaining deficit 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 fluid 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 fluid with a specified 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 fluids • Calculate expected change based on different fluid concentrations (see table below) used for rehydration (must take into account total daily fluid 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 reflection 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 reflexes, 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

Transcellular H2O Shift* (effective osmoles) • Hyperglycemia • Mannitol

Hypotonic

Lab Artifact† (ineffective osmoles) • Hypertriglyceridemia (>1000 mg/dL) • Hyperproteinemia (>10g/dL) • Glycine/sorbitol bladder irrigation (GU procedures)

Hypotonic hyponatremia (true hyponatremia)

Hypovolemic

Hypovolemic hyponatremia FENa>1–2% UNa>20

Isotonic

Hypervolemic

Euvolemic

Hypervolemic hyponatremia

Euvolemic hyponatremia

FENa<1% ↓UOSM (<100) ↑UOSM (>100) UNa< 20

FENa>1–2% UNa>20

FENa<1% UNa< 20

Renal Losses • Diuretics • Na-wasting nephropathy • Adrenal insufficiency • Cerebral salt wasting

Extra Renal • 1° polydipsia • SIADH • Renal • CHF Losses • low solute • Hypothyroidism failure • Cirrhosis • GI losses intake • Adrenal • Nephrotic • Increased (malnutrition, insufficiency syndrome insensibles alcoholism, • Third-spacing overdiluted (eg, pancreatitis) formula) • 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 automated analyzers. To calculate the effect on Na in mEq/L: [Triglycerides × 0.002] or [0.25 × (Total protein – 8)].

• Treat the underlying cause. Hypovolemic Hyponatremia Method 1 (Calculation Method) 1. Calculate the fluid deficit: (ie, account for isotonic Na losses): % Dehydration × wt (kg) 2. Calculate extra sodium deficit: Absolute Nadeficit = 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 fluid total volume. Example: 22-kg child; BSA, 0.87 m2; 10% dehydration = 2.2 L total fluid deficit Example: 22 kg child, serum Na 125, 10% dehydration, BSA 0.87 m2 (2.2 L total fluid deficit)

Deficit

Fluid

Na

10% dehydration

2200 mL (isotonic saline)

308 mEq (140 mEq/L × 2.2 L)

1392 mL

55 mEq

Extra Na deﬁcit Maintenance (24 h)

132 mEq

P E D I AT R I C S

Euvolemic Hyponatremia

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 Listed as pH (± 0.04)

PCO2 (± 4)

PaO2†

HCO3 (± 4)

7.4

40

Varies

24

CBG

7.35–7.4

40–45

Varies

24

VBG

7.30–7.35

45–50

Varies

24

ABG

†

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 diﬀerence in ↓ cardiac output states).

General Approach To Acid–Base Disorders (Figure 15-3)

Additional Testing

Differential Diagnosis OSM Gap Present

Anion Gap Present

Metabolic Acidosis

Additional Testing

Osmolal gap:

Ethanol Methanol Ethylene glycol Isopropanol Glycine Glycerol Mannitol CKD

OSM Gap Absent

ACID–BASE DISORDERS: DIFFERENTIAL DIAGNOSIS AND ADDITIONAL TESTING

Methanol Uremia DKA/AKA Paraldehyde INH, Iron Lactic acidosis: Type A (hypoxemic) or type B (nonhypoxemic) Salicylates CO Toluene

OSMmeas–OSMcalc (Normal <10)

Anion Gap∗: Na – (Cl + HCO3)† (Normal, 8–12)

OSM calculation: [2 × Na (mEq/L)] + [BUN (mg/dL)/2.8] + [Glu (mg/dL)/18] +

1

2

(continued on next page)

Fluids, Electrolytes, and Acid–Base Balance

+ UAG – UAG

Anion Gap Absent

Differential Diagnosis Renal Pathology: RTA (I or IV) Paraproteinemias Br- intoxication Mild CKD

Renal Pathology: RTA II Extrarenal Causes: GI losses of bicarbonate 4 (diarrhea; intestinal or pancreatic ﬁstula) Dilutional (rapid infusion IVF without HCO3) Posthypercapnia Acetazolamide TPN Ureterosigmoidostomy

Urine anion gap‡ : (UNa + UK) – UCl [+]→ renal cause [–] → nonrenal

Neuromuscular disorders: Myasthenia gravis, DMD, GBS, NMJ disorders, severe hypophosphatemia CNS depression: Sedatives, trauma, CNS lesions Central sleep apnea, OSAS Obstructive lung disease Secondary Hyperventilation (Hypoxia → Hyperventilation) Pneumonia Asthma exacerbation Pulmonary edema Restrictive lung disease Altitude sickness

5

6

<10

Primary Hyperventilation CNS: Pain, anxiety Drugs: Salicylates, progesterone, β-agonists, methylxanthines Pregnancy Sepsis Hepatic failure

3

Saline (Cl–) Responsive GI losses: vomiting, NG tube 7 Diuretics Posthypercapnia Volume depletion

>10

Metabolic Alkalosis§

Additional Testing

Saline (Cl–) Resistant Hypovolemic: Diuretic usage Euvolemic: 1° or 2° hyperaldosteronism (↑ BP) Moderate to severe ↓ K exogenous alkali Bartter’s syndrome Gitelman’s syndrome

Spot UCl

8

∗Rarely, decreased AG may be noted; diﬀerential diagnosis includes paraproteinemia, Br- intoxication, hypoalbuminemia, hyponatremia, and hypermagnesemia. † Must add 2.5 to ﬁnal 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).

P E D I AT R I C S

Respiratory Alkalosis

Respiratory Acidosis

Metabolic Acidosis

Additional Testing

165

ABG

166

Anion Gap (+)

pCO2 >40 Metabolic alkalosis with respiratory compensation

Acute 10 mmHg ↑pCO2 = 1 mEq/L ↑HCO3 ΔpH = 0.008 × ΔPaCO2

Acute 10 mmHg ↓pCO2 = 2 mEq/L ↓HCO3 ΔpH = 0.008 × ΔPaCO2

1 mEq/L ↑HCO3 = 0.7 mmHg ↑PaCO2 (least predictable among disturbances)

Chronic 10 mmHg ↑pCO2 = 3–4 mEq/L ↑HCO3 ΔpH = 0.003 × ΔPaCO2

Chronic 10 mmHg ↓pCO2 = 5 mEq/L ↓HCO3 ΔpH = 0.017 × ΔPaCO2

5

6

SPOT UCl

(+) (–)

(+) (–) 2

3

<10 7

>10 8

4

General approach to acid–base disorders. (Note: See preceding table for a differential diagnosis associated with each disorder represented by a boxed number.)

Step 4

UAG

1

pCO2 <40 Respiratory alkalosis

(–)

OSM Gap

Figure 15-3

pCO2 >40 Respiratory acidosis

Step 3

1 mEq/L ↓HCO3 = 1.2 mmHg ↓PaCO2 Estimate: PaCO2 = [1.5 x HCO3] + 8 Estimate: PaCO2 = last two digits of pH ΔΔ Gap (see text)

pH > 7.45 alkalosis

Step 2

pCO2 <40 Metabolic acidosis with respiratory compensation

Step 1

pH < 7.35 acidosis

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 60

40

50

30

120 110100 90 80

20 70

60

50

40

56 52

35

Arterial plasma [HCO−3] (mmol/L)

48

Chronic respiratory acidosis

44 40

Metabolic alkalosis

30

25

36 32 Acute respiratory acidosis

28 24

20 Normal

Acute respiratory alkalosis

20

15

16

10

12

Chronic respiratory alkalosis

4

PCO2(mm Hg)

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 pH

PaCO2 (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)

P E D I AT R I C S

Metabolic acidosis

8

168

Pediatrics

pH

PaCO2 (mm Hg)

HCO3

Acid–Base Status

7.35–7.40

>45

↑

Respiratory acidosis with maximal metabolic compensation Normal; no acid–base disturbance

7.35–7.45

35–45

Normal

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 HCO3 = (Normal – Measured HCO3), Δ AG = (Calculated – Normal AG) • ΔΔ Gap = Δ HCO3 – Δ AG (>5 is significant) • Δ HCO3 ≈ Δ AG → simple AG metabolic acidosis • Δ HCO3 > Δ AG → AG metabolic acidosis with superimposed metabolic alkalosis • Δ HCO3 < Δ 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 disor-

ders” algorithm.

Available at www.AccessPediatrics.com • Hypercalcemia • Hypocalcemia

Gastroenterology GASTROESOPHAGEAL REFLUX

169

P E D I AT R I C S

• Definitions: Gastroesophageal reflux (GER) is normal passage of gastric contents into the esophagus; GERD consists of symptoms and complications of GER; rumination is voluntary habitual regurgitation of gastric contents into the mouth for self-stimulation. • Complications of GERD can be divided into three systems: Respiratory (asthma and / chronic cough, apnea and ALTE, recurrent aspiration pneumonia), ENT (hoarseness, laryngitis, sinusitis, dental erosions, recurrent OM), and GI (esophagitis, esophageal ulcers, esophageal strictures, Barrett’s esophagus). • Prevalence of GER: 50% in infants age 0–3 mo; 67% in children age 4 mo; 5% of children age 10–12 mo; 1.4–8.2% in children age 3–17 yr (Arch Pediatr Adolesc Med 1997;151:569). The prevalence of GERD is unknown. • Diagnosis • History and physical exam: A thorough H&P is sufficient for diagnosis. The clinical presentation is based on the age of the child: • Infants and young children present with recurrent vomiting, arching of the back during feeds (Sandifer syndrome), irritability, and poor weight gain (2° to vomiting or dysphagia). Some present with wheezing or chronic cough, recurrent pneumonia, upper airway symptoms (eg, recurrent stridor), apnea, or ALTE. • Older children and adolescents present with heartburn or retrosternal chest pain and regurgitation. Some present with dysphagia, hoarseness of the voice, weight loss, anemia, wheezing or chronic cough, recurrent pneumonia, food impaction, and Barrett’s esophagus (rare). • History: Ask for details of meals (type, volume and frequency), recent change in appetite, reflux symptoms after feeding (regurgitation, pain, irritable, dyspepsia), presence of blood or bile, force of reflux, blood in the stool, trends in weight gain. Social history: Tobacco or alcohol use, psychological factors (eg, stressors, anxiety, depression). PMH: of eczema, neurologic issues (↑ or ↓ tone, hydrocephalus, presence of shunt), prematurity, surgery, ENT disease. Family history: Helicobacter pylori infection, reflux, atopic disease. • Signs suggesting non-GER cause of vomiting: Bilious or forceful vomiting, GI bleeding, diarrhea, constipation, abdominal pain or distension, fever, lethargy, HSM, seizures, microor macrocephaly, FTT, genetic d/o (trisomy 21), other chronic diseases (eg, HIV). • Laboratory studies/evaluation: None are required for the diagnosis of GERD. Consider H. pylori stool antigen testing for children and adolescents if the patient c/o abdominal pain ± dyspepsia or vomiting. In unclear cases, consider UGI to r/o anatomical abnormalities, esophageal pH monitoring or multichannel intraluminal impedance may be used to correlate reflux with symptoms; esophagoscopy may be used for complications (strictures, esophagitis) and to rule out anatomic abnormalities. • Treatment • Physiological GER: Reassurance • GERD in infants: • Step 1: Thicken formula or breast milk with rice cereal (add 1 Tbsp/oz of formula), reflux precautions (ie, sleeping supine at a 30- to 45-degree angle, small frequent feeds, frequent burping, maintain upright position for 30 min after feeding). • Step 2: If step 1 interventions fail, add pharmacologic therapy: H2R antagonist (eg, ranitidine) or PPI (eg, lansoprazole; not currently FDA approved). PPIs are more effective at acid suppression and are most effective if given 30 min before morning feeds. • Surface agents (eg, sucralfate, sodium alginate) help protect ulcerated gastric mucosa. Consider use in infants with esophagitis or ulcers. • Consider changing to casein hydrolysate formula (ie, Nutramigen, Alimentum, Pregestemil) if milk-protein allergy is strongly suspected as the cause of GER.

G E N E R A L C L I N I C A L I N F O R M AT I O N

C H A P T E R 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 five 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 Scenario

ALT

Acute HAV∗

↑

HBc HBc HCV HCV HBsAg IgM IgG HBeAg HBeAb HBsAb HBVDNA Ab RNA

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 vaccine

Normal

–

–

–

–

–

+

–

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 Adapted from: Tarascon Internal Medicine and Critical Care Pocketbook, 4th ed. 2009:68.

, HAV IgG ¢.

Gastroenterology

171

Noninfectious Hepatitis NONINFECTIOUS HEPATITIS: CAUSES, DIAGNOSIS, AND TREATMENT Cause

Diagnosis

Treatment

Comments

Hereditary hemochromatosis (HH)

↑ Transferrin saturation, ferritin, genetic testing, liver biopsy

Phlebotomy to keep ferritin <50 ng/mL; chelation (deferoxamine)

Autosomal recessive, ↑ iron absorption from intestine

Iron overload ↑ Iron, TIBC, ferritin (multiple transfusions)

Phlebotomy to keep ferritin <50 ng/mL; chelation (deferoxamine)

Sickle cell disease, β-thalassemia major, aplastic anemia

Steatohepatitis

Liver US, liver biopsy

No current medical treatments; however, modify risk factors (obesity, hyperlipidemia, DM control)

↑ Triglyceride accumulation in liver

Autoimmune hepatitis (AIH)

Serum ANA, antismooth muscle Ab (ASMA), anti-LKM1 antibody, total IgG

Steroids, azathioprine or 6-MP, liver transplant

Type I AIH: Associated with ANA, ASMA Type II AIH: Associated with anti-LKM1

Wilson’s disease

AST>ALT; ↓ Ceruloplasmin (<20 mg/dL); ↑ copper in urine (>40 mcg/24 h) and on liver biopsy (>250 mcg/g dry weight); genetic testing; Kayser-Fleischer rings; neurologic d/o (35%)

Chelation: Penicillamine (give pyridoxine); trientine is second line; give 1 h before or 2 h after meals; add PO zinc in maintenance therapy after chelation; liver transplantation for those with fulminant hepatic failure

1 in 30,000 births, AR defect in hepatocellular copper transport

`-1-antitrypsin ↓ serum AAT (<80 mg/dL; Liver transplantation (AAT) deficiency range, 100–300), PI typing ↑ CK, LDH, aldolase, and aminotransferases

Based on cause

Inborn errors of 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 • Definition: 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 specific causes; identification 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).

P E D I AT R I C S

Muscle disorders

In liver, retention of mutant AAT protein leads to demise of hepatocytes

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Clinical Presentation Fever, malaise, nausea or vomiting, diarrhea, jaundice, HSM, abdominal distension (± ascites), pain, asterixis, Dupuytren’s contractures, fetor hepaticus, coagulopathy, ↑ ammonia, encephalopathy (combative, lethargic)

Laboratory Studies ↑ AST, ALT usually >1000, ↑ Direct bilirubin >15–20 mg/dL, ↑ PT/PTT/INR, ↓ Factors V/VII

Fulminant Liver Failure INR >1.5 + encephalopathy or INR >2 ± encephalopathy

Start Investigation for Liver Failure Labs: CBC, ABG, Chem 10, ammonia, fibrinogen, ESR, lipid profile, UA with cx, urine Iytes, osmolality Metabolic screen: SAA; lactate; pyruvate, acylcarnitine profile; AFP; UA and urine organic acids reducing substances, ketones Autoimmune hepatitis screen: Immunoglobulins, ANA, anti-SM antibody, anti-LKM1 antibody Other screen: AAT, copper level, ceruloplasmin, ferritin, iron panel Viral tests: Hepatitis panel, EBV PCR, CMV antigenemia, adenovirus PCR and rapid screen, enterovirus PCR, parvovirus B19 titers Drug screen: Acetaminophen, aminosalicylic acid, urine/blood drug screen Radiology: Abdominal US with Doppler; head CT Other studies: EEG Biopsy: Transjugular liver biopsy + venogram (send tissue for virology, electron microscopy, 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 flow, ↑ 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.

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• 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 consciousness

Normal

Confused, irritable, loss of spatial orientation

Drowsy, responds to simple commands

Stuporous but arousable, marked confusion

Comatose with or without response to pain

Reflexes

Normal

Normal

Hyperreﬂexic

Hyperreﬂexic + Babinski sign

Areﬂexic

EEG

Normal

Minimal changes

Slow rhythm with triphasic waves

Grossly abnormal

Grossly abnormal with delta waves

Altered sleep habits

Dysarthria, incontinence, asterixis

Marked dysarthria, rigidity

Decerebrate or decorticate posturing

Other

DIAGNOSTIC APPROACH TO RENAL INSUFFICIENCY IN END-STAGE LIVER DISEASE

Clinical

Prerenal

Hepatorenal

Signs of hypovolemia; resolves with volume expansion

No hypovolemia and no response to volume expansion; hypothermia; usually accompanied by ascites and hepatic encephalopathy

ATN

(continued on next page)

P E D I AT R I C S

• 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 inflow, and blocks vasodilatation. See GI bleed section for treatment of acute variceal bleeding. • Hepatorenal Syndrome (Lancet 2003;362(9398):1819) • Definition: 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)

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Pediatrics

Labs oratory • Na (urine, mEq/L) • Fractional excretion of Na • UCr/PCr • UOsmol/POsmol • Urine sediment

Prerenal

Hepatorenal

ATN

<10 <1%

<10 <1%

>30 >3%

>30 >1.1 Normal ↑ in BUN > Cr

>30 >1.1 Normal Proportional ↑ in BUN and Cr

<20 1 Protein, casts, cellular debris

• Ascites • Definition: Pathologic accumulation of fluid 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 schistosomiasis 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 fluid 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 fluid 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 fluid) • Treatment: Treat underlying cause for ascites. Monitor serum and urine lytes, fluid 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 fluid 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 • Definition: Acute infection of the peritoneal cavity. • Presentation: Subtle signs and symptoms: fever, anorexia, vomiting, abdominal tenderness, rigidity, ↓ bowel sounds, fluid wave. • Diagnostic studies: Paracentesis with fluid analysis for cell count, LDH, TP, glucose, Gram stain, and culture. • Management: See table below. Antibiotics, fluid 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.

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DIFFERENTIATION AND TREATMENT OF BACTERIAL PERITONITIS Type

Risk Factors

Cell Count

Culture

Treatment

Primary

Ascites: Renal or liver disease (20% of patients with cirrhosis), CHF

PMN count ≥250 cells/mm3 TP <1 g/dL

Usually only one organism (Escherichia coli, streptococci, staphylococci, enterococci)

PMN count ≥250 cells/ mm3 and 2 of the following: TP >1 g/dL or Glucose <50 mg/dL or LDH > upper limit of normal for serum

Polymicrobial

Immediately start empiric 3rd generation cephalosporin (eg, cefotaxime). Modify antibiotic choice based on culture.

Secondary Intraabdominal infection

HYPERBILIRUBINEMIA Direct (Conjugated)

Indirect (Unconjugated) • Definition: 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 flow 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.

P E D I AT R I C S

• Definition: 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 (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 definitive diagnosis. • Management/Treatment: Treat based on etiology in consultation with GI service.

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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 • Definition • Acute: Inflammatory process resulting from ectopic activation of pancreatic enzymes characterized by abdominal pain, ↑ amylase and lipase, and supportive radiologic findings (see table below). • Chronic: Permanent structural changes of the pancreas (eg, calcification, fibrosis) or its duct (eg, stricture, dilatation); may lead to exocrine or endocrine insufficiency. • 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 identifiable etiology of acute pancreatitis. CF and other genetic mutations are the most commonly identified etiologies of chronic pancreatitis.

COMPARISON OF ACUTE AND CHRONIC PANCREATITIS IN CHILDREN Acute

Chronic

Etiology

• Idiopathic (23%) • Traumatic (22%) seat belt, bicycle handlebars, NAT • Anatomic or obstructive (15%) pancreas divisum (controversial), anomalous pancreaticobiliary union, choledochal cyst, cholelithiasis, sphincter of Oddi dysfunction, masses • Systemic disease (14%) HUS, Kawasaki, HSP, Crohn disease, SLE • Toxins and drugs (12%) azathioprine, 6-MP, L-asparaginase, valproic acid, corticosteroids, some antibiotics and diuretics, scorpion venom, organophosphate insecticides, cocaine, ethanol • Infection (10%): Usually viral; rarely bacterial, parasitic (eg, Ascaris) • Metabolic (2%) hypertriglyceridemia, hypercalcemia, refeeding syndrome, DM • Familial (2%) (J Clin Gastroenterol 2003;37(2):169) • Miscellaneous: Post-ERCP, malignancy

• Idiopathic • Genetic mutations: Serine protease 1 gene (PRSS1) Serine protease inhibitor Kazal type 1 (SPINK1) CFTR (± clinical manifestations of CF) • Anatomic or obstructive: See list under “acute” • Autoimmune: Secondary forms (eg, SLE) more common in children than primary autoimmune pancreatitis • Tropical calciﬁc pancreatitis

Pathophysiology

Premature activation of pancreatic enzymes in the acinar cell leads to parenchymal inﬂammation, ischemia, and necrosis

Repeated episodes of acute pancreatitis Protein plugs or calculi causing obstruction and secondary calciﬁcation Autoimmune vasculitis (continued on next page)

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177

Chronic

Abdominal pain: Epigastric classically, may radiate to back Nausea and vomiting ± intestinal ileus Anorexia Jaundice (with gallstones or biliary obstruction) Fever, RUQ pain, and jaundice (Charcot’s triad) indicative of cholangitis

Flares of chronic pancreatitis mimic acute pancreatitis Pancreatic exocrine or endocrine insuﬃciency (late signs) Steatorrhea Excessive appetite Growth failure

Physical exam

Tachycardia, pain, “third spacing” Abdomen: Inspect for signs of trauma, tenderness ± distension, ascites rarely, peritoneal signs, pseudocysts may be palpable, diminished bowel sounds Hemorrhagic necrosis (bluish discoloration): Flanks—Grey Turner’s sign; umbilicus—Cullen’s sign

May be normal Chronic abdominal tenderness may dominate the clinical picture late in the course of disease

Diagnosis

Physical exam ﬁndings of epigastric pain along with history of vomiting (afebrile) Serum amylase and lipase >3 times normal (no correlation to disease severity) Secondary hyperglycemia, hypocalcemia, hypoalbuminemia, hypertriglyceridemia, and acidosis may be observed LFTs and bilirubin elevated in gallstone pancreatitis Triglyceride level >1000 mg/dL after the acute episode is suggestive of hypertriglyceridemic pancreatitis Abdominal US, CT if necessary to assess for obstructive causes, pseudocysts, abscesses MRCP (after the acute episode): When an anatomical lesion is suspected

May present as acute pancreatitis; however, amylase and lipase may not be increased with progressive parenchymal destruction Spot fecal fat (increased) Fecal elastase-1 (low) Low vitamins A, D, E, K (rarely) KUB: Helpful when calciﬁc pancreatitis is suspected Abdominal US, CT, MRCP by deﬁnition should reﬂect parenchymal or ductal changes Endoscopic US: Helpful in select cases when noninvasive imaging is equivocal ERCP oﬀers diagnostic and therapeutic abilities (stent placement, sphincterotomy, 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)

P E D I AT R I C S

Acute Clinical manifestations

178

Pediatrics Acute

Chronic

Management

• NPO, NG decompression if vomiting; gastric acid suppression until feeding • Fluid resuscitation and electrolyte correction • Nutrition: Jejunal feeds are superior to TPN (↓ complications and cost) when severity of illness is expected to preclude PO feeding for several days (Gastroenterol Clin North Am 2007; 36(1):65). Initiate low fat diet when abdominal pain improves and vomiting resolves • Analgesia: NSAIDs (eg, ketorolac), narcotics; insuﬃcient evidence exists to routinely recommend meperidine over morphine (Am J Gastroenterol. 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

• Pain: • Small, low-fat meals; vitamin (especially fat-soluble) supplementation • Pancreatic enzyme supplements (enteric coated): Restore exocrine enzyme deﬁciencies and may reduce pain by minimizing CCKmediated secretory drive • Chronic opioids for persistent, signiﬁcant pain; long-acting agents are more eﬀective • ERCP with sphincterotomy ± stent placement • Surgery

Complications

Shock and multisystem organ failure (rare in children) Pancreatic necrosis, abscess, or pseudocyst formation

Bile duct and duodenal obstruction (5%-10%): Decompression may reverse secondary biliary ﬁbrosis Pseudocysts (~10%): May drain for rapid enlargement, compression of surrounding structures, pain, or infection Splenic vein thrombosis Sequelae of chronic nutrient malabsorption

CONSTIPATION • Definition: Delayed or difficult 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.

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MALABSORPTIVE SYNDROMES • Definition: 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, lytes, α1-antitrypsin. • Blood: CBC, ESR, LFTs, lytes, PT/PTT/INR, peripheral smear, immunoglobulins (more specific tests as indicated), intestinal biopsy.

INFLAMMATORY BOWEL DISEASE • Definitions • Ulcerative colitis: Chronic, idiopathic superficial inflammation 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 inflammation 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.

P E D I AT R I C S

• 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 first bowel movement; urinary incontinence or increased frequency (including enuresis); encopresis; retentive posturing; diet history (especially milk intake, fluid 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, fissures, 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 effluent 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 • Other: Increase dietary fiber and fluids, educate parents, and provide frequent follow-up. Maintain on therapy for ≥2 months after normal stooling has been established.

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Pediatrics

• Indeterminate colitis: In about 10% of patients with chronic colitis, it is not possible to make a definitive diagnosis by clinical presentation, radiologic, endoscopic, or histopathologic findings. • 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 flora. • 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 first-degree relative with the condition. The estimated risk in these individuals is 30–100 times greater than in the general population. • Pathogenesis • Chronic inflammation, tissue breakdown, and subsequent fibrosis. • 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 Recent studies show unimodal distribution (peak in the 20s–30s with diminishing incidence later)

16–20 yr

Incidence

4.5/100,000

2.1/100,000

Intestinal symptoms

Abdominal pain, diarrhea with mucus (bloody, if colonic involvement), n/v, perianal disease, ﬁstulas, abscess

Abdominal pain, grossly bloody diarrhea, tenesmus, urgency, painful defecation

Extraintestinal symptoms

Fever (50%), arthralgias, weight loss (90%), stomatitis, gallstones, kidney stones, uveitis (15%), delayed growth or sexual development (30%), erythema nodosum (15%)

Fever (50%), arthralgias, weight loss (70%), sclerosing cholangitis, pyoderma gangrenosum (5%)

Adapted from Pediatr Clin North Am 1988;35(1):189.

• Differential diagnosis: See table below. • Infectious colitis (especially pseudomembranous colitis from Clostridium difficile, other bacterial enteric pathogens, viral colitis in immunocompromised patients) • Allergic colitis • Milk protein intolerance of infancy • Hirschsprung’s colitis (before or within months of surgical correction). • Prestenotic colitis • Diversion colitis • Ischemic colitis • Radiation proctitis or colitis • Eosinophilic gastroenteritis • Congenital or acquired immunodeﬁciency syndromes • GVHD in transplant patients • Irritable bowel syndrome

• HUS (initially before the renal failure) • Appendicitis • Intestinal lymphoma • Rheumatoid arthritis • Behçet ‘s syndrome (rare in the United States) • Systemic vasculitis ie, SLE or dermatomyositis • Peptic ulcer disease • Typhlitis • Neonatal necrotizing enterocolitis • Laxative abuse • Malabsorptive syndromes • Henoch-Schonlein purpura

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• 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. difficile 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 Fecal α1-antitrypsin Lactose breath test Plain ﬁlms, 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 Endoscopic

Longitudinal or transverse deep ulcerations; skip lesions; strictures; ﬁstulae; cobblestone appearance of mucosa; thumbprinting

Asymmetric or discontinuous involvement; deep, longitudinal fissures; cobblestone appearance; mucosal edema; usually no mucosal friability; strictures (not always present)

Ulcerative colitis

Fine, superﬁcial ulcerations; continuous involvement from the rectum; shortening of the bowel; symmetric bowel contour; decreased mucosal pattern; pseudopolyps

Uniform involvement beginning at the anorectal junction; very friable mucosa; diﬀuse, uniform erythema; rectal involvement if active disease; pseudopolyps

• Treatment • Long-term treatment is required. Goals of therapy are induction and maintenance of remission. Medical treatment is not curative.

P E D I AT R I C S

Radiographic Crohn’s disease

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Pediatrics

PHARMACOLOGIC THERAPY OF INFLAMMATORY BOWEL DISEASE Crohn Disease

Ulcerative Colitis

Acute exacerbation Methylprednisolone 1–2 mg/kg/day IV divided BID–QID for 7–10 days. Change to PO (same dose) divided BID; then 1 mg/kg PO once daily; then 1 mg/kg PO every other day, continuing for total course of 4–6 wk.

Severe to moderate colitis Methylprednisolone 1–2 mg/kg/day IV divided BID–QID for 7–10 days. Change to PO (same dose) divided BID; then 1 mg/kg/day PO once daily; then 1 mg/kg PO every other day, continuing for a total course of 4–6 wk.

Remission Olsalazine 30–40mg/kg/day PO divided BID Folate 1 mg/day Mesalamine 50 mg/kg/day divided BID or TID

Mild or Localized Distal Colitis Olsalazine 30–40 mg/kg/day oral divided BID Folate 1 mg/day Mesalamine 50 mg/kg/day divided BID or TID Mesalamine enemas or rectal suppositories Hydrocortisone enemas

Perianal Disease or Fistula Metronidazole 15 mg/kg/day divided Q8h Refractory Disease Azathioprine 1–2 mg/kg/day divided BID or 6-Mercaptopurine 1.5 mg/kg/day divided BID or Methotrexate 10 mg/m2/week (PO or subQ) or Iniﬂiximab 5–10 mg/kg wk 0, 2, 6, and subsequently as needed

Refractory disease Azathioprine 2 mg/kg/day or 6-Mercaptopurine 1.5 mg/kg/d divided BID or Cyclosporine IV 1–2 mg/kg/d; then PO 4–8 mg/ kg/d or Tacrolimus or Iniﬂiximab 5–10 mg/kg wk 0, 2, 6, and subsequently as needed

• Correction of nutritional deficiencies with TPN, vitamins (especially vitamin D), or elemental formulas. • Surgery for disease refractory to medical therapy and complications such as perforation, fistulas, strictures, abscesses, fulminant colitis, or toxic megacolon. • Prognosis: Beyond the first 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 • Definition: No consensus definition. Working definition: 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 Inadequate Intake

Abnormal Utilization

Increased Metabolic Demand

• Food availability • Feeding technique • Dysphagia • Feeding aversion • Pyloric stenosis

• Short bowel syndrome • Celiac disease • Inﬂammatory bowel disease • NEC • Malabsorptive syndrome

• Congenital heart disease, CHF • Chronic inﬂammatory states • Chronic lung disease • Hyperthyroidism • CF (continued on next page)

Gastroenterology

Inadequate Intake

Abnormal Utilization

Increased Metabolic Demand

• Malrotation • GERD • Child abuse or neglect • Food inappropriate for age • Incorrect mixing of formula

• CF • Inborn errors of metabolism • Chromosomal abnormalities • TORCH infections • Lead toxicity

• HIV, toxoplasmosis • Diabetes mellitus • RTA • Malignancy • TB

183

DETERMINING SEVERITY OF MALNUTRITION IN CHILDREN WITH FAILURE TO THRIVE Method

Normal

Mild

Moderate

Severe

Weight for height∗

≥90% of median

80–89% of median

70–79% of median

<70% of median

Weight for age∗

≥90% of median

75–89% of median

60–74% of median

<60% of median

NOTE: values in table represent the percentage of the median age- and sex-speciﬁc 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

P E D I AT R I C S

• Diagnosis • History: Detailed pre- and postnatal history (infection risk), diet history (formula mixing, intake, juice and cow’s milk intake), reflux quantification, sleep–wake cycle, vomiting, diarrhea, bleeding, lead poisoning screen. Obtain weight, height, head circumference trend (from parent or child’s doctor). PMH significant for frequent infections (AOM, pneumonia). FHx significant 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 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 profile, chromosomal microarray, stool studies for malabsorption (if diarrhea present).

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, Brushfield spots, upslanting palpebral fissures, 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 fifth finger, single transverse palmar crease, sandal gap toe, hallucal arches • GI: Duodenal atresia, annular pancreas, imperforate anus, tracheoesophageal fistulas, 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 (continued on next page)

184

Genetics Age

Concern

Recommendation

1 mo–1 yr

Otitis media, hearing loss

ENT referral if abnormal ABER

1–5 yr

5–13 yr

Strabismus, cataracts, nystagmus

Ophthalmology referral by age 6 mo

Hypothyroidism

TSH at 6- and 12-mo visits

Growth

Plot on Down syndrome curves

Otitis media, hearing loss

Attempt tympanic membrane visualization, audiogram every 6 mo

Vision loss

Vision check annual, Ophthalmology every 2 yr

Atlantoaxial instability and subluxation

Spinal radiography at 3–5 yr

Hypothyroidism

Annual TSH

Sleep apnea

Sleep study, ENT referral if necessary

Obesity and osteoporosis prevention

Dietary counseling

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

Hearing loss

Annual audiology exam

Vision loss

Annual ophthalmology exam

Hypothyroidism

TSH annually

Leukemia

CBC annually

Reproduction

Review contraception, menstruation, recurrence risk

Pediatrics 2001;107(2):442.

P E D I AT R I C S

13–21 yr

185

CHRONOLOGICAL ORGAN SYSTEM EMBRYONIC DEVELOPMENT FROM WEEKS 3 TO 7 Cardiovascular Respiratory Musculoskeletal Gastrointestinal Urogenital

3

Neural plate appears and progresses to neural folds

Cardiogenic ﬁeld is established as myoblasts migrate from the cranial end of the embryo

4

Neural tube closure proceeds cranial to caudal

Primitive heart tube undergoing looping

Lung bud grows out from foregut (esophagus)

Sclerotome cells begin surrounding the spinal cord, transverse septum originates

5

Primary brain Septum primum vesicles form forming forebrain, midbrain, hindbrain

Lung bud branching into bronchi

6

Pons, cerebral development ongoing, neural hypophysis

Growth of muscular ventricular septum, outﬂow tract septation

Branches to main lobes of lung are formed in respiratory tree

7

Optic nerve

Septum secundum forming

Tracheal carti- Finger rays form, Gut rotation lage forms transverse septum around the superior completed (compo- mesenteric artery nent of diaphragm)

186

Week CNS

Head and Neck Ears

Eyes

Cloaca forms, liver primordium appears

Cloaca forms

Foregut formation

Pronephros, mesonephric duct

Mandible formation, tongue formation

Vertebral ossiﬁcaEvagination of tion centers, limb thyroid, liver, and bud formation pancreas (lower limb is always 1–2 d behind the upper)

Ureteric bud sprouts from mesonephric duct and migrates toward metanephric mesenchyme

Nasal pits give rise to nasal prominences

Otic Lens begins to invagina- invaginate into tion lead- optic cup ing to otic vesicle

Limb innervations, formation of hand and foot plates

Ureteric bud branching into metanephric mesenchyme creating renal pelvis and collecting system

Nasolacrimal swellings continue to grow

Cochlear duct, semicircular canals

Physiologic umbilical herniation, gallbladder formation, spleen formation

Eye grooves appear begin to induce surrounding ectoderm

Poles of Primary palate kidney form, and choana form nephrogenesis begins

Optic evagination forms

Lens is fully invaginated, pigmented cells appear in retina

Pigmented cells migrating into retina

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: Confirmatory 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

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

P E D I AT R I C S

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. • Vertebral defects • Anal atresia • Cardiac defects • TracheoEsophageal fistulas • Renal anomalies • Limb defects, particularly of the radius

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 disorders

Carbohydrate metabolism disorders

Inherited neurotransmitter disorders

Organic acidurias and acidemias

Peroxisomal metabolism disorders

Creatine deﬁciency disorders

Lysosomal metabolism disorders

Defects in heme pigment synthesis

Congenital disorders of protein glycosylation

Urea cycle defects

Disorders of metal metabolism

Signs and Symptoms Suggestive of Metabolic Diseases Neonatal Period and Infancy • Often nonspecific and after a symptom-free interval: Hypotonia, poor sucking reflex, lethargy, seizures, vomiting, diarrhea, or respiratory distress • Neonatal seizures: Pyridoxine responsive seizures, pyridoxal phosphate responsive seizures, biotinidase or holocarboxylase synthetase deficiency, glycine encephalopathy, molybdenum cofactor or isolated sulfite oxidase deficiency, 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 With hepatomegaly With lachic acidosis Without hepatomegaly

With ketosis Hypoglycemia Without lactic acidosis

• Glycogen storage diseases • Gluconeogenesis defects • Organic acidurias • Defects of ketolysis • Respiratory chain defects • Disorders of long-chain fatty acid oxidation • Ketotic hypoglycemia • Organic acidurias • Glycogen storage diseases type 0 and III • Adrenal insufficiency

Without ketosis

• Hyperinsulinism • Hypopituitarism • Disorders of fatty acid oxidation • Disorders of ketogenesis

With liver failure

• Fructose intolerance • 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 deficiency, 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)

Normal NH3

• Diabetes • Ketolysis defects

Lactic acidosis

• Respiratory chain defects • Organic acidurias

Hyperglycemia

Ketones ⊕

Normoglycemia Normal lactate

• Late - onset MSUD • Ketolytic defects

Lactic acidosis

• Glycogen storage disease type 0 • Defects of gluconeogenesis • Respiratory chain defects

Normal lactate

• MSUD (late onset) • Organic acidemias • Adrenal insufficiency

Normoglycemia

• Pyruvate dehydrogenase deficiency

Hypoglycemia

• Fatty acid oxidation defects • Glycogen storage disease type I

Hypoglycemia Metabolic acidosis

Lactic acidosis Ketones – Normal lactate Normoglycemia Figure 17-2 Differential diagnosis of neonatal metabolic acidosis.

• Renal tubular acidosis

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 ﬁsh

Trimethylamine, dimethylamine

Trimethylaminuria Dimethylaminuria (continued on next page)

P E D I AT R I C S

• Respiratory alkalosis: Urea cycle defects (although commonly not a neonatal presentation) • Sepsis: Propionic academia, galactosemia • Neutropenia: Organic acidemias, nonketotic hyperglycinemia, carbamoyl phosphate synthetase deficiency, 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 deficiency • Abnormal hair: Arginosuccinic acidemia, lysinuric protein intolerance, Menkes syndrome • Abnormal body odor: See table below

190

Pediatrics

Odor

Substance

Etiology

Sulphur

Hydrogen sulﬁde Methionine

Cystinuria 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

Brown or black

Red

Orange

Green or blue

Substance

Cause

Confirmation

Homogentisic acid

Alkaptonuria∗

Urine organic acids (elevated homogentisic acid)

Methemoglobin

Myoglobinuria

Urine dipstick (+ for blood), CK (elevated)

Hemoglobin

Hemoglobinuria

Urine dipstick (+ for blood), blood work c/w hemolysis

Erythrocytes

Hematuria

Urine microscopy

Porphyrins

Congenital erythropoietic porphyria (Günther disease) and hepatic porphyrias

Porphyrins in urine

Rifampin

Antibiotic treatment with rifampin

History

Urate†

Hyperuricosuria

Urine microscopy (urate crystals), uric acid in blood and urine

Indican†

Hartnup disorder (tryptophan malabsorption)

Urine amino acids (increase of neutral amino acids)

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

Episodic course

x

x

x

x

x

x

x

x

x

Mental retardation

x

x

x

x

(x)

x

(x)

Seizures

x

x

x

x

(x)

x

x

Failure to thrive

x

x

x

x

Macrocephaly Microcephaly

x x

x

x

(x)

x

x

x

x

(x)

x

x

x

x

x

x

x

P E D I AT R I C S

x x

Hepatomegaly

x

Liver disease

x

Cardiomyopathy

(x)

Hypoglycemia

x

(x)

Hyperammonemia

(x)

x

x

(x)

x

(x)

x

x

x

x

x

x

x

x

x

Metabolic acidosis

x

x

x

x

Lactic acidosis

x

x

x

x

Respiratory alkalosis

x

x

Ophthalmologic ﬁnding Abnormal odor

Congenital Disorders of Glycosylation

x

x

Disorders of Peroxisomal Metabolism

x

Disorders of Lysosomal Metabolism

x

Disorders of Fatty Acid Oxidation and Ketogenesis

x

Mitochondrial Disorders

x

x

Glycogen Storage Diseases

x

Chronic course

Urea Cycle Defects

Organic Acidurias

Acute onset

“Cerebral” Organic Acidurias

Clinical Finding

Aminoacidopathies

BROAD OVERVIEW OF INBORN ERRORS OF METABOLISM: CLINICAL AND LABORATORY FINDINGS*

x

∗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 ﬁnding.

x (x)

x

x

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 opacifications: 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 deficiency • 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 deficiency, 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-flowing 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 profile, bilirubin (rule out hepatopathy).

Genetics

193

Suspected IEM: Speciﬁc 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 Increased Amino Acids

Decreased Amino Acids

Underlying Factor

Tyr, Phe, Met, Orn, Lys, Pro, Ala, Gln

Leu, Ile, Val (branched chain AAs)

Hepatic disease

Asp, Glu, Gly, Orn

Arg, Gln

Hemolysis

Met, Phe, Cys (coeluting peaks on PAA analysis)

None

Antibiotics (amoxicillin, 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

KEY CHARACTERISTICS OF UREA CYCLE DEFECTS Disorder

Enzyme Defect

Inheritance

PAA

Urine

CPS deﬁciency

carbamoylphosphate synthetase

AR

↑ Glutamine, alanine ↓ Citrulline, arginine

Normal or ↓ orotic acid

OTC deﬁciency

Ornithine transcarbamylase

X-linked semidominant (females ± symptomatic)

↑ Glutamine, alanine ↓ Citrulline, arginine

↑↑ Orotic acid

Citrullinemia

Argininosuccinate synthetase (ASS)

AR

↑↑ Citrulline ↓ Arginine

↑ Orotic acid

(continued on next page)

P E D I AT R I C S

• 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.) • Acylcarnitine analysis: Tandem mass spectroscopy analysis of total and free carnitine, acylcarnitine profile, and free fatty acids. Indications: Diagnosis of fatty acid oxidation defects and some organic acidemias.

194

Pediatrics

Disorder

Enzyme Defect

Inheritance

PAA

Urine

Argininosuccinic aciduria

Argininosuccinate lyase (ASL)

AR

↑↑ Argininosuccinate ↑ Citrulline ↓ Arginine

↑↑ Argininosuccinic acid ↑ Orotic acid

Argininemia

Arginase

AR

↑↑ arginine

↑↑ Orotic acid

Urine excretion Benzoate∗ Hippurate

Glycine Glutamate

N-Acetylglutamate NH3 Glutamate NH3

α-ketoglutarate

Glutamine ∗Phenylacetate

– HCO3

OROTIC ACID

Aspartate

Phenylacetylglutamine

Urine excretion

NAGS Carbamoyl CPS 1 phosphate Citrulline Ornithine OTC ⊕

Ornithine

Urea

UREA CYCLE

ASS

Argininosuccinate

Arginase Arginine

ASL

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 first 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 deficiency and up to 200 mg/kg/d in OTC and CPS deficiencies. • 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 Citrulline level Normal

Full-term neonate

Abnormal (low or high)

Acidosis

Blood gas analysis

No Acidosis

Acidosis

Organic acidemias

THAN

Blood gas analysis

No acidosis

Urea cycle defects Plasma A.A. analysis

Citrulline↑ (100–300 μM)

Urine orotic acid

Argininosuccinic acidemia

Normal or low

Elevated

CPS deficiency

OTC deficiency

Citrulline↑↑ (>1000 μM) Citrullinemia

Figure 17-4 Differential diagnosis of neonatal hyperammonemia. THAN, transient hyperammonemia of the newborn. (Modified 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 deficiencies; 100–200 mg/kg/d in OTC and CPS deficiencies. • Citrulline: 50–150 mg/kg/d OTC and CPS deficiencies. • Sufficient fluid 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

P E D I AT R I C S

Citrulline low

CHAPTER 18

Hematology ANEMIA (RED BLOOD CELL DISORDERS) • Definition: ↓ in Hb, HCT, or RBC count <2 SD below age-specific norms • Mechanism: Hemorrhage, hemolysis, ineffective hematopoiesis

AGE-SPECIFIC RBC NORMAL VALUES Hemoglobin (g/dL) Mean

Lower Limit

0.5–4

12.5

5–10

13.0

11–14乆 11–14么

Packed Cell Volume (%) Mean

Lower Limit

11.0

36

11.5

38

13.5

12.0

14.0

12.0

15–19乆

13.5

15–19么

MCV (fl)

MCH (pg)

Mean

Lower Limit Mean

Lower Limit

32

80

72

28

24

33

83

75

29

25

39

34

85

77

29

26

41

35

85

77

29

26

12.0

40

34

88

79

30

27

15.0

13.0

43

37

88

79

30

27

20–44乆

13.5

12.0

40

35

90

80

31

27

20–44么

15.5

13.5

45

39

90

80

31

27

Age (Y)

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 deﬁciency or inﬂammatory 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 diﬀerence 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

Classification Anemia (MCV< normal range for age)

High (macrocytic)

Normal (normocytic)

Low (microcytic)

Iron deficiency Thalassemia minor Sideroblastic anemia Lead toxicity Anemia of chronic disease Chronic renal insufficiency Neoplastic Severe malnutrition Inborn errors of metabolism Hemoglobin C variant Hemoglobin E variant

See Figure 18-2

Vitamin B12 deficiency Folate deficiency Pernicious anemia Down syndrome Normal newborn nadir Post-splenectomy Ileal resection Drugs Hypothyroidism Aplastic anemia Diamond-Blackfan anemia Fanconi’s anemia Erythroleukemia Dyskeratosis congenita Paroxysmal nocturnal hemoglobinuria

Figure 18.1 Morphologic classification of normocytic, normochromic anemia.

Microcytic, Hypochromic Anemia LABORATORY DIFFERENTIATION OF MICROCYTIC, HYPOCHROMIC ANEMIAS

Condition

Bone Serum marrow Iron Transferrin Ferritin Iron TIBC

Iron Low deficiency

High

Low

Absent

High

Reticulocyte RDW

Mentzer Index∗

Low

<13

High

Thalassemia Normal Normal minor or high

Normal Normal Normal Normal or high or high or high

Normal >13

Anemia of chronic disease

Normal Normal Normal Normal or or or high high high

Normal N/A

Low

Low

∗Mentzer index = MCV/RBC.

P E D I AT R I C S

Further investigations: Serum B12 Serum and RBC folate Liver enzymes PTT Thyroid panel Hb electrophoresis Bone marrow aspiration

Further investigations: Iron panel (serum iron, ferritin, TIBC, TIBC % sat) Hb electrophoresis Lead level Bone marrow aspiration Newborn screen

198

Pediatrics

Normocytic, Normochromic Anemia Normocytic, Normochromic Anemia

Reticulocyte count∗ LOW

HIGH

Bone marrow failure

Hemorrhage or hemolysis

Thrombocytopenia or neutropenia?

Yes See Pancytopenia

↑ Bilirubin, LDH

No

Yes

Isolated RBC aplasia

Acquired: Transient erythroblastopenia of childhood Systemic illness (kidney, liver, hypothyroid) Infection Pure RBC aplasia Aplastic crisis (parvovirus B19)

Positive (antibody-mediated)

Alloimmune hemolytic anemia Autoimmune hemolytic anemia • Cold IgM: Mycoplasma • Warm IgG: RA, SLE Drug-induced hemolytic anemia • Cephalosporins, penicillins, quinidine

Hemolysis

Congenital: Diamond-Blackfan syndrome

No Hemorrhage

Direct Coombs

Negative (not antibody-mediated)

Extrinsic: Hypersplenism Shear stress (mechanical heart valve) Chemical agents Hypophosphatemia Paroxysmal nocturnal hemoglobinuria Microangiopathic (schistocytes): HUS, TTP, DIC

Intrinsic: Membrane defect • Hereditary spherocytosis • Elliptocytosis Hemoglobinopathy • Sickle cell anemia Enzymopathy • G6PD deficiency • Pyruvate kinase deficiency

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-deficiency anemia, or in assessing response to therapy. Normal values: < 2 yrs, 24.5-35.2 pg; 2+ yrs, 27.1-35.4 pg.

Iron-Deficiency 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.

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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 Minor (Heterozygous)

α-Thalassemia

β-Thalassemia Major (Cooley’s, Homozygous)

Presentation

Varies: Asymptomatic to hydrops fetalis

Severe hemolytic anemia in infancy, hepatosplenomegaly

Mild microcytic anemia

Pathogenesis

Deﬁciency in α-globin synthesis (severity depends on number of genes deleted)

Complete absence of β-globin synthesis (β0/β0) to partial reduction (β+/β+)

Reduced or abnormal β-globin synthesis (heterozygous)

Peripheral smear

Microcytic anemia

Severe hypochromia and microcytosis, fragmented RBCs, nucleated RBCs,

Hypochromia and microcytosis,

NBS or Hb electrophoresis ﬁndings

Hb Bart (γ4) Hb H (β4)

Hb A (α2β2) absent ↑ Hb F (α2γ2)

Increased Hb A2 (α2δ2) ± ↑ Hb F (α2γ2)

Typical population

Southeast Asia

Europe, Middle East, India, and Africa

Europe, Middle East, India, and Africa

Treatment

Folic acid or transfusion therapy

Transfusion; splenectomy if severe

None necessary

Reproduced with permission from Pediatr Clin North Am 2008;55:447.

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 identified on NBS or with positive FHx; send confirmatory 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– foot syndrome)

Painful swelling of the hands and feet (infancy)

Hydration, narcotics

Splenic sequestration crisis

Hypotension, anemia (caused by pooling of RBC in the spleen), splenomegaly

Transfusion (simple or exchange), oxygen, and splenectomy in severe cases (continued on next page)

P E D I AT R I C S

Intracellular Defects

200

Pediatrics

Name

Signs and Symptoms

Acute Treatment

Acute chest crisis

Fever, tachypnea, hypoxia, inﬁltrate (CXR)

Hydration, oxygen, transfusion (exchange or simple), incentive spirometry, positive-pressure ventilation if severe

Aplastic crisis

Severe anemia with reticulocytopenia

Transfusion

Stroke

Focal neurologic deﬁcits, altered mental status

Exchange transfusion; chronic transfusion 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 Age

Recommended Visits

Studies

Vaccines

Screening

0–6 mo

Every 2 mo

CBC, reticulocyte count, Hb electrophoresis, G6PD test

PCV7 per regular schedule

None

6–24 mo

Every 3–6 mo

CBC, reticulocyte count, Hb electrophoresis, LFT, Chem 7, iron studies

Annual inﬂuenza

None

2–5 yr

Every 6 mo

CBC, reticulocyte count, LFT, Chem 7, Iron studies, U/A

Pneumococcal 23-valent and a booster at age 5 yr

Transcranial Doppler (TCD) every yr for HbSS and S-β0 thalassemia; dentist

>5 yr

Every 6–12 mo

Same as 2–5 yr

Annual inﬂuenza

TCD, retinal 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.

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201

WHITE BLOOD CELL DISORDERS AGE-SPECIFIC WHITE BLOOD CELL NORMAL VALUES∗ Neutrophils†

Total Leukocytes Age

Mean

Range

Mean

Range

Birth

—

‡

%

—

4.0

2.0–6.0

—

12 h 24 h

—

—

11.0

7.8–14.5

—

—

—

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

1y

11.4

6.0–17.5

3.5

1.5–8.5

31

2y

10.6

6.0–17.0

3.5

1.5–8.5

33

4y

9.1

5.5–15.5

3.8

1.5–8.5

42

6y

8.5

5.0–14.5

4.3

1.5–8.0

51

8y

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

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

—

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

1y

7.0

4.0–10.5

61

0.6

5

0.3

3

2y

6.3

3.0–9.5

59

0.5

5

0.3

3

4y

4.5

2.0–8.0

50

0.5

5

0.3

3

6y

3.5

1.5–7.0

42

0.4

5

0.2

3

8y

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

Lymphocytes

Monocytes

Eosinophils

P E D I AT R I C S

∗Numbers of leukocytes are in X 109/L or thousands per mm3; ranges are estimates of 95% conﬁdence limits, and percentages refer to diﬀerential counts. †Neutrophils include band cells at all ages and a small number of metamyelocytes and myelocytes in the ﬁrst few days of life. ‡ Insuﬃcient 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 • Definition: 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 Hereditary MDS CML Secondary Infection Inﬂammation Drugs (steroids, β-agonists, lithium) Asplenia

Reactive Infectious Mononucleosis Pertussis Bartonella Toxoplasmosis Babesiosis Noninfectious Hypersensitivity Postsplenectomy Malignancy

Infectious Parasites HIV Fungal Allergic disorders Allergic rhinitis Asthma Connective tissue disease Medications Malignancy

Inflammation Infection Brucellosis Tuberculosis Mononucleosis Rickettsia Autoimmune SLE, RA, IBD Malignancy HD, JMML Sarcoidosis Lipid storage disease

PANCYTOPENI DIFFERENTIAL DIAGNOSIS OF PANCYTOPENIA1 Congenital

Acquired

Fanconi anemia Familial aplastic anemia Dyskeratosis congenita Schwachman-Diamond syndrome

Idiopathic Leukemia/Tumor inﬁltration Drugs 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) • Uremia • Myeloproliferative disorders

↑ Destruction

↓ Production

Congenital: • Glanzmann’s thrombasthenia • Giant platelet syndromes (Bernard-Soulier, Gray platelet, May-Hegglin)

Immune mediated: • Viral • Drugs (antiepileptics, antibiotics, heparin) • ITP

Bone marrow failure: See pancytopenia Congenital: • Amegakaryocytic thrombocytopenia (eg, TAR) • Wiskott-Aldrich syndrome

Hypersplenism

Acquired: • Vitamin B12 or folate deficiency • Leukemia or myelodysplasia • Liver failure (thrombopoietin) • Sepsis • Dengue fever

DIC TTP

Figure 18-3 Overview of platelet disorders. (Reproduced with permission from Pediatr Clin North Am. 2004;51:1109).

COAGULOPATHIES Diagnosis

PT

Nl

PTT

Nl

Platelets

Nl

↑

Nl

Nl

↑

Nl

Nl

Differential Diagnosis

Possible Follow-up Studies

von Willebrand disease Platelet function disorder Factor XIII deﬁciency Fibrinolytic defect

PFA-100 von Willebrand studies Platelet aggregation studies

Hemophilia A or B Circulating inhibitor von Willebrand disease Factor XI deﬁciency Heparin contamination

PTT mixing study Factor assays (VIII, IX, XI) von Willebrand studies

Circulating inhibitor Vitamin K deﬁciency Warfarin Factor VII deﬁciency

PT mixing study Factor assays (VII)

P E D I AT R I C S

DIFFERENTIAL DIAGNOSIS OF COAGULATION AND BLEEDING DISORDERS

204

Pediatrics

• History (Pediatr Clin North Am 49:1239) • Does child bruise easily? (↑ sensitivity, ↓ specificity) 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 deficiency; one in 5000 males) or hemophilia B (actor 9 deficiency; 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 Dose (% correction) Dose (% Correction) Comments

Event Hemarthrosis (any joint)

40–50 u/kg (80–100)

100–120 u/kg (80–100)

Ice x 20 minutes, immobilize x 48 hours

Hematoma (soft 25–35 u/kg (50–70) tissue)

60–85 u/kg (50–70)

Local ice pack x 20 minutes

Head trauma

50 u/kg (100)

120 u/kg (100)

Do not wait for neurologic changes CT after ﬁrst 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 GU bleeding

85–120 u/kg (70–100)

Search for cause of bleeding

35–50 u/kg (70–100)

∗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 (relative)

vWF antigen decreased

DDAVP eﬀective in almost all

2 (A/B)

10%–15%

Defective vWF

vWF activity decreased

DDAVP response variable

3

Rare

Deﬁciency of vWF (absolute)

vWF antigen absent

DDAVP ineﬀective

∗Treatment is based on patient history, response to prior interventions, and severity of bleeding and includes DDAVP, antiﬁbrinolytics (Amicar), plasma-derived vWF concentrates, and cryoprecipitate.

Hematology

205

RISK FACTORS FOR THROMBOEMBOLISM Congenital

Acquired

Common • Factor V Leiden • Prothrombin 20210 Uncommon • Antithrombin III deﬁciency • Protein C or S deﬁciency • Dysﬁbrinogenemia

• Stasis or immobility: Surgery, trauma • Central venous line • Inﬂammation: Infection, malignancy, SLE, ↑ factor VIII, ↑ vWF • Abnormal endothelium: Hyperlipidemia, ↑ age • Homocystinuria • 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∗ Mechanism

Route

Monitoring

Pros

Cons

UFH

Complexes with antithrombin to inactivate thrombin

IV drip Rarely sub-Q

PTT goal, 70–100 sec Anti-Xa activity goal 0.3–0.7 U/mL

Can be stopped quickly or reversed with protamine

Frequent monitoring Risk of HIT

LMWH

Inactivates factor Xa

Sub-Q

Anti-Xa goal 0.5–1.0

Does not require frequent monitoring Patient or parent dosing

Not fully reversible

Warfarin

Inhibits production of vitamin K–dependent factors (II, VII, IX, X)

PO

INR goal, 2–3†

Oral dosing Best option for long-term treatment

Drug and food interactions Diﬃcult to titrate in small patients 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 Definitions • 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 significant 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 insignificant 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.

P E D I AT R I C S

Drug

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 definitive evidence to advocate for empiric use.)

Red Blood Cells INDICATIONS FOR PACKED RED BLOOD CELL TRANSFUSION Hemoglobin (g/dL)

Patients Who May Benefit 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 (per mm3)

Patients Who May Benefit from Transfusion 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 benefit from transfusion intervention: • Active bleeding, surgery, or invasive procedure and • Prolonged PT or PTT caused by deficiency of coagulation factor(s) (except for fibrinogen, 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 deficiency • 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

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 confirmed primary cellular immunodeficiency or combined immune deficiency (eg, DiGeorge syndrome, SCID and Wiskott-Aldrich syndrome) (Note: Patients with partial DiGeorge syndrome may receive CMV-safe blood components.)

P E D I AT R I C S

• Components: Fibrinogen, factor 8, von Willebrand factor, factor 13, and fibronectin • 1 U of cryoprecipitate volume = 15 mL • Indications: Patients who may benefit from transfusion intervention: • Active bleeding with hypofibrinogenemia or dysfibrinogenemia • Active bleeding with suspicion of hypofibrinogenemia or dysfibrinogenemia and fibrinogen assay pending • Hypofibrinogenemia or dysfibrinogenemia, undergoing an invasive procedure • Undergoing cardiac surgery with excessive bleeding and fibrinogen assay pending • Known or suspected factor 13 deficiency undergoing an invasive procedure or actively bleeding • Dosing: 1–2 U/10 kg results in 60–100 mg/dL rise in fibrinogen (assume ideal recovery).

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 confirmed primary cellular immunodeficiency or combined immune deficiency • 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 fibrinogen replacement Desired fibrinogen level∗ – Initial fibrinogen level) mg/dL × PV (mL) ÷ 100 250 mg (fibrinogen 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 fibrinogen 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 deficiency • Vitamin B12 deficiency

C H A P T E R 19

High-Yield Ambulatory Care ROUTINE HEALTH SUPERVISION OVERVIEW The American Academy of Pediatrics has established guidelines for routine health supervision visits. Priorities of these visits are the physical exam, developmental observation, universal screening, immunizations (Figures 19-1 and 19-2) and anticipatory guidance (including nutrition, healthy habits, injury prevention, and evaluation of milestones). For complete AAP bright futures universal screening recommendations see: http://brightfutures.aap.org/3rd_Edition_Guidelines_and_Pocket_Guide.html

Age

Developmental Universal Observations Screening

Nutrition

Healthy Habits

Injury Key Prevention Milestones

Allow umbilical cord to air dry, avoid ill contacts, use rectal thermometer (fever ≥100.4 ºF)

Should First stool sleep on and void by the back, age 24 h Rear-facing car seat

Newborn

Periods of wakefulness, responsive to parent voice and touch

State metabolic screen, newborn hearing screen, height, weight, FOC

Breastfeeding or formula, start vitamin D for exclusively breastfed infants

1 wk

Brieﬂy ﬁxes on faces, primitive reﬂexes

Height, weight, FOC

Breastfeed- Avoid ing or direct formula sunlight

1 mo

Lifts head while Height, prone weight, FOC

Breastfeed- Tummy Set water ing or time while heater formula awake temp to <120 ºF

2 mo

Social smile, holds head up when prone, coos, follows visually past midline

Breastfeed- No bottle ing or propping formula

Never leave infant unattended on high surface

Moro, walking/ stepping reﬂexes disappear

4 mo

Babbles, rolls, Height, turns to sounds, weight, regards own FOC hand

May introduce cereal

Read books with baby

Check for sources of lead in the home

Rooting reﬂex disappears

6 mo

Sits, imitates Oral health, sounds, reaches height, for objects weight, FOC

Start singleingredient foods one at a time

Assess ﬂuoride source

Baby prooﬁng of home, choking awareness

Teething begins, tonic neck and palmar grasp reﬂexes disappear

Loss of umbilical stump (typically 10 d–3 wk), regains BW by 2 wk

P E D I AT R I C S

Height, weight, FOC

Keep home and vehicle smoke free, never shake baby

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210

Age

Pediatrics Developmental Universal Observations Screening

Nutrition

Healthy Habits

Injury Key Prevention Milestones

9 mo

Stranger anxiety, object permanence, feeds self, pulls to stand

Development, oral health, height, weight, FOC

Finger foods

Brush teeth with water or soft toothbrush

Lock up poisons, cleaners, chemicals

12 mo

Waves bye-bye, starts to walk, says “mama” and “dada” (speciﬁc)

Anemia, lead (high prevalence, Medicaid), height, weight, FOC

May introduce cow’s milk instead of formula

First dental visit, start bottle weaning

May use forwardfacing car seat if 12 mo and >20 lb

15 mo

Speaks two or three words, scribbles, walks well

Height, weight, FOC

Three Avoid meals/d nighttime with snacks bottle

18 mo

Speaks six words, runs, stacks blocks, uses spoon

DevelopLimit juice ment, auintake tism, height, weight, FOC

2 yr

Speaks 50 words, twoword phrases, follows twostep command, pretend play

Autism, lead (high prevalence, Medicaid), height, weight, FOC, BMI

2.5 yr

Speaks threeto four-word phrases, language understandable 50% of the time, throws ball, puts on clothes with help, points to body parts

Development, height, weight, FOC, BMI

Continue to read with child

Fire safety

3 yr

Self-care skills (feeding, dressing), language understandable 75% of the time, rides tricycle, walks upstairs, alternating feet, copies circle

Visual acuity, measure blood pressure, height, weight, FOC, BMI

Use “timeouts” for discipline, interactive play

Switch to beltpositioning booster seat when >40 pounds and ears reach top of car seat

Consistent discipline for teaching and protecting, avoid punishing

Prevent burns (eg, hot liquids on stove), no spanking

Transition Limit TV Supervise from whole viewing to child to low-fat <2 hr/d outside milk

Plantar reﬂex starts to disappear

Temper tantrums begin

Toilet training begins

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High-Yield Ambulatory Care

Age

Developmental Universal Observations Screening

Nutrition

211

Healthy Habits

Injury Key Prevention Milestones

Promote healthy daily routines

Teach to swim

Assess school readiness

Participation in organized activities, transitioning to kindergarten

4 yr

Tells stories, names four colors, speech mostly understandable, copies cross, hops, dresses self

Visual acuity, hearing, blood pressure, height, weight, BMI

5–6 yr

School readiness skills

Visual acuity, hearing, measure blood pressure, height, weight, BMI

Breakfast before school, eat 5+ servings of fruit and veggies per day

Limit candy, soda, and high-fat snacks; regular dental visits

Bike helmet, teach safe street habits (crossing and riding school bus)

7 and 8 yr

Physical, cognitive, emotional, social, moral competencies

Visual acuity, hearing (8-yr visit), blood pressure, height, weight, BMI

≥2 cups of low-fat milk or dairy per day

Be active at least 60 min/d, brush teeth twice per day

Teach home safety rules for ﬁre and emergencies

9 and 10 yr

Sense of selfconﬁdence, increasing responsibility and independence

Visual acuity, hearing (10-yr visit), measure blood pressure, height, weight, BMI

Encourage child to make healthy food choices independently

Be active at least 60 minutes per day

Switch from booster seat to safety belt when belt ﬁts (usually when greater than 4’9”)

11–14 yr Physical, emotional, academic, social well-being

Vision, blood pressure, height, weight, BMI

3+ servings Healthy of low-fat eating milk or dairy per day

Counsel to Puberty minimize risks (drugs, pregnancy, STIs, guns)

15–17 yr Physical, emotional, academic, social well-being

Vision, blood pressure, height, weight, BMI

Three balanced meals per day, eat with family

Protect hearing (headphones, music)

Assess for risky behavior

18–21 yr Physical, emotional, academic, social well-being

Vision, dyslipidemia, blood pressure, height, weight, BMI

Three balanced meals per day, eat with family

Self breast Assess and for risky testicular behavior exams

May be starting sexual development

Ability to vote, may transition to independent 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.

P E D I AT R I C S

Driver’s license

212

Pediatrics

Selective Screening

Visit

Notes

Oral health: Dental home

12, 18 mo; 2, 2.5, 3, 6 yr

Referral to dental home for patients at high risk of caries

Oral health ﬂuoride

12, 18 mo; 2, 2.5, 3, 6 yr

Prescribe oral ﬂuoride supplementation to children older than age 6 mo whose primary water source is deﬁcient in ﬂuoride (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 universal screening not performed

Age-appropriate evaluation for vision problems based on history and physical exam; children at high risk of eye problems (eg, those with developmental delay, systemic diseases associated with eye abnormalities) should be referred to an ophthalmologist

Hearing

4 mo–3 yr; 11–21 yr

Young children should be monitored at each visit for 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; then annually

Screen for anemia in infants who were premature 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 (when universal screening for high prevalence or per Medicaid requirement not done)

Test blood lead level if screening questionnaire results are positive for potential lead exposure (lives in home built before 1950, lives in home built before 1978 being renovated in past 6 months, or sibling or playmate with lead poisoning)

Tuberculosis

1, 6, 12, 18 mo; then annually

Annual TB skin test for children with HIV or incarcerated 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; annually when not universally screened

Screen children who have family history of premature coronary artery disease, stroke, or peripheral vascular disease (onset age <55 yr) or with parental hyperlipidemia; overweight or obese children may also be screened.

Chlamydia and gonorrhea

11–21y r if sexually active

Screen sexually active female patients annually

HIV and syphilis

11–21 yr if sexually active

Screen sexually active patients who have high-risk behavior

Cervical dysplasia

11–21 yr if sexually active

Screen all sexually active females within 3 years of onset of sexual activity or by age 21 yr

Vaccine

Age

Hepatitis B

Birth HepB

1 mo

2 mo

4 mo

6 mo

HepB

12 mo

15 mo

RV

RV

RV

DTaP

DTaP

DTaP

Haemophilus influenzae type b

Hib

Hib

Hib

Hib

Pneumococcal

PCV

PCV

PCV

PCV

Inactivated poliovirus

IPV

IPV

Rotavirus Diphtheria,tetanus,pertussis

18 mo

19–23 mo

2–3 yr

4–6 yr

11–12 yr

7–10 yr

HepB series

13–18 yr

HepB series

DTaP

Tdap

DTaP

Tdap

PPSV

IPV

IPV series

IPV

Measles, mumps, rubella Varicella

MMR

MMR

MMR series

Varicella

Varicella

Varicella series HepA series

HepA (2 doses)

Hepatitis A Meningococcal

MCV

HPV

* Range of recommended ages

Catch-up immunization

MCV

MCV

HPV (3 doses)

HPV series

Certain high-risk groups

Figure 19-1 2010 Recommended immunization schedule children birth to age 18 yr. Based on vaccination schedules released Jan 8, 2010. For full details, see http://www.cdc.gov/vaccines. Adapted from MMWR 2010;58(51 and 52):1–4. ∗First does may be administered at 9 years for females (HPV4 or HPV2) or males (HPV4)

P E D I AT R I C S

213

Influenza (yearly)

Influenza

214

Pediatrics Catch-up Vaccination Schedule∗

Vaccine

Minimum Interval Between Doses Minimum Age for Dose 1 to Dose 2 to Dose 3 to Dose 4 to 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 ﬁrst dose)

Rotavirus∗∗

6 wk

4 wk

4 wk

Diphtheria, tetanus, pertussis

6 wk

4 wk

4 wk

Haemophilus inﬂuenzae type b

6 wk

4 wk (if ﬁrst dose administered at younger than age 12 mo) 8 wk (as ﬁnal dose) (if ﬁrst dose administered at age 12-14 mo) No further doses needed (if ﬁrst dose administered at age 15 mo or older)

4 wk (if current age is younger than 12 mo)

4 wk (if ﬁrst dose administered at younger than age 12 mo) 8 wk (as ﬁnal dose for healthy children) (if ﬁrst dose administered at age 12 mo or older or current age 24 through 59 mo) No further doses needed (for healthy children if ﬁrst dose administered at age 24 mo or older)

4 wk (if current age is younger than 12 mo) 8 wk (as ﬁnal dose for healthy children) (if current age is 12 mo or older) No further doses needed (for healthy children if previous dose administered at age 24 mo or older)

Pneumococcal 6 wk

6 mo

6M

8 wk (as ﬁnal dose) (This dose only necessary for chil8 wk (as ﬁnal dren aged 12 dose) mo–through (if current 59 mo who age is 12 mo received 3 or older and doses before second dose administered at age 12 mo) younger than age 15 mo) No further doses needed (if previous dose administered at age 15 mo or older) 8 wk (as ﬁnal dose) (This dose only necessary for children aged 12 mo–59 mo who received 3 doses before age 12 mo or for high-risk children who received 3 doses at any age)

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High-Yield Ambulatory Care

215

Catch-up Vaccination Schedule∗

Vaccine

Minimum Interval Between Doses Minimum Age for Dose 1 to Dose 2 to Dose 3 to Dose 4 to Dose 1 Dose 2 Dose 3 Dose 4 Dose 5

Inactivated poliovirus

6 wk

4 wk

Measles, mumps, rubella

12 mo

4 wk

Varicella

12 mo

3 mo

Hepatitis A

12 mo

6 mo

4 wk

6 mo

Catch-up Vaccination Schedule for Children Aged 7 to 18 Years Tetanus, diphtheria/ tetanus, diphtheria, pertussis†

7 yr

4 wk

4 wk (if ﬁrst dose administered at younger than age 12 mo) 6 mo (if ﬁrst dose administered at age 12 mo or older)

Human Papillomavirus

9 yr

4 wk

12 wk (and ≥24 wk since 1st dose)

12 mo

6 mo

Hepatitis B

Birth

4 wk

8 wk (and ≥ 16 wk after 1st dose)

Inactivated Poliovirus

6 wk

4 wk

4 wk

Measles, mumps, rubella

12 mo

4 wk

Varicella

12 mo

3 mo (if <13 y) 4 wk (if ≥ 13 y)

P E D I AT R I C S

Hepatitis A

6 mo (if ﬁrst dose administered at younger than age 12 mo)

6 mo

∗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-specific relative contraindications to vaccination.

216

Pediatrics

For additional vaccine contraindication and precaution information: MMWR 2006;55(RR–15):10–14

True Contraindications

False Contraindications (Precaution)

Anaphylaxis to a previous vaccine or vaccine constituent

Local reaction to a previous vaccine

Moderate to severe illness Fever with signs that might be confused for adverse reaction to vaccine (advised to delay immunization)

Mild acute illness with low-grade fever, mild diarrheal illness in an otherwise well child, currently receiving antibiotic therapy, recent exposure to the vaccine-preventable disease

True Allergies Neomycin: MMR, varicella, IPV, OPV Streptomycin: IPV, OPV Polymyxin B: IPV, OPV Gelatin: MMR, varicella, yellow fever Egg: Inﬂuenza Yeast: Hepatitis B

Inﬂuenza: Nonsevere (eg, contact) allergy to latex or thimerosal

Pregnancy Approved: Tdap/Td, inactivated inﬂuenza vaccines Precaution: Hepatitis A, MCV4∗, IPV, and live vaccines†

Pregnancy in a household contact

Immunocompromised Patient (see “Immunization for Special Populations”)

Immunocompromised family member or household contact, asymptomatic or mildly symptomatic HIV infection, humoral immunodeﬁciency (may not be eﬃcacious)

DTap contraindicated if history of idiopathic encephalopathy within 7 days of previous dose or until patient’s progressive neurologic disease (infantile spasms, recent or uncontrolled seizures, progressive encephalopathy) excluded or stabilized

Family history of allergy, seizures, or an adverse event after immunization Precautions (not contraindications) for pertussiscontaining vaccines: • Fever of >40.5 C ≤48 h of receiving previous dose • Collapse or shock-like state ≤ 48h of receiving previous dose • Persistent, inconsolable crying for ≥ 3h ≤ 48h of receiving previous dose • Seizures ≤3 d of receiving a previous dose

Tdap contraindicated if history of idiopathic encephalopathy within 7 days of previous dose MMRV is contraindicated in patients with active febrile illness >101.3°F or active untreated tuberculosis

Mild acute illness with low-grade fever or mild diarrheal illness in an otherwise well child

Hib is absolutely contraindicated in infants <6 wk of age

Prematurity (all can be administered, hepatitis B vaccine does not “count” until 2 kg)

∗No data. † Live virus vaccines: MMR, varicella, OPV, intranasal inﬂuenza, rotavirus.

High-Yield Ambulatory Care

217

IMMUNIZATIONS FOR SPECIAL POPULATIONS Population

Immunization

Asplenic children (including: sickle cell disease)

13-valent conju2, 4, 6 mo gate pneumococcal vaccine

Timing

Pneumococcal 23-valent vaccine

2 yr

Quadrivalent meningococcal polysaccharide vaccine

2 yr

Pneumococcal 23-valent vaccine booster

5 yr

Inﬂuenza vaccine

Annually starting at 6 mo

Immune compromised host (eg. congenital immunodeﬁciency disorders)

Live viral and Contraindicated bacterial immunizations

Patients receiving corticosteroids (IV or PO only; excludes inhaled, topical, local)

Bacterial and live viral∗ immunizations

Inactivated: all Live: Measles vaccine if not severely immunocompromised; varicella vaccine if CD4 count >15%–25 % and patient asymptomatic

Hematopoietic stem cell transplant (HSCT) recipients

(See oncology chapter)

For recommendations for speciﬁc immunodeﬁciencies, see current Red Book or Clin Infect Dis 2009;49:817

Low dose: <10 kg: <2 mg/kg/d or equivalent >10 kg: <20 mg/d Administer per regular or catch-up vaccination schedule High dose: <10 kg: >2 mg/kg/d or equivalent >10 kg: >20 mg/d See notes

Depends on the duration of steroids: >14 d; wait 1 mo after discontinuing steroids before administering immunization <14 d: consider administration upon discontinuation of steroids or waiting ≤2 wk

Vaccines may be given if prednisone dose: >2 mg/kg/d or equivalent or >20 mg/d if patient >10 kg and duration of steroids <14 d

May administer second dose of MMR 4 wk after the ﬁrst dose May administer second varicella vaccine 3 mo after the ﬁrst dose

∗Live-virus vaccines: MMR, varicella, OPV, intranasal inﬂuenza, rotavirus.

P E D I AT R I C S

HIV Patients

Notes

CHAPTER 20

Infectious Disease ANTIBIOTIC GUIDE PENICILLINS Bactericidal: Inhibit bacterial cell wall synthesis via competitive inhibition of transpeptidase Antimicrobial Spectrum

Adverse Effects

• Penicillin G (IV) • Benzathine penicillin G (IM) • Procaine penicillin G (IM) • Penicillin V (PO)

• Streptococcus Group A, B, viridans • Most Streptococcus pneumoniae • Treponema pallidum • Neisseria meningitidis • Actinomyces spp. • Pasteurella multocida • Some anaerobes

• Anaphylaxis • Rash • Drug fever • Bone marrow suppression • Hemolytic anemia • Interstitial nephritis • Renal impairment

• Penicillin V is acid stable in the stomach • Resistance caused by degradation of antibiotic by bacterial penicillinases

• Ampicillin (IV, IM, PO) • Amoxicillin (PO)

• Streptococcus Group A, B, viridans • S. pneumoniae • Enterococcus spp. • Listeria monocytogenes • Haemophilus influenzae if β-lactamase negative • Kingella kingae • Some gramnegative organisms: Escherichia coli, Salmonella spp., Shigella spp., Proteus spp.

• GI disturbance • Elevated LFTs • Bone marrow suppression • Hemolytic anemia • Allergic reaction • Renal impairment

• Better PO with amoxicillin than ampicillin

Class

Examples

Narrow spectrum (β-lactamase susceptible)

Aminopenicillins

Miscellaneous

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218

Infectious Disease

219

Bactericidal: Inhibit bacterial cell wall synthesis via competitive inhibition of transpeptidase Class

Examples

β-Lactamase • Nafcillin (IV) resistant (anti- • Oxacillin (IV) staphylococcal • Dicloxacillin penicillins) (PO)

Antimicrobial Spectrum

Adverse Effects

• S. aureus (MSSA) • Streptococcus Group A, B, viridans • S. pneumoniae

• Interstitial nephritis • Renal impairment • Hepatic toxicity • Bone marrow suppression • Allergic reaction

• No activity against gram-negative organisms • Nafcillin causes more phlebitis than oxacillin (decreased with slow infusion, large-gauge IV)

Miscellaneous

• Piperacillin (IV) • Ticarcillin (IV) • Carbenicillin (PO)

• Pseudomonas aeruginosa • Streptococcus Group A, B, viridans • S. pneumoniae • Enterococcus spp. • Some gramnegative → Escherichia coli, Enterobacter spp., Salmonella spp., Shigella spp., Proteus spp., Citrobacter spp., Haemophilus spp. • Neisseria spp.

• Platelet dysfunction • High Na load • Hypokalemia • Serum sickness • Bone marrow suppression • Renal impairment

• S. viridans and Enterococci are only 30%-60% susceptible

Penicillin + β-lactamase inhibitor

• Amoxicillin + clavulanate (PO) • Ticarcillin + clavulanate (IV) • Ampicillin + sulbactam (IV) • Piperacillin + tazobactam (IV)

• Streptococcus Group A, B, viridans • S. pneumoniae • Enterococcus spp. • S. aureus (MSSA) • Gram-negative organisms: E. coli, Klebsiella spp., Salmonella spp., Shigella spp., Proteus spp., Aeromonas spp., Pasteurella multocida • P. aeruginosa (piperacillin/ tazobactam and ticarcillin/ clavulanate) • Anaerobes

• GI disturbance • Diarrhea (especially amoxicillin/ clavulanate) • Rash • Renal impairment

• S. viridans and Enterococci are only 30%–60% susceptible to ticarcillin/ clavulanate and piperacillin/ tazobactam

P E D I AT R I C S

Antipseudomonal penicillins

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 Spectrum

Adverse Effects

• Cefazolin (IV) • Cephradine (IV, PO) • Cephalexin (PO) • Cefadroxil (PO) • Cephapirin (IV)

• Streptococcus Group A, B, viridans • S. pneumoniae • S. aureus (MSSA) • Limited gramnegative activity

• Anaphylaxis • Rash • Delayed rash • Drug fever • Bone marrow suppression • Renal impairment

• Minimal CSF penetration • Renal excretion • Cephalosporins have no activity against Enterococcus spp.

Second Generation

• Cefamandole (IV, IM) • Cefuroxime (IV, PO) • Cefonicid (IV) • Cefaclor (PO) • Cefprozil (PO) • Cefotetan (IV) • Cefoxitin (IV, IM)

• Streptococcus Group A, B, viridans • S. pneumoniae • S. aureus (MSSA) • Some gram-negative organisms: M. catarrhalis, H. influenzae, E. coli, Klebsiella spp., Proteus spp. • Some anaerobes (cefotetan, cefoxitin)

• Allergic reaction • Coagulation disturbance • Bone marrow suppression • Renal impairment

• Minimal CSF penetration • Renal excretion • Decreased gram-positive activity compared with ﬁrst generation but improved gram-negative activity

Third generation

• Cefotaxime (IV, IM) • Ceftizoxime (IV, IM) • Ceftriaxone (IV, IM) • Ceftazidime (IV, IM) • Ceﬁxime (PO) • Cefpodoxime (PO) • Cefdinir (PO) • Ceftibutin (PO)

• Streptococcus Group A, B, viridans • S. pneumoniae

• Biliary sludging (ceftriaxone) • Allergic reaction • Bone marrow suppression • Renal impairment

• Good CSF penetration for cefotaxime, ceftriaxone, and ceftazidime • Renal excretion • Better gramnegative activity, less grampositive activity compared with ﬁrst- and secondgeneration cephalosporins except for S. pneumoniae • Ceftriaxone is a strong bilirubin displacer from albumin, limiting its use in neonates

Class

Examples

First generation

• Decreased antistaphylococcal activity • Neisseria spp. • Gram-negative organisms: M. catarrhalis, H. influenzae, E. coli, Klebsiella spp., Enterobacter spp., Salmonella spp., Shigella spp., Proteus spp., Citrobacter spp., Aeromonas spp. • P. aeruginosa (ceftazidime only)

Miscellaneous

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Infectious Disease

221

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 Class

Examples

Fourth generation

• Cefepime (IV, IM)

Antimicrobial Spectrum

Adverse Effects

• Pseudomonas aeruginosa • Streptococcus Group A, B, viridans • S. pneumoniae • Neisseria spp. • Gram-negative organisms: M. catarrhalis, H. influenzae, E. coli, Klebsiella spp., Enterobacter spp., Salmonella spp., Shigella spp., Proteus spp., Citrobacter spp., Aeromonas spp.

• Allergic reaction • Bone marrow suppression • Renal impairment

Miscellaneous • Good grampositive activity except ( S. aureus and Enterococcus spp.) and gram-negative activity, including Pseudomonas spp.

AZTREONAM (MONOBACTAMS) Bactericidal: Inhibit cell wall biosynthesis Antimicrobial Spectrum

• Aztreonam (IV, IM)

• Gram-negative organisms only: Neisseria spp., M. catarrhalis, H. influenzae, E. coli, Klebsiella spp., Serratia spp., Salmonella spp., Shigella spp., Proteus spp., Citrobacter spp., Aeromonas spp., Pseudomonas spp.

Adverse Effects • GI disturbance • Rash

Miscellaneous • Good CSF penetration • Renal excretion • No activity against gram-positive organisms or anaerobes

CARBAPENEMS Bactericidal: Inhibit cell wall biosynthesis Examples

Antimicrobial Spectrum

Adverse Effects

Miscellaneous

• Meropenem (IV, IM) • Imipenem (IV, IM)

• Streptococcus Group A, B, viridans • S. pneumoniae • S. aureus (MSSA) • Anaerobes • Gram-negative organisms: Neisseria spp., M. catarrhalis, H. influenzae, E. coli, Klebsiella spp., Serratia spp., Salmonella spp., Shigella spp., Proteus spp., Citrobacter spp., Aeromonas spp., Pseudomonas spp.

• GI disturbance • Allergic reaction • Seizures with imipenem in children with meningitis

• Renal excretion • No activity against Enterococcus spp., Burkholderia cepacia, Stenotrophomonas maltophilia

P E D I AT R I C S

Examples

222

Pediatrics

VANCOMYCIN (GLYCOPEPTIDES) Bacteriostatic: Inhibit cell wall biosynthesis (one step earlier than PCN) Examples

Antimicrobial Spectrum

• Vancomycin • S. aureus (MSSA & MRSA) (IV, PO) • Streptococcus Group A, B, viridans • S. pneumoniae • Enterococcus spp. • CONS • Bacillus spp. • Gram-positive anaerobes: Actinomyces spp., Clostridium spp., Peptostreptococcus spp. • Use in high doses as an alternative for treatment of Listeria in a penicillin allergic patient

Adverse Effects

Miscellaneous

• Red man syndrome • Ototoxicity • Renal toxicity, particularly in combination with other nephrotoxic drugs

• Renal excretion • Activity against most gram-positive organisms • No activity against gram-negative organisms except Flavobacterium meningosepticum • PO for C. difficile infections ONLY

MACROLIDES AND AZILIDES Bacteriostatic: Inhibit protein synthesis via binding to 50S ribosomal subunit Examples • Azithromycin (IV, PO) • Erythromycin (IV, PO, ophthalmic ointment) • Clarithromycin (PO)

Antimicrobial Spectrum • Atypical organisms→ Legionella spp., Mycoplasma spp., Chlamydia spp. • Bordetella pertussis • Streptococcus spp. • Mycobacterium avium • Gram-negative organisms: Neisseria spp., M. catarrhalis, H. influenzae, B. henselae

Adverse Effects

Miscellaneous

• GI disturbance • Rare cholestatic jaundice • Prolonged QT syndrome • Erythromycin ethylsuccinate use has been associated with pyloric stenosis in neonates

• Metabolized by cytochrome P450; thus, multiple drug interactions • Can use azithromycin or clarithromycin as empiric therapy for cat scratch disease

Infectious Disease

223

CLINDAMYCIN (LINCOSAMIDES) Bacteriostatic: Inhibit protein synthesis via binding to 50S ribosomal subunit Antimicrobial Spectrum

Examples

• S. aureus (MSSA & MRSA) • Streptococcus Group A, B, viridans • S. pneumoniae • Anaerobes • Toxoplasma gondii • Plasmodium falciparum and vivax

• Clindamycin (IV, IM, PO)

Adverse Effects

Miscellaneous

• Pseudomembranous colitis • Hepatotoxicity • GI disturbance • Bone marrow suppression • Rash

• Bile and urine excretion • No activity against gram-negative organisms • No activity against Enterococci • Minimal CSF penetration

LINEZOLID (OXAZOLIDINONES) Bacteriostatic: Inhibit protein synthesis via binding to 50S ribosomal subunit Examples • Linezolid (IV, PO)

Antimicrobial Spectrum • S. aureus (MSSA & MRSA) • CONS • Streptococcus Group A, B, viridans • S. pneumoniae • Enterococcus spp. (including VRE) • Nocardia spp.

Adverse Effects

Miscellaneous

• GI disturbance • Bone marrow suppression • Lactic acidosis • Peripheral neuropathy • Serotonin syndrome • Optic neuritis

• Metabolized partially in liver • Excreted in urine • Expensive • Side eﬀects associated with longer use (>4 wk) • 100% oral bioavailability • Active against some atypical mycobacteria

Bacteriostatic: Inhibit protein synthesis via binding to 30S ribosomal subunit Examples • Tetracycline (PO) • Doxycycline (IV, PO) • Minocycline (PO)

Antimicrobial Spectrum • Rickettsia spp. • Chlamydia spp. • Mycoplasma spp. • Entamoeba histolytica • Ehrlichia spp. • Anaerobes • Streptococcus Group A, B, viridans • S. aureus (MSSA & MRSA) • Gram-negative organisms: M. catarrhalis, H. influenzae, E. coli, Legionella spp., Brucella spp. • Propionibacterium acnes

Adverse Effects

Miscellaneous

• GI disturbance • Phototoxic dermatitis • Renal toxicity • Hepatic toxicity • Staining of permanent teeth • Fanconi syndrome • Teratogenic

• Absorption is impaired by food, milk, Ca, Mg • Avoid use in children <8 yr if alternate antibiotic is available except for treatment of Rocky Mountain spotted fever

P E D I AT R I C S

TETRACYCLINS

224

Pediatrics

AMINOGLYCOSIDES Bactericidal: Inhibit protein synthesis via binding to 30S ribosomal subunit Examples

Antimicrobial Spectrum

Adverse Effects Miscellaneous

• Amikacin (IV, IM) • Gentamicin (IV, IM) • Streptomycin (IV, IM) • Tobramycin (IV, IM, inhaled)

• Gram-negative enteric organisms • P. aeruginosa • Tularemia spp. • Yersinia pestis • Brucella spp. (plus TMP/SMX or azithromycin) • Mycobacterium tuberculosis and other atypical mycobacteria • Gram-positive synergy (GBS, E. faecalis, α strep)

• Ototoxicity • Renal toxicity • Competitive neuromuscular blockade

• Renal excretion • CNS penetration minimal even when meninges inﬂamed

FLUOROQUINOLONES Bactericidal: Inhibition of bacterial DNA gyrase and topoisomerase IV, blocking nucleic acid synthesis Class

Examples

First generation quinolone

• Nalidixic acid (PO)

Second generation quinolone

• Ciproﬂoxacin (IV, PO) • Oﬂoxacin (PO, ophthalmic, otic) • Levoﬂoxacin (IV, PO, ophthalmic)

Antimicrobial Spectrum

Adverse Effects

Miscellaneous • Not currently available in the United States

• Gram-negative organisms • P. aeruginosa • Legionella spp., Brucella spp. • Atypical mycobacterium • S. aureus (MSSA) • S. pneumoniae for levofloxacin

• Damage to cartilage in animals • GI disturbance • CNS symptoms • Tendonitis • Clostridium difficile colitis • Prolonged QT interval • Hepatic dysfunction • Rash • Drug interactions common, check prior to prescribing

• Use of ﬂuoroquinolones should be avoided in children <18 yr; ciproﬂoxacin is FDA approved in children <18 yr for postexposure treatment of inhalation anthrax and complicated UTI • Resistance develops by point mutations of DNA gyrase enzyme

Infectious Disease

225

Bactericidal: Inhibition of bacterial DNA gyrase and topoisomerase IV, blocking nucleic acid synthesis Antimicrobial Spectrum

Adverse Effects

• Gatiﬂoxacin (PO, ophthalmic)

• Streptococcus Group A, B, viridans • S. pneumoniae • Enterococcus spp. UTI • S. aureus (MSSA & MRSA) • Listeria spp. • Gram-negative organisms • Pseudomonas aeruginosa

• Damage to cartilage in animals • GI disturbance • CNS symptoms • Hyper- and hypoglycemia • C. difficile colitis • Drug interactions common, checked prior to prescribing

• Resistance develops by point mutations of DNA gyrase enzyme

• Moxiﬂoxacin (IV, PO, ophthalmic)

• Streptococcus Group A, B, viridans • S. pneumoniae • Enterococcus spp. UTI • S. aureus (MSSA & MRSA) • Listeria spp. • Gram-negative organisms • P. aeruginosa • Anaerobes

• Damage to cartilage in animals • GI disturbance • CNS symptoms • C. difficile colitis • Drug interactions common, check prior to prescribing

• Treatment of choice for open globe injuries • Resistance develops by point mutations of DNA gyrase enzyme

Class

Examples

Third generation quinolone

Fourth generation quinolone

Miscellaneous

Bacteriostatic: Inhibition of bacterial tetrahydrofolate synthesis, blocking DNA synthesis Examples • Trimethoprim/ sulfamethoxazole (IV, PO)

Antimicrobial Spectrum

Adverse Effects

• Gram-negative enterics • S. pneumoniae • S. aureus (MSSA & MRSA) • Pneumocystis jiroveci • Chlamydia spp. • Toxoplasma spp. • Nocardia spp. • Legionella spp. • Brucella spp. • Stenotrophomonas maltophilia

• Allergic reaction • Rash • GI disturbance • Bone marrow suppression • StevensJohnson syndrome

Miscellaneous • Metabolized in liver • Renal excretion • No Group A Strep activity • No Enterococcus activity • Contraindicated <3 months of age - due to risk of hyperbilirubinemia

P E D I AT R I C S

SULFONAMIDES

226

Pediatrics

METRONIDAZOLE (NITROIMIDAZOLES) Bactericidal: Indirect DNA damage and protein synthesis inhibition Examples • Metronidazole (IV, PO)

Antimicrobial Spectrum • Anaerobes • Clostridium spp. • Trichomonas • Entamoeba histolytica • No aerobic activity

Adverse Effects

Miscellaneous

• Neutropenia • Metallic taste • Reversible peripheral neuropathy • Antabuse eﬀect when consumed with alcohol

• Good CSF penetration

DAPTOMYCIN (LIPOPEPTIDES) Bactericidal: Binds to bacterial cell membranes leading to membrane depolarization and nucleic acid and /protein synthesis inhibition Examples • Daptomycin (IV)

Antimicrobial Spectrum • S. aureus (MSSA and MRSA) • Streptococcus Group A, B, viridans • S. pneumoniae • Enterococcus spp.

Adverse Effects

Miscellaneous

• GI disturbance • Rash • Headache • Insomnia • Myopathy (elevates CK)

• Renal excretion • Low lung penetration and decreased activity by pulmonary surfactant; should not be used to treat pneumonia

RIFAMPIN (RIFAMYCINS) Bacteriostatic: Inhibits nucleic RNA polymerase and blocks RNA transcription Examples • Rifampin (IV, PO)

Antimicrobial Spectrum

Adverse Effects

• S. aureus (MSSA and MRSA) • Streptococcus Group A, B, viridans • S. pneumoniae • CoNS • Listeria spp. • Neisseria spp. • M. catarrhalis, H. influenzae • Brucella spp. • M. tuberculosis

• Asymptomatic jaundice • Hepatotoxicity • Reddish/ orange discoloration of urine, sweat, tears

Miscellaneous • Penetrates into all ﬂuids and tissues • Excreted via liver • Rapid development of resistance when used alone • Synergistic applications (CONS and S. aureus) • Useful in treating devicerelated infections • Should not be used alone to treat infection • Many drug interactions

COMMON COMMUNITY ACQUIRED FUNGAL INFECTIONS Methods for Diagnosing Fungal Infections • Specific methods for diagnosing fungal infections: • Aspergillosis: 10% KOH prep or silver nitrate stain of tissue or BAL; fungal culture; BAL and serum galactomannan • Blastomycosis: 10% KOH or silver stain, fungal culture from biopsy or BAL; chemiluminescent DNA probes available • Candidiasis: Clinical diagnosis of skin infections. Invasive disease: Gram stain, 10%–20% KOH prep, endoscopy, eye exam; US or CT to evaluate for visceral involvement; ß-D glucan useful to diagnose and monitor treatment in selected invasive candida and zygomycoses infections • Coccidioidomycosis: Serologic tests preferred (IgM—latex agglutination, EIA, immunodiffusion detectable 1–3 wk to 3–4 mo after onset; IgG—immunodiffusion, EIA, complement fixation; titers increase with severity of disease), histopathology, fungal culture (highly infectious), DNA probes • Cryptococcosis: India ink stain or antigen test in CSF, culture, latex agglutination, EIA • Histoplasmosis: Polysaccharide antigen assay on serum and first urine in the morning, fungal culture, silver stain, radioimmunoassay, EIA, serology, and bone marrow aspirate or BAL (most useful in disseminated disease) • Paracoccidioidomycosis: 10% KOH, culture, serology • Sporotrichosis: Serologic tests (latex agglutination, complement fixation), fungal culture, histopathology with special stains • Alert the lab to what organism you are considering so the proper culture and staining techniques are used.

LYMPHADENITIS AND LYMPHADENOPATHY • Etiology: See table “Infectious and noninfectious causes of lymphadenitis and lymphadenopathy

INFECTIOUS AND NONINFECTIOUS CAUSES OF LYMPHADENITIS AND LYMPHADENOPATHY Noninfectious

Bacteria • S. aureus, GABHS, GBS in neonate (90% of all cases) • Bartonella henselae (cat-scratch disease) • Corynebacterium diphtheria • Anaerobic oral ﬂora (eg, Peptostreptococcus) • Mycobacterium tuberculosis, nontuberculous mycobacteria • Actinomyces israelii • Rickettsia tsutsugamushi (scrub typhus) • Zoonoses (rare; Brucella, Tularemia, Yersinia, Bacillus spp.) • Treponema pallidum, Leptospira interrogans, Salmonella typhi (all part of generalized lymphadenopathy)

• Connective tissue disorders (SLE, JRA) • Leukemia and lymphoma • Histiocytosis • Kawasaki disease • Kikuchi-Fujimoto syndrome (histiocytic necrotizing lymphadenitis) • PFAPA (periodic fever, aphthous ulcer, pharyngitis, adenitis) • Sarcoidosis • Postvaccination • Drugs (eg, phenytoin)

Viruses • Adenovirus, EBV, CMV, HIV, HSV, mumps, measles, rubella, Fungi • Histoplasmosis, blastomycosis, coccidioidomycosis Parasite • Toxoplasma gondii Data from Infect Dis Clin North Am 2007;21:523 and Pediatr Rev 2000;21:399.

P E D I AT R I C S

Infectious

Gram (+) Coverage Group A, B, S.viridans

S. pneumoniae

Gram (–) Coverage MSSA

MRSA

Enterococcus Spp.

VRE

Listeria Spp.

Neisseria Spp.

Moraxella H. flu

Gram (–) Pseudomonas enterics Spp.

Anaerobes Atypicals

Anaerobes

Penicillin Amino-PCN Anti-staphylococcus PCN Anti-pseudomonas PCN PCN+β-Lactamase inhibitor First generation Cephalosporin Second generation Cephalosporin Third generation Cephalosporin Fourth generation Cephalosporin

Ceftaz

Monobactams Carbapenems

228

Vancomycin Clindamycin Macrolides Linezolid Tetracyclines Aminoglycosides Fluroquinolones Sulfonamides

Strongest coverage ----------------------------------------------------------------------------------------------------------

Weakest coverage

Figure 20-1 Empiric antibiotic choice based on organism. (Reproduced with permission from Gilbert DN, Moellering RC, Eliopoulos GM, Sande MA, eds. The Sanford Guide to Antibiotic Therapy. Sperryville, VA: Antimicrobial Therapy Inc; 2008.)

Gram +

Cocci

Catalase +

Catalase –

Staphylococcus spp.

Streptococcus

Coagulase –

S. aureus

S. epidermidis S. saprophyticus Micrococcus Spp.

Oxacillin susceptible

Oxacillin resistant

MSSA

MRSA

PYR +

Spores +

Clostridium Spp. Bacillus Spp. PYR –

β Hemolysis

(γ or α) Hemolysis

S. pyogenes (group A)

Enterococcus (group D) Spp.

β Hemolysis

S. agalactiae (group B)* Group C Group G

Spores –

Catalase +

Listeria Spp. Corynebacterium Spp.

α Hemolysis

Optochin susceptible

Optochin resistant

S. pneumoniae

S. viridans

Algorithm for identifying gram-positive organisms.

∗Antigenic typing will determine Lancefield group. (Adapted from Murray PR: Manual of Clinical Microbiology, 9th ed, ASM Press; 2007.)

P E D I AT R I C S

229

Coagulase +

Figure 20-2

Rods (bacilli)

Catalase –

Lactobacillus Spp. Actinomyces Spp. Arcanobacterium Spp. Erysipelothrix Spp.

Gram –

230

Cocci

Coccobacilli

Neisseria spp. Moraxella spp. Acinetobacter spp.

Acinetobacter spp. Bordetella spp. Brucella spp. Francisella spp. Haemophilus spp. Kingella spp. Moraxella spp. Pasteurella spp. HACEK group

Oxidase +

Oxidase –

Thayer-Martin media

Acinetobacter spp.

Growth

No growth

Carbohydrate acidification tests

Moraxella spp.

Maltose fermenter

Maltose nonfermenter

N. meningitidis spp.

N. gonorrhoae spp.

Figure 20-3

Rods (bacilli)

Lactose fermenter

Oxidase –

E. coli (indole +) Enterobacter spp. Klebsiella spp. Citrobacter spp. Serratia spp.

Lactose nonfermenter

Oxidase +

Aeromonas spp. Burkholderia spp. Pseudomonas spp.

Algorithm for identifying gram-negative organisms. (Adapted from Murray PR: Manual of Clinical Microbiology, 9th ed, ASM Press; 2007.)

Oxidase –

Proteus spp. Morganella spp. Providencia spp. Salmonella spp. Shigella spp. Stenotrophomonas spp. Yersinia spp.

Infectious Disease

231

• Definitions: Lymphadenopathy: enlarged lymph nodes; lymphadenitis: enlarged lymph node secondary to inflammation or infection • Diagnosis • History and physical exam: Age of patient (see table “Age-specific 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 Neonates

Organism

2 mo–1 yr

1–4 yr

GABHS Group B streptococcus

++

+

S. aureus

+

++

Nontuberculous mycobacteria Bartonella henselae

+

5–18 yr

+

++

++

++

++

+

++

++

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 Clinical Presentation

Possible Infectious Causes

Acute bilateral lymphadenitis (most common)

Days

Small, rubbery nodes with little warmth or erythema

Viruses GABHS M. pneumoniae

Acute unilateral lymphadenitis

Days

Tender, overlying warmth and erythema, ± ﬂuctuance

S. aureus GABHS GBS B. henselae

Subacute or chronic lymphadenitis

Weeks to months

Preceded by a papule or pustule, with warm, erythematous node

B. henselae

Unilateral small node with overlying erythematous or violaceous hue, ± spontaneous drainage with sinus tract

M. tuberculosis complex, Nontuberculous mycobacteria

Unilateral or generalized lymph node involvement, ± fever, ⊕TST/IGRA

M. tuberculosis complex

Generalized lymph node involvement

T. gondii, Viruses (EBV and CMV)

P E D I AT R I C S

Duration of Onset

Child presents with lymphadenitis

Acute

Chronic

Bilateral

Unilateral

Unilateral

Etiology: Bartonella, TB, Atypical MTB, HIV

Etiology: Bacterial (most often)

Etiology: Viral (most often)

Bilateral

Systemic?

YES

Etiology: HIV, EBV/CMV, Adenovirus, TB, Syphilis, S. typhi, Toxoplasma, Brucella, fungal

Management: Reassurance, followup and supportive care

232

YES

Toxic?

NO

Etiology: MTB (+ atypical), Syphilis, Brucella, Actinomycosis, Norcardia, HIV, EBV, CMV, Toxoplasma

NO Management:

Abscess? YES

Management: 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)

Figure 20.7

Management: Labs: None (consider BUN/ Cr if CT needed, CBC, Blood cx) Radiology: US if unclear (or CT) Treatment: Admit, I&D + empiric antibiotics*

NO

Management: Labs: None (consider CBC, Blood cx) Radiology: US if unclear Treatment: Empiric antibiotics*

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) • Atypical MTB: Complete excision preferred or clarithromycin + Rifampin† • HIV: antiretroviral regimen

Differential diagnosis and management of lymphadenitis and lymphadenopathy.

∗Empiric bacterial therapy to cover staphylococci and streptococci → PO: cephalexin, clindamycin (an antibiotic with activity against MRSA should be selected in regions with high MRSA prevalence); IV: Cefazolin, nafcillin, clindamycin. †

Clin Infect Dis 2007;44:1057

Management: 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

Management: Labs: CBC, LFT, Blood cx, TST/ IGRA, HIV (as clinically indicated) test, other viral/ bacterial serology. Radiology: CXR Treatment: Based on etiology Consult: Consider ID

If no infectious etiology consider Oncology/ Rheumatology consult

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

Superﬁcial infection of the skin with little surrounding erythema; lesions can be papules or vesicles, superﬁcial pustules, or honeycolored crusted or bullous lesions

Folliculitis

Superﬁcial 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 inﬂamed follicles into a single inﬂammatory 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 flora.

BACTERIAL CAUSES OF SKIN AND SOFT TISSUE INFECTIONS BASED ON EXPOSURE Exposure

Pathogen

Human bites

S. aureus, Eikenella corrodens, anaerobes S. aureus, Pasteurella spp., anaerobes

Water exposure

Aeromonas spp., P. aeruginosa, Vibrio vulnificus or other GNR, Mycobacterium marinum

Soil exposure

S. aureus, S. pyogenes, many GNR, anaerobes, Nocardia spp., Actinomyces 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 inflammatory 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

P E D I AT R I C S

Cat or dog bites

234

Pediatrics

• Mild superficial 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 superficial 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 • Definition: 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, Mycoplasma hominis, Ureaplasma urealyticum

3 wk–3 mo

S. pneumoniae, viral agents (RSV, parainﬂuenza), Bordetella pertussis, Chlamydia trachomatis (2 wk–4 mo; frequently afebrile)

3 mo–5 yr∗

Viruses (RSV, parainﬂuenza, inﬂuenza, adenovirus, human metapneumovirus, rhinovirus, coronaviruses, human bocavirus, human echovirus), S. pneumoniae, nontypeable H. influenzae, 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 Presentation or Risk Factors

235

Etiologic Agents

Aspiration pneumonia

Anaerobic streptococci, Fusobacterium spp., Bacteroides spp., Prevotella melaninogenica

Eﬀusion 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 ﬁbrosis

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.

P E D I AT R I C S

• 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, influenza), recent antibiotic therapy (dose, duration, response), exposure history (TB, Chlamydia, animal contact), sick contacts, travel, daycare • Physical exam: Fever, tachypnea (most sensitive and specific sign—normal RR based on age), ↑ HR, hypoxia, cyanosis, general appearance (mental status, hydration status), ↑ WOB (retractions, flaring, grunting, accessory muscle use), pulmonary exam (crackles or rales, rhonchi, wheezing [suggests viral and atypical bacterial agents], 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 specific, 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, influenza, 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

Specific Test

• B. pertussis • C. trachomatis • C. pneumoniae • Mycoplasma spp.

Nasopharyngeal secretions for culture and PCR Conjunctival and nasopharyngeal specimens for testing by DFA or EIA Serologic titers or Chlamydia culture IgM/IgG serologies (low speciﬁcity); may consider cold agglutinins TST, IGRA, morning gastric aspirates (x3); see TB section. Urine antigen test (results are often negative unless disseminated disease is present) and serologies

• Tuberculosis • Histoplasma spp.

• Pleural fluid 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 fluid 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 infiltrates → bacterial etiology (not sensitive); diffuse bronchopneumonia pattern → M. pneumoniae and viruses (however, ≤40% of M. pneumoniae have single lobe involvement); infants with hyperinflation or interstitial process → C. trachomatis; hilar adenopathy → fungal pathogens, TB • Lateral decubitus radiography film (affected side down): Evaluate for effusion, determine if free flowing 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

Speciﬁc gravity

<1.016

>1.016

Protein (g/dL)∗∗ Fluid:serum ratio

<3.0 <0.5

>3.0 >0.5

LDH (IU)∗∗ Fluid:serum ratio

<200 <0.6

>200 >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 diﬀerential (neutrophil predominance consistent with CAP with eﬀusion; lymphocyte predominance suggests TB or malignancy). † Should collect anaerobically in heparinized syringe. ∗∗Always obtain serum for glucose, LDH, protein to compare with pleural ﬂuid levels. $ Infectious workup: Gram stain and cx, anaerobic cx, fungal stain and cx, AFB stain and cx. Consider latex agglutination studies or PCR for speciﬁc organisms if patient received antibiotics before specimen collection ∗If suspecting pancreatitis send serum and pleural ﬂuid for amylase. Pleural ﬂuid: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 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 inﬂuenza 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 >5 yrs

• Viral: Same as 3mo–2 yr 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 once PO × 1 day, max 500 mg/day followed by 5 mg/kg/day PO × 4 day, max 250 mg/day)

Aspiration pneumonia

Amoxicillin–clavulanate (80-100 mg/kg/day PO of amoxicillin component 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.

P E D I AT R I C S

Age

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 inﬂuenza if symptoms ≤ 48h • Bacterial: • Cefotaxime (150–200 mg/kg/day IV divided Q8h) ± macrolide for atypical organisms) • If S. aureus is in diﬀerential (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 inﬂuenza 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 ICU patients

IV cefotaxime + IV vancomycin ± azithromycin

Eﬀusion or empyema

IV cefotaxime + IV clindamycin, or IV cefotaxime + IV vancomycin (if higher rates of clindamycin-resistant S. aureus in community or patient is toxic appearing)

Aspiration pneumonia

IV clindamycin or IV ampicillin–sulbactam; if child is prone to aspiration or has CLD, consider broader coverage (eg, GNR and Pseudomonas coverage)

Immunocompromised

Broad-spectrum gram-negative and gram-positive coverage: IV 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)

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• Patients with moderate-large pleural effusions or empyema: • Pleural fluid 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 fibrinolytic 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 identified; 7–10 days total for uncomplicated CAP with transition from IV to PO and discharge when clinically improved and able to tolerate PO. Presence 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 ﬂuid 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

URINARY TRACT INFECTION • Definition: 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 flow (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

P E D I AT R I C S

• Definition: 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, influenza, parainfluenza) • Risk factors: ICU care, mechanical ventilation, artificial airway, indwelling catheters, broad-spectrum antibiotics, postoperative patients • Clinical features: Fever, cough, ↑ work of breathing, ↓ oxygen saturations, ↑ ventilator support, 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 specific 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) • Definitive 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

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ETIOLOGIC AGENTS FOR URINARY TRACT INFECTIONS AND OTHER RELATED INFECTIONS Disorder

Etiologic agent

UTI

• E. coli: 70%–90% of all UTIs and >90% of ﬁrst UTIs in outpatients • Other GNR (more common with underlying urinary tract abnormalities and h/o multiple previous UTI): Klebsiella, Proteus, 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 >3 days ↑ risk signiﬁcantly)

• GNR, yeast, S. aureus

Urethritis

• Chlamydia trachomatis, N. gonorrhea, Mycoplasma genitalium, HSV

Hemorrhagic cystitis

• E. coli, adenovirus types 11 and 21

• Diagnosis • History: H&P nonspecific; 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 continence, 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% specific; Bag: 76% sensitive/84% specific), nitrite reaction (53% sensitive/98% specific), microscopic exam for WBC (73% sensitive/81% specific)bacteria (81% sensitive/83% specific). 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 contaminant → 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)

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INTERPRETATION OF URINE CULTURE RESULTS∗ Method of Collection

Colony Count

Probability of Infection

Suprapubic aspiration

Any GNR GPC >1000

>99%

Catheterization

>100,000 10,000–100,000 1000–10,000 <1000

95% Infection likely Suspicious; repeat culture Infection unlikely

>10,000 >100,000 in three specimens >100,000 in two specimens >100,000 in one specimen 10,000–100,000

Infection likely 95% 90% 80% Suspicious, especially if symptomatic; repeat culture Infection unlikely

Clean Catch Boy Girl

<10,000

Data from Textbook of Pediatric Infectious Diseases, 6th ed. 2009:559. ∗1%–2% of older infants and children have asymptomatic bacteriuria (with no clinical signiﬁcance)

P E D I AT R I C S

• 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 hospitalization have equivalent outcome with oral vs. IV therapy • Empiric oral therapy: Cefixime (8mg/kg/day PO Q12h; max, 400mg/day), Cefpodoxime 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 first-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 inflammation caused by reflux of contaminated urine (controversial) • Common agents: Trimethoprim–sulfamethoxazole (> 6 mo age), amoxicillin (neonates), nitrofurantoin

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IMAGING MODALITIES FOR CHILDREN WITH URINARY TRACT INFECTION OR PYELONEPHRITIS Imaging Modality

Pros

Cons

Renal US

• Most useful modality for imaging kidneys, ureters, bladder; deﬁnes renal structure; evaluates for dilatation in collecting system

• Does not provide functional information or detect renal scarring

VCUG and RNC

• Deﬁnes the presence and grade of VUR; VCUG detects PUV in male infants

• VCUG has increased radiation exposure (VCUG 10-fold compared with RNC), RNC will not detect PUV in male infants

Technetium-99m DMSA scan∗

• Assessment of renal function and scarring

• Positive ﬁndings may not change management

∗ DMSA scan should be done if identiﬁcation 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 Boys 2–12 yr

RUS; if RUS is abnormal or the patient has any risk factor (sibling with VUR, ↓ renal function, proteinuria, HTN) also obtain VCUG

First UTI

Girls 6–12 yr

RUS

Consider based on clinical ﬁndings 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 • Definitions • Aseptic meningitis: Inflammation of meninges with no identification 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

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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 ﬂora organisms, GNRs (including Pseudomonas aeruginosa) Animal bites: Pasteurella multocida CSF leak: S. pneumoniae, Hib, GNRs

Immunodeﬁciency

Terminal complement deﬁciency: 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 ﬁstula, 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

P E D I AT R I C S

• Aseptic Meningitis • Common pathogens: Enteroviruses, arboviruses, HSV, Lyme disease, partially treated bacterial meningitis • Uncommon pathogens: M. tuberculosis, fungi, HIV, adenoviruses, influenza, parainfluenza, EBV, CMV, VZV, mumps, measles, lymphocytic choriomeningitis, Bartonella spp., spirochetes, Leptospira spp., Brucella spp., Mycoplasma spp., rickettsia, parasites, parameningeal 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 flexed to 90° + if passive extension of knee meets resistance) and Brudzinski’s sign (patient supine and limbs extended + if passive neck flexion results in involuntary hip or knee flexion), 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 nonspecific maculopapular rash very similar to viral exanthem)

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• 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 deficit 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, influenza or adenoviral screens

CEREBROSPINAL FLUID ANALYSIS WBC/ CSF Finding mm3

PMN Protein Cells (%) (mg/dL)

Glucose (mg/dL)

Preterm newborn

<25

57

65–150

25–65

Term newborn

<22

60

20–170

35–120

0

20–40

40–80

WNL <100

WNL‡

Healthy child <7 Viral

<1000 20–40∗

¢ Smear ¢ Culture Additional (%) (%) Considerations

HSV: rare; enterovirus: 20-40%

Enterovirus or HSV PCR, arboviral serologies

Bacterial

>1000† >85–95

>100–150

0–<40

>85

>95

Partially treated bacterial

>1000 >80

60–150

<40

40-60

<90

Lyme (Borrelia burgdorferi)

<500

<10 (>90% monos)

<100

WNL

Fungal

<500

<10–20

>100-200

<40

<40

>30∗∗

Histoplasma and Cryptococcus 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

Consider latex agglutination studies¶ B. burgdorferi antibodies

∗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 speciﬁcity ∗∗Better isolation rates for Candida spp. compared with Histoplasma and Cryptococcus

• Management • Bacterial Meningitis • Fluid resuscitation, scheduled pain control, antiemetic medications.

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• 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 first 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 findings, 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 Ampicillin + cefotaxime or ampicillin + gentamicin • Add vancomycin for infants >1 mo or if Gram stain is consistent with S. pneumoniae • Add acyclovir if HSV is on diﬀerential diagnosis (or if HSV PCR pending) • Consider broader spectrum of coverage for former NICU infants: Vancomycin + 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 or VPS

Cefotaxime or ceftriaxone + vancomycin (dosages as above) • 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)

P E D I AT R I C S

Neonatal (0–2 mo)

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• 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 ciprofloxacin) • Prognosis • Overall mortality: 5% in developed countries; 8% in developing countries • Neurologic sequelae: Hearing loss (11%), mental retardation (4%), seizures (4%), paresis 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 flora (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

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• Diagnosis and Management • History and physical exam: Fever, catheter malfunction (↓ or unidirectional flow), 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, nonspecific signs (apnea, bradycardia, hypotension) may be the only clinical symptoms.

TYPES OF CENTRAL VENOUS CATHETER RELATED INFECTIONS Definition

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 ﬂuid in the subcutaneous pocket of a totally implanted venous access device with or without overlying erythema, induration, tenderness, drainage

Catheter-related bloodstream infection

≥1 positive blood culture (bacteremia or fungemia) drawn from an intravascular catheter or a peripheral venipuncture in the presence of an intravascular catheter, signs and symptoms consistent with infection (ie, fever, apnea or bradycardia, hypotension, inﬂammation 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 >ﬁvefold CFU isolated from the blood drawn from CVC than from blood drawn peripherally • 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.

P E D I AT R I C S

Term

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

Tunnel infection Port abscess

Septic thrombosis Endocarditis Thrombophlebitis†,‡

ID consult, remove CVC and treat with antibiotics or antifungals

Uncomplicated

Candida spp, P.aeruginosa, S.aureus, etc§

CONS

Other microorganism

ID consult, may retain CVC and treat with antibiotics, consider antibiotic lock therapy

ID consult, catheter removal and treat with antibiotics

If clinical deterioration, persistent or relapsing 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 “contaminants” 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)

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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 ﬁrst 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, Stenotrophomonas spp., and Acinetobacter baumannii.

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

P E D I AT R I C S

• Complications • Death: Fatality rates from 10%–50%; higher in chronically ill patients, neonates, presence of malignancy, immunodeficiency. • 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. • 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.

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: Ccr =

Ucr × V Pcr

Ccr = creatinine clearance (mL/min) Ucr = urine creatinine (mg/mL) V = urine flow rate (mL/min, obtained by dividing total urine volume by total collection time in minutes) Pcr = plasma creatinine (mg/mL) • The resulting Ccr (~GFR) is standardized to BSA: Standardized Ccr = Standardized

Ccr × 1.73 BSA

Ccr = creatinine clearance (mL/min/1.73 m2) 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 predefined 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. GFR (mL/min/1.73 m2) =

k × Height (cm) 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).

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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 66 ± 25

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 office or clinic but normotensive outside clinical setting; ambulatory BP monitoring is helpful to confirm. • 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.

P E D I AT R I C S

2–8 wk

252

Pediatrics Sustained BP >95% for sex, age, height∗

Complete History • Neonatal history • Family history • Dietary history • Risk factors: Smoking, EtOH use, drug use∗ • Symptomatology∗ • ROS: Sleep, exercise, stress, daily activities

Complete Physical Exam • 4-ext BP • HT,WT,BMI • Diagnostic clues: Skin lesions,cardiac murmurs or gallops, abdominal masses, vascular bruits, retinal exam • ± Ambulatory BP 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 finding 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)

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EVALUATION OF RED URINE

UA dipstick for hemoglobin (blood) Urine microscopy for RBCs, casts

Foods (blackberries, beets, rhubarb), red food coloring, medications (levodopa, rifampin), metabolites (porphyrins†, urates or uric acid crystals‡, urobilin)

(+) Dipstick (+) RBCs

(+) Dipstick (-) RBCs

(-) Dipstick (-) RBCs

Hematuria

Myoglobinuria, hemoglobinuria (-) RBC casts

Glomerular or lower urinary tract pathology

(+) RBC casts Glomerulonephritis

Figure 21-2 Evaluation of red urine. ∗Colorless when first 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 with casts or protein, or UProt / UCr > 0.2

BP, hearing test, serum creatinine and C3/C4†, renal US with Doppler

FHx (-) for progressive renal disease, urine (-) for casts or protein, and UProt / UCr < 0.2

Check UProt /UCr ratio and

All WNL

serum creatinine

Normal creatinine

Pediatric nephrology consult, ± renal biopsy‡

UCa /UCr

(+) FHx of MH

UCa / UCr, (–) FH of MH

24-hr urine for calcium and creatinine, renal US, consider evaluation for stone

Familial microscopic hematuria

Isolated microscopic hematuria

Possible hypercalciuria

UCa /UCr

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 Contraindications” at www.AccessPediatrics.com. §May consider obtaining UA of family in evaluation of familial microscopic hematuria. (Pediatrics 1998;102(4);e42.)

P E D I AT R I C S

Abnormal creatinine

Any of above abnormal

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• Infection: Bacterial, viral, TB • Tumors: Wilms, leukemia, lymphoma • Reflex 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 Normal Component Value

Differential Diagnosis of Abnormalities

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 acidic: RTA, excess acid load (TPN)

Speciﬁc gravity

1.010–1.025 Low: Diabetes insipidus, water intoxication High: Dehydration, SIADH

Notes and Limitations

• Useful in w/u of stones (alkaline → Proteus spp.) and RTAs • Unreliable if excess urine is run over UA strip • Each thousandth of SG above 1.000 ~30 points of osmoles (eg, SG 1.020 ~ Uosm 600) • Large molecules (eg, glucose, proteins, radiocontrast dye, may elevate speciﬁc gravity falsely) • Infants <3 mo cannot concentrate urine well → SG unreliable (continued on next page)

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Normal Component Value

Differential Diagnosis of Abnormalities

255

Notes and Limitations

Negative

Glomerular dysfunction • Dipstick detects albumin only (eg, does not detect immuno(GN, nephrotic syndrome, nephritic syndrome), diabetic globulins) nephropathy (see proteinuria • Positive for values >300–500 in this chapter) mg/dL; not sensitive for microalbuminuria • 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: DM, HHNS Renal glucosuria: Proximal tubular dysfunction

• Occurs at plasma levels >180 mg/dL in patients with normal renal function • False-negative results: Ketones, high SG, elevated ascorbic acid • False-positive results: Oxidizing agents (bleach)

Hematuria

Negative

GN, nephrolithiasis, urinary tract malignancy or trauma

• Detects intact RBCs, hemoglobin, myoglobin • 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 esterase

Negative

Infectious pyuria • False-positive results: Drugs or Noninfectious (sterile) pyuria: foods rendering urine red • False-negative results: AntibiInterstitial nephritis, renal otics (gentamicin, cephalexin, TB, nephrolithiasis (see table tetracycline), proteinuria, below) glucosuria (continued on next page)

P E D I AT R I C S

Protein

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Pediatrics

Normal Component Value

Differential Diagnosis of Abnormalities

Nitrite

Negative

Infection with Enterobacteriaceae (convert nitrate to nitrite)

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)

Notes and Limitations • False-positive results: Vaginal secretions, phenazopyridine, red dyes or other chromogens, 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

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, Kawasaki’s disease (culturenegative pyuria), urethritis, 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: Inﬁltrative diseases (eg, chronic tubulointerstitial disease)

• Clinical signiﬁcance of eosinophils in urine unclear (Clin Nephrol 1994;41:163)

Epithelial cells

Negative

Tubular (ATN) or transitional (bladder, ureters)

• No signiﬁcance in isolation; epithelial cells noted on a aspirated or catheterized urine sample my indicate contamination (continued on next page)

Nephrology

Normal Component Value Casts

Negative

Differential Diagnosis of Abnormalities

257

Notes and Limitations

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 Description

Etiologies

Glomerular

Filtration barrier disruption → loss of albumin

Nephritic syndrome, nephrotic syndrome, HTN, DM, HUS

Tubulointerstitial

↓ Resorption of ﬁltered proteins → loss of globulins

Inherited: Cystinosis, Lowe syndrome Acquired: ATN, AIN, heavy metal poisoning, antibiotic induced

Overﬂow

↑ Production of ﬁltered proteins

Myoglobinuria, AML

Isolated

Benign by deﬁnition: Mild proteinuria, nl renal fx, nl urine sediment, nl C3/C4 levels, no h/o renal disease

Functional (fever, exercise, stress) Orthostatic (only when upright) Idiopathic (transient or persistent)

Quantification 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

P E D I AT R I C S

Category

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; confirmed with bedtime vs. first morning void PROTEINURIA DETECTED ON URINALYSIS Repeat U/A

Negative

Positive

• False-positive • Benign isolated proteinuria (fever, stress, exercise)

Trace

Repeat UA (first morning void) in 1 yr

Both WNL Orthostatic proteinuria

1+ to 3+

4+

• UPr: UCr ratio (compare first AM void with previous PM void to r/o orthostatic proteinuria) • UA and microscopy

Evaluate for nephrotic syndrome

Either is abnormal Idiopathic proteinuria (<1 g/d and all other tests WNL): Close follow-up and reevaluation over next 1–2 mo

• Lytes, BUN, creatinine, albumin, cholesterol, (consider hepatitis B/C serologies, HIV, ANA, C3/C4 levels) • Urine culture • Renal US • 24-h urine collection for protein RENAL BIOPSY* IF: • HTN • Hematuria • Decreased C3/C4 • Decreased GFR • Hypoalbuminemia† • Proteinuria >1 g/d

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 insufficiency, ± proteinuria • Nephrotic syndrome: Nephrotic range proteinuria, hypoalbuminemia, edema, hyperlipidemia, ± hematuria

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OVERVIEW OF NEPHRITIC AND NEPHROTIC SYNDROMES Nephritic Syndromes

Age

Labs

Biopsy

Acute Postinfectious GN • 1–2 wk after streptococcal pharyngitis (serotype 19) or 3–6 wk after skin infection (serotype 49) • 90% nephritic; 70% HTN • HTN/proteinuria resolves by 6 wk, microhematuria by 2 yr • Complications: ARF, HTN (60%), HTN encephalopathy (10%) • Tx: Supportive • Px: 95% recovery, 5% RPGN

5–12 yr

↓ C3 (nl by 8 wk) Normal C4 ⊕ ASO

LM: Mesangial proliferation

IgA Nephropathy (Berger Nephropathy) 15–35 yr • Hematuria ± proteinuria 1–2 d after viral infection → nephritic syndrome, HTN → resolves ~1 wk • Tx: Supportive • Px: 20%–40% → ESRD (all patients need adult follow-up)

Normal C3 ↑ Serum IgA (50%)

IF: IgA mesangial deposits

5–15 yr Henoch Schonlein Purpura • 1–3 wk post-URI → abdominal pain, palpable purpura, arthralgias, gross hematuria ± nephritic syndrome • Px: <1% develop persistent renal disease • Tx: Supportive, NSAIDs for arthralgia, 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

Normal C3 ↑ Serum IgA ↑ ESR

IF: Similar to IgA nephropathy but deposits also found in capillaries of skin, intestines

Nl C3/C4 UA: Oval fat bodies, ± hematuria

EM: Fusion of foot processes

IF: Granular patUA: RBC casts, PMNs, tern of diﬀuse IgG/C3 deposits proteinuria in subepithelial part of GBM and mesangium Biopsy if: EM: Glomeruli “lumpy-bumpy” ARF, nephrotic presentation, normal C3, and enlarged with subepitheor any of following lial deposits of beyond 2 months: Ig and C3) gross hematuria, proteinuria, ↓ C3, renal dysfunction

P E D I AT R I C S

Nephrotic Syndromes 2–6 yr Minimal Change Disease • HTN <10%; hematuria 10%–20% (75%– 80%) • Prognosis: Very good, relapse common 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)

(continued on next page)

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Pediatrics

Nephritic Syndromes

Age

Labs

Biopsy

Focal Segmental Glomerulosclerosis • HTN 20%; hematuria 60%–80% • Px: CKD in 50%–80% at 10 yr • Tx: Only 1/3 respond to steroids

2–10 yr (10%– 15%)

Nl C3/C4 UA: Oval fat bodies, hematuria

LM: Mesangial proliferation and segmental scarring

Membranoproliferative GN • HTN frequent; hematuria 80% • Prognosis: ESRD common at 10 yr • Tx: Variable steroid response

5–15 yr (10%)

↓ C3/C4

EM: Thickened, split “tram tracking” of basement membrane, subendothelial C3 deposits

PRIMARY AND SECONDARY NEPHRITIC AND NEPHROTIC SYNDROMES Primary Etiology

Nephritic Presentations

Nephrotic Presentations

Renal (Primary Diseases)

RPGN IgA nephropathy Immune complex (ANCAassociated, anti-GBM) MPGN

MCD FSGS Membranous GN (NSAIDS) MPGN (phenytoin) Mesangioproliferative GN IgA nephropathy Congenital nephrotic syndrome

Systemic (Secondary Diseases)

PIGN HSP SLE Endocarditis (chronic bacteremia) Cryoglobulinemia Goodpasture’s syndrome ANCA-associated (Wegener’s, Churg Strauss, microscopic polyangiitis)

SLE HSP Heavy metal toxicity (lead, mercury) Infection: Syphilis, HIV, Chronic HBV/ HCV, malaria Diabetes mellitus Lymphoma, myeloma Sickle cell disease

Approach to Workup Nephritic Syndrome • History, UA w/micro, blood culture, ASO, ANCA, C3/C4, AntiDNAse B, ANA, anti-GBM, renal biopsy with immunofluorescence. (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 significant 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).

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• Biopsy: Hematuria, HTN, renal insufficiency, 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

Complications of Nephrotic Syndrome • Edema • Malnutrition (protein loss) • Electrolyte disturbances

P E D I AT R I C S

ACEI/ARB • Used in persistent proteinuria; reduces proteinuria by 50%, monitor for increased Cr, hyperkalemia Steroid Responsive • Prednisone 60 mg/m2/d or 2 mg/kg/d divided Qday/BID (max, 80 mg/d) for 4–6 wk 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 defined 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), fluid 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

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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 flow 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: Refluxes into ureter only; no dilation • Grade II: Refluxes into ureter and pelvis; no dilation • Moderate • Grade III: Refluxes into ureter and pelvis; mild hydronephrosis (ureteral and calyceal dilation) • Grade IV: Refluxes into ureter and pelvis; moderate hydronephrosis • Severe • Grade V: Refluxes 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 confirmed VUR. • VCUG: Provides functional evaluation of ureterovesicular junction (evaluation of reflux). A normal VCUG does not rule out anatomic abnormalities. A VCUG should be performed in the following patients to r/o VUR:

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• Any boy with a first UTI • Girls younger than age 3 yr with a first 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 reflux 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)

P E D I AT R I C S

• Sudden deterioration in renal function (GFR) over hours to days leading to the inability to maintain electrolyte and fluid 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) • 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 classification of AKI (Pediatric modification of adult RIFLE criteria to standardize definition of acute kidney injury) (Kidney Int 2007;71:1028). • Risk: ↑ in serum creatinine (SCr) by 1.5X or ↓ glomerular filtration 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

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ETIOLOGIES OF ACUTE KIDNEY INJURY Etiology

Urine Characteristics

Prerenal Decreased intravascular volume: Dehydration, sepsis or systemic vasodilation, GI losses, nephrotic syndrome

Bland sediment, hyaline casts, ﬁne 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 (aminoglycosides, amphotericin, myoglobinuria, hemoglobinuria, ethylene glycol, contrast media)

Pigmented (brown) granular casts, RBCs or protein in UA

Interstitial Disease (interstitial nephritis): Drugs (penicillins, cephalosporins, sulfas, NSAIDS), pyelonephritis, protein deposition disorders

WBCs, WBC casts (urine eosinophils, rash, arthralgias speciﬁc to drug allergy)

Glomerulonephritis

RBC casts, RBCs, protein

Postrenal Urinary tract obstruction: UPJ obstruction, ureteral obstruction (nephrolithiasis), PUV, severe bladder neck dysfunction (neurogenic bladder, anticholinergics)

Bland sediment, hyaline casts

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 fluid losses or drug or toxin exposure.

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265

• Laboratory (before fluid 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. [FEurea = (U Urea × Serum Cr) × 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) → fluid 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 fluid 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, fluid 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

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 (hyperfiltration, microalbuminuria) (Kidney Int 2006;69(1):184).

CHRONIC KIDNEY DISEASE • Definition: 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).

P E D I AT R I C S

• 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 hyponatremia 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)

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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 (Congenital Causes)

Age > 5 yr (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 fixed daily intake once in fluid 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 (Dialyvite, 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.

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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

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)

P E D I AT R I C S

• 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 identified after ruling out prerenal and postrenal causes • Associated with nephritis, vasculitis, nephritic syndrome, or systemic disease • Difficulty 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 • Significant proteinuria • Persistently low C3 levels and suspected SLE or MPGN • FH of nephritis • Hearing deficit • Any associated renal insufficiency • 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) • 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 insufficiency • Renal allograft : • Delayed autograft function • Recurrence of disease • Suspected rejection • Complication of therapy

CHAPTER 22

Neurology NEUROLOGIC EXAM Observation • Developmental stage, social interaction • Gross and fine 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 ﬁelds, 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 reﬂex

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 ﬁnger 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 SR(R3)

SR(R3)

LR(R6) IR(R3)

IO(R3) MR(R3)

IR(R3) RIGHT

IO(L3) Nose

SO(R4)

SR(L3)

MR(L3)

269

SR(L3) LR(L6)

SO(L4)

IR(L3) LEFT

IR(L3)

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 Reflexes • 4+: Hyperreflexia with clonus • 3+: Hyperreflexia with spread across joint • 2+: Normal

• 1+: Hyporeflexia • 0: No movement

Motor • Muscle bulk and tone • Assess pronator drift for subtle weakness • Muscle strength: • 5/5: Full strength • 4/5: Full ROM against light resistance

• 3/5: Full ROM against gravity only • 2/5: Full ROM in horizontal plane (gravity eliminated) • 1/5: Trace (“flicker”) of movement • 0/5: No movement

Coordination

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 Reflexes Maneuver

Description

Babinski sign

Upgoing plantar response

Significance Localizes to corticospinal tract

Hoﬀman sign

Flicking of patient’s second or third ﬁnger causes contraction of the ipsilateral thumb

Localizes to corticospinal tract at or above cervical spinal cord

Abdominal reﬂex

Stroke abdomen toward umbilicus; lack of brisk contraction of abdominal muscles toward stroke is a ⊕ test

Localizes to the corticospinal tract at or above thoracic spinal cord

Cremasteric reﬂex

Stroke inner thigh caudal to rostral, resulting in contraction of cremasteric muscle

Localizes to the corticospinal tract at or above lumbar spinal cord (continued on next page)

P E D I AT R I C S

• Cerebellum and basal ganglia testing • Finger to nose, heel to shin, rapid alternating movements • Assess for head tilt or tremor, fluidity 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)

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Pediatrics

Maneuver Primitive reﬂexes • Glabellar • Snout • Palmomental

Description

Significance Suggest frontal lobe damage (except in neonates or infants)

Percuss forehead, and eye blink does not extinguish Percuss lips in the midline, and lips pucker 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 Supraclavicular nerves

C3 Post.

C4

Mid. Ant.

T2

Axillary nerve

Medial cutaneous nerve of forearm

Lateral thoracic rami

Lateral cutaneous nerve of arm (branch of radial nerve)

Lateral cutaneous nerve of forearm

Anterior thoracic rami

Medial cutaneous nerve of arm

C5

T3

X

T4 T5 T6 T7 T8 T9 T10 T11 T12 L1

T2

T1 C6

L1

* Radial

C6

† L2

Median

C8

Ulnar Lateral femoral cutaneous Obturator

C7 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 Nerve root

271

Peripheral nerve

Great occipital C2

Lesser occipital Great auricular

C3

Posterior rami of cervical nerves C4

Supraclavicular

T2

T1 C6

Lateral cutaneous nerve of arm Posterior cutaneous nerve of arm Medial cutaneous nerve of arm Lateral cutaneous nerve of forearm Posterior cutaneous nerve of forearm

X

L2

Medial cutaneous nerve of forearm Posterior lumbar rami Posterior sacral rami

S3 S4 S5

C6

Lateral thoracic

T2

Posterior thoracic rami

C5

rami

Axillary

T3 T4 T5 T6 T7 T8 T9 T10 T11 T12 L1

Radial Median Ulnar

C7

C8

L 3

Lateral femoral cutaneous Obturator Anterior femoral cutaneous

S2

Posterior femoral cutaneous Lateral cutaneous nerve of calf = Iliohypogastric

L5

Superficial peroneal

L4

Saphenous Sural

Calcaneal S1

Lateral plantar Medial plantar

B Figure 22-2 (Continued )

Primitive Reflexes NORMAL INFANT REFLEXES THAT APPEAR AT BIRTH Reflex

Description

Disappearance

Moro (startle)

Lift head 30 degrees and allow to fall to neutral Positive: Arm extension and abduction → arm adduction

1–3 mo

(continued on next page)

P E D I AT R I C S

X

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Pediatrics

Reflex

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. Positive: Ipsilateral arm/leg extension, contralateral arm and leg ﬂexion (“fencing posture”); normal infant tries to break reﬂex

5–6 mo

Babinski

Stroke lateral border of sole from heel to great toe Positive: Great toe dorsiﬂexion, fanning of other toes

1–2 yr

CLINICAL DISCRIMINATION OF UPPER AND LOWER MOTOR NEURON LESIONS UMN Lesion

LMN Lesion

Hyperreﬂexia (± Hoﬀman, Babinski signs) Hyporeﬂexia 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 arm up to 90°

C5, C6

Axillary nerve

Deltoid

Flexion of supinated forearm

C5, C6

Musculocutaneous

Biceps, brachialis

Extension of forearm

C6, C7, C8

Radial

Triceps

Extension (radial) of wrist

C6

Radial

Extensor carpi radialis longus

Adduction of ﬂexed arm

C6, C7, C8

Brachial plexus

Latissimus dorsi

Supination of forearm

C6, C7

Posterior interosseous

Supinator (continued on next page)

Action tested

Roots∗

Nerves

Muscles

Extension of proximal phalanges

C7, C8

Posterior interosseous

Extensor digitorum

Extension of wrist (ulnar side)

C7, C8

Posterior interosseous

Extensor carpi ulnaris

Pronation of forearm

C6, C7

Median nerve

Pronator teres

Radial ﬂexion of wrist

C6, C7

Median nerve

Flexor carpi radialis

Opposition of thumb against ﬁfth ﬁnger

C8, T1

Median nerve

Opponens pollicis

Abduction and adduction of ﬁngers

C8, T1

Ulnar

Interossei

Hip ﬂexion from semiﬂexed position

L1, L2, L3

Femoral

Iliopsoas

Hip ﬂexion from externally rotated position

L2, L3

Femoral

Sartorius

Crural

L2, L3, L4

Femoral

Quadriceps femoris

Adduction of thigh

L2, L3, L4

Obturator

Adductor longus, magnus, brevis

Abduction and internal rotation of thigh

L4, L5, S1

Superior gluteal

Gluteus medius

Extension of thigh

L5, S1, S2

Inferior gluteal

Gluteus maximus

Flexion of knee

L5, S1, S2

Sciatic

Biceps femoris, semitendinosus, semimembranosus

Dorsiﬂexion of foot (medial)

L4, L5

Peroneal (deep)

Anterior tibial

Dorsiﬂexion of great toe

L5, S1

Peroneal (deep)

Extensor hallucis longus

Eversion of foot

L5, S1

Peroneal (superﬁcial)

Peroneus longus and brevis

Plantar ﬂexion of foot

S1, S2

Tibial

Gastrocnemius, soleus

Inversion of foot

L4, L5

Tibial

Tibialis posterior

Contraction of anal sphincter

S2, S3, S4

Pudendal

Perineal muscles

∗ Predominant root(s) supplying a particular muscle are indicated in bold italic type.

P E D I AT R I C S

Extension of knee

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Pediatrics

NEUROIMAGING BASICS Modality Best For Examining Advantages

Disadvantages

US

Ventricles and gross brain Can be done at bedside structure of neonates Quick with open fontanelles No radiation TCD for sickle cell disease Relatively inexpensive

Poor resolution

CT

Intracranial blood or calciﬁcations Cranial bone integrity

Quick Able to be used if implantable device is present and MRI is contraindicated Relatively inexpensive

Poorly deﬁnes soft tissues Poor visualization of posterior fossa Radiation exposure

CTA

Intracranial arterial system

Quick Inexpensive

Radiation exposure May cause renal injury from contrast Possible iodine allergy

MRI

Brain parenchyma

Best deﬁnition of soft tissues Better resolution of structures Best for evaluating posterior fossa No radiation

Requires time to obtain images Slight risk of irreversible renal scarring (primarily in those with preexisting renal disease) May require sedation More expensive than CT

MRA

Intracranial arterial system, carotids, basilar arterial system Vascular malformations

No contrast necessary No radiation

Requires more time to obtain images More expensive than CT

MRV

Intracranial venous system (eg, r/o sinous venous thrombosis) Vascular malformations

No radiation

Requires more time to obtain images More expensive than CT

MRS

Suspected metabolic d/o No radiation Evaluation of neonatal HIE Noninvasive biochemical tumor typing (via assessment of molecular composition and biochemical changes in brain tissue)

Requires specialized neuroradiologist interpretation

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

T2

Dark

Very bright

Intermediate

Dark

Very dark

See below; depends on chronicity

COMMON MRI SEQUENCES AND POTENTIAL APPLICATIONS T1

T2

Flair

DWI

ADC

GRE/FFE SWI

Structure and anatomy (gray matter is darker, white matter is brighter)

Pathology (white matter is darker, gray matter is brighter)

Pathology (pathology causing any parenchymal edema is bright)

Acute ischemia (ischemia is bright within 30 min)

Acute ischemia (ADC is dark where DWI is bright if true ischemia is present and not artifact)

Blood (blood is dark)

Microhemorrhages (blood is dark)

EVALUATION OF INTRACRANIAL HEMORRHAGE USING MRI Acute (6 h–day 3)

Early Subacute (day 3–day 7)

Late Subacute (1 wk–1 mo)

Chronic (months–years)

T1

Isodense or dark

Bright

Bright

Dark

T2

Very dark

Dark

Bright

Dark

SEIZURES Practice Parameters • Treatment of a child with a first unprovoked seizure: Neurology 2003;60:166 • Evaluating a first nonfebrile seizure in a child: Neurology 2000;55:616 • The neurodiagnostic evaluation of a child with a first simple febrile seizure: Pediatrics 1996;97(5):769

CLINICAL SEIZURE CLASSIFICATION Type

Subtype

Typical Semiology

Simple partial

(Variable)

Manifestations depend on speciﬁc area of brain involved. Consciousness preserved (unlike complex partial).

Complex partial

Frontal

Hypermotor, brief, bizarre, contralateral eye deviation, rapid return to baseline

Temporal

Olfactory aura, quiet, staring, oromotor automatisms, postictal obtundation

Parietal

Sensory phenomenon with or without motor manifestations

Secondarily generalized

Occipital

Poorly formed visual phenomenon, ipsilateral eye deviation

Rolandic

Initial sensory changes in mouth, tongue, face; then speech arrest and facial clonic activity followed by secondary generalization Contralateral head and eye deviation as seizure generalizes

(continued on next page)

P E D I AT R I C S

Focal (Partial) Seizures

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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, ﬂexion, 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 spasm

Flexion, extension, or mixed ﬂexion and extension of axial and proximal muscles, which is brieﬂy 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 difficult 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 first • ~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

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277

• Motor and DTRs: Asymmetries of tone, movement, and reflexes • 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 findings, 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 first 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 first-time seizure and the patient has returned to baseline: Discharge home, seizure precautions (including no driving for teens), seizure first 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

EPILEPSY CLASSIFICATION SCHEME EEG

MRI/Labs Symptomatic (known cause)

Idiopathic

Cryptogenic

Generalized

Abnormal MRI or labs (genetic abnormality, metabolic disease) Diﬃcult to control Eg, lissencephaly

Juvenile myoclonic epilepsy Absence epilepsy

Normal MRI and labs Usually have developmental delay, MR, abnormal exam

Localization-related

Abnormal MRI May be surgically curable Eg, mesial temporal sclerosis

Rolandic epilepsy

Normal MRI and labs Localizable Focus on EEG

P E D I AT R I C S

• 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 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

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Epilepsy Classification Scheme • Based on etiology and seizure type • Etiology • Symptomatic: Confirmed underlying structural abnormality visible on imaging • Idiopathic: Presumed or confirmed genetic cause (ion channelopathy, or familial epilepsy syndrome) • Cryptogenic: No confirmed structural or genetic etiology (including chromosomal disorder or IEM) • Seizure type • Localization related (focal or partial seizures) • Generalized • Classification: Symptomatic localization related epilepsy, idiopathic generalized epilepsy, cryptogenic localization related epilepsy, etc.

COMMON EPILEPSY SYNDROMES Epilepsy Age of Onset Clinical Syndrome and Prognosis Characteristics EEG Pattern

Treatment Options

West Syndrome

Peak, 4–6 mo; 90% before 12 mo Prognosis: Generally poor (cryptogenic generally better than symptomatic)

Triad of: infantile spasms, developmental delay, hypsarrhythmia on EEG

Hypsarrhythmia

• ACTH • Lamotrigine, levetiracetam, felbamate, tiagabine, VPA, and topiramate have been tried with some evidence • Vigabatrin, especially in patients with tuberous sclerosis

Benign childhood epilepsy with centrotemporal spikes (benign Rolandic epilepsy, BRE)

Typical is 5–10 yr

Nocturnal tonic clonic seizures arising from the lower rolandic area of cortex, Daytime with facial twitching, preservation of consciousness, excessive pooling of saliva, and tonic or tonic-clonic activity of face

Spikes and sharp waves in mid temporal and central region and may be unilateral or bilateral

• Oxcarbazepine often ﬁrst choice • May use any drug used in partial onset epilepsy • Benign course, and not all physicians treat with AED

Absence epilepsy

Childhood form: 5–12 yr Juvenile form: Adolescence Prognosis: Majority remit by adulthood

Absence seizures; up to several hundred per day

3-Hz spike and wave activity that may be induced with hyperventilation

• Ethosuximide • Lamotrigine • VPA

Juvenile myoclonic epilepsy

12–18 yr Prognosis: Majority lifelong; good response to medications

Myoclonic jerks, generalized tonicclonic seizures, and absence seizures

Diﬀuse, bilateral, and symmetric spike and poly spike and wave 4–6 Hz activity

• VPA • Lamotrigine • Levetiracetam

Prognosis: Majority fully resolved by adolescence

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279

Epilepsy Age of Onset Clinical Syndrome and Prognosis Characteristics EEG Pattern

Treatment Options

LennoxGastaut syndrome

Childhood Prognosis: poor

Mixed seizure disorder with tonic, tonic-clonic, myoclonic, atypical absence, and/or head drops; often accompanied by mental retardation

Slow spike and wave pattern (1.5–2.5 Hz) on a slow background

• Very refractory to treatment • Most common AEDs used are VPA, phenytoin, felbamate, lamotrigine, topiramate, and benzodiazepines • Ketogenic diet

LandauKleﬀner syndrome

<10 yr Prognosis: Variable (earlier onset better)

Acquired aphasia and epileptiform discharges from temporal and parietal regions

No speciﬁc pattern; may have spikes, sharp waves, and spike and wave activity in temporal and parietal regions

• VPA and lamotrigine • High-dose diazepam • Steroids are sometimes used

Treatment of Status Epilepticus • See Chapter 9 (critical care).

Treatment of Epilepsy ANTIEPILEPTIC MEDICATIONS Typical Therapeutic Range mcg/mL

Adverse Effects† Pharmacokinetics Common Serious (metabolism, But half-life in hours, Rare other)

Drug∗

Target Use

Carbamazepine

Na

LRE

5–10

8–12

Hepatic, 8–24, auto induction

Hypona- Leukotremia penia, hepatitis

Phenytoin/ Na fosphenytoin

LRE

5

10–20

Hepatic, 10–30, nonlinear elimination

Gingival hyperplasia

Ethosuximide

Ca

ABS

10–15

40–100

Hepatic, 30–40

GI upset, None headache

Felbamate

Na, LRE, GABAR GE

15

20–100

Hepatic, 20–23

Anorexia, Hepatic insomnia failure, aplastic anemia

Gabapentin

Ca,

10

1-2

Renal, 5–7, abSedation, None sorbed in carrier- weight dependant way gain

LRE

Bone marrow suppression

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P E D I AT R I C S

Starting Dosage (mg/kg/ day)

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Pediatrics

Drug∗

Target Use

Starting Dosage (mg/kg/ day)

Typical Therapeutic Range mcg/mL

Adverse Effects† Pharmacokinetics Common Serious (metabolism, But half-life in hours, Rare other)

Lamotrigine Na, Ca LRE, GE

0.6 (not on 4–20 VPA) 0.15 (on VPA) ↑ slowly!

Hepatic, 15–30

Insomnia StevensJohnson syndrome

Levetiracetam

SV2

LRE

20

20–40

Renal, 6–8

SleepiNone ness, psychiatric disturbance

Lorazepam

GABAR LRE, GE

0.1

N/A

Hepatic

Sedation Respiratory depression

Oxcarbazepine

Na

10

20–50

Hepatic, 8–15

Hyponatremia, ataxia, diplopia

Symptomatic hyponatremia

Phenobarbital

GABAR LRE, GE

5

20–40

Hepatic, 100

Sedation (adults); hyperactivity (children)

Respiratory depression

Pregabalin

Ca

‡

Renal, 5–7

Sedation, None weight gain

Topiramate

Na, LRE, GABAR GE

5–10

5–25

Hepatic/renal, 20–30

Cognitive slowing, paresthesias, weight loss

Renal stones, glaucoma, oligohidrosis

Valproic acid

Na, Ca LRE, GE

15

50–150

Hepatic, 10–20

Tremor, hair loss, weight gain, thrombocytopenia

Hepatitis, pancreatitis

Zonisamide

Na, Ca, LRE, GABAR GE

1–2

10–40

Hepatic, 50–70, Weight no eﬀect on P450 loss, paresthesias

LRE

LRE

‡

Renal stones, glaucoma, oligohidrosis

∗ Bold, italicized drugs are considered ﬁrst-line therapies for the bold, italicized type of epilepsy. † Adverse effects: 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.

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281

HEADACHES (Cephalalgia 2004;24(suppl 1):1 or www.ihs-classification.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 findings, signs of increased intracranial pressure, significant 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 disorders (see http://www.ihsclassiﬁcation.org/en)

Headache attributed to substance or withdrawal from substances Headache attributed to infection 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-classiﬁcation.org/en.

Migraine Headaches

Migraine without Aura

Migraine with Aura

A. At least ﬁve attacks fulﬁlling criteria B–D B. Headache attacks lasting 4–72 h C. Headache has at least two of the following: 1. Unilateral location 2. Pulsating quality 3. Moderate or severe pain intensity 4. Aggravation by or causing avoidance of routine physical activity D. During headache, at least one of the following: 1. Nausea or vomiting 2. Photophobia and phonophobia E. Not attributed to another disorder

A. At least two attacks fulﬁlling criteria B–D B. Aura consisting of at least one of the following but no motor weakness: 1. Fully reversible visual symptoms including positive features (eg, ﬂickering lights, spots or lines) or negative features (eg, loss of vision) 2. Fully reversible sensory symptoms including positive features (eg, pins and needles) or negative features (eg, numbness) 3. Fully reversible dysphasic speech disturbance C. At least two of the following: 1. Homonymous visual symptoms or unilateral sensory symptoms 2. At least one aura symptom develops gradually over ≥5 min or diﬀerent aura symptoms occur in succession over ≥5 min ≤60 min D. Headache fulﬁlling criteria B–D for migraine without aura begins during the aura or follows the 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-classiﬁcation.org/en.

P E D I AT R I C S

DIAGNOSTIC CRITERIA FOR MIGRAINE HEADACHE

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Pediatrics

Complications of Migraine • Chronic migraine : >15 d/mo for >3 mo (not caused by analgesic overuse) • Status migrainosus: Defined as headache lasting >72 h • Persistent aura without infarction >1 wk • Migraine-triggered seizure

TREATMENT OF MIGRAINE HEADACHES Medication

Route

Dose

Maximum

PO PO

7.5–10 mg/kg Q6–8h 10–15mg/kg Q4–6h

2.4 g/day 15 mg/kg/dose, 75 mg/kg/ day, or 2.6 g/day

PO Nasal Sub-Q PO Nasal

25, 50, 100 mg 5, 20 mg 6 mg 2.5, 5 mg 5 mg

Two doses in 24-h period

Abortive therapy NSAIDS Ibuprofen Acetaminophen Triptans Sumatriptan

Zolmitriptan

Prophylactic Therapy AED Valproic acid

PO

500–1000 mg/day (9–17 yr) 15–45 mg/kg/day See “Status Migrainosus” Start at 12.5–25 mg Qhs and increase by 25 mg weekly to 100 mg/day 250–500 mg BID (consider starting at 10–20 mg/kg/day

Topiramate

IV PO

Levetiracetam

PO/IV

Antidepressant Amitriptyline

PO

0.25 mg/kg Qhs (<3 yr), or 10 mg Qhs (3–12 yr)

1 mg/kg/day or 10 mg/day (children)

Antihistamine Cyproheptadine

PO

0.25 mg/kg/day divided TID, or 2–8 mg/day divided TID

2–6 y: 12 mg/day 7–14 y: 16 mg/day adults: 0.5 mg/kg/day

Antihypertensive Propranolol

PO

20-35 kg: 10–20 mg/ dose TID >35 kg: 20–40 mg/dose 3 TID

4 mg/kg/day (children), or 160-240 mg/day (adults)

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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 fluids (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)

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-classiﬁcation.org/en

P E D I AT R I C S

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 E. Not attributed to another disorder

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DEMYELINATING DISEASES Definition CIS

Gender

First episode of acute inﬂammatory demyelination

ADEM Encephalopa- F:M ratio: thy with acute 0.4–0.8:1 multifocal inﬂammatory demyelinating process typically follows a viral illness

Course

Symptoms MRI Lesions Lab Studies

Monophasic

Monofocal or polyfocal without encephalopathy

Correspond with presenting symptoms May include optic neuritis or transverse myelitis

CSF: Cell count, protein, IgG synthesis and index, oligoclonal bands, myelin basic protein, EBV/ CMV/ Mycoplasma PCR Serum: NMO antibody (when optic neuritis or transverse myelitis present), EBV and CMV titers, EBV nuclear antigen, Mycoplasma titers or PCR

Typically monophasic, but there are recurrent and multiphasic forms

Monofocal or polyfocal with encephalopathy

Gray and white matter involved Lesions of the same age Lesions are more poorly deﬁned than in MS Spinal lesions usually encompass the entire diameter of the cord at a given level

Same workup as CIS Typically do not see oligoclonal bands

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Neurology Gender

Course

Episodes of inﬂammatory demyelination disseminated in space and time (in children, must have two additional nonADEM events if initial attack was diagnosed as ADEM) Progression: Primary progressive course: 2%–7% Relapsing and remitting course: 90% (~15% progress to secondary progressive course)

F:M ratio: <6 yr 0.8:1; 6–10 yr, 1.6:1; >10 yr, 2.1:1

In children, Polyfocal most often relapsing and remitting, may be secondary progressive

Symptoms MRI Lesions Lab Studies

NMO

Chronic F:M ratio: Relapsing inﬂammatory 3.2:1 demyelinating condition characterized by the major criteria of optic neuritis and acute myelitis Minor criteria (need 2/3 for dx) are spinal MRI lesion spanning at least three levels, serum NMO-IgG, brain MRI not meeting criteria for MS

Polyfocal

White matter and deep gray nuclei Lesions of various ages Brain lesions are typically located perpendicularly to the long axis of the corpus callosum and are often periventricular Spinal lesions typically span only a portion of the diameter of the cord and are not as long as in NMO

Same workup as CIS Oligoclonal bands present in 90% of children with MS but may not be present when ﬁrst diagnosed CSF WBC usually 0–30, although may be as high as 60

May see evidence of optic neuritis Brain lesions may be present but do not fulﬁll the criteria for MS Typically spinal lesions should span at least three levels longitudinally

CSF: Oligoclonal bands may be present May have higher CSF WBC than in MS NMO-IgG may be present

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 first line).

P E D I AT R I C S

Definition MS

285

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 Cord∗

Motor Peripheral Neuron Nerve

NMJ

Muscle

Hereditary Degenerative

SMA 1,2,3 CMT 1, 2 ALS Dejerine Sottas Friedrich’s ataxia Hereditary neuropathy with liability to pressure palsy Giant axonal neuropathy

Muscular dystrophies • Dystrophinopathies (Duchenne, Becker MD) • Sarcoglycanopathies (limb-girdle MD) • Myotonic dystrophy • FSH MD • Congenital MD Mitochondrial myopathies

Metabolic

GM2 Refsum’s disease gangliosi- Abetalipoprodosis teinemia Metachromatic leukodystrophy Krabbe’s disease

Metabolic myopathies • Acid maltase deﬁciency • Carnitine deﬁciency • Myophosphorylase deﬁciency • Phosphofructokinase deﬁciency Mitochondrial myopathies

Porphyria Tangier disease Fabry’s disease Congenital Congenital malformation

Congenital Congenihypomyelinating tal myasneuropathy thenia

Congenital myopathies • Central core disease • Nemaline rod myopathy • Centronuclear myopathy Myotonic disorders • Myotonia congenital • Paramyotonia congenital Periodic paralysis • Hypokalemia • Hyperkalemic (continued on next page)

Neurology CNS and Spinal Cord∗

Motor Peripheral Neuron Nerve

NMJ

Muscle

Transient neonatal myasthenia Autoimmune myasthenia gravis

Dermatomyositis Polymyositis Inclusion body myositis Parasitic myositis

287

Acquired Disorders Inﬂammatory Immunologic

MS NMO Transverse myelitis ADEM

AIDP/GuillainBarré syndrome Miller Fisher variant GBS CIDP Vasculitis Sarcoidosis

Toxic

Abscess

Other

Stroke Seizure (eg, Todd’s paralysis) Mass lesion Migraine

Polio

Myotoxic drugs Steroid myopathy

Herpes zoster Herpes simplex Bell’s palsy Mycoplasma TB Lyme disease Leprosy

Viral myositis Parasitic myositis

∗ If any combination of hyperreﬂexia, 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, vocalization, 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 defined 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 reflexes are absent.

P E D I AT R I C S

Infectious

Environmental Botulism toxins Tick Lead paralysis Mercury Organophosphates n-Hexene Neurotoxic drugs

288

Pediatrics

2. The clinical criteria identified 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 • Delays in two or more of the following areas (Figure 22-4): • Fine gross motor delays • Speech and language • Cognition

• Social and personal • Activities of daily living

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 findings suggestive of a specific etiology, including serum amino acids, urine organic acids, acylcarnitine profile, mucopolysaccharides, serum glucose, bicarbonate, lactate, pyruvate, ammonia, and creatine kinase. • Serum lead level.

Available at www.AccessPediatrics.com • Ataxia • Stroke • Weakness

C H A P T E R 23

Oncology ONCOLOGIC EMERGENCIES Fever and Neutropenia • Often the first and only sign of serious infection. It should be evaluated immediately. • Definition • Fever: Single temperature ≥38.3°C (101°F) or a temperature ≥38.0°C (100.4°F) on two occasions 1 h apart. (Note: The temperature should not be taken rectally for immunocompromised patients!) • Neutropenia: ANC <500/mm3. • Diagnosis • History and physical exam: HR (tachycardia) and/or BP (hypotension), mental status (AMS) are ominous signs; examine sites for infection (oropharynx, respiratory tract, perianal area, CVL sites, locations of recent procedures, skin and soft tissues), abdomen (eg, typhlitis). • Evaluation: CBC, blood cultures (all lumens of CVL), UA (no catheterization), do not I & D skin lesions. • Optional studies: Urine culture (only if UA abnormal; do not catheterize immunosuppressed patients), CXR (based on signs and symptoms), abdominal US, other cultures based on clinical suspicion (stool, CSF, CVL site, wound). • Empiric therapy: Will ↓ mortality from gram-negative infections (80% → 10 to 40%) • Low risk and patient appears well: Monotherapy with ceftazidime, piperacillin/tazobactam, imipenem/cilastatin, or meropenem (often dependent on institutional practice and/or previous infections/sensitivities). • High risk (ANC <100, infant ALL, AML, induction therapy) and/or patient with concern for sepsis: Triple therapy with vancomycin + amynoglycoside + antipseudomonal penicillin (ceftazidime, cefepime, or carbapenem) (Clin Infect Dis. 2002; 34:730). • Modifications to empiric therapy: Consider adding antifungal coverage if fever persists >5 d.

• Pathophysiology: Rapid lysis of tumor cells → release of intracellular contents into bloodstream → phosphorus, potassium, uric acid → renal failure, ↓ Ca2+; typically occurs 12–72 h after therapy starts (may occur at presentation). • More common in tumors with high proliferative rate, large volume, or sensitive to chemotherapy (NHL, ALL, AML, especially acute monocytic leukemia) • Prevention: Aggressive hydration with or without diuresis is fundamental • High risk: Rasburicase (recombinant urate oxidase) • Intermediate risk: Allopurinol • Low risk: Watch and wait • Alkalinization is currently not recommended • Management • Hyperuricemia: Hydration 2–3L/m2/day (200 mL/kg/day if wt <10 kg) with D5 ¼ NS + rasburicase (contraindicated in G6PD deficiency). • Hyperphosphatemia: Aluminum hydroxide, dialysis (severe case). • Hyperkalemia and hypocalcemia: See Chapter 15.

Spinal Cord Compression (Cancer Treatment Rev 1993;19:129) • History: Local or radicular pain in 80%, lower extremity weakness or numbness, bowel or bladder incontinence • Tumors: Sarcomas, NBL, germ cell tumors, lymphoma, leukemia, leptomeningeal spread (drop metastases) from CNS tumors

289

P E D I AT R I C S

Tumor Lysis Syndrome (J Clin Oncol 2008;26(16):2767)

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 • Definitive therapy: Emergent spinal decompression (laminectomy), radiation, chemotherapy (see figure below)

Acute onset paraplegia? Yes

No

1. Admit 2. Laminectomy 3. ±Dexamethasone (0.5–2mg/kg/day)

1. Admit 2. Dexamethasone (0.5–2mg/kg/day) 3. Biopsy

Laminectomy No

Positive effect?

1. Chemotherapy 2. Radiation (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 (allergic reaction)

Acute infusion reaction (cytokine release syndrome)

1

Transient ﬂushing or rash; drug fever <38°C (<100.4°F)

Mild Tx: Infusion interruption or intervention may not be indicated

2

Rash Flushing Urticaria Dyspnea Drug fever ≥38°C (≥100.4°F)

Moderate Tx: Requires infusion interruption and respond promptly to symptomatic tx (eg, antihistamines, bronchodilator, NSAIDs); prophylactic medication indicated for ≥24 h

3

Symptomatic bronchospasm ± urticaria Allergy-related edema or angioedema Hypotension

Severe (ie, prolonged or recurrent sx) Tx: Interrupt infusion; parenteral tx indicated as per symptoms (eg, antihistamines, bronchodilator, NSAIDs, epinephrine IM, steroids, IVF); hospitalization is indicated for other clinical sequelae (eg, renal impairment, pulmonary inﬁltrates)

Grade

(continued on next page)

Oncology

291

Grade

Hypersensitivity (allergic reaction)

Acute infusion 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 • Definition: 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 definitive 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

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 nonemetogenic

Asparaginase, mercaptopurine (PO), methotrexate (low dose, PO, IT), steroids, vincristine

Adapted from Principles and Practice of Pediatric Oncology, 5th ed. 2005.

P E D I AT R I C S

• Etiology: Chemotherapy induced (anticipatory also common), radiation induced, disease induced (eg, brain tumors, CNS leukemia, constipation), drug induced (Cancer J 2008;14(2):85)

292

Pediatrics

• Treatment: Antiemetic drugs and nonpharmacologic approach (see table below)

ANTIEMETIC AGENTS Agent

Efficacy

Routes

Side effects

5-HT3 antagonists (ondansetron)

Marked

PO, IV

Headache, constipation with prolonged administration

Aprepitant

Marked

PO

Fatigue, weakness, nausea, constipation

Dexamethasone

Moderate

PO, IV

Hyperglycemia

Dronabinol (tetrahydrocannabinol)

Moderate

PO

Dry mouth

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 significant 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) • Definition: 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 immunodeficiencies

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%; definition: epitrochlear or supraclavicular LN >5 mm, inguinal LN >15 mm, and >10 mm for all other LN; malignant LN are typically rubbery, firm, 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 definitive dx • Differential dx: JRA, osteomyelitis, ITP, pertussis, EBV, aplastic anemia, other malignancies (eg, neuroblastoma, EWS, RMS). • Classification: 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 FAB Classification

Frequency of ALL Cases (%)

Description

L1

Premature B-cell morphology

~85

L2

Intermediate morphology, (ie, ↑cytoplasm and dispersed chromatin); similar prognosis to FAB L1

~14

L3

Mature undiﬀerentiated morphology

<1

B-Cell

T-Cell

Pre–B cell, (most common) = 19, 20, ± CALLA Mature B cell (L3) = (10, 19, 20) + 22, 25, and surface Ig

2, 3, 4, 5, 7, 8

Distribution

70%–80% of ALL cases

15%–17% of ALL cases

Prognosis

Favorable prognosis associated with pre–B cell ALL

Poorer prognosis in some studies

Features

May rarely present with a primary mass; usually presents with bone marrow disease

么>乆, older age, higher incidence of mediastinal mass

CD markers

CALLA: Common ALL antigen (CD 10) found on 70% of leukemic cells with a B-precursor phenotype.

• Treatment: Consists of four or five 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).

P E D I AT R I C S

IMMUNOLOGIC CLASSIFICATION OF ALL

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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 ﬁrst 4-6 weeks

Consolidation

Consolidate remission and prevent CNS involvement (ie, IT chemo); commonly uses multiple agents with diﬀering 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 intensiﬁcation (re-induction or reconsolidation)

Similar to induction and consolidation periods; the goal is to ↓ overall leukemia burden to undetectable or to deﬁned level of 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) Risk Group Low

Features

Cases (%)

Hyperdiploidy∗ or trisomy 4, 10, 17

20

t(12,21) Standard

WBC <50,000/mm

20 3

15 Age 1–9.9 yr

Recommended Therapy

Approximate 4-yr Event-Free Survival (%)

Conventional antimetabolitebased therapy

92

Intensiﬁed antimetabolite therapy

82

Intensive multiagent therapy

73

46

No favorable cytogenetics High

Very high

T-cell phenotype

15

Age ≥10 yr or

15

WBC>50,000/mm3

6

t(9;22)

3

Intensive multiagent therapy + tyrosine kinase inhibitor (eg, imatinib)

t(4;11); age <1 yr

4

Hypodiploidy (≤44); induction failures and slow responders

2

Consider allogeneic HSCT after ﬁrst remission

∗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, specific 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)

Neuroblastoma • Definition: 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

P E D I AT R I C S

• Definition: ↑ 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 difficult and usually made late in dz. Nonspecific 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 fibrinogen (<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 definitive cure. Indicated for patients with poor response to chemotherapy, familial HLH with homozygous mutations, or in CNS dz. • 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).

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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, flushing • 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-specific 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 metastasis), head CT if clinically indicated • Tissue biopsy (small, round, blue cells on histology; immunohistochemical staining; and test for MYCN amplification, hyperdiploidy, CD44 expression, specific 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 highdose 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 amplification. • Unfavorable features: Age >2 yr, male gender, ↑ ferritin, advanced stage euploidy, MYCN amplification. Malignant CNS Tumors

CHARACTERISTICS OF CENTRAL NERVOUS SYSTEM TUMORS IN CHILDREN YOUNGER THAN 20 YEARS OF AGE International classification of childhood cancer (ICCC) group Astrocytoma

Brainstem Medulloblastoma Glioma

Ependymoma

Site

Cerebrum, cerebellum

Cerebellum

Midbrain, pons, medulla

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

Ventricles or spinal cord; fourth ventricle most common in <3 yr

(continued on next page)

Oncology

297

International classification of childhood cancer (ICCC) group Astrocytoma

Brainstem Medulloblastoma Glioma

Ependymoma

Brain CT and MRI; glial ﬁbrillary acidic protein (GFAP) tumor marker

Brain CT (hyperdense mass), MRI of the brain and spine with contrast (heterogeneous contrast-enhancing lesion with areas of necrosis or hemorrhage, cysts); LP after surgery (≥33% are positive)

Brain CT and MRI (grade I: welldemarcated lesion ± calciﬁcation; grade II: inﬁltrating lesion)

Brain CT (hyperdense mass with homogenous enhancement, calciﬁcation or cyst common), MRI of the brain and spine with contrast (hypointense T1, hyperintense T2 and prominent enhancing)

Histology and genetics

Glial cell origin; none

Embryologic origin; small blue cell tumor, Homer-Wright rosettes (40%); look for neuroepithelial cell markers;↑ in those with PTCH-1, APC gene mutation, Nmyc dysregulation

Biopsy to identify type except for GBM; incidence ↑ in those with NF-1

Ependymal rosettes (diagnostic); monosomy 22 in sporadic cases

Patient stratiﬁcation

Grade I or II: Diﬀuse Grade III: Anaplastic Grade IV: GBM

Stage M0: >3yr, <1.5 cm2 residual Stage M1: <3yr, >1.5 cm2 residual

Grade I: Focal Grade II: Diﬀuse Grade III: High-grade anaplastic Grade IV: GBM

Grade I: Myxopapillary Grade II: Low grade, diﬀerentiated Grade III: anaplastic

Treatment

Surgery + radiation+ chemotherapy

Maximal surgical resection + craniospinal irradiation + chemotherapy

Grade I: Observe if asymptomatic ± surgery Grade II–IV: Supportive care, including steroids to ↓ edema, radiation; no surgery or chemotherapy

Maximal surgery + radiation

Survival rate∗

74% at 5 yr

M0: >80% at 5 yr M1: 55%–76% at 5 yr

Grade I: 100% at 5 yr Grade II–IV: <1-yr survival

66%–75% at 5 yr if total resection

∗http://seer.cancer.gov/publications/childhood/cns.pdf

P E D I AT R I C S

Workup (ﬁndings)

298

Pediatrics

COMMONLY USED CHEMOTHERAPY AGENTS, TOXICITIES AND ANTITUMOR SPECTRUM Drug Class (Mechanism) Alkylating agents (cross-link DNA by covalent bonding, preventing replication and transcription)

Antimetabolites (structural analogs of vital cofactors or intermediates in DNA or RNA synthesis)

Antitumor antibiotics (DNA intercalation leading to inhibition of topoisomerases, strand breaks, and free radical formation)

Antitumor Spectrum

Examples

Toxicities

Cyclophosphamide

Myelosuppression, nausea and vomiting, alopecia, cystitis, water retention

Leukemia, lymphoma, sarcoma, neuroblastoma

Ifosfamide

Myelosuppression, nausea and vomiting, alopecia, cystitis, neurotoxicity

Sarcoma, GCT, leukemia, lymphoma

Cisplatin

Myelosuppression, nausea and vomiting, alopecia, ototoxicity, neurotoxicity

GCT, brain tumors, osteosarcoma, neuroblastoma, HD

Busulfan

Myelosuppression, nausea and vomiting, alopecia, pulmonary, neurotoxicity, hepatic

Leukemia (BMT)

Methotrexate

Myelosuppression, mucositis, rash, hepatic, renal, neurotoxicity

Leukemia, lymphoma, osteosarcoma

Mercaptopurine

Myelosuppression, hepatic, mucositis

Leukemia

Thioguanine

Myelosuppression, nausea and vomiting, mucositis, hepatic veno-occlusive disease

Leukemia

Cytarabine

Myelosuppression, nausea and vomiting, mucositis, neurotoxicity, ocular, skin

Leukemia, lymphoma, LCH

Doxorubicin

Myelosuppression, nausea and vomiting, alopecia, mucositis, diarrhea, cardiac

Leukemia, lymphoma, most solid tumors

Dactinomycin

Myelosuppression, nausea and vomiting, alopecia, mucositis, vesicant, hepatic venoocclusive disease

Wilms, sarcoma

Bleomycin

Nausea and vomiting, alopecia, lung, skin, fever, mucositis, vesicant, Raynaud’s disease

Lymphoma, testicular and GCT

(continued on next page)

Oncology Drug Class (Mechanism)

299

Examples

Toxicities

Antitumor Spectrum

Vincristine (vinca alkaloid)

Neurotoxicity, alopecia, SIADH, hypotension, vesicant

Leukemia, lymphoma, most solid tumors

Vinblastine (vinca alkaloid)

Myelosuppression, alopecia, mucositis, mild neurotoxicity, vesicant

Histocytosis, Hodgkin’s disease, testicular

Epidopophyllotoxins (inhibit topoisomerase II)

Etoposide (epipodophyllotoxin)

Myelosuppression, nausea and vomiting, alopecia, mild neurotoxicity, hypotension, allergic reaction, secondary leukemia

Leukemia, lymphoma, neuroblastoma, sarcoma, brain tumors, HLH

Miscellaneous Corticosteroids (receptor-mediated lympholysis)

prednisone, dexamethasone

Increased appetite, obesity, striae, diabetes, immunosuppression, AVN of hip, HTN

Leukemia, lymphoma, LCH

Asparaginase (asparagine depletion)

Asparaginase (eg, I-Asp, PEG-Asp)

Allergic reaction, coagulopathy, pancreatitis, hepatic, neurotoxicity

Leukemia, lymphoma

Plant products Vinca alkaloids (inhibits mitosis by binding to tubulin)

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

Malignant Conditions

Nonmalignant Conditions

Leukemia (high risk or relapsed) Lymphoma Solid tumors (eg, neuroblastoma) Brain tumors (eg, medulloblastoma)

Bone marrow failure (eg, aplastic anemia) Premalignant disorders (eg, MDS) Inborn errors of metabolism (eg, MPS I) Immunodeﬁciency (eg, SCID, Wiskott-Aldrich syndrome) 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 (continued on next page)

P E D I AT R I C S

ELIGIBLE CONDITIONS FOR BONE MARROW TRANSPLANT

300

Pediatrics

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) Inﬂuenza 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 deﬁciency) Gonadal dysfunction Cardiopulmonary toxicities Obesity Neurocognitive delay Psychiatric disorders

Radiation

Total dose and involved ﬁeld of radiation

Neurocognitive delay with craniospinal XRT or TBI (especially if age <6 yr) Poor skeletal growth and organ damage over involved ﬁeld

Surgery

Anatomic area involved

Amputations or extensive surgeries (especially in solid tumors)

HSCT

Type of conditioning regimen and initial disease burden

Chronic GVHD Secondary malignancies (eg, EBV-PTLD, solid tumors, leukemia) Conditioning related (see chemotherapy and radiation eﬀects)

Available at www.AccessPediatrics.com • Differential Diagnosis of Malignancies Based on Site and Age • Acute myeloid leukemia • Wilms tumor • Bone marrow transplantation

C H A P T E R 24

Orthopedics and Sports Medicine SPRAINS AND STRAINS Introduction • Goal of section: The reader will understand common causes of acute ankle, knee, shoulder, back injuries, and chronic back pathology injuries, their diagnoses and management. • 1%–19% of musculoskeletal injuries evaluated in the ED receive proper discharge instructions for optimal management and rehabilitation. • The mnemonic PRICEMMMS (see treatment section) includes the necessary components for proper care of acute musculoskeletal pain and swelling.

Definitions • Sprain: Stretch or tear of a ligament that connects two or more bones (localized tenderness, swelling, ± joint instability over injured ligament) • Strain: Inflammation and injury to a muscle or tendon • Acute: Pain less than 3 mo • Chronic: Pain greater than 3 mo • Valgus: A force or alignment that results in the joint opening medially • Varus: A force or alignment that results in the joint opening laterally (opposite of valgus) • Apophysitis: Inflammation of growth plate (epiphysis under tension at site of tendon insertion) • Spondylolysis: Stress injury or fracture of pars interarticularis • Spondylolisthesis: Anterior movement of one vertebrae in relation to adjacent vertebrae

Evaluation

Treatment of Acute Injury: PRICEMMMS • Treatment goals: Minimize swelling and pain, minimize loss of strength and ROM, and prevent injury • Protection: Non–weight-bearing (crutches, cast/splint, knee brace, ankle stirrup, sling), as appropriate. If unable to walk without limp crutches. Wean crutches when able to perform normal heel–toe gait. • Relative Rest: Do not do anything that hurts. Take out of sports or offending activity until normal strength, stability, mobility, and function return. → Provide “return to play criteria.” • Ice: Controls pain and decreases swelling. Apply ice daily until pain and swelling resolve. Recommendations: Use a bag of crushed ice or frozen peas directly on the skin for 20 min every hour, avoid refreezing cold gel packs, and never sleep with ice.

301

P E D I AT R I C S

• History • Physical exam: inspection, neurovascular, palpation, range of motion, provocative tests (a video demonstration of each exam is available at http://www.sportsmedkids.com ), function • Red flags: Fever; sweating; age <5 yo; local tenderness/warmth/redness; no history of injury; night pain; weight loss; migratory joint pain (SLE, rheumatic fever, HSP, subacute endocarditis, Lyme disease, gonococcal arthritis, viral or Mycoplasma infection, sepsis); elevated WBC, ESR, or CRP (evaluate for septic arthritis or osteomyelitis). • Radiographic studies • Two views minimum of entire bone: Add oblique view of foot, ankle, and elbow (foot injuries require weight-bearing views—so that a Lisfranc injury is not missed). • 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).

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 deficits.

FRACTURES AND SPLINTING Definitions • 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-defined 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: Inflammation ± 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 classification 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.

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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 five P’s—pain, pallor, paresthesia, paralysis, and pulseless (late finding). • 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 Fructure, 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 first 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

Scapular fracture • 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 • Suspect Hill-Sachs and Bankart fracture in acute anterior shoulder dislocation → shoulder X-ray series with AP, lateral axillary, and Y views

• Anterior → reduction • Posterior → Orthopedic consult prior to reduction

Traction apophysitis of proximal humerus (“little league shoulder”) • X-ray may show normal or wide physis

• Rest and ice daily • Sling if needed • No throwing 4–6 wk and no pitching 3–6 mo (continued on next page)

P E D I AT R I C S

SHOULDER

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. shortening (>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. signiﬁcant displacement >1 cm, 3. posterior diplacement, 4. posterior sternoclavicular dislocation

304

Pediatrics Considerations and management Proximal fracture • Complete displacement, ≤3 cm overriding and <60° angulation → splint • Open fracture, skin tenting, neurovascular injury, or unacceptable displacement → ortho consult, ORIF • Note: Proximal humeral ossiﬁcation not until age 6 mo, greater tuberosity at 1–3 yr, lesser tuberosity at 4–5 yr → fracture may be missed on X-ray

Splinting: • Swathe and sling immobilization or coaptation with double sugar tong Casting: • Long arm hanging cast

ELBOW

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 • At risk for radial or medial nerve and brachial artery injury. • Three types: • Type I—Nondisplaced with preserved Baumann angle (<4 ° of varus is accepted) → splint + orthopedic clinic f/u in 1 wk • Type II—Displaced with intact posterior cortex → ortho consult for closed reduction and pinning • Type III—Displaced with no contact with cortex → ortho consult for ORIF and pinning

Splinting: • Posterior elbow splint at 30° until X-ray • For type I only → long arm splint with elbow ﬂexed 90° and forearm neutral Casting: Long arm

Transphyseal fracture

→ Ortho consult for closed reduction and pinning

Lateral condylar fracture • Nondisplaced → splint, no surgery • Displaced >2–4 mm → ortho consult for reduction and pinning • Ortho consult for any fracture that extends to articular surface, capitellum, or trochlea

Splinting: • Posterior elbow splint at 90° and forearm in neutral

Medial epicondylar fracture • Potential ulnar nerve injury • Displaced <5 mm → splint • Displaced >5 mm → ortho consult for ORIF Medial epicondyle traction apophysitis (“little league elbow”) • Often due to repetitive throwing and valgus stress • X-ray may show normal or wide physis

• Rest and ice daily • Sling if needed • No pitching for 3–6 mo

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Considerations and management

RADIUS

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 ﬂexion Splinting: • Sling or posterior splint with elbow 90° and forearm neutral

Radial neck fracture • 50% of radial neck fracture have other associated fracture/ injury • Most Salter-Harris type I and II injuries • 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 translocation acceptable → splint • If not within above guidelines → closed reduction or ORIF

Splinting: • Posterior splint with elbow 90° and forearm neutral

Proximal and mid-radius fracture • Greenstick, buckle, or Galeazzi fracture → splint

Splinting (in general): • Proximal radius → long arm cast or sugar tong with forearm supinated • Middle radius → long arm cast or sugar tong with forearm neutral • Distal radius → sugar tong with forearm pronated → short arm cast after elbow immobilized for 2 wk

Distal radius fracture • Physeal (if nondisplaced) → splint • Physeal (if displaced) → ortho consult and closed reduction and pinning • Note: If Salter-Harris type III/IV, open fracture, nonreducible, neurovascular injury → ORIF • Metaphyseal (nondisplaced buckle fracture) → splint • If displaced, refer to acceptable fracture angulations and 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 (continued on next page)

P E D I AT R I C S

Radial head fracture • Ossiﬁcation at 5 yr • <30° angulation, nondisplaced → splint/sling • >30° → closed reduction/splint • >45° → closed reduction and pinning • If still >40° s/p closed reduction, translation >3 mm, or completely displaced → ORIF

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ULNA

Considerations and management Olecranon fracture • Nondisplaced → splint • Displaced >3 mm + extra-articular → closed reduction with immobilization/splint • Displaced >3 mm + intra-articular and/or comminuted → ORIF

Splinting: • Posterior splint with elbow ﬂexed at 75°–80° (leave partially extended) F/U: • PCP or ortho consult

Both radius and ulna fracture • Nondisplaced → splint + orthopedic clinic f/u • Plastic deformation (bowing fracture): If >20° angulation or unable to fully rotate → reduction under general anesthesia → ortho consult • Greenstick fracture + rotation and angular deformity present → closed reduction by reversing deforming forces → sugar tong splint or bivalved long arm cast → ortho consult • 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 30°–45° malrotation acceptable • Age ≥9 yr: <10° proximal/mid-shaft angulation acceptable, ages 9-14yr <20°–30° malrotation acceptable

Splinting (long arm cast or splint): • Proximal one-third → forearm pronated • Middle one-third → forearm neutral • Distal one-third → forearm supinated

Monteggia fracture • Fractured ulnar diaphysis with dislocation of radial head. Types I– IV radiographically deﬁned. Can only r/o with three-view (AP, oblique, lateral) X-ray • Axis of radius should point toward center of capitellum on all X-ray views. If disrupted, then consider radial neck fracture, elbow dislocation, or lateral condyle fracture • Management primarily determined by ulnar fracture type: • If ulnar plastic deformation or incomplete ulnar fracture (greenstick/buckle) → closed reduction with up to 10° angulation acceptable followed by radial head reduction • If complete transverse, oblique or comminuted fracture of ulna or unable to reduce radial head → ORIF

→ Ortho consult Splinting s/p reduction: • Place in long arm splint with elbow ﬂexed up to 110°–120° and forearm in midsupination or neutral • Note: Radial head dislocation may be easily missed (even with radiology); always review your own ﬁlms

Considerations

Management

WRIST

Scaphoid fracture • “Snuﬀ box” tenderness. • Nondisplaced → Splint for 6–12 wk. • Displacement ≥1 mm is diagnostic of instability → ORIF. Thumb MCP fracture • Non–intra-articular or complex head/shaft fracture → closed reduction and splinting. • Base fracture (metaphyseal ± Salter-Harris type II with fracture on medial side, lateral angulation) → reduction 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.

Splinting: • Short arm thumb spica cast for 4–8 wk or 6–12 wk if scaphoid fracture • Partial gamekeeper’s will then require hand-based thumb spica for an additional 4 wk

THUMB

HAND FRACTURE MANAGEMENT

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Orthopedics and Sports Medicine

THUMB

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 aponeurosis 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

METACARPAL

307

Neck fracture → closed reduction/splint • 2nd and 3rd MCP → <10° angulation tolerated • 4th and 5th MCP → 45°–60° angulation tolerated • Note: When positioning, MCP must be in maximum ﬂexion and all IP joints fully extended to prevent ﬂexion contraction.

Splinting: • 2nd and 3rd MCP fracture → teardrop splint • 4th and 5th MCP fracture → boxer splint • In both, the wrist should be extended 10°–15° with thumb aligned to forearm

Shaft fracture → closed reduction/splint • Note: When positioning, MCP ﬂexed 70° and IP joints extended (“beer can” position).

Proximal and middle phalanx fracture • Most common fractures of the proximal phalangeal base • Acceptable shaft fracture <30° angulation for <10 yr; <10°–15° angulation for >10 yr • Phalangeal neck fracture—Often unstable and displaced due to persistent attached collaterals to the distal fragment → ORIF • lntra-articular (displaced or >= 30 % of articular surface) fracture → ORIF ± pinning • Open, spiral, oblique, unacceptable angulation, or 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 ﬂexed position. Avulsion of ﬂexor digitorum profundus at the DIP may cause “Jersey ﬁnger” or reverse mallet with inability to ﬂex ﬁnger at DIP

Splinting: • Mallet ﬁnger → apply volar or dorsal splint to keep ﬁnger extended • Unacceptable reduction of mallet or open fracture → surgery • Jersey ﬁnger and reverse mallet → surgery

P E D I AT R I C S

PHALANX

Base fracture • Usually high energy with tissue disruption → ORIF ± pinning.

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KNEE

FEMUR

HIP

LOWER-EXTREMITY FRACTURE MANAGEMENT Considerations

Management

Avulsion fracture—At apophysis, describe sudden “pop” • Ischial tuberosity—Hamstring, forceful jumping • Anterior superior iliac spine—Sartorius, forceful kicking or sprint • Anterior inferior iliac spine—Rectus femoris, forceful kicking • Lesser trochanter—Psoas, forceful sprint, jump, kick • Iliac crest—Abdomen/obliques, repetitive contraction • Pubic symphysis—Leg adductors, swim, kick, jump • If displaced >2 cm or painful >6 mo → Consider surgical repair

• Rest and no weightbearing for 1 wk → gradual weightbearing with crutches → limited activity for 1–2 mo • Holster ACE wrap • Daily ice until pain and swelling resolved

Pelvic fracture • 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

→ Ortho consult

Femur shaft fracture • Middle third of shaft most common site • Suspect tumor from femoral shaft fracture occurring from low-energy trauma • Ortho consult required for all fracture • Management may consist of reduction, traction, Pavlik harness, spica casting, or ORIF

→ Ortho consult • One-half of femur fracture in infants and young children related to nonaccidental trauma

Distal femur fracture • Salter-Harris classiﬁcation • Nondisplaced fracture → splint • Displaced type II or metaphysis fracture → closed reduction under general anesthesia • All others including irreducible type II and displaced types III, IV, and V fracture → ORIF

→ Ortho consult Splinting: • Long leg cast with knee ﬂexed at 15°, molded against opposite side of impact

Patellar fracture • Nondisplaced → splint • >4 mm displaced or >3 mm stepoﬀ → ORIF

Splinting: • Long leg splint with knee fully extended (see ﬁgure below)

Sleeve fracture • Avulsion of distal pole of patella • Not obvious on X-ray → MRI to evaluation → ORIF Sinding-Larsen-Johansson • Apophysitis at inferior pole of patella Osgood-Schlatter • Apophysitis of tibial tubercle • Seen in early adolescents • Acute onset of pain should be distinguished from fracture → activity as pain allows

• Single or double ChoPat knee straps • Rest and ice daily • PT for hamstring and eccentric quad strengthening

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KNEE

Orthopedics and Sports Medicine Considerations

Management

Tibial tuberosity fracture • X-ray with knee extended • Type I: avulsion of tuberosity without involvement of physis, minimal displacement • Type II: avulsion with displacement, no intra-articular extension • 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

→ Ortho consult Splinting: • Long leg splint, knee immobilizer, or cast with knee mostly extended for 6 wk

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 • Classically at medial femoral condyle, AVN of a piece of osteochondral bone, which can then separate • Progressive pain, locking, and intermittent swelling → non–weight-bearing and immobilize in knee brace/cast • If fragment loose, or pain lasts >6 mo → surgery

• Non–weight-bearing crutches • ± Casting • Serial F/U X-ray to ensure OCD placement

Proximal tibial physis fracture • Risk of compartment syndrome and popliteal artery injury • Nondisplaced → splint • Displaced (requires reduction) → ORIF

Splinting: • Long leg splint/ cast with knee fully extended

Proximal shaft fracture • Risk of compartment syndrome and anterior tibial artery injury • Nondisplaced → splint • Displaced → ORIF

Splinting: • Long leg splint/cast with knee mostly extended + varus molding

Diaphysis fracture • Nondisplaced → splint • Displaced → attempt closed reduction • If failed reduction, unstable, or shortening → ORIF

Splinting: • Long leg splint/cast with knee ﬂexed at 45°

Toddler fracture • Distal tibia fracture in child age <5 yr, history of minimal trauma • X-ray series needs to include oblique views to see nondisplaced spiral fracture Distal fracture • Minor Salter-Harris types I and II or avulsion fracture → closed reduction and splinting • All other fracture (ie, intra-articular and joint instability) are high risk → ORIF

→ Ortho consult Splinting: • Long leg splint or cast with knee ﬂexed no more than 5° • Ankle neutral

P E D I AT R I C S

TIBIA AND FIBULA

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310

Pediatrics

ANKLE

ANKLE AND FOOT FRACTURE MANAGEMENT Considerations

Management

Ankle sprain • Classically graded I (mild), II (moderate), III (severe) • To determine if needs X-ray: (1) unable to bear weight immediately, (2) unable to walk four steps in emergency 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

Splinting: • Ankle stirrup splint or air cast • Non–weight-bearing initially for grade II/III

Talus fracture • Neck fracture most commonly seen • If nondisplaced → splint • If displaced >3 mm or varus rotation >5° → ORIF

Splinting: • Non–weight-bearing • Long leg splint/cast with knee ﬂexed • Ankle at 90°

Calcaneous fracture • Most immobilize with splint • If severely displaced or intra-articular → ORIF Sever’s disease (calcaneal apophysitis) • ⊕ heel squeeze on exam and pain at Achilles insertion • Resolves as growth plate closes → symptomatic treatment

FOOT

Kohler’s disease • Self-limiting AVN of the navicular bone from repetitive stress • Ages 5–7 yr • Symptomatic treatment

• Tuli’s heel cups 4–6 wk • Ice daily • Calf stretch • Rest and ice daily • Persistent pain treated with non–weight-bearing and short leg cast

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)

Lisfranc fracture • Fracture at base of 2nd MT with ligament injury • Frequently missed in ER and on X-ray, especially without fracture • Poor prognosis if no treatment • Late midfoot collapse a common sequelae • Obtain three-view with oblique X-ray series (weightbearing) • If >2 mm displacement or MT dislocated → ORIF

Splinting: • Non–weight-bearing • Short leg cast for 6 wk • Consider casting even when no fracture seen

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FOOT

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Considerations

Management

Freiberg’s infarction • Self-limiting AVN of 2nd MT head → MT pad • Typically females age >13 yr • Persistent pain → surgery

Splinting: • Short leg cast

Proximal and distal phalanx fracture • Attempt reduction using digital block for anesthesia

Splinting: • 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 flow (mottled skin appearance), temperature changes (typically cooler), and swelling.

Available at www.AccessPediatrics.com • Ankle Examination • Knee Examination • Shoulder Examination • Elbow Examination

P E D I AT R I C S

CHAPTER 25

Pulmonology WHEEZING AND ASTHMA Wheezing • Definition: Continuous high-pitched sound with musical quality emitting from the chest during expiration. • Differential diagnosis: Modified asthma predictive index (API; J Allergy Clin Immunol 2004;114(6):1282): Identifies 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 • Infection (viral upper or lower respiratory infections, bronchiolitis, tuberculosis, pertussis) • Bronchopulmonary dysplasia • Sinusitis • Foreign body aspiration • Anatomic abnormality (vascular ring, mediastinal mass) • Tracheobronchomalacia • Aspiration due to swallow dysfunction or GERD • Cardiac disease with congestive heart failure • Immunodeﬁciency, immotile cilia • CF

• Asthma • Vocal cord dysfunction • GERD • CF

MODIFIED ASTHMA PREDICTIVE INDEX Major Criteria

Minor Criteria

Parental history of asthma Physician-diagnosed atopic dermatitis Allergic sensitization to at least one aeroallergen

Allergic sensitization to eggs, milk, or peanuts Wheezing apart from viral illness Blood eosinophilia >4%

Asthma • Definition: Chronic inflammatory 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 airflow 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 inflammatory exudates and airway wall edema).

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313

Diagnosis

CLINICAL HISTORY AND PHYSICAL EXAM FOR DIAGNOSING ASTHMA History

Physical Exam

• Age at onset of wheezing

• Respiratory: Evaluate degree of air entry; evaluate for prolonged expiratory phase, tachypnea, retractions (subcostal, sternal, intercostal), wheezing vs stridor • Signs of atopy: Eczema, rhinorrhea, transverse nasal crease (allergic salute), Dennie’s lines (folds inferior to the lower eyelid), allergic shiners (periorbital darkening), conjunctivitis, pale or edematous nasal turbinates • Absence of clubbing • Normal growth

• Frequency, timing (day or night) • H/o prematurity, BPD • Use of urgent care ED visits, hospitalizations, need for O2 or intubation • Comorbid conditions: Eczema, allergies, chronic rhinitis, sinusitis, GERD • FHx of asthma and allergic conditions • Triggers for wheezing: URI or infection, exercise, cold air, allergens (eg, dust mite, animal dander, grass or tree pollen, molds, cockroach), irritant exposures (eg, tobacco smoke, air pollution), emotional stress • Environmental exposures: Pets, tobacco smoke, 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)

P E D I AT R I C S

• Diagnostic studies • CXR: May be normal or may show hyperinflation (flattened diaphragm ↑ chest A/P diameter) or peribronchial thickening. • Peak flow 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). • Spirometry: Obstructive pattern with ↓ FEV1 and ↓ FEV1/FVC ratio; scooped or concave pattern on expiratory flow–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. • Define 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)

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• Component 3: Control of environmental factors and comorbid conditions that affect asthma • Define specific 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 influenza vaccine, good handwashing. • Component 4: Pharmacologic therapy • All patients need access to quick-relief bronchodilator (short-acting β2-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 efficacy, 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∗

Risk

Impairment

Components of severity

Persistent Intermittent

Mild

Moderate

Severe

Symptoms

≤ 2 days/wk

>2 days/ wk

Daily

Throughout the day

Nighttime awakenings

0-4 yr: 0 ≥5 yr: ≤ 2x/mo

0-4 yr: 1-2x/mo ≥5 yr: 3-4x/mo

0-4 yr: 3-4x/mo ≥5 yr: >1x/wk

0-4: >1x/wk ≥5 yr: Often, 7x/wk

SABA use for symptoms

≤2 days/wk

>2 days/wk

Daily

Several times per day

Interference with normal activity

None

Minor

Some

Extreme

Lung function

Normal FEV1 between exacerbations FEV1 >80% predicted 5-12 yr: FEV1/FVC >85% ≥12 yr: FEV1/FVC normal

FEV1 >80% predicted 5-12 yr: FEV1/ FVC >80% ≥12 yr: FEV1/ FVC normal

FEV1: 60%-80% predicted 5-12 yr: FEV1/ FVC 75%-80% ≥12 yr: FEV1/ FVC reduced 5%

FEV1 < 60% predicted 5-12 yr: FEV1/FVC< 75% ≥12 yr: FEV1/ FVC reduced >5%

Exacerbations requiring oral corticosteroid

0-1/yr

0-4 yr: ≥2 in 6 mo OR ≥4 wheezing episodes per 1 year lasting >1 day ≥5 yr: ≥2/yr (continued on next page)

Pulmonology

Components of severity Recommended Initial Therapy (see table “Stepwise approach to management of asthma” below)

315

Persistent Intermittent

Mild

Moderate

Severe

Step 1

Step 2

Step 3

0-4 yr: Step 3 5-12 yr: Step 3 or 4 ≥12 yr: Step 4 or 5

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 Severity

Well Controlled

Impairment

Symptoms

>2 d/wk

Very Poorly Controlled Throughout the day

0–11 yr: ≤1x/mo ≥12 yr: ≤2x/mo

0–11 yr: ≥2x/mo ≥12 yr: 1–3x/wk

0–11 yr: ≥2x/wk ≥12 yr: ≥4x/wk

Interference with normal activity

None

Some limitation

Extremely limited

SABA use for symptoms

≤2 days/wk

>2 days/wk

Several times per day

>80% predicted or personal best >80%

60%–80% predicted <60% predicted or or personal best personal best 75%–80% <75%

Exacerbations requiring oral corticosteroids

0–1x/yr

<5yr: 2–3x/yr ≥5yr: ≥2x/yr

Treatment-related adverse effects

Medication side eﬀects do not correlate with speciﬁc levels of control but should be considered in the overall assessment of risk

• FEV1/FVC (> = 5 yr)

Recommended Action for Treatment

• Maintain current step • Regular follow-up q 1-6 mo • Consider stepdown if well controlled for ≥3 mo

Adapted from NHLBI, EPR 3, 2007:40,43

Step up 1 step and reevaluate in 2–6 wk

<5 yr: >3x/yr ≥5 yr: ≥2x/yr

• Consider short course of oral corticosteroid • Step up 1–2 steps and reevaluate in 2 wk

For side eﬀects, consider alternative treatment options

P E D I AT R I C S

Nighttime awakenings

Lung function • FEV1 or peak ﬂow

Risk

≤2 d/wk

Not Well Controlled

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MEDICATIONS COMMONLY USED FOR TREATING ASTHMA Medication Class Examples

Adverse Effects

Comments

Short-acting β-agonist (SABA)

Albuterol Levalbuterol

Tachycardia, nervousness, tremors

Short-term symptom relief and pre-exercise

Systemic corticosteroid

Prednisolone Prednisone Methylprednisolone Dexamethasone

Altered behavior, nausea or vomiting, pituitary adrenal axis suppression (long-term therapy)

Short courses are eﬀective for exacerbations or establishing control at initiation of therapy High-dose or extended therapy should be weaned as tolerated

Inhaled corticosteroid (ICS)

MDI: Fluticasone, beclomethasone, ﬂunisolide, triamcinolone DPI: Budesonide, mometasone Nebulized: Budesonide

Thrush Decreased height velocity∗ (temporary) Adrenal suppression (high dose)

Mainstay of preventive therapy Diﬀerent ICS have similar eﬃcacy but diﬀerent potency High-dose therapy should be weaned

ICS + long-acting β2-agonist (LABAs)

Fluticasone + salmeterol Budesonide + formoterol

As above for ICS, Headache

FDA alert: LABAs should not be used for symptom relief or without concomitant ICS

Leukotriene receptor antagonist

Montelukast Zaﬁrlukast

Headache, nausea, cough

FDA alert: Rarely neuropsychiatric events have been reported. Also used for allergic rhinitis

Anti-IgE monoclonal antibody

Omalizumab

Injection site reaction Anaphylaxis

For use in persistent allergic asthma refractory 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) (continued on next page)

Pulmonology

317

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 beneﬁt 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 fibrosis 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 identified. • Diagnosis: CF is a clinical diagnosis that requires laboratory corroboration.

CRITERIA FOR THE DIAGNOSIS OF CYSTIC FIBROSIS • ≥1 characteristic phenotypic feature or • Positive family history of CF or • Positive CF newborn screen result

Plus

Evidence of abnormal CFTR function as demonstrated by one of the following: • Elevated sweat chloride ≥60 mmol/L on ≥2 occasions∗ • Identiﬁcation of two disease-causing CFTR gene mutations • Abnormal nasal transepithelial ion transport

∗Should be performed at CF center or experienced laboratory. Adapted from J Pediatr 1998;132(4):589.

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.

P E D I AT R I C S

• 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.

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Pediatrics

COMMON SYMPTOMS AND SIGNS OF CYSTIC FIBROSIS IN VARIOUS AGE GROUPS Adolescence and Adulthood

Infancy

Childhood

Meconium ileus Obstructive jaundice Failure to thrive Hyponatremic dehydration or metabolic alkalosis Edema with hypoproteinemia and anemia Rectal prolapse Recurrent pneumonia or bronchiolitis Salty-tasting skin Acute salt depletion Chronic metabolic alkalosis

Failure to thrive Steatorrhea Distal intestinal obstruction Chronic sinopulmonary disease Recurrent pneumonia Chronic cough and sputum “Atypical” asthma with bronchiectasis, clubbing Persistent CXR abnormalities Pansinusitis Nasal polyps Symptoms of vitamin A, D, E, or K deﬁciency Heat prostration with hypoelectrolytemia

Delayed sexual development Obstructive azoospermia or infertility Congenital absence of the vas deferens Chronic bronchitis with Pseudomonas aeruginosa Bronchiectasis or clubbing Pansinusitis Chronic abdominal pain Idiopathic pancreatitis Cirrhosis Distal intestinal obstruction Diabetes mellitus Hemoptysis Pneumothorax

Adapted from Pulmonary Disease and Disorders 1997:803.

INCIDENCE, DIAGNOSTIC TESTS, AND TREATMENT FOR COMMON MANIFESTATIONS OF CYSTIC FIBROSIS Manifestation of CF Pulmonary Infection Haemophilus influenzae Staphylococcus aureus MSSA MRSA P. aeruginosa

Overall Incidence 16% 51% 21% 54%

Stenotrophomonas maltophilia Nontuberculous mycobacteria Burkholderia cepacia complex

13%

Pancreatic insufficiency

91%

Diagnostic Tests Treatment Double gag or sputum culture Bronchoalveolar lavage CXR and/or Chest CT

Oral, inhaled, or IV antibiotics (see Antibiotics section)

Fecal elastase 72-hr fecal fat study

Pancreatic enzyme replacement therapy

no data 3%

(continued on next page)

Pulmonology

Manifestation of CF

Overall Incidence

Malnutrition

57%∗

Chronic sinusitis with polyps without polyps

10-25% 75-90%

319

Diagnostic Tests Treatment Serial height, weight, and BMI measurements Serum vitamin ADEK levels

High-calorie, highprotein diet Oral supplements Acid blockers Appetite stimulants Enteral feeds via gastrostomy tube

Consider sinus X-rays or CT scan

Antibiotics Nasal steroids Nasal sinus washes Endoscopic sinus surgery

CF-related diabetes (do not see ketosis)

21%

Annual random blood glucose screening OGTT: Every other year for 10-16 yo, then annually when >16 yo.

Subcutaneous insulin Carbohydrate counting

Infertility

Males: >95% Females: ≤20%

Semen analysis Testicular or pelvic US

Genetic counseling Microsurgical epididymal sperm aspiration

Focal biliary cirrhosis

2%–5%

Abdominal US, LFT, liver biopsy

Ursodeoxycholic acid Liver transplantation

Cholelithiasis

≤12%

Abdominal US

Ursodeoxycholic acid Cholecystectomy for recurrent severe symptoms

CF-Related Liver Disease

• 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 (FEV1 >10% decrease), new CXR findings, ↓ 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).

P E D I AT R I C S

∗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.

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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 deficiency: 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

Meconium ileus

10%–20% of infants at birth

DIOS

~15% of older patients

ABPA

1%–10%

Risk Factors

Treatment Surgery PEG electrolyte solution (laxative bowel prep)

Pancreatic insuﬃciency Advanced lung disease

Aggressive bowel regimen (ie, PEG electrolyte solution bowel prep, laxatives, gastrograﬃn enemas) Laparotomy (rarely) Systemic steroids ± antifungal therapy (ie, itraconazole)

Hemoptysis Minor

Infrequent

Pulmonary exacerbations Vitamin K deﬁciency Liver dysfunction with abnormal PT/PTT

Treat infection Observation Vitamin K: Check PT/PTT

Major

~1% of patients each year

Age Advanced bronchiectasis

Acutely: O2, ABC Consider holding Pulmozyme and airway clearance Bronchial artery embolization

Arthritis (CF-associated arthritis, Hypertrophic osteoarthropathy)

~1% of older children

Pulmonary exacerbations Severe pulmonary disease

NSAIDs Occasionally, short course of steroids

Spontaneous pneumothorax (poor prognostic sign)

3%–4% of patients during their lifetime

Older age Advanced bronchiectasis Previous episode (50% recurrence)

Standard therapy for pneumothorax caused by other conditions (eg, chest tube) Pleurodesis for persistent air leaks should be performed in a manner to not preclude possible future lung transplantation

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321

Chronic Management Airway Clearance Therapies • Purpose: Loosen and clear airway mucus; may be preceded by bronchodilator therapy. • All methods should be done with huffing 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 sufficient salt from their diet. • Oral supplements: Vitamin and enzyme supplementation, high-calorie milkshakes, fortified 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 Effects

Comments

Pancreatic Enzyme Replacement Therapy (PERT) Infants: 2000–4000 lipase U/120 mL milk 1–4 yr: 1000 lipase U/kg/ meal + ½ dose with snacks >4 yr: 1000–2000 lipase U/kg/meal + ½ dose with snacks

Fibrosing colonopathy (at high doses) Diaper dermatitis Oral lesions (if the patient chews the beads) Constipation

Dose titrated according to clinical malabsorption Average dose, 1800 lipase U/kg/meal Max dose: 2500 lipase U/kg/meal or 10,000 U/kg/d

Hypervitaminosis

Supplementation required because of malabsorption of fatsoluble vitamins even with enzymes

Fat-Soluble Vitamin Replacement (ADEKs, AquADEKs, Source CF, Vitamax)

<1 yr: 1 mL/day 1–3 yr: 2 mL/day 4–10 yr: 1 tablet/day >10 yr: 2 tablets/day

Vitamin K

2.5–5.0 mg twice weekly (daily with liver disease)

Use in conjunction with oral or IV antibiotics

Mucolytics rhDNase (Pulmozyme)

2.5 mg nebulized once daily

Chest pain, pharyngitis

May use twice daily in acute illness (continued on next page)

P E D I AT R I C S

Pancrelipase (Creon, ZenPep, Pancreaze)

322

Pediatrics Dosage

Adverse Effects

Hypertonic (7%) saline (Hyper-Sal)

4 mL nebulized twice daily

Bronchospasm, sore Give SABA 15 min prior throat, chest tightness

Comments

N-acetylcysteine (Mucomyst)

1 mL of 10% or 20% nebulized three or four times a day

Bronchospasm, cough

Bad odor ↓ with refrigeration Give SABA 15 min prior

Antiinflammatory Therapy Azithromycin

<25 kg: 10 mg/kg 3 X a wk 25–40 kg: 250 mg 3 X a wk >40 kg: 500 mg 3 X a wk

Diarrhea, nausea Monitor LFT, renal function

+ P. aeruginosa AFB negative

Ibuprofen: High dose

20–30mg/kg/dose Q12h (max, 1.2 g/dose; 3.2 g/d) Do not change brands (kinetics can diﬀer)

GI bleeding Renal insuﬃciency

Requires periodic pharmacokinetic testing to ensure correct dosing

ORAL, INHALED, AND INTRAVENOUS ANTIBIOTIC OPTIONS FOR PATIENTS WITH CYSTIC FIBROSIS Drug

Dosage∗

Adverse Effects

P. aeruginosa

Ciproﬂoxacin

40 mg/kg/d divided Q12h (max, 2 g/d)

May cause hypoglycemia, avoid in patients with prolonged QT

S. aureus

Doxycycline

>8 yr: 2–4 mg/kg/d divided Q12–24h; max, 100 mg/dose or 200 mg/d

Tissue hyperpigmentation, enamel hypoplasia, or permanent tooth discoloration

S. aureus (MRSA) H. influenzae S. maltophilia

Trimethoprim/ sulfamethoxazole

10–20 mg/kg/d TMP component divided Q6–8h

GI upset, rash, urticaria, myelosuppression

A. fumigatus (ABPA)

Itraconazole

2–5mg/kg/dose Q12–24h

Liver dysfunction

S. aureus (MRSA)

Linezolid

10 mg/kg Q8–12h; max, 600 mg Q12h

Headache, myelosuppression Second-line; very expensive

P. aeruginosa

Tobramycin (TOBI)

300 mg BID in 28-day cycles

Dysphonia, bronchospasm

P. aeruginosa

Aztreonam (Cayston)

75mg once/day x 28days using Altera e-ﬂow device

Bronchospasm, cough

Organism Oral

Inhaled

(continued on next page)

Pulmonology

323

Drug

Dosage∗

Adverse Effects

P. aeruginosa

Aztreonam

50 mg/kg/dose Q6–8h; max, 50 mg/kg/dose or 2 g/dose

Rash, diarrhea, nausea, vomiting (1%–10%)

P. aeruginosa

Ceftazidime

50 mg/kg/dose Q8h; max, 50 mg/kg/dose or 6 g/d

Diarrhea, may ↑ INR in nutritionally deﬁcient children, hepatic or renal disease

P. aeruginosa

Colistimethate sodium

5 mg/kg/dose divided Q6–8h, increase 1 mg/ kg/dose until 8 mg/kg/ dose (max, 160 mg/dose) is reached or side eﬀects noted

Nephrotoxicity Neurologic abnormalities (primarily paresthesias, may also see dizziness, slurred speech, vertigo, headache, fever)

P. aeruginosa

Gentamicin/ tobramycin

3 mg/kg/dose Q8h (titrate to peak of 10–12 μg/L and trough <2 μg/L)

Nephrotoxicity Ototoxicity

P. aeruginosa B. cepacia

Meropenem

40 mg/kg/dose Q8h; max, 2 g/dose or 6 g/d

Headache, nausea, vomiting, diarrhea, hypoglycemia

P. aeruginosa S. aureus (MSSA) S. maltophilia

Ticarcillin/ clavulanic acid

400 mg/kg/d ticarcillin component divided Q4–6h; max, 24 g of ticarcillin component/d

Headache, nausea, vomiting, diarrhea, hepatotoxicity, hypoglycemia

S. aureus (MRSA)

Clindamycin

10 mg/kg/dose Q8h; max, 900 mg/dose or 2.7 g/d

Abdominal pain, nausea, vomiting, diarrhea, ↑ LFT, renal dysfunction

S. aureus (MRSA)

Vancomycin

13–15 mg/kg/dose Q8h; max, 1.5 g/dose or 4 g/d

“Red-man” syndrome Nephrotoxicity

Organism Intravenous

APPARENT LIFE-THREATENING EVENT (ALTE) • Definitions • 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 airflow 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. Identified 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 finding). • Circumoral cyanosis: Bluish “moustache” or purple perioral region (normal neonate/ infant finding).

P E D I AT R I C S

∗ These are recommended starting doses for commonly used antibiotics. Exact dosing for a particular antibiotic or class should be conﬁrmed for each individual patient.

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, intracranial bleed, meningitis, encephalitis, hydrocephalus, brain tumor, neuromuscular disorders, vasovagal reaction, malformation of the brainstem

15

Respiratory: RSV bronchiolitis, pertussis, aspiration, pneumonia, URI or LRTI, wheezing, foreign body

11

Otolaryngologic: Laryngomalacia, subglottic or laryngeal stenosis, OSA

4

Cardiovascular: Congenital heart disease, cardiomyopathy, arrhythmia, myocarditis

1

Metabolic or endocrine: Electrolyte abnormality, hypoglycemia, IEM

<1

Infection: UTI, sepsis Nonaccidental trauma (NAT): Shaken baby syndrome, intentional suﬀocation, ﬁctitious 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 specific focus on relationship to feeding, reflux 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. Considerations 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)

Volume

Inspiratory Reserve Volume (IRV)

Inspiratory Capacity (IC)

Vital Capacity (VC)

Total Lung Capacity (TLC)

Tidal Volume (TV) Expiratory Reserve Volume (ERV) Residual Volume (RV)

Functional Residual 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 6 FEF50

FEV1∗

2 FEF75

FVC

0 2 FIF25 FIF75 FIF50

4

Inspiration

Flow (L/sec)

FEV∗½

2

4

6

Volume (L)

6 8 10

Figure 25-4 Normal flow–volume loop from spirometry. Note: FEV1 is the volume of gas exhaled in the first 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 flow rate (Forced Expiratory Flow rate) between 25% and 75% of FVC. FIF, Forced Inspiratory Flow; FVC, Forced Vital Capacity.

P E D I AT R I C S

4

Expiration

FEF25

326

Pediatrics

INTERPRETATION OF ABNORMAL SPIROMETRY TEST RESULTS Lung Disease Pattern Obstructive

Spirometry Findings

Diseases

↓ or normal FVC ↓ FEV1

Small airway obstruction: Asthma, CF, ↑ production of or ↓ clearance of mucus Central airway obstruction: Subglottic and tracheal stenosis, tracheomalacia, vascular ring, vocal cord paralysis Loss of parenchymal elastic recoil: Emphysema, interstitial ﬁbrosis

↓ FEV1/FVC ratio ↓ FEF25%–75% Concave expiratory loop

Restrictive

↓ or normal FVC ↓ FEV1 ↑ FEV1/FVC ratio Normal/ ↑ FEF25%–75% ↓ Inspiratory VC

Interstitial lung disease (eg, ﬁbrosis) Scoliosis Neuromuscular disorders

Available at www.AccessPediatrics.com • Chronic cough • Hemoptysis

C H A P T E R 26

Rheumatology DIFFERENTIAL DIAGNOSES OF MUSCULOSKELETAL COMPLAINTS IN CHILDREN Mechanical/orthopedic problems: Joint hypermobility, benign joint hypermobility syndrome, localized hypermobility, Marfan syndrome, Ehlers–Danlos syndrome, irritable hip (transient synovitis), Perthes’ disease, other osteochondritis, slipped upper femoral epiphysis, chondromalacia patella, anterior patella syndrome, back pain Inflammatory disorders: JIA, JRA, spondyloarthritis, psoriatic arthritis, SLE (lupus), juvenile dermatomyositis, IBD, MCTD, linear scleroderma, progressive systemic sclerosis, panniculitis, CRMO/SAPHO syndromes, vasculitis, KD, HSP Infection/postinfective: Transient synovitis, rheumatic fever, septic arthritis, osteoarticular tuberculosis, brucella/lyme/fungal arthritis Hematologic problems: Sickle cell disease, other hemoglobinopathies, hemophilia Neoplasia: Leukemia, neuroblastoma, metastatic disease, primary bone tumors Idiopathic pain syndromes: Nocturnal idiopathic pain syndrome (growing pains), reﬂex sympathetic dystrophy, widespread idiopathic pain syndrome, ﬁbromyalgia Metabolic disorders: Gout, mucopolysaccharidoses, mucolipidosis type III, Fabry’s disease, alkaptonuria, Lesch–Nyhan syndrome Other: Sarcoidosis, immune complex deposition, cystic ﬁbrosis, serum sickness, septicemia, immunodeﬁciency related, drug induced

EVALUATION OF SYNOVIAL FLUID

Viscosity

WBC (cells/mm3)

PMN (%)

Miscellaneous Findings

Noninflammatory Normal

Yellow and clear

Very high

<200

<25

Traumatic arthritis

Xanthochromic and turbid

High

<2,000

<25

Debris

Inflammatory Chronic arthritis

Yellow and cloudy

Decreased

15,000–20,000

75

Reactive arthritis

Yellow and opaque

Decreased

20,000

80

Tuberculous arthritis

Yellow-white and cloudy

Decreased

25,000

50–60

Acid-fast bacteria

Septic arthritis

Serosanguinous and turbid

Decreased

50,000–300,000

>75

Low glucose, bacteria present

Pyogenic

327

P E D I AT R I C S

Color and Clarity

ACUTE ARTHRITIS

Single/few joints

Multiple joints

Fever YES

Fever NO

NO

• Infection/sepsis (gonococcal) • Other (malignancy, systemic JIA, SLE)

• Rheumatic (JIA, JAS, SLE) • Other (sickle cell disease, IBD, vasculitis)

328

YES

• Transient synovitis (low grade fever) • Infection (septic arthritis, osteomyelitis) • Vasculitis (serum sickness, hypersensitivity, KD) • Rheumatic (JIA, JAS, SLE) • Other (malignancy, IBD)

• Trauma • Transient synovitis • Lyme arthritis • Rheumatic (JIA, JAS, SLE) • Vasculitis (HSP) • Infection (TB, fungal) • Other (malignancy, IBD)

Figure 26-1 Differential diagnosis of a child presenting with signs/symptoms of acute arthritis.

Rheumatology

329

LABORATORY EVALUATION OF RHEUMATIC DISEASES Specificity/ Sensitivity

PPV

ANA Anti-dsDNA Anticardiolipin Ab (lupus anticoagulant) Anti-Smith Ab

57%/93% 97%/57% Yes/No

Moderate 95% Low

High/25%–30%

97%

Drug-induced lupus

Antihistone Ab1

High/95%

High

Scleroderma

ANA Anticentromere Anti–Scl-70

54%/85% 99.9%/65% 100%/20%

High High High

MCTD

ANA Anti-U1 ribonucleoprotein (RNP)1

No/93% High/Moderate

High High

Polymyositis, Dermatomyositis

CK Anti–Jo-1 Ab Muscle biopsy

No/High Yes/30%–50% Yes/Moderate

Low High High

Sjögren’s syndrome

ANA Anti-SSA/Ro (type A)2 Anti-SSB/La (type B)

52%/48% 87%/8%–70% 94%/16%–40%

Moderate 40% 40%

Wegner’s granulomatosus

Anti-proteinase 3 Ab c-ANCA Ab

High/moderate 50%/95%

High High

Disease

Test

Systemic lupus erythematosus (SLE)

JUVENILE IDIOPATHIC ARTHRITIS (JIA) • Definition: 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 classification 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), ESR, CRP, α1 antitrypsin (serum), serum amyloid A (SAA) protein, Ig (↑ or normal), ANA, RF, HLA-B27.

P E D I AT R I C S

1 False positive in SLE. 2 False 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.

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 Percent of cases

Systemic Disease1

30

10

Clinical presentation

≤4 joints involved; predominantly knees, ankles, ﬁngers, wrists, and elbows in an asymmetric fashion

>4 joints involved; large and small joints;

Variable number/types of joints involved; concomitant arthritis, quotidian fever, and salmon-colored evanescent rash that is sometimes pruritic; rash appears as fever subsides; HSM, LAD, serositis; ↓ H/H, ↑ plt, ↑ WBC; elevated inﬂammatory markers; ↑ transaminases

Age of onset

Peak 1–2 yo; early childhood

Peak 1–3 yo; all ages

No peak; throughout childhood

Sex ratio (♀:♂) Systemic involvement Occurrence of chronic uveitis

60

Polyarthritis

5:1 Absent; major morbidity is uveitis 5%–15%

3:1 Generally mild; possible unremitting articular involvement 5%

1:1 Often self-limited; 50% with chronic and destructive arthritis Rare

⊕RF ⊕ANA

Rare 75%–85%3

10%2 40%–50%

Rare 10%

Prognosis

Excellent except eyesight

Guarded to moderately good

Moderate to poor

Treatment

• NSAIDS • ± intraarticular steroid injections • MTX

• NSAIDS + therapies below • Corticosteroids • MTX, sulfasalazine, azathioprine • Biologic agents: TNF-α inhibitors (inﬂiximab, etanercept, adalimumab; IL-1 receptor antagonists), IL-1 inhibitor (anakinra)

Additional options for treatment

Other biologic agents: abatacept (FDA approved for adults); rituximab (FDA approved for adults)

Anti–IL-6 monoclonal, antibody tozilizumab, currently under investigation

1 Still’s disease: acute complication is development of macrophage activation syndrome (MAS) with considerable morbidity/mortality. 2 RF-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.

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331

PEDIATRIC SYSTEMIC LUPUS ERYTHEMATOSUS (pSLE) • Definition: Multisystem autoimmune disease characterized by immune complex deposition and inflammation 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 classification 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

Adapted from Arthritis Rheum 1997;40:1725.

• Diagnostic Evaluation • Clinical diagnosis of SLE is supported by laboratory findings. • 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 flare. • An ANA test is not specific for SLE in the absence of other laboratory or clinical findings. 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.

P E D I AT R I C S

1. Malar rash (also known as a “butterﬂy” rash—ﬂat 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 thombocytopenia [<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: hydralazine, procainamide, minocycline, INH, penicillin, sulfonamides, and anticonvulsants) 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, conﬁrmed negative by Treponema pallidum immobilization/ﬂuorescent treponemal antibody absorption test) 11. Neurologic disease (psychosis or seizures in the absence of drugs or metabolic derangements)

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 flare: 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 efficacy). • 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 significant pathogenic antibodies is merited (pulmonary hemorrhage, severe CNS disease). Does not inhibit ongoing pathogenic antibody production. Risks of plasmapheresis: hypogammoglobulinemia, 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 immunosuppressant 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 involvement (ie, sinusitis, OM)

Wegener granulomatosis

Mucocutaneous ﬁndings

Kawasaki disease (KD) Behçet syndrome

Abnormal pulses

Takayasu arteritis, KD, polyarteritis nodosa

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333

Henoch–Schönlein Purpura (HSP) • Definition: 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, inflammation, 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)

Renal

• Typically within 4 wk of onset of disease: microscopic or macroscopic hematuria, mild to nephrotic range proteinuria, peripheral edema, hypertension, renal insuﬃciency • 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 (↓), inflammatory 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; immunofluorescence (IF) confirms predominance of IgA and fibrinogen deposition

P E D I AT R I C S

• Chylous ascites, pancreatitis (very rare) • Intussusception

VASCULITIS

Large vessel vasculitis

Medium vessel vasculitis

Small vessel vasculitis

• Giant cell arteritis • Takayasu arteritis

• Childhood systemic polyarteritis nodosa • Cutaneous polyarteritis nodosa • Kawasaki disease

ANCA positive? NO

334

Immune-complex mediated small vessel vasculitis

• • • • • •

Henoch-Schönlein purpura Cryoglobuliinemic vasculitis Lupus vasculitis Goodpasture syndrome Sjogren disease Drug-induced immunecomplex vasculitis • Behcet syndrome • Infection-induced immunecomplex vasculitis Figure 26-2

Classification of vasculitides by vessel size.

YES

• • • •

Wegener granulomatosis Microscopic polyangitis Churg-Strauss syndrome Drug-induced

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335

Kawasaki Disease (Pediatrics 2004;114(6):1708) • Definition: 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 Pacific 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 findings (see table below).

P E D I AT R I C S

• Renal: Reserved for significant renal involvement, declining kidney status, or chronic proteinuria; biopsy reveals IgA and fibrinogen 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 insufficiency, 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 sufficient 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 benefit in severe GI involvement • Severe renal involvement, CNS disease, or significant pulmonary disease may require stronger immunosuppressive therapy, such as cyclophosphamide.

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 ﬁve principal features 1. Changes in extremities • Acute: Erythema and edema of hands and feet • Convalescent: Membranous desquamation of ﬁngertips 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 findings Cardiovascular ﬁndings

• 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)

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337

Other clinical findings Other ﬁndings

• Perineal rash and desquamation • Erythema, induration at previous BCG inoculation site • Beau lines: transverse furrows of ﬁngernails in convalescence phase • Macrophage activation syndrome

1 A diagnosis of KD can be made on the fourth day of fever when four out of ﬁve 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 ﬁeld (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.

P E D I AT R I C S

• Treatment • IVIG, 2 g/kg given as a single infusion over 10–12 hr. • 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 benefit from anti-TNF agents (infliximab 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/inflammatory 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 inflammation (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 first 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 criteria 1

Assess Patient Characteristics 2 Inconsistent with KD

Consistent with KD

KD Unlikely

Assess Laboratory Tests

CRP ≥ 3.0 mg/DL and/or ESR ≥ 40 mm/hr

CRP < 3.0 mg/DL and ESR < 40 mm/hr

< 3 Supplemental Laboratory Criteria 3

≥ 3 Supplemental Laboratory Criteria 3

Fever resolves

Echo

Treat and Echo 4

No Typical Peeling Peeling 7

Echo +

Follow Daily

Fever continues for 2 days

Persistent Fever

No f/u

Fever Persists

Echo 5

Repeat Echo, Consult KD Expert

Echo + 5

Fever Abates

Treat 6

KD Unlikely

Figure 26-3 Evaluation of suspected incomplete KD. (Reprinted with permission from Pediatrics 2004;114(6):1708.) 1 Infants ≤6 mo on day ≥7 of fever without other explanation should undergo laboratory testing; if evidence of systemic inflammation is found, obtain echocardiogram (even if infant has no other clinical criteria). 2 Characteristics 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”). 3

See the table LABORATORY FINDINGS SUGGESTIVE OF INCOMPLETE KD.

4

Do not delay treatment for echocardiogram.

5

Echocardiogram 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. 6 If 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 inflammation. 7

Typical peeling begins around nail bed of fingers and then nail bed of toes.

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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 fibrinolytic 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 hyperflexible 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 • Osteogenesis Imperfecta • Williams syndrome • Trisomy 21 (Down syndrome)

• 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 fibromyalgia • Complex regional pain syndrome • Juvenile dermatomyositis

P E D I AT R I C S

• Marfan syndrome • Homocystinuria • Stickler syndrome

CHAPTER 27

Toxicology • One to two tablets or 1 to 2 tsp (standard pediatric “swallow” ~5–10 cc) of the standardstrength 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 Diagnosis History Physical examination Toxidrome recognition Diagnostic testing

Treatment Airway Breathing Circulation Decontamination 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 quantification, 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, ganja, grass, joint, Mary Jane, pot, rope, reefer Amphetamines: Black beauties, crank, crystals, cat (methcathinone), ice, ecstasy, meth, pep pills, smart drug (Ritalin), speed, uppers Ecstasy: Adam, E, lollies, love drug, smarties, vitamin E, XTC Heroin: Boy, China white, dust, Harry, horse, junk, monkey, smack, speed ball (with cocaine), atom bomb (with marijuana)

PCP: Angel dust, goon, horse tranquilizer, hog, Sherman, tank, wickie stick (with marijuana) δ-hydroxybutyrate (GHB): Bioski, Georgia home boy, grievous bodily harm, liquid G, liquid ecstasy, somatomax, cow growth hormone Cocaine: All-American drug, coke, crack, girl, mother of pearl, nose candy, Peruvian powder, snow, toot, white lady LSD: Acid, blotters, microdots, paper acid, pyramids, window pane, Zen

AGENTS OF INTOXICATION WITH UNIQUE ODORS Odor

†

Agent

Wintergreen

Methyl salicylate

Garlic

Arsenic, DMSO, organophosphate insecticides, selenium

Rotten eggs

Hydrogen sulﬁde, 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

P E D I AT R I C S

• 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 toxicity).

342

Pediatrics

RAPID URINE TESTING FOR DRUGS OF ABUSE Drug

Duration of Urine Detectability

Drugs Causing False-Positive 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 with chronic moderate to heavy use

Dronabinol, efavirenz, hemp seed oil, ibuprofen, naproxen

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 Calcium Opiate or cocaine packets

Iron and other heavy metals Neuroleptic agents Sustained-release or enteric-coated agents

PHYSICAL EXAM FINDINGS OF SELECTED TOXINS* Symptoms

Intoxications

Withdrawals

Tachycardia

Anticholinergics, sympathomimetics, theophylline, levothyroxine, TCAs

Barbiturates, 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

Pulmonary edema (noncardiogenic)

Meprobamate, methadone, opioids, paraquat, phenobarbital, phosgene, propoxyphene, salicylates

Withdrawals

Hypoxia

Benzocaine (secondary to methemoglobinemia), carbon monoxide, opioids, sedative–hypnotics

Hypertension

Anticholinergics, caﬀeine, nicotine, PCP, sympathomimetics, levothyroxine

Ethanol

Hypotension

Antihypertensives, barbiturates, benzodiazepines, ethanol,∗ iron, opioids, rodenticides (containing arsenic, cyanide), TCAs

Barbiturates, benzodiazepines, ethanol

Miosis

Cholinergics, clonidine, organophosphates, opioids, oxymetazoline, phenothiazines, pilocarpine

Mydriasis

Anticholinergics, antihistamines, marijuana, sympathomimetics, TCAs

Opioid

Hyperthermia

Amphetamines, anticholinergics, cocaine, MAOIs, neuroleptic malignant syndrome, PCP, salicylates, serotonin syndrome

Ethanol

Hypothermia

Barbiturates, benzodiazepines, carbon monoxide, clonidine, ethanol, opioids, oral hypoglycemics, phenothiazines, TCAs

Seizures

Amphetamines, anticholinergics, atropine, bupropion, caﬀeine, camphor, carbon monoxide, chlorinated hydrocarbons (lindane), cocaine, cyanide, INH, inhalants, insulin, lead, lidocaine, lithium, methanol∗, mushrooms, nicotine, oral hypoglycemics, organophosphates, PCP, salicylates, strychnine, TCAs, theophylline

Anion gap metabolic acidosis (see Fluid, Electrolyte, and Acid–Base Balance, Chapter 15, for more detail)

Alcohols∗ (ethanol,∗ ethylene glycol,∗ methanol∗), carbon monoxide, cyanide, ibuprofen, INH, iron, metformin, salicylates

Hypoglycemia

Alcohols,∗ β-blockers, insulin, oral hypoglycemics, salicylates

Acute ataxia or nystagmus

Alcohols,∗ anticonvulsants, (especially phenytoin) antihistamines, barbiturates, carbon monoxide, organic solvents, PCP (rotary nystagmus, versus vertical nystagmus of brainstem lesion)

Emesis, severe

Boric acid, corrosives, ﬂuoride, iron, salicylates, theophylline

Renal failure

Carbon tetrachloride, ethylene glycol,∗ methanol,∗ mushrooms, oxalates

Skin Color

Red: Anticholinergics, boric acid, carbon monoxide, cyanide Blue: Methemoglobinemia

Barbiturates, benzodiazepines, ethanol

P E D I AT R I C S

Opioids

(continued on next page)

344

Pediatrics

Symptoms

Intoxications

Withdrawals

Diaphoresis

Organophosphates, PCP, salicylates, sympathomimetics

Opioids

Altered mental status

Anticonvulsants, antihistamines, antipsychotics (risperdone), benzodiazepines (Rohypnol), carbon monoxide, clonidine, cyanide, GHB, ethanol,∗ ethylene glycol,∗ heavy metals (lead), hemlock, INH, insulin, lithium, opioids, oral hypoglycemics, TCAs, thallium, toluene, toxininduced hepatic encephalopathy

Ethanol

∗ Associated with an increased osmolar gap.

TOXIDROMES

HR Adrenergic ↑

Anticholinergic

↑

Cholinergic

↓

RR Pupils

Other Skin and Neurologic Symptoms Mucous or Mental or Membranes Status Mnemonic Agents

↑

Dilated, reactive

Diaphoretic

Agitated, psychosis, delirium

± Hyperthermia, tremors, hypertension, hyperreﬂexia

Amphetamine, caﬀeine, cocaine, ephedrine, sympathomimetics, theophylline

↔

Dilated, sluggishly reactive

Dry, ﬂushed skin; dry mucous membranes

Depressed, confused, hallucinations, EPS

HOT as a hare, MAD as a hatter, RED as a beet, DRY as a bone, BLIND as a bat: Hyperthermia; delirium or hallucinations; ﬂushed, dry skin; dilated pupils

Antihistamines, atropine, belladonna alkaloids, benztropine, mushrooms, phenothiazines, scopolamine, TCAs

Constricted

Diaphoretic skin; salivation, tearing

Depressed, confused

DUMBBELLS: Diarrhea and GI upset, urination, miosis, bradycardia, bronchoconstriction, emesis, lethargy, lacrimation, secretions or salivation

Black widow spider bites, mushrooms, pesticides (carbamates, organophosphates), pilocarpine

(continued on next page)

Toxicology

345

Other Skin and Neurologic Symptoms Mucous or Mental or Membranes Status Mnemonic Agents

HR

RR Pupils

Opioid

↓/↑

↓

Constricted

Dry or no change

Depressed, confused

Constipation Narcotics or urinary retention, ± hyporeﬂexia, pulmonary edema

Salicylism

±↑

↑

Normal

No change

Confusion, seizures, tinnitus

Nausea, metabolic acidosis

Sedative– ↔/↓ ↓ hypnotics

Normal or constricted

No change

Depressed, confused

± urinary Benzodiazretention, epines constipation, hypotonia

Normal

No change

Confusion, coma, seizures

Ventricular arrhythmia, ↓ BP, anticholinergic eﬀects

TCAs

↑

↑

Aspirin, oil of wintergreen

Imipramine, amitriptyline

OVERVIEW OF ANTIDOTES AND RECOMMENDED INITIAL DOSING IN PEDIATRICS 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

Arsenic, mercury, lead, other heavy metals

Dimercaprol: 3–5 mg/kg/dose Q4h (duration depends on degree 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 ﬁrst 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, methanol

Fomepizole: No dosage data in pediatrics, may use: 15 mg/kg 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)

P E D I AT R I C S

Toxin

346

Pediatrics

Toxin

Antidote

Methemoglobinemia

Methylene blue: 1–2 mg/kg

Neuroleptics (resulting in acute dystonia)

Diphenhydramine: 5 mg/kg divided Q6–8h or benztropine 1–2 mg 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 Medications and Measures

Toxin

First-Line Measures∗

Additional Measures

Antihistamines

Sodium bicarbonate

Magnesium sulfate, propranolol, isoproterenol, ﬂecainide, magnesium sulfate

Class Ia and III

Class I antiarrhythmics

Sodium bicarbonate, run mildly alkalotic, and keep potassium low normal

Atropine, phenytoin

Class I (although lidocaine can be used for arrhythmias caused by Ia and Ic)

Class II antiarrhythmics

Atropine, glucagon, cardiac pacing

Adrenaline, isoproterenol, dopamine, dobutamine

Isoproterenol may result in tachyarrhythmias

Class III antiarrhythmics

Amiodarone: Toxicity is generally low Sotalol: Initial treatment as for other β-blockers

Lidocaine for sotalol, magnesium sulfate

Class IV antiarrhythmics

Calcium gluconate, cardiac pacing

Atropine, glucagon, dopamine

Cocaine

Sodium bicarbonate

Diazepam, NTG, calcium antagonists

β-blockers

Digoxin

Correct hyperkalemia (avoid calcium), digoxin antibodies, cardiac pacing

Atropine, lidocaine, amiodarone, phenytoin

Class Ia, Ic, DC cardioversion, calcium, inotropes

(continued on next page)

Toxicology

Toxin TCAs

347

Contraindicated Medications and Measures

First-Line Measures∗

Additional Measures

Sodium bicarbonate; try to avoid other agents as much as possible

Phenytoin, atenolol, glucagon, lidocaine for ventricular arrhythmias, magnesium sulfate

Class Ia

∗ In all cases, ﬁrst-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 3000

500

1300

200

1000 900 800 700 600 500 400

150

Probable hepatic toxicity

P E D I AT R I C S

50 ib

ss le

300 250 200

100

Po tic

No hepatic toxicity

ity

xic

to

100 90 80 70 60 50

pa

he

Acetaminophen plasma concentration

2000

10

40 30

25%

5

20

10

0

4

8 12 16 Hours after ingestion

20

24

Figure 27-2 Nomogram for prediction of acetaminophen hepatotoxicity after acute overdose. Note: The upper line defines serum acetaminophen concentrations likely to be associated with hepatotoxicity; the lower line defines 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 Companies, 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 0

-1

1

2

3

4

5

Posture

Square window (wrist)

>90°

90°

60°

45°

180°

0°

45°

140° to 180°

Arm recoil

30°

110° to 140°

90° to 110°

Popliteal angle <90°

160°

180°

140°

90°

100°

120°

Scarf sign <90°

Heel to ear

Total Neuromuscular Maturity Score Physical maturity 0

-1 Skin

Lanugo Plantar surface Breast

1

Stickey, friable, Gelatinous, transparent red, translucent None Sparse

Smooth, pink, visible veins

Heel toe 40–50 > 50 mm: no crease mm: −1 < 40 mm: −2 ImperceptibIe Barely perceptible

Faint red marks

Eye/Ear

Lids fused loosely: −1 tightly: −2 Genitals Scrotum flat, (male) smooth Genitals Clitoris (female) prominent & labia flat

Abundant

2 Superficial peeling &/or rash; few veins Thinning

Anterior transverse crease only Flat areola; no Stippled areola; bud 1- to 2-mm bud Lids open; Slightly curved Well-curved pinna flat; pinna; soft; slow pinna; soft but stays folded recoil ready recoil Scrotum empty; Testes in upper Testes faint rugae canal; rare descending; few rugae rugae Prominent Prominent clitoris Majora & clitoris & small & enlarging minora equally labia minora minora prominent

3

4

Cracking, pale areas; rare veins Bald areas

Parchment, deep cracking; no vessels Mostly bald

Creases anterior 2/3

Creases over entire sole

Raised areola; 3- to 4-mm bud Formed & firm instant recoil

Full areola; 5- to 10-mm bud

Testes down; good rugae

Testes pendulous; deep rugae Majora cover clitoris & minora

Majora large; minora small

5 Leathery, cracked, wrinkled

Thick cartilage; ear stiff

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

1

2

Heart rate

Absent

Slow (< 100)

>100

Respiratory effort

Absent

Slow, irregular

Good, crying

Muscle tone

Limp

Some flexion

Active motion

Response to catheter in nostrilb

No response

Grimace

Cough or sneeze

Color

Blue or pale

Body pink; extremities blue

Completely pink

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.) a

One 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.

b

Tested 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.

• 37-41 completed weeks’ gestation • No findings that require continued hospitalization. • Vital signs documented as normal (see “Newborn Exam” above).

NE ON AT OLO GY

EARLY DISCHARGE CRITERIA (<48 H OF LIFE) (institutional practice; adapted from Pediatrics 2010;125(2):405)

350

Neonatology

• Infant has urinated regularly and passed at least one stool spontaneously. • Infant has completed at least 2 successful, consecutive feeds • No significant 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 identified 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 fontanelles

Large or bulging fontanelles

Palpate skull and sutures

Overlapping/separated sutures, craniotabes

Face

Dysmorphisms, asymmetry

Eyes

Set and position, red reﬂex, pupillary reﬂexes (continued on next page)

Newborn Nursery

351

Physical Exam Component

Look for…

Ears

Set and position, pits, tags, malformations, patent ear canals

Nose

Nasal ﬂaring, asymmetry, obstruction, dislocation

Mouth, including buccal mucosa, tongue, palate and posterior pharynx

Rooting reﬂex, suck reﬂex, natal teeth, Epstein pearls, cleft lip and/or palate, gag reﬂex

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; count HR for 1 min

Cardiac murmurs, arrhythmias, clicks, rubs

Observe respirations; auscultate lungs; count RR for 1 min

Equality of breath sounds, crackles, stridor, wheezes; screen for bowel sounds in the chest

Inspect thorax and clavicles

Asymmetry, accessory nipples; palpate clavicles for crepitus Gynecomastia, masses, asymmetry

Auscultate abdomen in four quadrants

Bowel sounds in all areas

Palpate abdomen—light and deep

Organomegaly, masses, enlarged kidneys, diastasis rectus, umbilical hernias

Examine umbilical cord and count vessels

Odor, edema, erythema, discharge, bleeding

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 while infant is prone

Asymmetric skin folds, leg length discrepancies, 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, examine palmar creases

Reﬂexes

Rooting, Moro, clonus, Babinski, plantar and palmar grasps

NE ON AT OLO GY

Palpate breast tissue

352

Neonatology Caput Succedaneum

Cephalohematoma Subgaleal hemorrhage Extradural hemorrhage

Skin 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 Diﬀerential

• 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 ﬁlms; consider direct laryngoscopy, airway ﬂuoroscopy, and/or barium swallow

Management

• Consider otolaryngology consult; prepare for intubation if patient in distress

VOMITING∗ Diﬀerential

• 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 ﬂuids 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 Diﬀerential

• Pulmonary pathology: TTN, pulmonary edema, HMD/surfactant deﬁciency, 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∗ Diﬀerential

• Pulmonary disorder: hypoxemia from respiratory insuﬃciency 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).

• Circumcision • Newborn exam abnormalities

NE ON AT OLO GY

Available at www.AccessPediatrics.com

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 confinement (EDC) or estimated date of delivery (EDD) is calculated by adding 7 d to the first 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

Date of assessment

Expected date of delivery

Birth

Conception

1st day of LMP

Gestational age

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 first or second trimester supports a GA of 39 wk or greater.

EVALUATION OF FETAL LUNG MATURITY

Test

Predictive Value for Maturity Threshold When Test Value to Shows Indicate Maturity Maturity (%)

Predictive Value for Immaturity When Test Shows Affected by Immaturity Relative Blood or (%) Cost Meconium?

Can Pooled Vaginal Specimen Be Used?

L:S ratio

>2.0

95–100

33–50

High

Yes

No

PG

If present, indicates maturity

95–100

23–53

High

No

Yes (bacteria may cause falsepositive)

FSI

>47–48

95

51

Low

Yes

No

FLM-TDx >55 mg/g

96–100

47–61

Moderate Yes

Yes

Lamellar ≥50,000 body count

97–98

29–35

Low

Unknown

Blood only

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

NE ON AT OLO GY

• 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 • 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 • Definitions • 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 first 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 vasoconstriction, and hypertension Increased hydrostatic pressure

Systemic hypertension, intravascular hemolysis Generalized edema

Uteroplacental

Uteroplacental insuﬃciency

Fetal somatic growth deﬁciency; fetal hypoxemia and distress Abruptio placentae; placental infarcts Thrombocytopenia

Decidual ischemia Decidual thrombosis Renal

Decreased renal blood ﬂow and GFR; endothelial damage High AT-II responsiveness of tubular vasculature All of the above

Proteinuria; elevated Cr, decreased Cr clearance; oliguria Elevated uric acid

Cerebrovascular

Cerebral motor ischemia High CPP with regional ischemia Cerebral edema Regional ischemia

Eclampsia (seizures) Cerebral hemorrhage Coma Central blindness; loss of speech

Hepatic

Ischemia; hepatocellular injury Mitochondrial injury

Elevated LFTs Intracellular fatty deposits

Hematologic

Intravascular hemolysis

Schistocyte burr cells; elevated free hemoglobin and iron; decreased haptoglobin levels Thrombocytopenia; antiplatelet antibodies

Decidual thrombosis, release of ﬁbrin degradation products

ATN, renal failure

• Fetal and neonatal complications • Prematurity (often caused by medical intervention) • Uteroplacental insufficiency → fetal somatic growth deficiency, fetal hypoxemia or distress • Abruptio placentae

Fetal Assessment and Prenatal Diagnosis

357

FETAL AND NEONATAL COMPLICATIONS OF MATERNAL MEDICAL CONDITIONS Maternal Medical Condition

Maternal Complications During Pregnancy

Fetal and Neonatal Complications

DM

Hypoglycemia; DKA; hypertension; progression of diabetic retinopathy; polyhydramnios; cephalopelvic disproportion; increased risk of malpresentation, cesarean section, and operative vaginal delivery

Hypoglycemia, macrosomia, birth trauma, IUGR, hypoxia, caudal dysplasia, congenital heart defects, neural tube defects, intrauterine fetal demise

Hypertension

Generalized edema, intravascular hemolysis, thrombocytopenia, renal insuﬃciency, proteinuria, seizures, cerebral hemorrhage, coma, central blindness, elevated liver enzymes, abruption placentae, preterm labor

IUGR, fetal hypoxemia and distress, prematurity

Hypothyroidism

First trimester miscarriage, preeclampsia, placental abruption, preterm delivery, postpartum hemorrhage

IUGR, suboptimal neurodevelopmental outcome

Substance abuse

Tobacco: Perinatal death, spontaneous abortion, stillbirth, abruption placentae, placenta previa, premature delivery Cocaine: Abruption placentae, spontaneous abortion, premature rupture of membranes

Tobacco: Growth restriction, increased risk of SIDS and respiratory diﬃculties Cocaine: IUGR, adverse neurodevelopmental outcomes

SONOGRAPHIC AND FETAL ECHOCARDIOGRAPHIC ASSESSMENT Antenatal Ultrasonography

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• 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: Confirm 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 • 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 fistula, 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

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Fetal Echocardiography • Specific 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 Serum Marker

Trisomy 21

Trisomy 13

Trisomy 18

Neural Tube Defects

↑

Second Trimester AFP

↓

Normal

↓

hCG

↑

Normal

↓

∗

Unconjugated estriol

↓

Normal

↓

∗

Inhibin-A

↑

Normal

∗

∗

PAPP-A

↓

∗

↓

∗

hCG

↑

∗

↓

∗

First Trimester

∗Value not typically used for estimating the risk of this disorder. D, decreased; I, increased; N, no change; N/A, not applicable.

• US finding of aneuploidy • Nuchal measurements: Nuchal translucency at 11–14 wk (sagittal view) and nuchal fold at 15–20 wk (axial view); the size of fluid 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 findings are more commonly seen in aneuploidy but are neither sensitive or specific: 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 fluid cells, >99%. • Cytogenetic analysis can be completed 7–12 d after procedure. • Complications: Chorioamnionitis (<1 in 1000 procedures), leakage of amniotic fluid (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 insufficiency. 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 IUGR

Cyanotic heart disease

Multiple gestations

SLE

Postterm pregnancy (continued on next page)

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IDDM

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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 fluid volume (amniotic fluid index; see below) reduces the false-positive rate (referred to as the modified biophysical profile [modified 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 significant 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 significant variable decelerations are noted.

Biophysical Profile • 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 ﬂexion of a limb or trunk, or the opening or closing of a fetal hand

Amniotic ﬂuid volume

Single vertical pocket at least 2 cm deep

NST

Reactive test

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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 nonspecific. • No proven benefit 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 Mechanism

Interpretation

Accelerations

Increase in the fetal HR

Physiologic fetal response to movement

Reassuring

Early decelerations

Shallow and symmetric; occur at time of contraction

Fetal head compression during labor

Uncommon; generally not concerning

Variable decelerations

Slowing of the FHR with abrupt onset and return

Umbilical cord compression

Nonreassuring features include deceleration to <70 bpm, duration >60 sec, associated with change in baseline or decreased variability

Late decelerations

Decrease in FHR below baseline after contraction

Transient fetal hypoxia caused by decreased placental perfusion with contractions

Occasional or intermittent late decelerations are common; when persistent, are nonreassuring

Sinusoidal HR

Sinusoidal pattern lasting ≥10 min; relatively ﬁxed period of three to ﬁve cycles/min and an amplitude of 5–15 bpm above and below baseline

Unknown

Rare; associated with severe chronic fetal anemia, medications (eg, alphaprodine), severe hypoxia, and acidosis

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FHR Finding Description

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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 fluid with normal saline may be considered for significant 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

C H A P T E R 30

Stabilization, Delivery Room Care, and Initial Treatment of the VLBW Infant STABILIZATION IN THE DELIVERY ROOM Anticipation of High-Risk Delivery • Situations in which resuscitation may be expected: • Preterm delivery • Narcotics in labor • Maternal infection • Postterm delivery • Fetal malformation • Uterine tetany

• Thick meconium • Hydrops fetalis • Maternal diabetes • Multiple gestation • Fetal arrhythmia • Evidence of fetal distress

• Acute fetal/placental hemorrhage • Poly/oligohydramnios • Preeclampsia • Intrauterine growth restriction • Emergent cesarean delivery

• Equipment should be prepared in advance of known high-risk deliveries. • Radiant warmer: Should be turned on and pre-warmed to prevent rapid heat loss in VLBW or EBLW infants • Flow inflating bag and appropriately sized facemasks for the anticipated delivery: Be sure PEEP is set correctly and the bag is connected to an oxygen source. A flow meter, adequate tubing length, and oxygen blender may be necessary, as well as a pulse oximeter to monitor oxygen saturation. This is particularly important in the resuscitation of ELBW/VLBW infants and infants with known congenital cardiac disease (both scenarios in which excessive oxygen administration may need to be avoided). • Materials for endotracheal intubation (laryngoscope with Miller 00, 0, and 1 blades; appropriate sizes of endotracheal tubes [with 2.5-, 3.0-, and 3.5-mm internal diameters], stethoscope, suction catheters with suction source, CO2 detector to confirm endotracheal intubation). • Bulb suction. • Transport incubator with transport monitors. • Caveats: • When providing positive-pressure ventilation (PPV) with a bag or mask, you must ensure an adequate seal is formed around the infant’s mouth to ensure the pressure being delivered is transmitted to the airway. • Use extreme caution when providing PPV to avoid overinflating the lungs; you should provide enough pressure to achieve adequate chest rise → Remember that volutrauma and barotrauma can cause significant lung injury. • An emergent umbilical venous catheter can be placed as indicated to provide immediate venous access → The catheter should be placed only as far as necessary to obtain free flow of blood. • Epinephrine can be administered via endotracheal tube if venous access is not readily available.

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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 dilution), 0.1 mg/mL

0.1–0.3 mL/kg IV or via ETT*

• Give rapidly • Repeat q3–5 min as needed

Volume expanders (normal saline, blood)

10 mL/kg IV or IO

• Give over 5–10 min, slower for 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 (0.5 mEq/mL)

2 mEq/kg IV or IO

• Give slow push over at least 2 min • Must ensure adequate ventilation prior to dosing • Can repeat q5–10 min as needed

Naloxone (0.4 mg/mL)

0.25–0.5 mL/kg IV, IM, IO, SQ, or via ETT

• Give rapidly • 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 ﬁrst dose was via ETT.

COMMONLY USED INOTROPES IN THE NICU Medication

Infusion rate (μg/kg/min)

Dopamine

2.5 – 20

• 1st line for hypotension in neonates • Has been shown to increase cerebral blood ﬂow in neonates • Cochrane review showed dopamine to be superior to dobutamine, with no increased eﬃcacy 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

Indication

ENDOTRACHEAL TUBE SIZES

Weight <1000 g

Laryngoscope Blade

ETT size (internal diameter in mm; all uncuffed tubes)

Depth of insertion (cm; as measured at the lips)

00

2.5

1000–2000 g

0

3.0

6–7 7–8

2000–4000 g

1

3.5

8–10

>4000 g

1

3.5–4.0

10

Placement of Umbilical Catheters

(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.

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Umbilical Arterial Catheter • 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:

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 specific, 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 score

>7

4–6

0–3

Maternal diabetes

Type A1 and A2

All other classiﬁcations

All other classiﬁcations

Meconium

Asymptomatic with or without meconium below the cords

N/A

Symptomatic with meconium below cords

Respiratory distress

N/A

If no oxygen requirement, but still needs to be evaluated

All with oxygen requirement

Sepsis risk factors

Maternal fever or PROM without chorioamnionitis and asymptomatic term baby

Maternal fever and/or chorioamnionitis with mild symptoms

All infants with signiﬁcant symptoms

MECONIUM ASPIRATION • Acute and chronic hypoxia can result in passage of meconium in utero, and gasping by fetus or newborn can cause aspiration of fluid 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? (HR >100 bpm, and strong respiratory effort, and good muscle tone)

Not vigorous? (HR < 100 bpm, or poor respiratory effort, or poor muscle tone)

• Observe • Resuscitate as needed

• Intubate and suction trachea • 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 • Previous infant with invasive GBS disease • GBS bacteriuria during current pregnancy • Positive GBS screening culture during current pregnancy (unless a planned cesarean delivery in the absence of labor or amniotic membrane rupture is performed) • Unknown GBS status (culture not done, incomplete, or results unknown) and any of the following: • Delivery at <37 weeks’ gestation • Amniotic membrane rupture ≥18 hours • Intrapartum temperature ≥100.4°F (≥38.0°C)

Intrapartum prophylaxis not indicated • Previous pregnancy with a positive GBS screening culture (unless a culture was also positive during the current pregnancy) • Planned cesarean delivery performed in the absence of labor or membrane rupture (regardless of maternal GBS culture status) • Negative vaginal and rectal GBS screening culture in late gestation during the current 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

Obtain vaginal and rectal GBS culture and initiate IV antimicrobials

GBS positive

GBS positive

GBS negative

IV antimicrobials for ≥ 48 hours (during tocolysis)

No GBS prophylaxis

Stop antimicrobials

Intrapartum antimicrobial prophylaxis at 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 Companies. All rights reserved.)

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No growth at 48 hours

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Neonatology

MANAGEMENT OF THE INFANT AT RISK FOR EARLY-ONSET GBS DISEASE

Maternal antibiotics for suspected chorioamnionitis?

Maternal IAP for GBS?a

Yes

Yes Signs of neonatal sepsis?

Yes

Full diagnostic evaluationb Empiric therapyc

No Gestational age < 35 weeks?

Yes

No Duration of IAP < 4 h before delivery?d

Yes

Limited evaluation Observe ≥ 48 h If sepsis is suspected, full diagnostic evaluation and empiric therapyb

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 Term infant

Maternal fever ≥ 100.4°F within 24 hours before or after delivery and/or OB is considering maternal chorioamnionitis or systemic infection and infant is asymptomatic

Infant with clinical signs/symptoms of sepsis (regardless of maternal fever)

Limited sepsis workup, empiric antibiotics

Symptomatic infants: Respiratory distress, hypotension, lethargy, apnea, temp instability, seizures, tachycardia, vomiting, diarrhea, poor feeding

PROM (≥ 18 hr) prior to delivery

Infant symptomatic

Full sepsis workup, empiric antibiotics

Infant asymptomatic

Observe for 24 hrs, consider limited sepsis workup and empiric antibiotics, outpatient followup 2-5 d after discharge

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.

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Neonatology Preterm infant

Maternal fever ≥100.4°F prior to or within 24 hours before or after delivery and/or OB is considering chorioamnionitis or systemic infection and infant is asymptomatic

Infant with clinical signs/symptoms of sepsis (regardless of maternal fever)

Symptomatic infants: Same manifestations as term infants Limited sepsis evaluation, empiric antibiotics

Full sepsis evaluation, empiric antibiotics

PROM (≥ 18 hr) prior to delivery

Asymptomatic

Symptomatic

Limited sepsis evaluation, empiric antibiotics

Full sepsis evaluation, empiric 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 beneﬁts 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 inﬂation pressures >30 cm H2O are required, consider highfrequency 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 caﬀeine citrate (20 mg/kg loading dose, followed by 5 mg/kg daily). • Both of the above have shown some beneﬁt in the reduction of chronic lung disease of prematurity.

Cardiovascular

• Maintaining adequate tissue perfusion is the ultimate goal. • Limited data suggest adverse eﬀects 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 ﬁrst line for treatment of hypotension (rare instances where hypotension in this age group is due to hypovolemia, so avoid ﬂuid 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 signiﬁcant 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 insuﬃciency. • If symptomatic PDA persists, consider surgical ligation.

Fluids/ Electrolytes

• The lower the gestational age, the higher the ﬂuid requirements will be, secondary to tremendous insensible losses through immature, noncorniﬁed skin and an increased body surface area–to-weight ratio. • Total ﬂuid 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

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• 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 insulincontaining ﬂuid 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 ﬁrst 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 ﬁrst 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. • If serum sodium decreases, this may indicate excessive ﬂuid administration. • If serum sodium increases, this may indicate restricted ﬂuid administration.

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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 fortiﬁer to the expressed breast milk or by changing to an appropriate preterm formula.

Infection control

• Premature infants are susceptible to infectious complications for several 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 film 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 fluid intake and output. • Order humidified Giraffe Omnibed (or other humidified isolette) to servo-control mode. • Humidification protocol as per NICU nursing policy. • If a humidified 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 Rescue Treatment

• Most infants <28 wk gestation are intubated in delivery room and given surfactant, preferably within the ﬁrst 15 min of life. • Data suggests two doses are better than one. • Repeat surfactant dose q6h (up to a total of four doses*) if infant requires ventilation with mean airway pressure >6–7 cm H2O and FiO2 >30%.

• Rescue treatment by single- or multiple-dose surfactant replacement reduces mortality from RDS as well as pneumothorax. • Outborn infants <28 wk and between 2 and 48 h of age who require >30% oxygen should receive rescue surfactant, with repeat dosing as above. • Spontaneously breathing infants >28 wk with respiratory distress who require >40% FiO2 on nasal CPAP are also candidates for rescue surfactant. (continued on next page)

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Prophylactic Treatment

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 inﬂation pressures to prevent air leak and volutrauma. • Consider up to four doses as indicated. *This dosing speciﬁcally 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 Intermittent Mandatory Ventilation (SIMV)

• Most frequently used in newborns with respiratory failure to improve consistency of oxygenation and reduce patient discomfort • Values to be set (pressure-control SIMV): Rate (breaths/min), peak inﬂation pressure (PIP), positive end-expiratory pressure (PEEP), inspiratory time (Ti) • Weaning: Can wean rate, PIP to prevent overventilation

Pressure Support Ventilation (PS)

• Potential indications: • Infants >10 kg • 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 Guarantee (VG) (similar to Pressure Regulated Volume Control, PRVC)

• In time-cycled, pressure limited ventilation, tidal volume (Vt) can vary from breath to breath depending on the compliance of the lungs and whether the baby is at rest or awake and “ﬁghting” the ventilator • To make the delivered Vt more consistent breath-to-breath, VG mode can be used • Values to be set: Rate, Vt (4–6 mL/kg), maximal PIP allowable to reach preset Vt, Ti, and PEEP • 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 beneﬁt, use is limited to special circumstances (continued on next page)

Stabilization, Delivery Room Care, and Initial Treatment of the VLBW Infant 375 Assist Control (AC)

• All spontaneous breaths are supported by the ventilator • 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 beneﬁt, use is limited to special circumstances (ie, diaphragmatic hernia)

High-Frequency Oscillatory Ventilation (HFOV)

• Potential indications: • Infants ≥34 wk gestation with severe respiratory failure who are at risk for requiring ECMO • 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 hyperinﬂation and air leak • Values to be set: Paw (mean airway pressure; generally 1–2 cm H2O above the last Paw used on conventional IPPV), ΔP (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 hyperinﬂation, then q8–12h as indicated • Weaning: To prevent overventilation, ↓ ΔP 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

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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 newborn screen

All infants

Each state is diﬀerent in terms of timing of screening and which disorders are screened for; check with your state on the timing and sample preparation 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 ﬁrst screen

Some states only require one screening test, and others require two; check with your state on the number and timing of state screenings required

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)

376

(continued on next page)

Discharge Planning Planning

Criteria

Timing

377

Follow-up If grade II IVH or greater: • Weekly cranial US to follow for development of post-hemorrhagic hydrocephalus; more frequently if clinically indicated

Ophthalmologic screen

All infants <30 wk PMA or <1500 g birthweight or Infants 1500–2000g birthweight if the infant is at high risk for developing ROP

Audiology screen

All newborns ≥34 wk PMA Infants admitted to the level II nursery or NICU for ≥5 d require screening with an ABR

Car seat testing

All infants born <37 wk PMA or older infants with disorders that may impact the airway (eg, hypotonia)

31–33 wk PMA

Based on ﬁndings of initial screen (may be within a few days for pre-threshold disease to every 1–3 wk for immature retinas at risk of progressing to ROP) As needed for failed initial screen

Can be tested immediately before discharge home

Vaccinations See Chapter 19 (Infectious Diseases) for vaccination guidelines Occupational therapy or physical therapy

Infants who meet one of the As soon as possible during the hospitalization following: • Birth at ≤28 wk PMA • Birthweight <1000 g • Neurologic injury (IVH, PVL) • Any disorder that impacts movement • Orthopedic impairment

Early Childhood Intervention (programs are statespeciﬁc)

All infants <1500g birthweight or <32 wk PMA All infants who are believed to be at risk for abnormal neurodevelopment or abnormal physical development All infants who are believed to be discharged to a high-risk home situation (eg, multiple other children, young mother)

Women, Infant, and Children Program (programs are statespeciﬁc)

All premature infants Referral should be made before discharge All infants that are to be discharged on special medical formulas

As recommended by consulting therapist

Initial screen is usually after discharge from hospital, but referral should be made before discharge

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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 significant 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 first 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.)

C H A P T E R 32

Cardiology PATENT DUCTUS ARTERIOSUS • DA closed in 50% of full-term infants by 24 h, 90% by 48 h, >99% by 96 h. • Incidence in term infants: ~0.02%–0.04% (10% of all CHD in term infants). • Incidence in preterm infants: ~45% of infants <1750 g, ~80% of infants <1000 g. • Increased in: prematurity, hyaline membrane deficiency, asphyxia, high altitude, CHD, increased fluid administration • Decreased in: antenatal steroids, intrauterine growth restriction, prolonged rupture of membranes • Spontaneous closure of PDA occurs in 38%–85% of babies <1500 g and in 25%–34% of those <1000 g.

Clinical Manifestations • Large PDA can be diagnosed relatively accurately based on clinical findings. • Small PDA usually requires an echocardiogram with Doppler, because findings may be similar to pulmonary disease or sepsis.

Diagnosis • CXR • May be normal, or may see pulmonary edema or cardiomegaly (compare films serially) • Echocardiography with Doppler • Findings associated with hemodynamically significant PDA include: • Ductal diameter >1.5 mm • Predominantly left-to-right shunt • Disturbed diastolic flow in MPA • Reversal of end-diastolic flow in postductal aorta • Left atrial/left ventricular enlargement • Electrocardiography (no specific findings exist for PDA) • May be normal, or may see LVH, BVH, or LAE

Complications • Pulmonary edema • Heart failure • Pulmonary hypertension • Septic emboli (from vegetations located on the pulmonary side of PDA)

Management

379

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• Asymptomatic PDA without need for ventilator support: No long-term benefits established with medical or surgical treatment; may continue to feed these infants • Symptomatic PDA: No long-term benefits established with medical or surgical treatment, but treatment reduces the need for ventilator support and theoretically prevents progression to heart failure, pulmonary hypertension, and septic emboli • Ventilatory support (may increase PEEP to control pulmonary edema) • Fluid restriction (alone does not cause ductal closure, but excess fluid administration is associated with increased incidence of PDA) • PRBC transfusion (if significant anemia present, may reduce high-output state and decrease pulmonary overcirculation) • Definitive management (medical versus surgical [ie, indomethacin vs ligation])

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 first 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)

<48 h

0.2

0.1

Dose 3 (mg/kg) 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 significant 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 significant, 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 flow 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:benefit 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 Vitals (four-extremity BP, SpO2) Physical examination EKG CXR

History Vitals (four-extremity BP, SpO2) Physical examination EKG 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. • Specific 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 Squatting Loss of consciousness

Tachypnea (at rest or with activity) Diaphoresis (at rest or with activity) 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 finding is specific, not sensitive). A widely patent, nonrestrictive PDA may mask this finding, 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).

Differential Cyanosis (Preductal > Postductal)

Reverse Differential Cyanosis (Postductal > Preductal)

PPHN Left sided-obstructive lesions: • Critical aortic stenosis • Aortic arch hypoplasia • Aortic arch interruption • Aortic coarctation

d-TGA with either PPHN or systemic outﬂow obstruction

EKG • Many are normal in CHD.

EKG FINDINGS AND ASSOCIATED CARDIAC DISEASE Superior Axis (“Northwest” or Indeterminate)

TOF d-TGA TAPVR

AVCD Tricuspid atresia Pulmonary atresia with intact ventricular septum (continued on next page)

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Right Axis Deviation

382

Neonatology

Large QRS Complexes

Small QRS Complexes

All leads: Pompe’s disease Speciﬁc leads: • Right or left ventricular hypertrophy • Right or left bundle branch block • Pre-excitation • Intraventricular block • Artiﬁcial pacemaker

Myocarditis Pericardial eﬀusion (pericarditis) Hypothyroidism Thick chest wall (adults) Normal newborn infants

AO PA LA APP

SVC

AO PA 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 Increased pulmonary blood ﬂow

“Classic” CXR Finding

PDA d-TGA

“Egg on a string”

Tricuspid atresia with large VSD TAPVR Decreased pulmonary blood ﬂow

“Snowman” (unobstructed TAPVR)

Pulmonic stenosis Tricuspid atresia with small VSD TOF

“Boot-shaped heart”

Hypoplastic left heart syndrome Pulmonary atresia with intact ventricular septum Normal pulmonary blood ﬂow

Aortic coarctation

“Figure 3 sign” or rib notching

Arterial Blood Gases • PCO2 may be increased in pulmonary disease or heart failure. • Metabolic acidosis raises concerns about poor cardiac output and heart failure. • PO2 is lower at any given oxygen saturation for neonates compared to non-neonates due to an increased affinity of O2 by fetal hemoglobin.

Cardiology

383

Hyperoxia Test • Most sensitive and specific portion of initial workup of suspected CHD. • Empiric PGE1 should be started for any baby with SpO2 <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 Condition

Room Air PaO2 (mm Hg)/SpO2

FiO 100% PaCO2 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

<40 / <75% <40 / <75% 40–60 / 75%–93%

<50 / <85% <50 / <85% <150 / <100%

35 35 35

Cardiac disease: • Parallel circulation1 • Mixing with restricted PBF2 • Mixing without restricted PBF3 • Diﬀerential cyanosis4 • Reverse diﬀerential cyanosis4

Pre: 70 / 95% Post: <40 / <75% Varies Pre: <40 / <75% Post: >50 / >90% Varies

35-50 35-50

1 d-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 outﬂow 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 Severe cyanosis

Shock

Diﬀerential Dx

• PA / IVS • Critical PS • Ebstein’s malformation • d-TGA with IVS

• Critical AS • Obstructed • Interrupted aortic arch TAPVR • Coarctation of aorta • HLHS • Obstructed TAPVR • HLHS

0–3 d

Symptoms

Pulmonary edema

Symptoms

Cardiovascular collapse

Diﬀerential Dx

• Severe AS • Truncus arteriosus • Severe aortic coarctation • PDA • TOF with severe PS • AVM • Single ventricle with PS

Severe pulmonary overcirculation

(continued on next page)

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4–10 d

Pathophysiology: PDA closure (causing cardiovascular collapse) or PVR falls (causing pulmonary overcirculation)

384

Neonatology Pathophysiology: Heart unable to meet systemic O2 demand as PVR continues to fall Heart failure and pulmonary edema

Diﬀerential Dx

• Complete AV canal defect • TOF with mild PS • Unobstructed TAPVR • d-TGA with VSD • Single ventricle lesions without PS • ALCAPA (only one in this group that may present with shock)

2–18 wk

Symptoms

4–12 mo

Pathophysiology: Left-to-right shunting with mild pulmonary overcirculation Symptoms

Tachypnea, poor feeding, incidental murmur

Diﬀerential Dx

• VSD • ASD • PDA

Pathophysiology: Mild outflow tract obstruction Symptoms

Poor feeding, incidental murmur

Diﬀerential 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 definitive diagnosis 80%–85% to prevent potential pulmonary overcirculation. Prostaglandin E1 • Infants without other identified causes of cyanosis (and hyperoxia test suggestive of CHD), and infants in heart failure or shock (especially within the first 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 fluid 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 leftheart return and restrictive atrial septum. Once interatrial flow 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

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CHAPTER 33

Dermatology BENIGN NEONATAL RASHES Disease

Description

Course

Treatment

Other

Erythema toxicum

Erythematous macules, papules, pustules, vesicles, or wheals on the face, torso, proximal limbs, and buttocks Spares palms and soles

24–48 h after birth, may be seen ≤2 wk of age Resolve spontaneously and heal without sequelae

None

Aﬀects 50% of full-term neonates Eosinophils on Wright’s stain of pustules

Transient neonatal pustular melanosis

Fragile, superﬁcial pustules; no erythema After rupture → collarette of scale and hyperpigmentation Widespread, including the palms and soles

Present at birth Hyperpigmentation may last several months

None

Aﬀects darkerskinned, full-term neonates Sterile subcorneal neutrophilic pustules

Miliaria crystalline

Small, ﬂaccid vesicles on the forehead, neck, upper trunk, and occluded areas

Sometimes present at birth

Avoid overheating and overswaddling

Caused by obstruction of eccrine sweat ducts near the surface of the skin

Miliaria rubra

Small erythematous papules and pustules on the forehead, neck, upper trunk, and occluded areas

Usually after ﬁrst wk of life

Avoid overheating and overswaddling

Caused by obstruction of eccrine sweat ducts in the deeper layer of the epidermis

Milia

1- to 2-mm white or yellow epidermoid cysts usually on the face

Usually resolve by age 1 mo

None

If seen on palate, known as Epstein’s Pearls.

Neonatal cephalic pustulosis (neonatal acne)

Discrete, noncomedonal papules or pustules on an erythematous base Usually on the cheeks; also on the forehead, chin, eyelids, neck, upper chest, and scalp

Onset during ﬁrst 2–3 wk of life; spontaneously resolves within weeks

None necessary; may be improved with topical clotrimazole

May be caused by Malassezia spp.

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Disease

Description

Course

Treatment

Other

Acropustulosis of infancy

Crops of acral, pruritic vesicles and pustules on the hands, wrists, feet, and ankles

May present in the neonatal period but usually at 3–6 mo of age Last 1–2 wk and recur in 3–4 wk Less frequent relapses with age; complete resolution usually by age 3 yr

Topical corticosteroids or oral antihistamines If severe, consider dapsone Some pts respond to oral erythromycin

Must exclude scabies (burrows, genital involvement); microscopic exam of scraping

Nevus sebaceous

Hairless, thin, orange plaque on the scalp or face; may be seen on the neck or trunk

Progressive thickening and a verrucous appearance

Observation; complete excision for cosmesis

<1% develop secondary basal cell carcinoma

Congenital melanocytic nevus

Tan or brown, oval plaques; sometimes hairy

Commensurate growth with age; occasionally regress May become verrucous with pigment changes

Yearly skin check for changes Consider bx and excision based on clinical changes, melanoma risk, location, age, and FH

Giant nevi with greater risk of melanoma progression Neurocutaneous melanocytosis with some larger scalp or axial lesions

Nevus simplex or macular (vascular) stain (salmon patch, angel kiss, stork bite)

Salmon pink, vascular patch commonly on the forehead, upper eyelids, or nape of the neck May become more prominent with crying; blanches with pressure

Most fade or resolve spontaneously, but neck lesions usually persist

None necessary; pulseddye laser for cosmesis

Mongolian spot (dermal melanocytosis)

Bluish patches often on the lumbosacral or buttock areas Seen more commonly in patients with darker skin and Asians

Most fade with time

None

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Document in newborn skin exam to avoid misdiagnosis of bruising or child abuse Diﬀuse or unusual distribution may suggest systemic involvement (eg, storage disease, phakomatosis pigmentovascularis)

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ABNORMAL NEONATAL RASHES Disease

Description

Clinical Course

Treatment

Other

Neonatal lupus erythematosus

Annular plaques with raised, red borders and central clearing Predilection for the face (especially periorbital area) Photosensitivity

Typically resolve without scarring Dyspigmentation may persist for months May have residual telangiectasias

Evaluate for internal manifestations: Congenital heart block (ECG), hepatobiliary disease (LFTs), thrombocytopenia (CBC), CNS

Almost all have anti-Ro antibodies; may also see anti-La or U1RNP antibodies Cardiac NLE: 20% mortality; two-thirds require pacemakers

Lamellar ichthyosis

Collodion baby: Taut, shiny erythematous skin → scaling, ﬁssures, superﬁcial desquamation Ectropion Eclabion Hypoplastic nasal and auricular cartilage

First few weeks: Collodion membrane replaced with large platelike scales, superﬁcial ﬁssures Scalp scaling ± scarring alopecia ± nail dystrophy Ear canals occluded with scales → recurrent ear infections Obstructed sweat ducts → heat intolerance

Neonatal period: Humidiﬁed incubator, bland emollients, and nonadherent dressings for erosions Long-term: PO and topical retinoids, lactic acid or propylene glycol creams; may need ﬂuid, calorie, iron, protein supplementation

After birth, monitor in ICU for temperature instability, ﬂuid and electrolyte imbalances, and signs of sepsis Genetics referral for counseling, possible mutational analysis

Bullous congenital ichthyosiform erythroderma or epidermolytic hyperkeratosis (EHK)

At birth: Erythroderma, erosions, peeling, denuded skin Later: Severe hyperkeratosis

Blistering episodes, secondary bacterial infections, disﬁgurement, malodor ± scarring alopecia

Nonbullous congenital ichthyosiform erythroderma

Collodion membrane at birth Ectropion Eclabion

Collodion membrane replaced by generalized erythroderma with persistent scaling (variable severity) Nail dystrophy Obstructed sweat ducts → heat intolerance (continued on next page)

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Description

Clinical Course

Harlequin ichthyosis

Thick, platelike scale with extreme ectropion, eclabion May see autoamputation of distal digits

Usually premature and may die within days to weeks because of complications Delayed growth and development if the patient survives past infancy

Netherton syndrome

Generalized erythroderma, scaling May have sparse abnormal hair

Failure to thrive Atopic diathesis Ichthyosis linearis circumﬂexa: Serpiginous migratory annular or polycyclic rash with double-edged scale (usually after age 2 yr) Improves with age; intermittent ﬂares

Emollients, keratolytics, retinoids, corticosteroids Increased caloric and protein requirements Antibiotics for infection

Epidermolysis bullosa (EB)

Ranges from mild blistering to generalized ﬂaccid bullae or erosions → scarring, contractures, pigment changes ± eye, oral mucosa, GI, GU involvement

Onset at birth or early infancy Secondary infections common High incidence of squamous cell carcinoma → death (RDEB) Upper airway obstruction (JEB > RDEB)

Gentle cleansing Nonadherent dressings and topical antibiotics for erosions Loose-ﬁtting clothing Cool environment

Increased caloric and protein requirements Varied mutations

Ectodermal dysplasias

May see desquamation, erythroderma, hyperkeratosis, erosions as neonate Abnormal hair, teeth, nails (partial or complete)

Hair, nail, teeth, sweat gland abnormalities Hyperthermia Ear anomalies ± Cleft lip or palate ± Limb anomalies

Gentle cleansing Bland emollients Nonadherent dressings and topical antibiotics for erosions

Secondary infections of erosions common Genetics referral for counseling

Staphylococcal scalded skin syndrome

Superﬁcial bulla with desquamation Perioral crusting Diﬀuse tender Erythema No mucous membrane involvement

Prodrome: Fever, malaise, irritability Scaling or desquamation for 3–5 d after bullae formation Reepithelialization in 10–14 d

Parenteral antibiotics Bland emollients for denuded skin

Frequently seen in diaper area in infants

JEB, junctional epidermolysis bullosa; RDEB, recessive dystrophic epidermolysis bullosa

Other

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Neonatology

DIAPER RASHES Type

Description

Irritant: See below for additional treatment recommendations

Erythematous plaques or patches sparing the inguinal folds Caused by exposure to urine or stool May be perianal if diarrhea is present

Clinical course

Treatment

Exacerbated See below by scrubbing and use of commercial wipes or strong detergents Usually lasts <3 d after treatment is initiated

Other Complication: Secondary bacterial or yeast infection

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 sequestrant; possibly beneficial 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 inflammation; 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 flow • Nighttime: Diaper change at least once during the night Refractory Diaper Dermatitis • Always consider histiocytosis, nutritional deficiencies (zinc, biotin), child abuse, immunodeficiency syndromes, seborrhea, psoriasis, bacterial infection, and IBD Candidal diaper dermatitis

Beefy, red plaques involving the inguinal folds Satellite red papules or pustules Desquamation at border

May cause discomfort with urination or defecation

Topical nystatin or imidazole, barrier creams, frequent diaper changes (see above) Rarely, lowpotency topical corticosteroid

Suspect when irritant dermatitis does not improve within several days

Perianal streptococcal dermatitis

Bright red, sharply demarcated plaques May involve vulvar or penile area May have ﬁssuring, mucoid discharge, crusting

Itching, rectal pain; may have blood-streaked stools if skin is eroded Often misdiagnosed and treated for other causes before dx is made

1 wk course of cephalosporin; or 10–14 d course of PCN, amoxicillin, or erythromycin; ± topical antibiotics

Rapid strep test or skin cx of aﬀected area positive for GABHS

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Clinical course

Treatment

Shiny, bright red, well-demarcated plaques involving the skin folds Lacks the yellow scale often seen with seborrheic dermatitis

May have satellite spread of psoriasiform papules to the trunk, limbs, face, and scalp

Barrier creams, TCI, lowpotency TCS for no longer than 2 wk intervals (if symptomatic)

Seborrheic dermatitis

Greasy, scaly, crusted, erythematous plaques Involves skin folds, diaper area, scalp No satellite lesions May be psoriasiform

Usually begins 1 wk after birth May persist for months

Bathing Frequent moisturization Ketoconazole 2% cream if extensive or persistent Short course of low-potency topical corticosteroids if inﬂamed

Linked with sebum overproduction and Malassezia spp.

Acrodermatitis enteropathica (AR defect in intestinal absorption of zinc)

Perioral and perianal and acral erythematous patches and plaques with 2° scale and crust, erosions, vesicles, or bullae Chronic: Licheniﬁed psoriasiform plaques ± other mucocutaneous ﬁndings: Blepharitis, conjunctivitis, cheilitis, stomatitis

Usually appears within 1–2 wk after breast milk weaned or at 4–10 wk if bottle fed Secondary infections with Staphylococcus and Candida spp. are common

Zinc supplementation: 3 mg/kg/d

If no tx → FTT Low serum zinc with low alk phos

Langerhans cell histiocytosis

Tender, coalescent pink papules, pustules and vesicles on the scalp, neck folds, axillae, perineum, and trunk → erythematous eroded plaques, scaling, crusting ± plaques on gingivae

May become impetiginized Congenital form often limited to the skin and is self-healing Other forms often assoc with multisystem disease

Skin: TCS, topical antibiotics, PUVA Systemic: Chemotherapy

Multiorgan disease with high mortality rate, may appear like severe seborrheic dermatitis, with erosions, hemorrhagic crusts. Can see erosions in body creases.

Type

Description

Psoriasis

Other

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CHAPTER 34

Endocrinology ADRENAL AND PITUTARY INSUFFICIENCY IN NEONATES PRIMARY ADRENAL INSUFFICIENCY Inherited Causes Adrenocortical Impaired Steroid Dysgenesis Responsiveness

Disorders of Steroid Biosynthesis

• Caused by mutations in DAX1 and SF1 genes • These genes encode a nuclear transcription factor expressed in both gonads and the adrenal cortex • Results in deﬁciency of all adrenal steroids

StAR (acute steroid regulatory protein) deﬁciency: • Mediates transfer of cholesterol across mitochondrial membrane • Adrenals are large and lipid laden • Decreased levels of all adrenal steroids • 46 XY males appear female or only minimally virilized 3-β-Hydroxysteroid dehydrogenase deﬁciency: • Catalyzes the conversion of pregnenolone, 17-OHpregnenolone, DHEA, and androstenedione • Clinical manifestations: • Salt-wasting adrenal crisis • 46, XX female may be mildly virilized • 46, XY male is undervirilized • Elevated substrates: DHEA and 17-OH-pregnenolone • Elevated 17-OHprogesterone 21-Hydroxylase deﬁciency: • 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

Pseudohypoaldosteronism: • Mutation of aldosterone receptor gene or of epithelial sodium channel genes • Clinical presentation with salt wasting, hyperkalemia, shock, dehydration Familial unresponsiveness to ACTH: • Results in normal mineralocorticoid activity, with diminished glucocorticoid activity • Clinical presentation with profound hypoglycemia and hypotension

Acquired Causes Exogenous glucocorticoid administration: • Infants receiving high-dose glucocorticoids for >10–14 d are at high risk • May require hydrocortisone for unexplained hypotension or hypoglycemia or in preparation for surgery Bilateral adrenal hemorrhage: • Can be seen in LGA infants with diﬃcult delivery/ coagulopathy • Asymptomatic infants can have suprarenal calciﬁcations on plain ﬁlm of abdomen

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Inherited Causes Adrenocortical Impaired Steroid Dysgenesis Responsiveness

Disorders of Steroid Biosynthesis

Acquired Causes

• 46, XY infants have large phallus and hyperpigmented scrotum • Markedly elevated levels of 17-OH-progesterone Aldosterone synthase deﬁciency: • Rare condition • Hyponatremia and hyperkalemia

Diagnosis of Adrenal Insufficiency • 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 deficiency • 17-Hydroxyprogesterone in 21-hydroxylase deficiency • All C19 and C21 steroids are low in StAR deficiency

Treatment of Acute Adrenal Insufficiency • 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 fludrocortisone 0.05–0.1 mg once daily for hyperkalemia or salt-wasting

SECONDARY ADRENAL INSUFFICIENCY Clinical Presentation

Diagnosis

Treatment

• Secondary to single gene mutations • Malformations or injury to the sella turcica or hypothalamus

• Unexplained hypoglycemia after 4–5 postnatal days of age • Unexplained hypotension • Findings associated with hypopituitarism: • Lack of onset or abnormal progression of labor • Midline craniofacial or CNS deﬁcit • Nystagmus, optic nerve hypoplasia, and other ocular abnormalities • Hypoplastic genitalia in boys • Prolonged jaundice; elevated hepatic transaminases

• Random growth hormone is <5 ng/mL (nl is 8–15 ng/mL) • Low random and stimulated cortisol levels • Low random free T4 and TSH levels

• Fluid resuscitation in acutely hypotensive infant • Hydrocortisone 50–100 mg/m2 IV as a single dose, then to 10 mg/ m2/day in three divided doses daily • Growth hormone at 40 mcg/kg/day SQ once daily • Oral levothyroxine 15 mcg/kg/day

(continued on next page)

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Etiologies

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Neonatology

Etiologies

Clinical Presentation

Diagnosis

Treatment

• Hypernatremia, polyuria • Low TT4 and inappropriately normal TSH values on newborn screen • MRI ﬁndings: 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

Send repeat NBS

Check serum TSH, FT4

TSH and/or T4 abnormal

TSH and T4 normal

Repeat NBS with abnormal thyroid screen

No follow up needed

Repeat NBS normal

No follow 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 difficult, to distinguish central hypothyroidism from hypothyroxinemia of prematurity, and additional clinical findings should raise suspicion of central hypothyroidism: • Microphallus • Cleft lip/palate

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• Midline facial hypoplasia • Nystagmus • Hypoglycemia • Prolonged unconjugated hyperbilirubinemia • Cortisol, growth hormone, prolactin, or gonadotropin deficiency • 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 significantly 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 Definition • Serum potassium > 6.5 mEq/L

Etiology • Decreased excretion • Increased load • Redistribution • Factitious

CAUSES OF HYPERKALEMIA IN THE NEONATE Examples

Decreased excretion

• Acute kidney injury • Positive potassium balance in the VLBW infant in the ﬁrst few days of life • Adrenal failure (eg, congenital adrenal hyperplasia, bilateral adrenal hemorrhage) • Medications • Potassium-sparing diuretic • Propranolol • Indomethacin • ACE inhibitors

Increased potassium load

• Hemolysis

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Etiology

• Intraventricular hemorrhage • Hematoma • Excess potassium administration • Tissue necrosis (continued on next page)

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Neonatology

Etiology

Examples

Redistribution of potassium

• Secondary to metabolic or respiratory acidosis • 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 fluids 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 reflect total body potassium content to shifts to and from different body compartments in relation to pH. • Balance is maintained by regulation of intake (IV fluids and enteral) and excretion (renal and GI).

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• 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 • Nasogastric suction • Ileostomy drainage • Chronic diuretics • Renal tubular defects

• Serum and urine pH and electrolytes • ECG to evaluate for QT prolongation

• If possible, reduce potassium losses. • Supplement potassium as needed.

NEONATAL HYPERCALCEMIA Definition • Hypercalcemia is defined 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

• Primary (NSHPT) or secondary hyperparathyroidism

• Familial hypocalciuric hypercalecemia

↓ PTH

Check Vit D1 ↑ Vit D metabolites

Normal Vit D metabolites • Idiopathic infantile hypercalcemia • Williams Syndrome

↓ Vit D metabolites • Iatrogenic • Malignancy (PTHrP) • Hypervitaminosis A • Hypophosphatasia

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

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• Subcutaneous fat necrosis • Granulomatous disease • Jansen's metaphyseal chondrodysplasia • Hypophosphatemia • Vitamin D intoxication

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Neonatology

Management • Depends on cause of hypercalcemia • Asymptomatic hypercalcemia requires no specific treatment, although adjusting calcium intake and vitamin D supplementation may be considered. • Mild hypercalcemia (1.45–1.60 mmol/L) • No specific 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 Definition • In infants >1500 g, hypocalcemia is defined 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 • Definition • Usually occurs in the first 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 • Insuﬃcient 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)

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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 deﬁciency

Late Hypocalcemia • Definition • Occurs after the first 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 deﬁciency 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

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)

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Primary neonatal • PTH deﬁciency hypoparathyroidism

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Cause

Mechanism

Congenital abnormalities of parathyroid glands

• Inherited as X-linked or autosomal recessive • Rearrangement or microdeletions aﬀecting the short arm of chromosome 22q11 • Seen in DiGeorge and velocardiofacial syndromes • Incomplete development of the branchial arches, resulting in varying degrees of parathyroid and thymic hypoplasia

Abnormalities of PTH

• Mutation in the gene for PTH, leading to defective PTH

Defective regulation of PTH secretion

• Mutation of the parathyroid and renal CaSR, leading to excessive calcium-induced inhibition of PTH secretion

Vitamin D deﬁciency

• Can result from maternal vitamin D deﬁciency • Decreased intestinal and renal absorption of calcium

Infantile osteopetrosis

• Inherited as autosomal recessive • Failure of osteoclasts to resorb immature bone, leading to abnormal bone cavity formation • Classic features are fractures, visual impairment, and bone marrow failure

Bicarbonate therapy

• Decreases ionized calcium levels and bone resorption of calcium

Blood or blood • Citrated blood can form nonionized calcium complexes product transfusion Diuretic and xanthine therapy

• Promotes calciuresis and nephrocalcinosis/nephrolithiasis

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) • Nonspecific signs, such as lethargy, vomiting, and abdominal distention

Evalutation WORKUP FOR NEONATAL HYPOCALCEMIA Early Hypocalcemia

Late Hypocalcemia

• Serum ionized calcium: Measure at 24 h of life and every 12 h thereafter until the infant is receiving Ca either from TPN or a milk source and has a stable, normal ionized Ca. • Serum magnesium • Serum phosphorus

• Total and ionized serum calcium • Serum phosphorus and magnesium • CXR (thymic shadow, aortic arch position) • Intact PTH level • Genetic studies: FISH or CMA for chromosome 22q deletion • Consider sepsis/meningitis workup • Endocrine consult is optional if history is typical and thymus is seen on CXR • Consider EEG and CT scans if history and presentation are atypical

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TREATMENT Early Hypocalcemia

Late Hypocalcemia

Symptomatic infant of any gestation • IV administration of 100 mg/kg of 10% calcium gluconate 30–60 min or 20 mg/kg of calcium chloride over 10–20 min, then start maintenance therapy with IV calcium gluconate at 500 mg/kg/d; patients receiving calcium boluses should be placed on cardiorespiratory monitors • If concomitant hypomagnesemia, start IV maintenance therapy using magnesium sulfate 25–50 mg/kg/ dose over 1–2 h twice daily until levels normalize

IV therapy • Bolus infusion of Ca gluconate 100 mg/kg (10 mg/kg elemental calcium) over 30–60 min • If central line is in place, begin calcium gluconate infusion at 1000 mg/kg/day (~100 mg/kg/day elemental calcium) • If central line is not available, limit calcium gluconate infusion to 600 mg/kg/day ( ~60 mg/kg/day elemental calcium) regardless of iCa value • Measure iCa 1 h after the bolus, then every 4 h. When iCa is >1.0 mmol/L and symptoms have been controlled, decrease frequency of monitoring to every 6–8 h • If iCa remains <1.0 mmol/L after initial bolus, repeat infusion of Ca gluconate 100 mg/kg while continuing current rate of IV Ca infusion • If iCa is 1.0–1.20 mmol/L, no additional IV boluses of calcium needed, but maintain infusion rate • Consider oral feeds and start oral supplement with Ca glubionate (Neo-Calglucon; see below) • If iCa is 1.21–1.30 mmol/L, decrease Ca gluconate infusion to 250 mg/kg/d (~ 25 mg/kg/d elemental Ca) • Start oral feeds and oral supplement with Ca glubionate (Neo-Calglucon; see below) • Discontinue IV Ca infusion if iCa is >1.21 mmol/L on two measurements and patient is tolerating feeds with oral Ca glubionate • If iCa is ≥1.3 mmol/L and feeds and oral Ca supplements have been started, discontinue IV Ca infusion • If serum Mg is <1.6 mg/dL, give magnesium sulfate 25 mg/kg IV over 1–2 h • Measure serum Mg after completing infusion, and repeat bolus every 12 h until Mg level is ≥1.6 mg/dL • Use of calcitriol at the discretion of the endocrine service

Asymptomatic infants <1500 g • Start TPN with calcium as soon as possible • If TPN is not available, add Ca gluconate 500 mg/kg/d to IV infusion • If calcium will be used in TPN for more than 48 h, add phosphorus to avoid hypercalcemia Asymptomatic infants >1500 g • Treat if iCa is <1.0 mmol/L • For infants requiring IV therapy, begin IV Ca gluconate 500 mg/kg/d infusion • For infants on enteral feeds, intravenous Ca may not be needed, but monitor serum ionized Ca and phosphorus regularly

OSTEOPENIA OF PREMATURITY Definition • Osteopenia of prematurity is defined as postnatal bone mineralization that is inadequate to fully mineralize bones.

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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 glubionate or 23 mg of elemental Ca

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ETIOLOGY Cause

Examples

Deﬁciency of calcium and phosphorus (principal cause)

• Unfortiﬁed breast milk • Long-term TPN • Use of inappropriate formula to feed preterm infants • Furosemide therapy • Long-term corticosteroid use • Renal phosphorus wasting

Vitamin D deﬁciency

• Maternal deﬁciency → congenital rickets • 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 fluid restriction and on prolonged TPN and/or corticosteroids • “Washed out” or undermineralized bones—signs develop during the first few weeks of life • Signs of rickets will develop after 6 wk of age • Incidental finding of healing fractures on routine X-rays is common • Respiratory insufficiency/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 • Usually low, typically <4 mg/dL (<1.3 mmol/L) • Serum calcium • Can be low, normal, or elevated • Not a good indicator of metabolic bone disease • Serum alkaline phosphatase

• Wrist or knee ﬁlms and/or CXR • Epiphyseal growth plate widening • Cupping or fraying of metaphyses • Subperiosteal bone formation • Osteopenia (especially of skull, spine, scapulae, and ribs) • Pathologic fractures (new or healing) • Up to 40% of bone mineralization can be lost before radiographic changes occur • Bone mineral content measurements remain investigational

• Often, but not always, correlates with degree of disease severity (>1000–1200 IU/L in severe rickets) • Normal VLBW infant without osteopenia can have alkaline phosphatase in the 400–600 IU/L range • Alkaline phosphatase can also be elevated due to obstructive hepatobiliary disease; correlation with 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

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Prevention and Treatment • Early initiation of enteral feedings, as clinical condition allows • Use of human milk fortifiers 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 Definition • Plasma glucose >145 mg/dL or whole blood glucose >125 mg/dL. Values up to 250 mg/dL have not been associated with specific 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 significant 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

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• 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 blood glucose level). • Follow bolus with insulin infusion at 0.01 units/kg/h. Care should be taken to ensure that IV tubing is flushed 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.

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• 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 Definition • Definition 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 first 24 h, then >50 mg/dL beyond the first 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 (hyperinsulinism)

• LGA infants • 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/ production

• Prematurity • IUGR • SGA infants • Postmature infants • Severe maternal preeclampsia • Delayed initiation of feeds/inadequate glucose infusion

Mixed cause (combination of increased utilization and decreased production)

• Perinatal stress (sepsis, shock, hypothermia, asphyxia, postresuscitation) • 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 deﬁciency, glutaric acidemia type II) • Defects in fatty acid metabolism (eg, medium- and long-chain fatty acid deﬁciencies) (continued on next page)

Endocrinology Mechanism of Hypoglycemia

Examples

Impaired glucose mobilization (hormone deﬁciencies)

• Growth hormone deﬁciency • Glucagon deﬁciency • Cortisol deﬁciency • Panhypopituitarism • Resistance to ACTH • Epinephrine deﬁciency • Thyroid hormone deﬁciency • Hypothalamic hormone deﬁciencies

405

Clinical Features • Some infants may be asymptomatic until severely hypoglycemic • Weak or high-pitched cry • Irritability, jitteriness, tremors • Apnea, cyanotic spells • Feeding difficulties • Lethargy or stupor

• Grunting, tachypnea • Seizures • Hypothermia • Sweating • Hypotonia, limpness • Tachycardia

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 confirmatory test should be sent to the laboratory. • Treatment should not be delayed while waiting for results of a confirmatory 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 first 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 significant. • 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. (% dextrose concentration) × (mL/kg/day of fluids) 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

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GIR (mg/kg/min) =

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• 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 fluids. • 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 proﬁle • 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 Definition • Serum sodium >150 mmol/L

Etiology • Increased insensible water losses • Inadequate water intake

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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 Status

Possible Etiologies

Findings

Treatment

Hypovolemia or Euvolemia

• Increased renal and insensible free water loss • Diabetes insipidus (DI; central or nephrogenic)

• Weight loss • Tachycardia • Hypotension • Metabolic acidosis • Polyuria if DI; eventual ↓ in UOP if not DI

• Increase free water administration to decrease serum sodium at a rate no greater than 1 mEq/kg/h. • May need to use intranasal desmopressin for central DI. • Note: Correction of hypernatremia should be done over 48 h to decrease the propensity of cerebral edema.

Hypervolemia

• Excessive isotonic or hypertonic ﬂuid

• Weight gain with edema • Normal heart rate, blood pressure, and urine output, with an elevated FENa

• Restrict sodium intake

HYPONATREMIA Definition • Serum sodium <130 mmol/L

APPROACH TO THE NEONATE WITH HYPONATREMIA BASED ON VOLUME STATUS ECF Volume Status Hypovolemia

Findings

• Findings consistent • Administer sodium and with dehydration free water to replace • Decreased weight losses and make up deﬁcits • Rising BUN • Metabolic acidosis • Tachycardia • Poor skin turgor

Treatment

(continued on next page)

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Possible Etiologies • Renal water and salt wasting (especially in VLBW infants) • Diuretic use • Osmotic diuresis • Salt-wasting disorders (adrenal and renal—see below) • GI losses • Third-space losses (necrotizing enterocolitis and losses from skin sloughing)

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Neonatology

ECF Volume Status

Possible Etiologies

Findings

Euvolemic

• SIADH from: • Pain • Opiate administration • IVH • Asphyxia • Meningitis • Pneumothorax • Positive-pressure ventilation • Excess free water administration

• Weight gain w/o • Restriction of free water edema if sodium is >120 mEq/L • With SIADH: • If neurologic symptoms decreased UOP and are present: increased urine • Furosemide (1 mg/ osmolarity kg q6h) with replace• NOTE: Diagnosis ment of urinary of SIADH assumes sodium losses with no volume-related hypertonic saline (3%) reason for ADH • Return to simple free release. water restriction once serum sodium >120 mEq/L and neurologic signs improve

Hypervolemic

• Sepsis with decreased cardiac output • Necrotizing enterocolitis • Heart failure • Impaired lymphatic drainage • Neuromuscular blockade

• Weight gain with • Treatment of underlying edema disorder • Decreased UOP • Restrict free water as clinically allowed with • For infants with some degree of sodium mature renal function, ↑ BUN, ↑ urine restriction SG, and ↓ FENa

Available at www.AccessPediatrics.com • Disorders of sexual differentiation • Congenital hypothyroidism • Infant of diabetic mother • Disorders of magnesium

Treatment

C H A P T E R 35

Gastroenterology DELAYED PASSAGE OF MECONIUM • The delayed passage of meconium may be the result of a mechanical or functional bowel obstruction. • Virtually all infants, term and preterm, will have passed meconium by 48 h of age. • The evaluation of any infant with delayed passage of meconium should begin with a thorough physical examination and history. • For infants who are unstable, the infant must first be stabilized before the investigation begins as to the cause of delayed stooling.

DIFFERENTIAL DIAGNOSIS, EVALUATION, AND MANAGEMENT OF DELAYED PASSAGE OF MECONIUM Diagnosis

Management

Anorectal abnormality (imperforate anus, anal stenosis)

Imperforate anus should be evident on physical examination Anal stenosis may be evident on physical examination

Surgical consult Repogle to low intermittent suction IV ﬂuids Remember that high anal atresias may be associated with GU abnormalities

Meconium plug

Contrast enema shows the meconium plug with a normal-caliber colon

Enema is usually therapeutic If abnormal stooling continues, consider diagnosis of Hirschsprung’s disease and rectal biopsy

Meconium ileus

Contrast enema reveals a microcolon from ileal obstruction with stool

Enema can be therapeutic but may need surgical intervention

Hirschsprung’s disease

Contrast enema shows a distally narrowed segment (aganglionic) leading to a dilated proximal segment (normal colon) If suspected, rectal biopsy will provide the deﬁnitive diagnosis

Surgical consult Repogle to low intermittent suction IV ﬂuids Diverting colostomy is standard; end-to-end anastomosis if aﬀected segment is very short

Ileal atresia

Contrast enema shows no reﬂux of contrast into the terminal ileum

Surgical consult Repogle to low intermittent suction IV ﬂuids

Malrotation

Infants usually present with bilious emesis Upper GI or contrast enema shows a malpositioned cecum

Surgical consult Repogle to low intermittent suction IV ﬂuids

(continued on next page)

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Cause

410

Neonatology

Cause

Diagnosis

Management

Volvulus

Surgical emergency because the ischemic gut may progress to frank necrosis Plain ﬁlm of the abdomen reveals a massively dilated proximal colon Contrast enema reveals a midtransverse colon obstruction

Emergent surgical consult Repogle to low intermittent suction IV ﬂuids

Ileus

May be secondary to a number of factors: • Sepsis • NEC • Hypokalemia • Hypothyroidism • Hypermagnesemia • Narcotic analgesia therapy

Bowel rest IV ﬂuids Treatment of underlying condition causing the ileus

GASTROESOPHAGEAL REFLUX DISEASE (GERD) • GER is defined 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 specific treatment(GER) vs. infants who experience feeding difficulties, poor weight gain, failure to thrive, etc as a direct result of reflux (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 • Esophageal atresia repair • Gastroschisis • Omphalocele

• Short bowel syndrome (SBS) • Bronchopulmonary dysplasia • Neurologic deficits

Differential Diagnosis • Differential diagnosis for GER should include: • GI tract anatomic abnormalities: Esophageal webs or stenosis, duodenal web or stenosis, malrotation, gastric outlet obstruction

• Inborn errors of metabolism • Renal dysfunction • Neurologic deficits • Bronchopulmonary dysplasia

Clinical Presentation • Dysphagia • Odynophagia • Arching of the back with feeds

• Irritability • Failure to thrive • 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).

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• 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 efficacy 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 benefit 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 Major Risk Factors

Minor Risk Factors

• Predischarge TSB or TcB in high-risk zone • Jaundice in the ﬁrst 24 h • Known hemolytic disease • GA 35–36 wk • Older sibling received phototherapy • Cephalhematoma or signiﬁcant bruising • Exclusive breastfeeding (especially with poor feeding or excessive weight loss) • East Asian race

• Predischarge TSB or TcB in high-intermediaterisk zone • GA 37–38 wk • Jaundice observed before discharge • Older sibling with h/o jaundice • Macrosomic IDM • Maternal age <25 yr • Male gender

Factors that Decrease Risk • Predischarge TSB or TcB in the low-risk zone • GA ≥41 wk • Exclusive bottle feeding • African American race • Hospital discharge >72 h

Physiologic Unconjugated Hyperbilirubinemia

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• 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: • 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

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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 cavity

• Sequestered blood turnover contributes to bilirubin load • May be seen with bleeding into any body cavity (cephalhematoma, GI bleeding, pulmonary hemorrhage)

Conjugation defects

• Crigler-Najjar syndrome (types I and II; caused by relative deﬁciencies in UDP glucuronyl transferase) • Gilbert syndrome (caused by mild form of UDP glucuronyl transferase deﬁciency) • Lucey-Driscoll syndrome (caused by an undeﬁned maternal hormone that interferes with bilirubin conjugation)

Breast milk jaundice

• Jaundice that appears around 5–7 d of life, peaks later at 10–15 d, and declines over several weeks • Caused by an undeﬁned 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 jaundice

• Early onset jaundice caused by poor caloric intake and relative dehydration • Resolves as breastfeeding improves and milk supply increases

Metabolic disorders

• Galactosemia, hypothyroidism, maternal DM

Increased enterohepatic recirculation

• From any cause that delays transit through the gut (bowel obstruction at any level, CF, ileus from any cause)

Displacement of bilirubin from albumin

• Drugs (aspirin, sulfonamides, ceftriaxone) • Increased fatty acid concentration • 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 first-line therapy.

Gastroenterology 25

428

20

342 95th percentile

High risk zone 15

te r

edia

h

Hig

rm inte

Low

10

isk

te r

dia rme

e zon

257

e zon isk

μmol/L

Total Serum Bilirubin (mg/dL)

413

inte

171

Low risk zone 5

85

0

0 0

12

24

36

48

60 72 84 96 Postnatal Age (hours)

108

120

132

144

Figure 35-2 Bhutani Nomogram: Nomogram for designation of risk (likelihood) of a subsequent bilirubin level exceeding the 95th percentile, based on the hour-specific 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 Companies, Inc. All rights reserved.) For more information: Pediatrics 2004;114(1):297 and Pediatrics 1999;103:6.

25

428

20

342

15

257

10

171

5

μmol/L

Total Serum Bilirubin (mg/dL)

• 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.

85

Infants at lower risk (≥38 wk and well) Infants at medium risk (≥38 wk + risk factors or 35–37 6/7 wk and well)

0

Infants at higher risk (35–37 6/7 wk + risk factors)

Birth

24 h

24 h

72 h

96 h

5 days

6 days

0 7 days

Age

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.

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• 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). • 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.

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• 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 figure 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 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

15

257

0

Birth

24 h

24 h

72 h

96 h

5 days

6 days

μmol/L

Total Serum Bilirubin (mg/dL)

Infants at lower risk (≥38 wk and well)

171 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)] Birth Weight (g)

Consider Phototherapy at:

Consider Exchange 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: Pathophysiology and Management of the Newborn. Philadelphia: JB Lippincott; 1999:765–819.

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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 • NEC • Intestinal malrotation • Volvulus • Meconium plug or ileus • Ileus • Transpyloric passage of the feeding tube

• Advancing of feeds too rapidly • NEC • Stricture after episode of NEC • Gastric outlet obstruction • Ileus • Infection • Inborn error of metabolism • Constipation • Formula intolerance

• Traumatic nasogastric insertion • NEC • Swallowed maternal blood • Coagulopathy • Stress gastritis • Volvulus • Medications (corticosteroids, indomethacin)

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 profile

MANAGEMENT OF LARGE OR INCREASED GASTRIC ASPIRATES Nonbilious Residual

Bloody Residual

For surgical abdomen or NEC: • NPO • Decompression of stomach by placement of Repogle tube to low intermittent suction • Consult pediatric surgery service • Initiation of IV ﬂuids as appropriate • Obtain blood, urine and CSF cx and start broad-spectrum antibiotics (ampicillin, vancomycin, and gentamicin; add clindamycin if bowel necrosis or perforation is suspected) For ileus: • NPO • Decompress stomach by placement of Repogle to low intermittent suction • Investigate cause of ileus (infection, NEC, electrolyte disturbances)

Assuming the clinical exam remains entirely benign: • For aspirates containing undigested milk in which the volume is not >50%: May need to decrease volume of feeds • For aspirates with partially digested milk: May discard residual and resume feeds as prescribed • For concerns of surgical cause (NEC, stricture post-NEC): See management under “Bilious Residual” For suspected infection: • Make NPO and decompress stomach with Repogle to low intermittent suction • Obtain appropriate cx • Obtain CBC • Initiate broad-spectrum antibiotics (ampicillin, vancomycin, and gentamicin)

For NEC: • See management under “Bilious Residual” For suspected coagulopathy: • NPO • Decompress stomach with Repogle to low intermittent suction • Check PT, PTT, ﬁbrinogen, CBC, D-dimer • If evidence of DIC, treat underlying cause • Replenish platelets and coagulation factors as needed

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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 significantly 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 inflammatory 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 Apnea Bradycardia Respiratory distress Irritability Feeding intolerance Hypotension Temperature instability Acidosis Oliguria Coagulopathy

Poor perfusion Bloody stools Abdominal distension Abdominal tenderness Gastric residuals Ileus Abdominal wall erythema Localized abdominal mass Ascites Vomiting (bloody or bilious)

STAGING OF NECROTIZING ENTEROCOLITIS Stage

Systemic Signs

Abdominal Signs

Radiographic Signs

Stage 1: Suspected NEC

• Apnea • Lethargy • Bradycardia • Temp instability

• Gastric residuals • Feeding intolerance • Guaiac-positive stools

• Normal or nonspeciﬁc

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Stage

Systemic Signs

Abdominal Signs

Radiographic Signs

Stage IIA: Mild NEC

• As in Stage 1

• Abdominal distension • Abdominal tenderness • Absent bowel sounds • Bloody stools

• Ileus • Dilated loops of bowel • Focal pneumatosis intestinalis

As in Stage 1, plus:

• Further abdominal distension • Abdominal tenderness • Abdominal wall edema • Abdominal mass

• Extensive pneumatosis intestinalis • Ascites • ± Portal venous gas

Stage IIB: Moderate NEC

• Mild acidosis • Thrombocytopenia

Stage IIIA: Advanced NEC

• Mixed acidosis • Need for mechanical ventilation • Hypotension • Oliguria • Neutropenia • Coagulopathy

• Worsening abdominal wall edema • Worsening abdominal wall tenderness • Worsening abdominal wall discoloration (erythema or ecchymotic changes)

• Prominent ascites • Paucity of bowel gas • Sentinel loop of bowel

Stage IIIB: Advanced NEC

• Generalized edema • Intractable hypotension • Shock • DIC • Electrolyte abnormalities

• Tight abdominal distension • Signiﬁcant discoloration of abdomen

• Absent bowel gas • Pneumoperitoneum

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

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• Clinical examination: Systemic and abdominal signs/symptoms as outlined above • Laboratory studies: • CBC • Culture of blood, urine, CSF, ± stool • Blood gas measurement (preferably arterial) • Serum electrolytes • BUN/creatinine • Radiographic studies • Flat plate radiograph of abdomen • Add a left-lateral decubitus (ie, left side down) film of abdomen if pneumoperitoneum is suspected (bowel perforation commonly occurs within 48-72 h of symptom onset)

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MANAGEMENT OF INFANTS WITH NECROTIZING ENTEROCOLITIS Stage I

Stages IIA and IIB

Stages IIIA and IIIB

• Make NPO • Decompress bowel (place repogle tube to low intermittent suction) • Continuous cardiorespiratory monitoring • Controversial: Removal of umbilical catheters and placement of peripherally inserted venous and arterial lines • Broad-spectrum antibiotics (gentamicin, and ampicillin or vancomycin; clindamycin may be added if perforation or bowel necrosis is suspected) • Monitor for pathologic bleeding • Strict monitoring of “ins and outs” • Remove potassium from all ﬂuids • Cultures as outlined above • Other labs listed above can be followed serially as indicated • Serial abdominal plain ﬁlms ± decubitus views to evaluate for free air Q6–12 h for the ﬁrst 48–72 h; then as needed

• All stage I management plus: • Constitute TPN to deliver 100–120 kcal/kg/d • Adjust ﬂuids to allow for possible frequent transfusion of blood products, third-space losses, and renal failure • Respiratory support as required • Cardiovascular support as required with pressors (eg, dopamine) • Strongly consider obtaining a surgical consultation

• All stage I and II management plus: • Refractory hypotension may become an issue; will need support with pressors, intravascular volume expansion with blood products or crystalloid solutions • Common ﬁndings in this stage include severe thrombocytopenia, DIC, leukopenia or neutropenia • Surgical intervention may be necessary at this stage

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.

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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

Hepatocellular disease

• α1-Antitrypsin (A1AT) deﬁciency • 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 specific diagnoses based on clinical presentation and history.

EVALUATION OF DIRECT (CONJUGATED) HYPERBILIRUBINEMIA Rationale for Study

Diagnostic Studies 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 causes

A1AT with Pi phenotype, serum and urine amino acid proﬁle, urine organic acid proﬁle, ammonia, urine succinylacetone, urine ketones, serum lactate and pyruvate, serum ferritin, urine reducing substances, urinalysis, echocardiography (suspicious for cardiac disease)

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 capacity

HIDA scan Liver biopsy

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Evaluate for anatomic causes

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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. • Fortiﬁed human milk or standard premature formula is appropriate for premature neonates with cholestasis. • In infants with signiﬁcant 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)

• UDCA is a potent choleretic, increasing bile ﬂow and hence helping to improve cholestasis. • Its eﬃcacy 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 manganese

• Cu and Mn are excreted in bile. • 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 deﬁciencies 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

C H A P T E R 36

Genetics NONIMMUNE FETAL HYDROPS Definition • Presence of excess extracellular fluid in at least two fetal compartments (ascites, pleural effusion, pericardial effusion, skin edema, polyhydramnios) without any identifiable circulating antibody to red-cell antigens. • For a discussion on immune-mediated disease, see Chapter 37. • Prevalence is estimated at 1:1500-4000. • Highest prevalence in Southeast Asian population.

Diagnosis • Increased uterine size for dates • Decreased fetal movements • Generalized maternal edema (mirror syndrome)

• Polyhydramnios (AFI >24) • Placentomegaly

Management • Infants with nonimmune hydrops are at very high risk for fetal demise. • Intrauterine therapy is aimed at treating underlying causes (maternal digitalis therapy for fetal tachyarrhythmias); if this is not possible, the risks of intrauterine death versus premature delivery have to be weighed. • By organ system (see table below).

MANAGEMENT OF NONIMMUNE FETAL HYDROPS BY ORGAN SYSTEM System

Potential Difficulties/Management

Pulmonary

• Diﬃcult intubation due to severe edema of head/neck/oropharynx. → Consider ENT or anesthesia support for intubation as needed. • Varying degrees of pulmonary hypoplasia due to large pleural eﬀusions or other extrinsic in utero compression of lungs → May need emergent thoracentesis in delivery area to alleviate lung compression from large eﬀusions. • Chest tube placement for rapidly reaccumulating pleural eﬀusions.

Cardiovascular

• Hypotension should be treated with appropriate inotropic support. • Remember that most hydropic infants are euvolemic intravascularly, often with depressed cardiac function → Avoid large ﬂuid shifts. • Pericardiocentesis may be necessary if cardiac tamponade from pericardial eﬀusion is suspected → Should ideally be done under US guidance. • Arterial access is helpful to follow invasive blood pressures. • Echocardiogram should be obtained to evaluate for structural abnormalities as a cause of hydrops.

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Neonatology

System

Potential Difficulties/Management

Fluids and electrolytes

• Infants are total body ﬂuid overloaded but are usually euvolemic (intravascular 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 ﬂuid overload and to allow diuresis. • Vigilant attention to all ﬂuid intake and output to maintain an adequate circulating volume. • Electrolyte losses should be replaced accordingly in the IV ﬂuids. • 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 disease

• Workup should proceed as indicated to ﬁnd infectious etiologies for the infant’s hydrops. • Serum PCR can be sent to ﬁnd 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 ultraﬁltration has not been established in the treatment of ﬂuid overload found in hydropic infants, especially as the edema is known to improve with very careful monitoring of total ﬂuid 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 Craniofacial

Trisomy 21

Trisomy 18

Trisomy 13

Flat facial proﬁle Slanted palpebral ﬁssures Anomalous auricles

Prominent occiput Short palpebral ﬁssures Low-set “tulip shaped” ears

Microcephaly Sloping forehead Wide fontanels Microphthalmia Cleft lip Cleft palate Abnormal helices Cutis aplasia of scalp (continued on next page)

Genetics Clinical Presentation

423

Trisomy 21

Trisomy 18

Trisomy 13

Extremities

Dysplasia of midphalanx of ﬁfth ﬁnger Single palmar crease Sandal crease

Clenched hand Short hallux

Polydactyly Single palmar crease Posterior prominence of heel

Cardiac

Endocardial cushion defect, VSD, PDA

VSD, PDA, ASD

VSD, PDA, ASD

Neurologic

Hypotonia

Weak fetal activity

Holoprosencephaly Deafness Seizures

Other

Excess skin on back and neck

Polyhydramnios Small placenta Single umbilical artery Muscle hypoplasia Adipose tissue hypoplasia

Single umbilical artery

MAJOR TERATOGENIC AGENTS AND PRENATAL EXPOSURE EFFECTS Clinical Presentation

Ethanol

Growth deﬁciency (prenatal onset) Microcephaly Dysmorphic facial features (short palpebral ﬁssures, short nose, smooth philtrum, thin and smooth upper lip) Irritability

Phenytoin

Growth deﬁciency 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 ﬁngers and toes

Warfarin

Nasal hypoplasia and depressed nasal bridge Stippling and uncalciﬁed epiphyses Shortened ﬁngers with mild nail hypoplasia

Methotrexate

Growth deﬁciency Microcephaly with hypoplasia of cranial bones Wide fontanels, prominent eyes, and micrognathia Mesomelia

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Teratogen

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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 frequently seen in children born to mothers with DM

Vertebral anomalies Anal atresia Cardiac anomalies (conotruncal anomalies, CAVC) Tracheoesophageal ﬁstula with esophageal atresia Renal anomalies Limb anomalies (radial dysplasia, polydactyly, syndactyly) Single umbilical artery

CHARGE

CHARGE is caused by coding region mutations and large deletions of the CHD7 gene (8q12)

Coloboma Heart defect (TOF, PDA, CAVC) Atresia choanae 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

C H A P T E R 37

Hematology INDIRECT (UNCONJUGATED) HYPERBILIRUBINEMIA • See Chapter 35 (Gastroenterology). THROMBOCYTOPENIA • Occurs in 1%–5% of newborns (platelet count <150,000/mm3); severe thrombocytopenia (<50,000/mm3) occurs in 0.1%–0.5%. • Sick newborns have an incidence as high as 22%–50%.

Ill-appearing infant∗ ↑ PT, PTT

Normal PT, PTT • Congenital Infection (eg, CMV, toxoplasmosis, rubella) • Hypersplenism • Marrow infiltration • NEC

• DIC (Sepsis) • Hypoxia • Acidosis • Cold stress • Severe liver disease

Well-appearing infant∗

Mother’s platelet count normal

Mother’s platelet count ↓ • Maternal ITP • Maternal drug exposure • Familial

Figure 37-1 Brief differential diagnosis for thrombocytopenia in neonates. *One of the most common causes of thrombocytopenia is improper specimen collection; confirm with peripheral smear to exclude laboratory error

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• NAIT (Neonatal Alloimmune Thrombocytopenia) • Neonatal drug exposure • Hemangioma • Congenital thrombocytopenia (see below) • Maternal ITP in remission

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Neonatology

Immune Thrombocytopenias: Decreased Platelet Survival COMPARISON OF IMMUNE-MEDIATED CAUSES OF THROMBOCYTOPENIA IN NEONATES Autoimmune Thrombocytopenia

Alloimmune Thrombocytopenia

Deﬁnition

• Antibody made against maternal platelet antigen; antigen is also found on fetal platelets

• Antibody made against paternal platelet antigen; antigen is also found on fetal platelets

Clinical ﬁndings

• Mild to moderate thrombocytopenia (20,000–50,000/mm3) • Petechiae and bruising are common • Mother usually has thrombocytopenia or history of ITP • Maternal platelets may be normal because she may have adequate production of platelets to compensate for increased destruction

• May lead to severe thrombocytopenia (<20,000/mm3) and in utero hemorrhagic complications (~20% of infants with NAIT have intracranial hemorrhages) • Infant appears healthy but may have petechiae and bruising • Maternal platelet count is usually normal • Most common antigen is HPA-1

Pathophysiology

• Maternal autoantibodies cross the placenta and bind to neonatal platelets, causing increased destruction

• Maternal alloantibodies cross the placenta and bind to neonatal platelets, causing increased destruction

Diagnosis

• Identiﬁcation of autoantibody in maternal serum against antigens on her own platelets

• Identiﬁcation of alloantibody using paternal platelets and maternal serum

Prenatal management

• Use of steroids to prevent fetal thrombocytopenia is controversial; not shown to be of beneﬁt • Use of immune globulin to prevent fetal thrombocytopenia is controversial; not shown to be of beneﬁt • PUBS (Percutaneous Umbilical cord Blood Sampling) seems to be safe but is invasive, and its use is controversial; not shown to be of beneﬁt • Mode of delivery (cesarean section vs vaginal) does not change maternal or fetal outcomes; cesarean section is not shown to be of beneﬁt

• Use of steroids, immune globulin, PUBS, fetal scalp platelet counts during labor, and elective cesarean delivery can be used on a case-by-case basis

Postnatal management

• May include platelet transfusions (pooled donor), steroids, immune globulin or exchange transfusion • Transfuse platelets for levels <20,000/mm3 or for clinical bleeding

• If diagnosis is made before delivery, maternal platelets are collected 24 h before delivery • If infant requires platelet transfusions postnatally, use collected maternal platelets that have been washed and resuspended in plasma (continued on next page)

Hematology Autoimmune Thrombocytopenia

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Alloimmune 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 hemangioma (Kasabach-Merritt syndrome)

• Transfuse platelets as necessary • Replenish clotting factors as needed • Treatment of hemangioma may involve corticosteroid administration, surgical removal, or embolization of hemangioma

• NEC

• Treatment of underlying disease • Transfuse platelets and replenish clotting factors as needed

• Immune thrombocytopenias

• See table immediately prior • Drug-induced thrombocytopenia is treated with removal of the oﬀending agent

• Hypersplenism

• Associated with viremic illnesses, portal hypertension • Transfuse platelets as needed • Splenectomy in severe cases

• Wiskott-Aldrich syndrome

• Transfuse platelets as needed

Platelet destruction

Intrinsic platelet dysfunction

• May-Hegglin anomaly • Bernard-Soulier syndrome

• Injury to megakaryocytes • Marrow failure or infiltration

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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 • Defined as a central hematrocrit >65% (free-flowing 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 RBC mass from placenta to infant at the time of delivery

Delayed cord clamping Cord stripping Positioning the infant below the placental vascular bed Maternal–fetal hemorrhage Intrapartum asphyxia or acidosis Twin-to-twin transfusion Forceful uterine contractions

Increased fetal erythropoiesis

Stimulus for increased fetal erythropoiesis from fetal hypoxia

Placental insuﬃciency related: • Maternal hypertension • Chronic placental abruption • Postmaturity • Cyanotic heart disease • IUGR • Maternal cigarette smoking

Stimulus for increased fetal erythropoiesis from increased oxygen consumption

Infant of a diabetic (chronic or gestational) mother Congenital hyperthyroidism Beckwith-Wiedemann syndrome Congenital adrenal hyperplasia

Unknown

Trisomies 13, 18 and 21

Concentration of RBC mass in smaller volume of plasma (hemoconcentration)

Dehydration

Decreased relative plasma volume

Clinical Presentation • Multiple organ systems may be affected. • The clinical presentation depends on the extent of involvement of each system.

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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 Central Hematocrit >70%

Expectant management Increase ﬂuid administration by 20–30 mL/ kg/day and repeat HCT within 4–6 h

Partial exchange transfusion

Symptomatic

Partial exchange transfusion

Partial exchange transfusion

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Central Hematocrit 65%–70% Asymptomatic

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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 severe acidosis or hyperammonemia

Partial exchange (40–70 mL/kg) may be suﬃcient to decrease metabolite levels until dialysis can be started.

Severe hyperkalemia or other severe electrolyte abnormality

Partial exchange (40–70 mL/kg) may be suﬃcient to 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 hypervolemia or in normovolemia in which large-volume transfusions may not be tolerated)

Partial exchange (40–70 mL/kg)

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 flow 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 final 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 • ABO incompatibility

Type O, Rh-negative, low anti-A and anti-B titers; cross-match to maternal plasma and RBCs Type O, Rh-compatible (continued on next page)

Hematology Indication

Blood Typing and Cross-Matching

• Minor blood group incompatibilities

Type O, Rh-compatible

Metabolic disorders causing severe acidosis or hyperammonemia

Type and cross-match against infant plasma and RBCs

Severe hyperkalemia or other severe electrolyte abnormality

Type and cross-match against infant plasma and RBCs

Severe anemia (in presence of hypervolemia or in normovolemia when large volume transfusions may not be tolerated)

Type and cross-match against infant plasma and RBCs

431

• 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 flush. 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

• 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.

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ANEMIA

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Neonatology

BRIEF DIFFERENTIAL DIAGNOSIS OF ANEMIA IN NEONATES Etiology

Mechanism

Examples

Blood Loss • ↓ or normal hematocrit • ↑ or normal reticulocyte count • Normal bilirubin (unless blood is retained)

Obstetric causes

Placental abruption Placenta previa Placental trauma Rupture of anomalous vessels (vasa previa, velamentous insertion) Cord hematoma Cord rupture

Occult loss

Fetomaternal hemorrhage (chronic or acute) from placental 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)

Immune-mediated

Rh incompatibility ABO incompatibility Minor blood group incompatibility Maternal autoimmune disease (eg, SLE) Maternal or neonatal drug exposure (eg, penicillin)

Hereditary disorders of RBC

Membrane defects (spherocytosis, elliptocytosis) Metabolic defects (G6PD deﬁciency, pyruvate kinase deﬁciency) Hemoglobinopathies (α and β thalassemia syndromes)

Acquired hemolysis

Infection DIC Nutritional deﬁciencies (eg, vitamin E deﬁciency) Microangiopathic hemolytic anemia Hemangioma Renal artery stenosis Severe aortic coarctation

Hemolysis • ↓ Hematocrit • ↑ Retic • ↑ Bilirubin

Diminished production • ↓ Hematocrit • ↓ Retic • Normal bilirubin

Diamond-Blackfan syndrome Congenital leukemia Neoplasms Osteopetrosis Drug exposure (eg, penicillin) 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 oﬀered the option of donor-directed blood (irradiation of this blood is of particular importance because of the HLA compatibility among ﬁrst-degree relatives and the risk of foreign lymphocyte engraftment)

Whole blood

• Indicated for large acute blood loss

Partial exchange transfusion (isovolemic transfusion)

• Indicated for infants with severe anemia in whom transfusion of regular PRBC units would present a signiﬁcant volume overload (eg, hydropic infants)

• Calculation of the volume of PRBC or whole blood transfusion:

(∗): 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.)

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TBV∗ × [(HCTdesired−HCTobserved) / HCTblood to be given∗∗]

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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 deﬁciencies

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 concentrates

Given for known, speciﬁc factor deﬁciencies to avoid overload of nondeﬁcient factors

Cryoprecipitate

Best source of concentrated ﬁbrinogen 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 specific 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 Product Principles

Indications and Dosing and Contraindications Administration Side Effects

PRBCs

For hematocrit <35%–40%: • Mechanical ventilation with FiO2 >35% or mean airway pressure >6 cm H2O • Hypotension • Chronic or recurrent bleeding

• RBCs provide increased oxygen-carrying capacity • Preservative solutions are used to extend the storage life of PRBCs (shelflife, 21–35 d depending on which solution is used; check with your blood bank to determine the shelf life of PRBCs used at your institution) • Average hematocrit, 70%–80%

• Usual transfu• Acute hemolytic sion, 5–15 mL/ transfusion reaction kg at ~5 mL/ • Usually caused kg/h by antibodies in • Adjust dose and patient plasma time of transfureacting to donor sion depending RBCs on the infant’s • Rare in neonates ability to handle unless there is volume expanhigh titer maternal sion isohemagglutinins (anti-A, anti-B) For hematocrit • Allergic reactions <25%–30%: • Usually caused by • HR >180 bpm antibodies in pafor 24 h tient plasma reacting with proteins • Apnea >9–12/h in donor plasma requiring b-m • Rare in neonates ventilation • Volume overload • Wt gain <10 g/kg/ day w/ full caloric • Hypocalcemia intake • Hypothermia (continued on next page)

Hematology Blood General Product Principles

Platelets

435

Indications and Dosing and Contraindications Administration Side Effects

• PRBC units undergo changes during storage as the unit approaches its expiration date • pH ↓ from ~7.40–~6.50 • Potassium concentration increased from ~4.2 mM to ~50–75 mM • 2,3-DPG levels decrease over the ﬁrst 14 d but are replenished within hours of being transfused

• Unexplained lethargy • Plan for major surgery

• Each unit of platelets contains >5 x1010 platelets in 50 mL of anticoagulated plasma • Stored at room temperature for ≤5 d

• No data exist on minimum platelet level in patients at risk for intraventricular hemorrhage, but levels of 50,000–100,000 platelets/mm3 are generally accepted • In all other neonates, transfuse for levels <20,000 • Transfuse when there is active bleeding

• TRALI • Caused by antibodies in donor plasma reacting with patient’s HLA antigens • More likely with components with high plasma content (platelets, FFP) • Hyperkalemia • Febrile nonhemolytic transfusion reactions • Caused by cytokines released in donor unit; occurs less often in leukocyte reduced units • Bacterial contamination • Transfusion associated GVHD • May be prevented with irradiation of blood products before transfusion

For hematocrit <20%–25%: • May consider transfusion independent of symptoms

• More likely to be contaminated with bacteria • ABO-incompatible plasma in platelet transfusion may cause hemolytic transfusion reaction

(continued on next page)

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• 5–10 mL/kg over 30–60 min • Should increase the platelet count (in a nonconsumptive clinical situation) by 30,000– 60,000/mm3 • If alloimmune thrombocytopenia, may need to use washed maternal platelets • Adjust dose and time of transfusion depending on the infant’s ability to handle volume expansion

436

Neonatology

Blood General Product Principles

Indications and Dosing and Contraindications Administration Side Effects

Fresh Frozen Plasma (FFP)

• ~1 U/mL of each coagulation factor (may have lower levels of unstable factors V and VIII) • Sodium content is 160–170 mEq/L • Potassium content is 3.5–5.5 mEq/L • Contains all plasma proteins (including albumin and antibodies)

• To correct coagulopathies caused by factor deﬁciencies

• 10–20 mL/kg over 30–60 min • Adjust the dose and time of transfusion depending on the infant’s ability to handle volume expansion

• Hyperkalemia does not occur • TRALI • Acute hemolytic reactions are extremely unlikely • Hypocalcemia (caused by sodium citrate in FFP)

Granulocytes

• Therapy is controversial

• In septic neonates not responding to antimicrobial therapy • If used, can only be used as a temporizing measure until the infant is able to produce his or her own neutrophils

• 10–15 mL/kg over 2–4 h • Adjust the dose and time of transfusion depending on the infant’s ability to handle volume expansion

• All of the potential adverse reactions seen with PRBC transfusion • Pulmonary complications • Transmission of CMV

Available at www.AccessPediatrics.com • Neonatal thrombosis • Abnormal bleeding

C H A P T E R 38

Infectious Diseases COMMON ANTIBIOTICS IN NEONATES

Antibiotic

Organisms Covered

Dose

Notes

Ampicillin

Gram-positive organisms (Streptococcus spp.) Susceptible Escherichia coli Listeria monocytogenes

Piperacillin

Pseudomonas • ≤7 d: 50 mg/kg/dose q8h aeruginosa Entero• >7 d: 50 mg/kg/dose q6h coccus spp. Other Gramnegative enteric and anaerobes PCN-susceptible Staphylococcus spp. Streptococcus spp.

Penicillin GK

GBS Treponema pallidum

GBS meningitis: • ≤7 d postnatal age: 450,000 units/kg/d divided every 8 h • >7 d postnatal age: 450,000– 500,000 units/kg/d divided every 4 h Other GBS infections: 200,000 units/kg/d divided every 6 h

Nafcillin

Methicillin-sensitive Staphylococcus aureus

Non-CNS infections: • <30 wk postmenstrual age (PMA): • ≤7 d: 25 mg/kg/dose q12h • >7 d: 25 mg/kg/dose q8h • 30–37 wk PMA: • ≤7 d: 25 mg/kg/dose q12h • >7 d: 25 mg/kg/dose q8h • >37 wk PMA: • ≤7 d: 25 mg/kg/dose q12h • >7 d: 25 mg/kg/dose q6h Meningitis: • Use 50 mg/kg/dose at same interval as listed above

Empiric treatment for early- or late-onset (age >72 hrs) sepsis: • ≤7 d old: 150 mg/kg/dose IV q12h • >7 d old: 75 mg/kg/dose IV q6h Treatment >48 h: • Meningitis or no CSF obtained: 75 mg/kg/dose IV q6h • Sepsis without meningitis: 75 mg/kg/dose IV q12h Moderate CSF penetration

(continued on next page)

437

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Cleared primarily by the liver → monitor LFTs on treatment Can cause interstitial nephritis → monitor renal function weekly on treatment Can cause bone marrow suppression → monitor CBC weekly on therapy

438

Neonatology

Antibiotic

Organisms Covered

Dose

Notes

Vancomycin

Aerobic and anaerobic Gram-positive cocci and bacilli Methicillin-resistant S. aureus (MRSA) Coagulase-negative staphylococci Clostridium difficile Bacillus spp. Ampicillin-resistant Enterococcus

• <30 wk PMA: • ≤7 d: 20 mg/kg/dose IV q24h • >7 d: 20 mg/kg/dose IV q18h • 30–37 wk PMA: • ≤7 d: 20 mg/kg/dose IV q18h • >7 d: 15 mg/kg/dose IV q12h • >37 wk PMA: • ≤7 d: 15 mg/kg/dose IV q12h • >7 d: 15 mg/kg/dose IV q8h • >44 wk PMA (meningitis): • 15 mg/kg/dose IV q6h

Only 10%–15% of serum concentration enters CSF. Optimal serum concentration: • Trough: 15–20 mcg/mL

Gentamicin, amikacin, tobramycin

Broad Gramnegative bacillus coverage Synergistic against S. aureus, GBS, L. monocytogenes, enterococci

Gentamicin • Indications: early- or late-onset sepsis (age >72 h); covers Gram-negative rods; use for synergy • <35 wk PMA: 3 mg/kg/dose IV q24h • ≥35wk PMA: 4 mg/kg/dose 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

CSF penetration depends on meningeal inﬂammation. Monitor peak and trough levels, as these antibiotics can cause nephrotoxicity and ototoxicity.

(continued on next page)

Infectious Diseases

Antibiotic

Organisms Covered

Dose

439

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 Gram-positive cocci Anaerobes (including Bacteroides fragilis)

• ≤37 wk PMA: • ≤7 d: 5 mg/kg/dose q8h • >7 d: 10 mg/kg/dose q8h • >37 wk PMA: • 13 mg/kg/dose q8h

Poor CSF penetration Cleared by the liver → monitor LFTs while on therapy

First-generation cephalosporins (cefazolin, cephalexin)

Susceptible Staphylococcus, Streptococcus, and pneumococci

Cefazolin: • ≤7 d postnatal age: • 20 mg/kg/dose q12h • >7 d postnatal age: • <2000 g: 20 mg/kg/dose q12h • >2000 g: 20 mg/kg/dose q8h

Poor CSF penetration

Secondgeneration cephalosporins (cefuroxime, cefoxitin, cefotetan, cefprozil)

Same as ﬁrst generation plus Haemophilus influenzae E. coli Citrobacter Klebsiella Enterobacter cloacae

Improved activity over ﬁrstgeneration against β-lactamase– producing organisms Little data in neonates, so use is limited

Thirdgeneration cephalosporins (ceftriaxone, cefdinir, ceftazidime, cefotaxime, ceﬁxime)

Gram-negative Cefotaxime: enterics • <1200 g, 0–4 wk: 50 mg/kg/ dose q12h H. influenzae Neisseria gonorrheae • ≤7 d postnatal age: • 1200–2000 g: 50 mg/kg/ Neisseria menindose q12h gitidis • >2000 g: 50 mg/kg/dose q8–12h • >7 d postnatal age:

Ceftazidime can be used for adequate coverage of Pseudomonas aeruginosa. Ceftazidime, cefotaxime, and ceftriaxone all achieve good CSF penetration. Ceftriaxone displaces bilirubin from albumin, raising serum levels of free unconjugated bilirubin → not recommended for use in neonates except in treating gonococcal infection in nonjaundiced neonates. In jaundiced neonates, use cefotaxime.

• 1200–2000 g: 50 mg/kg/ dose q8h • >2000 g: 150–200 mg/kg/d divided q6–8h Ceftazidime: • <7 d postnatal age: • 50 mg/kg/dose q12h • 1–4 wk postnatal age: • 30–50 mg/kg/dose q8h

(continued on next page)

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Clindamycin

440

Neonatology

Antibiotic

Organisms 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 (azithromycin) bacteria MRSA Neisseria spp. T. pallidum Chlamydia trachomatis Bordetella pertussis

Infants <6 mo: • Pertussis (IV, oral): 10 mg/kg daily for 5 d

Oxazolidinone Resistant Enterococ(linezolid) cus faecium, S. aureus, Streptococcus pneumoniae

Neonates: • 10 mg/kg/dose q8h Preterm infants: • 10 mg/kg/dose q12h

Carbapenems (meropenem)

Aerobic and anaero- 0–7 d postnatal age: bic Gram-positive • Non-meningitis: 20 mg/kg/ and Gram-negative dose q12h bacteria • Meningitis: 40 mg/kg/dose q12h >7 d postnatal age: • Weight 1200–2000 g: • Non-meningitis: 20 mg/kg/ dose q12h • Meningitis: 40 mg/kg/dose q12h • Weight >2000 g: • Non-meningitis: 20 mg/kg/ dose q8h • Meningitis: 40 mg/kg/ dose q8h

Use must be approved by infectious disease service

Use must be approved by infectious disease service Good CSF penetration Resistant organisms: Burkholderia cepacia, E. faecium, Stenotrophomonas maltophilia

Infectious Diseases

441

NEONATAL MENINGITIS OVERVIEW OF ETIOLOGY AND TREATMENT OF NEONATAL MENINGITIS Age of Infant

Most Common Etiologies

<1 mo

Empiric Therapy

Length of Therapy

L. monocytogenes, GBS, Enterobacteriaceae (E. coli)

Ampicillin and cefotaxime OR ampicillin and gentamicin If Gram-negative bacilli, use cefotaxime instead of gentamicin, as gentamicin has poor CSF penetration.

14–21 d: GBS, L. monocytogenes 21 d: Enterobacteriaceae (cefotaxime + aminoglycoside)

1–3 mo

GBS, S. pneumoniae, N. meningitidis, H. influenzae, Enterobacteriaceae

Ampicillin and cefotaxime

10–14 d: S. pneumoniae 7 d: N. meningitidis 7–10 d: H. influenzae

>3 mo

S. pneumoniae, N. meningitidis, H. influenzae, above neonatal pathogens

Cefotaxime or ceftriaxone Add vancomycin if possible PCN-resistant S. pneumoniae until susceptibilities return

Same as above

Consider less common forms of neonatal meningitis if index of suspicion is high based on history or physical examination findings: viral (HSV (meningoencephalitis), enterovirus, VZV), tuberculosis, fungal, and noninfectious causes (eg, leukemic infiltrates).

Clinical Features • Neurologic: seizures, lethargy, irritability, decreased tone; full fontanelle • Fever (>38°C) or hypothermia (more common in preterms) • Respiratory distress: grunting, tachypnea, nasal flaring • 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

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• 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: • Classic finding 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 Weight CSF Component (grams)

Postnatal Age (days) 0-7

8-28

29-84

≤1000 1001–1500

335 (0–1780) 407 (0–2450)

1465 (0–19,050) 1101 (0–9750)

808 (0–6850) 661 (0–3800)

Leukocytes/mm3

≤1000 1001–1500

3 (1–8) 4 (1–10)

4 (0–14) 7 (0–44)

4 (0–11) 8 (0–23)

Neutrophils (% of total leukocytes)

≤1000 1001–1500

11 (0–50) 4 (0–28)

8 (0–66) 10 (0–60)

2 (0–36) 11 (0–48)

‡

Glucose (mg/dL)

≤1000 1001–1500

70 (41–89) 74 (50–96)

68 (33–217) 59 (39–109)

49 (29–90) 47 (37–76)

Protein (mg/dL)

≤1000 1001–1500

162 (115–222) 136 (85–176)

159 (95–370) 137 (54–227)

137 (76–260) 122 (45–187)

†

Erythrocytes/mm3

*

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 first week of life.

GROUP B STREPTOCOCCAL INFECTIONS CLASSIFICATION OF GROUP B STREPTOCOCCAL DISEASE Early-Onset Disease*

Late-Onset Disease

Late, Late-Onset Disease

Time of onset

0–7 DOL Mean time: 8 h

>7 d–3 mo of life Mean time: 36 d

>3 mo of life

Commonly aﬀected population

• All infants

• Predominantly term infants

• Predominantly neonates <32 wk gestation or immunocompromised patients

Symptoms

• Respiratory distress • Apnea • Hypotension

• Fever • Lethargy • Irritability • Nonspeciﬁc signs • Respiratory distress → cardiovascular collapse

• Fever • Irritability • Nonspeciﬁc signs

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Infectious Diseases Early-Onset Disease*

Late-Onset Disease

443

Late, Late-Onset Disease

Infectious foci

• Bacteremia (40%–55%) • Pneumonia (30%–45%) • Meningitis (6%–15%)

• Bacteremia without focus (55%) • Meningitis (35%) • Osteoarthritis (~5%) • Cellulitis/adenitis (~2%)

• Bacteremia without focus • Rarely focal infections • Can aﬀect any organ system

Serotypes

AII (Ia, II, III, V most common)

Type III predominates

Type III

∗Maternal risk factors speciﬁc 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 Chlamydial

Gonococcal

Dacryostenosis

Age at presentation

First 48 h of life

1–2 wk of life

2–5 DOL

Usually by 2–4 wk of life

Symptoms

Mild to moderate conjunctivitis Can have tearing

Varies: Mild conjunctivitis with watery/mucopurulent discharge to marked swelling of eyelids and inﬂamed, thickened conjunctivae (chemosis) with pseudomembrane formation

Intense purulent discharge, chemosis, lid edema Can progress to corneal perforation if left untreated

Tearing and mucoid discharge Swelling in the nasal portion of eye with or without mild erythema

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Chemical

444

Neonatology Chemical

Chlamydial

Gonococcal

Dacryostenosis

Diagnosis

This is a diagnosis of exclusion

Conjunctival swab culture of everted eyelids Antigen detection and PCR also available

Swab culture of discharge

Clinical → may have unilateral or bilateral swelling, discharge is usually sterile, or with common skin ﬂora

Treatment

No speciﬁc therapy; discontinue use of oﬀending agent

Not prevented by erythromycin or silver nitrate prophylaxis In most patients, spontaneous resolution occurs Oral erythromycin for 10–14 d

IV or IM ceftriaxone as a single dose Full SBI evaluation should be done for invasive gonococcal disease

~90% of cases resolve with lacrimal sac massage in the ﬁrst year of life If infant appears ill, further evaluation for invasive infection should be undertaken

Vaccinating the Term Infant • See Chapter 19.

Vaccinating the Preterm Infant • All vaccines (DTaP, HIB, IPV, influenza, 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 birth, and immunize with four doses Hep B vaccine: 0, 1, 2–3, and 6–7 mo

HepB vaccine + HBIG ≤12 h of birth, and immunize with three doses Hep B vaccine: 0, 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 of birth

Hep B vaccine ≤12 h of birth, HBIG ≤7 d if mom tests HBsAg +

HBsAg negative

First HepB vaccine at 30 d if clinically stable, or at discharge if ≤30 DOL Immunize at 2, 4, 6–18 mo (three doses)

First HepB vaccine at birth Immunize at 2, 4, 6–18 mo (three doses)

Available at www.AccessPediatrics.com • Torch Infections • Neonatal Hepatitis

C H A P T E R 39

Nephrology ACUTE KIDNEY INJURY (ACUTE RENAL FAILURE, ACUTE RENAL INJURY) IN NEONATES Definition • Oliguric: Anuria or oliguria (<0.5 mL/kg/h in children; <1 mL/kg/h in infants) with an associated increase in serum creatinine • Non-oliguric: Increased serum creatinine with normal or increased urine output (usually seen with nephrotoxic medications)

ETIOLOGY OF ACUTE KIDNEY INJURY IN NEONATES Prerenal

Intrinsic Renal

Postrenal

• Reduced intravascular volume • Hemorrhage • Dehydration • CHD • Polycythemia • Indomethacin use • Adrenergic drugs • Birth asphyxia • Sepsis

• ATN • Congenital abnormalities • Renal agenesis • Renal dysplasia • Polycystic disease • Thromboembolic disease • Nephrotoxins • Medications • Radiographic contrast • Maternal ACE inhibitor or indomethacin use

• Urethral obstruction (eg, posterior urethral valves) • Ureterocele • Ureteropelvic obstruction • Ureterovesicular obstruction • Extrinsic compression of ureters • Neurogenic bladder • Megacystis or megaureter syndrome

Diagnosis • Perform history to elicit predisposing factors listed above and physical exam to palpate for abdominal masses and other congenital urogenital abnormalities. • Bladder catheterization to confirm inadequate urine output and r/o obstruction. • If prerenal failure is suspected on the basis of history or physical exam and there is no evidence of heart failure or volume overload, a fluid challenge of 10–20 mL/kg of normal saline can be administered over 30–60 min. Lack of response suggests intrinsic renal or postrenal failure. • Laboratory studies • Serum electrolytes, BUN, creatinine • CBC, platelet count • Urinalysis with microscopic analysis • Urinary sodium and creatinine with simultaneous serum sodium and creatinine to calculate FENa (These studies are not valid if diuretic is used) Urine Na × Plasma Cr × 100% Urine Cr × Plasma Na

• Imaging: US examination of kidneys and urinary system

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FENa (%)=

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Neonatology

Urine osmolality (mOsm)

Prerenal

Intrinsic Renal

>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 fluids that contain potassium and phosphorus. • Please see chapter 34 for management of hyperkalemia in neonates. • Fluid management should be strict, with administration of fluids equal to insensible fluid losses plus urine and other fluid 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 fluid 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 Definition • 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 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)

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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

Available at www.AccessPediatrics.com • Congenital syndromes and disorders with renal manifestations

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• Treat any underlying cause of hypertension (eg, fluid overload, pain or agitation, medications). • Management guidelines for hypertension in neonates are controversial. • For hypertension that is symptomatic (nonspecific cardiac findings 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 not improve or worsens, treat as above.

CHAPTER 40

Neurology NEONATAL SEIZURES ETIOLOGIES OF NEONATAL SEIZURES Underlying Defect

Points to Remember

Hypoxic–ischemic encephalopathy

• Leading cause of neonatal seizures in full-term infants. • 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/ infarction

• Second most common cause of neonatal seizures in full-term infants. • 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 hemorrhage

• In term infants, subarachnoid hemorrhage is more associated with 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 CNS

• Can occur in utero (CMV, toxoplasmosis) or perinatally (herpes simplex, bacterial meningitis with GBS or Escherichia coli being most common). • Prognosis can be very grim.

Metabolic derangement

• Transient causes (hypoglycemia, hypocalcemia, hyponatremia); see 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 deﬁciencies, 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 Infection Hypocalcemia

Maternal drug use Hypoglycemia

2–3

All of the above Inborn errors of metabolism Drug withdrawal

CNS malformation Hypernatremia Hyponatremia

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CLASSIFICATION OF NEONATAL SEIZURES Seizure Type

Clinical Manifestation

Subtle

Oral–buccal–lingual or ocular movements Autonomic dysfunction (Δ in HR, BP, SpO2)

Stereotypical stepping/swimming

Clonic

Rhythmic, slow jerking Facial, extremity, or axial involvement

Focal or generalized

Tonic

Sustained limb posturing Asymmetric position of trunk/neck

Focal or generalized

Rapid isolated jerks

Generalized, multifocal, or focal

Myoclonic

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 sleep myoclonus

Bilateral or unilateral Synchronous or asynchronous Occurs during sleep Not due to a stimulus

Stimulus-evoked myoclonus

Focal or generalized Severe CNS dysfunction EEG may show cortical spike-wave discharge

Hyperekplexia (stiﬀ-man syndrome)

Generalized stiﬀness Autosomal dominant and recessive forms Excessive startle responses to unexpected stimuli Excessive stiﬀness following startle response Benzodiazepines reduce symptoms

Management

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• 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. • 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 efficacy of these medications in neonates.

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INTRAVENTRICULAR HEMORRHAGE • Definition: 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 first 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 nonspecific 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 classification is most frequently used to describe the severity of encephalopathy and is most appropriate for infants with HIE.

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SARNAT STAGES OF HIE

Level of consciousness

Stage 1 (Mild)

Stage 2 (Moderate)

Stage 3 (Severe)

Hyperalert

Lethargic

Stuporous, comatose

Tone

Normal

Hypotonic

Flaccid

Posture

Normal

Flexed

Decerebrate

Reﬂexes

Hyperactive

Hypoactive

Absent

Pupils

Mydriasis

Miosis

Unequal, poor light reﬂex, midline

Oculovestibular

Normal

Overactive

Weak or absent

Seizures

None

Common

Decerebrate

EEG

Normal

Low voltage with seizures

Burst suppression to isoelectric

Duration of symptoms

<24 h

2–14 d

Hours to weeks

Outcome

Nearly 100% normal

80% normal

~50% die; survivors 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 Manifestations

CNS

HIE (see Sarnat classiﬁcation above)

Pulmonary

Persistent pulmonary hypertension RDS

Cardiovascular

Hypotension Left ventricular dysfunction

GI

Hepatic injury

Tricuspid insuﬃciency Myocardial infarction

(continued on next page) ∗

As defined in a joint statement by the American Academy of Pediatrics (AAP) and American College of Obstetricians and Gynecologists (ACOG).

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Organ System

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Neonatology

Organ System

Manifestations

Renal

ATN Oliguria/anuria

Acute cortical necrosis

Hematologic

Increased nucleated RBC Thrombocytopenia

DIC

Metabolic

Acidosis SIADH

Hypoglycemia Hypocalcemia

• Hypothermia to treat neonatal HIE may be effective in moderate HIE, but long-term efficacy and safety data are lacking at this time.

CAUSES OF NEONATAL HYPOTONIA Location of Hypotonia

Examples

Central (upper motor neuron lesion)

Acquired: HIE, electrolyte abnormality, infection, IVH, trauma Congenital: cerebral malformation, chromosomal and metabolic disorders

Peripheral (lower motor neuron disease)

Spinal muscular atrophy, hereditary motor/sensory neuropathy Peripheral neuropathy: familial dysautonomia (Riley–Day 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 Horn

Peripheral

Neuromuscular junction

Normal strength

Generalized weakness

Weakness distal > proximal

Weakness face, eyes, bulbar

Weakness proximal > distal

Normal or ↑ DTRs

↓ or absent DTRs

↓ or absent DTRs

Normal DTRs

↓ DTRs

± Seizures

Fasciculations

± Fasciculations

No fasciculations

Central

Persistent primitive reﬂexes

Muscle

Sensation loss

• Diagnostic workup may include: • Cranial imaging (US, CT scan, MRI) • EEG • Genetics studies (karyotype, chromosome microarray, specific 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 first 24 h; false-positive increase with acidosis)

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• Nerve conduction studies • Muscle biopsy

NEUROMUSCULAR DISORDERS NEUROMUSCULAR DISORDERS PRESENTING WITH NEONATAL HYPOTONIA Disorder

Genetics

Presentation

Prognosis

Congenital muscular dystrophy

AR, M=F

Diﬃculties with suck, swallow, and respirations; joint contractures

Normal intellect; severe disability

Central core disease

AD

Generalized weakness

Normal life span

Spinal muscular atrophy type 1 (Werdnig–Hoﬀmann disease)

AR; rarely AD

Absent DTRs, weak cry, poor suck; facial muscles spared

1–2 yr life expectancy

Hereditary motor and sensory neuropathy type III (Dejerine– Sottas disease)

AD; rarely AR

Generalized weakness, delayed motor milestones, ataxia, sensory loss, decreased DTRs

Variable disability; usually live to adulthood

Nemaline rod myopathy

AD or AR

Generalized weakness, weak respiratory muscles

Early death due to respiratory failure

Riley–Day syndrome

AR

Sweating with feeds, no response to painful stimuli, decreased DTRs

Few live beyond adolescence

Congenital ﬁber type disproportion myopathy

Unknown

Generalized weakness, delayed motor milestones, hip dislocation, contractures

Nonprogressive after 2 yr; normal life span

HYDROCEPHALUS Definition • 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 Acquired Hydrocephalus

• Aqueductal stenosis • Neural tube defects (up to 80% of these infants have hydrocephalus) • Dandy–Walker malformation • Syndromes with vermian agenesis

• Posthemorrhagic (see “Intraventricular Hemorrhage” section) • Hydrocephalus ex vacuo from cerebral atrophy after severe insult • Postinfectious

• Vein of Galen malformation • Arachnoid cysts • Achondroplasia • Osteopetrosis

• Neoplasms of the CNS

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Congenital Hydrocephalus

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Neonatology

Presentation • Bulging or full fontanelle • Split sutures • Rapid head growth • Macrocephaly • Vomiting

• Apnea • Bradycardia • Irritability • Altered level of consciousness

Diagnosis • Many of the congenital causes of hydrocephalus may have accompanying physical findings (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 shunt until more deﬁnitive CSF diversion can be performed (most common therapy) • Serial LPs (can be done for communicating hydrocephalus) • Medications to reduce CSF production (acetazolamide ± furosemide; may lead to signiﬁcant metabolic derangements)

• Ventriculoperitoneal shunting

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 findings. • 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 3

Right Eye

Zone 2

Zone 1

Optic Nerve

Left Eye

Figure 40-1 The zones of the retina. (Adapted with permission from: Committee for the Classification of Retinopathy of Prematurity. An International Classification of Retinopathy of Prematurity. Arch Ophthalmol. 1984;102(8):1130-1134.)

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• The five 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 benefit 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

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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 defined 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 flow. • 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 flexed and close to the trunk • Pacifiers: 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 first 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 pacifier should be offered as a secondary source of pacification.

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)

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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 pacifier, 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

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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 Factors

Clinical Manifestation

• Prematurity • Presentation • Precipitous within 6 h of birth delivery • Tachypnea, typ• C-section ically 60–120 delivery breaths/min + without mild-to-moderlabor ate respiratory distress • Physical examination: good air entry ± crackles • Symptoms tend to last 12–72 h

Differential Diagnosis

Evaluation

Treatment

• Pneumonia • Sepsis • RDS (may complicate TTN, especially if infant is premature) • Cyanotic heart disease • Meconium aspiration • Persistent pulmonary hypertension

• ABG: may see mild hypoxemia and mild respiratory acidosis • CXR: prominent perihilar streaking and mildto-moderate cardiomegaly • May also see hyperinﬂation, pleural eﬀusions, and widened ﬁssures

• Supportive with supplemental O2, as TTN is a self-limited disease • May need CPAP for lung recruitment (may increase the risk of air leak) • May oﬀer PO feeding when RR <70 breaths/ min and weaned to room air • Diuretics have not been shown to improve symptoms or shorten course and are contraindicated

RESPIRATORY DISTRESS SYNDROME (RDS) Risk Factors

Clinical Manifestation

• Prematurity • Male sex • Caucasian race • Maternal diabetes • Perinatal asphyxia • C-section without labor • Thoracic malformations • Genetic disorders of surfactant production

• Hypotension Clinical: (treat as ap• Tachypnea, propriate) grunting, and • A PDA can retractions lead to poor • O2 requirement tends to increase recovery from RDS, and over the ﬁrst 48 closure should h if not treated be considered Laboratory/ if patient is radiographic 3–4 d old with findings: hemodynamic • CXR: diﬀuse, ﬁne compromise granular densior continued ties that develop RDS with poor during the ﬁrst weaning from few hours of life mechanical ventilation

Monitoring

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Treatment Surfactant therapy: • Many centers start CPAP and do not give “prophylactic” surfactant therapy. • Many formulations are available. Check with your institution to determine the appropriate dosage/interval/ number of doses. • Consider prophylactic surfactant therapy as soon as clinically feasible for infants <27 wk gestation who require intubation. • For all other infants, early rescue surfactant (within 1–2 h after birth) is indicated for worsening respiratory distress on exam or increasing FiO2 requirement above 30%–40%.

(continued on next page)

Pulmonology Risk Factors

Clinical Manifestation

• Lack of antenatal corticosteroid therapy in infants 24–34 wk gestation

• ABG: hypoxia, hypercarbia, mild metabolic acidosis, ± elevated lactate

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Monitoring

Treatment

Monitoring/ supportive therapy: • ABG: should be checked within 30–60 min of surfactant therapy or with changes in ventilator settings • Temperature: neutral thermal environment should be maintained • Antibiotics: RDS is diﬃcult to distinguish from pneumonia and sepsis; consider appropriate cultures and initiate broadspectrum antibiotics (ie, ampicillin and gentamicin) for 48 h

• Ensure appropriate ETT position and equal lung inﬂation prior to giving surfactant. • Dosage: 4 mL/kg (Survanta dosing) per ETT q4–6h for up to four doses. • Pulmonary hemorrhage can be seen after surfactant therapy; this is thought to result from rapid change in lung compliance. Oxygen: • O2 saturations alarms should be 85%–97% if ≥1250 g and 85%–93% if <1250 g to limit exposure to high FiO2 (these are oximetry alarm limits, not targets; targets are ≥88%). NCPAP: • Early NCPAP administration may ↓ need for mechanical ventilation. • Indicated in infants with mild respiratory distress; FiO2 requirement <40% and PaCO2 <55–60 mm Hg. • Start with 5–6 cm H2O, and increase as required by 1–2 cm increments to a max of 8–10 cm H2O. • Place an NG tube to decompress gastric air. • Monitor via CXR for lung overdistention leading to decreased tidal volume and hypercarbia. Mechanical ventilation: • Indications for mechanical ventilation include 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 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.

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Background

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• 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 circulatory compro• Vitals: tachycardia or bradycar• If the pneumothorax is found mise can lead to dia, ↑ blood pressure (can be ↓ incidentally and if patient is in progressive aciif tension pneumothorax → deno respiratory distress, has no dosis (respiratory creased venous return and CO), underlying lung disease, and is and metabolic) and tachypnea, apnea, desaturation, not mechanically ventilated, the cyanosis. patient may be closely observed. death if untreated. • Respiratory: grunting, ﬂaring, • 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, hyaﬀected side. O2is not recommended. poxia, and ﬂuctuating cerebrovascular • Cardiac: shift in PMI. • Needle aspiration: pressures. • GI: abdominal distention from • Should be performed in all displacement of the diaphragm. patients who are rapidly dete- • SIADH may occur. • CXR: riorating. • Can be a temporizing measure • AP view—hyperlucent hemithoin patients who are mechanirax, ﬂattened diaphragm, cally ventilated and may be demediastinal shift if tension ﬁnitive treatment for patients pneumothorax. not receiving mechanical • Cross-table lateral—may allow ventilation. for visualization of small collections 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 ventilation. • Transillumination: • Consider removal of the • May be able to illuminate catheter or chest tube after pneumothorax by placement no air has been drained for of a high-intensity light source 24–48 h; directly on the skin. Some centers will ﬁrst place • ↓ sensitivity if severe PIE, chest the chest tube to water seal wall edema, full-term, very small and/or clamp, with a follow-up infants, or infants with dark skin. CXR to evaluate for reaccumu• Needle aspiration: lation before removal. • If the patient is rapidly decompensating, needle aspiration can be diagnostic and therapeutic. (continued on next page)

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Management

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Complications

Pulmonary Interstitial Emphysema • PIE can occur in mechanically ventilated infants during the ﬁrst 48 h of life. • Risk factors include extreme prematurity, RDS, and sepsis. • Vitals: hypotension, bradycardia. • CXR: linear lucencies radiating from the hilum and occasionally cyst-like blebs. • ABG: acidosis, hypercarbia, hypoxia.

• Ventilator strategies • PIE can lead to pneumothorax, • ↓ mean airway pressure by pneumoperi↓ PEEP and Ti and ↑ respiracardium, and air tory rate. • Consider HFOV to avoid swings embolus. in lung volume. • Positioning: Place aﬀected lung in a dependent position. • Avoid suctioning and bag ventilation. • In very severe cases, selective bronchial intubation or surgical resection may be considered (although no proven beneﬁt).

Pneumomediastinum • PE: Muﬄed heart sounds. • Pneumomediastinum is usually • CXR: Air is best seen on the lateral of little clinical signiﬁcance and rarely needs treatment. view. • Rare cardiorespiratory eﬀects can occur if the air is under tension and will require mediastinotomy drainage.

• Can lead to pneumothorax.

Pneumopericardium • Vitals: initial tachycardia followed • Observation: • Cardiac tamponade by bradycardia, hypotension, • If the patient is asymptomatic • Tension pneumocyanosis. and is not receiving mechanimediastinum • PE: Muﬄed 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• Serial CXRs should be moni• Labs/imaging: ration) tored until the pneumopericar• CXR: AP view demonstrates air dium resolves. surrounding the heart. It is most often seen at the inferior aspect • Needle aspiration: • Pericardiocentesis should be of the heart. performed immediately if car• EKG: Decreased voltages diac tamponade develops. throughout. • This is best accomplished • Transillumination: Illumination under US guidance to avoid may occur in the substernal puncturing the myocardium. region. Flickering with cardiac • Continuous pericardial drainage: cycle is sometimes seen and can help to diﬀerentiate from • If recurrence of cardiac tampneumomediastinum. ponade occurs, a pericardial tube will need to be placed.

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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.

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• 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 waterdrainage 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 Differential Diagnosis Fetal risk factors: • Meconium-stained amniotic ﬂuid • Post-term • Pulmonary parenchymal disease • Lung hypoplasia • In-utero closure of the ductus arteriosus • Pneumonia, sepsis, and intrauterine or perinatal asphyxia

Diagnosis

Treatment

PE: • Usually develop symptoms within the ﬁrst 12 h of life • Diﬀerential cyanosis, with preductal (right upper extremity or head) > postductal (lower extremity or abdomen)

Oxygen: • Hypoxia and hypercarbia are potent pulmonary vasoconstrictors; supplemental oxygen and correction of hypercarbia are important. • Continuous pre- and post-ductal saturations should be monitored. • Goal postductal saturations are >92%. • ABGs should be drawn postductally.

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Pulmonology Risk Factors and Differential Diagnosis

Diagnosis

Treatment Mechanical ventilation: • If hypoxemic with FiO2 100%, mechanical ventilation should be initiated. • Ventilatory strategy depends on underlying etiology; maintain normoxia and normocarbia to prevent acidemia. • HFOV is often used in patients with severe pulmonary parenchymal disease. iNO: • iNO is a potent pulmonary vasodilator. • Standard dose is 5–20 ppm, and it is most eﬀective with adequate alveolar recruitment. • Wean iNO if the infant responds by increasing PaO2 by >10–20 mm Hg, and FiO2 is <0.6. • Rebound hypoxemia can occur when weaning from 5 ppm, so wean below 5 ppm gradually. • ECMO: • ECMO should be considered for patients with a reversible cause of PPHN who fail conventional management (including mechanical ventilation with iNO). • See ECMO section for additional information. Hemodynamic support: • Maximize O2 delivery to the tissues by maintaining adequate cardiac output. • In the short term, ↑ systemic BP to overcome the ↑ PVR (with volume expansion [normal saline, PRBCs] and/or vasopressors [dopamine, dobutamine, epinephrine]). • Avoid polycythemia, which can cause hyperviscosity and ↑ in PVR. Metabolic considerations: • Metabolic alkalosis → ↓ PVR. The use of NaHCO3 is controversial and should be limited to infants with signiﬁcant acidosis. • Hypoglycemia and hypocalcemia can interfere with myocardial function and should be corrected. (continued on next page)

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Maternal risk factors: • If gradient is >10% with no structural • Anemia heart disease, highly • Fever suggestive of PPHN • Pulmonary disease • Cardiac: prominent • DM precordial impulse, single S2 and/or tri• UTI during pregnancy cuspid regurgitation • Maternal medication use murmur (including SSRIs and NSAIDs) • Skin: cyanosis Differential diagnosis: Labs/imaging: • CHD • CXR: • Sepsis • Normal • Severe pulmonary parenchy- • Pulmonary parenchymal disease mal disease • Secondary pulmonary • “Classic” idiopathic hypertension can be caused PPHN hyperlucent by CHD: TAPVR, HLHS, LV lung ﬁelds, reﬂecting disease, or obstruction to ↓ pulmonary blood LV outﬂow. It can also be ﬂow caused by LV or RV dysfunc- • ECG: RV predominance tion with right-to-left (normal for age); may shunting. rarely have signs of • Pulmonary hypertension ischemia or infarction can be caused by hypoxia, • Echocardiogram: hypothermia, hypoglycemia, evaluate shunting, and polycythemia. ventricular function, and pulmonary artery pressures • Tricuspid jet, if present, can be used to estimate the RV/pulmonary artery pressures • Estimated RV pressure (in mm Hg) = 4 × v2, where v = velocity of the tricuspid regurgitaton jet, in m/sec • If tricuspid valve is competent, qualitative measures can suggest the diagnosis of PPHN, such as the following: • Flattened/paradoxical interventricular septal wall motion (bowing into the left ventricle during systole) • Dilated or hypertrophied right ventricle • Dilated right atrium

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Risk Factors and Differential 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 • Meconium can be passed in utero with acute or chronic hypoxia or infection. • Meconium staining rare <34 wk gestation. • ~ 5% of infants with meconium staining will develop meconium aspiration syndrome. • Complete peripheral airway obstruction → atelectasis and V/Q mismatch. • Partial obstruction → ball-valve eﬀect with air trapping. • Clinically, the patient can have acidosis, hypoxemia, and hypercapnia.

Management

Complications

Meconium-stained fluid: • If infant is vigorous—Provide routine infant care. • If infant is not vigorous—Intubate, and suction trachea with a 3.0–3.5 ETT. • Vigorous: HR >100, spontaneous respirations, good tone.

• Pneumothorax/ pneumomediastinum: occurs in 15%–33% of patients • PPHN: occurs in up to 33% of patients • Consider echocardiogram to determine degree of PPHN and to exclude CHD as etiology

Observation: • Any infant who is depressed and has meconium suctioned from the trachea should be observed for signs of meconium aspiration syndrome. • CXR: normal or diﬀuse, asymmetric patchy inﬁltrates ± hyperinﬂation. • Routine care should be provided; ﬂuid restriction may help lessen pulmonary edema. 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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Pulmonology Pathophysiology and Clinical Manifestations

Management

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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 diﬃcult to distinguish from pneumonia on CXR. • iNO—may ↓ need for ECMO in infants with associated PPHN. • iNO in conjunction with HFOV is more eﬀective than iNO with conventional ventilation. • Corticosteroids—not currently recommended.

BRONCHOPULMONARY DYSPLASIA (BPD) Classification, Diagnosis, and Clinical Course

Management Oxygen: • ↑ FiO2 contributes to pathogenesis of BPD, and SaO2 should be carefully monitored early in the clinical course of all premature infants. • Saturation alarms should be 85%–97% in infants >29 wk PMA and 85%–93% in infants <29 wk PMA or <1250 g. • Periodic blood gas monitoring should be obtained, with a goal PaO2 >55 mm Hg. Mechanical ventilation: • Acute phase • Permissive hypercapnia (PaCO2 of 50–55 mm Hg) to minimize airway pressure and lessen further lung injury. • Chronic phase • After the patient is on stable ventilator settings, weaning should be judicious until adequate weight gain is established.

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Classification/Diagnosis: • Radiographic changes and treatment with supplemental O2 for at least 28 d, and • Mild: breathing RA with saturations ≥90% at 36 wk PMA or discharge home (infants <32 weeks at birth) or at DOL 56 or discharge home (infants ≥32 weeks at birth) • Moderate: requiring <30% FiO2 to keep SaO2 ≥90% at 36 wk PMA or discharge home (infants <32 weeks at birth) or at DOL 56 or discharge home (infants ≥32 weeks at birth) • Severe: requiring ≥ 30% FiO2 or positive pressure support to keep SaO2 ≥90% at 36 wk PMA or discharge home (infants <32 weeks at birth) or at DOL 56 or discharge home (infants ≥32 weeks at birth)

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Classification, Diagnosis, and Clinical Course Clinical course—“classic” BPD: • Acute course • Initial improvement in ﬁrst 1–2 wk, then worsening pulmonary function (↑ O2 requirements, tachypnea, retractions, rales on exam, and worsening lung opaciﬁcation on CXR) • O2 requirement ﬂuctuates; pulmonary edema worsens • Evaluate for PDA and infection as causes for worsening symptoms • Chronic course • Airway obstruction becomes uneven as hypertrophy of smooth muscle, increased interstitial edema, and bronchiolar metaplasia occur. • After 4–6 wk, ﬁbrosis, hyperinﬂation, and pulmonary edema ↑ and the patient’s course becomes more static. • Lung remodeling begins over the next 3–9 mo. Weaning from positive pressure ventilation should be gradual, as rapid changes may lead to large ﬂuctuations in oxygenation, and chronic hypoxemia can lead to right-sided heart failure and cor pulmonale. • When discharged home, patients require close monitoring of SaO2 to prevent ↑ in PVR → right-sided heart failure. Clinical course—“new” BPD: • Since the introduction of surfactant and use of prenatal steroids, the initial course is characterized by a milder respiratory distress prior to development of the chronic condition. • The hallmark of this “new BPD” is arrest in alveolar development and simpliﬁcation of terminal airways.

Management Fluid restriction/nutrition: • Fluid restriction is a common strategy to control pulmonary edema. • Moderate ﬂuid restriction to 140–150 mL/kg/d of a preterm 24 kcal/oz formula will meet most nutritional needs. • For severe cases, may need to restrict to 110–130 mL/kg/d; concentrate feeds to 27–30 kcal/oz to achieve adequate growth. • Weigh q1–3d; length and FOC measured weekly. • Monitor BUN, calcium, phosphorus, and alkaline phosphatase activity. • Nutrition consult warranted in all patients who require ﬂuid restriction. Prevention: • Vitamin A • Has been shown to ↓ incidence of BPD in ELBW infants • No long-term data available at this time • Dosage: 5000 IU IM three times/wk × 12 doses (TCH institutional practice) • Caﬀeine • Has been shown to ↓ incidence of BPD in infants 500–1250 g when started in the ﬁrst 10 DOL • Also improved survival without neurodevelopmental disability • Dosage: 20 mg/kg loading dose, then 5 mg/kg/d IV or PO Diuretics: • Diuretics: ↓ O2 requirements and improve shortterm lung mechanics • No long-term beneﬁts demonstrated on mortality or duration of O2 therapy • Thiazides • Work on the proximal part of the distal renal tubule • Hydrocholorothiazide • 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. (continued on next page)

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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 longterm beneﬁts 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 puﬀs 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.

NEJM 1967;276:357, Am J Respir Crit Care Med 2001;163:1723, Pediatrics 2004;114:1305

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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% • Patient has a PCO2 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.

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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 significant apneic episodes are noted for 5–7 d. • Evaluation: • Further evaluation should be strongly considered after the first 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.

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• 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

EXTRACORPOREAL MEMBRANE OXYGENATION ECMO is an advanced life-support technique that is offered for specific 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.

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• 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 flexion/extension of the neck). • Xanthines: • CNS stimulant to increase the medullary receptor center’s sensitivity to CO2 → stimulates 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.

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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 definitive 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

C H A P T E R 43

Surgical Disorders ABDOMINAL SURGICAL DISORDERS

Gastroschisis

Omphalocele

• Right-sided defect lateral to the base of the umbilical stalk through which a portion of the GI tract has herniated • May be secondary to vascular accident with disruption of body wall formation or weakness at the insertion of the umbilical cord after involution of the right umbilical vein • Exposure to amniotic ﬂuid and partial closure of the defect may result in mesenteric vascular constriction → further bowel injury • Bowel may be edematous and matted with inﬂammatory “peel” • Small bowel with villous atrophy and blunting, muscular hypertrophy, and serosal inﬂammation

• Developmental arrest of somites in the abdominal wall or failure of midgut to return to the abdominal cavity after herniation into the umbilical stalk • Central defect; umbilical ring fails to contract and leaves a round defect • Defect is covered by a translucent mesenchymal membrane that protects the underlying abdominal organs from exposure to amniotic ﬂuid • The sac usually remains intact but occasionally is ruptured during delivery • The liver and small intestine usually occupy part of the sac along with variable other abdominal organs

• Sporadic; 1.5 of 10,000 live births • Risk factors: Young maternal age; low SES; exposure to vasoconstricting decongestants, NSAIDs, cocaine, cigarette smoking, pesticides • Can be associated with malrotation; associated with intestinal atresias in 5%–25% • Not commonly associated with anomalies unrelated to the GI tract

• Sporadic; 2–2.5 of 10,000 live births • Seen with mothers at extremes of reproductive age • Associated with maternal obesity and SSRIs • Associated with other structural or genetic defects in 50%–75% • Associated syndromes: VACTERL association; Beckwith-Wiedemann syndrome; pentalogy of Cantrell; CHD; pulmonary hypoplasia; congenital malrotation of the colon; EEC syndrome; OEIS complex; trisomies 13, 18, and 21

• Usually diagnosed antenatally on US • Mother has elevated AFP levels • Most may still be delivered vaginally without further injury to the bowel

• Most diagnosed prenatally; should have a thorough evaluation for any other anomalies and consider chromosomal analysis • Mother may or may not have elevated AFP levels (continued on next page)

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Presentation and Diagnosis

Epidemiology

Pathophysiology

ABDOMINAL WALL DEFECTS

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Neonatology Gastroschisis

Omphalocele

Treatment

• May be delivered vaginally, but consider cesarean section for giant omphalocele because of concern for rupture • In delivery room, stabilize airway; wrap intestine with warm, sterile saline dressings; place-large bore orogastric tube to continuous suction; and place peripheral IV for ﬂuid management and broad-spectrum antibiotics • Place the infant in clear plastic bowel bag to minimize heat and water loss • Inspect bowel for evidence of ischemia, torsion, and atresia • Place the infant in lateral decubitus position to avoid mesenteric kinking • Reduce or place the bowel in a sterile silo as soon as possible; delay may lead to bowel swelling and resultant ischemia • If bowel is forced into abdominal cavity, may cause decreased diaphragmatic excursion, requiring increased ventilator support; may also impair mesenteric, hepatic, and renal perfusion • During staged closure, parenteral nutrition, gastric decompression, and spontaneous breathing are preferred • When reduction of silo contents is complete, ﬁnal closure is performed • Repair of atresias includes primary anastomosis, or if peel exists, internalization of uncorrected atresia and later reexploration and repair after peel resolves • Await bowel sounds, passage of meconium, and cessation of bilious gastric aspirates before starting enteral feeds • Conservative advancement of enteral feeds • May have return of bowel function in a few days to weeks • Those who fail to demonstrate bowel patency within 3–4 wk of closure should have contrast study to rule out unrecognized 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)

• In the delivery room, stabilize the airway; wrap the sac with warm, sterile saline dressings; place large-bore orogastric tube to continuous suction; and place peripheral IV for ﬂuid management and broad-spectrum antibiotics • Do not attempt reduction of the sac because it may rupture, cause respiratory compromise, or impair venous return • Same management if the sac is ruptured; small rents in the sac may be sutured shut • Small omphaloceles can often be closed in one-stage surgical repair • Cases associated with signiﬁcant other anomalies or large omphaloceles may be managed nonoperatively; the membrane is preserved and treated with silver sulfadiazine to allow epithelialization of the amnion over weeks or months, resulting in durable coverage; if the patient survives other conditions, he or she can have eventual closure later in childhood • Survival rates are 30%–80% because of associated anomalies; with isolated omphalocele, survival rates approach those of gastroschisis • Complications include GER, volvulus secondary to nonrotation, and ventral hernias • Giant omphaloceles can be associated with pulmonary hypoplasia, and in severe cases, may cause neonatal death.

Surgical Disorders

473

Epidemiology

Pathophysiology

OBSTRUCTIVE LESIONS OF THE SMALL BOWEL Duodenal Atresia and Stenosis

Jejunoileal Atresia and Stenosis

• Midgut = duodenum to transverse colon • Undergoes two 270o counterclockwise rotations during 6–12 wk of gestation; improper rotation or ﬁxation → narrow vascular pedicle with wide mesenteric base → obstruction and compromised blood supply • Ladd bands form between ectopic cecum and right lateral abdominal wall and traverse the duodenum → intermittent, incomplete duodenal obstruction • If ﬁxation has not occurred normally, the intestine is susceptible to torsion on the axis of the SMA → gangrene of the midgut (almost uniformly fatal)

• Complete or partial; from intrinsic causes or external compression • Intrinsic: Failure of recanalization of duodenum during 8–10 wk of gestation → solid from epithelial proliferation • External: Annular pancreas; may encircle the second portion of the duodenum and cause obstruction • Type I atresia: Luminal web or membrane, may be fenestrated; marked size discrepancy with mural continuity; often associated with anomalies of the common bile duct • Type II atresia: Dilated proximal segment connected to small distal segment by a ﬁbrous cord • Type IIIA atresia (most common): Complete discontinuity between segments

• Potential causes: Ischemic insult to intestine, internal herniation of bowel, volvulus, bowel perforation, mesenteric thrombosis, epithelial plugging, lack of complete revacuolization of intestinal lumen • Types I–IIIA as in duodenal atresia, plus: • Type IIIB: “Apple peel” or “Christmas tree” deformity (distal small bowel segment forms a corkscrew around the terminus of the ileocecal artery) • Type IV: Multiple atresias (“string of sausages” appearance); most often involve the proximal jejunum • Dilatation of the bowel at the proximal end always occurs → large size discrepancy between the proximal and distal ends; dilated bowel has impaired peristalsis

• 1 in 100 have some form of improper rotation or ﬁxation; clinically signiﬁcant disease occurs in one in 6000 live births • Associated with CDH, omphalocele, and gastroschisis; may be associated with annular pancreas and bowel atresias

• 1 in 7000 live births; intrinsic duodenal atresia account for 50% of all small bowel atresias • Associated with other conditions in 50%–80% of patients; most commonly trisomy 21 and CHD (30% each) • Other anomalies: Intestinal malrotation (20%), esophageal atresia or imperforate anus (10%–20%), heterotaxy, biliary atresia, and gallbladder agenesis

• 50% in jejunum (30% proximal; 20% distal) and 50% in ileum (15% proximal; 35% distal) • ~90% of small bowel atresias are single • Associated with malrotation (10%–18%), meconium peritonitis (12%), meconium ileus (10%) • 15%–30% associated with CF

• Bilious emesis in any child <1 yr is malrotation until proven otherwise; emesis (bilious or not) is the most common presentation

• May have polyhydramnios (50%) and “double bubble” on antenatal US

• Antenatally: Polyhydramnios from inability of the fetus to absorb amniotic ﬂuid and distended loops of fetal bowel on US caused by obstruction (continued on next page)

NE ON AT OLO GY

Malrotation and Midgut Volvulus

Malrotation and Midgut Volvulus

Duodenal Atresia and Stenosis

Jejunoileal Atresia and Stenosis

Presentation

Neonatology

• If intermittent obstruction is present, the patient may have periods of normal feeding with episodes of emesis • Abdominal distension usually does not occur because the obstruction is high in the GI tract • >50% present in the ﬁrst month of life; 75% present within the ﬁrst year • Bloody stools and abdominal tenderness are ominous signs of vascular compromise; the patient may subsequently develop sepsis, shock, and luminal perforation

• Emesis of bile-stained ﬂuid within hours of birth; 85% of obstructions are distal to the ampulla of Vater • Swallowed air cannot pass the duodenum → distended upper abdomen and scaphoid lower abdomen • May pass a small amount of meconium in the ﬁrst 24 hr and then have no further stools

• Newborns: Abdominal distension and bilious vomiting and often failure to pass meconium • Usually occur in otherwise normal newborns but rare cases are seen with other malformations

• KUB: Duodenal obstruction, scant gas in rest of bowel; gasless abdomen may be seen when bowel infarction has occurred • Gold standard is Upper GI with small bowel follow through: right-sided location of ligament of Treitz, spiraling or beaking of the duodenum suggesting obstruction • US: Abnormal position of the SMV relative to the SMA • Contrast enema: High cecum in the RUQ or failure of contrast to extend past the transverse colon (suggestive, but not conclusive, for malrotation).

• Abdominal radiography with classic “doublebubble” sign: Two distinct gas collections in the upper abdomen representing a dilated stomach and proximal duodenal bulb • The distal abdomen may be gasless or have a small amount of air because of stenosis or fenestration of a duodenal web • Diagnosis also suggested by aspiration of >30 mL gastric contents before feeding

• Abdominal radiography shows distended, air-ﬁlled bowel loops and multiple air-ﬂuid levels • Contrast enema may show microcolon because of little or no material passing distal to the obstruction

Diagnosis

474

• Initial treatment: Airway stabilization, placement of a large-bore nasal or orogastric tube to lowintermittent suction, peripheral IV placement, ﬂuid resuscitation, correction of electrolyte abnormalities, and surgical consult

• Initial treatment: Airway stabilization, placement of large-bore nasal or orogastric tube to low intermittent suction, peripheral IV placement, ﬂuid resuscitation, correction of electrolyte abnormalities, surgical consult, and thorough evaluation for other anomalies

• Initial treatment: Airway stabilization, placement of large-bore nasal or orogastric tube to low intermittent suction, peripheral IV placement, ﬂuid resuscitation, correction of electrolyte abnormalities, and surgical consult

(continued on next page)

Treatment

Surgical Disorders

475

Malrotation and Midgut Volvulus

Duodenal Atresia and Stenosis

Jejunoileal Atresia and Stenosis

• Volvulus → surgical emergency; malrotation without signs of torsion is less urgent • Ladd’s procedure: Manual inspection of the bowel, detorsion of volvulus, lysis of bands, passage of tube through the duodenum to rule out intraluminal obstruction, widening of the mesenteric base, incidental appendectomy, and nonrotational return of bowel to the abdomen • If viability of the intestine is in question, the bowel should be detorsed and reexploration done in 24–36 h to reassess; infarcted areas should be resected and enterostomies created • Mortality, 3%–9%; higher in patients with volvulus, necrosis, prematurity, or other abnormalities • Complications: GI motility disturbances, recurrent volvulus, DIC, sepsis, short gut (if <40 cm small bowel left), reperfusion injury, small bowel obstruction, strictures

• Surgical treatment: Primary duodenoduodenostomy (preferred) or duodenojejunostomy to establish intestinal continuity • GI function usually returns in 5–7 d, at which point enteral feeds can be initiated and progressively advanced • Complications: Delayed transit caused by a persistently dilated and dyskinetic proximal duodenum; GER because of delayed gastric emptying • Survival rate, 95%; morbidity and mortality are usually related to associated anomalies

• Operative intervention is based on the type of atresia, presence of comorbid conditions, and condition of the bowel at surgery • The dilated proximal end is tapered or resected for end-to-oblique-end anastamosis • Distal lumen of bowel is irrigated to ensure no other atretic segments or webs are present • Multiple atresias are managed by multiple resections and anastomoses or by intramural stenting • If bowel inﬂamed or ischemic, anastomosis is postponed, and diverting ostomy is performed • Often require parenteral nutrition until bowel function returns; then may require elemental formulas to aid absorption before transitioning back to regular formula • Complications: Anastomotic leakage, sepsis, strictures, impaired mobility, malabsorption

PRIMARY PULMONARY DISORDERS ASSOCIATED WITH PULMONARY HYPOPLASIA Congenital Cystic Adenomatoid Malformation

• Majority caused by failure of development of posterolateral portion of the diaphragm; results in persistence of foramen of Bochdalek, allowing viscera to enter the thoracic cavity • Rarely may have anterior retrosternal hernia of Morgagni

• Failure of maturation of bronchiolar structures or focal pulmonary dysplasia arising in wk 5–6 • Pulmonary maldevelopment causing replacement of normal parenchyma with cystic proliferation (continued on next page)

NE ON AT OLO GY

Congenital Diaphragmatic Hernia

476

Neonatology

• Rapid vascular and epithelial growth, accelerated cellular proliferation, and decreased apoptosis suggest possible benign neoplasm • Growth of CCAM is exponential between 20–25 wk; then reaches a plateau and may decrease in size • Stocker histologic classiﬁcation: Type I CCAM with single cyst or small number of large cysts (50%), type II CCAM with multiple small cysts (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 • One in 3000 live births; male and female equal • >40% have associated anomalies of the heart, brain, limbs, GU system, or craniofacial region • Has been associated with trisomies 13 and 18 and 45 XO, Goldenhar, Beckwith-Wiedemann, Pierre Robin, Goltz-Gorlin, rubella, Fryns, and Pallister-Killian syndromes • Poor prognostic indicators: Diagnosis earlier 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

• Almost all unilateral; 2% bilateral • Sporadic; males > females • Associated anomalies (these are rare, but can be seen): Renal agenesis or dysgenesis, truncus arteriosus, tetralogy of Fallot, jejunal atresia, CDH, hydrocephalus, and skeletal anomalies

• May be seen as early as 15 wk but may not be detected until after routine 16–20 wk US • Further delineated with fetal MRI • Presents with cyanosis and severe respiratory distress immediately after birth, scaphoid abdomen, diminished breath sounds, bowel sounds heard in left chest, heart sounds in right chest • CXR shows loops of bowel in chest; heart is displaced to the opposite side of the chest

• Usually found antenatally as a mass in the fetal chest using US or MRI • If microcystic and takes up a large portion of the lung, the fetus may develop hydrops secondary to mediastinal shift and IVC or cardiac compression and has poor prognosis • Macrocystic lesions may present with respiratory distress and be mistaken for CDH

• In delivery room: Immediate intubation to prevent herniated bowel from ﬁlling with air, positive-pressure ventilation with a bag and mask should be avoided; large bore orogastric tube placement to continuous suction, IV access

• Development of nonimmune hydrops is an indication for prenatal treatment, including cyst aspiration, thoracoamniotic shunt, and resection of CCAM

Pathophysiology

• Always associated with some degree of pulmonary hypoplasia; the ipsilateral lung has a decreased airway and alveolar numbers, and the pulmonary artery is small; the contralateral lung is often also abnormal secondary to mediastinal shift with decreased alveolar numbers and increased PA muscularization • Pulmonary hypertension with ﬁxed component (caused by pulmonary hypoplasia) and variable component (caused by PA reactivity)

Epidemiology

Congenital Cystic Adenomatoid Malformation

Presentation and Diagnosis

Congenital Diaphragmatic Hernia

(continued on next page)

Surgical Disorders

Treatment

Congenital Diaphragmatic Hernia • Treatment is aimed at maximizing cardiovascular function and minimizing pulmonary hypertension and barotrauma • Administration of iNO is recommended if the patient who is >34 wk GA on mechanical ventilation has an oxygen index (OI) > 25 on two separate measurements OI = ([Mean airway pressure x FiO2] / PaO2) x 100 • Consider ECMO for OI >40 on two separate measurements • ECMO has been used pre-, intra-, and postoperatively to improve survival in patients with poor pulmonary function • In severe cases, fetal ex utero intrapartum treatment (EXIT) to ECMO may be 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 thoracolumbar scoliosis

477

Congenital Cystic Adenomatoid Malformation • If fetal surgery is not an option, maternal steroids have been reported to arrest the growth of fetal CCAMs • Those that do not self-resolve are resected later to prevent infection and malignant potential within the malformation • CXR should be taken after delivery and a CT scan of the chest should be done at 6–8 wk of age, even if the CXR is normal; any residual lesion is surgically resected, as there is a risk for malignancy.

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 difficulty 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.

NE ON AT OLO GY

Course • Typically present within first 2 weeks of life. • 50% resolve by age 9 mo. • 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 efficacy 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 reflux, cor pulmonale, pulmonary hypertension. • Flexible fiberoptic laryngoscopy by pediatric otolaryngologist. • Direct laryngoscopy and bronchoscopy if: • Complicated by “severe symptoms” above • Stridor or symptoms are out of proportion to the fiberoptic 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 figures or tables, respectively.

A AAT (α-1-antitrypsin) deficiency, 171t Ab screen, 205 Abbott powder formulas, 46–47t Abdominal pain, acute, 139–140 Abdominal reflex, 269t Abdominal wall defects, 471–472t Abducens nerve, 268t ABPA (allergic bronchopulmonary aspergillosis), 320t Abscess brain, 245t retropharyngeal, 136–137t skin characteristics, 114t, 233t incision and drainage, 32–33, 33t treatment, 114t Absence epilepsy, 278t AC (assist-control) ventilation, 87t, 375t ACE (angiotensin-converting enzyme) inhibitors, 73 Acetaminophen antidote, 345t dosing, 8–9t, 12t, 456 for migraine headache, 282t in neonates, 456 Acid–base disorders differential diagnosis, 164–165t, 166–167t, 166f in inborn errors of metabolism, 189f, 191t mixed, 168 neonatal, 189, 189f nomogram, 166f with partial compensation, 166–167t Acne, neonatal, 386t Acrodermatitis enteropathica, 391t Acropustulosis of infancy, 387t Acute chest crisis, in sickle cell disease, 200t Acute disseminated encephalomyelitis (ADEM), 284t Acute generalized exanthematous pustulosis (AGEP), 121t Acute infusion reaction, 290–291t Acute kidney injury (acute renal injury, acute renal failure) categories, 264 classification, 263 definition, 263 etiologies, 264 evaluation, 264–265 management, 265 in neonates, 445–446 prognosis, 265

Acute lymphoblastic leukemia (ALL) definition, 292 diagnosis, 293 epidemiology, 292 immunologic classification, 293t morphologic classification, 293t prognosis, 295 treatment, 293–294 Acute otitis media (AOM), 125–126 Acute postinfectious glomerulonephritis, 259t Acyclovir, 55t Acylcarnitine analysis, 193 ADEM (acute disseminated encephalomyelitis), 284t Admission orders (ADC VANDALISM), 1 Adolescents eating disorders in, 56–59, 57–58t emergency contraception for, 59 gynecologic examination, 51–52, 51t human papillomavirus infection in, 56 pediculosis pubis in, 56 pelvic inflammatory disease in, 55–56t scabies in, 56 sexually transmitted infections in, 53–54t vulvovaginal disorders in, 52–53t Adrenal hemorrhage, bilateral, 392t Adrenal insufficiency primary, 392–393 secondary, 393–294t Adrenergic toxidrome, 344t Adrenocortical dysgenesis, 392t AGEP (acute generalized exanthematous pustulosis), 121t Albumin 5%, 158t Albuterol adverse effects, 316t for anaphylaxis, 61t for asthma, 316t for status asthmaticus, 91t Alclometasone dipropionate, 124t Aldosterone synthase deficiency, 393t Alkylating agents, 298t ALL. See Acute lymphoblastic leukemia (ALL) Allergic bronchopulmonary aspergillosis (ABPA), 320t Allergic contact dermatitis, 111t Allergic rhinitis, 62–63t, 127 Allergic salute, 62 Allergic shiners, 62 Allergy testing, 60 Alloimmune thrombocytopenia, 426–427t α-1-antitrypsin (AAT) deficiency, 171t

479

480

Index

α-thalassemia, 199t ALTE (apparent life-threatening event), 323–324 Altered mental status, 141 Ambulatory care health supervision overview, 209–211t screening recommendations, 212t Amcinonide, 123t American Society of Anesthesiologists (ASA), physical status classification, 15t Amikacin, 224t, 438–439t Amino acid analysis, 193t Amino acid metabolic disorders, 191t Amino acid transport disorders, 191t Aminoglycosides, 224t Aminopenicillins, 218t Aminophylline, 92t Amitriptyline, 282t Amniocentesis, 358 Amoxicillin, 218t for acute otitis media, 126t for community-acquired pneumonia, 237t for infective endocarditis prophylaxis, 80t Amoxicillin–clavulanate, 219t for acute otitis media, 126t for community-acquired pneumonia, 237t Amphetamines, 341t, 342t Ampicillin, 218t, 437t Ampicillin–sulbactam, 219t AMPLE history, 15 Anal stenosis, 409t Anaphylaxis, 60–61, 61t, 121t Anemia of chronic disease, 197t definition, 196 diagnosis, 196, 197f, 198f iron-deficiency, 197t, 198–199 macrocytic, 197f microcytic, 197f morphologic classification, 197f neonatal, 431–433, 432t screening, 212t Aneuploidy, screening for, 354, 358, 358t Angioedema, 61–62, 121t Angiotensin-converting enzyme (ACE) inhibitors, 73 Anion gap metabolic acidosis, 168 Ankle fractures, 310t Ankle sprain, 310t Annular pancreas, 140 Anorectal abnormality, 409t Anorexia nervosa, 56–57, 57–58t Antiarrhythmics overview, 77t poisoning/overdose, 346t Antibiotics for acute otitis media, 125–126t aminoglycosides, 224t for bacterial tracheitis, 136t for bite wounds, 135t carbapenems, 221t cephalosporins, 220–221t

Antibiotics (cont.) in cystic fibrosis, 322–323t empiric choices for bacterial meningitis, 245t based on organism, 228f for community-acquired pneumonia, 237t, 238t for epiglottitis, 136t for fever without localizing signs, 130f, 131f fluoroquinolones, 224–225t lincosamides, 223t lipopeptides, 226t macrolides, 222t for mastoiditis, 127t monobactams, 221t for neonatal infections, 437–440t nitroimidazoles, 226t oxazolidinones, 223t penicillins, 218–219t for retropharyngeal abscess, 136t rifamycins, 226t for septic arthritis, 134t for sinusitis, 128 for skin and soft tissue infections, 234 sulfonamides, 225t tetracyclines, 223t vancomycin, 222t Anticholinergic toxidrome, 344t Anticoagulants, 205t Antiemetics, 292t Antiepileptics in increased intracranial pressure, 101 for migraine headache prophylaxis, 282t in pregnancy, neonatal effects, 399t, 423t for seizures, 279–280t Antihistamines for allergic rhinitis, 62t poisoning/overdose, 346t Antimetabolites, 298t Antipseudomonal penicillins, 219t Antithrombin (AT) replacement, 208 α-1-Antitrypsin (AAT) deficiency, 171t Antitumor antibiotics, 298t AOM (acute otitis media), 125–126 Apgar score, 349t Aplastic crisis, 200t Apnea, neonatal definition, 465 differential diagnosis, 468–469 evaluation, 468 incidence, 465 management, 469–470 monitoring, 468 Apophysitis, 301, 302 Apparent life-threatening event (ALTE), 323–324 Appendicitis, 139 Apple juice, 157t Aprepitant, 292t Argininemia, 194t Argininosuccinic aciduria, 194f, 194t

Index Arrhythmias, 75t, 76f, 77t Arsenic poisoning, antidote, 345t Arterial blood gases in congenital heart disease, 382 in mechanical ventilation, 89 normal values, 164t SI laboratory value conversion table, 8t Arterial switch operation, 81 Arthritis in cystic fibrosis, 320t differential diagnosis, 328f juvenile idiopathic, 329–330 synovial fluid evaluation in, 327t Ascites, 174 Asparaginase, 299t Aspergillosis, 227 Aspiration pneumonia, 235t, 237t, 238t Asplenia, secondary immunodeficiency in, 64t Assist-control ventilation (AC), 87t, 375t Asthma definition, 312 diagnosis, 313 exacerbation, 137f history and physical exam, 313t management assessment of control, 315t components, 313–314 initial therapy, 315t medications, 316t stepwise approach, 316–317t therapy adjustment, 315t modified predictive index, 312 pathophysiology, 312 severity classification, 314t Astrocytoma, 296–297t Athlete’s foot (tinea pedis), 118t Atopic dermatitis, 110–111 Atrial septal defect (ASD), 66 Atrial switch operation, 82, 82f Atrioventricular septal defect, 67, 67f, 81 Atrophy, 109 Auditory nerve, 268t Augmented betamethasone dipropionate, 123t Autoimmune diseases, secondary immunodeficiency in, 65t Autoimmune thrombocytopenia, 426t Avulsion fracture, 302, 308t Azalides, 222t Azithromycin, 222t for acute otitis media, 126 for chancroid, 54t for chlamydia, 54t for community-acquired pneumonia, 237t, 238t in cystic fibrosis, 322t for infective endocarditis prophylaxis, 80t for neonatal infections, 440t Aztreonam, 221t, 322t, 323t B Babinski sign/reflex, 269t, 272t Bacterial peritonitis, 174, 175t

481

Bacterial tracheitis, 136–137t Bacterial vaginosis, 52–53t Ballard score, 348t Barbiturates, 18, 18t Barium enema, pre-procedural diet, 4t Basal metabolic rate, 41t Behçet syndrome, 332t Benign childhood epilepsy with centrotemporal spikes, 278t Benign neonatal sleep myoclonus, 449t Benign Rolandic Epilepsy (BRE), 278t Benzodiazepines. See also specific drugs antidote, 345t overview, 17, 17t Berger (IgA) nephropathy, 259t Bernard-Soulier syndrome, 427t β-blockers as antiarrhythmics, 77t antidote, 345t for dilated cardiomyopathy, 73 for hyperthyroidism, 149 β-lactamase resistant penicillins, 219t β-lactamase susceptible penicillins, 218t β-thalassemia major, 199t β-thalassemia minor, 197t, 199t Betamethasone, equivalencies, 10t Betamethasone dipropionate, 123t Betamethasone valerate, 124t Bicarbonate, in fluid replacement, 154 Bilevel positive airway pressure (BiPAP), 85t Biliary cirrhosis, in cystic fibrosis, 319t Biophysical profile, 360–361t Birth weight, 3 Bisacodyl, 179 Bites, 134–135 Bitter almond odor, 341t Blalock-Taussig shunt, 81, 81f Blastomycosis, 227 Bleeding disorders differential diagnosis, 203t history, 204 laboratory evaluation, 204 treatment of acute bleeding in, 204t Bleomycin, 298t Blood component transfusion CMV-seronegative, 207 cryoprecipitate, 207 definitions, 205 granulocyte, 207 irradiated blood, 208 leukocyte-reduced blood, 207 in neonates, 433t, 434–436t packed red blood cells, 206t, 433t, 434t plasma, 207, 435t platelets, 206t, 207, 435t risks, 206 Blood gases in mechanical ventilation, 89 normal values, 164t SI laboratory value conversion table, 8t Blood pressure screening, 212t. See also Hypertension

482

Index

Blood transfusion. See also Blood component transfusion; Exchange transfusion for shock, 98 typing and cross-matching for, 430–431t Blood type, 205 Bloodstream infections central venous catheter-related, 247–249, 247t, 248f, 249t intravascular catheter-related, 246–247, 246t Body mass index (BMI), 49 Body surface area, 4 Bone marrow transplantation, 299–300 Bone scan, pre-procedural diet, 4t Boost, 156t Borrelia burgdorferi, 115t Brachial muscles, actions and nerve root supply, 272–273t Bradycardia, 76f Brain abscess, 245t Brain death, 287–288 Brainstem glioma, 296–297t Breast milk jaundice, 412t Breastfeeding, 35–36. See also Human milk Breastfeeding jaundice, 412t Bronchiolitis, 138–139 Bronchopulmonary dysplasia (BPD), 465–468t Bronchoscopy, pre-procedural diet, 4t Buckle (torus) fracture, 302 Bulimia nervosa, 57–58t Bulla, 109 Bullous congenital ichthyosiform erythroderma, 388t Bupivacaine, 12t Busulfan, 298t Buttock laceration, 31t C Caffeine, 466t, 469 Calcium conversion, 43t daily requirement, 43t ECG changes and, 77 for neonatal hypocalcemia, 401t in shock, 98 Calcium channel blockers, as antiarrhythmics, 77t Calcium deficiency, 152t Candida infections, 52–53t, 119t, 227, 390t Carbamazepine, 279t Carbamoyl-phosphatase synthetase (CPS) deficiency, 193t, 194f Carbapenems, 221t, 440t Carbenicillin, 219t Carbohydrates, in total parenteral nutrition, 42, 43t Carbon monoxide, antidote, 345t Carbon tetrachloride, antidote, 345t Carbuncle, 233t Cardiac ischemia, 75 Cardiogenic shock, 94t, 96t, 98 Cardiomyopathy dilated, 72–73, 72t in inborn errors of metabolism, 192 Caries, dental, 106–107

Carrot odor, 341t Casts, in urine, 257t Cat bites, 135t, 233t Cataracts, 192 Cefaclor, 220t Cefadroxil, 220t Cefamandole, 220t Cefazolin, 80t, 220t, 439t Cefdinir, 220t Cefepime, 221t Cefixime, 53t, 220t Cefonicid, 220t Cefotaxime, 220t, 238t, 439t Cefotetan, 55t, 220t Cefoxitin, 55t, 56t, 220t Cefpodoxime, 220t Cefprozil, 220t Ceftazidime, 323t, 439t Ceftibuten, 220t Ceftizoxime, 220t Ceftriaxone, 220t for acute otitis media, 126t for chancroid, 54t for gonorrhea, 53t for infective endocarditis prophylaxis, 80t for neonatal infections, 440t for pelvic inflammatory disease, 56t Cefuroxime, 220t Cellulitis, 114t, 233t, 234 Central core disease, 453t Central diabetes insipidus, 150–151t Central nervous system tumors, 296–297t Central shunt, 81 Central venous line (CVL) access, 25–27, 26t, 27f infections complications, 249 management, 247, 248f, 249t types, 247t Cephalexin, 80t, 220t Cephalosporins, 220–221t, 439–440t Cephapirin, 220t Cephradine, 220t Cerebral edema, 99, 101 Cerebral salt wasting (CSW), 150t Cerebrospinal fluid analysis, 244t, 442t Cerumen, 5–6, 6f Ceruminolytic preparations, 6t Cervical adenitis, 231t Cervical dysplasia, screening recommendations, 212t Chancroid, 54t CHARGE syndrome, 187 Chemical conjunctivitis, in neonates, 443–444t Chemistry studies SI laboratory value conversion table, 8t tube colors, 6, 7t Chemotherapy agents antitumor spectrum, 298–299t emetogenic potential, 291t hypersensitivity reactions to, 290–291t toxicities, 298–299t

Index Chest pain differential diagnosis, 78–79 green flags, 78 red flags, 78 workup, 79 Chest tube placement, 22–23, 22f, 22t Chest x-ray in congenital heart disease, 379, 382f, 382t in persistent pulmonary hypertension, 463t in respiratory distress syndrome, 458t in transient tachypnea of the newborn, 458t Chicken broth, 157t Chickenpox, 116t Child abuse, 141–142 Childhood weakness, 286–287t Chlamydia trachomatis infection, 54t, 212t Chlamydial conjunctivitis, in neonates, 443–444t Chloral hydrate, 18, 18t Chloride conversion, 43t daily requirement, 43t in mechanical ventilation, 89 Chlorothiazide, for bronchopulmonary dysplasia, 467t Cholelithiasis, in cystic fibrosis, 319t Cholestasis, in total parenteral nutrition, 44 Cholinergic toxidrome, 344t Chorionic villus sampling (CVS), 358–359 Chronic arthritis, 327t Chronic kidney disease, 265–267 Churg-Strauss syndrome, 333t Ciprofloxacin, 224t adverse effects, 322t for chancroid, 54t for P. aeruginosa, 322t Circumcision, 350 Cisplatin, 298t Citrullinemia, 193t, 194f Clarithromycin, 80t, 222t Clavicular fracture, 303t Cleft lip and palate, 128–129 Clindamycin, 223t adverse effects, 323t for bacterial vaginosis, 53t for infective endocarditis prophylaxis, 80t for neonatal infections, 439t for pelvic inflammatory disease, 56t for S. aureus, 323t Clinical Respiratory Score (CRS), 90–91t, 138t Clobetasol propionate, 123t Clotrimazole, 53t CMV-seronegative blood components, 207 Coagulation studies, tube colors for, 6, 7t Coagulopathies. See Bleeding disorders Coca Cola Classic, 157t Cocaine, 341t, 342t, 346t Coccidioidomycosis, 227 Codeine, 13t, 14t Colistimethate sodium, 323t Colitis, indeterminate, 180. See also Crohn disease; Ulcerative colitis Collection tubes, 7t

483

Coma, 141 Comminuted fracture, 302 Common warts, 117t Compensated (warm) shock, 93, 97f, 98. See also Shock Complement deficiency, 63–64, 64t Complex partial seizure, 275t. See also Seizures Computed tomographic angiography (CTA), 274t Computed tomography (CT) brain, 274t pre-procedural diet, 5t signal density, 274t Condyloma acuminata (genital warts), 56, 117t Congenital fiber type disproportion myopathy, 453t Congenital heart disease acyanotic, 66–67 arterial blood gases in, 382 chest x-ray findings in, 382f, 382t cyanotic, 67–70, 381t differential diagnosis, 383–384t in Down syndrome, 184 EKG findings in, 381–382t empiric approach to evaluation, 380t four-extremity blood pressures in, 381 history, 381 hyperoxia test in, 383, 383t infective endocarditis prophylaxis in, 80, 80t initial stabilization, 384 management, 384–385 oximetry in, 381 pathophysiology and age at presentation, 383–384t prenatal testing, 381 surgical procedures, 81–82, 81f, 82f symptoms, 381t, 383–384t Congenital hypoventilation syndrome, 469 Congenital melanocytic nevus, 387t Congenital muscular dystrophy, 453t Conjugated (direct) hyperbilirubinemia, 175 Conjunctivitis, in neonates, 443–444 Constipation, 39t, 179–180 Contact dermatitis, 111t Continuous positive airway pressure (CPAP), 85t Contraception, emergency, 59 Contraction stress test, 360 Controlled mechanical ventilation (CMV), 86t Cooked cabbage odor, 189t Coordination testing, 269 Copper, for direct hyperbilirubinemia, 420t Cordocentesis, 359 Corneal opacifications, 192 Corticosteroids adrenal insufficiency and, 392t as chemotherapy agents, 299t immunizations in patients receiving, 217t inhaled, 316t intranasal, 61t systemic, 9–10t, 137f topical, 110t, 123–124t Cortisone, equivalencies, 9t Cow’s milk, 156t Cow’s milk–based formulas, 46

484

Index

Coxsackie A16, 116t CPS (carbamoyl-phosphatase synthetase) deficiency, 193t, 194f Cradle cap, 111t Cranial nerves, examination methods, 268t Creatinine, serum, 251 Creatinine clearance, 250–251 Cremasteric reflex, 269t Crigler-Najjar syndrome, 412t Crohn disease clinical features, 180t definition, 179 endoscopic features, 181t epidemiology, 180t radiographic features, 181t treatment, 181–182, 182t Cromolyn sodium, 63t Cross-match, 205 Croup, 136–137t CRS (Clinical Respiratory Score), 90–91t, 138t Crural muscles, actions and nerve root supply, 273t Crust, 109 Cryoglobulinemia, 332t Cryoprecipitate, 207, 208 Cryptococcosis, 227 Crystals, in urine, 256t CSW (cerebral salt wasting), 150t CT. See Computed tomography (CT) CTA (computed tomographic angiography), 274t Cutaneous innervation, 270–271f CVL. See Central venous line (CVL) CVS (chorionic villus sampling), 358–359 Cyanosis, 353t, 380t, 381t Cyclophosphamide, 298t Cyproheptadine, 282t Cystic adenomatoid malformation, congenital, 475–477t Cystic fibrosis complications, 319–320, 320t diagnosis, 317 epidemiology, 317 genetics, 317 management airway clearance therapies, 321 antibiotic options, 321, 322–323t nutrition, 321 pharmacologic, 321–322t manifestations, 318–319t pneumonia in, 235t, 318t, 319 symptoms and signs, 318t treatment, 318–319t Cytarabine, 298t Cytokine release syndrome, 290–291t D D5 1/2 NS, 158t D5 1/4 NS, 158t D5W, 158t Dacryostenosis, 443–444t Dactinomycin, 298t Dactylitis (hand-foot syndrome), 199t Damus-Kaye-Stansel procedure, 81

Daptomycin, 226t De Quervain thyroiditis, 149 Decompensated (cold) shock, 93, 97f, 98. See also Shock Deep tendon reflexes, 269 Deferoxamine, 345t Dehydration classification, 55 intravenous rehydration, 157, 158t oral rehydration, 155–157 symptom-based determination, 154t weight-based determination, 154 Dejerine–Sottas disease, 453t Delayed puberty, 151 Demyelinating diseases, 284–286 Dennie’s lines, 62 Dental caries, 106–107 Dental procedures, infective endocarditis prophylaxis for, 80t Dermal melanocytosis, 387t Dermatomyositis, 329t Desonide, 124t Desoximetasone, 123t Developmental observations, 209–211t Dexamethasone adverse effects, 316t as antiemetic, 292t for asthma, 316t as chemotherapy agent, 299t equivalencies, 10t for spinal cord compression, 290 Dexmedetomidine, 18, 19t Diabetes insipidus, 150–151t Diabetes mellitus blood glucose goals, 146t cystic fibrosis and, 319t diagnosis, 143t HbA1c goals, 146t hyperglycemic emergencies in, 98–99, 99t, 100f hypoglycemia management in, 147, 148f inpatient management of, 145 insulin for, 145–147 in NPO patients, 146 in pregnancy, 355, 357t, 399t secondary causes, 144 secondary immunodeficiency in, 64t type 1, 143, 143t type 2, 143–144, 143t Diabetic ketoacidosis (DKA), 98–99, 99t, 100f Dialysis, indications for, 265 Diaper dermatitis, 119t, 390, 390t Diaphragmatic hernia, congenital, 475–477t Diarrhea, with enteral feeding, 39t Diazepam, 17t Dicloxacillin, 219t Diet, pre-procedural guidelines, 4–5t Diflorasone diacetate, 123t Digoxin as antiarrhythmic, 77t antidote, 345t for dilated cardiomyopathy, 73 poisoning/overdose, 346t

Index Dilated cardiomyopathy, 72–73, 72t Dimercaprol, 345t Diphenhydramine, 61t Diphtheria, tetanus, pertussis vaccine catch-up schedule, 214t, 215t contraindications, 216t regular schedule, 213t Direct Coombs test, 206 Discharge criteria neonates, 376 post-sedation, 20t Discharge orders, 1 Discharge summary, 2 Disseminated intravascular coagulation (DIC), 427t Dissociative shock, 95t Distal intestinal obstruction syndrome (DIOS), 320t Distributive shock, 94t, 95t Diuretics for bronchopulmonary dysplasia, 467t for dilated cardiomyopathy, 73 in mechanical ventilation, 89 DMSA scan, 242t Dobutamine, 96, 96t Dog bites, 135t, 233t Dopamine in neonatal resuscitation, 365t for shock, 96, 96t Down syndrome (trisomy 21), 64t, 183, 184–185t, 422–423t Doxorubicin, 298t Doxycycline, 223t adverse effects, 322t for chlamydia, 54t for lymphogranuloma venereum, 54t for pelvic inflammatory disease, 55t, 56t for S. aureus, 322t Dronabinol, 292t Drug hypersensitivity syndrome (DHS), 122t Drug monitoring collection tube colors, 7t SI laboratory value conversion table, 8t urine testing for substances of abuse, 342t Drug reaction with eosinophilia and systemic symptoms (DRESS), 122t Drug reactions, 120–123t Drugs of abuse. See Substance abuse Duodenal atresia and stenosis, 473–475t Dyslipidemia, screening recommendations, 212t E Ear wax (cerumen), 5–6, 6f Eating disorders, 56–59, 57–58t ECF (extracellular fluid), 158t Echocardiography, pre-procedural diet, 5t Eclampsia, 356 ECMO (extracorporeal membrane oxygenation), 463t, 470 Ecstasy, 341t Ectodermal dysplasias, 389t Eczema, 110–111

485

Eczematous/papulosquamous eruptions, 111–113t Edema, cerebral, 99, 101 ELA-Max, 11t Elbow fractures, 304t Electrocardiogram (ECG; EKG) in congenital heart disease, 381–382t drugs and changes in, 77 electrolytes and changes in, 76–77 in hypertrophy, 74–75 intervals, 74 in ischemia and infarction, 75 low voltage, 75 normal values, 73t in pericarditis, 71, 71f QRS depolarization axis, 74, 74f rate, 74 rhythm, 74 Electrolytes, 43t, 153 EM (erythema multiforme), 122t Embryology, 186t, 187 Emergency contraception, 59 EMLA, 11t Encephalopathy, neonatal, 450–452 End-stage liver disease (ESLD) ascites in, 174 bacterial peritonitis in, 174, 175t clinical presentation, 172 diagnosis, 172 etiology, 172 hepatic encephalopathy in, 173, 173t hepatorenal syndrome in, 173, 174–175t portal hypertension in, 172 treatment, 172 varices in, 173 End-stage renal disease (ESRD), 266 Endotracheal tubes, 16t, 365t Energy, DRI by age, 40t Enfalyte, 156t Enfamil HMF, 48t Enfamil Lipil, 156t Ensure, 156t Enteral feeding bolus or intermittent, 38t complications, 38t, 39t continuous, 38t delivery routes, 38t in direct hyperbilirubinemia, 420t indications, 37, 38t preterm infants, 39t principles, 36, 37f Enterovirus 71, 116t Eosinophilia, 202t Eosinophils, 201t Ependymoma, 296–297t Epidermolysis bullosa (EB), 389t Epidermolytic hyperkeratosis, 388t Epididymitis, 131–132t Epiglottitis, 136–137t Epilepsy classification scheme, 277–278t syndromes, 278–279t treatment, 279–280t

486

Index

Epinephrine for anaphylaxis, 61t, 97f in neonatal resuscitation, 264t, 365t for shock, 96, 96t warnings, 11, 12t Equianalgesic doses, 14, 14t Erosion, 109 Erysipelas, 114t Erythema infectiosum (fifth disease), 116t Erythema multiforme (EM), 122t Erythema toxicum, 386t Erythromycin, 222t for chancroid, 54t for lymphogranuloma venereum, 54t ESLD. See End-stage liver disease (ESLD) ESRD (end-stage renal disease), 266 Ethanol, prenatal exposure effects, 423t Ethosuximide, 279t Ethyl chloride topical spray, 12t Ethylene glycol, antidote, 345t Etomidate adverse effects, 19t dosing, 19t onset and duration, 19t pharmacologic properties, 18 in septic shock, 98 Etoposide, 299t Exanthem subitum (roseola), 116t Exanthematous drug reaction, 120t Exchange transfusion complications, 431 for hyperbilirubinemia, 414f, 414t, 430t indications, 430t partial, 433t for polycythemia, 430t preparation, 430t procedure, 431 typing and cross-matching for, 430–431t Excoriation, 109 Extracellular fluid (ECF), 158t Extracorporeal membrane oxygenation (ECMO), 463t, 470 Extraocular muscles, innervation, 269 Extremely low birth weight infants, 369. See also Preterm infants Extremity laceration, 31t Eyelid laceration, 31t F Face masks, for O2 delivery, 84–85t FACES pain scale, 11f Facial laceration, 31t Facial nerve, 268t Factor 8 replacement, 204t Factor 9 replacement, 204t Factor H deficiency, 64t Failure to thrive, 182–183, 191t Famciclovir, 55t Fanconi syndrome, 152t, 428 Fatty acid oxidation disorders, 191t Febrile seizures, 276 Feeding hypoxemia, 469

Felbamate, 279t Femoral vein, 26, 27f Femur fractures, 308t Fentanyl dosing, 13t, 14t, 457 in neonates, 457 onset and duration, 13t in patient-controlled analgesia, 14t weaning from, 20 Fetal heart rate (FHR) monitoring, 361–362, 361t Fetal hydrops, nonimmune, 421–422t Fetus antepartum surveillance biophysical profile, 360–361t contraction stress test, 360 indications, 359–360t non-stress test, 360 complications of maternal medical conditions, 354, 355, 357t complications of maternal substance abuse, 357t genetic diagnosis techniques, 358–359 intrapartum heart rate monitoring, 361–362, 361t lung maturity evaluation, 355, 355t serum screening for chromosomal abnormalities, 358t sonographic assessment, 357, 358 Fever, as oncologic emergency, 289 Fever without localizing signs in patients 2 months and younger, 130f in patients 2 months to 36 months old, 131f FFP (fresh frozen plasma), 435t Fifth disease (erythema infectiosum), 116t Finger fractures, 307t Fissure, 109 Fixed drug eruption, 121t FLM-TDx, 355t Fluconazole, 53t, 119t Fludrocortisone, 10t Fluid requirements, 153–154 Flumazenil, 17, 345t Fluocinolone acetonide, 124t Fluocinonide, 123t Fluoride consumption, 106 Fluoroquinolones, 224–225t Fluoroscopy, pre-procedural diet, 5t Fluorosis, 106 Flurandrenolide, 123t Fluticasone acetonide, 124t Fluticasone propionate, 123t, 124t FOC. See Head circumference (FOC) Focal segmental glomerulosclerosis, 260t Folliculitis, 113t, 233t Fomepizole, 345t Fontan procedure, 81, 81f Fontanelles, 4 Foot fractures, 310–311t laceration, 31t Formulas, infant, 46–47t Fosphenytoin, 104f

Index Fractures ankle, 310t in child abuse, 141 elbow, 304t evaluation, 302 femur, 308t foot, 310–311t hand, 306–307t hip, 308t knee, 308–309t management principles, 303 radius, 305t shoulder, 303t tibia and fibula, 309t types, 302, 302f ulna, 306t Free amino acid formulas, 46 Free water deficit, 161 Freiberg’s infarction, 311t Fresh frozen plasma (FFP), 435t Fresh hay odor, 341t Fruity odor, 341t FSI, 355t Fungal infections, 118–119t, 227 Furosemide, for bronchopulmonary dysplasia, 467t Furuncle, 233t G Gabapentin, 279t GABHS (group A β-hemolytic streptococcus), 114t, 125 Galeazzi fracture, 305t Gallstones, 140 Gamekeepers thumb, 307t γ-hydroxybutyrate (GHB), 341t Garlic odor, 341t Gastric aspirates, large or increased, 414–415 Gastric emptying study, pre-procedural diet, 5t Gastroesophageal reflux, 169–170 Gastroesophageal reflux disease (GERD), 169–170, 410–411 Gastrojejunal feeding, 38t. See also Enteral feeding Gastroschisis, 471–472t Gastrostomy, 38t. See also Enteral feeding Gatifloxacin, 225t Gatorade, 157t GBS. See Group B streptococcus (GBS) infections Gell and Coombs classification, hypersensitivity immune responses, 60t Generalized seizures, 276t. See also Seizures Genital warts, 56, 117t Gentamicin, 56t, 224t, 438t Gentamicin/tobramycin, 323t German measles (rubella), 116t Gestational age assessment, 354, 354f Gestational hypertension, 356 GHB (γ-hydroxybutyrate), 341t Gianotti-Crosti syndrome, 117t Giant hemangioma, 427t Gilbert syndrome, 412t Glabellar reflex, 270t Glenn anastomosis, 81, 81f

487

Glioma, brainstem, 296–297t Glomerular filtration rate (GFR), 250, 251t Glossopharyngeal nerve, 268t Glucagon, 245t Glucose for neonatal hypoglycemia, 405–406 requirements, 153 in urine, 255t Glycogen storage diseases, 191t Glycopeptides, 222t Glycosylation disorders, 191t Gonococcal conjunctivitis, in neonates, 443–444t Gonorrhea, 53t, 212t Goodpasture syndrome, 332t Gram-negative organisms algorithm for identification, 230f empiric antibiotic choices, 228f Gram-positive organisms algorithm for identification, 229f empiric antibiotic choices, 228f Granulocyte transfusion, 436t Graves disease, 149 Greenstick fracture, 302 Griseofulvin, 118t Group A β-hemolytic streptococcus (GABHS), 114t, 125 Group B streptococcus (GBS) infections classification, 442–443t intrapartum prophylaxis, 367f, 368f treatment, 443t Growth charts, 49, 50f Gynecologic examination, 51–52, 51t H H2R antagonists, 169 Haemophilus ducreyi, 54t Haemophilus influenza in acute otitis media, 125 in cystic fibrosis, 318t, 322t immunization schedule, 213t, 214t in sinusitis, 128 Hair, abnormal, 189 Halcinonide, 123t Halobetasol propionate, 123t Hand fractures, 306–307t laceration, 31t Hand-foot-mouth disease, 116t Harlequin ichthyosis, 389t Hashimoto’s thyroiditis, 147 HbA1c, 146t Head circumference (FOC) by age for boys, 2t, 3 by age for girls, 3t by gestational age, 50f rate of gain, 3, 4 Headaches chronic daily, 283 classification scheme, 281t migraine. See Migraine headaches neuroimaging in, 281 tension type, 283

488

Index

Health supervision, 209–211t Hearing screening, 212t Heart disease arrhythmias, 75t, 76f, 77t athletic restrictions in, 80–81 congenital. See Congenital heart disease dilated cardiomyopathy, 72–73, 72t infective endocarditis prophylaxis in, 80, 80t myocarditis, 70–71, 70t pacemakers for, 77 pericardial, 71–72, 71f Heavy metal poisoning, antidote, 345t Height/length by age for boys, 2t by age for girls, 3t by gestational age, 50f rate of gain, 3 Heliox for respiratory failure, 85t for status asthmaticus, 92t Hematology studies SI laboratory value conversion table, 8t tube colors, 6, 7t Hematuria, differential diagnosis, 252–254, 253f, 255t Hemoglobin, 196t Hemolysis effect on lab values, 7t hyperbilirubinemia and, 412t Hemolytic disease of the newborn, 430t Hemophagocytic-lymphohistiocytosis (HLH), 295 Hemophilia, 204, 204t Hemoptysis, in cystic fibrosis, 320t Henoch Schönlein purpura, 333, 335 Hepatic encephalopathy, 173, 173t Hepatitis infectious, 170 noninfectious, 171 Hepatitis A, 170t Hepatitis A immunization, 212t, 215t Hepatitis B, 170t Hepatitis B immunization in preterm infants, 444 schedule, 213t, 214t, 215t Hepatitis C, 170t Hepatomegaly, 192 Hepatorenal syndrome, 173–174t Hepatosplenomegaly, 192 Hereditary angioedema, 62 Hereditary hemochromatosis (HH), 171t Hereditary hypophosphatemic rickets with hypercalciuria (HHRN), 152t Hereditary motor and sensory neuropathy type III, 453t Hernia congenital diaphragmatic, 475–477t incarcerated, 140 Heroin, 341t Herpes simplex virus (HSV) diagnosis, 54t genital infection, 54t, 55t, 117t

Herpes simplex virus (HSV) (cont.) oral infection, 117t superinfection in eczema, 110t treatment, 55t, 117t Herpes zoster (shingles), 117t HHV-6, 116t HIDA scan, pre-procedural diet, 5t HIE (hypoxic-ischemic encephalopathy), 448t, 451–452t High-frequency oscillatory ventilation (HFOV), 87t, 375t Hip fracture, 308t Hirschsprung’s disease, 140, 409t Histoplasmosis, 227 HIV immunizations in, 217t screening recommendations, 212t HLHS (hypoplastic left heart syndrome), 69, 69f, 81, 81f Hoffman sign, 269t HSV. See Herpes simplex virus (HSV) Human bites, 135t, 233t Human milk characteristics, 45 composition, 45, 156t contraindications, 45 fortifiers, 48t with infant formula powder, 47t storage durations, 36t vitamin and mineral supplementation, 35t Human papillomavirus (HPV), 56, 117t, 212t, 215t Hybrid Norwood procedure, 81–82 Hydrocephalus, 453–454 Hydrocodone, 13t, 14t Hydrocortisone, 124t for anaphylaxis, 61t equivalencies, 9t Hydrocortisone butyrate, 124t Hydrocortisone valerate, 124t Hydromorphone, 13t, 14t 21-Hydroxylase deficiency, 392t 3-β-Hydroxysteroid dehydrogenase deficiency, 392t Hyperammonemia, 194–195, 195f Hyperbilirubinemia direct (conjugated) definition, 175, 418 diagnosis, 175, 419, 419t etiologies, 419t management, 420t in inborn errors of metabolism, 189 indirect (unconjugated), 175–176, 411 nonphysiologic causes, 412t evaluation, 412 management, 412–414, 413f, 414f physiologic, 411 Hypercalcemia ECG changes in, 76 neonatal, 397–398, 397f Hyperekplexia, 449t

Index Hyperglycemia with enteral feeding, 39t neonatal, 403–404 in total parenteral nutrition, 44 Hyperglycemic hyperosmolar state (HHS), 98–99, 99t, 100f Hyperkalemia causes, 158–159 ECG changes in, 76 exchange transfusion for, 430t neonatal, 395–396 signs and symptoms, 158 treatment, 159 workup, 159 Hyperleukocytosis, 291 Hypermagnesemia, ECG changes in, 77 Hypernatremia dehydration in, 155t neonatal, 406–407 signs and symptoms, 160 treatment, 161–162 workup, 161, 161f Hyperoxia test, 383, 383t Hypersensitivity immune responses, 60t, 290–291t Hypersplenism, 427t Hypertension definition, 251 initial workup, 252f in neonates, 446–447 in pregnancy, 356, 356t, 357t Hyperthyroidism, 149 Hypertonic saline, 158t Hypertriglyceridemia, in total parenteral nutrition, 44 Hyperventilation, 165t Hypocalcemia early neonatal, 398–399, 400t, 401t ECG changes in, 76 late neonatal, 399–401, 400t, 401t Hypoglossal nerve, 268t Hypoglycemia in inborn errors of metabolism, 188, 188f, 191t, 192, 404t neonatal, 188f, 404–406 in type 1 diabetes mellitus, 147, 148f Hypokalemia causes, 160 ECG changes in, 76 neonatal, 396–397 signs and symptoms, 159–160 treatment, 160 workup, 160 Hypomagnesemia ECG changes in, 77 neonatal, 399t Hyponatremia causes, 163f dehydration in, 155t neonatal, 407–408 signs and symptoms, 162 treatment, 162–164 workup, 163f

489

Hypoparathyroidism, neonatal, 399t Hypophosphatemia, 152t Hypopituitarism, 393t Hypoplastic left heart syndrome (HLHS), 69, 69f, 81, 81f Hyposplenism, secondary immunodeficiency in, 64t Hypotension, 94, 357t. See also Shock Hypothermia, induced, 102 Hypothyroidism, 147, 149 Hypothyroxinemia, in preterm infants, 394–395, 394f Hypotonia in inborn errors of metabolism, 188 neonatal, 452 Hypovolemic shock, 94t, 95t Hypoxic-ischemic encephalopathy (HIE), 448t, 451–452t I Ibuprofen in cystic fibrosis, 322t dosing, 9t, 12t for migraine headache, 282t ICP (increased intracranial pressure), 101–102 Idiopathic thrombocytopenic purpura (ITP), 202 Ifosfamide, 298t IgA (Berger) nephropathy, 259t Ileal atresia, 409t Ileus, 410t Imipenem, 221t Immediate hypersensitivity skin test (IHST), 60 Immunizations after bone marrow transplantation, 299–300 catch-up schedule, 214–215t contraindications, 216t in preterm infants, 444, 444t recommended schedule, 213t for special populations, 217t Immunodeficiency disorders immunizations in, 217t primary, 63, 63t secondary, 64–65t Immunotherapy, for allergic rhinitis, 63t Imperforate anus, 409t Impetigo, 113t, 233t IMV (intermittent mandatory ventilation), 87t Inborn errors of metabolism acute and recurrent attacks, 192 chronic and progressive symptoms, 192 classes, 188t clinical and laboratory findings, 191t hypoglycemia in, 188f, 404t laboratory tests, 192–193 management, 194–195 metabolic acidosis in, 189f signs and symptoms, 188–189, 188f, 189f urine and body odors in, 189–190t urine discoloration in, 190t Incision and drainage (I&D), abscess, 32–33, 33t Increased intracranial pressure (ICP), 101–102

490

Index

Indirect Coombs test, 205 Indomethacin, 12t, 380, 380t Infants bacterial meningitis in, 245t feeding bottle weaning, 106 enteral. See Enteral feeding formula mixing, 46–47t formula selection, 45–46 vitamin and mineral supplementation, 35t fever without localizing signs in, 130f, 131f preterm. See Preterm infants reflexes, 271–272t skin and soft tissue infections in, 234 total parenteral nutrition. See Total parental nutrition (TPN) Infections central venous catheter-related, 247–249, 247t, 248f, 249t fungal, 118–119t, 227 intravascular catheter-related, 246–247, 246t in neonates, 437–440t odontogenic, 108 pneumonia. See Pneumonia skin, 233–234 urinary tract. See Urinary tract infections Infectious rhinitis, 127 Infective endocarditis, prophylaxis, 80, 80t Infertility, in cystic fibrosis, 319t Inflammatory bowel disease, 180, 180t, 181t. See also Crohn disease; Ulcerative colitis Influenza vaccine, 212t Infuvite, 44t Inhaled nitric oxide (iNO) for persistent pulmonary hypertension, 463t for preterm infants, 373 Insulin for diabetes mellitus dose adjustment, 147 regimens, 145–146, 146t sliding scale, 146–147 types, 145t for neonatal hyperglycemia, 403 Insulin aspart, 145t Insulin detemir, 145t Insulin glargine, 145t Insulin glulisine, 145t Insulin lispro, 145t Insulin NPH, 145t Insulin pump, 146 Insulin regular, 145t Intermittent mandatory ventilation (IMV), 87t Internal jugular vein (IJ), 26 Interventional radiology, pre-procedural diet, 5t Intestinal lymphangiectasia, secondary immunodeficiency in, 65t Intracranial hemorrhage intraventricular, 450, 450t MRI evaluation, 275t neonatal seizures and, 448t Intraosseous (IO) access, 24–25, 25t Intraventricular hemorrhage, 450, 450t

Intussusception, 140 Ionizing radiation, secondary immunodeficiency and, 65t Ipratropium bromide, 92t, 137f Iron-deficiency anemia, 197t, 198–199 Iron overload, 171t Iron poisoning, antidote, 345t Irradiated blood, 208 Irritant contact dermatitis, 111t Isolyte M, 158t Isolyte P, 158t Isonatremic dehydration, 155t ITP (idiopathic thrombocytopenic purpura), 202 Itraconazole, 322t Ivermectin, 120t J Jejunoileal atresia and stenosis, 473–475t Jejunostomy, 38t. See also Enteral feeding Jevity, 156t Jock itch (tinea cruris), 118t Joint pain, non-traumatic causes, 132–133t Juvenile idiopathic arthritis (JIA), 329–330 Juvenile myoclonic epilepsy, 278t K Kasabach-Merritt syndrome, 427t Kawasaki disease clinical findings, 332t, 336–337t definition, 335 diagnosis, 335, 336t, 338f differential diagnosis, 336t epidemiology, 335 incomplete, 337t treatment, 337 Keppra, 103t Keratosis pilaris, 112t Ketamine adverse effects, 18t dosing, 18t onset and duration, 18t pharmacologic properties, 18 for status asthmaticus, 92t Ketoconazole for seborrheic dermatitis, 111t for tinea versicolor, 120t Ketogenesis disorders, 191t Ketorolac, 12t Kleihauer-Betke preparation, 433 Knee fractures, 308–309t Kohler’s disease, 310t Konno-Rastan procedure, 81 L Laceration repair, 30–31t, 30–32 Lactated Ringer’s solution (LR), 158t Lactic acidosis, in inborn errors of metabolism, 191t Lactose-free formulas, 46 Lamellar body count, 355t Lamellar ichthyosis, 388t Lamotrigine, 280t Landau-Kleffner syndrome, 279t

Index Langerhans cell histiocytosis, 391t Laryngomalacia, 477–478 Laryngoscope tube, 16t Lead poisoning antidote, 345t screening recommendations, 212t Left ventricular hypertrophy (LVH), 74 Length. See Height/length Lennox-Gastaut syndrome, 279t LET (lidocaine, epinephrine, tetracaine) solution, 11t Leukocyte esterase, in urine, 255t Leukocyte-reduced blood, 207 Leukocytes, total, 201t Leukocytosis, 202, 202t Leukotriene receptor antagonist, 63t, 316t Levalbuterol, 91t, 316t Levetiracetam, 280t, 282t Levofloxacin, 224t Levonorgestrel, 59 Levothyroxine, 147 Lice, 120t Lichenification, 109 Lidocaine, 12t Limp, 132–134 Lincosamides, 223t Linezolid, 223t, 322t, 440t Lip laceration, 31t Lipids, in total parenteral nutrition, 42 Lipopeptides, 226t Lisfranc fracture, 310t Lithium, antidote, 345t Little league elbow, 304t Little league shoulder, 303t Liver failure. See also End-stage liver disease (ESLD) in cystic fibrosis, 319t fulminant, 171–172, 172f in inborn errors of metabolism, 189, 191t, 192 in secondary immunodeficiency, 64t L.M.X. 4%, 11t Local anesthetics injectable, 12t for laceration repair, 30–31t topical, 11–12t Lorazepam adverse effects, 17t dosing, 17t onset and duration, 17t for seizures, 280t for status epilepticus, 104f Low birth weight infants, 369. See also Preterm infants Low-carbohydrate formulas, 46 Low-molecular-weight heparin (LMWH), 205t Low T3 syndrome, 149 Lower motor neuron lesions, 272t, 452t L:S ratio, 355t LSD, 341t Lucey-Driscoll syndrome, 412t Lumbar puncture, 23–24, 23t, 24f Lyme disease, 115t

491

Lymphadenitis clinical presentation, 231t definition, 231 differential diagnosis and management, 232f infectious causes, 228t, 231 noninfectious causes, 228t Lymphadenopathy definition, 231 differential diagnosis and management, 232f infectious causes, 228t noninfectious causes, 228t, 231 Lymphocytes, 201t Lymphocytosis, 202t Lymphogranuloma venereum, 54t Lysosomal metabolism disorders, 191t M Macrocephaly, 191t, 192 Macrocytic anemia, 197 Macrolides, 222t, 440t Macular stain, 387t Macule, 109 Magnesium, 43t, 77 Magnesium sulfate, 92t Magnetic resonance angiography (MRA), 274t Magnetic resonance imaging (MRI) brain, 274t fetal, 359 in intracranial hemorrhage, 275t sedated, pre-procedural diet, 5t sequences and potential applications, 275t signal intensity, 274t Magnetic resonance spectroscopy (MRS), 274t Magnetic resonance venogram (MRV), 274t Malabsorptive syndromes, 179 Malassezia furfur, 119t Mallampati classification, 15, 16t Mallet finger, 307t Malnutrition in cystic fibrosis, 319t, 320 definition, 49 secondary immunodeficiency in, 65t severity determination, 183t Waterlow criteria, 49 Malrotation clinical presentation, 140, 473–474t diagnosis, 409t epidemiology, 473t management, 409t, 474–475t pathophysiology, 140, 473t Manganese, for direct hyperbilirubinemia, 420t Mannitol, 101, 102 Maple syrup odor, 189t Marijuana, 341t, 342t Mast cell stabilizer, 63t Mastoiditis, 126–127 May-Hegglin anomaly, 427t McBurney’s point, 139 Mead Johnson powder formulas, 46–47t Mean cell hemoglobin (MCH), 196t Mean cell volume (MCV), 196t Measles (rubeola), 116t

492

Index

Measles, mumps, rubella vaccine, 212t, 215t Mechanical ventilation adjustments affecting oxygenation and ventilation, 88t blood gases and clinical parameters in, 89 for bronchopulmonary dysplasia, 466t complications, 89 diuresis and metabolic alkalosis in, 89 fluids in, 88 modalities, 86–87t, 87–88, 88t in neonates, 374–375t for respiratory distress syndrome, 459t sedation and analgesia in, 88 stepwise approach, 86–90 weaning and extubation, 89–90, 90t Meckel’s diverticulum, 140 Meconium, delayed passage of, 409–410 Meconium aspiration, 366–367, 366f, 464–465t Meconium ileus, 320t, 409t Meconium plug, 409t Medial epicondyle traction apophysitis, 304t Medulloblastoma, 296–297t Melanocytic nevus, congenital, 387t Membranoproliferative glomerulonephritis, 260t Menarche, 151 Meningitis aseptic, 243, 245 definitions, 242 diagnosis, 243–244, 244t etiology, 243t follow-up, 246 isolation and prophylaxis, 246 management, 244–245, 245t neonatal, 441–442 prognosis, 246 risk factors, 243t Meningococcal vaccine, 212t Meningococcemia, 115t Mercaptopurine, 298t Mercury poisoning, antidote, 345t Meropenem, 221t, 323t, 440t Metabolic acidosis additional testing, 164–165t differential diagnosis, 164–165t general approach, 166f, 167–168 in inborn errors of metabolism, 189f, 191t neonatal, 189, 189f with partial compensation, 167–168t Metabolic alkalosis differential diagnosis, 165t general approach, 166f, 167–168 in mechanical ventilation, 89 with partial compensation, 167–168t Metacarpal fracture, 307t Metatarsal fracture, 310t Methadone, 13t, 14t Methanol, antidote, 345t Methemoglobinemia, 346t Methimazole, 149 Methotrexate, 298t, 423t

Methylprednisolone adverse effects, 316t for anaphylaxis, 61t for asthma, 316t equivalencies, 9t for status asthmaticus, 91t Metoclopramide, 292t Metronidazole, 226t for bacterial vaginosis, 53t for pelvic inflammatory disease, 56t for T. vaginalis infection, 53t Miconazole, 53t Microcephaly, 191t, 192 Microcytic anemia, 197f, 197t Midazolam adverse effects, 17t dosing, 17t onset and duration, 17t for status epilepticus, 103t weaning from, 20 Midgut volvulus, 140, 473–475t Migraine headaches complications, 282 diagnostic criteria, 281t prophylaxis, 282t status migrainosus, 283 treatment, 282t Milia, 386t Miliaria crystalline, 386t Miliaria rubra, 386t Milk of Magnesia, 179 Milk scan, pre-procedural diet, 5t Milrinone in neonatal resuscitation, 365t for shock, 96, 96t Minerals, in total parenteral nutrition, 44t Minimal change disease, 259t Minocycline, 223t Mite infestations, 119–120t Mitochondrial disorders, 191t Mixed connective tissue disease (MCTD), 329t Molluscum contagiosum, 118t Mometasone furoate, 123t, 124t Mongolian spot, 387t Monobactams, 221t Monocytes, 201t Monocytosis, 202t Monteggia fracture, 306t Montelukast sodium, 63t, 316t Moraxella, 125, 128 Morbilliform drug reaction, 120t Moro reflex, 271t Morphine dosing, 13t, 14t, 457 in neonates, 457 in patient-controlled analgesia, 14t Mosteller’s formula, body surface area, 4 Mothball odor, 341t Motor testing, 269t Mousy odor, 189t Moxifloxacin, 225t MRA (magnetic resonance angiography), 274t

Index MRI. See Magnetic resonance imaging (MRI) MRS (magnetic resonance spectroscopy), 274t MRV (magnetic resonance venogram), 274t Mucolytics, 321t Mucositis, 292 Multiple sclerosis (MS), 285t Murmur, asymptomatic, 380t Muscles, principal, 272–273t Muscular dystrophy, congenital, 453t Musculoskeletal complaints, differential diagnosis, 37 Mustard procedure, 82, 82f Myocarditis, 70–71, 70t Myoclonus benign neonatal sleep, 449t stimulus-evoked, 449t N N-acetylcysteine, 322t Nafcillin, 219t, 437t Nailbed laceration, 31t Nalidixic acid, 224t Naloxone, 13, 346t, 365t Naproxen, 12t Nasal cannula, for O2 delivery, 84t Nasal continuous positive airway pressure (NCPAP) for neonatal apnea, 470 for respiratory distress syndrome, 459t Nasal decongestants, 63t Nasoduodenal feeding, 38t. See also Enteral feeding Nasogastric feeding, 38t. See also Enteral feeding Nasogastric tube insertion, pre-procedural diet, 5t Nasojejunal feeding, 38t. See also Enteral feeding Nasojejunal tube insertion, pre-procedural diet, 5t Natal tooth, 108 Nausea. See Vomiting/nausea Neck laceration, 31t Necrotizing enterocolitis (NEC) clinical presentation, 416t diagnosis, 417 differential diagnosis, 417 management, 418 platelet consumption in, 427t prognosis, 418 risk factors, 415–416 staging, 416–417t Needle aspiration/decompression of pneumopericardium, 461t of pneumothorax, 21, 21t, 460t Neisseria gonorrhea, 53t Neisseria meningitidis, 115t Nemaline rod myopathy, 453t Neocate Infant, 157t Neocate Jr., 157t Neonatal cephalic pustulosis (neonatal acne), 386t Neonatal lupus erythematosus, 388t Neonatal resuscitation algorithm, 364f endotracheal tube sizes, 365t medications for, 364–365t preparation, 363

493

Neonatal resuscitation (cont.) risk factors, 363 triage, 366t umbilical catheter placement, 365–366 Neonatal tooth, 108 Neonates abnormal rashes in, 388–391t acute kidney injury in, 445–446 anemia in, 431–433 antibiotic use in, 437–440t Apgar score, 349t apnea in. See Apnea, neonatal bacterial meningitis in, 245t benign rashes in, 386–387t blood product transfusion in, 433t, 434–436t bronchopulmonary dysplasia in, 465–468t circumcision of, 350 complications of maternal medical conditions, 354, 355, 357t complications of maternal substance abuse, 357t congenital cystic adenomatoid malformation in, 475–477t congenital diaphragmatic hernia in, 475–477t conjunctivitis in, 443–444 cyanosis in, 353t delayed passage of meconium in, 409–410 discharge criteria, 376 discharge planning considerations, 376–377t duodenal atresia and stenosis in, 473–475t early discharge criteria, 349–350 encephalopathy in, 450–452 extracranial bleeding sites in, 352f gastric aspirates in, 414–415 gastroesophageal reflux disease in, 410–411 gastroschisis in, 471–472t group B streptococcal disease in. See Group B streptococcus (GBS) infections hydrocephalus in, 453–454 hyperbilirubinemia in. See Hyperbilirubinemia hypercalcemia in, 397–398, 397f hyperglycemia in, 403–404 hyperkalemia in, 395–396 hypernatremia in, 406–407 hypertension in, 446–447 hypocalcemia in, 398–401 hypoglycemia in, 188f, 404–406 hyponatremia in, 407–408 hypotonia in, 452 intraventricular hemorrhage in, 450, 450t jejunoileal atresia and stenosis in, 473–475t laryngomalacia in, 477–478 malrotation in. See Malrotation meconium aspiration in, 366–367, 366f, 464–465t meningitis in, 441–442 necrotizing enterocolitis in. See Necrotizing enterocolitis neuromuscular disorders in, 453 neuromuscular maturity assessment, 348 nonsterile delivery, 353 omphalocele in, 471–472t pain management in, 456–457 persistent pulmonary hypertension in, 462–464t

494

Index

Neonates (cont.) physical exam, 350–351t physical maturity assessment, 348 pulmonary air leak syndromes in, 459–462 respiratory distress in, 353t respiratory distress syndrome in, 458–459t resuscitation. See Neonatal resuscitation routine care, 348–349 seizures in, 448–449 sepsis evaluation and empiric treatment, 369f skin and soft tissue infections in, 234 stridor in, 352t thrombocytopenia in, 425–428 transient tachypnea in, 458, 458t vomiting in, 352t Nephritic syndromes management, 261 overview, 258, 259t primary, 260t prognosis, 261 secondary, 260t workup, 260 Nephrogenic diabetes insipidus, 150–151t Nephrotic syndromes complications, 261–262 management, 261 overview, 258, 259–260t primary, 260t prognosis, 261 secondary, 260t secondary immunodeficiency in, 65t workup, 260–261 Nepro, 157t Nesiritide, 73 Nestle powder formulas, 46–47t Netherton syndrome, 389t Neuroblastoma, 295–296 Neuroimaging modalities, 274t Neuroleptics, antidote, 346t Neurologic exam, 268–270 Neuromuscular blockade, in traumatic brain injury, 102 Neuromuscular disorders, 453 Neuromyelitis optica (NMO), 285t, 286 Neutropenia in inborn errors of metabolism, 189 as oncologic emergency, 289 Neutrophilia, 202t Neutrophils, 201t Nevus sebaceous, 387t Nevus simplex, 387t Newborns. See Neonates Nitric oxide, inhaled (iNO) for persistent pulmonary hypertension, 463t for preterm infants, 373 Nitrite, in urine, 256t Nitroimidazoles, 226t Nodule, 109 Non-stress test, 360 Nonbullous congenital ichthyosiform erythroderma, 388t Nonimmune fetal hydrops, 421–422t

Noninvasive positive pressure ventilation, 86t Nonopioid analgesics, 12, 12t. See also specific drugs Nonrebreather face mask, for O2 delivery, 85t Norepinephrine, 96t, 97f Normal saline (NS), 158t, 264t Norwood procedure, 81, 82f Notes discharge summary, 2 on-service, 1 progress, 1–2 Nursemaid’s elbow, 305t Nutramigen Lipil, 157t Nutren 1.0, 156t Nutren 2.0, 156t Nutren Jr., 156t Nystatin, 119t O Obstructive lung disease, 326t. See also Asthma; Cystic fibrosis Obstructive shock, 94t, 95t Obstructive sleep apnea, 128, 129f Obturator sign, 139 Oculomotor nerve, 268t Odontogenic infections, 108 Odors abnormal, 189–190t of agents of intoxication, 341t Ofloxacin, 224t Old fish odor, 189t Olecranon fracture, 306t Olfactory nerve, 268t Omalizumab, 316t Omphalocele, 471–472t On-service notes, 1 Oncologic emergencies fever and neutropenia, 289 hyperleukocytosis, 291 hypersensitivity reactions to infusions, 290–291t spinal cord compression, 289–290 tumor lysis syndrome, 289 Ondansetron, 292t Ophthalmia neonatorum, 443–444 Opioid analgesics. See also specific drugs antidote, 346t conversion between, 14, 14t dosing, 13t, 14t indications, 13 in patient-controlled analgesia, 13, 14t toxidrome, 345t urine testing, 342t weaning from, 14–15 Optic nerve, 268t Oral hygiene, 106, 212t Oral rehydration solutions and formulas, 156–157t strategies, 155–156 Orders admission, 1 discharge, 1 preoperative, 1

Index Organ systems, embryonic development from weeks 3 to 7, 186t Organic acidemias, 194f Organic acidurias, 191t Organophosphates, antidote, 346t Ornithine transcarbamylase (OTC) deficiency, 193t, 194f Orogastric feeding, 38t. See also Enteral feeding Osgood-Schlatter disease, 308t Osteochondritis dissecans, femur, 309t Osteopenia of prematurity, 401–403 Osteopetrosis, infantile, 400t Ostium primum, 66 Ostium secundum, 66 Otitis media, acute, 125–126 Otitis media with effusion (OME), 126 Oxacillin, 219t Oxazolidinones, 223t, 440t Oxcarbazepine, 280 Oxycodone, 13t, 14t Oxygen delivery modes, 84–85t P P. aeruginosa, in cystic fibrosis, 318t, 322–323t Pacemakers, 77 Packed cell volume, 196t Packed red blood cells (PRBCs), 206t, 433t, 434t Pain assessment, 11, 11f Pain management in neonates, 456–457 nonpharmacologic, 11 pharmacologic. See also specific drugs nonopioid analgesics, 12, 12t opioid analgesics. See Opioid analgesics patient-controlled analgesia, 13, 14t topical preparations, 11–12t Palivizumab, 378 Palmar grasp, 272t Palmomental reflex, 270t Pancreas, annular, 140 Pancreatic enzyme replacement therapy, 321t Pancreatic insufficiency, in cystic fibrosis, 318t Pancreatitis, 176–178t Pancrelipase, 321t Pancytopenia, 202t Papile’s grading, intraventricular hemorrhage, 450t Papular acrodermatitis, 117t Papule, 109 Paracentesis, in ascites, 174 Paracoccidioidomycosis, 227 Paramyxovirus, 116t Partial rebreathing face mask, for O2 delivery, 85t Parvovirus B19, 116t Patch, 109 Patellar fracture, 308t Patent ductus arteriosus (PDA), 67, 379–380 Patient-controlled analgesia (PCA), 13, 14t PCP, 341t Peak flow monitors, 313 Pear odor, 341t

495

Pedialyte, 156t PediaSure, 156t Pediatric Appendicitis Score (PAS), 139t Pediatric systemic lupus erythematosus (pSLE), 329t, 331–332 Pediculosis pubis, 56 Pediculus capitis, 120t PEG 3550, 179 PEG-electrolyte solution, 179 Pelvic examination, 51–52, 51t Pelvic fracture, 308t Pelvic inflammatory disease, 55–56t Penicillin G, 218t Penicillin G benzathine, 54t, 218t Penicillin GK, 437t Penicillin V, 218t Penicillins, 218–219t Penis laceration, 31t noncircumcised, care of, 350 Pentobarbital, 18, 18t, 103t Percutaneous umbilical blood sampling, 359 Perianal streptococcal dermatitis, 390t Pericardial disease, 71–72, 71f Pericardiocentesis, 462 Peripheral nerves, 270–271f Permethrin, 120t Peroxisomal metabolism disorders, 191t Persistent pulmonary hypertension, 462–464t PG, 355t pH, urine, 254t Phalanx fractures, 307t, 311t Phencyclidine, 342t Phenobarbital, 104f, 280t Phenotype matching, extended, 206 Phenytoin/fosphenytoin, 279t, 423t Phosphate deficiency, 152t Phosphate enema, 179 Phosphorus, daily requirement, 43t Photodrug reaction, 123t Phototherapy, for hyperbilirubinemia, 413f, 414t Physical abuse, 141–142 Pigtail catheter placement, 460t, 461–462 Pinna laceration, 31t Piperacillin, 219t, 437t Piperacillin–tazobactam, 219t Pityriasis alba, 112t Pityriasis rosea, 112t Plan B, 59 Plaque, 109 Plasma glucose, 143t Plasma transfusion, 207, 435t Plasma volume (PV), 208 Platelet disorders, 203f, 427t Platelet transfusion, 206t, 207, 435t Pleural effusions, 239t Pleural fluid analysis, 236t Pneumococcal vaccine, 213t, 214t Pneumococcus, 125, 127 Pneumomediastinum, 461t

496

Index

Pneumonia community-acquired complications, 237 definition, 234 diagnosis, 235–236, 236t etiologic agents, 234–235t inpatient management, 237–239 outpatient management, 237t risk factors, 235t in cystic fibrosis, 235t, 318t, 319 nosocomial or hospital-associated, 239 Pneumopericardium, 461t Pneumothorax in cystic fibrosis, 320t needle decompression, 21, 21t in neonates, 460t Poisoning antidotes, 345–346t commonly ingested substances, 340 history, 341 initial evaluation, 340f physical exam findings, 342–344t secondary survey, 341 substances detectable with conventional radiography, 342t substances with unique odors, 341t toxidromes, 344–345t urine color changes associated with, 342t urine testing, 342t Poliovirus vaccine, 212t, 215t Polyarteritis nodosa, 332t Polycythemia clinical presentation, 428, 429t definition, 428 differential diagnosis, 428t exchange transfusion for, 430t. See also Exchange transfusion management, 429, 429t in nonphysiologic hyperbilirubinemia, 412t Polymyositis, 329t Portal hypertension, 172 Potassium conversion, 43t daily requirement, 43t, 153 ECG changes and, 76 Potassium channel blockers, as antiarrhythmics, 77t Potts shunt, 81 Poxvirus, 118t PRBCs (packed red blood cells), 206t, 433t, 434t Precocious puberty, 151 Prednisolone adverse effects, 316t for asthma, 316t equivalencies, 9t for status asthmaticus, 91t Prednisone adverse effects, 316t for asthma, 316t as chemotherapy agent, 299t equivalencies, 9t for status asthmaticus, 91t

Preeclampsia, 356 Pregabalin, 280t Pregestimil, 157t Pregnancy diabetes mellitus during, 355, 357t, 399t fetal chromosomal abnormalities screening during, 354, 358, 358t fetal lung maturity evaluation during, 355, 355t genetic diagnosis during, 358–359 hypertension in, 356, 356t immunization during, 216t teratogenic agents in, 187, 423–424t ultrasound screening during, 354 Prehn’s sign, 132t Prenatal care. See Pregnancy Preoperative orders, 1 Prescriptions, essential components, 2 Pressure regulated volume control (PRVC, VC+), 87t Pressure support (PS) ventilation, 374t Preterm infants admission orders, 372–373 cardiovascular care, 370–371t catch-up times, 4 CSF profiles, 442t developmental follow-up, 378 discharge criteria, 376 discharge planning considerations, 376–377t feeding enteral, 39 formulas, 46 total parenteral nutrition. See Total parental nutrition (TPN) vitamin and mineral supplementation, 35t fluid/electrolyte management, 371t growth chart, 50f hypothyroxinemia in, 394–395, 394f infection control, 372t nitric oxide administration, 373 nutrition, 372t osteopenia in, 401–403 respiratory care, 370t retinopathy of prematurity in, 454–455, 454f RSV prophylaxis, 378 secondary immunodeficiency in, 64t sepsis evaluation and empiric treatment, 370f surfactant administration, 373–374t ventilation modes, 374–375t PRICEMMMS mnemonic, for treatment of acute musculoskeletal injury, 301–302 Primary immunodeficiency, 63, 63t Primitive reflexes, 270t, 271–272t Progress note (SOAP note), 1–2 Promethazine, 292t Propofol, 18, 19t, 103t Propranolol, 282t Propylthiouracil, 149 Prostaglandin E1, 384–385 Protein, DRI by age, 41–42t Protein hydrolysate formulas, 46 Proteinuria, 255t, 257–258 Proton pump inhibitors (PPIs), 169 Pseudohyperkalemia, 158

Index Pseudohypoaldosteronism, 392t Pseudohypokalemia, 160 Pseudomonas, 127 pSLE (pediatric systemic lupus erythematosus), 329t, 331–332 Psoriasis, 113t, 391t Pubarche, 151–152 Puberty, 151–152 Pulmocare, 157t Pulmonary air leak, in neonate complications, 460–461t management, 460–461t pathophysiology, 459–460 procedures, 461–462 risk factors, 459 syndromes, 460–461t Pulmonary artery banding, 82 Pulmonary atresia with intact ventricular septum (PA/IVS), 69–70, 69f Pulmonary blood flow, abnormal, 381 Pulmonary function testing (spirometry), 325–326 Pulmonary hypoplasia, 475–477t Pulmonary interstitial emphysema, 461t Pustule, 109 PV (plasma volume), 208 Pyloric stenosis, 140 R Rabies prophylaxis, 135 Radial head subluxation, 305 Radionuclide cystogram (RNC), 242t Radius fractures, 305t Ranitidine, 61t Rastelli operation, 82 Reactive arthritis, 327t Red blood cells (RBCs) normal values, 196t transfusion, 206, 206t, 208 in urine. See Hematuria Red urine, 252–254, 253f Refeeding syndrome, 59 Rehydralyte, 156t Renal flow study, pre-procedural diet, 5t Renal salt wasting (cerebral salt wasting), 150t Renal scan, pre-procedural diet, 5t Renal stones, 140 Renal ultrasound, 242t Respiratory acidosis, 165–168 Respiratory alkalosis, 165–168, 191t Respiratory distress, in neonates, 353t Respiratory distress syndrome (RDS), 458–459t Respiratory failure classification, 83 clinical predictors, 83 management mechanical ventilation. See Mechanical ventilation noninvasive ventilation modalities, 85–86t oxygen delivery modes, 84–85t pathophysiology, 84f workup algorithm, 83f

497

Respiratory syncytial virus (RSV), prophylaxis, 378 Restrictive lung disease, 326t Resuscitation, neonatal. See Neonatal resuscitation Retinitis pigmentosa, 192 Retinoic acid, 424t Retinopathy of prematurity (ROP), 454–455, 454f Retropharyngeal abscess, 136–137t rhDNase, 321t Rhinitis, 127 Rickets, 152t Rickettsia rickettsii, 115t Rifampin, 226t Rifamycins, 226t Right ventricular hypertrophy (RVH), 75 Riley–Day syndrome, 453t RNC (radionuclide cystogram), 242t Rocky Mountain spotted fever, 115t Romberg test, 269 Root reflex, 272t Roseola (exanthem subitum), 116t Ross procedure, 82 Rotavirus, 213t, 214t Rotten egg odor, 341t Rovsing’s sign, 139 Rubella (German measles), 116t Rubeola (measles), 116t Rumination, 169 S Salicylism, 345t Salter-Harris fracture classification, 302, 302f Sandifer syndrome, 169 Sarcoptes scabiei, 119–120t Sarnat stages of hypoxic-ischemic encephalopathy, 451t Scabies, 56, 119–120t Scale, 109 Scalp laceration, 30t Scapular fracture, 303t Scar, 109 Scarlet fever, 114t Schwartz formula, for GFR estimate, 250 Scleroderma, 329t Screening recommendations, 209–211t, 212t Scrotum laceration of, 31t pain and swelling in, 131–132t Seborrheic dermatitis, 111t, 391t Secondary immunodeficiency, 64–65t Sedation continuum of, 15 discharge criteria, 19, 20t emergency equipment, 16, 16t medications, 16–19, 17t, 18–19t monitoring following, 19 patient preparation, 15–16, 15t, 16t Sedative-hypnotics, toxidrome, 345t Segmental fracture, 302

498

Index

Seizures. See also Epilepsy breakthrough in known epilepsy, 277 classification, 275–276t evaluation of first nonfebrile, 276–277 neonatal, 188, 448–449 in poisonings, 343t practice parameters, 275 simple febrile, 276 Selenium sulfide shampoo, 118t Self-mutilation, 192 Senna, 179 Senning procedure, 82 Sensory testing, 269 Sepsis, 94t in preterm infant, evaluation and empiric treatment, 370f in term infant, evaluation and empiric treatment, 369f Septic arthritis, 134t, 327t Septic shock, 94t Serum sickness-like reaction, 121t Severe sepsis, 94t Sever’s disease, 310t Sexual development, 151–152 Sexually transmitted infections, 53–54t, 212t Shaken baby (shaken impact) syndrome, 142 Shingles (herpes zoster), 117t Shock classifications, 95–96t clinical findings, 94t clinical pearls, 96, 98 definition, 93 management, 95–96t, 97f in sepsis, 94 stages, 93 Shoulder dislocation, 303t Shoulder fractures, 303t SI units, laboratory value conversion table, 8t SIADH (syndrome of inappropriate antidiuretic hormone), 150t Sick euthyroid syndrome, 149 Sickle cell disease diagnosis, 199 health maintenance in, 200t immunizations in, 217t pneumonia in, 235t secondary immunodeficiency in, 64t signs and symptoms, 199–200t treatment, 199–200t Similac Advance, 156t Similac HMF, 48t Simple febrile seizure, 276 Simple partial seizure, 275t. See also Seizures SIMV (synchronized intermittent mandatory ventilation), 87t, 88t, 374t Sinding-Larsen-Johansson syndrome, 308 Sinus tachycardia, 75t Sinus venosus, 66 Sinusitis, 128, 319t SIRS (systemic inflammatory response syndrome), 94t Sjögren’s syndrome, 329t

SJS (Stevens-Johnson syndrome), 122t Skin infections, 233–234 Skin lesions, 109–110t Sleeve fracture, 308t Snoring, 129f Snout reflex, 270t SOAP equipment, for sedation, 16 SOAP note (progress note), 1–2 Sodium, 43t, 153 Sodium bicarbonate, in neonatal resuscitation, 365t Sodium channel blockers, 77t Soft tissue infections, 233–234 Soy-based formulas, 46 Specific gravity, urine, 254t Spinal accessory nerve, 268t Spinal cord compression, 289–290 Spinal muscular atrophy type 1, 453t Spirometry (pulmonary function testing), 325–326 Spironolactone, 174 Splenic sequestration crisis, 199t Spondylolisthesis, 301 Spondylolysis, 301 Sporotrichosis, 227 Sprains, 301–302 Staphylococcal scalded skin syndrome, 115t, 389t Staphylococcus aureus in cellulitis, 114t in cystic fibrosis, 318t, 322–323t in folliculitis, 113t in impetigo, 113t in mastoiditis, 127 in skin abscess, 114t superinfection in eczema, 110t StAR (acute steroid regulatory protein) deficiency, 392t Startle reflex, 271t STATS, for intubation preparation, 86 Status asthmaticus clinical respiratory score, 90–91t definition, 90 management advanced, 92–93 clinical pearls, 93 first-line, 91t second-line, 92t risk factors for ICU admission and sudden death, 90 symptoms, 90 Status epilepticus, 102–103 causes, 103 clinical pearls, 103 management algorithm, 104f medications, 103t types, 103 workup, 105f Status migrainosus, 283 Steatohepatitis, 171t Stevens-Johnson syndrome (SJS), 122t Stiff-man syndrome, 449t Stimulant laxatives, 179 Stimulus-evoked myoclonus, 449t Strains, 301–302

Index Streptococcus pneumonia, 128 Streptococcus pyogenes, 113t Streptomycin, 224t Stress factors, energy expenditure, 41t Stridor, 135–137, 352t Stroke, in sickle cell disease, 200t Subclavian vein (SCV), 26 Substance abuse in pregnancy, 357t street names of drugs of abuse, 341t urine testing for, 342t Sucrose, oral, 12, 456 Sulfonamides, 225t Sulphur odor, 190t Sumatriptan, 282t Superior cavopulmonary anastomosis, 81, 81f Suplena, 157t Supracondylar fracture, elbow, 304t Supraventricular tachycardia (SVT), 75t Surfactant, for preterm infants, 373–374t Sutures cranial, 4 for laceration repair, 30–31t Swallow study, pre-procedural diet, 5t Sweat chloride test, 317, 317t Sweaty feet odor, 190t Synchronized intermittent mandatory ventilation (SIMV), 87t, 88t, 374t Syncope, 79 Syndrome of inappropriate antidiuretic hormone (SIADH), 150t Synovial fluid, evaluation, 327t Syphilis, 54t, 212t Systemic inflammatory response syndrome (SIRS), 94t Systemic lupus erythematosus, 329t, 331–332, 388t T Tachycardia, 75t, 76f Takayasu arteritis, 332t Tanner stages, 151–152t TAPVR (total anomalous pulmonary venous return), 68, 68f TAR (thrombocytopenia-absent radii) syndrome, 428 TBV (total blood volume), 208 Teeth, 107, 107f, 108 Teething, 107 Temperature, conversion formulas, 4 TEN (toxic epidermal necrolysis), 122t Tension type headache, 283 Teratogens, 187, 423–424t Terbutaline, 92t Terconazole, 53t Testicular torsion, 131–132t Tetanus prophylaxis, 32, 32t Tetracycline, 223t Tetracyclines, 223t Tetralogy of Fallot (TOF), 67–68, 67f, 81, 81f TGA (transposition of the great arteries), 68, 68f, 81, 82, 82f α-Thalassemia, 199t

499

β-Thalassemia major, 199t β-Thalassemia minor, 197t, 199t Thelarche, 151–152 Thiazides, for bronchopulmonary dysplasia, 467t Thioguanine, 298t Thrombocytopathy, 203f Thrombocytopenia alloimmune, 426–427t autoimmune, 426–427t congenital, 428 with decreased platelet survival, 427t differential diagnosis, 203f, 425f idiopathic, 202 in inborn errors of metabolism, 189 in neonates, 425–428 Thrombocytopenia-absent radii (TAR) syndrome, 428 Thromboembolism, 205t Thrombophilia, 205t Thumb fractures, 306–307t Thyroid storm, 149 Thyroiditis, 147, 149 Ticarcillin, 219t Ticarcillin/clavulanic acid, 323t Ticarcillin–clavulanate, 219t Tinea capitis, 118t Tinea corporis, 118t Tinea cruris, 118t Tinea pedis, 118t Tinea versicolor, 119t Tinidazole, 53t Tobramycin, 224t, 322t, 438t Toddler fracture, 309t TOF (tetralogy of Fallot), 67–68, 67f, 81, 81f Tonic neck reflex, 272t Topical anesthetics, 11–12t Topiramate, 280t, 282t Total anomalous pulmonary venous return (TAPVR), 68, 68f Total blood volume (TBV), 208 Total parental nutrition (TPN) carbohydrate/amino acid requirements and rate, 42, 43t complications, 44 electrolyte requirements, 43t energy requirement, 40–41, 40t, 41t final check, 44–45 intravenous fluid requirement, 39–40, 40t laboratory monitoring, 45t lipid requirements and rate, 42 protein requirement, 41–42t stress factors, 41t vitamins, minerals, and trace elements, 44t Toxic epidermal necrolysis (TEN), 122t Toxic shock syndrome, 115t Toxicology. See also Poisoning collection tube colors, 7t SI laboratory value conversion table, 8t Toxidromes, 344–345t Trace elements, in total parenteral nutrition, 44t Traction apophysitis of proximal humerus, 303t Transient neonatal pustular melanosis, 386t

500

Index

Transient synovitis, 134t Transient tachypnea of the newborn (TTN), 458, 458t Transposition of the great arteries (TGA), 68, 68f, 81, 82, 82f Trauma, nonaccidental, 141–142 Traumatic arthritis, 327t Traumatic brain injury, 101–102 Treponema pallidum, 54t Triamcinolone, 10t Triamcinolone acetonide, 123t, 124t Trichomonas vaginalis infection, 52–53t Tricuspid atresia, 69, 69f Tricyclic antidepressants antidote, 346t poisoning/overdose, 347t toxidrome, 345t Trigeminal nerve, 268t Trimethoprim/sulfamethoxazole, 225t, 322t Trisomy 13, 422–423t Trisomy 18, 422–423t Trisomy 21 (Down syndrome), 64t, 183, 184–185t, 422–423t Trochlear nerve, 268t Truncus arteriosus, 68–69, 68f, 82 Trunk laceration, 31t Tube colors, for lab samples, 6, 7t Tuberculosis screening, 212t Tuberculous arthritis, 327t Tumor, 109 Tumor lysis syndrome, 289 Turner syndrome, 64t Tympanostomy tube, 126 Type 1 diabetes mellitus. See Diabetes mellitus Type 2 diabetes mellitus. See Diabetes mellitus U Ulcer, 109 Ulcerative colitis clinical features, 180t definition, 179 endoscopic features, 181t epidemiology, 180t prognosis, 182 radiographic features, 181t treatment, 181–182, 182t Ulna fractures, 306t Ultrasonography cranial, 274t, 376t fetal, 354, 357, 358 pre-procedural diet, 5t Ultraviolet B exposure, secondary immunodeficiency and, 65t Umbilical artery catheterization (UAC), 27–29, 28f, 28t, 365 Umbilical blood sampling, percutaneous, 359 Umbilical vein catheterization (UVC), 28f, 29–30, 29t, 365–366 Unconjugated (indirect) hyperbilirubinemia, 175–176 Unfractionated heparin (UFH), 205t Upper extremity fracture, 303–306t

Upper GI series, pre-procedural diet, 5t Upper motor neuron lesions, 272t, 452t Urea cycle, 194f Urea cycle defects, 191t, 193–194t, 195f Uremia, secondary immunodeficiency in, 64t Urinalysis, 254–256t Urinary tract infections definition, 239 diagnosis, 240, 241t etiologic agents, 240 imaging modalities, 242t management, 241 prevention, 241 risk factors, 239 Urine discoloration, 190t, 342t organic acid analysis, 193 unusual odors, 189–190t Urine culture, 241t Ursodeoxycholic acid (UDCA), 420t Urticaria, 61–62, 120t V Vaccines/vaccinations. See Immunizations Vaginitis, 52–53t Vagus nerve, 268t Valacyclovir, 55t Valgus, 301 Valproic acid, 280t, 282t, 423t Valvotomy, 82 Valvuloplasty, 82 Vancomycin, 222t, 323t, 438t Varicella zoster virus, 116t, 117t Varicella zoster virus immunization, 212t, 215t Varices, 173 Varus, 301 Vasculitides, 332t, 334f Vasopressin, for shock, 96, 96t VATER/VACTERL association, 187 Vaughan-Williams classification, antiarrhythmics, 77t Ventricular septal defect (VSD), 66 Venturi mask, for O2 delivery, 84t Verruca vulgaris, 117t Very low birth weight infants, 369. See also Preterm infants Vesicle, 109 Vesicoureteral reflux (VUR), 262–263 Vinblastine, 299t Vincristine, 299t Vision screening, 212t Vitamin A, for prevention of bronchopulmonary dysplasia, 466t Vitamin D deficiency, 152t, 400t, 402t Vitamins, in total parenteral nutrition, 44t Voiding cystourethrography (VCUG), 5t, 242t, 262 Volume guarantee (VG) ventilation, 374t Volvulus, 410t Vomiting/nausea chemotherapy-related, 291–292 with enteral feeding, 39t in neonates, 352t von Willebrand disease, 204t

Index W Warfarin, 205t, 423t Waterlow criteria, malnutrition, 49 Waterston shunt, 81 Weakness, childhood, 286–287t Wegener granulomatosis, 329t, 332t Weight by age for boys, 2t by age for girls, 3t at birth, 3 conversion, 4 by gestational age, 50f rate of gain, 3 Werdnig–Hoffmann disease, 453t West syndrome, 278t Wheal, 109 Wheezing, 312 White blood cells (WBCs) normal values, 201t in urine, 256t Wilson’s disease, 171t

Wintergreen odor, 341t Wiskott-Aldrich syndrome, 427t Withdrawal, 342–344t World Health Organization (WHO), oral rehydration solution, 156t Wounds repair, 30–31t, 30–32 tetanus prophylaxis, 32, 32t Wrist fracture, 306t X X-linked hypophosphatemia, 152t Xanthines, for neonatal apnea, 469 Y Yeast vaginitis, 52–53t Z Zafirlukast, 316t Zinc, oral, 156 Zolmitriptan, 282t Zonisamide, 280t

501