Pocket.pediatrics

N OT E B OO K

The MassGeneral Hospital fo r Childreir Handbook o f Pediatrics

jWolters Kluwer Lippincott Health Williams & Wilkins

POCKET NOTEBOOK

IATRICS Second Edition

E d ited by

P a r it o s h P r a s a d ,

MD, DTM&H

The MassGeneral Hospitalfo r Childrerr Handbook o f Pediatrics

0 , Wolters Kluwer I Lippincott Williams & W ilkins Philadelphia • Baltimore • York • Landon Buenos Aires • Hcng Kong • Sydney • Tokyo

A B B R E V IA T IO N S A A - abdom inal a orta A b - antibody abd — abdomen A B G - a rterial blood gas abn - abnorm al A b so rp - a bsorptlon A b x - antlbiotics accel - accelerate accum - accum ulation ACEI - anglotensin co nverting enzyme in hiblto rs A cq - acqulred adenoCa - adenocarclnom a adj - adjacent adol - adolescent adolesc - adolescent A fib - atrial fib rllla tio n A flu tte r - atrial flu tte r Ag - antlgen a lk phos - alkaline phosphatase A m p - am plltude o r am plcillin depending on c o n te x t a m t - am ount A m y - amylase A N A - a nti-nuclear antibody A N C - actlvated n eu tro ph il co un t anom - anomalous antag - antagonlst a n te r - a n te rio r antlchol - antlcholinerglc AR - a o rtic re g u rg ita ro n ARB - anglotensin re c e p to r blocker AS - a o rtic stenosis ASA - asplrln A S D - atrial septal defect assoc - associated asym - asym m etric avg - average A z ith ro - azithrom ycln bact - bacterial BB - beta b locker b/c - because bld - blood BNP - braln natueretic peptlde BP - bloo d pressure bpm — beats per m inute brady - bradycardia b tw - between B U N - bloo d urea nitrogen bx - blopsy carbs — carbohydrates cath - catheterizatlon C B C - com plete blood co un t c/b - com plicated by C C B - calclum channel blocke r C D H - congenital diaphragmatlc hernia CF - cystlc fibrosis C H D - congenital h ea rt dlsease chem o - chem otherapy C H F - congestive h ea rt fallure c h orio - chorioa m n lo nltis

ch ro m o - chrom osom e chrono - chronological C lp ro - ciprofloxacln circ - circum clslon C K D - chronlc kldney disease clinda - cllndam ydn C M V - cytom egalovlrus coags - coagulatlon studies co arct - coarctatlon co lo - coloscopy com m unic - com m unication compens - com pensation conc - co ncentration congen - congenital conj - conjugated constip - co nstip aron consump - consum ption C o rt - co rtic o s te ro ld C r - creatinine C rC I - creatinine clearance cres-decres - crescendo-decrescendo c r lt - crlte rla C TA - clear to auscultaron C T D - connective tissue dlsease C T X - chest x-ray o r ceftrlaxone ex - cultures C X R - chest x-ray d/c - discontinué D C M - dilated cardiomyopachy D d x - differential diagnosis dec - decrease decom p - decompression degen — degenerative dehyd - dehydratlon deliv - delivery depol - depolarized deprlv - deprlvation D erm - derm atology desc - descending dev - developm ent D e x - dexamechasone diff - differential d¡g - dlgoxin discrep - dlscrepancy dlssem - disseminated D M - diabetes m ellitus d /o - dlsorde r D O L - day o f Ufe d s D N A - double-stranded D N A D TR - deep tendón reflex dx - diagnosis dysfxn - dysfuncclon dz - disease EBV - E pste in -B arr virus ED - emergeney dep artm en t EMG - e le ctro myelograph eos - eosinophils epi - epinephrine epo - epoetin alfa E ryth ro - e rythrom ycin esoph - esophageal

esp - especially ESR - e ryth ro cyte sedim entation rate essent - essential E tO H - alcohol eval - evaluation evid - evidence exacerb - exacérbate exp - e xp ira to ry explan - explanatlon e x t - e xtre m ity FB - foreign body FHx - fam ily h isto ry FMF - famillal M edlterranean fever func - functlon f/u - fo llo w up fx - fra ctu re o r functlon depending fxn - function GAS - g roup A Streptococcus G astro - gastroenteritis G ERD - gastro-esophageal reflux disease gest — gestatlon gluc - glucose G V H D - gra ft versus host dlsease Gyn - gynecology H A - headache H c t — h e m a to crit H lb - Haem ophllus Influenza B H IV — human ¡m m unodeficlency virus H o N a - hyponatrem ia H o T N - hypotension H&P - h isto ry and physical HR - heart rate HSM - hepacosplenomegaly H T N - hypertension H x - h istory hyperaldo — hyperaldosteronlsm H yperC a - hypercalcemia hypercoag - hypercoagulabillty hyperK - hyperkalemia H yperN a - hypernatremla hyperphos - hyperphosphatem la h ypervent - hyperventllatlon H ypoC a - hypocalcemia H yp oN a - hyponatremia hypophos - hypophosphatemia hypoplast - hypoplastic Ig - im m unoglobulin im m unocom p - ¡m m unocom prom ised im p e rf - ¡m perforate ¡m prov - ¡m provem ent ¡nadeq - ¡nadequace inc - ¡ncrease ¡ncld - ¡ncidence ¡ncomp - ¡ncom patlbllity ¡nflamm - ¡nflam m atory in fxn - in fection ing - ingestión ¡nhib - ¡n h lbito r innom in - innom inate inpts - ¡npatients

inslg - ¡nsignlficant ¡nsp - ¡nsplratory Insuff - insufficient intracard — incracardlac ¡ntravag - ¡ntravaglnal inv - inverted ¡rreg - irregular IVF - intravenous flulds IVIG — Intravenous im m unoglobulin jnts - jo in ts JVD - jugular venous distensión JVP - jugular venous pressure LA - le ft arm L A D - lym phadenopathy Leuks - leukocytes Levo - Levofloxacin LFT - live r function tests LL - le ft leg LLSB - le ft lo w e r sternal b o rd e r LN - lymph nodes L O C - loss o f consclousness LUSB - le ft upper sternal b o rd e r LV - left ventrlcle LVH - left v e n trlcu la r hype rtro ph y lym p b o p ro llf - lym phoproliferative m aint - malntenance Malfxn - m alfunction maiig - malignancy/malignant m alnut - m a ln utrltion m at - maternal max - máximum M . cat - Moraxella catorrhalis mee - m econium mech - mechanism meds - medicatlons m gm t - management MI - myocardial ¡nfarction M in e ra lo c o rt - m ln e ra lo co rtico id M ito c - m itochondrlal m od - m odérate monic - m o n ito r MR - m itra l re g u rg ita ro n MS - m itral stenosls m u ltl - m últiple muse - muscular m u t - m utatlon MV — m itral valve m vm t - m ovem ent MVP — m itral valve prolapse nec — necrotizlng NE C - necrotizing e nte ro colitis neonat - neonatal N H L - N o n-H o dg ld n lym phom a N IC U - neonatal ¡ntenslve care u nit N K C s - natural k llle r cells nml - norm al N. mening - Neisseria meningitidis nontyp - nontypeable norepi - norepinephrine N S A ID - non-steroidal antl-inflam m atory drug N /V - nausea/vomltlng

PA - p ulm onary a rte ry palp’s - palpitations PALS - pediatric advanced life supporc Pancr - pancreatic parasymp - parasympachetic PCN - penicillin PCR - polym erase chain reacción PDA - patent ductus arteriosus PE - pulm onary embolism peds - pediatrics periph - peripheral PFT - pulm onary function test Phenobarb - phenobarbital pheo - pheochrom ocytom a p H T N - pulm onary hypercension Plts - platelecs PMI - p o in t o f maxlmal impulse PMNs - p olym orphonuclear cells P N A - pneumonía PO — per oral p olya rtic - polya rticu la r pop - population poss - possible p ost - p o s te rio r PPI - p ro to n pum p ¡n h ibito r pRBCs - packed red blood cells p redom - p redom inant Preg - pregnancy pres - pressure prev — previous PRN - p er requested need prog - prognosis progest - progestin pro ph y/pp x - prophylaxis p ro t - pro te in p ro x - proxim al PS - pulm onic stenosis p t - patient PTX - p ne um oth orax pulm - pulm onary PVM - pulm onary venous markings PVR - p ulm onary vascular resistance p /w - presents w ith pyelo - pyelonephritis RA - righ t arm RA D - reactive airway disease RAE - rig h t atrial enlargem ent RBBB - rig h t bundle branch block RCT - random ized c o n tro lle d tria l rec - recom m endation refrac - re fra c to ry regurg - re g u rg ita ro n renovase - renovascular req - required resp - response resusc - resuscitation resxn - resección re tic - reticulocyte

RF - rh e um a toid fa cto r rhabdo - rhabdom yolysis rp t - repeat RSV - re sp ira to ry syncytial virus RV - rig h t vencricle RVH - rig h t ve n tricula r h ype rtro ph y RVOT - righ t ve n tricula r o u tflo w tra c t Rx - tre a tm e n t rxn - reaction sat - saturation SBI - spontaneous bacterial infección SBP - systolic blood pressure SEN - systolic ejection m u rm u r sens - sensitivity sev - severe sign - significan! signif - significant sinopulm - sin opulm onary SOB - shortness o f breath spec - specificity S. pneumo - Streptococcus pneumoniae sp on t - spontaneous SSRI - selective sero to n in reuptake ¡nh ibito r Staph/S. aureus - Staphylococcus oureus std - standard STI - sexually tra nsm itte d infection subclav - subclavian subseq - subsequent suff - sufficient sugg - suggests suppl - supplem entation supravent - supraventricular Surg - surgery SVR - systemic vascular resistance SVT - supra-ventricular tachycardia sx - sym ptom s symp - sym pathetic syn - syndrom e sz - seizure szr - seizure tachy - tachycardia TB - tuberculosis thal - thalassemia col - tolerance to x - to x ic ity TR - tricu sp id re g u rg ita ro n TS - tricu sp id stenosis T V - tricuspid valve uncirc - uncircum cised U ncom p - uncom plicated univ - universal unk - unknow n URI - upper re sp ira to ry infección U ro - urology US - ultrasound U/S - ultrasound UTI - u rin a ry tra c t infection Vaneo - vancomycin ve n tric - v e n trid e V fib - ve n tricula r fib rilla tio n V it - vitam in

A bbreviations

o b st - o bstru ctio n occ - occasionally O C P - oral contraceptive pills o p th o - ophchalm ology O T C - o ver the co un ter o u tp t - o utp atie nt

vol - volum e VSD - ventriculoseptal defect V T - v e n tricu la r tachycardia Vz/vac - vaccine V Z V - varicella zo ste r virus w / - w ith w /i - w ith in w /o - w ith o u t w n l - w ith in norm al lim its

W P W - W o lf-P a rk in s o n -W h ite w /u - w o rk up xfe r - transfer xfusion - transfusión xp lan t - transplant XRT - radiation therapy yo - years oíd

CONTENTS Contributors Foreword Preface Abbreviotions

iii v vi vii

PRIMARY CARE A N D ADOLESCENT MEDICINE Meredith Eicken, Aura Obando, andYoung-HoYoon V ital Signs b yA g e D evelopm ental M ilestones H ealthcare M aintenance

1-1 1-1 1-3

Im m unizations O ve rV iew o f G ro w th Failure to T h r iv e O v e rw e ig h t and O b e sity

1-5 1-6 1-7 1-8

Breast-Feeding Sudden Infant D eath Syndrom e (SIDS) Skull D e fo rm itie s

1 -9 1-10 1-11

N eonatal Jaundice A u tis m Spectrum D is o rd e r (ASD ) Lead Screening and T o xicity C o n tra c e p tio n

1 -12 1-15 1 -17 1-19

G ynecologic Exam Eating D iso rd e rs

1-20 1 -20

EMERGENCY DEPARTMENT Sylvia Romm, Nina L. Gluchowski, Hasan S. Merali, and Linda T. Wang Rapid Evaluation and M anagem ent o f C o m m o n P ediatric Emergencies S trid o r A naphylaxis A p p a re n t Life-T hreatening Event (ALTE) Fever W ith o u t an Identified Source in Infants and C h ild re n

2-1 2-4 2-5 2-6 2-8

A p p en d icitis Intussusception Burns C arb ó n M o no xid e Inhalation Traum a O verV iew

2-11 2 -12 2 -12 2 -14 2 -14

Head Trauma Foreign Bodies A s p ira tio n and Ingestión

2-15 2 -17

The C ryin g Infant Toxicolo g y

2-18 2-19

Facial Trauma

2-22

ALLERGY A N D IM M U N O LO G Y Dominica P. Donnal and Elizabeth C. TePas Food A lle rg y

3-1

A to p ic D e rm a titis (A D ) D rug A lle rg y U rtic a ria

3-2 3-3 3-4

Im m une D eficiencies

3-6

X¡¡ CONTENTS

B-C ell D eficiency (H u m o ra l Im m u n ity) T-C ell D eficiencies (C e llu la r Im m u n ity) C om b in e d Im m une D eficiencies C o m p le m e n t D eficiencies Phagocytic D iso rd e rs

3-6 3-8 3-8 3-9 3-10

C AR DIO LO G Y Elena K. Grant, M atan Setton, Deepak Palakshappa, and Ana María Rosales EKG In te rp re ta ro n H e a rt M u rm u rs Syncope C he st Pain C yan o tic C hild C ongenital H e a rt Disease Essential H y p e rte n sio n P ediatric D ysrhythm ias P ericarditis and Pericardial Effusion C ard iom yo p a th ie s (C M )

4-1 4-2 4-3 4-4 4-5 4-7 4-9 4-11 4-13 4 -1 4

C ongestive H e a rt Failure

4-15

E N D O C R IN O LO G Y Sarabeth Broder-Fingert, Julia Elisabeth von Oettingen, Manasi Sinha,and Lynne L. Levitsky D iabetes M ellitus

5-1

D iabetes M ellitu s Type 1 D iabetes M ellitu s Type 2 D ia b e tic Ketoacidosis

5-1 5-3 5-3

H ypoglycem ia T h y ro id Function Testing H y p e rth y ro id is m

5-5 5-6 5-6

H y p o th y ro id is m A drenal Insufficiency (A l)

5-7 5-8

H y p o p itu ita ris m A m biguous G enitalia Precocious P u b erty Delayed P u b erty S h o rt S tature A m e n o rrh e a Polycystic O varían Syndrom e (PCOS)

5 -10 5 -1 1 5 -1 1 5-12 5-12 5-13 5-14

FLUIDS A N D ELECTROLYTES David A. Lyczkowski and Avram Traum Body and P arenteral Fluids D eh yd ra tio n and R ehydration

6-1 6-1

H y p o n a tre m ia H y p e rn a tre m ia H ypokalem ia

6-3 6-5 6-7

H yperkalem ia H ypocalcem ia H ypercalcem ia Hyperm agnesem ia/H ypom agnesem ia

6-8 6-11 6 -12 6 -14

H ypoph osp h a te m ia /H yp erp h o sph a te m ia

6-15

6 -16 6 -16 6 -19 6-20

GASTROENTEROLOGY 7-1 7-1 7-2 7-4

P yloric Stenosis G a stro in te stina l Bleeding A c u te D ia rrh ea C h ro n ic D ia rrh ea C eliac Disease In fla m m ato ry Bowel Disease (IB D ) Jaundice

7-5 7-5 7-7 7-9 7-10 7-11 7-14

A b n o rm a l Liver Function Tests H epatitis

7-14 7-15

B iliary T ra ct Disease A c u te Pancreatitis C h ro n ic Pancreatitis

7-18 7-19 7-20

HEMATOLOGY Fei J. Dy and Eric F. Grabowski A nem ia H em og lo b ino p a th ie s P latelet D is o rd e rs C oagulation Bone M a rro w Failure

8-1 8-2 8-6 8-7 8-12

O N C O LO G Y Olga Rose and Alison Friedmann Lym phadenopathy in th e Pediatric Patient

9-1

P ediatric O n c o lo g ic Emergencies N e u tro p e n ia in the Pediatric Patient A c u te Lym phoblastic Leukemia A c u te M yelogenous Leukemia H odgkin Lym phom a N o n -H o d g k in Lym phom a Transfusions P ediatric B ra in T u m o rs

9-1 9-4 9-5 9-5 9-6 9-7 9-8 9 -10

N eu ro b la sto m a O steosarcom a O th e r C h ild h o o d Tum ors C hem o -A sso cia te d N ausea/Vom iting

9-11 9 -12 9-13 9 -14

C h e m o th e rap y A dverse Effects

9-15

x iii

Pañtosh Prasad and Jeffrey A. Biller A c u te A b d om in al Pain Peptic U lc e r Disease (P U D ) V o m itin g G astroesophageal R eflux Disease (G ER D )

CONTENTS

A cid-B a se D iso rd e rs M etabolic A cidosis M etabolic A lkalosis R esp irato ry A cidosis and Alkalosis

CONTENTS

X ÍV

INFECTIO US DISEASE Rebecca Cook, Emily 8. Rubín, Sophia Delano, and Chadí M. El Saleeby Fever o f U n kn o w n O rig in Infectious M eningitis P e rio rb ita l (Preseptal) and O rb ita l C e llu litis

10-1 10-1 10-3

A c u te O titis M edia Lym phadenitis Lyme Disease U T I/P yelo n ep h ritis C e llu litis Septic A r th r itis and O steo m ye litis Sexually T ransm itted Infections Tuberculosis

10-4 10-5 10-6 10-7 10-8 10-9 10-11 10-16

H IV Pediatric Pneumonía

10-17 10-19

GENETIC A N D METABOLISM Paritosh Prasad Inb o rn E rro rs o f M etabolism

11-1

Emergencies Hypoglycem ia H yperam m onem ia

11-2 11-2 11-3

A b n o rm a l N e w b o rn Screen Galactosem ia

11-3 11-3

Phenylketonuria/Phenylalaninem ia M anagem ent o f K n o w n In b o rn E rro rs o f M etabolism P o stm o rte m Labs Trisom y 13 Trisom y 18 Trisom y 21 T u rn e r S yndrom e Fragile X K lin e fe lte r Vacterl Lysosomal Storage Diseases M ito c h o n d ria l D efects E h le rs-D an lo s Syndrom e

11-4 11-4 11-6 11-6 11-6 11-6 1 1-7 11-8 11-8 11-9 11-9 11-1 0 11-11

Marfan Disease

11-1 2

NEUROLOGY Kristen A. Lindgren, N\axy Zelime Ward, Casey Olm-Shipman, and Verne S. Caviness Febrile Seizures

12-1

F irst N o n fe b rile Seizure in C hild re n Epilepsy Status Epilepticus (SE)

12-1 12-2 12-4

D yskinesias/M ovem ent D iso rd e rs Tics & T o u re tte Syndrom e (TS) A b n o rm a l G a it/A ta xia W eakness/P eripheral N eu ro p athie s

12-5 12-5 12-6 12-7

D em yelinating Diseases

12-11

12-13

Headache (H A ) N e u ro cu ta ne o u s Syndrom es ADHD

12-14 12-15 12-17

PULMONARY

C ough W heeze H em o p tysis P leu ritic C he st Pain APNEA D iagnostic Studies

XV

Harmony Catón, Anna Tien Labowsky, Sze Man Tse, LaeIYonker, and Natan Noviski Q u ic k Reference fo r R e sp irato ry Signs Tachypnea S trid o r

13-1 13-2 13-2 13-3 13-5 13-8 13-9 13-11 13-1 2

RENAL Melissa A. Watker and Avram Traum Urinalysis A c u te Kidney In ju ry (A K I)

14-1 14-1

C h ro n ic K idney Disease S econdary H yp e rte n sio n H em a tu ria , N e p h ritic Syndrom es U rin a ry T ra ct C alculi N e p h ro tic S yndrom e Renal Tubular Acidosis V esicoureteral Reflux C ongenital Renal M alform a tio n s

14-3 14-4 14-4 14-5 14-6 14-6 14-7 14-8

RHEUMATOLOGY Paritosh Prasad and Holly Rothermel Juvenile Idiop a th ic A rth ritis (JIA) Reactive (E nthesitis-related) A rth ritis Systemic Lupus E rythem atosus V asculitides D erm a to m yo sitis/P o lym yo sitis

15-1 15-2 15-3 15-5 15-9

N IC U Ashley A. Ferullo and Joseph H. Chou D e liv e ry R oom M anagem ent Basic N IC U M anagem ent P u lm o n a ry/R esp iratory C ardiovascular G a s tro e n te ro lo g y Infectious Disease H e m a to lo g y N e u ro lo g y

CONTENTS

C ere b ra l Palsy

16-1 16-4 16-7 16-9 16-10 16-13 16-16 16-17

CONTENTS

xvi

PICU Abigail R. Woodhead and Brian M. Cummings Prophylaxis ¡n C ritica l lllness Pain C o n tro l and Sedation R esp irato ry Failure Mechanical V entilation P ediatric ECM O/ECLS V entilator-associated Pneumonía (VAP) A c u te R esp irato ry D istress Syndrom e (ARDS) Septic Shock Ino tro p es, C h ro n o tro p e s , and Vasopressors Increased Intracranial Pressure Rapid Sequence In tu b a tion

C LIN IC A L IMAGES IN PEDIATRIC DERMATOLOGY IN D EX

1

H e a r t Rate

R e s p ira to ry Rate

P re m a tu re

120-170

40-70

75-55/45-35

0-3 m o

100-150

35-55

85-65/55-45

BP (S B P /D B P )

3 -6 m o

90-120

30-45

90-70/65-50

6 -1 2 m o

80-120

25-40

100-80/65-55 105-90/70-55

1-3 y r

70-110

20-30

3 -6 y r

65-110

20-25

1 1 0 -9 5/7 5-60

6 -1 2 y r

60-95

14-22

120-100/75-60

124-y r

55-85

12-18

135-110/85-65

Reproduced fro m N dson Tcxlbook o f Pediatrics. 18 th ed. Saunders; 2007 :7 0-74 , 677,24 34 .

• A recent systematic review of 69 observational studies suggests that previously published reference ranges fo r HR & RR may require updating.These centile charcs & an interactive calculator available at http://madox.org/tools-and-resources (Lancet 2011:377:1011)

A b o v e : R espiratory rate centiles fo r children fro m b irth to 18 y r

D E V E L O P M E N T A L MILE STONES ('ñrigbí Fuíures Gwcteiines for Health Super/ision ofín/ants, Children, and Adolescerrs. 3rd ec. 2008:39: Pediatr Rev 2010:31:267: Pediatr Rev 2010:31:364; Pbdiatr Rev 2011:32533)

rITAL SlGNS BY AGE 1-l|

i

V IT A L SIGNS BY AGE

C o g n itio n and C o m m u n ic a tio n

S o c ia l-E m o tio n a l & S elí-he lp

• Hands cightly fisted • Hands to mouth

• Throaty noises • Startles to sounds

• F ixa tes on faces (sh o uld do by 2 m o ) • Discriminates parent’s voice

• Lifts chin when prone • Head bobs if held sitting

• T ra cks past m id lin e (by 4 m o) • Hands unfisted V 2 of time, holds hands together

• Coos • Alerts to voice & sounds

• S ocial sm ile (b y 6 m o ) • Recognizes parent

4 mo

• Props on wrists when prone • N o head lag w h e n p ulled to s it • Rolls fronc to back

• • • •

• O rie n ts to voice (by 6 m o ) • A lt vocalization w/ speaker; “ converses" • Repeacs actions if results are interesting

• Laughs o ut loud • Enjoys looking around • Smiles spontaneously

6 mo

• S its u n s u p p o rte d (b y 9 m o ) • Commando crawis (8 mo)

• Reaches w/ one hand • Transfers hand to hand • Rakinggrasp

• Babbles “ dada” • L isten s, th e n vocalizes w h en sp e a ke r stops (by 9 m o )

• Recognizes strangers

9 mo

• Pulís to stand • Cruises • Crawis

• Pincer grasp (9-12 mo) • Bangs blocks together

• Babbles “ m a m a ” (by 12 m o) • Imitates sounds • Responds to ñam e (by 12 m o )

• Waves “ bye-bye” • Reciprocates gestures (by 12 m o ) • Uses sound to get attention • Stranger anxiety

12 mo

• Stands alone • W a lk s few step s alone (by 18 m o )

• Primitive marks on paper • Finger feeds part o f meal

• 1 word • Immature jargon

• Proto-imperative pointing • Pat-a-cake • Imitates • Follows 1-step command w•! gesture

15 mo

• Walks carrying objects • Stoops & recovers • Climbs on furniture

• Scribbles in imita tion • Stacks 3 -4 cubes • Turns pages * Uses spoon, cup

• 3 -6 w o rd s (by 24 m o ) • Says no correctly

• Follows singlestep command w/o gesture • P ro to d e c la ra tiv e p o in tin g

18 mo

• Walks up steps with hand held • Runs well • Throws ball

♦ Scribbles spontaneously • 4-cube tow er

• 10-25 words • Points to people and 3 body parts when named • Spoken languagel gesture combos

• Helps in house • Removes clothing • Im a g in a tiv e play

2 yr

• Walks down steps using rail • Throws ball overhand, kicks ball

• Lines cubes up as train * Imitates circle and/or line

• >50 words 50% intelligible • 2 -w o rd phrases

• Follows series of 2 independent commands * Takes off clothing • Parallel play

2.5 yr

♦ Jumps • Walks on toes • Alternates feet going up stairs

• Turns paper pages in book • 8-cube tow er

• Uses pronouns • Recites parts of known books

• Washes & dries hands • Puts on clothing • Imitates adult accivities

A ge

G ross M o to r

Fine M o to r

1 mo

• Lifts chin when prone • Turns head when supine

2 mo

Tracks to 180° Shakes rattle Mouths objects Reaching for objeccs

• >200 words • 3 -w o rd sentences • Speech 75% intelligible • Uses plurals

• Brushes teeth w/ help • Ñames friends • Imaginativo play • Begins sharlng • Knows ñame, age,sex • Toilet trained

4 yr

• Hops on one foot • Gallops

• Copies a cross and square • Draws 4-6part person • Buttons

• Follows 3-step commands • 100 % intelligible • Knows colors • Has memorized songs • Understands adjectives

• Tells tall tales • Interactive play (elabórate fantasy) • Group play • 1 cióse friend

S yr

• Skips

* Copies a triangle • Cuts w / scissors • W rites first ñame

* Identifies most letters, numbers out of order • Counts to 10 • Future tense • Reads 25 words

• Has group of friends • Apologizes fo r mistakes

6 yr

* Tándem walk

• Ties shoes • Draws diamond • W rites first & last ñames, short sentences

• 8 -1 0 word sentences • Knows days of the week ♦ Reads 250 words

• Same-sex best friend • Distinguishes fantasy from reality

Bolded milestones are red flogs if missed by age specified in parentheses. R ed Flags • Missed m ilestones (particularly bolded ones) o r loss o f previously acquired milestones should prom pc fu rth e r developm ental & medical assessmenc • Persistent fisting a t 3 m o may represent e arliest indicación o f n e u ro m o to r dysfxn • Rolling 17 mg/dL) • Cephalocaudal progression w ith increasing bilirubin level (face to tru n k to palms and soles): Estímate o f level fro m visual assessment; face = 5 mg/dL, chest = 1 0 mg/dL, abdomen = 12 mg/dL, and palms/soles >15 mg/dL. N o t visible if 6% re ticu locyte count, hem oglobin < 1 3 , hepatosplenomegaly) • C oom bs (+ ):AB O , Rh, and m in o r antigen incom pa tib ility • Coom bs (-): RBC memb defects (spherocytosis), enzyme def (pyruvate kinase, G 6 PD), Hgb defects (SCD, chal), drugs (streptom ycin,Vit K) - N o n h e m o ly t ic (norm al reticu locyte co u n t and hem oglobin) • Extravascular blood: Cephalohem atom a, bruising, CNS bleed • Intravascular blood = polycythem ia (high H b /H C T ): 2/2 delayed co rd clamping, feta l-m ate rn al xfusion, tw in -tw in xfuslon, m aternal D M o r smoking, high a ltitude • Intestinal = T EH circ; J- stoollng, CF, Hlrschsprung, pyloric stenosis, o b stru ct • i b ili c o n j (unconj): Breast m ilk jaundice, hypothyroid, G llb e rt and C rlg le r-N a jja r • I m p a ir e d b ilir u b in e x c r e tio n (conjugated) • Biliary obstru ctio n: Biliary atresia, choledochal cyst. 1° sclerosing cholangitis, gallstones, Dubin-Johnson, and R o to r syndromes • M etabolic disease: a -1 a ntitrypsin def, CF, galactosemia, glycogen storage dz, G aucher,W ilson, Niem ann-P ick, genetic dz,Trisom y 21 and 18,Turner • Infection: UTI, sepsis, id iopathic neonatal hepatitis, Hep B .TO R C H • J. A lbum in binding (unconj): L ow albumin, meds (C T X , sulfa, steroids), acidosis

[Neonatal Jaundice

B ilir u b in M e ta b o lis m (Pediatr Rev 2006:27:443) • Reciculoendothehal system: Hgb degraded by heme oxygenase and biliverdin reductase to unconj bilirubin, which binds albumin. Unconj bili fat soluble; able to cross the b lo o d brain barrier, can be neurotoxic • Liver; U ridlne diphosphateglucuronosyltransferase (U G T 1A1) converst unconj bili to conj bilirubin, conj bile excreted into blle, w a ter soluble, does n ot cross blood-brain barrier • Intestlne: Much o f conj bili hydrolyzed back to unconj fo rm and absorbed in to e nterohepatic circula tio n (EH). re st is e xcreted in stool. Intestinal bacteria reduce conj bili to urobilinogen, reducing EH circulation b ut new born gut initially sterile

H y p e r b ilir u b in e m ia N e u r o t o x ic lt y R is k F a c to rs (Pediatrics 2004:114:297: Pediatrics 2009:124:1193) • Isoimmune hem olytic dz, G 6 PD def, asphyxia, sepsis, acidosis, albumin 3 w l< ):Tbili/D bil¡ review th yroid & galactosemia screen results, eval infant fo r clinical evidence o f hypothyroidism ’ Can use online calculators using Bhutani nom ogram ; w w w .b ilito o l.o rg R x o f U n c o n ju g a te d H y p e r b ili ( \ Erigí J Med 2008:358:920; Pediatrics 2C04::14:297) • P F io to th e ra p y ( P T X ) : Light in blue-green spectrum (wavelength 430-490 nm) convert unconj bili to m ore water-soluble form excreted in bile and uriñe w /o conjugation • Congenital o r fam ily h is to ry o f p orphyria is absolute contraindication to PTX • If bili does noc fall o r continúes to rise despite PTX, hemolysis is likely • Serum albumin 38 wk and well) - Infants at mediun risk (>38 wk + risk factors or 35 -37 6/7 wk and well) Infants at higher risk (35-37 6/7 wk + risk factors)

w k and w ell)

;

s k (3 5 - 3 7 6/7 w c + ris k factors)

_

r"!

—

—-

-

—

-y'" -

Bi th

24 hr

4 8 hr

72 hr

96 hr

5 d

6 d

7 d

Age

• Pharmacology • Phenobarbital and ursode oxych o lic acid lo w e r bili levels by facilitating bile flo w • Tin-m eso po rp h yrin - inhibits p ro du ction o f heme oxygenase (n o t FDA approved) C O L IC See Gl section.

AUTISM SPECTRUM DISORDER (ASD) (Pediatrics 2007:120:1183: Pediatr Rev 2008:29:86: BMj 2011:343:d6238) I n t r o d u c t io n • N eurodevelopm ental co nd itio n w ith crite ria cu rre n tly undergoing revisión; see b elo w • ASD includes autistic dísorder,Asperger disorder, and pervasive developmental disorder n o t otherwise specified - these, plus childhood-disintegrative disorder, likely to be merged in to single category o f ASD. Rett syndrome would be sepárate • C D C : 1 in 88 US children id entified, male:female ra tio 4-7% recurrence risk in youn ge r/fu tu re sib C r it e r i a f o r D x o f A u t is m (D S M -IV - T R 2 0 0 0 .7 5 ) ( 'C rite ria applicable to p: < 3 yo) • Im p airm e nt in reciprocal social ¡nteraction • *lm p a ire d nonverbal behavior (eye contact, facial express, posture, and gestures) • *A b se n t seeking ¡nteraction (no pointing, showing, o r bringing objects o f interest)

1-15

ifan ts a t lo’ .re r ri >k (>3 8 w k and w ell) nfanls a t m Bdium risk > 38*. 'k + r sk fa .to rs o r 3 5 - 3 7 6/ 1ifa n ts a t hi jh e r

ASO

• E x c h a n g e tra n s fu s ió n : Removes bilirubin and damaged erythrocyte s fro m circulation • Reaching exchange transfusión levels (bili >25 mg/dL) is a medical emergency • In isoim m une h em olytic dz. may avoid exchange transfusión rx w / IVIG (0.5-1 g/kg over 2 hr). should give if bili is rising despite intensive P TX o r if bili level is w /i 2 -3 mg/dL o f the appropriate exchange level (see below ), can repeat dose in 12 h r • Im m ediate exchange transfusión if bili >5 mg/dL above these lines o r infant has ABE, also if b ili reaches these levels despite intensive PTX • C o nside r exchange if T bili remains above exchange level a fte r 6 h r o f intensive PTX • Can calcúlate “ bilirubin/album in” ra tio to help determ ine need fo r exchange transfusión along w / o th e r risk factors • Infants >38 w k: 8 ; if higher then concerning • Infants 35-37 .9 w k and well, o r >38 w k if higher risk o r h em olytic dz: 7.2 • Infants 35-37.9 w k and higher risk, o r hem olytic disease: 6.8 G uidelines f o r Exchange Transfusión in Infants >35 W k (AAP G uidelines 2004)

1-16 ASD

• *Lacl< o f social o r em o tion al re cip ro clty • Lack o f peer relationships • Im pairm ent in com m unication • *Delay o r lack o f spoken language (w /o com pensation via gestures) • If w / adeq speech. inability to initiate o r sustain a conversation • S tereotyped and rep etitive use o f language; lack o f make-believe o r im itative play • Repetitive patterns o f behavior, in terest, and activities • Intense preocc w / stereotyped interest; persistent preocc w / parts o f objects • Inflexible adherence to specific rou tine s o r ritu a l’s • Repetitive m o to r mannerisms (hand-flapping, w h ole-bo dy movements) P ro p o s e d D S M - V R e v is io n s : M ust m eet crite ria fro m A, B, C , and D {www.dsm5.org/ProposedRev:sion/Pages/proposedrevision.aspx?r¡d=94) ■ Persistent déficits in social com m unication & ¡nteraction, manifest by all 3 ■ D éficits in social-em otion re cip ro city (anml social approach, failure o f nml back & fo r th conversation, lack o f in itia tion o f social ¡nteraction) • Déficits in nonverbal communicative behaviors used fo r ¡nteraction (poorly integrated verbal/nonverbal com m unication, abnml eye co nta ct & body language, déficits in understanding/use o f nonverbal com m , lack o f facial expression/gesture) • D éficits in developing/maintaining relationships (difficulties w ith adjusting behavior to social co n te xt, d ifficulties in sharing imaginative play, lack o f in terest in people) ° R estricted. rep etitive patterns o f behavior, ¡nterests, o r activities, manifest by 2 o f • S tereotyped o r re p etitive speech, m o to r m ovements, use o f objects • Excess adherence to routines, ritualized patcerns o f behavior, resistance to change • Highly re stricte d fixated intereses th a t are abnml in intensity and focus • H yper-/hyporeactivity to sensory in pu t o r fascination w ith sensory aspeets o f env • Symptoms m ust be present in early childhood • Symptoms lim it and ¡mpair everyday functioning • DSM 5 likely to include all 3 diagnoses u n d e rA S D only, subdivided into severity levels S u r v e illa n c e a n d S c re e n in g (Pediatrics 2007:120:1183) • A AP recs surveillance at each well visit (risk factors include sib w ith autism, pediatrician concern, and parental o r o th e r caregiver concern), also screening at 18 and 24 m o w ith autism-specific screening to o l (i.e., M -C H A T fo r toddlers, SCQ fo r children >4 yo) • If autism suspected (tw o o r m ore risk factors, positive o r concerning results on autism screening to o l o r eval o f communication and social skills), refer to autism dx clinic, early intervention (3 yo), and audiology • A bso lu te indications fo r im m ed eval: “ R e d F la g s” (N eu ro log y 2000:55:468) • N o babbling, pointing, o r o th e r gestures by 12 m o; no single w o rd s by 16 mo • N o 2 -w o rd spontaneous phrases (n o t ju st echolalia) by 24 m o • A ny loss o f any language o r social skills at any age • Siblings o f children w ith A SD should undergo heightened surveillance as above D ia g n o s tic S tu d ie s (Pediatrics 2007:120:1183; BMJ 2011;343:d6238) • Hearing tests (behav audiom etrics, middle ear fxn, and electrophys procedures) • Lead level, Hgb (pe rio dic screening if pica) • D etailed h isto ry (esp family), physical fo r d ysm o rph ism s,W oo d ’s lamp exam • G enetic testing (karyotype - e ithe r high res o r w ith microarray; chromosomal microarray) and D N A testing fo r fragile X if p t has G DD/M R , MECP2 testing in girls if concern fo r Rett • Targeted studies (selective m etabolic testing, EEG, MRI) considered if cyclic vomiting, lethargy, seizures, dysm orphic o r coarse facial features, MR, hypopigm ented macules, o r if new born screening is inadequate o r unavailable • C o nside r referral to neurology, genetics, child psych o r developm ental pediatrician as indicated. Include speech therapists, OT, special ed/IEP, S W • D d x includes D ow n, C H A R G E assoc, fragile X , tuberous selerosis, PKU, fetal alcohol syndrom e, Angelm an, Rett, and S m ith -L e m li-O p itz syndromes T r e a t m e n t A p p ro a c h e s : Early in itia tion is im perative, best outeom es • Educational approaches: Early s ta rt D enver m odel and TE A C C H (¡mprove cognitive perform ance, language skills, adaptive behavior skills) • D isruptive behavior best targeted w ith functional behavioral assessment (IDs modifiable behaviors & teaches new skills and desirable behaviors) • Speech/language tx (p ro m o te functional com m unication), social skill instrucción, oceupational therapy • T x o f psychiatrlc com orbidities - best data fo r risperidone.aripiprazole, methylphenidate • N o 2 -w o rd spontaneous phrases (n o t ju st echolalia) by 24 mo • A ny loss o f any language o r social skills at any age “ Siblings o f children w ith A S D should undergo heightened surveillance as above

LEAD SC REEN IN G AND T O X I C I T Y (Pediatr Rev 2010:31:399; Pediatr es 2005:116:1036: NEJM 2003:348:1517; Environ Health Pcrspect 2005:113:894: Pediatrics 2007:120:e.1285: Pediatr Clin N c r th A m 2007:54:271) S ources o f Lead • Lead paint (banned in US in 1977) chips o r dust, contam inated soil o r household dust (fro m e x te rio r paint o r p rio r use o f leaded gasoline fro m nearby traffic) • A ir: H istorically im p o rta n t u ntil leaded gas phased o u t 1973-19 8 6 w ith >96% reducción in lead levels 1980-2005, n ow m ost comes fro m industrial emissions, esp lead smelters • W a te r fro m lead pipes and solder, also brass fittings; w o rse if standing/stagnanc o r h o t • Im p orte d o r antique toys, co okw are, ceramics • Im p orte d folk/e thn ic/h erba l remedies, cosmetics, foods, and spices • O ccupational: Ceramic/glass w o rk, auto/ship repair, plumbing, painting, mining, soldering • Transplacental (infant lead levels approxim ate m aternal levels) L e ad S cre e n in g • M ost at risk:African-Am erican children, pts on Medicaid, lo w e r SES o r urban areas, recent immigrants, developmental delays.and repetitive oral behaviors. those w / siblings w ith elev lead levels • Begin 6 mo, assess p t risk (pre-1950 home w / peeling paint; pre-1978 w / renovating; sibling o r friend w / toxicity; household adult in high-risk occupation; high-risk home location) • C hildren w / gov assistance (M ed ica id,W IC ) screen b tw 9 -1 2 m o and again at 24 m o • Non-Medicaid eligible pts, selective screening according to State recs. Screen at age 3 to 6 yo if n ot screened previously • Immigrants, refugees, and internacional adoptees screened upon arrival to US • C o nside r screening in all pts w / PDD, pica, o r those w h o are neglected o r abused P athogenesis • Toxic to CNS and PNS, hematopoiesis, kidneys, liver, and endocrine systems; children a t inc risk b/c ¡m m ature b io o d -b ra in barrier. Lead interferes w ith neurotransm ission and disrupts cell m igration during brain developm ent • Inhibits enzymes in heme synthesis 5-am inolevulinic acid dehydratase (A L A ) and ferrochelatase (resulting in T p ro to p o rp h y rin levels) • Inhibits pyrim idine 5’ nucleotidase (results in basophilic stippling [BS]) C lin ic a l S y m p to m s • N e u r o : Dev delay, cogn d é ficits.A D H D , aggression, delinqueney, hearing loss. periph neuropathy, encephalopathy (a MS, szr, ataxia, papilledem a/cerebral edema, coma) • IQ decline o f 3.9 fo r levels 2 .4 -1 0 mcg/dL, by 1.9 fo r levels 1 0 -2 0 mcg/dL, and by 1.1 fo r levels o f 2 0 -3 0 mcg/dL (Environ Health Perspect 2005; 113:894) • Relationship nonlinear 2/2 differential lead saturation pathways (highest10 mcg/dL = + (if capillary >10 mcg/dL need venous confirmation) • If lead level is elevated, screen all siblings, housemates, and friends • Blood lead levels peak at 1 8 -3 0 mo, then gradually decline • Free e ryth ro cyte p ro to p o rp h yrin o r zinc-chelated p ro to p o rp h yrin : t w / iron def & lead poisoning (VLLs >30 mcg/dL), may help assess ch ro nicity & response to rxs • CB C, re tic count, iron le v e l,T IB C .fe rritin level; if hx ¡ngestion/pica, obtain KUB • For chelation, check Chem 20 and U /A ; if w / d im ercaprol o r succimer. check G 6PD M anagem ent • N o RCTs th a t chelation ¡mproves neurocognitive outcom es; p ro to co ls based on clinical judgm ent and experience Recom m endations fo r C onfirm ed Venous Lead Levels Level m g/dL

Recom m endations

Any level

Obtain environmental history; provide risk-reduction and nutrition education Calcium and ¡ron supplements (prevent lead absorption) Vitamin C (encourages renal excretion o f lead); consider zinc therapy Rearing in nurturing and stimulating env may dec severity of neurotoxicity Any level >10 must be reported to local department o f public health

4 h r • Succimer (D M S A); indication:V LL 4 5 -6 9 mcg/dL • Side effects: H ypersensitivity reactions, G l sx. transient transaminitis, i hem oglobin, reversible neutropenia; m onitoring: LFTs and CBC • D im ercaprol (BAL = “ B ritish anti-Lew isite” ): Indication: VLL 70 mcg/dL o r lead enceophalopathy • Side effects: Pain, hemolysis in G 6 PD, to xic complexes if given w / iron, H T N , N N, fever, lacrim ation, paresthesia, renal dysfunction, zinc depletion, headache, leucopenia, tachycardia, hyperpyrexia • C ontraindications: G 6 PD, hepatic disease, peanut allergy • M o n itoring : C V and mental status; alkalinize u riñe during tx

CONTRACEPTION

O C P S id e E ffects, M o n ito r in g , and C o n tra in d ic a tio n s • Estrogen side effects include b lo o d clots, irregular menses, breast tenderness, fluid re te n tio n , nausea, increased appetite, headache, and hypertension (can tria l pill containing lo w e r estrogen dose) • Progestin effects include m enstrual A, bloating. m o o d A. H A . nausea, w eight gain. D ro sp ire n o ne (inYasmin) has d iu re tic and antiandrogenic activity; caution in pts at risk o f hyperK+ o r w ith renal ¡nsufficiency • A ndrogenic side effects (less com m on; incl acné, hirsutism . male p atte rn hair loss) • Class IV contraindications; H /o DVT, PE, CVA, A M I. Factor V Leiden o r o th e r th ro m b o p h iiia . m igraine w / aura o r neurologic changes. (Refer to com plete W H O guidelines at h ttp ://w w w .w h o .in t/re p ro d u ctive -h e a lth /p u b lica tio n s/m e c/3 cocs.pdf) O t h e r O p tio n s • V a g in a l rings: (N u v a R in g ') C om bined h orm one-containing silicone ring, horm ones absorbed vaginally, avoids 1st-pass metab. Intravaginal 3 w k. T rate o f p t satisfaction • T ra n s d e rm a l: A bsorb E&P through skin;less effective in pts >90 kg, avoids 1st-pass metab • Each patch should be w o rn fo r 7 d before replacing, on a new site each tim e • FDA warning: 60% m ore to ta l estrogen in patients’ b lo od c/w 35 mcg O C P • In je c ta b le : D e p o t m e d roxyprogesterone acétate (progestin only, D epo-P rcvera) IM q3m o, i reliance on p t adherence • High d is c o n tin u a ro n 2/2 side effects (m enstrual irreg. w t gain, i in bone density) • F e rtility can take up to 10 m o to re tu rn • C om bined injectable contraceptives injected q lm o and o ffe r advantage o f both im proved adherence w /o side effect p ro file o f progestin only injections • S u b d e rm a l c o n tra c e p tiv e ¡m p la n ts : Progestin-only ro d (Im planon) inserted b elow the skin, effective fo r up to 3 yr. F e rtility re turns p ro m p tly a fte r rem oval • Irregular bleeding is a com m on side effect, b u t diminishes w ith continued use • In tr a u te r in e devices ( I U D ) • The levonorgestrel-releasing IU D has been approved fo r up to 5 yr o f use • C opper-containing IU D acts via a local ¡nflam m atory response • Chance o f ectopic pregnancy is 75%. Effectiveness show n fo r up to 120 h r a fte r u np ro te cte d sex • Plan B (O T C ) consists o f 2 x 0.75 mg tabs o f L N G q12 hr. Single dose (1.5 mg) a d m in is tra ro n has sim ilar effectiveness (C ochrane Database Syst Rev 2008;16;(2))

1-19

T h e O r a l C o n tra c e p tiv e Pili ( O C P ) • E ither co m b o synthetic estrogen (ethinyl estradiol [EE] o r m estranol p ro -d ru g ) and progestin (o f varying potency) o r a progestin only pill (POP) • Estrogen suppresses g onadotropin surge prevention o f ovulation • Progestins thicken cervical m ucus.alter tubal peristalsis.and create endom etriai atrophy —> d e te r sperm m o tility. egg fe rtiliz a ro n , and im plantation • T h e o re tica l failure rate -0.3%; ty p ic a l use fa ilu re r a t e : -8 % . 2/2 p o o r adherence • “ E strogen-dom inant” (full-figured, significant m enstrual sym ptom s) pts may benefit fro m less estrogenic o r m ore p o te n tly androgenic p ill.“ A n d ro g e n -d o m in a n t" (hirsute, acné, PCOS) pts may benefit fro m m ore estrogenic vs. less androgenic • G enerics have equivalent to le ra b ility and efficacy: often significantly m ore affordable • N e w extended-cycle fo rm u la tion s (w / 1—4 w ithdraw al bleeds/yr) have good efficacy and can reduce effects o f h o rm o n e w /draw al • Benefits: H elp tx D U B. dysm enorrheal. acné, hirsutism , PCOS. and dec risk o f u terine and ovarían cancers • Initiate w ith either monophasic o r multiphasic b ut at lo w dose estrogen (20-35 mcg) and titra te up as needed after 3-mo trial. Initiate on d 1 o f menstrual cycle o r on Sunday after menstrual cycle begins;take pill same tim e every day. Encourage condoms in conjunction w ith OCPs. F/up 6 w k to 2 m o after initiation

C ontraception

(Pediatrics 2007:120:1135: Pediatr Rev 2008:29:386)

• “ Yuzpe regim e": Uses O C Ps as EC (less effective, large # pills, 1' side effects) • Patients may experience vaginal spotting, nausea/vom iting a fte r use o f EC

G Y N EC O LO G IC EXAM (Pediatrics 2010:126(3)583) B a c k g ro u n d • Extcrnal genital exam should be conducted at all annual exams. N o speculum/bimanual exam required p rio r to rx o f m ost horm onal contraception (can test uriñe hCG and STIs) • STI testing n o w uriñe o r vaginal swab based; does n o t require speculum exam • C u rre n t guidelines fo r Pap te s t:A t age 21, unless HIV-» o r im m une suppressed fo r w hich paps initiated a t onset o f sexual activity • D espite high exposure to HPV, m o st sexually active adolescents clear infection w ith o u t in te rv e n tio n ; avoids potencial pregnancy com plications in fu tu re • L o w grade lesions and ASCUS fo llo w e d by repeat Pap a t 1 y r intervals; co lp o only fo r persisten t a b n o rm a lity o r high grade lesión o ver 2 y r p erio d In d ic a tio n s fo r Pelvic E x a m • Persistent vaginal discharge, dysuria in sexually active teen, dysmenorrheal unresponsive to NSAIDs, amenorrhea. abnml vaginal bleeding, lo w e r abdominal pain, IUD o r diaphragm placement, suspected rape/sexual abuse, pregnancy, pap test

EATING DISORDERS (Pediatr Kev 2011:32:508; P edatr Rev 20C6;27:5) D e fin itio n C rite rio n

D S M -IV A n o re x ia Nervosa

Body weight

Refusal to maintain w t >85% expected for ht/age (DSM-V proposed change: Restriction o f caloric intake leading to signif low body wt). Restrictive and binge/purging types

Menstruation

Absence o f 3 consecutive menstrual cycles in poscmenarchal females (DSM-V likely exeludes this criterion)

Fear of w t gain

Intense fear of (DSM-V: OR persistent behavior to avoid) w t gain though underweight (DSM-V: Significara low-weight)

Body image

Disturbance in way w t or body shape is experience; denial of seriousness of condition;undue influence o f wt/shapc in self-perception (DSM-V: N o change)

C rite rio n

D S M -IV B ulim ia Nervosa

Binge eating

Eating large amounes in discrete period (2 hr), larger than average

Compensatory behavior

Recurrent self-induced vomiting. laxative use, diuretics. enemas, fasting, o r excess exercise to prevent w t gain

Frequency

Binging/compensatory behavior at least 2x/wk fo r 3 mo (DSM-V: binge/ compen behav on avg >1x/wk fo r 3 mo

Self-evaluation

O verly influenced by body shape/weight

• E a tin g d is o rd e r N O S ; Pts m eet some, n o t all o f diagnostic c rite ria fo r above EDs, includes binge eating d is o rd e r (lack com p en sa tory behaviors) • F e m a le a th le te tria d : Hypothalam ic amenorrhea, osteoporosis, lo w energy availability (+ /- eating disorder) in female athlete. Low body fat -> ie stro g e n -> amenorrhea and lo w bone mineral density • A p p ro x im a tio n o f IB W 9 : 1 0 0 Ib fo r 60 in., + 5 Ib each added in.; 6 :1 0 6 Ib fo r 60 in., + 6 Ib fo r each in. (Pediatr Rev 2006:27:5) • Expected w t (kg) fo r adolescent: (Height in m eters)2 x 50th percentile BMI fo r age and sex E p id e m io lo g y • A N : 0.9% o f 9 ,0 .3 % o f 6 mo, annually if am enorrhea perslsts M e d ic a l C o m p lic a tio n s /P h y s ic a l F in d in g s • D erm /orofacial: Erosión o f cooth enamel/cavities, parotld gland hypertrophy, calluses on knuckles (Russell slgn), hypercarotenem ia, alopecia, acné, lanugo, halitosis • M etabolic derangements: H y p e r n a tr e m ia 2/2 re stricte d intake: h y p o n a tre m ia 2/2 w a te r loading: h y p o k a le m ic , h y p o c h lo re m ic m e ta b o lic alkalosis 2/2 vom iting, and diuretlcs; h y p o p h o s p h a te m ia as p a rt o f re fe e d in g s y n d ro m e in rx phase • Cardiac: B ra d yc a rd ia , H o T N , orthostasls, a rrh y th m ia , prolonged QT, MV prolapse/ m urm ur, perlcardial effusion, cardiom yopathy and CHF, sudden cardiac death • P ulm onary:Aspiration P N A and PTX fro m forceful vom iting, pulm edema 2/2 refeeding • GkVague abn pain, constipation, delayed gastric emptying, esophageal irrita tio n and chest pain, hematemesis 2 /2 M a llo ry-W e iss tears/esoph ru p tu re , gallstones, rectal prolapse, SMA syndrom e, LFT abn, usually nml albumin (¡f i , eval fo r o th e r dx) • GU: Renal stones, a tro p h ic vaginitis, a trophy o f genitalia • N e uro: Szr (hypoN a), p eripheral neuropathy, brain atrophy, lo ng -te rm neurocog abn • Endocrine: iL H /F S H and estrogen, am enorrhea, o s te o p e n ia , a n d os te oporosis (fra c tu re s ); i th yro id fxn (hypotherm ia), often sick euthyroid • Hem e/im m uno: Mild anemia (folate o r iron def),T E S R .W B C .p lt count, altered im m unologic m arkers T r e a tm e n t : Requires m ultidisciplinary team; use o f eating d isorde r p ro to c o l w ith privileges as incentives. O fte n stabilized inpatient, transferred to residential tx center. • M o n ito rin g and rx o f e le ctro lyte dlsarray, sudden death may o ccu r fro m hypoK • Cautlous n u trition al su pp ort ¡n severely mainourished ( 1 0 kg 70 mm Hg (+ 2 x age in yr, w hen age 2 sec). Later w /' obtu nd atio n and p o o r periph pulses • Tachycardia is often the earliest and m o st sensitive sign o f early shock but it is nonspecific; hypotension itse lf is often a late and om inous finding

Specific H X and Exam

Cardiac O u tp u t

Peripheral (system ic) Vasocon­ striction

M anagem ent

1

T

t 4

4 (warm) t (coid)

Hx o f congenital heart dz, sweats w 1 feeds, etc.

4

T

Eval fo r pulm edema; if no rx w / volume; cards consult

Spinal cord trauma Allergic exposure (w/ assoc rash, etc.) Toxin (drug) related

T

4

Initially w / volume - Epinephrine w / anaphylaxis - Pressors for neurogenic shock

H ypovolem ic

Volume loss (diarrhea, vomiting, polyuria, blood loss)

Septic - Early - Late

Fever, infectious source (indwelling lines, PNA, etc.)

Cardiogenic

D istributive

Volume replacement (NS bolus 20 cc/kg x 3, then RBC transfusión) Initially w / volume, then Abx and pressors (see PICU chapter)

• A lso consider o b s tru c tiv e shoclt 2/2 tam ponade, massive PE, tensión PTX; if present tre a t underlying etiology • D ia g n o stic studies: C o nside r stat C B C .glucose, K, Ca, lactate.A B G , S v02 • M a n a g e m e n t: O bta in large bore IV access and give NS 20 cc/kg bolus, repeat up to 3x, then consider blood produets. If unable to obtain IV access, obtain IO access • Patient may need v e n tila to ry su p p o rt to ensure adequate oxygenation • Pressors: O fte n dopamine 2 -2 0 meg/kg/m (can use peripherally) (see PICU chapter) • Ensure p t is euvolem ic before in itia tion o f pressors • In pes w h o are volum e & pressor unresponsive, consider IV stress dose steroids • In pts w / evidence o f anaphylaxis (u rtica ria l rash.airw ay involv) use epinephrine • C entral access is required fo r che use o f m o st pressors S eizu re s (Emerg Med Clin N o r th A m 2007:25:1061) (See PICU and N e urolog y chapters fo r fu rth e r management) • E tiology: Infectious (febrile, meningitis, brain abscess), neurologic (hypoxic-ischemic encephalopathy,VP shunt malfxn, neurocutaneous syn), metabolic (ele ctrolyte abn, hypoglycemia, hypoxia, inborn e rro rs o f metab), traum a (abuse, ICH), tox, neoplasm • F e b rile s eizu re : Seizure w / febrile illness in p t aged 6 m o -5 yo • Simple if < 15 min, single episode and generalized seizure, non-focal n euro exam • C o m p le x if > 15 min, recurs w ith in 24 h r o r focal seizure • P a rtia l s z r arises in 1 hemisphere, is focal, and classified as sim ple if consciousness is n o t im paired (just m o to r o r sensory effect) and com plex if consciousness is altered • G e n e ra liz e d s zr b oth hemispheres; consciousness depressed; convulsive o r nonconvulsive • S ta tu s e pilepticus: Continuous seizure >30 min o r >1 seizures w /o return to baseline • E v a lu a tio n and M a n a g e m e n t: • A BC s (su p p o rt as needed), check finger stick glucose and tem pe ra ture, p e rtin e n t h istory: h /o szr, anti-epileptics, family history, medications and toxins, recent illness, traum a, obtain IV o r IO access, recheck ABCs

If febrile, tre a t fever & in fectious w /u based on age. If afebrile, cali neurology Lorazepam 0.05-0.1 mg/kg IV (max 4 mg); r p t q5m in to max to ta l dose 10mg in 20 min; place patie nt on th e ir side to avoid aspiration - Reassess A BC s and need fo r airway su p p o rt a fte r each dose • Diazepam, (2 -5 y r 0.5 mg/kg; 6 -1 1 yr 0.3 mg/kg; >11 0.2 mg/kg PR; max 5 -1 0 mg), less effective and leads to m ore respiratory depression than lorazepam A fte r 2 doses o f lorazepam; consider fosphenytoin 20 PE/kg IV; a fte r fosphenytoin consider levetiracetam 2 5 -5 0 mg/kg IV (Pediatr N e u ro l 2009;41:37)

ST RID OR D e fin itio n • Hig h-pitched sound o f tu rb u le n t a irflo w in upper airway indicates airway o bstru ctio n • Insp irato ry s trid o r usually indicates o b stru ctio n above the vocal cords • Expiracory s trid o r usually indicates o b stru ctio n b elo w the vocal cords D iffe r e n tia l Diagnosis • Causes include croup, epig lo ttitis, and bacterial tracheitis (BT may be the m o st freq life-threatening u pp er airway infection cu rre ntly) (Pediatrics 2006:118:1418) • C o nside r differential diagnosis anatom ically based on in sp ira to ry o r e x p ira to ry s trid o r • N o s e : Insp irato ry strid o r, snoring; in neonates consider choanal atresia • P h a ry n x : G urgling/m uffled voice • A febrile: Macroglossia, micrognathia, tonsil/adenoid h ypertrophy • Febrile: R etropharyngeal/peritonsillar abscess • L a ry n x : H igh-pitched in sp ira to ry strid o r, voice change, hoarseness • A f e b r ile : Laryngomalacia, laryngcal web, cyst, vocal co rd paralysis, laryngotracheal stenosis, ¡ntubation, foreign body, cystic hygroma, s ubglottic hemangioma, laryngospasm, psychogenic strid o r, vocal co rd paralysis • F e b rile : C rou p, epig lo ttitis • T ra c h e a : Insp & exp stridor:Tracheom alacia, bact tracheitis, e xte rn a l com pression, TEF C ro u p (L a r y n g o tra c h e o b ro n c h itis ) • Characterized by barking c o u g h ,+ /- in spira to ry s trid o r,+ / - re sp ira to ry distress • Peale incidence 1 -2 yo, Sept to Dec, M > F. Parainfluenza virus accounts fo r >50%, the n e xt m o st com m on cause is RSV (Pediatrics 1983:71:871) • M ild : Dexam ethasone 0.6 mg/kg PO/IM l rp t visits, length o f sx, and parental stress, and T sleep (N Engl J Med 2004:351:1306). A lso consider co ol m ist, hydration, & antipyretics • Can use oral prednisolone 1 -2 mg/kg PO; tm o f prednisolone 24 h r;tic¡ o f D ex 32 h r • M o d é r a te to severe: • M ist te n t o r hum idified oxygen near ch ild ’s face (n o t supported by C ochrane review) • Dexam ethasone 0.6 mg/kg P O /IM /IV (N Engl J Med 1998:339:498; meta-analysis in BMJ 1999:319:595) • Equivalence o f PO vs. IM dosing shown in study o f m odérate croup. (Pediatrics 2000:106:1344) • Racemic epi (2.25%) 0.05 mL/kg/dose in 3 m L NS (m ax 0.5 mL) q 15 min up to 3x PRN, watch HR (Pediatrics 1992;89:302) • C ochrane review (C D 00 6 61 9) supported benefit at 30 min post-nebulized epi but n o t at 2 h r and 6 h r post though decreased rate o f hospitalization • If epi given, need obs (effects wears o ff in 2 hr). O bs in ED fo r min 4 -6 hr • Decrease epi dose fo r known cardiac disease E p ig lo ttitis • Usually 2/2 Hib. incidence o f H ib 4- by >99% since in tro o f conj vaccine in 1998 (M M W R 2002:51:234). P/w to x ic child, droollng, sitting fo rw a rd , s trid o r • T ru e e m e rg e n e y requiring im m ediate intubation in co n tro lle d environ m e n t (if possible), any m anipulation o f child may cause full o bstru ctio n • Give O 2 as accepted by child, a llo w parent to accompany child to allay anxiety • Summon sénior pediatrician, anesthesiologist, and E N T o r pediatric surgeon • If u n s ta b le, in tubate em ergently; bag-mask w / high pres, may need to disable p op -o ff • If sta b le w ith h igh s u s p iá o n (to xic, febrile, leaning fo rw a rd , audible strid o r, uncertain vaccination re co rd) e scort p t to O R fo r laryngoscopy/intubation

• If m o d e ra te llo w su spicion , obtain lat neck x-ray (th u m b p rin t sign), w ill agítate them • Once a irw a y is secure, check C B C /diff, ex o f blood and epigiottis, s ta rt A b x (such as ceftrlaxo n e) coverlng Hib, S. pneumo, and G rp A strep B a c te ria l T ra c h e itis {Pediatrics 2000;118:1-118; Emerg Med Clin N o rth A m 2007:25:961) • C o m m o n ly seen in fall/w inter, 6 rno - 8 y r • P re s e n ta tio n : V ira l p ro d ro m e follow ed by acute onset o f to x ic appearance, high fever (mean 101.8°F/38.8°C), cough, resp distress. U nllkely to d ro ol, may be able to lie fíat • M a n a g e m e n t: To O R fo r endoscopy to obtain sample fo r GS and cultures and in tubation. If intubating in ER consider sm aller ETT than usual because o f airway edema • A b x to cover S. aureus, S. pneumo, M. catarrhalis, H. flu, andalpha-hem olytic strep • CXRs usually norm al o r sim ilar to croup (steeple slgn), blood ex usually negatlve L e m ie r r e ’s D isease (Pediatr C r t Care Med 7003:4:107: A m J O lolaryng o l 2010:31:38: j Emerg Med 2010:39:436:.' Q n M icrobio! 2003:41:3445) • Jugular vein suppuratlve throm bosis preceded by pharyngitis o r dental infections; in ternal ju gular vein throm bo ph le b itis leads to metastatic com plications; m o st com ­ monly caused by Fusobacterium necrophorum; may present w ith re sp ira to ry distress • C rite ria fo r diagnosis: • Previous oropharyngeal infection • Septicemia follow ing oropharyngeal infection • Swelling o r unilateral tenderness o f the neck, jaw • Metastatic abscesses to the lung, liver, kidneys, o r joints • Fusobacterium necrophorum isolated fro m blood cultures o r abscess aspiration • Rapid progression • Diagnostic procedures: B lood culture, ultrasound, C T neck w ith co ntra st • Treatm ent: ABCs, a ntibiotics, e.g., a m picillin-sulbactam and m etronidazole. C onsider surgery and ancicoaguladon D ia g n o s tic S tu d ie s fo r S tr id o r in G e n e ra l • Initial eval w / C X R la t/AP neck film : E N T (d lre ct laryngoscopy), consider flu o ro if available. D eterm in e cause: S ta rt in itial management, but e tiolo g y can define specific treatm ents

A N A P H Y L A X IS (Pediatr Emerg Care 2007:23:49: J Allergy Clin Immunol 2010:126:477) D e fin itio n (Pecialrics 2000:106:762;. Allergy Clin Immunol 2006:117:391) • Anaphylaxis is a serlous systemic reacción, w hich is rapid in onset and may cause death • IgE hypersensicivity 2/2 systemic m e d iato r fro m sensitized mast cells & basophlls • U n ip h a sic r e a c tio n occurs im m ediately a fte r exposure • B iphasic r e a c tio n includes a recurrence o f sx th a t develops a fte r re so lutio n o f inicial reaction. 1-20% o f anaphylaxis episodes & o ccur b tw 8 -7 2 h r a fte r in itial reaction • P ro tra c te d re ac tio n : A ny anaphylaxis episode lasting fo r hrs to d beyond inicial rxn S y m p to m s o f A n a p h y la x is Skin

Diaphoresis, flushing, pruritus, urticaria, warm sensation, angioedema

Respiratory

Oropharynx/lip tingling o r itching, chroat/chest tightness, hoarseness, stridor, wheezing, dyspnea, respiratory failure

Gl

Nausea, diarrhea, vomiting, cramps

CV

Arrhythmias, hypotension, shock, arrest

N euro

Dizziness, visual changes, tremor, dlsorientation, syncope, seizures

O thers

Impending sense of doom, metallic taste, rhinorrhea.tearing

C r it e r ia fo r A n a p h y la x is • Highly likely when any 1 o f the follow ing 3 crite ria is fulfilled: • A cute onset (min to hrs) involving skin & /o r mucosal tissue & >1 o f follow ing: • Respiratory com prom ise (e.g., dyspnea, wheeze, strid o r, hypoxemia) * Reduced SBP o r assoc sx o f end-organ hypo-perfusion (syncope, hypotonia)

• > 2 o f the follow ing occurrin g rapidly (min to severa! hrs) afte r exposure to allergen • Skin & /o r mucosal involv (hives, ¡tching, flushing, & swollen lips, tongue, o r uvula) • Reduced SBP o r associated sym ptom s o f end-organ hypo-perfusion • R espiratory com prom ise • Persistent G l symptom s • Reduced SBP a fte r exposure to a k n o w n allergen fo r th a t p t (m in to several hrs) M anagem ent • Remove allergen. ABCs; C V R /O 2 m o n itor, continuous BP m onitor. Place patient in recum bent position w ith the lo w e r extrem icles elevated if tolerate d • IM epinephrine is firs t line tre a tm e n t (1:1,000 solution, 0.01 mg/kg [0.01 mL/kg] max 0.3 mg [0.3 m L]) • Repeat q5~15m in as needed • C o nside r epinephrine infusión fo r persistent hypotension • Supplemental oxygen • O btain IV /IO access:Aggressive volum e resuscltation, s ta rt w ith 20 cc/kg and repeat fo r orthostasis, hypotension o r ¡ncom plcte response to IM epinephrine • Inhaled |32-agonists fo r wheeze • H i blocke r: Diphenhydram ine IV (1.25 mg/kg/dose, up to SO mg/dose); w o rks fo r u rtica ria and p ru ritis, w ill n o t help w ith re sp ira to ry symptom s, Gl sym ptom s. o r shock • H 2 blocker: Ranitidine IV (0.5—1 mg/kg, up to 50 mg/dose) • C o rtico ste ro id s: • M ethylprednlsolone IV 1 -2 mg/kg up to 125 mg/dose • O b s e r v a t io n : Usual observación is 6 -8 h r • Tryptase level: C o nside r sending w ith in 4 -6 h r o f presentación f o r unclear cases to im prove diagnostic accuracy Tryptase levels can be norm al during foo d anaphylaxis. Rem em ber th a t tryp ta se levels w ill n o t help you in th e acute setting • T h e r a p y f o r p a t ie n t a t d is c h a rg e : • First line therapy EpiPen (0.3 mg) fo r pts >30 kg and EpiPenJr (0.15 mg) fo r pts 1 5 -3 0 kg. C o nside r EpiPenJr fo r pts 3 m o w / fe v e r > 4 0 °C ; -3 8 % found to have severe bacterial Infxn (SBI) • D u ra tlo n o f fever does n o t p re d lct bacteremia • H x o f fever per parents a t hom e (rectal tem p) in afebrile patient in office w arrants fu rth e r eval (1 study 6/63 afebrile pts w / H x o f fever as above found to have SBI) ■ M últiple studies evaluated lo w -risk crite ria and institutio na l practices vary Id e n tifie d S ources & D ia g n o stic E v a lu a tio n ¡Ann Emerg Med 2030:36:002) (i.e., w h a t counts as "ide n tified so urce" o f fever th a t eliminates o r modlfies the workup? < 2 8 d oíd Identified Source • N o th in g counts as a source, pt needs full sepsis w o rku p • D e fin itio n : R e ctal te m p > 1 0 0 .4 °F /3 8 °C • For newborns, re fer to "sepsis eval in the n ew b o rn ” in the N IC U chapter • O f pts 3 8 "C to ED -12% w / SBI (Emerg Med C lin N o rth A m 2007:25:1087) • M o st com m on bacterial infxns are UTIs and o ccu lt bacteremia • RSV+ is n o t a source: consider C X R if resp sym ptom s are present • Neonatal HSV (1:3,200) deliveries; the 1st 2 w k o f life and only m in o rity w / fever • A dd acyclovlr 20 mg/kg IV ¡f risk factors present • Risk factors: 1° maternal infection (esp w / vaginal dellvery), PROM, use o f fetal scalp electrodes, skin, eye o r m o u th lesions, seizures, CSF pleocytosis DiagnosislEvaluationlManagement • Labs: Bcx, C B C /dlff, Sterile Ucx (cath o r bladder tap )/U A , LP, C X R (if resp sx, chest findings o r O í sat 1 0 0 .4 °F /3 8 °C • L o w -ris k c r it e r ia fo r febrile infants 2 9 -9 0 d • C lin ic a l c r ite r ia : Previously healthy FT w / uncom p course. N o n to x ic , well appearlng, no suspicion o f meningitis (i.e., fussiness, lethargy, p o o r feeding) Reliable access to f/u care (no language, financial, etc. b arrie r)

2-9

• L a b o r a to r y c rite ria : • W B C co u n t 5 -1 5 ,0 0 0 /m m 3 • U riñe: Neg GS unspun (best), o r neg U A (Leukocyte esterase and n itrite neg), o r 5 W B C in stoo l, send stoo l and blood ex. A b x n o t indicated before sto o l ex results, unless child is to x ic • Rapid stre p+ (n o t ve ry com m on in this age group) • URI: Can co e xist w / bacteremia, c annot be considered solé source in children M in sim ilar sports. Football highest fo r boys, soccer fo r girls • W h e n seen in the ED, athlete should n ot re tu rn to play th e same day S te p w is e R e tu rn to Play (AAP Guidelines: Pediatr/cs 2010:126:597) • Each stage in concussion rehabilitation should last no less than 24 h r w ith a m íni­ m um o f 5 d required to consider a full re tu rn to co m p e titio n . If sym ptom s re cu r during the rehabilitation program . the athlete should stop immediately. O nce asympto m a tic a fte r at least a n o th e r 24 hr. the athlete should resume at the previous asym ptom atic level and tr y to progress again.Athletes should co n ta ct th e ir healthcare p ro v id e r if sym ptom s recur. A ny athlete w ith m últiple concussions o r prolonged sym ptom s may require a longer concussion-rehabilitation program . w hich is ideally created by a physician w h o is expcricnced in concussion management Rehabilitation Stage

Functional Exercise

1 .N o a ctivity 2. Light a e ro b ic a ctivity

Complete physical and cognitive rest Walking. swimming, stntionary cyding at 70% máximum heart rate: no resistance exercises Specific sports-related drills but no head impact More complex drills. may start light resistance training A fte r medical dearance. particípate in normal training Normal game play

3. 4. 5. 6.

S port-specific exercise N o n c o n ta c t tra in in g d rills F u ll-co n ta ct practice R e turn to play

F O R E I G N B O D I E S A S P I R A T I O N AND I N G E S T I O N (C u rr G astroenerol Rcp 2005 7:212; Pediatr Rev 2009:30:295) A s p ira tio n • Classic H x : A cute choking episode follo w e d by coughing/w heezing/stridor • Unless seen, h is to ry unreliable; should be on differential w / H x o f chronic cough • E x a m : Cough (m o st com m on sx), localized wheeze, & localized í breath sounds • L o c a tio n : Can be e ith e r side as children have approx sym m etric bronchial angles • E v a lu a tio n : S tart w / AP/lateral in s p ira to ry /e x p ira to ry films • If unable to cooperate. consider le ft and rig h t lateral decubitus in sp ira to ry Films • i inflation on affected side. CXR can be nml. Freq w / localized air trapping o r atelectasis • Clinical sym ptom s and radiologic findings before bronchoscopy have lo w diagnos­ tic valué. Usually foreign bodics are nuts/vegetables -80% , both radiolucent • M a n a g e m e n t: If concern fo r aspiration o r partial o b stru ctio n , rigid bronchoscopy under general anesthesia • Postbronchoscopy w ill require observation. pulm onary to ile t. and possible antibiotics • C o m p le te airway o b s tru ctio n requires back slaps and chest th rusts in head dow n position fo r infants o r abdominal th rusts fo r o ld e r children • A sym ptom atic patients w h o have norm al exam and norm al radiography can be observed a t hom e Ingestió n • C o m m o n foreign bodies ingested are coins (m ost com m on). toys, sharp objects, batceries, magnets, bones, & food • 80-90% o f foreign bodies th a t com e to medical a tte n tio n pass uneventfully, 10-20% require endoscopic rem oval & 10 cm cannot pass in adults. Unclear in children • Have greater concern fo r sharp objects, such as pins/needles • Disc batteries often pass w /o issue; some cause ulccrs & may need endoscopy • In te s tin e : Safety pins in duodenum need removal bccause they can becom c lodged • Coins/disc batteries cvcntually pass • Rarely o b stru ct unless w / anatomical abn (Meckel diverticulum o r in appendix) • Magnets - if m últiple and beyond reach o f endoscope, need careful fo llo w -u p o r surgical in terven tio n • O u t p a t ie n t m a n a g e m e n t: N o t necessary to sieve feces to fínd object • Follow -up x-ray in 1 -2 w k fo r passage • If witnessed ingest o f radiolucent FB. may need f/u endoscopy o r contrast x-ray eval

T H E C R Y I N G INFANT D e fin itio n (Emerg Med C lr k r r t h A m 2007;25:1137) • In o u tp a tie n t setting, 101.3°F), tC R P (>2 mg/dL), ÍESR (40 m m /hr), and Í W B C (>12 x 10 9/L) w / in ability to bear weight. if all the five factors present, then 98% probability o f septic a rth ritis. Elevated CRP is an ¡ndependent risk factor. Diagnosed by >50,000 W B C in jo in t aspírate (J Bone Joint SurgAm 2006:88:1251) S a lt e r - H a r r is C la s s ific a tio n (S A L T R ) • T ype I (S tra ig h t): Fracture through physis. N m l x-ray w / pain o ver site (open g ro w th píate) • T ype II (A b o v e ): Fracture extends in to metaphysis • T ype III (L o w e r): Fracture extends in to epiphysis • T ype IV (T h ro u g h ): Fracture extends through both metaphysis and epiphysis • T ype V (Ruined/need E R ): Physis is crushed o r compressed axially • Severity o f in ju ry & assoc m o rb id ity Ting SALTR class; ty p e V m o st severe F ra c tu r e s R e q u ir in g I m m e d ia t e , S a m e -d a y , A t t e n t io n • S u p ra c o n d y la r fr a c tu r e o f th e h u m e ru s • Supracondylar fx can com prom ise (1) brachial artery, (2) median, & (3) radial nerve • Test che median nerve sensory pathway on the ventral Índex finger and the m o to r pathway by asking to make an O K sign w ith the thum b and forefinger • Test the radial nerve sensor pathway in the dorsal web-spaces and the m o to r pathway by asking the patient to hold up th e ir hand indicating “ stop ” • O p e n fra c tu re s • S lip p e d c a p ita l fe m o r a l epiphysis (A m Fam Physician 1998;57:2135) • Can lead to osteonecrosis o f fem oral head • Usually obese, early puberty, p /w pain and altered gait (several w k) 25—40% bilateral O t ta w a A n k le R u le s • Predicción rules designed to elimínate unnecessary x-rays o f ankle in adults • A D U L T S do n o t require an x-ray if they are • A N K LE : (1) A ble to w a lk im m ediately follow ing an in ju ry o r can take 4 steps in the ER and (2) have no tenderness o ver the p o s te rio r malleoli o r • M ID FO O T: (1) A ble to w a lk im mediately follow ing an injury o r can take 4 steps in the ER and (2) have no tenderness over the navicular, o r the proxim al 5th metatarsal • Sensitivity o f 1 (i.e., the re is zero likelihood o f having a fra ctu re if these crite ria are n o t m et) (JAMA 1993:269:1127) • In c h ild re n , these rules likely apply a fte r g ro w th is compleced • W ill miss 14 fractures p e r 1,000 children w / a neg exam by the O tta w a ankle rules (A rch Dis C hild 2005:90:1309) F ra c tu re s S uggestive o f N o n -a c c id e n ta l T r a u m a • Fracture Type: Fractures in various stages o f heallng; metaphyseal-epiphyseal frac­ tures; distal hum erus transphyseal fra ctu re : fém ur fra ctu re in child before walking; hum erus diaphyseal fra ctu re 7.5 g is considered to x ic • PE: A s above; in the -1 st 24 h r nonspecific. Evidence o f h e p ato toxicity in 2 4 -3 6 h r • L a b s: Plasma acetaminophen level at 4 h r predictive (use R um ack-M a tthe w nom o ­ gram) (Pediatrics 1975:55:871) o r available online at w w w .utoron to.ca /kids/a ceta . htm . C heck baseline Chem 7, LFTs, coags • Serum transaminases peak by 3 -A d a fte r ingestión. Serum and uriñe to xicolo g y • T r e a tm e n t • A ctivated charcoal given if q12h fo r 14 d.

Lead

D im ercaprol (B A L): 2.5-3 mg/kg q4h fo r 2 d -» q4-6h for 2 d —» q4—12h fo r 7 d. E D T A 50-75 mg/kg/d divided q3-6doses; Penicillamine: 15-20 mg/kg/d divided q6h; D M S A 10 mg/kg q8h fo r 5 d -> q12h fo r 14 d.

M ercury

D M S A : 10 mg/kg q8h for 5 d -> 10 mg/kg q12h for 14 d; Penicillamine: 25-100 mg/kg/d divided in 2-4 doses; BAL: 3-5 mg/kg/q4h fo r 3 d -» 2.5-3 mg/kg q6h for 2 d —> 2.5-3 mg/kg q 15h fo r 7 d

Iron

D eferoxam ine: 15-35 mg/kg/hr IV— use higher end dose for severe symptoms

Isoniazid

Pyridoxine: 5-10% : 1 g/1 g INH ingested (5 mg if dose unknown)— IV over 30-60 min

M ethanol and ethylene glycol

Ethanol to achieve blood level o f 100 m g/dL. Adults 0.6 mg/kg/7-10 g infused over 1 hr. Child 0.6 mg/kg over 1 hr. Maintenance: 110 mg/kg/hr in adults; 66 mg/kg/hr in children; if levels of methanol o r ethylene glycol exceed 20 mg/dL o r if high anión gap acidosis give Fom epizole: 15 mg/kg x 1 —» 10 mg/kg doses q 12h x 4 -» 15 mg/kg q 12h until leaves 40%

O p io id s

Narcan: Infants, children 20 kg o r >5 yo: 2 mg/dose, may repeat PRN q2-3m¡n

Phenochiazines

D iphenhydram ine: 1.25 mg/kg IV/IM: B enztropine: 1-2 mg IM/IV Benzos: Diazepam : 0.2-0.5 mg/kg q5mln; Lorazepam : 0.050.1 mg/kg; Cyproheptadine: (Perlactln) 60 mcg/kg q6h max: 12 mg/d

Sulfonylureas

Dextrose: 0.5-1 g/kg (2 -4 cc/kg o f D25); O ctreo tld e : adult 50-100 mcg SC q6—12h N a H C O í 1-2 mEq/kg IV (serum pH 7.45-7.55); MgSulfate 50 mg/kg IV

W a rfa rin

V itam in K Child: 1-5 mg;Adu!t 5 -1 0 mg

FACIAL TRAUMA E ye T r a u m a (Emerg Med C in N o rth A m 2008:26:199; Int J Clin Pract 2008:62:17/6; PhllosTrans R Soc Lond B Biol Sci 2011:366:251. CD00416Ó) • C o rn e a l abrasión • Traumatic defect in corneal epithelium • Symptoms o f pain, photophobla. tearing, foreign body sensation • Topical anesthetic (proparacaine) can facilítate exam. Conjunctival injection (co m ­ m on), visual acuity usually norm al.V ery im p o rta n t to e ve rt u p p c r/lo w e r iids • Diagnosis made w ith topical flu orescein staining • Treated w ith a n tlb io tic o in tm e n t and + / - o ra l analgesics, C o n ta ct lens wearers need to have co nta ct lens rem oved, pseudomonas coverage, and referral to ophthalm ology. Eye patchlng is n o t recom m ended • T r a u m a tic h y p h e m a • Layering o f blood in th e a n te rio r cham ber • Caused by blunt traum a d irectly to eye, May be associated w ith head traum a o r fall • Symptoms o f pain, photophobia, visual loss, nausea and vom iting • Rem em ber ABCs and traum a evaluation. O fte n traum a can be seen w ith pen-light exam. M icrohyphem a requires slit lamp exam • A pply eye shield im mediately. D o n o t patch. Place on bed re st w ith head o f bed elevated 30—45 degrees. Emergent ophthalm ology exam • O p e n g lo b e in ju rie s • Full-thickness w ound o f eye wall • Caused by sharp objects, BB guns, ball sports, MVAs • Males 1 0 -3 0 years oíd a tg re a te s t risk • Symptoms o f pain, diplopia, decreased visual acuity • D o n o t touch the eye. Usually presents w ith sub-conjunctival hem orrhage, hyphema and ceardrop pupil (n a rro w segmenc poines to w a rd ru p tu re ) • A pply eye shield Immediately. Can use boctom o f Styrofoam cup as shield. Immediate referral to ophthalm ology • P in n a h e m a to m a • O fte n due to athle tlc in jury, fall, b lo w to head. May cause disru ptio n o f p erichondrlal bloo d vessels causlng cartilage necrosis • Emergent evacuation to avoid caullflow er ear com pllcatlon • C S F o to r r h e a • May be secondary to tem po ra l bone fra ctu re • D o n o t use otoscope o r other instruments. Place on bed rest and elevate head o f bed • Neurosurgical referral and head imaging N a s a l T r a u m a Pediatr Clin N o rth A m 2006:53:195; Pediatr Rev 1998:19:142; Int | Pediatr O to rb n o la ryn g o l 2011 ;75:186) • E pistaxis • 90% due to a n te rio r bleeding and usually arises fro m Kiesselbach’s piexus. A n te rio r bleeding is slow, persistent oozing • C o m m o n ly due to traum a, nose picking, URI, allergic rh initis, foreign body • Management ¡neludes ¡nternal/external exam, then d ire ct nasal pressure fo r 5 -1 0 min w hile patient is sittlng upright

2-23 F acial T rauma

• P o ste rio r bleeds origínate fro m sphenopalatine a rte ry and bleed m o re profusely. Hay be associated w ith hem optysis, hem atem esis, b lo o d in p o s te rio r pharynx, and failure to id en tify an a n te rio r source o f bleeding. H ig h e r risk fo r airway c o m p ro m ise , a spiratio n o f b loo d and hem orrhage. Requires E N T re fe rra l • N a sa l fra c tu re s an d sep tal h e m a to m a • C h ild re n have m ore so ft cartilage w hich can cause m o re so ft tissue swelling w ith traum a. Septal hem atom a develops w hen th e re is d isru p tio n o f septal cartilage fro m p e rich o n d riu m , w h ich can develop pressure-induced avascular necrosis • Require interna l/exte rn al exam which may be d ifficult due to edema. Septal hema­ tom a has septal asym m etry and swelling o f nasal mucosa w ith o b stru ctio n o f nasal passage. Size o f mass does n o t change w ith topical va soco nstrictor • Radiographs are n o t helpful • If n o t septal hem atoma, intracranial o r o cula r injury, should fo llow -u p in 3—4 d when swelling has subsided • Management o f septal hematoma includes p ro m p t surgical evacuadon and antim lcrobial therapy if nasal septal abscess is suspected. • Im p ro pe rly treated septal hem atoma can lead to saddle nose d efo rm ity • C le a r r h in o r r h e a • D ifferential is broad b ut th ln k o f CSF leak caused by skull base fracture • A llo w rh in orrh ea to d rip o n to piece o f paper and classic pattern is central area o f bloo d w ith halo o f clear CSF. N o t a sensitive test • If CSF rh in o rrh e a is suspected, place patie nt on bed rest and elevate head o f bed 30 degrees. C o nsu lt neurosurgery and o tolaryngology O r o p h a ry n g e a l In ju rie s (Pediatr Clin N o rth A m 2006:53:195; Pediatrics 2010;126:c1578) • D e n ta l In ju rie s • Patients w ith a fra ctu re , luxation, to o th pain, o r discoloratio n should undergo dental radiography • Uncom plicated fractures affect the o u te r enamel o r dentin only. Patient can be seen by d en tist in 48 hr • C om plicated fractures involve enamel, dentin, and pulp. Symptoms include to o th pain w ith pressure, tem pe ra ture sensitivity, bleeding fro m co re o f to o th , and malocclusion. Requires im m ediate dental referral • Avulsión refers to com plete displacement o f to o th fro m socket. If prim ary to o th , do n o t reim plant. Permanent teeth begin to e ru p t a t age 6 . If perm anent to o th , handle by crow n, rinse w ith w a te r o r norm al saline and a tte m p t reim plantation. If unable to reim plant, place in m ilk o r o th e r com m ercial product. Patients require im mediate dental referral.Tooth survival outside oral cavity at 1 h r is near 0 • To n g u e an d fre n u lu m in ju rie s • Careful exam ination o f teeth. oropharyngeal foreign bodies, bite fo r malocclusion (m andibular fra ctu re ) andTM J (condylar fracture) • M ost frenulum in juries heal spontaneously and do n o t require repair • Tongue lacerations 1 cm, in to muscle o r lateral tongue, large flaps, o r do n o t achieve hemostasis usually require repair • P a la te injurie s • Superficial and punccure wounds to the central palate tha t are 2 cm, o r w ith unknow n depth o r foreign body w ill likely need repair.These in juries ca rry a small risk o f in ju ry to the carotid a rteries and jugular veins. C o nside r fu rth e r imaging and cióse o bservation fo r neurologic d e te rio ra tio n . O btain o to laryngology consult

FOOD A L L E R G Y N IA ID -S ponsored Food A lle rg y Guidelines (J A lle rg y C lin Im m unol 2010;126:S1) www .niaid.nih.gov/topics/foodA llergy/clinical/Docum ents/FA G uidelinesExecS um m ary.pdf D e f in itio n (Pediatrics 2011:128:955) • Food a lle rg y (FA ): Adverse health effect arising fro m a specific response th a t occurs rep rod u cib ly on exposure to a given food • A n a p h y la x is : A serious ¡m munologic reaction tha t is rapid in onset and may cause death (see ED chapter fo r m ore on anaphylaxis) C la s s ific a tio n (Pediatr Clin N A m 2011:58:315) • IgE m e d ia te d : U rticaria/angioedem a, rhinoconjunctivitis/asthm a. anaphylaxis. p ollen -fo od allergy syndrom e (PFAS) (aka oral allergy syndrom e (O AS)) • M ix e d IgE a n d c e ll m e d ia te d : Acopie derm atitis (A D ), eosinophilic gastrointestinal d isorders (EGIDs) • C e ll m e d ia te d : D ie ta ry p rotein-induced pro cticis/pro ctoco litis, food protein-induced e n te ro colitis syndrom e (FPIES), Celiac disease, H e in er syndrome P a th o p h y s io lo g y (Annu Rev Med 2009:60:261) • IgE mediated: D e n d ritic cells in te ra ct w ith dieta ry antigens -> T-helper-2 response -> B-cell IgE p ro du ction IgE binds on the surface o f mast cells • PFAS: C ross-rea ctivity b tw p roteins in pollen & p roteins in certain fruits/veg • FPIES: May relate to ¡ncreased T N F -a , decreased TGF-|3 E p id e m io lo g y (Pediatr G in N A m 2011:58:327) • S elf-re po rted FA is 10 tim es higher than w h a t can be confirm ed w ith testing • FA is m o re com m on in early childhood and decreases w ith age • S elf-re po rted FA ranges fro m 3-35% ; confirm ed FA ranges fro m 1-10.8% • M ost com m on allergens (kids): C o w ’s milk, egg, wheat, soy, p eanut/tree nut, fish/shellfish C lin ic a l M a n ife s ta tio n s (Pediatr Clin N A m 2011:58:315) • IgE-mediated: O n se t o f sx min to 2 h r a fte r ingestión (urticaria, angioedema, rh in oconjunctivitis, asthma, G l sx, anaphylaxis) vs. Cell Mediated: Delayed rxn • OAS; P ruritis, tingling, mild swelling o f lips, tongue, palate, and th roa t; 10% have systemic findings; 1 - 2 % develop anaphylaxis • Eosinophilic esophagitis: P resentation varios w / age: Feeding d ifficu lty + FTT in young kids, vo m itin g r abd pain in o ld e r kids, dysphagia + fo o d im pa ction in teens • Eosinophilic gastroenteritis: A bd pain, nausea, diarrhea, w eight loss 2/2 malabsorption • Dietary protein-induced proct/tis/proctoco/it/s.Typically breastfed infants age 2 -8 wk, mucus + bloo d in stools b ut oth e rw ise well-appearing, rem oving allergenic foo d fro m m other's d iet leads to rapid im provem ent • FPIES: Peak incidence 1 w k -3 mo, usually form ula fed; severe G l symptom s:Vomit¡ng, diarrhea, FTT, anemia, hypotension and le thargy 2/2 dehydration E v a lu a tio n (j Allergy Clin Immunol 2010:126:51, Ann Allergy Asthma Immunol 2006;96:S1.J Allergy G in Im m unol 2004:114:213) • H isto ry is key: Identify c u lprit foods, tim e course o f rxn, quancity ingested, ancillary factors, H x o f sim ilar sx.and FHx and personal hx o f atopy • IgE mediated: Skin p rick testing (SPT) and specific serum IgE (slgE) measurements can be helpful but n o t diagnostic; to avoid falser, pts should be tested only to suspect foods and when the re is high pre te st probability • Skin p ric k tests (fo r IgE-mediated d iso rd e rs):A wheal >3 m m is considered positive • SPT: Sensitivity >90%; specificity approx 50% • CAP-FEIA (fo rm e rly RAST): Measures food-specific serum IgE • Im m unoC A P is th e p referred CAP-FEIA • D ouble-blind, p lacebo-controlled foo d challenge gold std fo r dx; only in co ntro lle d setting; should be done if dx o f FA unclear o r to co nfirm suspected resolución o f FA • EGIDs: SPT, slgE, atopy patch testing may be helpful b u t mucosal bx needed fo r dx • D ie tary protein-induced proctitis/proctocolitis/FPIES: D x based on history, sx resolution w ith causacive food elimination.and sx recurrence w ith food challenge M a n a g e m e n t a n d P re v e n tio n (Pediatrics 2011;128:955, Pediatr C m N A m 2011:58:481, J Allergy Clin Immunol 2011:127:654) • Key to m gm t is avoidance o f allergen (w w w .fo od a lle rg y.o rg has practical tips) • Tx:A ntih istam in es fo r O AS and nonsevere rxns, epi fo r all pts w / systemic rxns • C u rre n t research f o r tx o f FA includes im m unotherapy and anti-lgE antibodies

A topy

3 -2

• O ra l im m unotherapy has been show n to induce desensitization and enable patients to ingest a greater am o un t o f allergenic fo o d p ro te in • R estricting m o th e rs diet in pregnancy o r lactation to prevent FA n o t recom m ended • N o evidence that delayed in tro o f solid food >4 m o prevents FA and some evidence that delayed in tro o f solids may prom ote allergy • Vaccines containing egg include influenza. MMR, yellow fever. rabies • MM R vaccine is n o t contraindicated fo r children w ith egg allergy • Flu vaccine: If m ild rx n to egg (hives only) > safe to give vaccine in office w ith precautions (resuscitative equipm ent available and observe p t fo r 30 min); if severe rx n (CV. resp, Gl sx) -> allergy consultation fo r evaluation o f egg allergy and vaccine adm inistración (Pediatrics 2 01 1 :12 8 :81 3 -8 2 5)

A T OP I C D E R M A T I T I S ( A D ) D e fin itio n ;J Allergy Clin Immuno 2006:118:152) • C h ro n ic, ¡m m une-m ediated, inflam m atory. p ru ritic skin dz o ccu rrin g in pts w / atopic diathesis, w / variable clinical p atte rn depending on age P a th o p h y sio lo g y (J Irwest Dermatol 2012:132:949) • Impaired epiderm al b a rrie r: S tratum corneum defects -> i epiderm al w a te r co n te n t • M utations in the filaggrin gene predispose t o A D (filaggrin is a p ro te in in the stratum corneum th at helps maintain hydration and has anti-staph properties) • D ry skin —> p ru ritis and scratching -> traum a and inflam m ation • W a te r loss -> changes in epiderm al lipids -> cracks in the stratum corneum • A ntigenic and irrita n t agents penétrate the skin and actívate im m une cells • Immune dysfunction w / exaggerated T»,2 response: IgE prod, eosinophilia, and p ro in fla m m a to ry cytokines -> hyperactive im m une response —> extravasaron o f inflam m atory cells, cellular signaling at in ju ry site • P ruritus mechanism n o t just 2/2 histamine • Triggers: Stress-induced im m unom odulation, food + inhalant allergens, Chemical irritants, skin infection, hot/hum id o r c o ld /d ry weather. viral infections esp w / fever E p id c m io lo g y (N Lngl j Med 2008:358:1483. N Engl J Med 2005:352:2314) • A ffects 15-30% o f children and 2 -1 0 % o f adults • Age o f onset: 45% in 1st 6 m o o f life, 60% before age 1; 85% before age 5 • 70% o f children have spontaneous remission before adolescence • 77% concordance rate fo r m onozygotic tw ins; 15% fo r dizygotic • A sthm a develops in approx 30% and allergic rh in itis in 35% o f children w ith A D C lin ic a l M a n ife s ta tio n s 0 Allergy Clin lmrr.unol 2006:118:152) • Infantile stage (infancy-2 yo) • Location: Cheeks, forehead. scalp, may spread to tru n k • Intensely p ru ritic . erythem atous, scaly lesions, may have vesicles o r serous exúdate in severe cases • Childhood stage (2 y o -p u b e rty ) • Location: Flexural surfaces, w rists, anides, hands, feet, neck. dorsum o f e xtrem itie s • Less exudation; m ore lichenified papules and plaques • Adult stage (p u b e rty -) • Location: Flexural surfaces. face, neck, upper arms, back, hands. feet • D ry, scaly erythem atous papules & plaques: lichenified plaques in areas o f ch ronicity • W / severe cases, any area involved, b ut axillary. groin, & gluteal areas usually spared • Com plications: Bacterial o r viral superinfxn o f eczematous sites (e.g.. eczema herpeticum ) D ia g n o s tic S tu d ie s (N Engl J Med 2005:352:2314) • Clinical crite ria : Evidence o f itchy skin + 3 o f the follow ing: • H /o ¡nvolvem ent o f skin creases • H /o generally d ry skin in th e past year • H /o asthma o r hay fe v e r ( o r FH x atopy in 1st-degree re la tive fo r pts 6 mo, self-resolves, usually vaccine Abs nml) • M a n a g e m e n t: (X -linked A gamm aglobulinem ia in GeneReviews 1 9 9 7-20 1 1) • Mainstay o f tre a tm e n t is IVIG; some centers use chro nic prophylactic antibiotics • W ith acute infections tx course should be 2x as long as in healthy pts • Live viral vaccines (esp oral p olio) should be avoided • C o m p lic a tio n s : • Unclear if same predisposition fo r malignancy as o th e r im mune deficlencies • C h ro nic meningoencephalitis fro m coxsackie o r e nterovirus • H igher incidence o f aseptic p o lya rth ritis, JIA, derm atom yositis C o m m o n V a r ia b le Im m u n o d e f ( C V I D ) (j Allergy Clm Immunol 2005:109:581) • D e fin itio n : Hypogammaglobulinemia w ith onset later in life; often associated w ithT-cell dysfunction, autoimmunity, malignancy • P athophysiology: N o single m olecular dx; catch-all fo r several ¡mmunodefs • D ru g induced: Phenytoin, gold, o r sulfasalazine may be trigger • B cells usually nml in # b u t do n o t differentiate in to Ig producing cells • E p id e m io lo g y : Average age o f onset is 25 yo w / even sex d istrib utio n • C lin ic a l m a n ife s ta tio n s : • Similar to X L A ; encapsulated organisms, sinopulm infxns (see previous discussion) o ften leading to bronchiectasis if continued pulm onary infections • Exam: Lymphoid hyperplasia (in co ntra st to X -linked): Large tonsils, nodes, spleen • Gl tra c t affected in a bo ut Vz o f pts: Lym phoid p ro liferatio n o f gut, chro nic diarrhea, m alabsorption, lactose intolerance, infection w ith Campylobacter.Yersinia, Giardia • A p p ro x 22% o f pts have autoim m une disorders: RA, hem olytic anemia, pernicious anemia, a utoim m une endocrinopathies • Increased incidence o f malignancy (esp involving G l tra c t + lym phoid tissues) • D ia g n o stic studies: • Total Ig is m arkedly decreased, b ut generally n o t as depressed as in X L A • A ny o r all classes o f Ig can be affected: degree o f hypogammaglobulinemia is variable • T-cell function is variable (can be affected in a bo ut 50% o f patients) • Abn A b response to vaccines • M a n a g e m e n t: Same as above fo r X LA ; m o n ito rin g pulm onary fun ctio n Ig A D e fic ie n c y (j C lh Immunol 2010:30:10) • D e fin itio n : IgA antibody deficiency w ith norm al levels o f o th e r Ig isotypes in pts >4 yo • P a th o p h y s io lo g y : • B cells fail to differentiate in to plasma cells expressing/secreting IgA • N o w ell-defined genetic susceptibility; likely heterogeneous g roup o f genetic defects • E p id e m io lo g y : M o st com m on in M iddle East, Africa, and Caucasian populations • Incidence 1:223 to 1:3000 in US, m ost com m on p rim a ry im m unodeficiency • C lin ic a l m a n ife s ta tio n s : Asymp in 85-90% o f pts • If sym ptom atic: R ecurrent sin opulm onary in fections (S. pneumoniae, H. influenzae), Gl infections and disorders (lactose intolerance, celiac, U C ) • P redisposition to allergic and autoim m une disorders • D ia g n o s tic studies: Send tota l Ig and Ig isotypes and subclasses • IgA prophylactic abx; if c o n cu rre n t IgG subclass deficiency -> IVIG • C o m p lic a tio n s : Risk o f anaphylaxis w ith transfusions as may develop anti-lgA Ab: Blood producís should be fro m IgA d eficient individual o r saline washed RBCs

T-CELL DEFICIENCIES (CELLULAR IMMUNITY) D iG e o r g e S y n d ro m e (D G S )/T h y m ic A p ia s ia (N Engl J Med 2000:3-43:13 í 3} • D e f in itio n (J Pediatr 2001:139:715) • Thym ic and parathyroid aplasia/hypoplasia w / 4 T cells and frequenc o p p o rtu n istic infections as w ell as hypocalcemia, presents neonatally • Divided in to partial and complete types: 1% o f pts have com plete DGS (a form o f SCID) w / severe immunodeficiency; pts w / parcial DGS have m ilder immunodeficiency • P a th o p h y s io lo g y : Embryologically 3rd and 4th pharyngeal pouches form incorre ctly * M icrod e letio n o f 22 q 1 1 . 2 is th e m o st com m on defect, generally de novo mutación • E p id e m io lo g y : 1:4000 to 1:6000 prevalence • C lin ic a l m a n ife s ta tio n s : P/w tetany/szrs 2/2 hypocalcemia in 1st few days o f life * A ll T-cell def generally present w ith in 1 st 1 -3 m o o f age w / o p p o rtu n istic infections, viral infections, fungal in fections (PCP), ¡ntracellular bacteria • Can have sim ilar facies to fecal alcohol syndrome: S ho rt filtru m , lo w set ears • D ia g n o s tic s tu d ie s : Absoluce lym phocyte co un t 4, B-cell co un t T, Ig nml ♦ i mitogen stim ulation response, can have delayed hypersensitivity skin testing ■ M a n a g e m e n t: Bone m a rro w transplant w / H L A match * Thym ic transplant in neonatal period (N Engl J Med 1999:341:1180) • C o m p lic a tio n s : Can have o th e r stru ctu ra l anomalies; conotruncal cardiac anomalies, right-sided a o rtic arch, esophageal atresia, bifid uvula, congenital heart disease, hypertelorism , mandibular hypoplasia, lo w set ears • G V H D to nonirradiated blood produces o r to BM T w it h T cells

COMBINED IMMUNE D E F I C I E N C I E S S e v e re C o m b in e d Im m u n o d e fic ie n c y (S C ID ) • D e fin itio n : (N Engl J Med 2000:343:1313) • M ost severe 1o ¡m munodef, lym phopenia, no thym ocytes, incom patible w / life • M ostlyT-ccIl deficiency, b u t can also involve B cells and N K cells (com bined) • P athophysiology: (J A lle rg y Clin Im m unol 2009:124:1161) • M últip le gene loci including: T -B + S C ID : IL2RG encoding y-chains o f interleukins (m ost co m m o n),Jak3, IL7RA, CD3, CD45; T - B - S C ID : R A G 1/R A G 2.A D A deficiency, O m enn syn drom e ,A rtem is deficiency • Inheritance autosom al recessive and X -lin ke d (fo r IL2RG) • G enerally small thymus, w / p o o r thym ocyte p ro du ction (n o T cells) • E p id e m io lo g y : A ffects 1 in 100,000 (Pediatrics 2010;125:e1226) • For X -lin ke d all are male, b u t overall SCID has small female predominance • C lin ic a l m a n ife s ta tio n s : (| Pediatr 1997;130:378) • Infant p /w FTT, chronic diarrhea, PNA, O M , sepsis, o p p o rtu n istic infxns, cutaneous Candida, thrush, re cu rre n t RSV, fre qu e nt HSV outbreaks • Candida albicans, PCP, varicella, measles, Paraflu3, CMV. EBV.Adeno • D ia g n o stic studies: A t b irth , W B C repeat analysis o f TRECs and |)-actin (to ensure in te g rity o f D N A ) -» TRECs still lo w —> flo w c yto m e try • M a n a g e m e n t: P e d ia tric e m e rg e n c y (E ur J Pediatr 2011:170:561) • H em a top oietic stem cell transplant (success rate -90% in best circumstances) • For A D A deficiency: Enzyme replacem ent is an a lternative tx • N e w innovations: Gene Rx (fo r A D A and IL2RG) • C o m p lic a tio n s : G V H D to nonirradiated blood produets o r to BM T w / T cells • Severe sepsis, severe viral infections because o f im m unocom prom ised State

A ta x ia -T e la n g ie c ta s ia • D e f in itio n : (Pediatr A lle rg y Im m unol 2005:16:615) • Progressive d lso rd e r w / cerebellar ataxia, oculocutaneous telangiectasias and com bined im m unodeficiency (T and sometimes B) • P atho p h y sio lo g y • M utation in AT on long arm ch ro m o 11 q22—23 (encodes D N A -d e pe n de nt p rotein kinase involved in D N A repair, cell cycle signaling and meiocic co n tro l) • 1 C D 3 & C D 4 c o u n ts .l response t o í - & B-cell mitogens,helperT-cell & B-cell defects • E p id e m io lo g y : Equal male and female incidence, 1 in 40,0 00 -1 00 ,00 0 birth s • A uto som al recessive, so consanguinity increases risk o f disease • C lin ic a l m a n ife s ta tio n s : () Pediatr 2004:144:505) • Early d e te rio ra tio n o f gait beginning 1 -4 yo w ith ataxia (w heelchair by 1 0 -1 2 yo) • Extrapyramidal d e te rio ra tio n , o c u lo m o to r apraxia, nystagmus, p o o r a rticulation • Telangiectasias in conjunctiva and skin appear by age 3 -6 y r a fte r neurologic signs • C o n c u rre n t sinopulm onary Infections (70%) severe PNA • D ia g n o s tic studies • Selective absence o f IgA (50-80% ), IgG and IgE generally i , o ften T-cell deficiency (60-75% ), and m o re rarely B cells 4 as well • Elevatcd AFP, abnorm al ATM kinase activity (if lab can obcain test) • MRI w / degeneration o f granular and Purkinje cells (N eu ro ra dio lo gy 2003;45:315) • M a n a g e m e n t: Prophylactic antibiotics if indicated; IVIG fo r hypogammaglobulinemia o r specific antibody defect; supportive measures • C o m p lic a tio n s : T incidence (200x) malignancies; lymphoma, leukemia.and adeno Ca • E xtrem e sensitivity to radiation W is k o t t-A ld r ic h • D e f in itio n : (N Engl J Med 2006:355:1759, C u rr O pin Hemacol 2008:15:30) • X -lin ke d d/o w / A D, th ro m bo cytop en lc purpura, dysfunction o f platelets leading to bleeding and predisposition to infection • P atho p h y sio lo g y (C u rr O pin Hemacol 2005:12:284) • W ASP (W is k o tt-A ld ric h syndrom e p ro te in ) m utated ( X p l 1.22—11.23) >160 muts • WASP, norm ally expressed in iym phocytes and megakaryocyces, Controls actin assembly fo r microvesicles Involved w ith tyroslne kinase and p ro te in kinase c signaling affecting B,T, and N K cells • T cells cannot in te ra ct w / A PC, B-cell adhesión inhibited by p o o r cytoskeleton reorganization and p o o r cell m o tility • E p id e m io lo g y : X -lin ke d recessive syndrome, generally only affects males • C lin ic a l m a n ife s ta tio n s : (N Engl J Med 1995;333:431) • Bloody diarrhea, bruising, bleeding a fte r circ, throm bo cytop en ia neonatally • Frequent O M , PNA, sinusitis, and o p p o rtu n istic infections; severe eczema • D iag n o stic studies: Serum IgM decreased, IgA and IgE o ften increased, to ta l Ig norm al • T cells lo w w / p o o r m itogen response, B cells can be increased • Thro m b ocyto pe nia 200 m utations o f C 1 -IN H gene id entified • C1 activates dassical co m p iem en t pathway; C 1 -IN H prevents spont activation E p id e m io lo g y : Usually presents in 1st o r 2nd decade o f life: 1:10,000 to 1:150,000 • 25% o f pts have no fam ily h isto ry and are presumed new mutations C lin ic a l m a n ife s ta tio n s : • 50% have attacks 12 tim e s/yr • Patients generally feel p ro d ro m e 1 -2 h r before onset • R ecurrent edema lasting up to 1 w k a fte r stress o r traum atic events • Edema tends to be nonpainful, nonpitting; subcutis (face, tru n k, genitals, extrem ities) and submucosal (intestines, larynx), laryngeal swelling can be life-threatening • Intestinal swelling -» significant abdominal pain, vom iting, diarrhea; sx can be sim ilar to a ppendicitis/other causes o f acute abdomen D ia g n o s tic s tu d ie s : • I C 1 -IN H and i levels o f C4 (T C1 levels re su lt inT cleavage o f C4 fro m pathway) • N m l com piem ent levels and C1 inhib levels reached fro m 2—3 yo, infant eval uncertain M a n a g e m e n t: • N o t a histam ine release so typical agcnts (antl-histamines, epi.ste ro ids) w lll n o t help • A cute attacks: H ydration, pain relief, plasma derlved C 1 -IN H o r ecallantlde (kalllkrein inhibito r) o r icatibant (bradykinin B2 re ce pto r antagonist); 2nd-line agents: FFP and solvent detergent-treated plasma • S ho rt-te rm ppx (before high-risk pro ced ure):C 1-IN H (off-label);or danazol (androgen) + /- C 1 -IN H , icatibant, o r ecallantide; o r FFP • L ong-term ppx: (If attacks >1/m o); danazol o r a n tifib rln o lytic agent (tranexam ic acid) • N e w therapies: N a no -filte re d C 1 -IN H concéntrate (FD A approved fo r long-term prophy), recom binant human C 1 -IN H (under FDA review fo r acute attacks) C o m p lic a t io n s : C ritica l airway management • ACE in hibito rs, O C P (estrogen), dental w o rk can bring on an eplsode • H lgher incidence o f autoim m une disease.no higher incidence o f atopy

O t h e r C o m p ie m e n t D e fic ie n c íe s ;'Mol Irritriuriol 2011:48:1643) • C 1 q def; sepsis, meningitis, pneumonía; S. pneumoniae, N. meningitidis; SLE-like syndrom e • C2 def; sepsis, meningitis, pneumonía; S. pneumoniae, N. meningitidis, S. aureus; rheum atic disease, C V disease • C5, C 6 , C7, C 8 , C9 def; meningococcal meningitis • C D 59, C D 5 5 def:Throm bosis, h em atopoietic cytopenia

PHAGOCYTIC DIS ORDERS O v e rV ie w (N Engl J Med 2000:343:1703) • Include congenltal neutropenlas (cycllc neutropenla, severe congenital neutropenia, S hw achm an-Diam ond), adhesión defects (leukocyte adhesión deficiency), abnormal chem otaxis (H ype r IgE syndrom e), intra cellula r killing defeccs (C G D ), defeccs in form a tion /fxn o f neutro ph il granules (Chediak—Higashi) • Consider phagocytic d isorder if p t continúes liaving severe o r unusual bacterial o r fungal infxns and all o th e r w o rku p fo r B- and T-cell deficiencies negative C h r o n ic G r a n u lo m a to u s D is e a s e ( C G D ) (N Engl j Med 2000:343:1703) • D e fin itio n : D cfe ct in N A D P H oxidase resulting in im paired ability to kill bacteria + fungi • P athophysiology: • Norm ally, N A D P H oxidase -> hydrogen peroxid e fo rm a tio n -> hypochlorous acid (bleach) fo rm a tio n -> re sp ira to ry b urst • In C G D , 5 know n gene m utations affect assembly and activation o f N A D P H oxidase -> failure to actívate n eu tro ph il resp b urst —> failure to kill catalase positive bacteria • M o st com m on m utation (gp91phox) is X -linked, accounts fo r 70% • E p id e m io lo g y : Q u ite rare, 4 -5 /m illio n , 2/3 are m ale;can be X -linked o r AR • C lin ic a l m a n ife s ta tio n s : (J A lle rg y C lin Im m unol 2011; 127:1319) • M o st infxns 2/2 S. aureus, S. marcescens, Burkholderia eepacia, noeardia, & Aspergillus ' C o m m o n ly develop P NA, lym phadenitis, liver abscess, osteo, skin + so ft tissue infxn • Noncaseating granulomas in brain, lung, liver, spleen, G l tra ct; a utoim m une dz • X -linked: Earlier diagnosis, higher m o rta lity rate

i

• D ia g n o stic studies: (C lin Rev A lle rg y Im m unol 2010:38:3) • See“ Evaluating fo r PID” above:Abnorm al neu tro ph il oxidase fun ctio n suggests C G D • N B T testing replaced by d ihydrorhodam ine o xida tio n (D H R ) testing • M a n a g e m e n t: (J A lle rg y C lin Im m unol 2011:127:1319) • H e m a top oietic cransplant is only curative Rx, 90-95% survival o ver previous 10 y r • A ntib a cte ria l (TM P-SM X) and antifungal (¡traconazole) prophylaxis + /im m u n o m o du la to ry therapy (IFN-gamma) • Steroids used co decrease granulomas, low -dose prednisone • C o m p lic a tio n s : G astric o u tle t o r ureteral o b stru ctio n fro m granulomas C h e d ia k - H ig a s h i S y n d ro m e N Engl ] Med 2000:343:1703) • D e fin itio n : Rare defect in chem otaxis w / t susceptibility to bacterial infections, neuropathy, platelet dysfxn. oculocutaneous albinism • P athophy siology : AR d iso rd e r w / abn degranulation o f lysosomal granules • M utation in LYST cytoplasm ic p ro te in involved in vesicle tra n s p o rt affeccing all cells including melanocytes, which results in p o o r delivery pigm ent to skin and hair • E p id e m io lo g y : Rare; 1 in 1 m illio n.A R , dx early childhood, fatal by early adulthood • C lin ic a l m a n ife s ta tio n s : • O culocutaneous albinism, progressive periph neuropathy, m ild MR, period o nta l dz • Infections: Sinopulmonary, skin, susceptible to S. oureus, and ¡i-hemolytic-strep • Defective platelets: Easy bruising, mucosal bleeding • D iagnostic studies: # o f neutrophils slightly l and smear w / giant cytoplasmic granules • M a n a g e m e n t: Prophylactic antibiotics • BM T (does n o t co rre ct/p re ve nt central and peripheral neuro defects) (Bone M a rrow Transplant 2007:39:411) • C o m p lic a tio n s : (J C lin O n co l 2006:24:3505) • A ccelerated dz in 85% o f pts: Lymphoma-like syndrome (nonmalignant cells) w / pancytopenia, fever, lym phocyte infiltration o f liver, spleen, nodes tha t may be related to EBV infection, often becomes uncontrolled and leads to death • If p t survives, can lead to severe neuro manifestations by 20 s and wheelchair bound

EKG IN T E R PR E T A T IO N

EKG

4-1

A p p ro a c h to th e E K G • Indicación fo r E KG :W /u fo r chest pain, syncope, cyanotic episodes, drug ingestión, C H D eval, palpitations, pericarditis, Kawasaki dz, myocarditis, rheumatic heart fever, FHx sudden death, and electrolyte abn (Emerg Med Clin N o rth A m 2006;24:195) • Basic EKG: 12 leads w / 6 precordial leads and 3 lim b leads (BMJ 2002;324:1382) • Paper speed usually 25 mm/sec so each small b ox 0.04 sec, 5 boxes 0.20 sec • Standard voltage is 10 m m /m V; 1 mm 0.1 mV; can be m odified on request • Leads: R and L arm, R and L leg give rise to I, II, III, aVL, aVR, aVF • D ip o lar: I, II, III; re present differential fro m one lead to a nother • In I, positive d cflection o f wave is signal traveling fro m RA co L A • In II, positive deflection o f wave is signal traveling fro m RA to L L • In III, positive deflection o f wave is signal traveling fro m L A to L L • U n ip ola r: + deflect - center o u t to lim b; aVR (RA), aVL (LA ), aVF (LL) • Pericardíal leads:V¡ews cardiac activity in the horizon tal plain

aVF

V1 V2 Anterior • Initial EKG read:Always take a system atic approach; check paper speed and voltage • Rhychm: Regular o r irregular; then if sinus (every P follow ed by QRS, unique P wave m orphoiogy, constant PR) • Rate: # o f large (5 mm ) boxes b tw R waves; 1 = 300 bpm, 2 = 150, 3 = 100; pattern is 300 ,1 5 0 ,1 0 0 ,7 5 ,6 0 ,5 0 ; can also use 1500/# small boxes • Axis: If R + in lim b lead, ve cto r goes tow ard tha t lead; nml axis based on age • R waves +l and + aVF - 0 to -9 0 ° (noted as norm al axis; b u t can be abn fo r age) • R waves +l and -aV F = 0 to - 9 0 ° (le ft axis deviación) actually -3 0 to -9 0 rj • R waves I and -raVF = 9 0 -1 8 0 ° (rig h t axis deviation) • R waves - I and -aV F = -9 0 ° to -1 8 0 ° (e xtre m e rig h t/N W deviation) • Neonates w / transition in g fro m R-sided dom inance; initially w / R axis as nml • P wave axis; if sinus then +l, +aVF, if n o t consider ectopic atrial pacer (EAP) • P waves: Should have same m orp ho io g y in a given lead, oth e rw ise multi-pacemakers • 2.5 mm w id e in II a n d /o r biphasic in V I - p m itrale; le ft atrial enlargement • 2.5 mm high in II = p pulmonale; rig h t atrial enlargem ent • Q wave: Can be nml (II, III, aVF,V5,V6), max amp at 3 -5 yrs (0.6—0.8 m V nml) • QRS com plex: R:S ra tio initially >1 in V1 and V2, and 10 mm, u p rig h tT wave in V I, RSR' p attern in V I, w h ere R' >15 mm (10 mm (>1 yo) (Ped ECG Interpretación 2004) • Intervals: In te rp re ta tio n varies based on age group (H e a rt 2005;91:1626) • PR: 1 w / t vagal ton e , h ea rt block, endocarditis w / abscess, hyperK, digoxin, to x, s h o rt w / p re -excita tio n (W P W ), EAP, glycogcn storage dz • QRS: >0.08 msec if 0.10 msec if >8 yo bundle branch block, junctional o r ventricular rhythm (n o t via His-Purkinje) (Emerg Med Clin N o rth A m 2006:24:195) • Q T: S ta rt o f Q to end o f T; c o rre c t fo r HR w / Bazett form ula Q T/vR R • B oth oíd and re ce nt reviews place upper lim it nml Q T c at 450 msec

A g e - d e p e n d e n t C h a n g e s (cm erg Med Clin N o rth A m 2006:24:195) • N m l lim lts prev fro m Davignon et al. (2,141 Caucasian pts), m ore recent by Rljnbeek e t al. w / higher sampling rate w / sign d iff in nml lim its (Euro H e a rt J 2001,22:702) HR

PR In te rv a l

QRS A x is

QRS In te rv a l

Q T c L im it

90-160

0.08-0.15

60-180

0.03-0.08

5.5 m g/dL in 89% pts w / essent H T N ; 30% w / 2o HTN

H y p e r t e h s io n

E tio lo g y Pediatr Rev 2007:78:283) • M ost childhood H T N due to 2o causes (60-70% renal dz, rarely essential H T N 10 mm Hg is a rpulsus (JAMA 2007:297:1810) T r c a t m e n t (Eur hedí t J 2004:25:587) • Management depends on type and underlying e tiolo g y o f pericarditis • Pain management and tre a tm e n t o f inflam m ation w ith NSAIDs, the o re tical risk o f h em orrhagic conversión exists b u t n o t established • Colchicine dem onstrated to be effective in adult triáis, n o t approved in peds

• Acutely, steroids only fo r pts re ca lcitra nt to NS A ID s o r pts w / acute pericarditis 2/2 connective tissue disease, autoim m une pericarditis o r urem ic pericarditis • P urulent pericarditis w / severe inflam resp may benefit fro m 1 -2 w k steroids, as m ayTB pericarditis both acutely & chronically (Pediatr Infect Dis J 2006;25:165) • Pericardiocentesis indicated in tam ponade physiology, o r if purulent, tuberculous, o r malignant effusion suspected C o m p lic a tio n s • Fibrosis and constrictive pericarditis can o ccur 2/2 purulent pericarditis resulting in heart failure w / a small ra the r than large globular appearing heart

R e s tric tiv e C a rd io m y o p a th y • D e fin itio n : Diastolic dysfxn w / preserved systolic fxn w /o ventricular hypertrophy o r dilation • Im paired ve n tricula r filling w / nml o r v diastolic volum e 2/2 heart muscle dz • E p id e m io lo g y (H e a rt 2 00 5;9 1:1 199; N EnglJ Med 1997:336:267) • Rare in children (only 2-5% o f p t w / pediatric cardiom yopathy) • Etiologies: Idiopathic, familial, in filtra tive dz (Gaucher, H urler, am yloid), storage dz (Fabry, glycogen storage, hem ochrom atosis), hemosiderosis, drugs, X R T • C lin ic a l m a n ife s ta tio n s • Etiology dependent; dyspnea, tachypnea, fatigue, PND, o rtho p ne a. periph edema

4 -1 4

H y p e rtr o p h ic C a rd io m y o p a th y (JAMA 2002:287:1308} • D e f in itio n : C om plex, relatively com m on genecic dz; presents a t any age • A D inheritance 2/2 m utations in any 1 o f 10 genes (m ost com m only (i-myosin heavy chain, cardiac tro p o n in T , o r myosin-binding p ro te in C) • E p id e m io lo g y : M ost common genetic C V d z;m ost common cause sudden death in kids • A prevalence o f 1:500 in the general population • C lin ic a l m a n ife s ta tio n s • M o st H C M pts w / n onobstructive dz (75% w /o sizable resting o u tflo w tra c t obst) • May p /w sudden death, CP. syncope, h ea rt m urm ur, + FHx, o r abn EKG • D ia g n o s tic s tu d ie s : EKG abn in 75-95% o f pts • Echo w / hypcrtrop hicd nondilatcd LV in the absence o f o th e r cardiac o r systemic dz • MRI may show asym m etric LVH undetectable on echo • P ro g n o s is : O verall annual m o rta lity rate is 1% • Risk faccors fo r sudden death: P rio r H x o f cardiac arrest, spontaneous VT, FHx o f sudden death, syncope. hypotension during exercise, and extrem e LVH • T r e a tm e n t • G enotype w /o Phenotype • G enotype + Phenotype— exercise restriction, c o ntro l arrhythmias. pacemaker therapy • C o nside r autom ated IC D efib • G enotpy + Phenotype + H e a rt failure— drug therapy, pacemaker. consider myocomy/ m yo m e ctom y/E tO H septal ablation • End-stage systolic dysfxn— h ea rt transplant

Cardiomyopathy

D ila te d C a rd io m y o p a th y ( D C M ) • E p id e m io lo g y : Annual incidence ¡s 0.57 p er 100.000 kids (JAMA 2006:296:1867) • M o st com m on cardiom yopathy and cause o f cardiac transplantation in children • M o re com m on M > F, A frican-A m ericans > W hices,a nd infants ( children • E tio lo g ie s : Idiopathic m o st com m on; also 2/2 myocarditis, doxorubicin, neurom uscular dz (Duchenne, Becker), inborn e rro rs o f metab, m alform ation synd, & familial • C lin ic a l m a n ife s ta tio n s (C ircu latio n 2006:114:2671) • Severe sx are found in m a jo rity o f pts presenting to early medical a tte ntio n • Presenting sx C H F (89.7%), sudden death (4,9%), exercise in tolerance o r arrhythm ias (2.2%), o r on ro u tine screening (3.3%) in one study • T r e a tm e n t : Etiology dependent, dluretics, digoxin,AC EI, BB, o r aldosterone antag in CHF, anticoagulation • Immune m odulators (cyclosporine, steroids, y-globulin) used in some pts w / myocarditis • P ro g n o s is (JAMA 2006:296:1867: C irculatio n 2006; 114:2671) • Risk factors f o r death o r transplantation include o ld e r age at dx (>6 yo), those w / idiopathic disease, and CHF at tim e o f dx • M o rta lity o r transplantation m o re com m on to o ccu r w /i 2 y r o f presentación • 1- and 5 -yr rate o f death o r transplantation found to be 31% and 46% in 1 study

H eart

F ailure

4-15

• Cardiac conduction abnorm alities are also com m on • Elevated JVP, S3, w / tachycardia and lo w pulse volum e can be found on exam D ia g n o stic e v a lu a tio n • C X R usually w / norm al cardiac size b u t p ulm onary congestión often seen • EKG often w / nonspec ST and T wave abn, b u t BBB, LVH, and co nd uct abn as w ell • D o p p le r echo w / 1 early diastolic filling velocity, i atrial filling velocity. T ra tio o f early diastolic filling to atrial filling ratio, and i relaxation tim e T r e a tm e n t: Specific Rx varies w / e tiology • Sym ptom atic therapy includes d iu re tic fo r venous congestión, antiarrhythm ics o r pacemaker f o r conducción abnorm alities, and w arfa rin f o r throm bu s fo rm a tio n Prognosis: W o rse than in adults w / a median survival o f 1.4 y r in 1 study • Pts presenting w / pulm onary venous congestión have w o rse outcom es

C O N G E S T IY E HEART F A IL U R E D e fin itio n • A cquired o r inborn State in which the heart cannot m eet metabolic demands o f the body at nml physiologic venous pressures • A ccounts fo r -10% o f pediatric h e a rt transplant, w / D C M as m o st com m on cause P a th o p h y s io lo g y • Preload loading forcé on che hea rt (amt o f venous blood re turn) tha t stretches myocardial fibers. which (to a point) results in T contraction strength and thus t cardiac o u tp u t (represented by Frank-Starling law) (Pediatr Rev 1980;1:180) • As filling pressures T beyond p o in t o f maxim al co ntra ctile response, myocardial co ntra ctio n becomes increasingly inefficient, resulting in í cardiac o u tp u t • As tissue perfusión im paired 2 /2 J. cardiac o u tp ut, renin—angiotensin sys activated resulting in T renal Na & H tO re ten tio n t extrace llu la r volum e & cardiac preload • Response, while initially adaptive, is maladaptive in the long run -> t afterload against w hich the heart must w o rk and results in volume overload E tio lo g y (Pediali Rev 1980:1:321: H e art 2002:88:198) • In cre a se d d e m a n d fo r c ard ia c o u tp u t (h ig h-ou tpu t cardiac failure) • H yperm etabolic States: H yperthyro id ism , anemia, sepsis • Valvular insufficiency: Can be inhe rite d o r acquired • Fluid overload: Renal disease o r iatrogenic • Left- to right-sided shunting: PDA, VSD, ASD, etc. • In cre a se d a fte rlo a d • A o r tic o r pulm onic valvular stenosis • C o arctatio n o f the aorta, pulm onary a rte ry stenosis • Systemic o r pulm onary hypertension • Im p a ire d m y o c a rd ia l fu n c tio n /c o n tr a c tility • M yocarditis: Lym phocytic myocarditis accounts fo r 10% o f recent onset CM • Viruses, m o st com m on causes in dev countries; coxsackic B and adenovirus • Chagas disease is the m o st com m on cause in C. and S. A m erica • D ilated cardiom yopathies: 1o in dication fo r xp lan t aside fro m C H D in infaney • Prognosis f o r D C M is 60% a t 5 y r fro m presentation • D C M genetic etiolo g y at present a “ m olecular maze” ; m utations assoc w / cytoskeleton, tro p o n in T, and o th e r sarcom ere p ro te in genes • C o ro n a ry a rte ry disease, rare aside fro m anomalous cardiac vasculature o r high-risk patients (ESRD, familial hyperlipidemia, D M , etc.) • M etabolic abnorm alities (Pompe disease) • N u tritio n a l o r to x ic insults (thiam ine deficiencies, chem otherapeutics) • E lectrolyte disturbances • Dysrhythmias H is to r y and Physical E xa m • Flx p o o r feeding, p o o r w eight gain, sweacing w / feeds, p o o r exercise tolerance, cyanosis, chest pain, nocturnal cough, orthopnea, paroxysmal nocturnal dyspnea • Physical exam may reveal tachycardia o r tachypnea • Edema n o t com m on; in infants, assess eyelids & sacrum (m o st dependent areas) • H e a rt may be enlarged w / displaced p o in t o f max im pulse • H e a rt m u rm u r may be present, as may e xtra h ea rt sounds (S3, S4, etc.) • Crackles on pulm on a ry exam indícate pulm on a ry edema w ith left-sided failure • Elevated ju gular venous pulsations o r enlarged live r seen w ith right-sided failure

L

E v a iu a tio n (H ea rt 2002:88:193) • EKG rarely nml b ut very nonspecific, C X R may have cardiac enlargement, pulm edema • BNP (norm al valúes vary w ith age) • Echocardiography can assess cardiac function and fo r anomalous co ro na ry anatomy • Myocarditis:V¡ral PCR (coxsackie, adenovirus, echo, influenza, parainfluenza.VZV, RSV, rubella, CMV. EBV, HIV, parvovirus, Mycoplasma, and o th e r endemic infections such as Chagas, dengue, diphtheria, Coxiella), tro po n in, C B C (fo r lymphocytosis), and myocardiai bx fo r hiscology and PCR, toxicology (cocaine) • A utoim m une: A n ti-R o and La,A N A , RF, ESR, d sD N A , and o th e r autoantibodies • M itochondrial: C arnitine.acylcarnitine, lactate.glucose, CB C (fo r neutro pe nia),u riñ e A A fo r methylglutaconic aciduria, muscle bx, m olecular genetics (Barch syndrom e) T r e a t m e n t (H e a -: 2002:88:198) • Pharm acokinetlcs ¡n pedlatrics n o t as clear fo r the core CHF drugs • ACE inhibitors: 1 retrospectlve study demonstrating reduced m ortallty in children w / DCM compared to standard Rx w ith dlgoxln and diuretics. (Pediatr Cardlof 1993:14:9) • BB: In children, 2 RCTs have shown ¡m provem ent o f LV fx, inc exercise tolerance and dec need fo r h e a rt xplanc in idiopathic, drug-induced, o r inhe rite d DCM . (H e a rt 1998:79:337; J H e a rt LungTransplant 1999:18:269) • D iuretics: C lear clinical benefit b u t little publishcd in the last 30 y r * C hlo ro th ia zid e, e thacrynic acid, and furosem ide are all used • S plronolactone; small RCT in peds showed safety and efficacy; no m o rta lity im pact • Use derived fro m b enefit seen in la rger RALES scudy in adults • D igoxin: Long-standing c ó rn e r stone o f pediatric CHF management * O nly studies published th a t evalúate efficacy o f digoxin in children sh ow m odest benefits in small nonrandomized o r unblinded triáis (all were ¡n infants w / large VSDs) (A m J C ard io l 1999;83:1408:Am J C a rd io l 1991:68:1377) • Increased c o n tra c tllity does n o t conslstently co rre la te w ith clinical ¡m provem ent • O ld e st co re o f CHF therapy is digoxin and diuretics, n o w w / data supporting use o f ACE-ls and BB as w e ll as spironolactone

DIABETES MELLITUS D e f in itio n (Pediatr Diabetes 2009:10(Suppl. 12):3) • Fasting glucose >126 mg/dL, 2 h r oral glucose tolerance te s t (O D T T ) glucose >200 mg/dL, o r random glucose >200 mg/dL in the presence o f symptom s. In the absence o f sym ptom s, level needs to be repeated on d iff day C lassification • Ty pe 1 d iab ete s : A u to im m un e disorde r w / T cell-m ediated destru ctio n o f pancreatic islet cells, causing insulin deficiency. +pancreatic autoantibodies. Rx w / insulin • Type 2 d iab ete s : Peripheral resistance to insulin action and variably dysregulated/ diminished insulin secretion. Rx w / oral hypoglycemic agents a nd /or insulin • Ochers: • M o n o g e n ic d ia b e te s (fo rm e rly m a tu rity-o n se t diabetes o f the young [M O D Y ]): Heterogeneous g ro up o f genetic disorders causcd by m utations in beta-cell genes • A D inheritance, mild to m odérate hypcrglycemia, absence o f autoantibodies • —1-5% o f diabetes Rx w / oral hypoglycemic agents a n d /o r insulin • M ito c h o n d r ia l d ia b e te s : May be assoc w / sensorineural deafness; characterized by progressive non-autoim m une beta-cell failure • Maternal transm ission o f m utatcd m ito D N A = m aternally inhe rite d diabetes • S e c o n d a ry diab ete s : • CF-related D M : i insulin secretion 2/2 pancreatic damage & amyloid deposition • D rug induced: 2/2 meds (steroids, g ro w th h orm on e , p-agonists, diazoxide, atypical antipsychotics, cyclosporine A, L-asparaginase (reversible D M ) • H em osiderosis/hem ochrom atosis: Fe overload (chronic transfusión) 4- secrete and T resistance insulin • 2/2 genetic syndrome: D o w n * T u rn a r* . K lin e fe lte rL W o lfra m syndrom e (a.k.a, D ID M O A D , diabetes insipidus, diabetes m ellitus, o p tic atrophy, deafness), P ra d e r-W illi, B ardet-B iedl, etc. (*O fte n autoim m une) • G estational diabetes

DIABETES MELLITUS T YPE 1 (Pediatr Diabetes 2C09:10(Suppl 12):1: ISPAD Cí nica' Practice Consersus Guiáélines 2009 Com pendiurn) E p id e m io lo g y • W estern c o u n trie s:T 1 D M >90% o f childhood/adolescent D M ; incidence greatest in Finland > Sardinia > Cañada > Sweden > U K > USA • O nse t bim odal (1 st peale a t 4 -6 yo & 2nd at early pub erty) & T in w in te r • N o recognizable pattern o f inheritance though familial aggregation -10%; 2 -3 x m o re com m on in offspring o f diabetic men than w om en • C oncordance rates fo r m onozygotic tw ins 30-50% ; genetic factors: H LA DR 3, 4— and as ye t unknow n environm ental triggers C lin ica l M a n ife s ta tio n s • A sym ptom atic incidental hyperglycemia/glycosuria o r • C la s s ic s y m p to m s : Polyuria and polydipsia (70%). w eight loss (34%) o ften w / inc in a ppetite (polyphagia), le thargy (16%), and nocturnal enuresls • D iabetic ketoacidosis (D K A ): Classic sx + /— vom iting and abdominal pain, fru lty breath (acetone), Kussmaul respirations, obtu nd atio n , coma • If identified th ru antibody screening and f/u (DPT1 tria l) app ro x 70% asym ptom ­ atic b ut D K A initial presentation 15-70% in Europe and N A • D K A is freq in very young children, in families w /o FHx o f diabetes, and lo w e r socloeconom ic status • D ehydration: Mild to severo, bocause o f o sm o tlc diuresis • Visual changes; 2/2 o sm otic shifts in lens o r cataracts ¡f prolonged hyperglycemia • Candidal infections (m ore com m on in younger children) E p id e m io lo g y ÍPediatrics 2004:113:e133) • D K A as 1st presentation o f DM 1 m o re often in pts -s tota

• Hyperglycemia + acidosis —> o sm o tic diuresis, dehydration, e lectrolyte loss • Severity: M ild w / venous pH 100 pg/mL) & lo w co rtis o l (often testosterone • -» w olffian ducts (vas deferens sem iniferous tubules, epididymis) • conversión to D H T —> scrotum . penis • M üllerian d u ct inhib substance (MIS o r A M H — antim ullerian h orm one produced by S ertoli cells) —> disappearance o f müllerian ducts C lin ica l M a n ife s ta tio n s • O v e rt genital ambiguity (cloacal exscrophy), 2 genitalia w / enlarged clitoris, post labial fusión, labial mass, o r ogenitals w / micropenis, b/l undesc testes, perineal hypospadias Physical E x a m • Phallic length, presence/absence o f palpable gonads D ia g n o s tic S tu d ie s • FISH f o r Y chrom osom e material (quicker); karyotype: • M a jo rity o f 46 X X have C A H ; only 50% o f 46 X Y receive definitive d x (G W AS may im prove this) • A bdom in op e lvic ultrasound • 1 7 -O H progesterone, testo stero n e, gonadotropins, MIS, inhibin B, lytes, and U A M a n a g e m e n t (Pediatrics 2006:118:e488) • G eneral concepts o f care • A void gender assignment u ntil e x p e rt evaluation • M ultidisciplinary team: Endo, surg, uro, psych, gyn, genetics, neonatology • G ender assignment: Many issues considered • >90% pts w / 46 X X C A H and all patients w ith 46 X Y CAIS are assigned female • 60% o f 5 -a-reductase def pts assigned 9 firs t & virilize at p u b erty & live as a male

PRECOCIOUS P U B E R T Y D e fin itio n (Pediatrics 1999:104:936: Pediatr A nn 2006:35:916) • G irls w / thelarche (breast dev) o r pubarche (pubic hair) before 7 yo in obese & before 8 yo in non-obese need eval. O besity inc risk o f early p u b e rty in girls • G irls w / pubarche and no thelarche 1 -2 y r advanced looks f o r late-onset C A H • G irls w I thelarche a fte r 7 yo need eval if: • Rapid progression o f pub erty w / adv bone age (>2 y r above ch ro no age) a nd/or p re dictcd adult h t >2 SD b elo w genetic targe t h t (fa th e r’s h t + m o th e r’s h t - 5)/2) • N e w CNS sym ptom s (headache, seizure, o r focal neurologic déficits, underlying CNS disease including hydrocephalus, behavioral concerns) • Boys inc height 3 -6 cm; can also use aromatase inhiblto rs/G nR H analogs to delay puberty (H o rm Res Paediatr 2 0 1 1;76(Suppl 3):27; C u rr O pin E ndocrinol Diabetes Obes 2 0 1 1;1:3; Pediatr E ndocrinol Rev 2 0 1 1;9:579;J C lin E ndocrinol Metab 2008:93:4210; J C lin E ndocrinol M etab 2010:95:328; Pediatrics 2008;121:e975; Pediatr C lin N o rth A m 2011:58:1167)

P u b er ty

M anagem ent • Treat underlying cause If identified • For male co nstitu tion al delay o f puberty, low -dose testo stero n e can achieve 2° sexu­ al characteristics and g ro w th w /o p rem ature epiphyseal closure • C o n t hypogonadism o ff supplemental testosterone a fte r age 18 suggests GnRH def • For female co nstitu tion al delay o f puberty. s h o rt courses o f estrogen therapy (w / t r i ­ áis o f w ith draw al) can achieve sim ilar ends • A fte r age 18, if co n t hypogonadism, G nRH def is likely • Replacement doses o f estrogen and progesterone should continué

ID elayeo

D ia g n o stic S tudie s • If signs o f p u b erty are present, A M testo stero n e (males) o r estradiol (females) • If not, FSH/LH, thyroxine.TS H , IG F-1, prolactin, bone age, te s t smell (Kallmann) - K aryotype fo r hypergonadotropic hypogonadism, androgen in sensitivity,Turner • Pelvic U/S (girls)

G r o w t h H o r m o n e D e fic ie n c y ( G H D ) (j Rédialr 2003:143:415) • Suspect in child w ith persistently sub-nml g ro w th rate and no identifiable cause • Classic G H D "cherub," high pltched voice, I w eight fo r height, truncal adiposlty • G H stim t e s t : A p p ro x 10% o f people w h o do n o t respond to 2 tests, may still be nml • If p t passes G H stim test, tria l Rx recom m ended ¡f ¡t meets M O ST o f the follow ing • H t >2,25 SD below mean fo r age o r >2 SD b elo w m id-parental height percentile • G ro w th ve locity < 25th percentile fo r bone age • Bone age >2 SD below mean fo r age • Low IGF-1 a n d /o r IGFBP3 • O th e r clinic features suggestive o f G H D • M R I/C T— to rule o u t e m pty sella, p itu ita ry hypoplasia, tum ors, etc. However, tru e G H D is n o t assoc w ith a nm l response to stim uli except if previous cranial irrad

A m e n o rrh e a

5-13

F D A A p p ro v e d U se s o f R e c o m b in a n t H u m a n G H in P e d ia tric s (J Pcdialr 2003:143:415) • G H D /insufficiency,T urner syndrom e, N oonan syndrom e, P ra d e r-W illi syndrom e, S H O X gene defect • C h ro nic renal insufficiency pre-transplantation • C hildren w ith H x o f IUGR (SGA) w h o have n o t reached nml height by 2 yo • ISS >2.25 SD b elo w mean height & unlikely to catch up in height S a fe ty o f G H • K now n adverse d rug reactions () Pediatr 2003:143:415) • Raised ICP. edema, SCFE, hyperglycemia, w orsening o f scoliosis, gynecomastia Increased m o rta lity (JCEM 2 012:97:416;JCEM 2 012;97:E213) • D ru g m o n itoring : C heck IGF-1 and IGFBP3 q yr and w ith dose changes • C h eckT S H , free T i b/c hypothyroidism can develop during Rx;also check H g b A lc fo r glucose in tolerance

AMENORR HEA D e fin itio n • N o rm a l menses:Avg age menarche 12.8 y r (Pediatr Rev 1992:13:43) • 2 -2 .5 y r a fte r breast budding; 1 y r a fte r g ro w th sp urt • 1o am enorrhea: A ny one o f the follow ing: • N o menses by age 16 + nml pubertal g ro w th and developm ent • N o menses by age 15 + abn pubertal g ro w th and developm ent • N o menses 2 y r a fte r com pleted sexual m aturation • 2° amenorrhea: Absence o f menses fo r 6 m o o r 3 cycles in p t w / established menses E v a lu a tio n o f T A m e n o r r h e a • 4 groups based on pubertal m aturatio n and ¡nternal genitalia • B re a s t (- ) /u t e r u s (+ ): Lack o f estrogen 2/2 lack o f gonads, H P O axis problem , o r defect in estrogen p ro du ction . C h e c k F S H to d ire c t studies • B re a s t (- ) /u t e r u s ( - ) : Rare; suspect genetic male w hose gonads produce MIS (suppresses internal F genital dev) b ut insuff te sto stero n e to produce M genitals • B re a s t ( ; )/u te r u s ( - ) : Phenotypically female, b u t check karyotype fo r D d x • C A IS (te s tic u la r fe m in iz a tio n ): Develop breasts 2/2 unopposed estrogen fro m gonad + adrenals. No/sparse a xillary o r pubic hair. Gonadal testes m ust be rem oved a fte r pubertal dev is com plete 2/2 T rate malignancy • M ü lle ria n agenesis (R o k ita n s k y -K ü s te r -H a u s e r s y n d ro m e ): T risk renal (30%), skeletal (12%), and cardiac problem s • B re a s t (+ )/u te r u s (+ ): Eval HPO axis, U/S fo r o b stru ctio n (often cyclic pain) E v a lu a tio n o f 2 A m e n o r r h e a • M u lti causes: Stress, anorexia nervosa, systemic dz (IBD, DM , th yro id dz, PCOS) • H is t o r y : C a lo ric Intake, w t A, d iet, meds, headaches, visual change, galactorrhea • PE: BMI, anorexia stigmata, visual fieles, C N , breast exam, androgen excess, pelvic • Labs: [3-hCG. LH. FSH, fT i.T S H , prolactin (Va w / galactorrhea), DHEA-S, and testos­ teron e (if signs/symptoms) o f viriliza tion • Prolactin: M ild t usually 2 /2 meds, breast stim , stress, hypothyroid • O t h e r labs: A d o l w / nml uterus/vagina, FSH, LH if elevated • If T, check karyotype; r/o T u rn er mosalcism w / ovarían failure vs. o th e r causes o f ovarían failure (autoim m une. galactosemia, etc.) • If ¿ o r nml, th in k hypothalamus x image; if no tum or, consider stress, A N , etc. '

• Progesterone challenge: Give PO m edroxyprogesterone acétate 5 -1 0 mg qd x 5 -1 0 d • + w ¡t h d r a w a l blee d : U terus nml & prlm ed by estrogen, so ovarles in tact; PCOS • - w ith d ra w a l blee d : A bn u terus o r no estrogen, e.g.,Ashcrm an syn d rom e ,A N , and o th e r causes o f hypothalam ic am cnorrhea • Trlal o f com blned estrogen/progesterone

PCOS 5-14 P ath o p h y sio lo g y 'N Engl/ Med 2005:352:1223) • Associated w / T ’d incra-ovarian androgens & often associated w ith insulin resistance • Visceral adiposity assoc w / hyperandrogenemia, insulin resistance, glucose in to le r­ ance, dyslipidemia • Hyperinsulinem ia is also central. Insulin t thecal androgen pro du ction , I sexh orm on e -b ind in g globulin, w hich T fra ctio n o f free testo stero n e E p id e m io lo g y (N Eng1J Med 2005:352:1223) • A ffects -5 -1 0 % o f w om en; 30-75% o f wom en w ith PCOS are obese • C u rre n tly considerad a com plex, multigenic d lsorder D ia g n o s is (N Engl j Med 2005:352:1223) • R otterdam C rite ria , 2003 (2 o f 3): O llgo/am enorrhea; hyperandrogenism o r hyper-androgenemia; radlographic evidence o f polycystic ovarles O R • A ndrogen Excess Society 2006 (all): Hyperandrogenism . ovarían dysfunction, exelude ocher androgen dlsorders/excess • Polycystic ovaries are n o t necessary o r sufficient to confirm dx (functional condition) • M ust r/o hyperprolactinem ia, C A H , Cushing syndrom e, acromegaly, androgen-secreting neoplasm • C o nside r the fo llo w in g labs: H C G , p ro lactin , 1 7 -O H P, D HEA. SHBG, LH/FSH, testosterone, fasting glucose, insulin,TFTs ("T h e Polycystic O vary Syndrome: C u rre n t Concepts O n Pathogenesis A nd Clinical Care. Legro, RS 2007) • Symptoms o f hyperandrogenism include hirsutlsm , acné, and m ale-pattern alopecia • O fte n dlsordered ute rlne bleeding & in fe rtlllty 2/2 anovulation, acanthosis nlgricans 2/2 hyperinsulln • T LH o r LH:FSH ra tlo (>2) less rellable, as levels vary th ro u g h o u t m enstrual eyele • Risk assessment f o r endom ecrial carcinom a, glucose Intolerance (O G TT, random glucose, A 1c), dyslipidemia (fasting llplds), o bstru ctive sleep apnea T r e a tm e n t (N Eng! J Med 2005:352:1223) • H yperandrogenism (hirsutism and acné) • C om bined e strogen-progestin contraceptives: C hoose low est androgen activity • Antíandrogens: Spironolactone; reserve steroids fo r marked androgen excess • O lig om en o rrh ea and am enorrhea • C om bined e strogen-progestin Rx o r cyclic progestin adm inistration may in hibit endom etrial p ro life ra tio n fro m chro nic anovulation • W e ig h t loss and lo w e rin g insulin levels are shown to ¡m prove o vu la to ry function • Insulin resistance and glucose intolerance: W e ig h t reductio n, m e tfo rm in

BODY AND P A R E N T E R A L FLUID S C o m p o s itio n o f Basic Fluids and R e p la c e m e n t S o lu tio n s [N a ] (m E q /L ) Gastric

[C l] (m E q /L )

70

120

Pancreatic

140

Bile

130

[K ] (m E q /L )

[H C O ,] (m E q/L)

pH

5-15

0

Acidic

50-100

5

100

Basic

100

5

40

Acidic Variable

Diarrhea

50

40

35

50

Heostomy

130

120

15-20

25-30

NS (0.9%)

154

154

0

0

5.5

1A NS (0.45%)

77

77

0

0

5.5

V« NS (0.23%)

38

38

0

0

5.5

Ringer Lácrate

130

109

4

28

6.5

Basic

M a in te n a n c e Fluids & E le c tr o ly te C a lc u la tio n s (Pediatr Rev 2001:22:380) • Basal State maintenance flu id needs determ ined by basal m etabolic rate; am t o f fluid needed to dissipate heat via re sp ira to ry tra c t and skin • M últiple m ethods: BSA m ethod, basal calorie m e tho d .a n d Holliday-Segar system. O nly last (H olliday-Segar) does n o t require a table o f valúes • Holliday-Segar form ula equates kcal w ith m L (1 :1) o f fluid needed fo r dissipation W e ig h t (kg)

kcal o r cc ( 1 :1 equivalence)

kcal/hr o r cc/hr ( 1 : 1 )

0 -1 0

100/kg/d

4 cc/kg/hr

11-20

1,000 + 50/kg/d

40 cc + 2 cc/kg/hr

>20

1.500 + 20/kg/d

60 cc + 1 cc/kg/hr

Adapted from: Pediatrics 1957:19:823.

• E lectrolyte maintenance needs (n o t fo r neo n ates ): Na 2—4 mEq/kg/d, K 1 -3 mEq/ kg/d, Ca 2 -3 mEq/kg/d. Phos 0 .5 -1 .5 mEq/kg/d, Mg 0 .1 -1 mEq/kg/d • D5 1/2 NS usually used fo r maintenance w / 20 mEq/L K CI added once p t has u rin a te d ;fo r pts T A D H , susceptibility to hypoNa if repleted w ith hypotonic fluids/H^O H is t o r y a n d E x a m .JAMA 2004:291:2746} • H x fever (insensible losses), 4- oral intake, types o f intake, freq o f urin atio n ( t U O P w / dehydration —> diabetes insipidus), diarrhea (frequency), o th e r sites o r sources o f loss (ostom ies, bilia ry tubes, etc.) • Assessment o f w e ig ht loss via H&P as above o r fro m actual docum ented weights • W e ig ht loss (kg) = fluid d éficit (L): based on radio-labeled albumin experim ents • Inaccurate in setting o f "3 rd spaced fluids” (n e ph ro tic syndrom e, CHF, cirrhosis) w here patient is intravascularly deplete b u t w eight is up • C apillary refill; compress and release superficial cap bed (palmar finger-tip w / arm h e a rt level), varíes as fxn o f tem pe ra ture, site, lighting, meds, & auto no m ic A • Skin tu rg o r (ST): skin pinch at lateral abd wall a t umbilical level. Less accurate w / H yperN a (false nml) and w / m alnutrition (falsely prolonged). Com plicated in 1o skin dz • Can assess dehydration d inically based on history, exam, & assessment o f w e ig ht loss

D ehydration

Mild

M odérate

Severe

Sens/Spec '1

W e ig h t loss— ¡nfant

5%

10 %

>15%

—

W e ig h t loss— child

3-5%

6-9%

> 10 %

—

HR/BP

Nml

Nmltachycardic and orthostatic

Tachycardiac and orthostatic-shock

0.52/0.58 (for inc HR)

RR

Nml

Nml-increased

Hyperpnea (deep rapid breathing)

0.43/0.79

A n te rio r fontanelle

Nml

Sunken

Very sunken

0.49/0.54

Mucous m em branes

Nml

D ry

Cracked

0.86/0.44

Tears

Nml

Decreased

Dry. sunken eyes

0.63/0.68

Skin (less accurate if H y pe rN a or

Cap refill (CR) 1.020 + /oliguria

Oliguria to anuria

Behavior

Nml

Irritable

Lethargic/obtunded

Total fluid déficit

30-50 cc/kg

60-100 cc/kg

>100-150 cc/kg

yo) U riñ e outp ut and SG

20 mmoi/L

0.46

0.74

Lab Param eters

Adapted from: JAMA 2004:291:2746.

M a n a g e m e n t ( A n Fam Fhysician 2009:80:692: Aj-ch D s Child 2007:92:546: M M W R 2CQ3;52:RR-16; Pediatr Rev 2001:22:380) • For severe dehydration, c o rre c t hemodynamics w ith 20 cc/kg boluses NS (o r LR); repeat u ntil stabilized ( C rit Care Med 2009:37:666) • If H yper/FloN a, see m gm t sections on H yp e r/H o N a below. In hypernatrem ic dehy­ d ra tion , intravascular volum e is preserved, so degree o f dehydration cannot reliably be estim ated by physical signs. Th erefo re , c o rre c t fluid déficit as per FiyperNa recs instead o f per dehydration recs • For m ild/m od & fo r severe dehydration s/p NS o r LR resuscitation, give aggressive ORT (5 0 -10 0 cc/kg o ver 3 -4 hr) follow ed by maintenance and replacement o f ongoing losses • PO ondansetron p rio r to O R T —4 T cessation o f vom iting, I need fo r IVF, 1 race o f im m ediate hospitalization (C ochrane Database 2 0 1 1;9:CD005506) • O RT prom ptly resolves [N a] abn; no need fo r IVF in 90% (Am J Clin N u tr 1980:33:637) • O RT com parable to IVF, w ith lo w e r rates o f h ospitalization (1/3 o f O RT vs. V 2 o f IVF; Pediatr 2005:115:295) and acceptably lo w failure rates (4.9% PO vs. 1.3% IV; C ochrane Database 2006;3:CD004390) • O R T used N a loss) o r Na re ten tio n • Free w a te r loss can o ccu r fro m skin and re sp ira to ry tra c t o r w / dilute uriñe (d iu re t­ ics o r osm otic d iu re tic agents [glucose. m an nito l]). diarrhea is variable in com positio n b ut can see excess w a te r loss w / osm otic o r m alabsorptive diarrhea • Body attem pts to c o rre c t H yp e rN a w / inc A D H release —) concentrated uriñe (occurs at Pojm > 280 m O sm /L) & by driving th irs t (rare fo r p t to be hypernatrem ic w / access to H 2 O ) • H yp e rN a (w / resultant hyperosm olality) —> cellular dehydration. particularly at brain resulting in the sym ptom s assoc w / H yperN a • A cute ly can be severe enough to cause subdural bleed o r SAH (Pediatr Rev 1996; 17:395) • Subacutc o r chronic H yp e rN a allows brain cells to adapt by p ro d u ctio n o f intraccllular osm oles to balance gradient (w/¡ 1 h r); overrapid c o rre c tio n —» cerebral edema • H ypernatrem ia w / [N a ] > 160 mEq/L has m o rta lity o f 10-15% E p id e m io lo g y (Pediatr Rev 2002:23:371) • High risk include debilitated pts w / acute o r ch ro n ic illness, infants. & particularly p re te rm (small mass: BSA ra tio ) and reliance on caretakers fo r fluids (ineffective breastfeeding)

C lin ic a l M a n ife s ta tio n s (Pediatr Rev 2002:23:371; Pediatr N ephrol 2005:20:1637) • Assess patie nt’s access to free H jO , hx o f polyuria (D I, D M , nephropathy), absence o f th irs t (in setcing o f H yp erN a and inc Posm, this reflects hypothalamic lesión) ■ Patients are generally irrita b le b ut can progress to lethargy, seizures, coma, o r death • N e urolog ic exam may reveal increased tone, brisk reflexes, o r nuchal rigidity • H yp erN a can re su lt in “ doughy" skin textu re ; falsely normalizes ST E tio lo g ies and D ia g n o s tic S tudies • C heck basic e le ctro lyte panel, U /A , serum O sm , u r iñ e O s m , uriñe sodium

• D ia b e te s insipidus (P e d ia tr C lin N A m 2 0 1 1 ;5 8 :1 2 7 1 ): C o m p le te o r partial failure in secretion o f (central) o r response to (nephrogenic) A D H • Renal w a te r abso rp tion decreases, resulting in d ilute uriñe • P/w polyuria and polydipsia before developing H yperN a • To establish diagnosis, do w a te r deprivation te st (fasting w ith o u t fluids x 8 -1 0 h r w ith regular m o n ito rin g o f Sn 3, Sosm, U volMe, Uosm). If Sosm > 300 m O sm /kg and Uosm < 300 mO sm /kg, p t has DI. Interm edíate valúes may indícate partial D I.To distinguish central fro m nephrogenic D I, check AVP level then adm iniste r DDAVP (desmopressin) and m o n ito r response in Snj, Sosm, Uvoiumo, Uosm • C e n tr a l D I (responds to DDAVP) can be idiopathic, 2/2 neurosurgery (transsphenoidal surg), neoplastic (craniopharyngioma), 2/2 hypoxic/ischemic encephalopathy (Sheehan syndrome, s/p arrest), congenital (2/2 hypothalamic/pituitary malformadon o r AVP-NPII gene m utation) o r o th e r (infectious, infiltrative o r granulomatous diseases, anorexia nervosa, histiocytosis X ) • N e p h ro g e n ic D I (no/m inim al resp to DDAVP): Congenital (m utations in AVPR2 o r AQP2), drugs ( L ith iu m , ifosfamide, dem eclocycline), o bstrucdve uropathy, siclde cell, pregnancy, 2/2 hyperCa o r hypoK • D ehydration may be d ifficu lt to differentiate fro m salt poisoning based on uriñe [N a ] alone; also consider history, clinical appearance (edema? signs o f dehydration?), and FENa ( - [U N a ][P C r]/[U C r][P N a ]; BMJ 2003:326:157) M a n a g e m e n t (Ped a l' Rev 1996:17:395) • Rapid c o rre ctio n o f H yperN a can re su lt in cerebral edema, seizures, perm anent CNS sequelae, o r death; unless p t is significantly sym ptom atic, c o rre c t slowly • If p t hem odyn unstable 2 /2 hypovolemia, rx w / IV NS 20 cc/kg boluses u ntil stable • Máximum safe rate fo r low ering [N a ] is 0.5 m E q/L/hr o ver 24 h r o r 12 mEq/L/d

• If significant sx fro m H yp erN a (seizing), lo w e r sodium m o re rapidly u ntil sx resolve (1 .5 -2 m E q/L/hr fo r 3—4 hr), then t r y n o t to lo w e r > 1 2 mEq/L/d o ver all • Calculation o f w a te r d éficit as follow s: W a t e r d é fic it (L) = 0.4 x lean b o d y w e ig h t (kg) x

• • • • • •

-1

• Total body w a te r calculated as 0.4 (40%) o f lean body w e ig ht (instead o f usual 60%) as assumes p t som ew hat dehydrated (w ate r deplete) • So for 25 kg pt v/l [N a ] 760; water déficit is (0.4 x 25) x ((160/140) - 1) = 1.4 L H 2O • Assume c o rre c t 10 m E q/d;so needs to c o rre c t over 2 d ;a p p ro x 30 cc/h r H 2O • Seizure may o ccu r during corrección (may re fle ct cerebral edema); if occurs, rate o f corrección should be slowed o r a dm inister h ype rto nic saline. Usually self-lim ited and n o t reflective o f lo ng -te rm sequelae (Pediatr Rev 2002,23:371) • Malte sure to account fo r insensible losses and maintenance as w ell A rough rule o f thum b is th a t 4 cc/kg o f free H iO w ill dec [N a ] by 1 mEq/L W a te r d éficit is the am ount o f positive w a te r balance needed to c o rre c t sodium to 140 Provide such th a t c o rre ctio n is o r < expected, there may be a 2nd 1° process • P aC O i to o lo w implies a conco m ita nt re sp ira to ry acidosis • P a C 0 2 to o high implies a co ncom itant re sp ira to ry alkalosis • H C O 3 to o lo w implies a co nco m ita nt m etabolic acidosis • H C O j to o high implies a co nco m ita nt m etabolic alkalosis S u s p e c t p re s e n c e o f t w o , 1° a c id - b a s e p ro c e s s e s i f s e ru m p H n m l b u t: • Increased P a C 0 2 and increased H C O j; re sp ira to ry acidosis and m etabolic alkalosis • Decreased P aC O j and decreased H C O 2; re sp ira to ry alkalosis and m etabolic acidosis • N m l PaC O í and nml HCO ? w / + A G ;A G m et acidosis and m e t alkalosis • N m l PaCO 2 & nml H C O j w / no AG; N m l o r nonanion gap (N AG ) m et acid & m et alk

M ET ABOLIC ACIDOSIS D e f in itio n (Pediatr Rev 2004:25:350: Pediatr Rev 2011:32:240} • N e t gain o f H f o r loss o f H C O 3 and can be divided in to A G o r N A G • A G acidosis: Implies presence o f unmeasured anions; t organic acids fro m ingestión, p ro du ction , in bo rn e rro rs o f metab, o r i e xcre tion 2 /2 renal failure • A G = [N a ] - ([C L ] + [H C O 3"]); norm al defined as 8 -1 2 w / norm al valúes believed to be higher in pts 10, presence o f unmeasured O sm ; mechanol, ethylene glycol, etc. • W / +A G ; to check ¡f >1 cause f o r lo w H C O 3 can check A IA = A A C IA HCO3 • A l A 2

C h ro n ic

3.5 mEq/L [H C O 3] increase expected fo r every 10 mm Hg increase in PaCC>2

R e s p ira to ry alkalosis A c u te

2 mEq/L [H C O 3] decrease expected fo r every 10 mm Hg decrease ¡n PaCCh

C h ro n ic

4 m Eq/L [HCCb) decrease expected for every 10 mm Hg decrease in PaCO?

O f note: C o rre c tlo n s assum e n m l H C O 3 24 and P C O 2 40; b u t in pts w / und e rlyin g resp d z (C L D , B P D , e tc .) use H C O 3 and P C O 2, th e y live a t as nm l • A lso o f note, infants maintain a lo w e r average H C O 3 (21.5-23.5 mEq/L) than o ld e r children (2 3 -25 mEq/L) (Pediatr Rev 1996:17:395) If change in PaCCh o r H C O 3 is > o r < expected, th e re may be a 2nd 1“ process • P aC O j to o lo w implies a co nco m ita nt re sp ira to ry acidosis • P aC O j to o high implies a conco m ita nt re sp ira to ry alkalosis • H C O 3 to o lo w implies a co nco m ita nt m etabolic acidosis • H C O 3 coo high implies a conco m ita nt metabolic alkalosis S u sp e c t p re se n c e o f tw o , I o a c id -b a s e processes if s e ru m p H n m l but: • Increased PaCCh and increased H C O 2; re sp ira to ry acidosis and m etabolic alkalosis • Decreased P aC Ü 2 and decreased H C O 2; re sp ira to ry alkalosis and metabolic acidosis • N m l PaCCh and nml H C C h w / + A G ;A G m et acidosis and m et alkalosis • N m l PaCCh & nml H C O 2 w / no AG; N m l o r nonanlon gap (N AG ) m et acid & met alk

METABOLIC ACIDOSIS D e f in itio n (Pediatr Rev 2004:25:350: Pediatr Rev 2011:32:240) • N e t gain o f H* o r loss o f H C O 3 and can be divided in to A G o r NA G • A G acidosis: Implies presence o f unmeasured anions; T organic acids fro m ingestión, pro du ction , inborn e rro rs o f metab, o r I e xcre tion 2/2 renal failure • AG = [N a +] - ([C l ] + [H C O 3 ]); norm al defined as 8 -1 2 w / norm al valúes believed to be higher in pts resp failure • A t pH < 7 -7 .1 , cardiac co n tra c tllity can be ¡mpaired and the risk o f malignant arrhythm ias is increased. Can p /w a rte rio la r dilation. H o T N , p ulm onary edema • CNS: C erebral edema, lethargy, coma • O th e r: O xyhem oglobin dissociation curve shifts right, hyperK, insulin resistance, p ro te in denaturing

E tio lo g ies (Rose & Post. Cínica! Physiobíy ofAcr.í-Base & Electrolyie Disorders 2001:535; Pediatr Rev 2011:32:240) • A G acidosis: Due to exogenous and endogenous H + excess: M U D P IL E S • M ethanol: Found in w o o d alcohol, varnishes, shellac, and sterno, m etabollzed to form aldehyde, O sm gap >10; p /w sx 1 2- 36 h r a fte r ingestión w / weakness. N/V, can re su lt in blindness, coma, and death • U rem ia (2/2 renal failure w / decreased clearance o f sulfate, urate, phosphate) • D iabetic kctoacidosis, starvation ketosls • Paraldehyde (solvent, anticonvulsant and hypnotic, n o t available in the U nited States b u t still used elsewhere) • Iro n, ¡soniazid, and ingestions (o thcr):T olue ne (glue sniffing), sulfur, etc. • Lactic acidosis: M ost com m on, 2/2 anaerobic metab, can be 2/2 t p ro du ction (severe hypoxia, ¡schemia, shock, C O o r cyanide poisoning, szr, inborn e rro rs o f metab) o r I clearance (hypoperfusion, live r disease) • Ethylene glycol (in antifreeze. w / glycolate. oxalate. and O sm gap >10; Ethylene glycol ingestión p/w drunkenness o r even coma, then pulm onary edema and then renal failure. consider fom epizole a nd /or dialysis fo r rx). E thanol (alcoholic ketoacidosis) • Salicylate: Results ¡n com bination resp alkalosis and m e t acidosis, tinnitus • If concern fo r ingestions, check O sm o la r gap = Measured O sm - Calculated O sm • Calculated O sm = 2 [N a ] + [glucose]/18 + [B U N ]/2 .8 + [E tO H ]/4 .6 • If O sm gap >10, presence o f unmeasured O sm ; methanol, ethylene glycol, etc. • W / +A G ; to check if >1 cause fo r lo w H C O 3 can check AJA = A A G IA HCO3 • A l A 2; loss o f H C O 3 less than expected (AG acidosis + m etabolic alkalosis) • N A G acidosis: 2/2 T G U o r Gl loss o f H C O 3 o r Inability to e xcrete H“ : H A R D U P • H yperalim e nta tion , H ypoaldosteronism , H yp erP T H • A cetazolam ide. A m m o n iu m chloride • RTA (see later). Renal loss 2/2 rapid co rre c tio n o f chronic resp alkalosis • R T A II (proxim al RTA): Dec H C O j reabsorption, p /w norm al o r lo w serum [K +], variable uriñe pH, fractional e xcre tion o f H C O 3 (FeHco3) >1 5 -2 0% • Can ro su lt in rickets o r osteomalacia • C arbonic anhydrase in hibito rs (e.g., acetazolamide) im pair H C O 3 re a bsorption • Treat w / 1 0 -1 5 mEq/kg H C O 3 divided m últiple tim es a day • Renal dysfunction: Some cases o f renal failure and RTA • R T A IV (hypoaldosteronism ): W / norm al o r inc serum [K~], uriñe pH < 5.3, Fencoj < 3%, check serum aldo; tre a t w / H C O j 1—3 mEq/kg qd • R T A I (distal RTA): Dec H secretion w / uriñe pH >5.3, lo w serum [K '],a n d fractional e xcre tion o f H C O 3 intestinal H C O T loss) • P a r e n te r a l N a C I (com m on cause, due to rapid dilución o f H C O 3 by C l ; sim ilar effect fro m K CI o r M g C lj), P ancreatic fístula • U riñe A G can distinguish between situations w / intacc NH.T secretion (G l losses RTA II. rapid co rre c tio n o f chronic resp alkalosis) vs. those w h ere secretion o f N H / is ¡mpaired (renal failure, RTA I, and IV) • UA G is ¡naccurate w / high A G acidosis o r w / significant volum e depletion

81-9 sisoaov ía w

M a n a g e m e n t (Peciatr Rev 2004:25:350) • C o rre c t underlying abnorm alities as described above • S odium -bicarb is the agent o f choice fo r severe m etabolic acidosis (especially N A G ) b u t controversial as evidence o f im proved outcom es is weak • A m t bicarb to infuse = (w eight in kg) x (15 - [measured H C O 3]) x (0.5) • M ix am o un t calculated in hypotonic solutio n and infuse o ver 1 HR • Provides enough bicarb to c o rre c t pH >7.2 o r bicarb conce ntratio n >15 mEq/L • Rapid co rre c tio n can re su lt in acidification o f CSF (w / worsening sym ptom s); volum e overload; d evelopm ent o f alkalemia, hypocaicemia, and re sp ira to ry depression

METABOLIC A L K A L O S IS

M et A lkalosis 6-19

D e f in itio n (Pediatr Rev 2004:25:350; Pediatr Rev 2011:32:240) • Processes resulting in net loss o f H 1- o r gain o f H C O 3 ; alkalemia is a serum pH >7.44 P a th o p h y s io lo g y (Pediatr Rev 2004:25:550: Pediatr Rev 2011:32:240) • Gain o f H C O 3- can be 2/2 T intake, i renal e xcre tion , o r volum e co ntra ctio n around stable am o un t o f bicarbonate • Healthy kidneys can excre te a large load o f bicarbonate rapidly, so to maintain a m etabolic alkalosis renal bicarbonate e xcre tio n m ust be im paired • Renal bicarbonate e xcre tion is im paired w hen p ro x tubule bicarb reabsorp is inc 2/2, dec effective circ volum e and chlorid e depletion (results in 2 o hyperaldo, dec tubular C l inhibiting C P /H C O s exchanger), [K +] depletion (creates ¡ntracellular acidosis, stim ulates H 7 N a * exchanger), o r posthypercapnia adaptation C lin ic a l M a n ife s ta tio n s (Pediatr Rev 1996:17:395: Pediatr Rev 2011:32:240) • Can present w / lethargy, confusión, and eventually seizures • Can see tlssue hypoxia, C NS effects, and muscular irrita b illty • Body compensates w / re sp ira to ry acidosis and some w / dec re sp ira to ry excursión E tio lo g ie s (Pediatr Rev 2004:25:350: Pediatr Rev 2011:32:240) • Can be divided in to chlorid e responsive and chloride-unresponsive etiologies • C h lo rid e responsive (u rin a ry C L 1 0 mEq/L) • A drenal dysfunction (hyperaldosteronism o r Cushing syndrom e) • Exogenous steroids (glucoco rtico id s, m ine ra loco rtico id s, and licorice) • Inherited channelopathies (B a rtte r syndrom e and G itclm an syndrom e) • A lkali ingestión, largo volum e blood transfusions (due to citra te in blood) • Edematous States Rx’d w / diuretics (e.g., CHF, cirrhosis, nephrotic syndrome) • Refeeding alkalosis • Hypokalemia Metabolic alkalosis | U C|> 10 m Eq/L

) m E q /L | - Gl losses, vomiting, NGT suction, laxative abuse, diarrhea, - Prior diuretic use - posthypercapnia - Severe prerenal azotemia - High dose IV PCN - Cystic Fibrosls

Assess volume status

Hypovolemic

Current diuretic use

k

Hypertensive

Hyperaldo Cushinq, CAH Exogenous steroids RAS Renin secretlng tumor

-

Bartter syndrome Gitelman syndrome Alkali ingestión Refeeding alkalosis Hypokalemia

M a n a g e m e n t (Róse & Post. CWcaí Phvsioiogy o fA a d Base & E/ectroiVte Disorders 2001:551; Pediatr Rev 2011:32:240) • Rx underlying co nd itio n and c o rre c t m e t alkalosis by renal secretion o f H C O f • For saline responsive etiologies, provide IV saline (m o n ito r efficacy via uriñ e pH [which is 7 w ! re p letio n ] and Uci [w hich rises above lO m Eq/L w ith tx ]) and replete K as needed • For saline unresponsive etiologies • If edematous State (CHF, cirrhosis, nephrotic syndrom e): W ith h o ld d iu re tic if possible, acetazolamide, H C I.A rg inine C h lo rid e o r dialysis • Hypokalemia: Replete K • Hyperaldosteronism : K-sparing diuretics/aldo antagonists o r removal o f parathyro id adenoma C o m p lic a tio n s (Pediatr Rev 2004:25:350: Pediatr Rev 2011:32:240) • Cardiac: A rte r io la r co n strictio n . re fra c to ry SVT, and ve n tricula r arrhythm ias • C erebral: Reduction o f cerebral bloo d flo w , tetany, seizures, lethargy, stu p o r • R espiratory: H ypove n tila tion w /' hypercapnia and hypoxia • M etabolic: H ypoK , hypoMg and hypoPhos, stim ulation o f glycolysis, oxyhem oglobin dissociation curve shifts le ft

R E S P I R A T O R Y A C I D O S I S AND A L K A L O S I S

E tio lo g y ¡Pedida Rev 2004:25:350; Pediatr Rev 2011:32:240) Causes o f A c u te R e s p ira to ry A cid osis

Causes o f R e s p ira to ry A lka lo s is

A c u te C N S D e pression Drug O /D (benzos, narcotics, barbíturates) Head trauma, CVA, CNS infections

H y p o x ia

A c u te N e u ro m u s c u la r Disease Guillain—Barré syndrome. myasthenic crisis Botulism, organophosphate poisoning Spinal cord injury

M e ch an ica l v e n tila tio n H y p e rv e n tila tio n syn d ro m e s P regn an cy (2/2 progesterone) P a ren chym al L u n g Disease PNA, asthma. diffuse interstitial fibrosis Pulmonary embolísm. pulmonary edema

A c u te A irw a y Disease Status asthmaticus, upper airway obstruction

M e d ic a tio n s Salicylate, xanthines (caffeine, theophylline), nicotine, catccholamines

A c u te P are n ch ym a l and V a scu la r Disease Pulmonary edema, acute lung injury Multilobar PNA

M e ta b o lic d iso rd e rs Sepsis, pyrexia, hepatic disease

Massive P u lm o n a ry E m b o lísm A c u te P le u ra l o r C h e s t W a ll Disease Pneumothorax, hemothorax, flail chest, severe scoliosis, obesity hypoventilation syndrome

C N S D is o rd e rs Meningitis, encephalitis, CVA Head trauma Space-occupying lesión Anxiety

R esp A cio B ase

D e fin itio n (Pediatr Rev 2004:25:350: Pediatr Rev 2011:32:240) - R espiratory acidosis and alkalosis re su lt fro m a 1o increase o r decrease in P C O 2 • Resp acidosis = P C O 2 >40 mm Hg, Resp alkalosis = P C O 2 2 sec skin pinch, coid ext, deep a cidotic breathing, H o T N , tachycardia

Diagnosis & T re a tm e n t (A m Farr, Physician 2.000:61:2791:) Heoiatr Gastroeníercl N u ;r 2001:32:512: Pediatr Rev 2008:6:183) • D efinitive management as w e ll as diagnostic testing depends on underlying etiology • N o n b ilio u s e m e s is : G enerally less concerning; some emergendes, p yloric stenosis • B ilio u s e m e s is is alm ost always concerning sx w a rra n ting fu rth e r evaluation • N G T placem ent fo r decom pression if o b stru ctio n suspected • Diagnostic evaluation varíes b ut generally indudes KUB a nd /or UGI • W / neonate, bilious emesis can indícate surgical disease • D u o d e n a l a tr e s ia : Congenital o b stru ctio n o f 2nd p a rt o f d uode n um ,2 /2 failure to recanalize in útero, vom iting w /i hrs: pregnancy often w / polyhydramnios • 1 in 5,0 0 0-10 ,00 0 and M > F, seen in 1/4 Dow n's syndrom e pts, 20% w / C D H • Membranous o r ¡nterru pte d lesión at papilla o fV a te r (PV), 80% w / PV open to proxim al duodenum resulting in bilious emesis. • K U B w / “ double bubble": G astric air bubble and distended p ro x duodenum • Surgery necessary b u t n o t u rgent ( phenothiazines (compazine) • H igher CNS ce nte r involvem ent: Can actívate o r suppress; rx anxiolytics • A ll stim u la teV C (final com m on pathway): Stimulated by parasymp and H¡R, acts via parasymp and m o to r efferents

GASTROESOPHAGEAL REFLUX DISEASE (GERD) D e f in itio n (J Pediatr G astroenterol N u tr 2009:49:498) • Passage o f gastric contents to esophagus, nml & w /o sx (GER), o r pathologic (GERD) P a th o p h y s io lo g y (Pediatr Rev 2007:3:101) • In te rm itte n t relaxation o f LES, acid refluxing to esophagus w / esophagitis, chronically causes change fro m colum nar to squamous (B arrett) E p id e m io lo g y • Prevalence physiologic re flu x -50% at 0 -3 mo, 67% by 4 mo, 5% at 12 m o, and in children 3 -1 7 yo, rates vary fro m 1.4-8.2% C lin ic a l M a n ife s ta tlo n : Varíes B yA gc • In fa n ts : Vom iting, FTT, irrita b ility, congestión, ALTE, re cu rre n t PNAs • C h ild re n /a d o le s c e n t: A bd pain, re tro ste rn a l CP, dysphagia, regurg, asthma/cough D ia g n o s tic S tu d ie s • H&P only, unless complicacions present o r dx in question; in infants H&P n o t diagnostic • UG I: N o t sensitive o r specific fo r GERD b ut identifies m alro tatio n , esophageal/antral webs, p yloric stenosis, Schatzki rings, hiatai hernia

• Esophageal pH probe: Checks freq and duration o f acid exposure. Reflux Índex (Rl) = % tim e pH 1 yr): Left-side positioning and elevation o f head o f bed in sleep • Lifestyle A (adoles): N o caffeine, c hocolate, spicy foo d , tobáceo, E tO H ; n o t data-driven • A cid suppression: P P Is > H 2R A s ; if long-term PPI, check fo r H. pylori (risk o f a trop h ic gastritis w / chronic >6 m o PPI use and untreated H. pylori) (Pediatr Rev 2003;24:12) • S pa ce d o s in g o f P P Is a n d H 2R A s as PPI require acidic environm ent fo r activation • M a jo rity o f children develop tachyphylaxis to H 2RAs w /i 2 w k • There is evidence we are o ver prescribing (Pediatrics 2007:120:946) • Prokinetic:Aside fro m cisapride (lim ited access 2/2 side effects) no prokinetics w / benefit • Surgical Rx: Case series show generally favorable outeom es P ro g n o s is : M ost outg ro w sx by 12 mo; p oo re r prognosis w / neuro im pairm ent, esophageal atresia, prematurity. C o m p lic a tio n s • R espiratory (asthma, apnea, ALTE, cough), E N T (sinusitis, dental erosions, laryngitis), esophageal strictures, B arre tt, adenoC A , UGI bleeding, FTT, Sandifer syndrom e • 2A o f children w / asthma im prove to some degree w / rx fo r GERD • N eurologically im paired at high risk o f re cu rre n t aspiration (P N A , pulm fibrosis)

P Y L O R IC STENOSIS D e fin itio n (Pediatr Rev 2000:21:249:A dv Pediatr 2011:58:195) • Gastric o u tle t obstruction 2/2 hypertrophy and edema o f pyloric canal, and antropyloric distensión and muscle spasm -> vomiting, dehydration, and hypochloremic, hypokalemic, metabolic alkalosis; thought to be an acquired condition E p id e m io lo g y • Incidence o f 1 in 250-1,000, M 4 -8 x > F, Caucasian predilection C lin ic a l M a n ife s ta tio n s • Mean age 3 w k, b u t anytim e b irth to 5 mo; begins w / regurgitation -> nonbilious vom iting + /- projectile vom iting • Classically w / “ o live-like” mass palpated in epigastric región, pathognom onic; n o t always appreciable; exam enhanced by N G T decom p and prone positioning D ia g n o stic S tudies • U/S is study o f choice, pyloric thickness >4 mm, length > 16 m m w / sens 89%, spec 100%; may need repeat U/S given o p e ra to r variability • M ost com m on cause o f m etabolic alkalosis in infaney; hypochlorem ic m etabolic alkalosis 2/2 acid loss fro m vom iting and decreased H C O 3 secretion • Excess bicarb can be e xcreted in uriñe w / oblígate Na loss, follow ed by H 20 , also 2° hyperaldo 2/2 inc renin release causes distal H* secretion and paradoxic aciduria • Can have lo w o r nml K b ut usually tota l body K depletion T re a tm e n t • Reverse m etabolic derangements and volum e status • P ylorom yotom y is curative, incisión through serosa and mucosal layer. Essentially 100% success rate

G A S T R O IN T E S T IN A L B L E E D I N G D e fin itio n (Pediatr Rev 2008:29:39) • Intralum inal bleeding at any site fro m o ro ph arynx to the anus; definition o f u pp er Gl bleed as proxim al to the ligament o f Treitz and lo w e r Gl bleed as distal

• Can p /w bloo d y v o m it (hematemesis), “ coffee g ro u n d " emesis, hem atochczia (BRBPR; LGIB, o r rapid UG IB [>20% bloo d volum e]) o r melena (ta rry black 2/2 digestión, darkness correlates w / tim e to pass); r/o o th e r site (nasopharynx) • Check fo r false coloring; red food co lo rin g .fru it juice, beets can make v o m it o r stool red. Pepto-Bismol, iron, grape juice, spinach, and blueberry can make it black E tio lo g y o f U p p e r G l B le e d D ifferential o f UG IB

Cl n Pediatr : t il. . : 2007;46:16':

Com m on

U ncom m on

Neonate

• Swallowed maternal blood (use A pt-D owney test w / KOH, color ú w / maternal blood) • Milk protein allergy • Traumatic N G T placement

• • • • •

Infant

• Esophagitis 2/2 GERD

Hemorrhagic dz of newborn Esophagitis Vascular malformation Sepsis w / coagulopathy Congenital coagulopathy

• Stress ulcer/gastritis • Acid peptic disease • Gl duplication • Gastric/esophageal varices

Child

♦ • • *

Esophageal varices Acid peptic dz Gastritis (H. pylori, NSAID) Caustic ingestión, Mallory—Weiss

• Bowel obstruction • Crohn's disease • Hemobilia • Vasculitis

E tio lo g y o f L o w e r G l B le e d (Pedíale Emerg Care 2002:13:319) • A n a l fissure: M ost com m on cause LGIB 13 consistent w / iron def; 50% daily feeds: 1 mg/kg/d oral Fe startlng at 4 m o • Universal screening at 12 mo: C heck risk facto rs and serum Hgb. If + anemia. measure fe rritin and CRP levels o r re tic Hgb conc; O R em pirical tria l o f ¡ron supps (retese Hgb a fte r 1 mo; should in cr by 1 g/dL)

• Rx: 6 mg/kg elem ental Fe x 6 w k in 2 -3 doses, IV Fe in severe def: RBC xfusion • V it C ¡ncreases iron absorption.Tea, phytates (e.g., corn) decr iron absorption (see A AP statem ent Pediatrics 2010 fo r advised foods) • Typically im pro ve m e nt in re tic co u n t in 2 -3 d, M C V and Hgb in 1 -4 w k • A n e m ia o f c h r o n ic d ise a se : Can be m icrocytic o r norm ocycic. (N Engl J Med 2005:352:1011): hepcldin (incr w / ¡nflam) blocks Fe release • Treat underlying d iso rd e r (i.e.. epo fo r renal disease) N o r m o c y tic A n e m ia (Pediatr Rev 1988:10:77} • Low retic: Diamond-Blackfan, trans-erythroblastopenia o f childhood, aplastic crisis (see later section on Puré RBC Aplasia) • High retic: H e m o ly t ic a n e m ia s • Intrinsic: Inh abnl Hgb (fo r sickle cell & thalassemia see below, unstable Hgb mutations e.g., congenital Heinz body anemia. Hgb Hasharon); abnl RBC membrane (e.g., spherocytosls, elliptocytosis), abnl RBC enzymes (e.g., pyruvate kinase o r G6PD deficiency) • E xtrinsic:Autoim m une hem olytic anemia (w arm -reactive o r coid agglutinin), liver disease, hypersplenism, o xidant agents, microangiopathies, paroxysmal coid hem oglobinuria, paroxysmal nocturnl hem oglobinuria • H e r e d ita r y s p h e ro c y to s is : ~75% autosomal dom inant, deficient, o r abnl membrane stru ctu ra l pro te in (usually spectrin); splenomegaly, jaundice. chronic anemia; dx: smear, FHx, osm otic fragility • G 6 P D d eficie n cy: X-linked, lack of G6PD allows oxidant metabolites o f drugs to denature Hgb, acute hemolysis occurs w ith exposure to sulfa.antimalarials, naphthoquinones, orfava; hemoglobinemia and hemoglobinuria w ithin 24-48 hr o f ingestión, self-resolution in 3 -4 d • A I H A : A b against in trin sic m em brane Ag, positive D A T (C oom bs); pailón jaundice, hemoglobinuria, splenomegaly; may be a/w resp infxn o r chronic dz,e.g.,SLE o r lymphoma M a c ro c y tic A n e m ia (Ped Rev 1988:10:77: N Engi ] Med 1999:341:1986) • V i t B 12 d e fic ie n c y : Rare in kids, 2/2 pernicious anemia and ¡leal disease (C rohns) • Assoc w / pancytopenia w / macrocytosis, hyperseg PMNs • Exam: G lossitis and decreased vib ra tion and position senses • N e u ro manifestations -» can be irreversible if untreated • Rx: O ra l o r parenteral V itam in B n supplem entation • F o la te d e fic ie n c y : Rare 2/2 in cr in folate supplem entation fo r pregnancy • Found in malabsorption syndromes, E tO H use. chronic hemolysis, drugs (M T X ) • R/o V it B u def (folate supps fix RBC parameters; B 12 def can be missed)

H E M O GLOB IN O PA TH IE S S ic k le C e ll D is ea se (S C D ) (Pediatr Rev 7007:28:259: Am J Hematol 2010:85(5):346) • D e fin itio n : C h ro n ic h em olytic anemia; includes Hgb variants SS, SC, S-(3 thal. SO Arab, SD. and o th e r rare S-Hb genotypes • SS disease: Both |3-globin genes w / m utation (valine fo r glutamate at. A A 6 on 3-chain) • S C disease: 1 [3-globin chain w / mutation (lysine fo r glutamate at A A 6); longer survival o f Hgb SC; m ilder anemia, 50% less pain crises. lo w e r risk o f silent ¡nfarcts/stroke, low er rate o f fatal bacterial infxn, later osteonecrosis; splenlc ¡nfarct/sequestrum at any age • C C disease: Relatively m ild-m icro cytic anemia • S ic k le -p -th a l: 1 (3-globin gene w / S m ut, o th e r nonfxnl. Similar course as SS dz • A S (sickle cell tr a it ) : N o rm a l lifespan and pro te ctive c a rrle r tra it, b u t a/w rare fatal m edullary cáncer in adults, exercise-related deaths, splenic infarction, hematuria, hyposthenuria, venous th rom bo em bo lism (VTE), com plicated hyphema, and fetal loss (A m J Med 2009;122(6):507) • P atho p h y sio lo g y • Nucleotlde sub (G TG fo r GAG; codon 6) o f p-globln gene (chrom o 11); valine fo r glut acid; HbS polym erlzes on deoxygenation, d isto rts RBC in to crescent • Sickled cells less deformable and Incr adherence to vasc endothellum; lead to vascular occlusion, organ Ischemia, and chronic end-organ damage • E p id e m io lo g y • A frican-A m erican: 1 ¡n 375,9% ca rrle r prev ¡n US; Híspanles: 1 in 1,200 • Sickle cell-related death decr 42% 1999-2002, coincldlng w ith pneumococcal vaccine. In Dallas N ew b orn C o h o rt, 93.9% HbSS and Hb SB0 pts survlved to adulthood. M ost recent deaths in pts >18 yo after transitlon to adult care (Blood 2010; 115(17):344) • N o consistent early predictive factors Identified fo r m o rb ld ity o r m o rta lity

• C lin ic a l m a n ife s ta tio n s : Appear in firs t y r as fetal Hb concentrations decline (see table) • Fetal H b pro te ctive because it inhibits deoxy-HbS polym erization in the RBCs • Those w / persistence o f fetal H b (HbF >30%) have m ild o r no symptom s • D ia g n o s tic s tu d ie s : N e w b o rn screening (NS) perfo rm ed ¡n 44 States and D C • If NS n o t offered, high risk infants tested by electrophoresis before 3 mo • Slckledex (rapid test based on solubility) inappropriate in newborns, does n ot identify Hgb C o r (J-thal • Lab monitoring: CBC/retic annually. Hgb electrophoresis at 1 -2 yo, RBC Ag at 1 -2 yo o r before first transfuse, L FT/bili/B U N /C r/U A annually • Screening: PFTs baseline when adolescent (e a rlie r ¡f se vere/recurrent ACS); EKG/ echo as needed, O p h th o exam annually a fte r age 10,Transcranial D o p p le r (T C D ) (see below ) • P ro p h y la x is : (Pediatrics 2002;109(3):526) • PCN b irth — 36 mo: 125 mg PO bid 3 -5 yo: 250 mg PO bid >5 yo: Discontinué unless splenectom y (alt: E rythrom ycin 20 mg/kg divided bid) • Vaccination: Hib, pneum ococcal, meningococcal (after age 2), influenza • T C D : If flo w ve locity >200 cm/sec, in cr risk fo r stroke • Screening all kids w / Hb-SS and Hb-S-p every 6 -1 2 m o at 3 -1 6 yo. D /c o f Rx afte r 36 m o o f Rx resulted in reversión to abn T C D velocity o r stro ke in 45% o f pts • T r e a tm e n ts : • Transfuse w ith sickle negative, C M V -irradiated, leukoreduced, extended phenotype cross-m atched (if available) • Folate 400 m cg-1 mg PO daily • Hydroxyurea: Induces Hgb F; decr V O C , ACS, dactylitis, admission, transfusión; in cr Hgb and Hgb F; used in children as young as 9 mo, 20 mg/kg per d; a/w m ild -m o d neutropenia, mild decr plts, rash (Pediatrics 2008; 122:1332, BAB Y H U G trial. Lancet 2011 ;377(9778):1663) C o m p lic a tio n s and M a n a g e m e n t Featu re s

E va lu a tio n and M a n a g e m e n t

70% of all pts; 5% (Hb-SS) account fo r 30% o f admissions (#1 cause of hospitalizations) Triggered by coid, stress, infxn, menses, EtOH, dehydration but majority w /o identifiable cause 50% wI fever, swelling, tenderness, tachypnea, N/V

Sickle cell care plan at home • Trial o f oral analgesia p rio r to parenteral narcotics at home o r in acute care setting w/ opioids/ toradol • PO régimen: Long-acting opioid (for basal rate) and short-acting opioid (for bolus); NS bolus if dehydrated, then 1.25 maintenance (IV + PO), if concern fo r acute chest lim it to 273—3/4 maintenance, consider i after 24 hr Labs: CBCD, Retic M onitor: CV, SaOj (keep >95%) Manage side effects: Bowel régimen, itch, Gl discomfort/nausea, incent spiro

In fe c tio n

Fever >101.5"F(38.5CC) Assume functional asplenia Pts with acute chest may not present with resp sx

Strep pneumo sepsis/meningitis

Reduced by vaccination and expedient abx

Osteomyelitis

Salmonella, Staph aureus (6 mo • R/o etiologies: Evan syndrom e (ITP w / A l hem olytic anemia), lupus • G enerally benign w ith Plt co un t fro m 3 0 -8 0 /u L • Prednisone, IVIG, and a nti-D Ig raise platelet co un t b u t n o t curative (see above) H e m o ly tic -u r e m ic S y n d ro m e ( H U S ) a n d T h r o m b o tic T h r o m b o c y t o p e n ic P u rp u ra ( T T P ) (Pediatric Rev 2011:32(4):1 S.b: Fur j Pediatr 2010;169(1 ):7) • T h ro m bocytopenia, 2/2 Plt consum ption, 2/2 endothelial cell in jury, vasculitis, and p ro th ro m b o tic State (m icro th ro m b i confined I o to kidney in HUS; systemic in T T P ) • H U S : H e m o lytic anemia, throm bo cytop en ia , and acute renal failure. • Classic D (-) HUS: 90% w ith diarrhea, m ost often caused by shiga/shiga-like toxin from £. coli (0 1 5 7 /H 7 ) o r o th e r bacteria (Shigella, Strep pneumo), verotoxin inactivates A D A M TS 13 -> undeaved vW F m ultim ers initiate p lt aggregation • A typical D ( -) HUS: N o diarrhea, alm ost all have m utation in com plem ent fa c to r H, fa c to r I o r membrane co -fa cto r p ro te in -> u n co ntrolled com plem ent actlvation (Pediatr N e p h ro l 2010;25:97) • C o m m o n ly 9 m o -4 y r in sum m er & fall; 1° re se rvo ir o f bacteria = cattle • P/w abd pain, then diarrhea (30-90% ); becomes bloody. A void abx • 2 -1 4 d (mean 6 d) a fte r diarrhea 1 0-15 % develop HUS (40-50% need dialysis) • Pts w / H T N do w orse, decr plts w /o signif bleeding, 15-20% w / neuro sx (szr, coma) • Lab: Check C B C , C oom bs, smear, B U N /C r, hemolysis labs, sto o l culture • T reatm ent supportive, abx controversial. may need dialysis fo r renal failure • Eculizumab is a p otential therapy fo r atypical D (-) HUS: Blocks com plem ent activity o f C5 (N Engl J Med 2011:364:2561) • T T P : Prim arily in adults;children have autoim mune inhibition o f ADAM TS13 o r autosomal recessivc def -> v W F m ultim ers trigger coagulation in m últiple organ Systems D is s e m in a te d In tra v a s c u la r C o a g u lo p a th y ( D IC ) (Pediatric Rev 2011;32(4):135) • Pathologic activation o f coagulation —> microvascular throm bosis end-organ ischemia; consumption o f plts/coag factors -> hemorrhage • Sepsis, asphyxia, m econium aspiration, ARDS, extensive traum a • D e cr plts, fragmented RBC, prolonged PT/apt, decr fibrinogen, increased FDR Factor VIII levels differentiate D IC (decr) fro m liver failure (incr, released during hepatocyte necrosis) • Treat underlying cause, tem po rizing p lt transfusions fo r bleeding/severe decr plts and FFP fo r coag/antithrom b factors

COAGULATION D e fin itio n (Pcciatr Rev 2008:29:121; G in Pediatr 2010:49(5):422) • V hem ostasis form ation o f platelet plug by ¡nteraction b tw plts and exposed subendothelial layer; p lt adhesión via glycoprotein Ib and vW F -> p lt activation by glycoprotein llb/llla, vWF, and fibrinogen p lt aggregation • 2o hem o stas is fo rm a tio n o f organized fib rin c lo t fo r stabilization o f platelet plug through activation o f the bloo d coagulation system • Physiologic in h ib ito rs Tissue fa c to r pathway in hibito r, a n tith ro m bin, activated p ro te in C and co fa cto r p ro te in S ,fib rino lytic pathway (plasmin) • H e m o s ta s is in th e n e w b o rn : N eed age a ppropriate assays • Im m ediately postnatally, conc o fV it K dependent coag p roteins (FU, FVII. FIX, and FX) and in hibito rs p ro te in C and S are 50% o f adult valúes • C once n tratio n s o f vW F are Incr at b irth and fo r firs t several postnatal mos

k

• Factor VIII,V, X III, and fibrinogen are at/'above adu lt levels • Inherlted severe bleeding disorders present m ost ofcen in neonatal period o r early chlldhood -> may p/w clrcumcislon bleeding, umbilical stump bleeding, cephalohematoma, and subgaleal hem orrhages (as w / vacuum extractio n s) C lin ic a l M a n ife s ta tio n s o f B le e d in g D is o rd e rs • Severe bleeding disorders (hem opliilia) usually present at to d d le r stage, b u t may present in 1st y r a fte r b irth , less severe bleeding disorders, (von W ille b ra n d dz) o r platelet fxn abnorm ality may be clinically silent fo r yrs • Easy bruisability; unexpected surgical hem orrhage • Mucosal bleed (epistaxis, menorrhagia, oral, G U o r Gl bleed) th in k 1o hemostasis • Deep tissue bleeding in to muscles and jo in ts (hem arthrosis) - » th in k 2o hemostasis « Be sure to always th in k about child abuse as a cause fo r bruislng • Family hx, coexisting illness, m edication D ia g n o s tic S tu d ie s (Pediatr Rev 2008:29:121) • CB C , peripheral blood smear • PT (p ro th ro m b in tim e): Measures e xtrin sic and com m on pathways (FVII, FV, FX, p ro th ro m b in , fibrinogen); m o st co m m only prolonged w / V it K def • IN R (inte rna tio na l norm alized ra tio ):A d ju s t fo r d iffe re n t reagent sensitivitles fo r PT • PTT (activated PTT): Measures co nta ct system (prekallikrein, FXII) as w e ll as intrinsic (FVIII, FIX, FXI) and com m on pathway; hepzyme p rio r to fu rth e r eval • M ixing study (1:1 p t and norm al plasma, PT/aPTT norm alizes if missing factor(s) replenished by 50%, PT/aPTT persistent in cr suggests presence o f in hibito r/a ntib od y • Fibrinogen, th ro m b in tim e (measures fib rin form a tion , tim e reqd to fo rm c lo t on addition o f th ro m b in to plasma), bleeding tim e (p it ¡nteraction w ith vascular wall. p o o r predictability, sens, spec), platelet fun ctio n assay • Specific fa cto r issues: FXIII n o t measured by PT/PTT need specific assay, FV only facto r n o t made in liver, FVII sh o rte st 1/2 life o f all factors Abnl C B C o r Periph Blood S m ear

PTT onlv brolonved H em ophilia A o r B, Factor X I def, v W D w ith F V III dysfxn, Lupus anticoag, H eparin contam ination • check FVIII, FIX, FXI, lupus anticoag PT onlv proloneed early V it K def, Factor V II deficiency, W a rfa rin excess • check FVII

PT & aPTT brolonped. normal blatelets Liver d z .V it K def, C o m m o n path def (F a c to r X ,V , prothrom bin, fibrinogen), dysfibrinogenem ia • check FV, FX, prothrombin, mixing study, fibrinogen PT & aPTT omlonped. low blotelets D IC , liver disease • check FVIII

von W ille b ra n d dz:Check vVJF antigen, ristocetin cofactor activity, ristocetin-induced plt aggregation (RIPA), FVIII, vWF multimers analysis A cute o r chronic ITP • check platelet count, platelet function assay, meds, systemic disease

N o Abnl FXIII assay Connective fissue dz Child abuse

Pedbtr Rev 200 8.29 :1 21 ; C lin Pediatr (Phila) 2010:49:422

V on W ille b r a n d D z (Pediatr Rev 2008:29:121; Haemophilia 2008:1-1:171) • M o st com m on genetic bleeding disorder, 1% prevalence • vW F is a large m u ltim e ric g lycoprotein required fo r p it adhesión to damaged endothelium and acts as ca rrle r p ro te in fo r FVIII. High m olecular w eight m ultim ers have m o re p it binding sites and adhesive prope rtie s • N o te vW F is an acute phase reactant, can in cr w ith stress, exercise, pregnancy, ¡nflamm • O fte n asym ptom atic, positive FHx, easy bruising, repeat epistaxis, m enorrhagia (50% o f w om en), postop bleeding • T y p e 1: 70-80% o f cases, autosom al dom ina n t pardal quantltadve decr o f vW F and FVIII —> d ecr vW F a ctivity/A g and FVIII, m ild sx • T y p e 2: 15-20% o f cases, autosom al dom inant o r recessive, qualitative defect in vW F • 2A: A utosom al dom inant, norm al-re du ce d level o f FVlIlc/vW F and decr ristocetin co fa ctor activity due to decr interm ediate/high m olecular w eight vW F m ultim ers • 2B: A utosom al dom inant, d ecr high m olecular w eight vW F m ultim ers -> d ecr a ffinity fo r GPIb com plex; in te rm itte n t throm bo cytop en ia • 2M: D e cr p lt-d ire cte d fun ctio n, d ecr vW F activity • 2 N :A u to so m a l recessive, d ecr affinity o f v W F fo r FVIII > 5% FVIII levels (appear like hemophilia)

8 -8

Abnl P T and aPTT

COAGULATION

Abnl P T o r a P T T

• T y p e 3: M ost severe fo rm , autosom al recessive, marked deficiency o f v W F and FVIIIc, no vW F on plts/endothelium , no response to DDAVR severe clinical bleeding • A c q u ir e d f o r m s w ith W ilm s tum or, lym phoproliferative d/o, congenital hea rt dz, andphospholipid antibody syndrom e, a o rtic valvular stenosis, SLE, angiodysplasia, seizure disorders o nV a lproic acid. hypothyroid, essential throm bo cythe m ia • T r e a t m e n t (J Emerg Med 2010;39:158) • D e s m o p re s s in (D D A V P ) IV, IN , S u b Q : Rx o f choice fo r Type 1 v W D andTypes 2A/2M vW D , ineffective inType 3 and m ost Type 2B disease (may cause p lt drop) • Incr endogenous vW F plasma conc 2—4-fold w / sim ilar rise in FVIII activity • Dose fo r hemostasis -1 5 x used f o r DI. Peak valúes w ith in 1 h r a fte r admin • Side effects; facial flushing, HA , tachycardia, H o N a (esp pts 5 -7 d • Usually managed as ¡npts u ntil afeb w ith evident n eu tro ph il re covery • For lo w e r-risk patients consider IV o r oral rx and o u tp a tie n t management :|:D o n o t take rectal temps.

9-1

PED IATRIC 0 N C 0 L 0 G IC

LAD

D ia g n o s tic E v a lu a tio n and M a n a g e m e n t (Pediatr Rev 2008:29:53; Pediatr Clin N o rth A m 2002:49:1009) • See figure on n e xt page

O nc E m er g en c ies 9-2

S u p e rio r V en a C a v a (S V C ) S y n d ro m e (Pediatr Clin N o rth A m 1997;44:8C9) • D e fin itio n : Signs and sx fro m com pression & /o r o bstru ctio n o f SVC • E tio lo g y: O fte n a presenting feature o f in tra th o racic malignancies • Malignancies p /w mediastinal mass m o st co m m only include N H L.T-cell ALL, and Hodgkin dz. Less com m om Teratom a, sarcoma, neuroblastoma, thym om a • P athophysiology: Mediastinal mass compresses SVC causing venous stasis • Compression & /o r clotting o f SVC i venous return from head, neck, & upper thorax • Tracheal com pression may also be present, esp w ith a n te rio r masses • P re s e n ta tio n : Cough, dyspnea, dysphagia.orthopnea, s trid o r,“ wheeze,” & hoarseness • Later sx o f anxiety, confusión, lethargy, HA , A visión, and syncope may = C O 2 re te n tio n : can also see facial + /- UE swelling, plethora, chest pain, pleural effusions • Sx w o rse when patie nt is supine; should raise suspicion fo r mediastinal mass • D ia g n o s tic studies: C X R : typically w ill show a nte r mediastinal mass; trach deviation, and narrow ing on lateral vlew. C T neck/chest crucial to assess airway pateney • CB C , Chem 10, L D H , and uric acid; obtain dx tissue sample before Rx if possible • Anesthesia may be contraindicated if tracheal com pression • T r e a t m e n t: Depends on underlying malignaney • If significant C V o r resp com prom ise, em ergent X R T a nd /or IV m ethylprednisolone/ dexamethasone tre a tm e n t may be indicated

H y p e rle u k o c y to s is (Pediatr Clin N o rth A m 1997:44:809) • D e fin itio n /e tio lo g y : W B C >100.000; presence o f high s o f circ leukemic blast cells

E m e r g e n c ie s

S pinal C o rd C o m p re s s io n (S C C ) (Pediatr Clin N o rth A m 1997;44:809) • D e fin itio n /e tio lo g y : O ccurs in 2.7-5% o f children w / cáncer • M o st cases 2/2 epidural com pression fro m extensión o f paravertebral tu m o r • T risk w / neuroblastoma, Ewing sarcoma, non-Hodgkin lymphoma, and Hodgkin lymphoma • O steosarcom a and rhabdom yosarcom a typically cause SCC only w / recurrence •C lin ic a l m a n ife s ta tio n s : Back pain present in 80% pedi pts w / cord com pression • Sx typically present fo r an avg o f 2 w k before dx is made • Weakness, sensory loss, and incontinence are later and m ore concern-causing findings • E v a lu a tio n /tr e a tm e n t • D etailed neuro exam in any pt p /w suspected malign; rectal exam fo r sphincter tone • Plain radiographs o ften perfo rm ed but only show findings in V 2 o f affected patients • MRI w / co ntra st is study o f choice to assess presence and e xte n t o f SCC • C hildren w / neuro findings a n d /o r rapidly progressing spinal co rd dysfxn should receive dexamethasone 1 mg/kg IV and have em ergent spinal MRI • Surgery, XRT, and chem o are o th e r em ergent Rx options depending on tu m o r type

O nc

T u m o r Lysis S y n d ro m e ( T L S ) (N a t Clin Pract O ncol 2006:3:433) • D e fin itio n : Metabolic abn 2/2 cell death and subsequent release cell contents in to circ • M etabolic disturbances can result in severe end-organ im pairm ent, esp renal • E tio lo g y /ris k fa c to rs • O ccurs in tum ors w / T g ro w th fra ction and large tu m o r burden/volum e • Malignancies m ost com m only assoc w /TLS include B urkitt lymphoma, A LL (particularly T-cell variant), and lymphoblastic lymphoma;TLS rare in AM L • Can o ccu r before onse t o f Rx b u t typically occurs w /i 1 2 -7 2 h r o f in itia tion o f Rx • Risk factors: W B C > 50,000. T LD H , T u ric acid on adm it, C r > 1.6 o r i GFR • D ia g n o s tic studies: Elevated u ric acid (>10) - caused by breakdow n o f nucleic acids • Hyperphosphatem ia and secondary hypocalcemia; hyperkalemia • C o n s e q u en c e s o fT L S • H yperuricem ia > precipitación o f uric acid in collecting ducts o f renal tubules, causing resultant nephropathy and acute renal failure • Hyperkalem ia -> cardiac arrhythm ias and sudden death • Hypocalcemia -> hypotension, EKG changes, tetany, and seizures • Hyperphosphatem ia -> renal precipitación; exacérbate nephropathy and renal failure • M a n a g e m e n t/p re v e n tio n o fT L S : E lectrolyte abn managed acutely as indicated • U pon d x o f malignaney and before starting Rx, aggressive m gm t to preventTLS • Aggressive hydration (2 -4 x maintenance) to t GFR and T u rin ary o u tflo w • U rin a ry alkalization w / D 51/4N S w /N a H C C h (4 0 -8 0 mEq/L) to uriñe pH > 7 co p revent u ric acid precipitation • A llo p u rin o l (2 5 0-5 0 0 mg/m2/d) inhibits xanthine oxidase; l u ric acid fo rm a tio n • A lternatively, rasburicase (reco m b in an t urate oxidase) in place o f allopurinol. M o re effective & 1sc choice in high-risk cases • A lkalinization n o t necessary a fte r u ric acid level falls • Cióse observation o f electrolytes, Ca, Mg, Ph, LD H , and uric acid (q 6 -1 2 h upon in itia tion o f Rx) essential to m o n ito r fo r developm ent ofTLS

• Clinically signif hyperleukocytosis >200,000 ¡n A M L, >300,000 ¡n A LL and C M L • O ccurs in 9 -1 3% o f patients w ith A LL and 5-22% o f patients w ith A M L P a th o g e n e s is : Excessive leukocytes o b s tru c t circulation in brain, lung, and o th e r organs form in g aggregates and w h ite th ro m b i in small veins • Excessive leukocytes also com pete fo r oxygen and damage vessel walls • M o rb id ity is d ire ctly related to blood viscosity • Myeloblasts and m onoblasts are larger (A M L) and m o re likely to cause o b stru ctio n C lin ic a l m a n ife s ta tio n s • P ulm onary leukostasis -> dyspnea, hypoxia, and righ t vé ntricula r failure • Intracerebral leukostasis -> A m ental status, fro n ta l HA , szr, and papilledema • O th e r possible com plications include priapism, renal failure, and dactylitis • M ajor com plications o f hyperleukocytosis in A LL usually re su lt o f TLS • C om plications o f hyperleukocytosis in A M L usually are re su lt o f in tracerebral leukostasis and include stro ke and hem orrhage T r e a tm e n t: Aggressive hydration,alkalize,& rasburicase o r a llopurinol (to i risk ofTLS) Maintain platelet co un t >20,000 minim ize RBC xfusion to prevent fu rth e r t in viscosity C o rre c t coagulopathy w / FFP and vitam in K as indicated Exchange xfusion and leukophoresis also used to help rapidly 4 leukocyte count P ro m p t in id atio n o f chem otherapy (o r ATR A fo r acute prom yelocytic leukemia)

NEUTROPENIA IN THE PE DI ATRI C PATIENT D e f in itio n ' Pediatr Rev 2008:29:12) • A b s o lu te n e u tro p h il c o u n t ( A N C ) = W B C (cells/pL) %(PMNs + bands)/100 • Mild n eu tropenia:A N C 1 ,000-1.500/uL; moderace neutro pe nia:A N C 5 00 -1 ,000/uL; severe neutro pe nia:A N C < 500/uL. A N C < 500 assoc w ith significant risk o f infections • N o te : Low e r lim it nml A N C = 1,500 fo r pts >1 yo. For pts 2 w k -6 mo, nml A N C > 1,000. Pts females, w hites > blacks • Risk factors: D o w n syndrom e, neurofibrom atosis type 1, ataxia telangiectasia, Fanconi, o th e r syndromes C lin ic a l P re s e n ta tio n (Pediatr Rev 2005:26:96) • Fever (55%), bleeding +/- petechiae/purpura (45%), malaise (40%). bone pain (30%), hepatomegaly (70%), splenomegaly (50%), L A D (50%), abd pain (10%) • CBC: Leukocytosis or leukopenia and anemia (88%) a n d /o r throm bo cytop en ia (80%) • Blasts may be visible on peripheral blood smear, b u t are n o t always present P ro g n o s tic F a c to rs a n d O v e r a ll P ro g n o s is (N Engl | Med 2006:35-1:166) • O v e ra ll s urvival: -80% • F a v o ra b le pro g n o s tic fe a tu re s : Age at presentation 1 -9 yr, presenting W B C 50 ch ro m o) w / triso m ie s o f ’ 4, 10, and 17, t(12;21 )ITEL-AML1 fusión gene • U n fa v o ra b le p ro g n o s tic fe a tu res : Age 9 yr, presenting W B C >50,000, highly unfavorable cytogenetics: H yp op lo id y (3 3 -3 9 ch ro m o) o r near haploploidy (2 3 -2 9 chrom osom os), t(4;11)/MÜL-AF4 fusión gene in infants (present in 80% o f infant A LL), and t(9;22)/B C R -A B L protein/Philadelphia chrom osom e • O th e r unfavorable features: Fail to achieve m orph remission a fte r ¡nduction o r >1% blasts detectable by PCR o r flo w c y to m e try (m in residual dz) at the end o f ¡nduction

ACUTE M YELOGENOUS L E U K E M I A D e f in itio n (Pediatr Clin N o rlh A ir T997:44i847) • Clonal p ro life ra tio n o f any o f the follow ing (Parentheses denote French-American British Morphologic Classification): m inim ally differentiated m ycloid cells (M 0), myeloblasts (M 1 and M2), prom yelocytic (M3), myelom onocytic (M 4), m onocytic (M5), erydiroleukem ias (M 6), o r megakaryoblastic (M 7) • A M L distinguished fro m myelodysplastic syndromes by >20% blasts in BM E p id e m io lo g y (Pediatr Rev 2005:26:96; Pediatr Clin N o rth A m 2008:55:71) • -5 0 0 new pedi cases/yr in the U nited States: represents 4% o f all childhood cancers • Males - Females: equal incidence in black and w h ite children • M o re com m on than A LL ¡n neonates; no age peak in childhood (median age = 65 yr)

AML 9-

T r e a t m e n t (Pediatr Q in N o rth An 20CS;S5:1: N Engl J Med 2006:354:166) • Total tre a tm e n t duratio n is typically 2 -3 y r and consists o f 3 pilases: • Induction (4 -6 w k): Prednisone o r dexamethasone, vincristine, PEG L-asparaginase + /- anthracycline, also w / ¡ntrathecal Rx • C o n so lid a ro n (4 -6 mo): High-dose m e tho tre xate , cyclophosphamide, cytosine arabinoside (A ra C ), 6-MP, and PEG L-asparaginase • M ost p ro to co ls have delayed inten sifica ro n o r rein du ctio n phase; 4 -6 w k pulse intensive Rx sim ilar/identical co induction during 1sc 6 m o o f remission • Maintenance (2 -3 yr): O ra l M T X and 6-MP, steroid & vincristine pulses, IT chemo • R ole o f B M T : Reserved fo r pts a t ve ry high risk; w ith p o o r in itial response to tre a tm e n t o r w ith relapse • R ole o f X R T : Cranial radiation therapy reserved only fo r ve ry high-risk patients o r chose w ith significant CNS leukemic ¡nvolvem ent • W / effective risk-adjusted chemo, prophy cranial XRT can be safely o m itte d fro m Rx o f childhood A LL (N Eng J Med 2009,360:2730)

Risk F a c to rs (Pediatr Clin N o rth A m 2008:55:21; • E n v ir o n m e n ta l: Exposure to chem o (alkylating agents, topo-2-lsom erase inhibito rs) o r ionizing radiation, exposure to organic solvents, herbicides, pesticides • I n h e r ite d : D o w n syndrome, Fanconi anemia, Kostmann syndrome, ShwachmanDiamond syndrome, Diamond-Blackfan syndrome, neurofibrom atosis Type I, K lin efcltcr syndrome, Bloom syndrome, Li-Fraum eni syndrome C lin ic a l P re s e n ta tio n (Principies and Practica. ofPediuiái. Oncotogy. 6 th ed Phiíadelpnia, PA: L W W : 2011:566-587.) • Fever (30%), bone pain (20%), lym phadenopathy (100.000 (20%) • Blasts may be visible in periphcral blood smear Prognosis (Pediatr Clin N o rth A m 2008:55:21) • O v e r a ll s urvival: -50% • F a v o ra b le pro g n o s tic fe a tu re s : Age 80% cure rate) favorable cytogenetics: t(8;2 1 ), ¡nv(16), t(1 5 ;1 7), possibly c(9; 11) • U n fa v o ra b le p ro g n o s tic fa c to rs : Black ra ce .W B C >100,000 at dx, m onosom y 5 o r 7. FLT3 gene m utations. Residual dz a fte r induction e ith e r m orphologically o r by PC R /flow c y to m e try (m inimal residual disease) T r e a t m e n t (Pediatr Clin N o rth A m 2008;5S:21) • G enerally s h o rte r ( U/S/CT, l&D, Bcx • Bilateral (acute) -> usually no w /u aside fro m th ro a t swab fo r group A strep; likely viral • Unilateral/bilateral (subacute/chronic) -» consider CBC/diff, ESR, PPD (o r IGRA fo r pts >5 yo), serologies fo r EBV/CMV/Bonone/to/Tularemianbxoplasma, HIV, excisional blopsy M anagem ent • Unilateral (acute) -> A b x cover fo r staph, GAS, + /- oral flora; ¡f mild sx -> cephalexin, clinda, am ox/clav,TM P -S M X (¡f CA -M R SA prevalence high, b u t need additional agent if w a n t to cover GAS). If m od/severe sx, consider IV ccfazolin, nafeillin, a m p id llin / sulbactam, clindamycin, o r vancomycin

LYME D IS EA SE (Clin Infecí Dis 20C6;43:1089) E p id e m io lo g y • M ost com m on ve cto r b orn dz in U S, T trend; peak incidence in summer, incubation p eriod (fo r early localized disease) 2 -3 1 d, mean 11 ' Endemic areas include N o rth ea st, G re at Lakes, m id -A tla ntic regions, usually in rural, w o oded areas (fo r local prevalences:Am erican Lyme disease foundation: h ttp ://w w w . aldf.com/usmap.shtml) • M o st prevalent in children 2 -1 5 yo (Pediatrics 1998; 102:905) M ic r o b io lo g y • S pirochete Borrelia burgdorferi spread by tic k (Ixodes scapularis) on deer and mice • C oinfection w / Babesio, and o th e r rickettsial species n o t uncom m on (up to 10%), may co n trib u te to prolonged sx despite Rx fo r Lyme • Infection usually requires tic k actachment >36 hr C lin ic a l M a n ife s ta tio n s

System

Stage 1 (Early Localized - w k)

Stage 2 (Early Dissem inated - m o)

Stage 3 (L a te Chronic - y r)

Cardiac

N /A

A V block; myopericarditis, pancarditis

N/A

Constitutional

Flu-like sx

Malaise; fatigue

Fatigue

Lym phatic

Regional LAD

Regional o r generalized LAD

N/A

MSK

Myalgia

Migratory arthralgias, myalgias, oligoarthritis

Prolonged/recurrenc arthritis, synovitis

Neurologic

Headache

M eningitis, CN7 palsy, cranial neuritis, mononeuritis multiplex, transverse myelitis

Encephalopathy, polyneuropathy. leukoencephalitis

Cutaneous

E ryth em a migrans (-80%), macular lesions w ith central dearing, 6 -40 cm

Múltiple annular lesions

Lymphocytoma; acrodermatitis chronica atrophicans. panniculitis

From: N Engl J Med 2001:345:115; Lancet 2003:362:1639: Ann Intern Med 2002:136:421.

D ia g n o stic S tudies • Clinical dx during early stages (erythem a migrans),Ab against 6. burgdorferi n ot detectable w /i first few wks after infection • In early disseminated o r late dz, dx based on clinical findings and serologic tests • 2-step approach: 1 s t screening te s t fo r serum A b ’s (IFA o r EIA) • If +, then standardized W e stern b lo t (False +’s 2/2 EBV, o th e r spirochete, HIV, SLE) ' Early dz, IgG and IgM; late dz, IgG (lots o f IgM false +) • A + IgM test needs 2 o f 3 bands (Ab's). A + IgG te s t requires 5 o f 10 bands • N o te : Rx’d individuáis early in course o f in fection might, n o t develop A b ’s • C o nside r PCR in jo in t fluid, and serologies in CSF. C u lture is n o t recom m ended T r e a tm e n t • Prophylaxis: R C T (>12 yr) w / efficacy doxycycline 200 mg x 1 w /i 72 h r o f tick bite (m ust have seen and rem oved tick) to prevent Lyme dz (N Engl J Med 2001;34S:79) • Recom mended tre a tm e n t o f Lyme disease in children (Lyme Disease. Red B oo k 2009) Disease C a te gory

Drug(s) and Doses*

Early localized disease3 >8 yo

Doxycycline 100 mg PO bid x 14-21 db

A ll ages

Amoxicillin 50 mg/kg/d PO divided tid (max 1.5 g/d) fo r 14-21 d

-O RCefuroxim e 30 mg/kg/d PO divided bid (max 1 g/d) fo r 14-21 d

V

Early dissem inated and late disease Múltiple erythema migrans

Same oral régimen as fo r early localized dz but fo r 21 d

Isolated facial palsy

Same oral régimen as fo r early localized dz but fo r 21-28 de'd

A rthritis

Same oral régimen as fo r early localized dz but fo r 28 dc d

Persistent o r recurrent a rthritis'

Ceftriaxone 75-100 mg/kg IV o r IM qd (max 2 g/d) fo r 14-28 d -O R Penicillin 300.000 U/kg/d IV, divided q4h (max 20 million U/d) for 14-28 d

-ORSame oral régimen as fo r early disease Carditis

Ceftriaxone o r penicillin: See persistent o r recurrent arthritis

Meningitis/ encephalitis

Ceftriaxone o r penicillin: See persistent o r recurrent arthritis for 14-28 d

JF o r p ts w h o a re a lle rg ic t o P C N . c e fu ro x im e . an d e r y th ro m y c in a re a lte rn a tiv e drugs. ^ e tr a c y c lin e s c o n tra in d ic a te d in pregnancy.

^Corticosteroids should not be given. dR x has no effecc on the resolution o f facial nerve palsy; its purpose is co prevent late disease. ‘•'Arthritis not considered persistent o r re cu rre nt unless objectivc evidence of synovitis exists at least 2 mo after R x initiated. Sonic exp erts administer 2nd course of oral agent before using IV antimicrobial agent.

UTI/PYELONEPHRITIS E tio lo g y • M o st 2/2 ascending infxns; only -4% children w / U TI/pyelonephritis are bacterem ic M ic r o b io lo g y • 80% o f infections 2/2 E. co// • G ram-neg rods (Klebsiella, Proteus, Enterobacter, Citrobacter) = 2nd m o st com m on group • G ram -pos cocci (Enterococcus, Staph. saprophyticus [m o stly adol], Staph. aureus [ra re ]) • T rates bacterial resistance in co m m u nity acquired strains; risk fo r resistant in fection inc w /p ro lon g ed o r recent hospitalization, ¡nstrum entation, indwelling Foley • Mediated by in teractio n o f bacterial adhesins and re ce pto rs on host cells (e.g., E. coli pili - virulence fa c to r -> adhere to uroep ithe liu m and ascend) R isk F a c to rs ¡A rrh Dis Ch le 2006;91:845; Pediatrics 1998:102;e16) • Age: Females p o s te rio r u re th ra l valves • -1 % prevalence in childhood; 40% o f children w / feb rile UTIs; less com m on in A As • Grades l-V, depending on p ro x vs. distal reflux and presence/severity o f ureteral dilatation; -95% o fV U R is Grades l- lll • Equivocal studies a b o u t link between V UR and pyelonephritis/renal scarring • M o st w / re c u rre n t pyelo o r scarring do not have VUR • M ost VU R resolves w /i 5 y r • O b stru ctio n (anatom ic [p o st urethral valves. UPJ o bstru ctio n . co nstip atio n ] -1 -4 % ; neurologic bladder; functional w ith ho ld in g) • Sexual activity (strong c o rre la tion in sexually active adolescent and young adult females) C lin ic a l M a n ife s ta tio n s • Fever,abd o r back pain, dysuria, T u rin ary frequeney, urgeney o r in continence,hem aturia, suprapubic tenderness (JAM A 2007:298:2895) D ia g n o s tic S tu d ie s (Pediatrics 2011:128;c749: Pediatr Infect Dis | 2002:21:1) • Samples fo r U A and ex: Midstream clean catch if possible. O therw ise, cath o r suprapubic

Test

S e n s itiv ity (%)

S p e c ific ity (%)

Leukocyte esterase (LE)

84

78

N itrite (several hr req'd in bladder fo r +)

50

98

N itrite or leukocyte esterase

88

93

N itrite and leukocyte esterase

72

96

>10 W BC/cc - all ages (uncentrifuged)

77

89

>10 W BC/cc - under 2 yr

90

95

Bacteriuria (Gram stained)

93

95

Pyuria or bacteriuria

95

89

• “ Enhanced U /A ": uncentrifuged U /A + GS quantitative W B C /cc; m o st accurate screening test • D ifficu lt to distinguish cystitis fro m pyelonephritis via clinical crite ria (some show pyelo on DM SA) -> tre a t feb rile U TI like pyelo in children 1,000-50,000 C FU /m L especially if U A suggestive o f an U TI if single pathogenic organism and consistent clinical picture • U riñe ex >50,000 CFU /m L indicator o f significant bacteriuria if single pathogen present • Clean-catch u riñ e ex significant if >100,000 CFU /m L • Up to 85% o f -f-cx’s fro m bag u riñe specimens represent false-+ results • Suprapubic bladder tap ex significant if any pathogenic bacteria present • Blood cultures n o t ro u tine ly recom m ended in children >2 mo • Need LP in children 3 m o and children) are o u tp t Rx candidates (based on resistance): A m o xicillin ; am oxicillin/clavulanate;TM P/SM X; cefixim e; quinolones (effective, though safety concerns in younger children, n ow w / FDA warning, risk o f a rthopathy) • IV therapy fo r neonates/infants and children w / u rin ary tra c t abn orm a litie s/to xic/ unable to P O /concern fo r noncom pliance w / tre a tm e n t and fo llow -u p • Rx duration: For younger children typically 1 0 -1 4 d w / pyelonephritis (IV and PO) and 7 d fo r cystitis; 3 d fo r uncomplicated 1st UTI in o ld e r adolescents, males w / UTI typically considered com plicated (10—14 d Rx) • Patients and families should be instructed to seek medical care w ith any recurrence o f U TI sym ptom s a fte r in itial U TI diagnosis to p revent subsequent scarring

CELLULITIS D e fin itio n • Infection o f superficial, deep dermis, subcutaneous fat, and lym phatic system in the absence o f an underlying suppurative focus

M ic r o b io lo g y • Skin flora: Strep/stapl) (increasingly, C A-M RSA) • D og/cat bites: Pasteurella multocida, bacteroides, Fusobacterium, Erysipelothrix • Human bites: Eikenella • Fresh w a te r exposure: Vibrio vulnificus • Puncture wounds/piercings: Pseudomonas C lin ic a l M a n ife s ta tio n s • Pain, w a rm th , swelling, erythem a, te n d e r L A D o f draining LN, may o r may n o t have assoc abscess, lymphangitis. Less co m m only systemic sx -> fevers, chills, myalgias • Red flags (see D d x below): Pain o u t o f p ro p o rtio n to clinical findings, rapidly progressive erythema, paresthesias, crepitus, bullae, o r signs o f systemic to xicity D if f e r e n t ia l D ia g n o s is • Distinguished fro m o th e r potentially fatal infxns, including necrotizing fasciitis and clostrid ia l myonecrosis. Eval fo r underlying process, such as colle ction , septic a rth ritis , o r osteom yelitis • Erythema migrans.foreign body reactions.folliculitis.drug reactions, ¡nsect stings,contact derm atitis, lymphedema, DVT D ia g n o s tic S tu d ie s 'N Engl J Med 2004:350:904} • V irtu a lly always a clinical d x as blood cultures have lo w yield f-2% ) • Radiographs n o t necessary fo r ro u tine evaluación o f patients w / cellulitis • U/S if collections suspected • C x ’s o f drainage, pus, bullae. C x ’s o f in tact skin are generally n o t helpíul T r e a tm e n t • Incisión and drainage o f any large co lle ction o f fluid w ith in the pustule o r abscess • W a rm compresses and soaks to facilítate spontaneous drainage • Elevation o f lim b to decrease edema • For C A-M RSA infections, effectiveness o f decolonization uncertain (Lancet Infect Dis 2 011:11:952) • A n t ib io t ic R x • O u tp t -> cephalexin, didoxacillin. If CA-MRSA rates t , known colonization o r previous infection w / CA-M RSA and o th e r MRSA risk factors, consider em piricTM P -S M X o r dindamycin. However, the utility o f antibiotics in uncomplicated superficial infections ¡s uncertain (Pediatrics 2 0 1 1;127:e573:J Pediatr 2011:158:861-862. commentary) • Inpt -> IV nafeillin. cefazolin, dindam ycin. If concern f o r MRSA, unresponsive o r severe disease -> IV vancomycin firs t line; alcernative: Linezolid

S E P T I C A R T H R I T I S AND O S T E O M Y E L I T I S E tio lo g y • S e p tic a r t h r it is : M ost cases in kids seeds ¡o in t space • Spread fro m adj osteom yelitis (m ost com m on in spreads to com p act/cortical bone • Hem atogenous (bacteremia) > d ire ct invasión (e.g., nail, open fracture, puncture w ound, pressure ulcers, sinusitis, mastoiditis, dental abscess) > vascular insuff • 50% o f cases in children 12 y r and n o t on HAART: IN H and Rifapentine x 3 mo; INH-resistance: Rifampin Q D x 6 mo T r e a t m e n t o f A c tiv e T B • A F B i, culture+, o r high level o f suspicion • Isolate p t (te st fam ily and cióse contacts/prophylaxes as needed) • 1st-line régim en is 4 drug Rx (usually HREZ - see later) x2 mo. then HR x4 mo • Do not give few er than 3 drugs to prevent resistance • If TB meningitis: H R Z (+ /- ethionamide 20 mg/kg/d) x 2 m o and prednisone 1 -2 mg/kg/d taper o ver 3 w k, then HR x 9 -1 0 m o • In developing c o u n trie s .W H O recom m ends d ire ctly observed therapy (D O T ) to increase com pliance/cure and decrease resistance • M ultid ru g-resista n t (M DR) TB: W o rld w id e prevalence in 2007 -5%, defin itio n -> resistant to at least HR -> re fer to ID fo r Rx;also X D R -T B (extre m e ly resistant)

Pediatric Dosing of Antituberculosis Medications (non-MDR) Dosing3 (daily, mg/kg) Common Side Effeets Drug Hepatitis, peripheral neuropathy, Gl upset

Isoniazid (H)

5 (4-6)

Rifampin (R)

10 (8-12)

Orange uriñe, elevated LFTs, Gl upset Arthralgia, Gl upset, HA, malaise

Ethambutol (E)

20 (15-25)

Pyrazinamide (Z)

25 (20-30)

Hepatitis, arthropathy, hyperuricemia

Streptomycin (S)

15 (12-18)

Ototoxicity, nephrotoxicity

’ Might utilize higher doses in invasive disease and meningitis. In some cases, serum drug level testing might be appropriate. Adap te d fro m W H O "H o s p ita l C are fo r C h ild re n ’’ 2005: 352.

HIV E tio lo g y (AAP Redbook 2009) • HIV-1 m o st com m on in US, HIV-2 m o re com m on in W e st A frica • Retrovirus infection, which infects and depletes C D 4 cells over tim e, leading to severe ¡m m unocom prom ise (AIDS) and o p p o rtu n istic infections (Oís)

Tra n sm is sio n ( .AM A 2000:283:1175) • Vertical transm ission: In ú te ro (T risk w / T m aternal viral load): 5 -1 0% transm ission • D uring delivery (T risk w / vaginal delivery): 10-20% transm ission • Breast-feeding ( t risk w / m lxed form u la + breast m ilk): 5-20% transm ission • H o rizo n ta l transm ission: Sexual contact, injection d rug use, blood transfusions C lin ic a l M a n ife s ta tio n s (AAP Redbook 2C09) • Early manifestations: Unexplained fevers, generalized LAD, HSM, FTT, persistent/' re c u rre n t oral & diaper candidiasis, re c u rre n t diarrhea, parotitis, hepatitis, central nervous system (C NS) disease, re c u rre n t invasive bacterial in fections. and o th e r o p p o rtu n istic infections (e.g., viral and fungal) • Median age u ntil sx a fte r perinatal infxn is 1 2 -1 8 mo, some asym ptom atic >5 y r • H istorically, 15-20% m o rta lity in perinatally infected pts by 4 yo if no Rx available • N e w ly HlV -infected adolescents and adults may be asymp fo r yrs (latent infxn) until they progress to severe ¡m m unocom prom ise D ia g n o stic S tudies (N Engl] Med 1988:319:961; M M W R 1990:39:380) • H IV ELISA: 1st-line screening te st (99+% sensitivity and specificity) • W e stern blot: C o n firm a to ry test (99+% sensitivity and specificity) • HIV-1 PCR: (99% sensitivity, 98% specificity) • Used to dx acute H IV before H IV ELISA turns + (usually w /i 3 m o)

HIV 10-17

E p id e m io lo g y • Preadolescent infections: 1 0 0 -2 00 ¡nfant in fections/year in US • Adolescent infections on the rise: In 2005,-14% o f newly diagnosed HIV-1 infections in US were among 13-24 yo, m ost asymptomatic and unaware o f HIV status (RF: liin o rity, MSM)

C D 4 absolute co u n t predicts risk fo r o p p o rtu n is tic infections • CD4% m o re reliable in young children (less variability between tests) Indications to initiate a ntire tro vira l therapy (www.aidsinfo.nih.gov); in itia tion o f th e r­ apy depends on a com bination o f factors including the age o f the child, and virologic, ¡mmunologic, and clinical crite ria O ld e r C hildren and Adolescents (>5 yo)

Infants ( FTT, feeding problem s, vom iting, neuro sx, lethargy, ataxia, szrs • Teens/adults: C h ro n ic neuro o r psych sx, behav probs, lethargy,psychosls • O f note, arginase deficiency w /o hyperammonemla, p /w progressive neuro dete rio ra tion D ia g n o s is • Check NFb. D x based on abn plasma & uriñe am lno acid levels, ro u tln e labs o fte n nml O r n ith in e T r a n s c a r b a m y la s e D e fic ie n c y ( O T C ) • M ost com m on; 1:14,000; X -linked, many w / residual enzyme activity; T o ro tlc acid level • Can present between 1 m o o f age to childhood w ith significant illness; Inc uriñe o ro tic add T r e a tm e n t • A cute therapy -» see the previous discussion • Long-term management: M etabolic team to assess diet, lo w -p ro te in dlets, good fluid intake, vaccinations, and tre atln g infections early A m in o a c id o p a th ie s D e f in itio n (Vademécum Metabolicum 2004:57'; ^ediaii Rev 2009:30:e22) • D e f o f enzymes fo r A A metab —> to x ic substances accumulate in brain, liver, and kidneys • If kn ow n d isorde r o fA A metabolism and ill -> cali m etabolic team; o ften p /w acidosis • Labs as above and emergeney Rx glucose as above, stop pro te in Intake, keep Na >140 to prevent cerebral edema, A bx, deto x prn w / diuresis o r H D .V its and carnltine depending on dz

T y r o s in e m ia (A rri | Med Genet C Serrun Med G cnet 2006¡1-'12C:T21: Vademécum Metábolicum 2004:72) • A ccum ulation o f tyrosine in fluids and tissue • Type I is the m o st severe - 4 liver failure, neurologic crises, rickets, hepatocarcinom a • 1:100,000 newborns; deficiency o f fum arylacetoacetate hydrolase (FAH) • U ntreated -> death before 2 yo • Type II: Deficiency o f tyrosine am inotransferase (TAT) • Presents w ith hype rke ra to tic plaques on the hands and soles o f the feet and photophobia secondary to tyrosine crystals w ith in the cornea • Type III: Extrem ely rare 2/2 deficiency o f 4-hydroxyphenylpyruvate dioxygenase • Treatm ent -> urgent therapy w ith nitisinone (blocks accumulation o f to xic metabolices) • Long te rm —> phenylalanine and tyrosine re stricte d diets M a p le s y ru p u r iñ e d ise a se (Pediatrics 20C6;118:e934:Vademecum Metábolicum 20C4:7Q) • Deficiency in activity o f branched-chain a -o xoa cid dehydrogenase com plex -> accum ulation o f leucine, isoleucine, and valine • A R w ith 1:185,000. M ore com m on in the M ennonite population • Best outeom es when tre ate d w ith in firs t 2 w k o f life • ' Encephalopathy a t 4 -7 d w / lethargy, feeding probs, somnolence, cerebral edema, coma • U riñe w / maple s yru p /b u rn t sugar smell. If breast fed, see in 2nd w k (¿ pro te in intake) • In te rm itte n t dz may go undx’d u ntil 5 m o -2 y r o f age —> d x ’d during a m ild illness • Interm edíate dz -> progressive neurologic probs w / MR & d x ’d b tw S m o & 7 y r • D x -> T valine, leucine (plasma > 4 mg/dL) and isoleucine in plasma. U riñe w / branchedchain oxo-/hydroxyac¡ds • Rx —> glucose and insulin infusión, avoid deficiency o f isoleucine and valine • Long te rm fo llo w these A A s in the plasma and adjust d iet • M ust have lo w level o f these A A s fo r g ro w th and developm ent • Trial o f thiam ine supplem entation 5 0 -3 0 0 mg/d 3 w k is recom m ended

x

O r g a n ic A c id u r ia s D e f in itio n (Pedat-ics 1998:102:e69; Vademécum Metábolicum 2004:65) • D /o o f in term ed ia ry metabolism w / accum ulation o f acids in uriñe • Presents w ith systemic illness ± cerebral abnorm alities • Neonatal -4 m etabolic encephalopathy, lethargy, feeding problem s, truncal hypotonia, lim b hypertonia, m yoclonic jerks, cerebral edema, coma, m ultiorgan failure • C hronic in te rm itte n t -4 present up to adulthood, recurring ketoacidotic coma, lethargy, focal neurologic signs • C h ro nic progressive form > FTT, chro nic vom iting, anorexia, osteoporosis, hypotonia, p sycho m o tor retardation, re c u rre n t infections P re s e n ta tio n • Ketosis/ketoacidosis, t lactate. 7 N H 3, hypo- o r hyperglycemia, neutropenia, throm bo cytop en ia , pancytopenia, hypocalcemia

U rea

C ycle

D/O

1 1 -5

D ia g n o s is • A bn o rm a l organic acids in the uriñe T r e a tm e n t • As above w ith glucose, elim ínate pro te in , supplem ent w ith carnitine • Propionic O A ->2 isoleucine, valine, m ethionine, threonine in diet. Give L-carnitine 5 0 100 mg/kg/d • Methylm alonic O A - 4 as fo r p ro pio n ic + vitam in B 12 < Isovaieric O A —> L-carnitine 5 0 -1 0 0 mg/kg/d ± L-glycine 1 5 0 -2 50 mg/kg/d. L ow leucine diet, lo w pro te in F a tt y A c id O x id a t io n D e fe c ts D e f in itio n (Pediatrics 2006:118:E934: Pediatr Rev 2009:30:e22) • Unable to use stored fa t during fasting • P/w h ypoketotic hypoglycemia & m etabolic acidosis, t transaminases & hyperammonem ia ± hepatomegaly M e d iu m -c h a in A c y l- C o A D e h y d ro g e n a s e D e fic ie n c y ( M C A D ) D e f in itio n ¡Pediatrics 20O6;118£934) • M o st com m on d /o o f fatty acid oxidation: AR, 1:6,500^16,000 • D efect in m ito p-o xida tio n -4 affeets liver (unable to A fats to ketones -> hypoglycemia)

i

C lin ic a l M a n ife s ta tio n s • V om iting and lethargy a fte r fasting in a 3 -1 5 m o child • M o st diagnosed may develop coma (from hypoglycemia + to xicity o f fatty acids and mecabolites) • Muscle weakness worsens w ith increased delay ¡n diagnosis D ia g n o s is - D e tecte d on NBS • C o n firm d x w ith plasma acylcarnitinc analysis and u rin a ry organic acids • May need skin bx fo r enzyme eval o f fibroblasts to n arrow dow n actual enzymatic defect M anagem ent • A void fasting o r decreased dietary fat Intake • Supplement w ith L-carnitlne (especially during illnesses) • Treat aggressively even during m ild illnesses w ith IV glucose and carnitine

POSTMORTEM LABS (Pediatrics 1998;1C2:e69; Urea Cyclc Disorders.Vademécum Metabolicum; 2004:25) • Serum and plasma: C entrifuge several ccs im m ediately and store frozen • D rie d bloo d sp o t on filte r paper card • U riñe: Freeze Immediately • Bile: Spot on filte r paper and store, if available • 3 -1 0 cc EDTA w h o le bloo d fo r D N A analysis • Skin bx: Up to 24 hr postm ortem . stored at room tem p o r 37cC in tissue cx med o r sterile saline • C o nside r CSF and vitre o us fluid; both should be frozen • A uto psy is encouraged

T RISO M Y 13 D e f in itio n (A m J Med G enet A 2006:140:1749: Nclson Texibook of Pediatrics, 17th ed.) • Patau syndrom e • 0.85:10,000 live birth s, large percentage term ln ate d before b irth • Death frequ e ntly in I s t m o o f life • Clinical manifestations: C le ft lip, polydactyly, lo w -se t ears, holoprosencephaly, mlcrophchalm ia, cardiac defects, absent ribs, visceral and genital anomalies

TRISO M Y 18 D e f in itio n (A m J Med G enet A 2006:140:1749; Neison Textbook o f Pediatrics. 17th ed.) • Edwards syndrom e • 1.29:10,000 live birth s, large percentage term ln ate d before b irth • Death fre qu e ntly in 1st m o o f life, 5% survival to 1 st birthday • Clinical findings: Closed fists w / índex finger overlapping 3 rd digit and 5th digit overlapplng 4 th digit, ro cke r-b o tto m feet, microcephaly, micrognathia, cardiac/renal m alform

T RIS O M Y 21 D e f in itio n (Lancel. 2003:361:1281: A m Fam Physician 1999:59:381) • D o w n ’s syndrom e; m o st com m on genetic syndrom e. 1:800-1,000 live b irth s • Congenital h ea rt disease, myelodysplasia in n ew born and duodenal atresia highly specific fo rT ris o m y 2 1 • 95% 2/2 nondisjunction (nonsegregation) ch ro m o 21 in oocyte o r sperm atocyte

• •

4-5 % caused by translocation o f one chrom osom e 21 to ano the r 1% o f cases are mosaics (nondisjunction o ccurrin g a fte r conception)

D ia g n o s is • A t b irth : C onstellation o f features and co nfirm atio n by karyotype • Prenatal: Quad screen: M aternal a -fe to p ro te in & Estriol lo w e r than nml and ¡5-HCG & Inhibin A higher (70-84% sensitivity) • Fetal US w / nuchal translucency, s h o rt fem urs, cardiac anomalies, and duodenal atresia • W om en >35 yo w/increased risk. C h orio nic villus sampling can be done b tw 9 and 11 w k gestation, amnio b tw 16 and 18 w k. Fecal cells examined fo r chromosomal abn • Physical actributes: H ypotonia. fíat face, upward/slanted palpebral fissures, epicanthic folds, Brushfield spots, mental retardation. cardiac m alform ations. simian crease C o m p lic a t io n s • Congenital h ea rt disease: 40-60% o f infants -4 ECG and TTE • C o m p le te AV canal defects (60% o f h e a rt defects);VSD (32% );TOF (6%) • Gl defects: Esophageal atresia,TEF, p yloric stenosis, duodenal atresia, Meckel, H irschsprung, ¡m perforate anus, and GERD; 5 -1 5% w / Celiac dz • ENT: Midfacial m alform ations interfere w ith nml drainage o f Eustachian tube and sinuses • R ecurrent o titis media, sinusitis, and pharyngitis • O rtho p ed ic: • A tlan to-occip ita l instability, hyperflexibility, scoliosis • Atlancoaxial instability: 13% asymp & need m o n itoring . N o co nta ct sports • Late hip dislocation (>2 yo),SC FE,patellar subluxation o r d islo ca tio n .fo o t d eform ities • Thyroid dz follow ed by yearly TSH. G H def and gonadal dysfunction may also be present • 'Congenital cacaracts and o th e r eye disease • Transient m yeloproliferative d iso rd e r (leukem oid reaction) in 10% o f new borns (rare in n o n -D o w n ’s infants). Increased risk o f ALL • Seizure d iso rd e r in 5-10% • D ental problem s and feeding difficulties • Refer fo r early in terven tion to help w ith developm ent

T U R N E R SYNDROME D e f in itio n (A m Fam Pnysidan 2007:76:405: Clin Pediatr (Phiia) 2006:45:301) • Partial o r co m p lete absence o f X chrom osom e, 45 X karyotype • 50 per 100,000 live female births D ia g n o s is (N a l Cl n Pract Endocrinol M etab 2005:1:41) • C o nside r ¡n girls w ith s h o rt stature (2 SD below mean height fo r age), prim a ry am enorrhea. lack o f brease developm ent, delayed pub erty 4 C o nside r in fetus w / hydrops, T nuchal translucency, cystic hygroma, o r lymphedema 4 D x made w ith ka ryotyping -4 chrom osom al analysis o f 30 peripheral lym phocytes 4 50% w / missing X chrom osom e in all cells studied, o th e rs w / 45, X /46, X X mosaic C lin ic a l M a n ife s ta tio n s 4 Risk o f congenital hea rt defects -» 75% w ith e ithe r coarctation o f the aorta o r bicuspid a o rtic valve. Risk o f progressive a o rtic ro o t dilation o r dissection 4 Risk o f cong lymphedema, renal m alform , hearing loss, osteoporosis, obesity, and diabetes 4 N o rm a l IQ , although may have difficulty w / nonverbal, social, and p sycho m o tor skills 4 Physical exam: Misshapen o r ro tate d ears, lo w p o s te rio r hairline, w ebbed neck, broad chcst w ith w idely spaced nipples and cubitus valgus, shortened 4 th metacarpal 4 A lm o st all are in fe rtiie M a n a g e m e n t (E ndocrhe 2011 PMID 22147393) Treat s h o rt stature w ith G H therapy through bone age o f 14 yo. • Estrogen in adolescence fo r pubertal developm ent and prevention o f osteoporosis w ith Ca + V it D. C ontinué thro u g h o u t life 4 Hearing tests, pediatric o p th o fo r hyperopia and strabismus, regular dental visits 4 Echocardiogram to río congenital h ea rt defects, 4 e x t BPs to fo llo w fo r coarctation • Renal ultrasound f o r renal m alform ations • >4 yo r/o celiac w ith tissue transglutaminase im m unoglobulin A & rp t q2—4yr

C lin ic a l M a n ife s ta tio n s • V om iting and lethargy a fte r fasting ¡n a 3 -1 5 m o child • M ost dlagnosed ischem ia/infarction • Average age o f diagnosis ¡s 29 yo, w ith a life span o f SO y r • 1:40,000-6 0,0 00 males, X -lin ke d recessive. Female carriers may develop mild manifestations • N o t associated w ith MR o r physical abnorm alities • Angiokeratomas, hypohidrosis, and acroparesthesia (burning/tingling pain in extrem ities) C lin ic a l M a n ife s ta tio n s ( 4 - 1 6 y o ) • N e urop a th ic pain (burning/tingling) th a t usually begins in hands and feet • May have feve r + elevated ESR, diarrhea, abd pain, N/V, FTT • Triggered by stress, heat, fatigue, o r exercise (cannot sweat) Angiokeratom as (purplish/red nonblanching telangiectases); T in size and # w / age • Eyes w ith w h o rle d corneal opacity C lin ic a l M a n ife s ta tio n s (T e e n s -> A d u lt h o o d ) • Renal com plications -> urem ia + H T N -> ESRD • May have MI. valve abnorm ality. arrhythm ias, LVH, early strokes, and dyspnea D ia g n o s is • D eficient o r absent a-galactosidase A activity • Can be d x’d prenatally w ith ch o rio n ic villi o r cu ltured am niocytc

k

T re a tm e n t • a-galactosidase A replacem ent (| In h e rit M etab Dis 2012:35:227) • A void pain triggers such as heat, coid, stress, o r e xe rtlo n • Some benefit fro m carbamazepine, gabapentln, dlphenylhydantoln, NSAIDs • Gl sym ptom s are helped w ith pancrelipase o r m e to d o p ra m id e • C heck baseline renal, heart, and brain MRI before enzyme Rx to fo llo w disease F o llo w -u p • CB C , chem istries, U /A , creatinin e :A lb u m in ratio, C rC I • In adolescents: Every o th e r y r echo and ECG to m o n ito r fo r cardiac abnorm ality P o m p e D isease D e f in itio n íj Pediair 20C4;144:S35) • Glycogen storage type II disease o r acid maltase deficiency; lysosomai storage d isorde r • C onsidered a neuromuscular, m etabolic myopathy, & glycogen storage disease • Muscle d /o caused by deficiency o f acid a-glucosidase -> lysosomai glycogen accum ulation in cardiac, skeletal, and sm o o th muscle cells In fa n tile O n s e t • Death w ith in 1st y r o f life; present in 1st few m o —> floppy baby • H ypotonia, muscle weakness, H C M -> death fro m cardiopulm onary failure J u v e n ile a n d A d u lt O n s e t • Less severe cardiac issue; presents at any age; survival: Early childhood to late adults • Progressive skeletal muscle dysfunction. calf muscle pseudohypertrophy • G o w e r slgn -> using hands and arms to stand up fro m a lying position • Require w heelchairs and eventual artificial ventllation -> re sp ira to ry failure D ia g n o s is • Clinical syndrom e and muscle bx —> check acid a-glucos¡dasc activity in skln/muscle fibroblasts • O th e r fam ily m em bers should be tested; genetic counseling recom m ended T r e a tm e n t • S upportive care M u c o p o ly s a c c h a rid e D is o rd e rs (M P S ) D e fin itio n (Peciatr Rev 2ü09:30:e22:j Pediatr 2004;":44:527) • D e f o f enzyme fo r degradation o f glycosaminoglycans (previously mucopolysaccharides) • A ccum ulation o f glycosaminoglycans ¡n lysosomes cell, tissue, organ dysfunction • Incidence:-1:22.500; A R e xc e p tty p e II (H u n te r syndrom e), which ¡s X -lin ke d recessive P re s e n ta tio n • N m l a t b irth —> ch ro nic progressIve coursc w / multisys involv, abn facies, organomegaly • Loss o f developm ental skills, fre qu e nt pneumonías, cardiom yopathy D iagnosis • Specific enzyme assays fo r each type • 7 types: I—IV,VI,VII, IX; III and IV havlng subtypes • Recom mend genetic counseling

MITOCHONDR IAL D E FEC TS D e f in itio n (A m J Med G enet 2001:106:4; P edatr Rev 2009;30:e22) • Enzyme o r enzyme com plex d isorde r involved in ATP p ro du ction via o xidative phos • Enzymes involved include pyruyate dehydrogenase com plex, trica rb oxyllc acid cyd e .th e re sp ira to ry chain and ATP synthase • Affects h igh-energy-requlring organs -» brain, skeletal muscle, heart, kidney, & retina • Inheritance can be recessive, dom inant, X -linked, o r maternal w ith variable penetrance

D z 11-10

H u n t e r S y n d ro m e (M P S II) • Severe MPS II disease, X -linked, seen in males • Deficiency o f ¡duronate sulfatase -> dermatan sulfate and heparan sulfate stored • S upportive therapy

P ompe

H u r ie r S y n d ro m e • M o st severe fo rm (MPS I) • Deficiency o f a-L-iduronidase -> dermatan sulfate and heparan sulfate stored • Usually norm al a t b irth ; death before 10 yo • Presents ¡n early ¡nfaney o r childhood w / severe somatic & neurologic dz, progressive MR • Bone m a rro w transplantation ¡s helpful; enzyme replacem ent also available

C lin ic a l P re s e n ta tio n • Suspected in the follow ing: C o m b o o f neurom uscular a nd /or non-neurom uscular sx • Progressive course; unrelated organs o r tissues involved in disease process • N e urolog ic presentation: • C entral a n d /o r peripheral sx, seizures, hypotonia, abn m ovements, resp distress, encephalopathy, coma, p o o r head co n tro l as an infant, cerebellar ataxia, MR, p o o r p sycho m o tor developm ent, o r loss o f skills • M uscular presentation • Can range fro m fatal infantile myopathy -> progressive muscle weakness • Generalized weakness, resp distress, lactic acidosis, exercise intolerance and rhabdo • Fatal fo rm results in death before 1 yo • M ultisystem disease • Anemia, FTT, live r dysfunction, diarrhea, s h o rt stature, D M , cardiomyopathy, FSGS, retinopathy, hearing loss, feeding difficulties D ia g n o s is • Full assessment o f muscle function, CK, EMG, neuro exam w ith EEG • Lactic acid, CSF lactate. u riñe organic acids, plasma and CSF am ino acids, CSF p rotein • MRI, consider N M R spectroscopy • Surgical muscle bx in m itochondrial center —> EM fo r quant m itochondria and morphoiogy, enzyme histo, ¡mmunohisto, genetic studies, enzyme studies, and light microscopy T re a tm e n t • Fluids. electrolytes, re s tric t glucose, and avoid drugs th a t affect the re sp ira to ry chain (valproate, tetracyclines, chloram phenicol) • Treat acidosis; consider cofactors: Coenzym e q 10, b iotin , creatine

E H L E R S - D A N L O S SYNDROME D e f in itio n (Clin G enet 2012 PMID: 22353005;A dv Neonatal Care 20055:301) • Heterogeneous connecclve tissue disorders involving skin, organs, and ¡oints • A utosom al dom inant, recessive, o r X -lin ke d inheritance • Villefranche classification w / 6 subtypes; many rare, uncom m on form s E p id e m io lo g y « O verall prevalence 1:5,000; Classic type 1:10,000-20,000 • A ffects males and females o f all racial and ethnic backgrounds D ia g n o s is • Based on fam ily h isto ry and clinical exam

Mito

D z 11-11

P ro g n o s is • Based on type; sudden death fro m vascular ru p tu re o r p erfo ra tion is n o t uncom m on • C hildren w ith CVA should be evaluated fo r EDS C la s s ic E D S • Affects 20,000-40,000 people • A D m utations o f collagen type 1 a 1 (COL 7A 7), COL 1A2, COL5A 7, COL5A2 • D x confirm ed by FHx and clinical features • Clinical features: Skin hyperextensibility, IUGR, prem ature b irth , jo in t hyperm obility, redundant skin folds, skin scarring, congenital diverticula o f the bladder and inguinal hernias (in males), muscle hypotonia, delayed gross m o to r developm ent • MVP and regurgitación H y p e r m o b ilit y " AD, m ost com m on type: 1:10,000 -15,000 • N o known genes and diagnosis is by clinical exam and confirm ed by FHx • Clinical features: Sm ooth, velvety skin; easy bruising, jo in t hype rm o b ility w ith unusual ROM, inguinal hernias (males), re c u rre n t jo in t dislocation, chro nic jo in t/lim b pain • MVP and regurgitación V a s c u la r • 1 : 100 ,000 - 200,000 • A D mutations o f COL3A 7 w ith over 320 mucacion variations. Responsible fo r procollagen, which provides strength in connective tissue • D x is confirm ed by skin biopsy

• Clinical features:Thin tra nsluce nt skin o ver chest and abdom en, acrogeria (loss o f subcutaneous fa t and collagen o f hands and feet), lobeless ears, s h o rt stature, extensive bruising, h ype rm o b ility o f small jo in ts C lin ic a l M a n a g e m e n t • Classical and hyperm obile types may develop a o rtic ro o t d ilatation (up to 28%) -s r o o t should be measured at 5 y r o f age then q5yr • Less strenuous activities recom m ended in o rd e r to avoid jo in t strain and damage

MARFAN D IS EA SE D e f in itio n (H ea rt 2011 Aug;97:1206; EurJ Hum G en e l 2007:15:724) • Connective tissue d /o secondary to fibrillin m utation (FBN 1) affecting CV, eyes, & bones • Variable autosom al dom inance, fibrillin-1 on ch rom osom e 15 in up to 91% o f cases • Transform ing g ro w th fa c to r |)-re ce p to r 1 and 2 genes may also be factors • A d u lt diagnosis is made w ith new G hent crite ria although it is found to be unreliable in children E p id e m io lo g y • 1:9,800 b irths; 27% are fro m a new mutación D ia g n o s is (j Med G enet 2010:47476) • Suspect if tall, chin, long limbs, arachnodactyly, pectus deform ity, a nd /or scoliosis • Family h isto ry o f a o rtic aneurysm o r familial tho ra cic a o rtic aneurysms • O riginal G he n t crite ria replaced by new G hent crite ria (sec J Med G enet 2010:47:476) • C V :TTE eval o f a o rtic d iam eter; use pediatric nom ogram (A m J C ard io l 1989:64:507) • O phthalm ology: Myopia and lens subluxation • Skeletal: Pectus, w ris t and thum b signs, scoliosis, arm spamheight >1.05 C o m p lic a tio n s • Progressive a o rtic dilation, usually a t sinus ofValsalva -> AV ¡ncompetence -» a o rtic dissection and ru p tu re ; T risk o f a o rtic dissection in pregnant w om en • LV dilatación —» cardiac failure • M itral valve prolapse -> re g u rg ita ro n • Lens dislocación, myopia, and retinal detachm ent • Scoliosis in approxim ately 60% • Joint h ype rm o b ility in 85% a o rtic dissection C lin ic a l M a n a g e m e n t (N Engl J Med 2008:358:2787) • p -blockcrs if a orta is dilated; ARBs/ACEl can slo w dilation • Follow a o rtic diam eter w / biannual/annual TTE, and consider surgery when >5 cm • Surgery usually ¡nvolves replacing the valve and a orta (Bencall procedure) • Should avoid high-intensity activity *

F E B R I L E S E IZ U R E S D e f in itio n (Pedialrics 2008:17.1:1281: Pediatr Rev 2007:28:363) • S im p le f e b r ile s e iz u re : B rie f (15 min), focal com ponent, a nd/or >1 episode w ith in 24-hr period. O fte n requires ancillary workup/neuroim aging to r/o focal etiology. E p id e m io lo g y (J Child N e urol 2002:17:544) • M o st com m on szr d iso rd e r in children, affects -2 -5 % between ages 6 -6 0 m o • Risk factors: 1st-/2nd-degree relative h/o feb rile szr, peak tem p, & rate o f rise P a th o p h y s io lo g y ¡J Child N e urol 2002;17:S44;Trends Neurosci 2007:30:490) • Mechanism unclear, may be related to rate o f rise o f fever o r actual peak tem p (usually >102). Possible cytokine & tem p effect on ion channels & neuronal tissue D ia g n o s tic S tu d ie s (Pediatrics 2011:127:389) • In general, focus should be on fever w o rku p and n o t w o rk u p o f seizure itself * I s t s im p le f e b r ile s e iz u r e : N o w o rk u p * C o m p le x f e b r ile s e iz u re : C B C w / diff, Chem 10, EEG; lum bar puncture (LP) (as below ), neuroimaging if focal (MRI preferred) • L P ; N o t ro u tin cly w a rra n te d fo r sim ple fe b rile szr b u t recom m ended fo r: * Signs suggestive o f meningitis o r in tracranial in fection. Be aware th a t meningeal sx may be absent in infants 50%)

EPILEPSY D e f in itio n (Pediatr Rev 2007:23:363: Epilepsia 2010:51:676) • E p ile p s y : >2 seizures w /o clear underlylng cause • F o c a l s e iz u re s : Unilateral hemispheric origin w ith consistent focal m o to r manifestations. Seizures often propágate and lead to global excitation • A s s o c ia te d s y n d ro m e s : • Benign partial epilepsy (benign rolandic): Presents 3 -1 3 yo.Tonlc o r clonic mvmts, often unilateral paresthesias o f lo w e r face.TypIcal e lectrical corre la te in sleep • Temporal lobe epilepsy: Presents childhood, may re m it in adol. re tu rn in adulthood. O fte n w / aura, psychic sx.and automatisms. May/may n o t arise fro m tem po ra l lobe • Frontal lobe epilepsy: Frequently occurs ¡n nlghttlm e clusters. O fte n involves auras and bizarre autom atism s (e.g., bicycle pedaling, pelvic thrusting) • Parietal lobe epilepsy: O fte n involves som atosensory sx, including paresthesia and detailed visual hallucinations • O ccipital lobe: O fte n involves vague visual sx o f flashes o f llght/colors • G e n e ra liz e d se izu re s: Bilateral excitation w ith ¡nconsistent localization and lateralizatlon patterns. M o to r manifestations bilateral and often synchronous • S u b ty p e s : • Absence: “ Staring spells.” Sudden b rle f L O C , + /- eye flickering. letal EEG shows 3 Hz splke/wave pattern. Activated by hyperventllation • M yoclonic: Sudden muscle co ntractions • C lonic: A sym m e tric/irreg u lar jerking • Tonic: Sustained co ntra ctio n w /o clonic phase. Assoc w / diffuse cerebral damage • T onic-clonic: Has to n ic. clonic, and postictal phases • A to n ic :"D ro p seizure.” B rie f lapse in muscle tone • A s s o c ia te d s y n d r o m e s (E p ile p s ia 2 0 1 0 ;5 1 :2 1 7 5 ; L a n c e t N e u r o l 2 0 0 9 ;8 :8 2 ): • Infantile spasms: Usually presents 5 -1 2 mo, rernitting by -3 yo. Symmetric, bilateral, brief, and sudden contractions o f axial muscle groups. Assoc w / p oo r neurocog outeomes

and Lennox-Gastaut syndrome, Freq ranges fro m few to 100s o f szrs daily. Typical EEG correlate o f hypsarrhythmia (Irregular, disorganized, high amplitude waves and spikes) • Lennox-G astaut: Usually presents 2 -8 yo. C haracterized by m ental retarda tion and m últiple generalized seizure subtypes. p articula rly to n ic and atonic.Typical EEG co rre la te is a slo w spike-wave p attern w ith highest voltage in th e fro nta l regions E p id e m io lo g y (=ediatr Rev 2007;28:363) • Prevalence o f epilepsy 1%. A b o u t 1/3 have developm ental disabilities E tio lo g y (Pediatr Rev 2007:28:363) • 65-70% idiopathic/cryptogenic, i.e., no identifiable stru ctu ra l abnorm alities • Remainders are ''symptom atic,'' o r w ith identifiable abnorm ality impacting brain function • I n h e r ite d /g e n e tic : Channelopathies, chrom osom al abnorm alities, m ito ch on dria l D N A disorder, m etabolic disorder, h ered itary neurocutaneous disorders • C o n g e n ita l: Cortical malform & dysplasia, polymicrogyria, vascular malform, prenatal injury • A c q u ir e d : Trauma, infection, tum ors, vascular disease, hippocampal sclerosis, neurodegenerative disorders, to xic disorders D ia g n o s is p e d ia tr Rev 2007:28:405; Epilepsia 2009:50:2147) » E E G : N m l in 10-20% . Can induce szr w / hypervent, p h o tic stim, sleep depriv • B ra in im a g in g : Recommended in pts w / focal szr. N o t needed w / generalized szr if nmi neurodev,3 mo after 1st event & >1 mo after completion of steroid therapy • No new sx/ lesions by hx, exam, imaging; original MRI lesions may have t ’d

Same as ADEM above

ADE M M u ltiphasic

• New ADEM event w/ new anatomic CNS lesión >3 mo after 1st event & >1 mo after completion of steroid therapy • Brain MRI musí show new lesions and complete/partial resolution of prior lesions

Same as ADEM above

NMO

• Dx requires both ON &TM, plus 1 of 2 • Serum +N M O lgG+ or ♦ MRI spinal lesions encompassing >3 segments • Can see brain lesions (usu hypothalamus, bstem, or diffuse cerebral WM)

+serum NMO IgG (sens 47%; T’s w/ relapses) -CSF NMO IgG Variable T CSF prot & WBC (can be >50) Rare OCB

Pediatric MS (children/ adolesc 4 w k apart; o r • MRI: New T2 o r G AD i-lesions >3 mo after 1st clinical event (vs. adult 2005 McDonald Criceria w/ 3rd option o f newT2 lesión any time after reference baseline MRI done >30 d after 1st event) • DIS (1 of 3 options) • Clinical/exam features of anatomically separated lesions; or • 2 MRI lesions (ac least 1 in brain) in combo w / abn CSF (OCB o r T IgG Índex); o r • Combo o f 3 o f 4 MRI features: >3 periventric lesions; > 9 W M lesions o r 1 GAD-I- lesión; 1 juxtacorcical lesión; 1 infratentorial lesión • Clinical event cannot meet ADEM criteria • If 1st event c'wAEDM, then still need 2 more events meeting MS criteria, wi all 3 events separated by 3 mo

• CSF WBC

4 w k apart; o r • M RI: N e w T 2 o r G A D + lesión com pared to baseline sean, regardless o f tim ing o f baseline M R I; o r • M RI: Sim ult p resence o f G A D - & G A D - le s io n s at any tim e on any 1 MRI • DIS (1 o f 2 options) • C lin ical/exam features o f anatom ically separated lesio ns; o r • M RI: >1 T 2 (do n o t need G A D -f) lesión in 2 o f 4 areas: Ju xta co rtica l, p erive n tricu la r, infrate nto rial, spinal cord (if pt has bstem o r sp cord syndro m e then sym ptom ­ atic lesio n s exclu d ed fro m cou nt) • N ew study found PPV 76% in kids >11 yo, similar to PPV for _____________________ adults; PPV only 55% in kids < 11 yo (even excluding AD EM )____________________________ A D E M .A c u te disseminated encephalomyelitis; DIS, dissemination in space; D IT, dissemination in time; G AD-r, gadolinium enhancing; MS, m últiple selenosis; NM O . neuromyelitis Optica; O C B . oligoclonal bands; O N , optic neu ritis;TM , transverse m yclicis;W M , w hite matter.

E p id e m io lo g y ( \ e u r o o g y 2007;68:S23: N eurology 2007:68:537; N eurologist 2010:16:97) • ADEM : M o re com m on in kids than adults; avg age: 5 -8 ; no gender predom ; seasonal (usually w lnter/spring ); 70-77% re p o rt antecedent infection o r vaccination • MS: 2-5 % o f all MS pts w / onset 2:A ltitu d e • Increased diffusion gradient: P ulm onary hypertension, in te rstitia l lung disease • Shunt: C ard io pu lm o n ary and ¡ntrapulm onary shunts • Anem ia • C om pensation fo r m etabolic acidosis • Sepsis, RTA, diabetic ketoacidosis. (MUDPILES) W o r k u p : CXR, CT, CBC w ith diff, glucose, nasopharyngoscopy, bronchoscopy, pulm onary fun ctio n tests, lung biopsy

S T RID O R L a ry n g o m a la c ia (Pediatr Rev 2006:27:e33) • Floppy tissue above vocal cords th a t falls in to airway w / inspiración • Collapse o f supraglottic structures (a rytenoid cartilages and epiglottis) w / inspiration • E p id e m io lo g y : M o st com m on cause o f s trid o r in infants (- 65-75% o f all cases) • C lin ic a l m a n ife s ta tio n s • Symptoms appear during the firs t 2 m o o f life: infant usually happy/thriving • Noises are in sp ira to ry and may sound like nasal congestión • Exacerbated w ith crying, agitación, o r during an upper re sp ira to ry infection • Prone p osition may diminish the s trid o r • D ia g n o s tic studies: Hiscory/physical, flexible laryngoscopy, a nd /or bronchoscopy • Prognosis • Self-lim ited co nd itio n, usually resolves w /o Rx by 1 2 -1 8 m o o f age • In 10% o f affected pts, upper airway o b s tru c t severe enough to cause apnea o r FTT: may have expiratory/biphasic s trid o r • May co exist w ith o th e r airway m alform ations W h e n to re fe r: FTT. feeding difficulty, re sp ira to ry distress/apnea/hoarseness, cyanosis, atypical clinical course/persistent strid o r, sleep disturbances In te rv e n tio n s : Surgery: Supraglottoplasty, tracheostom y

T ra c h e o m a la cia (Ped al * Rev 2006;27:e33) • Weakness o f the airway cartilage th a t results in “ floppiness” o f airway • Positive in trathoracic pressure can cause intrathoracic crachea to collapse and o b s tru c t on expiratio n ; e xtra th o ra cic trachea may collapse on inspiration • May be secondary to com pression to mediastinal mass o r vascular rings/slings • H is to r y /e x a m • W heeze is often e x p ira to ry central, lo w pitched.and hom ophonous, possibly s trid o r • Unlike the wheezing heard in asthma (w hich tends co be diffuse, high pitched.and musical). Unlike asthma the re are no signs o f hyperinflation • W heezing a fte r p-agonist therapy remains unchanged o r even worsens • B e tte r in th e prone position

• Diagnosis: H&P, CX R, chest C T w ith contra st, airway fluoroscopy, bronchoscopy • P rognosis: M o st im prove spontaneously by 6 -1 2 m o o f age if p rim a ry tracheomalacia • In te rv e n tio n s • Nasal CPAP can help maintain airway pateney te m po ra rily • A o rto p e x y o r tra che o sto m y fo r long-term re lie f o f o b stru ctio n • Treat coexiscing co nditions such as GERD; consider avoiding |1-agonists;Atrovent C r o u p (see ED sección fo r evaluation and management o f croup) • L a ryngotrac he obronch itis : Inflammation & edema o fsubglottic larynx.trachea.bronchi • Clinical diagnosis fo r acute onset o f barky cough, s trid o r, and re sp ira to ry distress • D D x f o r re c u rre n t croup: Asthm a, laryngomalacia, laryngospasm, s ubglottic stenosis

COUGH

C ough

13-3

P n e u m o n ía • Inflam m atory cond itio n o f th e lung affecting the alveoli typically associated w ith fever, re sp ira to ry symptom s, and consolidation on chest x-ray • U n ila te r a l: Bacterial - strep pneumo, aspiration (especially w ith RML), m ycobacterial • M u ltifo c a l: A typical (mycoplasma), viral (RSV, paraflu, m etapneumo, adeno) • N e o n a ta l: A fe b rile m o re likely Chlamydia; febrile m ore likely GBS • R ecu rre n t, sam e location: Suggests anatomic abnormality: Foreign body o r obstru ctive mass, C C A M , sequestratlon, focal bronchiectasls • R e c u rre n t, d iffe re n t locations: Aspiration, im munodeficiency, diffuse bronchiectasis (CF, prim a ry ciliary dyskinesia), cardiac disease, pulm onary hypertenslon, underling Interstitial lung disease • W o r k u p : C X R , C T w ith co ntra st (lo o k fo r C C A M , sequestration, cardiac vessels) o r w ith o u t co n tra st (in te rstitia l lung disease). fluoroscopy (diaphragmatic excursión), bronchoscopy (foreign body, airway mass, laryngeal cleft/aspiration), s w allow study (aspiration), im munoglobulins and vaccine tit e r response (im m une deficiency), PPD (if C X R o r h is to ry is suggestive o f TB) • T r e a t m e n t: See ID section fo r tre a tm e n t o f specific m icrob io lo gy guidelines fo r pneumonía P e rtu s s is (hüp:.'/www .cdc.gov/vacánes/pubs/pinkbook/pert.htm l) • Highly contaglous, toxin-m ed ia ted re sp ira to ry dz 212 the bacterium Bordetella pertussis • S y m p to m s : Uncontrollable, v io le nt coughing, afte r fits o f many coughs sufferers often take deep breathes which result ¡n a “ w hooping” sound, apnea in infants • C lin ic a l course • Incubation period: C o m m o n ly 7 -1 0 d. w ith a range o f 4—42 d • Catarrhal stage (1 -2 w k): Characterized by coryza (runny nose), sneezing, low-grade fever, and mild cough • Paroxysmal stage (1 -1 0 w k): Bursts o f numerous, rapid coughs and difficulty expelllng th lck mucus; m ore com m on at nlght; post-tussive vom iting • Convalescent stage (w ks to mos): G radual re covery • 50% o f infants i [C l] secretion, T N a a bsorption across resp epithelium (reverse in sweat) -> i m ucocillary clearance, viscous secretions, I bacterial killing • M o st ¡m po rta nt tissues affected: Airways, bile ducts, pancreatic ducts. & vas deferens • Physical e x a m : Salty skin, w eight loss, failure to thrive , wheezing, m id insp crackles, cough, clubbing, nasal polyps, steatorrhea • D ia g n o stic studies • Sweat test (pilocarpine io ntophoresis): G old standard test > age 48 hr, need 2 sepárate tests to make dx, [Clsweat] >60 mEq/L is 95% specificity (J Pediatr 2008;153:S4) • G enetic testing • Stool colle ction fo r fecal elastase: nml >500 (ind ica to r o f pancreatic e xocrine insuff) • PFTs: i FEV1 • CX R : Early - hyperinflated, patchy atelectasis. Late - bronchiectasis (upper lobes) • M a n a g e m e n t o f lu n g d ise a se (BMJ 2007;335:1255) • Segregation to prevent spread o f resistant organisms (especially B. cepacia, P. aeruginosa, MRSA) • S ta g e I: Pre-infection • A irw a y clearance techniques: Chest PT, positive e x p ira to ry pressure (weak evidence) • M ucolytics: RhDNase (C ochrane Rev 200 3;3 :C D 0 01 127), hype rto nic saline (N e w Eng J Med 2006:354:229) • Early eradication: Beneficial against P. aeruginosa (C ochrane Rev 2 006;C D 004197), uncertain benefit against S. aureus • Influenza vaccination • S ta g e II: C h ro nic in fection • Maintenance therapy (A m J Resp C r it Care Med 2007:176:957) • A irw a y clearance: C hest PT to keep airways open, facilítate mucus removal • Mucolytics, inhaled p 2-agonists (C ochrane Rev 2005;4:CD003428) • Eradication/reduction o f bacterial load: Rx based on isolated organisms (i.e., P. aeruginosa:. Inhaled tobramycin, colistin, cayston [aztreonam] Cochrane Rev 2006:CD004197) • Reduce inflam m ation • A zithrom ycin (C ochrane Rev 2004;2:CD002203) • Ibuprofen, 2 0 -3 0 mg/kg bid., goal serum peak 50 mcg/mL (J Pediatr 2007:151:249; C ochrane Rev 2007;4:CD001505) • Inhaled & oral co rtico ste ro id s w /o benefit unless treating asthma co m p on en ! • A cute exacerbations • O ral/inhaled a ntibiotics (ta ilo r based on cultures/susceptibility, synergy studies useful fo r resistant organisms); com m on organisms include P. aeruginosa, nontypeable H. influenza • ABPA: C o rtico ste ro id s, antifungals • A typical m ycobacterial infxn: E tham butol, rifam picin, azithrom ycin, amikacin • S ta g e I II: End stage, com plicated CF • Severe hemoptysis: Bronchial a rte ry embolización, lobectom y • Pneum othorax: C hest tube, pleurodesis (may com plícate transplant) • R espiratory failure, heart failure 2 /2 pulm onary H T N : Lung (+ /- heart) transplantation • E x tr a p u lm o n a r y m a n ife s ta tio n s and m a n a g e m e n t • ENT: Nasal polyps (15%), re cu rre n t sinusitis (-100% ) • Nasal saline rlnses, nasopolypectom y • Gl: M econium ileus (10%), distal ileal obstru ctive syndr (1 0 -15 % ), rectal prolapse • Laxative, stoo l softeners. P ro-kin etic agents generally n o t helpful • Gl: Pancreatic exocrine insuff (85%), chronic pancreatitis, V it A, D, E, K def, malnut/FTT • Pancrelipase enzym es.A, D, E, K vitamins, high-fat/high-protein d iet • Biliary cirrhosis (2%); U rsod io l • G l hyponatrem ia • H yd ra tion , sodium chloride supplements • Endocrine: Pancreatic endocrine insufficiency (C F-related diabetes), osteopenia • Insulin, vitam in D • Reproductive: Male sperm tra n s p o rt defects (95% M in fe rtility), a m enorrhea/thick cervical mucus (20% F in fe rtility) • In v itro fe rtiliz a ro n • Renal: Renal failure (due to underlying abnorm alities and accumulated renal to x ic ity o f medications), kidney stones • Minim ize renal to xicity, U ro c it-K

A s t h m a (EPP3: Guidelines fo r Diagnosis and Management o f Asthma, N IH 2007) • C h ro n ic d is o rd e r o f re cu rrin g sym ptom s resulting fro m airway inflam m ation, hyperresponsiveness, and o bstru ctio n • Im p o r t a n t in fo rm a tio n to o b ta in in h is to ry • D e scrip tio n o f sx: W h ccze , nighttim e cough, chest tightness, difficulty breathing • Pattern o f sym ptom s: C ontinual/cpisodic, onset, duration, frequeney • Precipitating/aggravating factors:V iral infection, environm ental allergens (dust mites, cat/dog dander, cockroach. p o llu tio n ), smoke exposure, exercise, em otion. meds (such as aspirin p-blockers), changes in environm ent, co m o rb id conditions (obesity. GERD, sinusitis, rhinitis) • Hx: # o f hospitalizations, ICU admits. o r intubations; age o f dx; h/o p rio r airway in ju ry (BPD. parencal smoking, early PNA/RSV infection); meds used and compliance; need fo r oral co rtico ste ro id s and frequeney o f use; num ber o f fiares in last yr • Family h is to ry o f atopy: Asthm a, eczema, allergy, sinusitis, rhinitis, nasal polyps • Social history: Day care, social factors that may interfere w / adherence, social supports, smoke exposure • Impact o f asthma: N u m b e r o f school days missed, lim ications o f activity • Assessment o f patients and fam ily’s perception o f disease • Knowledge o f asthma and Rx plan.ability to recognize severity o f exacerbation • E x a m in a d o r) • O verall patient c o m fo rt, hyperinflated chest, accessory muscle use. wheeze o r prolonged e x p ira to ry phase, nasal secretions o r polyps, eczema • • Respiratory rate & trend o f respiratory rate is im portant; slowing can be sign o f fatigue • C la ss ific atio n o f a s th m a

In te rm itte n t

Mild Persistent

M odérate Persistent

Severe Persistent

Sx o r use of albuterol

2 d/wk, but not daily

Daily

Throughout the day

N ig h ttim e sx

0

1-2/m o

3-4/m o

>1/wk

Lung function

FEV, nml btw exacerbations FEV, >80% predicted

FEV, = 60-80% predicted

FEV, 80% predicted

Low-dose ICS, cromolyn o r montelukast

ICS, inhaled corticosteroids; LA B A , long-acting (3-agonist.

• O u tp a tie n t m a n a g e m e n t o f a s th m a • M ethod o f delivery.age o f child. and ability to execute p ro p e r tcchnique are im p o rta nt tre atm en t considerations • Short-acting (i-agonist: A lbuterol (Proair. Proventil), levalbuterol (Xopenex). Mechanism: Bronchodilator. Side effects:Tachycardia, hypertension. trem or, nervousness. paradoxical bronchospasm. tachyphylaxis (w ith long-term use) • Inhaled corticosteroids (ICS) Budesonide (Pulmicort). fluticasone (Flovent), beclomethasone (Q var).flunisolide. ciclesonide. Mechanism: Acts locally in the lungs to inhibit the inflam m atory process. Side effects:Thrush (use spacer o r valved holding chamber and rinse m outh w ith w a te r to reduce the incidence). dysphonia/hoarseness (use spacer o r valved holding chamber), reflex cough/bronchospasm (use spacer o r valved holding chamber and slower rates o f inspiration to reduce incidence), behavioral disturbances • Regular use o f nebulized budesonide m o re effective than budesonide used only as needed (A rch Dis C hild 2008;93:654-659) • Daily use o f budesonide n o t su pe rior to in te rm itte n t use in preschool children w ith wheezing (N Engl J Med 2011:365:1990) • Beclomethasone may be used as rescue plus albuterol as a step-down fo r children w ith m ild asthma (Lancet 2011:377:650) • D oubling dose o f ICS w / URI n o t effective (J A lle rg y Clin Im m unol 2011 ;128:278) • L e u k o trie n e in h ib ito rs : M ontelukast (Singulair), zafirlukasc (Accolate). & zileuton (Zyflo). Mechanism: Leukotriene re c e p to r antagonists (LTRA) prevent leukotriene binding (m ontelukast/zafirlukast) o r leukotriene re ce p to r inh ib itors (zileuton). Side effects: Elevated liver transaminases

W heeze 13-1

• LTRAs provide m odest ¡m provement ¡n lung fxn when used as m onoRx ¡n children as young as S & in aschma c o n tro l outcom es (o th e r than lung fxn) in pts as young as 2 (EPR3: Guidelines for Diagnosis and Management o f Asthma, N IH 2007) • Fluticasone vs. m ontelukast: Fluticasone m o re effective in im proving pulm onary fxn, asthma sym ptom s, and rescue albu terol use (J Pediatr 2 005;147:213-220) • M ontelukast can o ffe r p ro te ctio n fro m exercise-induced bronchospasm (Treat Respir Med 2004;3:9;Ann A lle rg y A sthma Im m unol 2001:86:655) • L o n g -a c tin g |3-agon¡st (LABA) combined w ith ICS: Fluticasone/salmeterol (Advair), budesonide/form oterol (Symbicort). Mechanism: Long-acting bronchodilation. Side effeets: Tachycardia, tre m o r • In adolescents & adults (n o t children), LABAs com bined w / low /m ed dose ICS may be beneficial fo r p o o rly c o n tro lle d asthma (C ochrane Rev 2 010;C D 005533) • Black-box warning: Increased risk o f death when LABA used alone, esp in A fricanAm erican population (SMART, C hest 2006:129:15) • T io t r o p iu m (Spiriva):M echanism :Anticholinergic, reduces sm ooth muscle contracción. Side effeets: Hypersensitivity reaction, anticholinergic effeets (d ry mouth, u rinary retention, blurred visión, mental status changes), constipation, thrush • Equivalent to fluticasone/salm eterol fo r step-up therapy in aschma (N Engl J Med 2010:363:1715) • T h e o p h y llin e : Mechanism: Mechylxanthine, relaxes bronchial sm ooth muscle and a nti-inflam m atory. Side effeets: N a rro w therapeutic w indow , cardiac arrhythm ias, seizures, tre m o rs, agitation, nausea/vomiting, e lectrolyte abnorm alities (hypokalemia and m etabolic acidosis) • O ra l xanthines as maintenance fo r pediatric asthma suitable in the absence o f ICS o r in conju n ction w / o th e r therapies in severe asthma (C ochrane Rev 2006;CD 002885) • O r a l s te r o id s (Prednisolone, Prcdnisone): Mechanism: A nti-infla m m ato ry. Side effects:W eight gain, hyperglycemia, m ood changes, osteoporosis, adrenal insufficiency, im m unosuppression,gastritis o r ulcers, sodium /fluid re ten tio n & H T N • Used in acute setting in s h o rt bursts typically fro m 5 to 7 d -2 w k. M o re effective than inhaled steroids in severe acute asthma (N Engl J Med 2000:343:689) • R efra cto ry asthma may require daily low -dose o r alternate-day dose oral steroids - IgE m e d ia to rs : Omalizumab (X o lair) effective maintenance therapy fo r patients w ith severe, persistent asthma, which cannot be controlled even w ith high doses o f corticosteroids. Mechanism: Recombinant D N A -derived humanized Ig G lk monoclonal antibody that selectively binds to IgE. Side effect: Anaphylaxis, expensive (J A llergy Clin Immunol 2009:124:1210) • C r o m o ly n s o d iu m (Intal): M echanism :A nti-inflam m atory, mast cell stabilizer. Side effeets: Non-specific • Inhaled co rtico ste ro id s m o re effective than crom olyn sodium fo r asthma co n tro l in adults and children (C ochrane Rev 2006;CD 003558) • W h e n t o r e f e r t o p u lm o n o lo g is t • Patient has had a life-threatening asthma exacerbation • Patient is n o t m eeting th e goals o f asthma therapy a fte r 3 -6 m o o f tre atm e n t • A typical signs and symptom s • Com plicating conditions (e.g., sinusitis, nasal polyps, aspergillosis, severe rhinitis.VC D, GERD, C O P D ) • Need fo r additional diagnostic testing (e.g., allergy skin testing, rhinoscopy. com plete pulm on a ry fun ctio n studies, provocative challenge, bronchoscopy) • Patient requires additional education and guidance on com plications o f therapy. problem s w ith adherence, o r allergen avoidance • Patient is being considered fo r ¡m munotherapy • Patient has required m o re than tw o bursts o f oral co rtico ste ro id s in 1 y r o r has an exacerbation requiring hospitalization • Patient has a h isto ry suggesting an occupational/environm ental inhalant o r ¡ngested substance is p rovoking o r co n trib u tin g to asthma • R isk f a c t o r s f o r s ta tu s a s th m a tic u s • Asthm a history: P rio r severe exacerbation: Intubation/P IC U stay • 2 o r m o re hospitalizations fo r asthma o r 3 o r m ore ED visits f o r asthma in past yr, o r hospitalization/ED visit fo r asthma in past mo • Using >2 canisters/m o o f inhaler • Poor com pliance/understanding • Social h istory: L ow SES, illic it drug use, psychosocial problems • C o m o rb idities: Cardiovascular dz, o th e r chronic lung dz, psychiatric dz

• M a n a g e m e n t o f status a s th m a tic u s • ABCs, m edications (see below ) • C onsider NPPV o r intubation (ketamine is the induction drug o f choice) fo r persistent hypoxia/hypercarbia/WOB, altered mental status, F iO j >60% • V entilation strategy:Treat obstruction/atelectasis, lim it hyperinflation and barotraum a • Volume c o n tro l p referred (ensures consistent min ventilation despite changing airway resistance) • L im it T V (8 -1 0 cc/kg) & RR (8 -1 2 ) w / "perm issive hypercapnia” (goal pH > 7.2) • L im it l-tim e (l:E 1.3 -1 .5) to a llo w co m p lete exhalation and minim ize auto-PEEP • A void paralysis • For re fra c to ry cases, consider inhalational anesthetics (e.g., ¡soflurane, halothane [b ron ch od ila tors o f unknow n mechanism] o r ECM O ) • M e d ic a tio n s fo r status a s th m a tic u s Ñam e

Dose

A lb u te ro l ((3-agonist)

0.15 mg/kg neb q1h (2.5-5 mg) 10-15 mg/hr continuous mínimum dose 2.5 mg

C o m m e n ts

Ipratropium

250-500 mcg neb x 3 then q2h prn

Methylprednisolone anti-inflammatory

2-4 mg/kg/d PO div bid; 1 mg/kg IV q6h (max pedi 60 mg/d, adult 125 mg/d)

M g S O p Inhibits Ca influx bronchial smooth muscle relax

25-75 mg/kg IV (max 2 g)

Severe obstruction not responding to bronchodilators; unk effectiveness in less-severe cases (Chest 2002; 122:489)

Terbutallne p2-agonist

10 mcg/kg IV load -> 0.1-10 mcg/kg/min

Acute severe asthma not responding to bronchodilators

Am inophylline PDE ¡nhibitor -> smooth muscle relaxation

6 mg/kg IV load 1.5 mg/kg/hr

Acute severe asthma not responding to bronchodilators. Therap e u tic level 1 0-20 m cg/m L (m easure 6 h r post load). Risk tachycardia, arrh yth m ia, sz

H e lio x (80% He/20% O ;) Low density -> reduced airway resistance

Nebulized (with or w ithout bronchodilator)

>0.6-

Costly; no evidence for ¡mproved outcomes (PFTs. admits, need fo r intubation) may be beneficial in the most severe acute asthmatics. (Cochrane Rev 2003;(4):CD002884)

W

heeze

13-7

• C o m p lic a tio n s • Dynam ic hyperinflation (auto-PEEP) • Progressive airtrapping -> hyperinflation -> alveolar rupture/hemodynamic compromise • To assess f o r auto-PEEP: C heck plateau pressure (e n d -e xp ira to ry pressure airway pressure; goal < 30), e x p ira to ry pause maneuver • Mechanical ventilation com plications (PTX, H o T N , myopathy.VAP, GIB) • Prognosis: 2-3% m o rta lity w / mech ventilation (C rit Care Med 2002:30:581) B r o n c h io lit is (Pediuli pleural pressure -> lung pressure —> lung collapse • P atho p h y sio lo g y • Spontaneous: 1o (bleb ru p tu re in young/tall/thin males; high-risk activities like diving/ flying; smoking) o r 2o (CF, abscess,TB, PCP, Marfan, B irt-H o g g -D u b é ) • Traumatic: Lung puncture (traum a, thoracentesis, barotraum a fro m vent, C V C ) • Tension:Tissues at p o in t o f a ir e ntry act as 1-way valve allowing air e ntry but no exit eventually total lung/cardiac compression w / hemodynamic collapse • C lin ic a l m a n ife s ta tio n s • Symptoms depend on baseline pulm onary status and PTX size: Sudden onset o f SOB and pleuritic CR hypoxia, absent o r decreased BS on affected side • Small PTX { 1o, m o re com m on in smokers, tall/thin); VATS I recurrence to 2-14% ; 2 o PTX tends to have w o rse course/outcom e

P le u ra l E ffusion (Pediatr Rev 2007:28:462: Pediatr Rev 2002:23417) • P athophy siology : Fluid colle ction between visceral and parietal pleura • T ra n s u d a tio n : Imbalance b tw hydrostatic and oncotic forces w ith normal vasculature • C H F o r pulm onary embolism - j T pulm onary venous pressure • Renal o r liver dz -> i colloid o sm otic pressure (can also see ascitic fluid; leakage across small defects in diaphragm) • E x u d a tio n : Secondary to leaky vasculature • Pneumonía, malignancy, connective tissue d iso rd e r -> pleural inflam mation, ? capillary perm eability, at tim es w / associated im paired lym phatic drainage • Parapneumonic effusions are the m o st com m on type o f effusion • Exudative stage (uncom plicated): P ro tein-rich flu id 2/2 endothelial inflam m ation • Sterile fluid w /n orm al chem istries and PMN p redom inant • Fib ro pu ru le nt stage: Bacterial g ro w th ; T PMNs (T L D H ), i glucose &T lactic acid • O rganization stage: Inc fib rin and collagen deposition w / developm ent o f pleural "p e e l/rin d ” fu rth e r im pairing drainage • M ost com m on organisms isolated Strep pneumoniae, Staph aureus and GAS • Pleural-based metástasis in childhood: N eph ro b lasto m a .W ilm s tum or, hepatoblastoma, malignant germ cell tu m o rs and rhabdom yosarcoma • T h o r a c ic d u c t: Trauma o r abn orm a lity - r I lym phatic drainage (results ¡n ch ylothorax; ¡f above T5 results in L-sided chyloth orax, if lo w e r then R-sided) • Can be 2/2 congenital (Noonan,Turner, D o w n ) o r b irth traum a (extensión o f spine) • E p id e m io lo g y (Pediatr Rev 2002;23:417; Pediatr Emerg Care 2007:23:330) • P N A w / parapneum onic effusion (50-70% ) » C H F (5 -15% ) > malignancy (5-10% ) • Bacterial P N A m o st likely -> effusion, viral & atyplcal infxn m o re com m on in kids • Empyema causes significant childhood m orbidicy b u t rarely causes death (3-6% ) • Congenital ch yloth orax is the m o st com m on cause in newborns • C lín ica ! m a n ife s ta tio n s (Pediatr Rev 2002:23:417; Pediatr Emerg Care 2007:23:330) • If 2/2 PNA, cough, fever, chills SOB; w /o P N A often asymp u ntil large then SOB • Can p /w sharp chest pain associated w ith inspiration o r cough • Clinical exam w / decreased breath sounds o ver area and dullness to percussion • Can note dec tactlle frem itus and H o o ve r slgn (lagging o f chest wall m ovem ent) • C hest wall abscess and costal ch on dritis = empyema necessltatis • Early in developm ent may hear a p le u ritic fric tio n rub (rare finding) • D ia g n o s tic studies (Pediatr Rev 2002:23:417) • C X R (PA, lat, and lat decub films w ith affected side dow n ), ultrasound, chest C T (if loculation, empyema necessitatis, o r malignancy is suspccted) • Thoracentesis: For sym ptom atic re lie f o r diagnostic evaluation • Precautions: D e m ónstrate layerlng on lateral decubitus film to ensure th a t fluid is n o t loculated (>10 mm fluid is safe fo r tap); best if done w / U/S guidance • Standard studies: Cell count/diff, pH (send heparinized, on ice), glucose, tota l protein/ albumin, LDH, Gram stain and culture, cytology; also send serum protein/albumin, LD H , and glucose fo r reference at the same tim e • C o lo r can give info as well: Palé yellow -> transudate; m ilky w h ite -> chyle; bloody —> malignant, infectious, PE, o r traum atic; chocolate brow n -> amebiasis • O th e r studies: Cholesterol & trigs (if suspect chylothorax), amylase (2/2 esophageal rupture),adenosine deaminase (>40 U /L is 90% sens fo rT B ), IFN-y (T inT B ), serum N T proBNP (T in CHF) galactomannan (aspergillus), hem othorax if hem atocrit of fluid >50% o f serum hem atocrit • In te r p r e tin g p le u ra l flu id studies (N Engl J Med 2002:346:843) Exúdate

Serous, palé yellow

Cloudy, pus if empyema

Cell count

Few cells

W B C >10,000

pH

>7.45

60 mg/dL

1.2 g/dL

3 organs are involved; -10% ped pes w /A K I develop C K D in 1-3 y r (Am J Kidney Dis 2012:59:523)

CHRONIC K I D N E Y D IS EA SE D e fin itio n (Pediatr Rev 20C8;29:335) • C K D n o w classified as any kidney damage o r GFR 3 m o • K D O Q I G ro up classified C K D in to 5 stages. Stage 1: Kidney damage w / nml/T GFR (>90). Stage 2: l GFR to 6 0-89 . Stage 3: i GFR to 30-59. Stage 4: i GFR to 15-29. Stage 5: Kidney failure w / GFR 2 yo E tio lo g y (Pediatr Rev 2008:29:335) • 30—33% w / uro log ic anomalies, 25-27% w / glom erulopathies, 16% w / hered itary nephropathies and -1 1 % w / renal hypoplasia and dysplasia C o m p lic a tio n s (Pecir.x Rev 2008:29:335; Pediatr N ephro! 2003:18:796) • Infections p ro m p t 45% o f hospital admissions in one series • O th e r com plications include: Anem ia (keep Hgb 1 1 -1 2 m g/dL w / Fe & Epo), H T N , bone disease (r x ’d w / V it D ), e lectrolyte abn (m et acidosis rx'd w / NaBicarb, hyperK) • G ro w th retardatlon ¡s a m ajor complication; degree matches age o f onset o f CK D, likely 2/2 effect on G H & IGF-1 axis: treatm ent w / nutrltlonal su pp ort + /- G H therapy P rognosis (Pediatr N e p lv o l 20C8;23 705; J A m Soc Nephro] 2005;16:2796) • C K iD is large prospective c o h o rt study o f pts aged 1 -1 6 y r co ¡dentlfy risk factors fo r progression and the effect o f - GFR on cognición, g ro w th, behavior, cardiovasc risk factors (C lin J A m Soc N e ph ro l 2006:1:1006) • Intensive (50th percentile) BP co ntro l w /A C E -I slows GFR l (N Engl J Med 2009:361:1639) • P roteinuria, lo w H ct, hypoalbuminemia, hypoCa. hyperphos, hyperPTH all assoc w / rate o f progress to ESRD, as is age at d x and the dx itse lf • Rx o f anemia, hypoCa, and hyperphos leads to im proved outeom es in the s h o rt te rm • G lo m e ru la r disorders, including FSGS, increase risk o f progression to ESRD • Cardiac and vascular abn (LVH. diastolic dysfxn, T carotid intim a-m edia thickness, Mónckeberg selerosis) are progressive and may be related to t calcm m -phosphorus produce (N a t Rev N e p h ro l 2011:7:624) M a n a g e m e n t (N Eng J Med 2009:361:1639; C u rr O pin Pediatr 7010:22:170) • ESCAPE trial, fixed-dose A CE -Inhlbltor - additional anti-hypertensives to i BP 3 -4 mm Hg • R-A blockade may also benefit by I p ro te in uria , c o rre c tio n o f acidosis, hyperuricem ia • W / Stage V C K D ultim are management is renal cransplancation

SECONDARY H Y P E R T E N S IO N D e f in itio n s (Pediatr Rev 2007:28:283; Pediatrics 2004:114(2 S upol,4th Report}:555; JAM A 2003:289:2560) • 2 H T N (BP >95ch percentile fo r age and ht) - 1 BP 2/2 underlying, identifiable cause • Stage 1 = BP a t 95th %¡le - 5 mm Hg above 99th %¡le; Stage 2 - BP >5 mm Hg above 99th %ile • H ypertensive urgency H T N w /o severe sx o r evidence o f end organ damage • H ypertensive emergency - H T N w / severe sx - evidence o f end organ damage (in children, retinopathy, encephalopathy— lethargy, coma, sz— m o re com m on than CHF, p ulm onary edema) (A rch Dis C h ild 1992:67:1089) E tio lo g y & D x (N at Rev Cardiol 2010:7:155: Pediatr Rev 2007:28:283) • Evaluation begins w ith th o ro u gh H&P & exam. 75% cases 2/2 renal parenchymal dz • H ypertensive emergency in children is m o st likely renal in origin • M e d s (amphetamines, corcicosteroids, OCP, cyclosporlne, o th e rs) can cause H T N • R enovascu lar disease (may be assoc w / high renin levels b u t n o t a consistent finding) • Ultrasonography can show decreased flo w ; renal a rteriography is “ gold standard" • MRA, CTA, and ca pto pril-M A G 3 scannlng each have strengths and lim itations • Renal pa ren c h y m al disease (evidence o f glom erular o r tubular dysfxn, dec GFR) • US shows size, location, echogenicity. Scarring can cause H T N and is a m ore com m on cause o f 1 hypertension than glom erulo n ep h ritis • R enal s c a rrin g occurs 2/2 m ú ltiple, o ften overlapping etiologies; congenital dysplasia, vesicoureteral reflux, and infxn. Regardless etiology, scarring is prerequisite to develop H T N as sequelae (J U ro l 2005:173:697) • 5 -44% o f children w ith A D P K D have secondary H T N (Lancet 2007:369:1287) • S te r o id o g e n ic e n z y m e d e fe c ts (11 -fj-hydroxylase def, 1 1-a-hydroxylase def), hyperaldo, apparent m in e ra lo co rtico id excess, and nonsteroidal defects (Liddle syndrom e, G o rd o n syndrom e) can be assoc w / lo w renin levels • C ardiovascular d isorders (c o a rc ta tio n , m id a o r tic s y n d ro m e ); 4 e x tre m ity blood pressures, differential cyanosis, echocardiography can be diagnostic • O th e r: Um bilical a rte ry catheterization, collagen vascular dz, SLE, hyper-/hypothyroid, W illiam s syndrome (and assoc renal vasc dz),Turner syndrome (and assoc coarctation), Cushing syndrom e (and assoc steroid excess), n eurofibrom atosis (renovase H T N , p heochrom ocytom a), lo w e r e xtre m ity tra ctlo n • Possible assoc exists b tw hyperuricem ia and H T N (uric acid >5.5 mg/dL found in 89% o f children w / essential H T N b u t 30% 23 H T N ); mechanism unknow n T h e r a p y (Pedia!- N epnro: 2009:24:1101; Pediatr Rev 2007:28:283) • Based on underlying e tiology • H ypertensive urgency - tx w /i hours • Hypertensive emergency - must continually m o n ito r BP & avoid excessively rapid reduction ( i 1/3 o f t o t reduction in 6 h, 2/3 t o t by -2 4 h, to maintenance by -4 8 -7 2 h) using short-acting agents (labetalol, nicardipine most studied, no agents proven in children) • See C ardiology C h ap ter and (J Pediatr 2006:149:746) on tre a tm e n t o f hypertension

H EM ATU RIA , N E P H R IT IC

SYNDROMES

D e f in itio n (P e da tr Clin N o rth A m 2001:48:1519) • Macroscoplc hem aturia is visible to the naked eye (Pediatr C lin N o rth A m 1997;44:1191) • M icroscopic hem aturia definitions vary by study, > 5 -1 0 RBCs/high-power, midstream colle ction (A dolesc Med C lin 2005;16:229) E p id e m io lo g y (Pediatrics 1977:59:557; J Ped:at- 1979:95:676) • M acroscopic hem aturia has an estim ated incidence o f 1.3 per 1,000 • Prevalence o f m icroscopic hem aturia 0.5-2% depending on population— incidence o f m icroscopic hem aturla 0.32% ¡n girls and 0.14% o f boys E tio lo g y Urol Clin N o rth A m 2004;31:559) • In 342 children w / a s y m p to m a tic m ic ro s c o p ic h e m a tu r ia : 81% idiopathic, 16% hyperCa, 1% P S G N ;o f 228 children w / gross h e m a tu r ia : 38% idiopathic, 22% hyperCa, 15% IgA nephropathy, 4% stru ctu ra l abnorm alities (A rch Pediatr Adolesc Med 2005:159:353) • Mlmlcs include meds (chloroquine, ¡ron, ¡sonlazld, rifampin), foods (beets, blackberry), pigments/toxlns (bile, h e m oglobinuria , m yoglo bin uria, lead, phenol, porphyria, urates)

• G lo m e r u la r dz: Recurrenc gross hem aturia (IgA nephropathy, benign familial hematuria, A lp o rt syndrome), acute postinfectious G N (PIG N), m em branoproliferatlve G N (M PG N ), SLE, m em branous nephropathy (M N ), rapidly progressive G N (RPG N), H enoch-S chónlein purpura, G oodpasture dz • In te r s titia l an d tu b u la r D z : A cute pyelonephritis, acute in terstitial nephrltis.TB , hem atologic (sickle-cell dz, coagulopathies including von W ille b ra n d dz, renal vein throm bosis, throm bo cytop en ia ), meds (AGs, NSAID, a m itrip tylin e, anticonvulsants, chlorprom azine, coum adin, cyclophospham ide, d iuretics, PCN, thorazine) • U rin a ry tra c t: Bacterial o r viral (adenovirus) infxn related, urolithiasis and hypercalciuria, structural anomalies (including polycystic kidney disease). trauma, tum or, exercise E v a lu a tio n (U rol Ciin N o rth A m 2004:31:559) • Careful h isto ry and physical exam ination, including family h isto ry • M acroscopic h e m a tu ria w /o significant p ro te in u ria o r R B C casts: Likely nong lo m e ru la r bleeding; requlres uriñe cx (exelude infxn), renal & bladder U/S (exelude malig o r cystic renal dz). C T (urolithiasis), & /o r cystoscopy (exelude malig, o th e r process) • H e m a t u r ia plus any o f th e fo llo w in g is suggestive o f g lo m e ru lo n e p h ritis : Edema, H T N , significant proteinuria. Initial eval: CB C (HUS), CMP, sedim ent, throac cx, s treptozym e panel, & com piem ent levels (P IG N ) • See P roteinuria section fo r eval and Rx o f disorders, fo r which this is a p rim a ry feature D x & M a n a g e m e n t o f S p e c ific D is o rd e rs (Uro! Clin N o rth A m 2004:31:559) • P ostin fec tio u s G N : Up to 7 -2 1 d a fte r incícing infxn, o ften skin o r so ft tissue • Infxn w / G roup A Strep o r o th e r infections; w / supportive care, excellent prognosis • D ark, tea-colored uriñe is com m on • Pts can be asym ptom atic, o r have malaise, fatigue, H T N . edema, o r oliguria • C3 levels lo w during illness, im prove o ver 6 -8 w k • A ntistre p to lysin O tite rs may be neg a t first, streptozym e pos w /i 10 d • H e n o c h -S ch ó n le in purp u ra : (See Rheumatoiogy chapter) w / renal involvement -50% cases, extent variable (proteinuria. hematuria, nephrotic syndr, glom erulonephritis, AKI) • Relapses can occur, lo ng -te rm prognosis depends on degree o f renal com prom ise • Ig A n e p h ro p a th y com m on cause hem aturia, path w / mesangial deposition o f IgA • Poor p rognostic indicators: H T N , nep hrotic range proteinuria, renal insufficiency • C o ntrove rsy exists regarding ucility o f biopsy • Rapidly progressive g lo m e ru lo n e p h ritis : A K I,g lo m e ru la r crescents on biopsy • E M E R G E N C Y : Need p ro m p t Rx w / pulse steroids, can still progress to ESRD w /i wks. Aggressively pursue/address underlying condition

URINARY TRAC T CALC UL I E p id e m io lo g y (Kidney ,nt 2011:80:1278) • N e phrolithiasis accounts fo r 1 in 1,000 to 1 in 7,500 pediatric hospital admissions • Prevalence T ing in US. Caucasians m ore affected than A A s (J Pediatr 2010:157:132) • Stone recurrence 6.5-54% , tim e to recurrence 3 -6 y r (U ro l C lin N o rth Am 2004:31:575) • M etabolic disorders increase the rate o f stone form a tion C lin ic a l M a n ife s ta tio n s (U rol Clin N o rth A m 2004:31:575) • P/w abd/flank/pelvic pain (50%), hem aturia (33%), incidental radiology findings (15%), infection (11%); younger children (75% u rin a ry tra c t calculi in US. Ca-oxalate o r Ca-phos; infectious stones 15-25% • Metabolic o r urin ary tra c t abn account fo r 30-50% o f pts w / u rin ary tra c t calculi • Hypercalciuria w / o r w /o hypercalcemia m ost com m on cause (34%) o f pedi urolithiasis • G enetic hypercalciuria causes: Familial idiopathic hypercalciuria, distal RTA, B a rtte r syndrom e, hypercalciuria/hypomagnesemia, D e n t disease • O th e r causes: U ric acid urolithiasis (as in ketogenic diet, lymphoproliferative disorders. some in born e rrors o f metabolism), struvite stones (infectious), cystinuria (2-7%), hyperoxaluria (i.e., C roh n ’s). hypocitraturia • A cidic uriñe p ro m ote s fo rm a tio n o f calcium oxalate, uric acid, and cystine stones • A lkaline uriñe p rom otes fo rm a tio n o f stru vite and calcium phosphate stones

E v a lu a tio n (U rol Clin N o rth A m 2004:31:575: U rol Kadiol 1992:14:139) * Serum: CBC, Chem 10, alk phos, u ric acid, P T H ,V it D (2 5 -O H and 1,2 5 -O H i) * Uriñe studies: U /A w / pH, uriñe cx; 24 h r uriñe fo r Ca++. Phos, Mg, oxalate. Na, uric acid, citrate, cystine, Cr, volume (spot measure 2 -4 h r after m ilk if child is not to ile t trained) * Stone analysis • Radiographic: N o n co n tra st helical C T m o st sens fo r urolithiasis; T radiation dose by ro u tine surveillance in asymp children w / fíat píate plain film s & renal U/S • Radiation fro m stone p ro to c o l C T at M G H equivalent to 4.5 KUBs T h e r a p y a n d P ro g n o s is (U rol C!¡n N o rth A m 2004:31:575) • A t all ages, ureteral stones >5 mm rarely pass w /o help; may need in terven tion • Pain c o n tro l and hydration fo r sx; pharm acologic Rx depends on e tiology o f stone

NEPHROTIC SYNDROME D e f in itio n (Kidney Int 2004:66:1294) • Conscellation o f edema, p roteinuria, hypoalbuminemia, and T plasma cholesterol levels E tio lo g y (Kidney Int 2004:66:1294} • Heterogenous disorder w ith mutations in múltiple slit diaphragm and podocyte proteins n ow identified (N EnglJ Med 2006:354:1387) • Minim al change dz used to account fo r -6 0 -8 5 % o f nephrotic syndrome; follow ed by idiopathic focal segmental glom erulosclerosis (FSGS), mesangial p ro lif (MP), m e m b ra no p ro lif g lom erulo n ep h ritis (M PG N ), and m em branous nephropathy (M N ) • T ing fraction attributable to FSGS in recent past, particularly w / African-Am ericans E v a lu a tio n (Kidney Int 2004:66:1294) • Bx may be indicated fo r those p /w typical features o f FSGS (H T N , hematuria. renal insuff) o r fo r those failing to respond to steroids • A dolesc may be biopsied before steroids as FSGS and M N are m o re com m on T h e r a p y (Pediatr N eph ro 2011:26:881) • Inicial rx prednisone 60 mg/m2/d divided doses. 12 w k course may i rate o f relapse • Steroid responsiveness confers favorable prognosis; check PPD before Rx • W / failure to respond to steroids, may use cytotoxic agents, calcineurin inhibitors (cyclosporine, tacrolimus; all require long-term tx), o r mycophenolate mofetil and assoc w / worsening renal fxn over time: choice of subsequent therapy may depend on bx results

RENAL T U B U L A R ACIDOSIS D e f in itio n (Int J Biochem Cell Biol 2005:37:1151) • M etabolic acidosis 2/2 im paired renal acid excre tion

C la s s ific a tio n /E tio lo g y (Int J B kxtie m Cell Biol 2005:37:1151) • Isolated tub u lar defects can be due to drugs, autoim m une disease, o bstructive nephropathy, o r any cause o f m edullary nephrocalcinosis • Can be genetic, associated w ith deafness, osteopetrosis, o r o cular abnorm alities • D is ta l (T y p e 1 R T A ) 2/2 im paired distal acid excretion. Acidosis may n o t be present. H ypoK can occur. Bone dz and nephrocalcinosis can occur w / hypercalciuria • Type 1 RTA can be acquired; 2 /2 autoim m une dz (Sjógren syndrom e o r SLE) • P r o x im a l (T y p e 2 R T A ) leads to bicarb wasting and high uriñe pH; eventually m ore acidic as plasma H C O 3 levels i and less filte re d. T frac e xcre tion o f H C C V (>15%) characteristlc. O sm o tic effect o f H C O 3' can lead to loss o f K as well • Type 2 RTA can be p a rt o f generalized tubular defect, (i.e., Fanconi syndrom e [proxim al cell dysfxn]: P rox renal tub u lar acidosis (bicarb wasting), hypophos (phos wasting). polyuria (N a wasting), glucosuria, and aminoaciduria) • Type 2 RTA can o ccur in cystinosis, hered itary fru cto se intolerance, and W ilso n disease, o r can be caused by ifosfamide, acetazolamide

awoaauASDUoaHdaNl

C lin ic a l M a n ife s ta tio n s (int | Biochem Cell Biol 2005:37:1151) • O fte n p /w hyperchlorem ic metab acidosis w / nm l/near-nm l AG & w /o diarrhea • Can also present w ith hypokalemia, m edullary nephrocalcinosis, re c u rre n t calcium phosphate stone disease, g ro w th retarda tion /ricke ts

I

• T y p e 4 R T A also a distal RTA assoc w / hyperK ¡nstead o f hypoK (effective hypoaldo), and can be 2/2 slckle-cell dz, u rin a ry tra c t o bstru ct, amyloidosis, xp ln t • Can be 2/2 drugs:Aldosterone ¡nhibitor diuretics such as spironolactone.ACE-l/ARBs, trim eth op rim , heparin, pentamidine, NSAIDs D ia g n o s is & R x (Rose & Post Oinical Ph/stology ofAcd-Base and Bectrclyte Disorders; 5th ed,. McGraw-Hill; 2001) Type 1 - D ista l

Type II - P ro x im a l

Type IV

P ath olog y

Dec distal acidification

Dec prox H C O 3 reabsorp

Aldosterone def7 resistance

FeHCO ¡ at n m l [ H C 0 3] “

5-10% in children 15-20%

5.3

Variable

Usually 9 slightly • Etiology: Unknown, infxns (i.e., viral hepatitis, strep and parvo) im plicated.Assoc w / FMF • C r ite r ia fo r c lassificatio n (1990 A m erican College o f Rheum atology C rite ria ) • C o m m o n ly w / fever, w eight loss. malaise, and non-specific abdom inal pain • Classification crite ria o f A C R n o t validated fo r children; 3 o f the follow ing • Unexplained w eight loss >4 kg; livedo reticularis; testicu la r pain o r tenderness; myalgias (except shoulder and hlp girdle), muscle weakness, leg muscle pain; mononeuropathy o r polyneuropathy; new onset DBP >90 mm Hg; T BUN (>40 mg/dL) o r C r (>1.5 mg/dL): hepatitis B virus infection; characteristic arteriographic abn;bx o f small o r medium -sized a rte ry w / PMNs • D iagnostic studies: Labs— t E5R/CRP. TW B C , T im munoglob, can also see proteinuria, hematuria, inc B U N /C r, com piem ent usually nml. +HBsAg (30%). p -A N C A (28 w k G A: Every o th e r w k • Chem 10, alk phos • Breast-fed 0.30 o r CPAP o r mechanical ventilation required • In c id e n c e : (Pediatrics 2009:123:1562) A lm o st always in 90% o ccu r w ith in 1st 3 d o f life • C lin ic a l m a n ife s ta tio n s • Sx usually subtle and nonspecific, and often is asymp • Can present w / bulging fontanelle, change in level o f consciousness, seizures, acidosis, bradyeardia, apnea, d ro p in h e m a to crit • C a ta s tr o p h ic s y n d r o m e : Rapid bulging o f fontanelle, coma, decerebrate posturing, fixed pupils, seizures, re sp ira to ry sx, paralysis (emergency) • D ia g n o s tic s tu d ie s • M odality o f choice: Cranial ultrasound • For G A 36 w k, age 6 m o

- Prophy

D V T P ro p h y (J Trauma 2010:68:52; J Pediatr Child Health 2010:46:288) • See P ulm onary Embolism in P ulm onary section fo r details on tre a tm e n t • Incidence o f D V T 10x lo w e r fo r children com pared to adults • M ajor ICU risk facto r is CVL (18-26% assoc w /V T E in ICU). O thers include prolonged im mobility/paralysis, malignaney, sepsis, surgery/trauma, long-term TPN (up to 66%) • Peak incidence: Infants w / C V L & adolesc s/p surgery, prolonged im m obilization • D x: U/S m ost ofte n used, b u t has lo w sensitivity (30-80% ) • In ICU, a neg U/S does not rule o u t DVT. If high suspicion, treat until able to confirm w / contrast C T o r venogram (gold standard) • Hypercoag w o rk u p recom m ended fo r all patients (same incidence as in adults) • Prophy: EBM guidelines fo r ppx in long-term TP N use and complex cardiac patients w / assoc procedures; extrapolaron fro m adults difficult 2/2 diff in developmental hemostasis (varying levels/response o f clotting cascade proteins) & pharmacokinetic/dynamic properties o f anticoag agents in children • M ethods:TE Ds o r pneum oboots, rarely L M W H • Pediatric evidence: N o benefit o f prophy in trauma pts splanchnic hypoperfusion -> gastric mucosal breakdow n and im paired gastric m otility, leading to prolonged gastric acid exposure • pH has significant, nonlinear c o rre la tio n w / stress ulcer occurrence and bleeding • pH 7.0 p rotective, b elo w w / increased risk • A fte r bleed, 50% I in c lo t stability when pH dec fro m 7.4 to 6.5 ( C rit Care Med 2002:30:5351) • G enerally during 3 rd -7 th IC U d; can cause signif bleed (up to 4x inc m o rta lity) • Prophylaxis indicated fo r high risk: Sepsis, shock, operative procedure >3 hr, traum a/ dosed-head injury, status epilepticus, acute renal o r hepatic failure, anticoagulation o r coagulopathy, burns >35% BSA, co n cu rre n t steroids, parenteral n u tritio n (C rit Care Med 1992:20:1519) • Regimens: Meta-analysis o f available data failed to dem ónstrate 4 mortality, i ICU stay, 4- rate HAP/VAR1 rate ulcer, (Pediatr Cric Care 2.010; 11:12.4) did see L erythema on EGD • Procon pump inhib: Preferred (though no benefit to any specific drug in meta-analysis) • M o st p o te n t (dose dependent, 99% achieve pH = 7), max effect n o t u ntil 48 hr • Risks: CYP450 metabolism, poss assoc w / C. d iff infxn, acute in te rstitia l nephritis • Histam ine 2-re c e p to r antagonists • Q uicker onset o f action b u t less effective. Máxim um achievable gastric pH 4.0-5.0. A fte r 2 4 -4 8 hr, pH stabilizes ac 3.0-4.0 • Risk o f throm bocytopenia: Use PPI if Plt 0.5-1 meg/kg/hr: titrate upward. Children: Intermittent: 1-2 meg/kg/dose; may repeat at 3O-60-min ¡ntervals. Continuous: 1-2 meg/kg load -> 1 meg/kg/hr; titrate upward (usual: 1-3 meg/kg/hr)

Versed

1-5 min

2 -6 hr

N /A

0.05 mg/kg IV x 1, repeat q2-3 min (max 0.4-0.6 mg/kg IBW); if vented cont at 0.5-1 meg/kg/min titra te to effect

Ativan

15-30 min

8 -1 2 hr

N /A

0.05 mg/kg IV (also IM) q4-8h, max 2 mg/dose

S ta rtin g Dose (IV )

Thcsc are suggested doses & do n o i replace c inical judgment. F o llo w institucional guidelines where available.

RESPIRATORY FAILURE (Pediatr Rev 2009:30:470) • D e fin itio n : Failure o f oxygenation, ventilation. gas exchange o r airway p ro te c tio n • A rte ria l 0 2 tensión 50 m m Hg and pH 300;A LI: P a 0 2/ F i0 2 2 0 1 -3 0 0 :A R D S : P a 0 2/ F i0 2 7 d: PIP > 35, PEEP > 1 0 , MAP > 18, O I > 40, P aO j/F iO j > 150 , F iO , x MAP OI (O xygen Index) = ----- -------------

• N o o th e r significant organ dysfunction o r • Bridge fo r cardiac supp ort (C H D postop, myocarditis, arrhythmias, bridge co transplant— must be at a transplant cencer, postresuscitadon care fo r rapid cooling) • Severe hypotherm ia, sepsis Basic M a n a g e m e n t/M o n ito r in g • Lung rest: PEEP to keep lung open, FÍO 2 2 1 -3 0 • Goals • PaÜ2 > 60. P C O 2 40—45 • pRBC 20 cc/kg fo r H C T < 35, FFP 10 mL/kg fo r PT > 17, A C T 180-220, Pit >100 (>150 if bleeding), cryo 1 U /kg fo r fibrinogen > 150 • MAP 4 5 -6 5 (m ight need ¡no trop ic su pp ort, esp in W )

• Sedation: Ativan, m orphine, possibly in te rm itte n t midazolam; paralysis not ro u tine • N u tritio n : Enteral feeds O K ; fre q u e n t lyte rep letio n ; Q w k LFTs; lipid q48h • Heme: A m ica r avoided if possible (decreases life o f E C M O circuit). Use if bleeding despite maintaining lo w e r A C Ts and adequate platelets • Renal: Frequent volum e overload, edema, may need d iu re tics/H D • Pharmacokinetics/dynamics fo r many drugs altered on E C M O circuit: Hydralazine, nicardipine, furosem ide, epin ephrine, & dopam ine can be used at regular doses, b u t esm olol, am iodarone, n esiritide, bum etanide, sildenafil, & prostaglandins require dose m odification (J Cardiovasc Pharmacol 2011:58:126) P ro g n o s is /C o u rs e (‘’ ediatr Rev 2009:30:470) • C o m p lic a t io n s : H em orrhage, hemolysis, c lo t in circuit. neuro (hem orrhage, szr, air e m boli), renal dysfxn, infection, cardiac stunning (VA), equipm ent failure • P ro g n o s is : Survival rate fo r pediatric patients on E C M O fo r viral pneumonía - 64% • N eurologic: 7 2-91% no/m ild disability, 6% cerebral infarction, 10% seizure • Rare chro nic pulm disease • P o s t-E C M O m o n it o r in g : Head U/S, C T sean, caro tid D o p p le rs.a u d ito ry brainstem evoked response testing. eye exam, fo llo w BPs

V EN TILATOR-ASSO CIATED PNEUMONIA (VAP) D e fin itio n (Clin Infect Dis 2010:51:5136 PMID 20597664) • National Health Safety N e tw o rk definition: Pt w /o underlying dz w / serial x-ray w / 1 of follow ing (2+ if underlying dz); new o r progressive infíltrate, consolidation o r cavitation in addition to 3 o f the follow ing (age >1, 38.4 o r 15,000/mm! , new purulent sputum/A sputum/T secretions, new/ worse cough/dyspnea/apnea/tachypnea, rales / bronchial BS, w orse gas exchange E p id e m io lo g y :Clin Infect D s 2010:515136: j Pediatr 2009:154:582) • Rates 2 .1 -1 1 .6 /1 ,0 0 0 vent d ;w / i to 0.3/1,000 w /V A P prevention bundle (see later) • 2nd m o st com m on nosocom ial infxn ¡n PICU (a fte r bacteremia);VAP -3 2 % cases • Risk factors: Immunosuppressant drugs, immunodef, N M blockade, genetic syndrome, transportación o u t o f unit, reintubation, and transfusión. O th e r assoc include 1c bacteremia, trach, recent bronch, burns,TPN, steroids, H2-R blockers (Pediatrics 2002:109:758) • C o m m o n pathogens: G ram -neg especially Pseudomonas aeruginosa (up to 44%) and Klebsiella specles, Enterobacter species, nontypable H. infu. M o st com m on GP: S. aureus C lin ic a l M a n ife s ta tio n s /W o r k u p Clin infect Dis 2010;51:S136) • Sputum GS and ex can guide Rx and help distinguish in fxn (high #polys, diffe re n t organisms) in patients w / chro nic colonización (lo w # polys, sim ilar organisms) • ET aspírate 90% sens/40% spec, B AL GS 50% sens/81% spec, BAL ex 50% sens/80% spec T re a tm e n t • Empiric A b x should in clude broad coverage fo r gram-neg (PSA) and gram-pos * Vancomycin (coverage fo r MRSA) and Cefeplme com m only used O R ’ Piperacillin/tazobactam 300 mg/kg/d div q 6 -8 h (max 12 g/d) O R • M eropenem 60 mg/kg IV qd div q8h (up to 3 g/d) ♦ Im m unocom prom ised. may w a rra n t coverage fo r unusual pathogens (PCP, fungus) • A b x tailored by ex results, 7 -1 0 d ¡f uncomp; longer if S. aureus (by response if comp) o r Pseudomonas aeruginosa • S upportive care: O ptim ize vent settings (keep O 2 sac >95%, m o n ito r fo r SIA D H ) • Prevention bundle: M outh care w / chlorhexidine, H O B at 30^15° ¡f possible, draln secretions fro m Circuit q2-Hh, hand hygiene (J Pediatr 2009;154:582) P ro g n o s is (Pediatrics 2009:123:1108} • C om plications: Lung abscess,ARDS • VAP has risk up to -2 x lo nger PICU, ~2x longer hospital length o f stay and higher m o rta lity (10.5 vs. 2.4%) vs. o th e r PICU pts. Early approp abx saves lives

CUTE RESPIRATORY DISTRESS SYNDROME (ARDS) D e f in it io n s (1994 Arrencan-European Ccnseosus o r ARDS) • A cute lung in ju ry (A LI): A cu te onset o f hypoxem ia, bilateral in filtra tes on C X R and noncardiogenic pulm onary edema w ith P a C V F iO j > 200 b u t 3 w k): Remodeling and fibrosis • In jury patchy, w / airway collapse in dependent lung >V /Q m ism atch and hypoxemia C lin ic a l M a n ife s ta tio n s • Hypoxia o u t o f p ro p o rtio n to underlying dz, progress to dyspnea. tachypnea, diffuse rales T re a tm e n t • Rx underlying illness & ensure adequate O 2 (may re cu ire CPAP. BiPAP, o r intubation) • P rotective ve n tilatio n strategy per A R D S N e t: A d u lt data (N Engl J Med 2000:342:1301) • “ Small lungs": 2/2 patchy involvem ent/collapse as little as 25% o f lung tissue may particípate in air exchange, b u t “ n o rm a l" lung is at risk o f overdistension • Maintain oxygenation: 100% FÍO 2 during acute period. then increase PEEP to minimize O 2 w hile maintaining oxygen delivery • M inim ize baro/volutraum a w ith Ppiat 0.04 U/mín

In o tro p e Useful for: 4 CO Normal co high SVR

Dobutamine

P 1.P 2

Sepsis

4 SVR and splanchnic perfuslon.W orks best w 1 dopamine

In o tro p e + P ressor Useful for: 4 C O 4 SVR

Dopamine

DA < 2

1st line 15 Norepinephrine

a, pi

Sepsis

t afterload; constricts resistance = capacltance vessels; decreases splanchnic/ renal flow; raises PAP; hyperglycemia and tissue necrosis

Eplnephrine

(3 0.005-0.02 a > 0.02 Renal > 0.C35

Anaphylaxis status asthmaticus Cardiogenic shock from 4 HR, sepsis

Profound peripheral vasoconstriction (splanchnlc + renal); increases mV 02 , arrhythmia, Ischemia, RF, lactic acidosis

Milrinone

PDEin Inhibitor

Heart failure

Véntricular arrhythmlas, Vi-llfe 2.5 hr

Table adapted with permission courtesy of R. Scotc Harris. MD.

M a n a g e m e n t o f S e p t ic S h o c k

Picu

F lu id re fra c t o r y - c a te c h o la m in e r e s is ta n t s h o c k

17-'

B egin hydrocortisone if at risk of ad ren al insufficiency | Monitor C V P in P IC U . attain nml M A P -C V P & S c v 0 2 > 7 0 %

/ C o id s h o c k w / n o rm a l b loo d p re s s u re

\ C o id s h o c k w ith lo w b lo o d p re s s u re

• Titrate fluid & epinephrine, * Titrate fluid 8 epinephrine, S c v 0 2 >70%, Hgb > 10 g/dL S cvO g >70%, Hgb > 10 g/dL * If still H oTN con sider • If S c v O j still >70% add vaso dilator w/ volum e load norephinephrine (nitrovasodilators, * If S c v 0 2 stiil 7 0% • Ifstill H o TN , co n sid er va so p re ssin , terlip ressin , or an gictensin • if S c v O a still < 7 0 % consider low-dose epinephrine

P e r s is te n t c a t e c h o la m in e - re s is ta n t s h o c k : R/o and correct pericardlal efiusion, pneum othorax. & intraabdom inal p re ssu re -12 m m H g. C o n sid er P A , P IC C O , or F A T D cath eter &/or Doppler U /S to guide fluid, ¡notrope, vaso dilator. hormonal therapies G oal C l >3.3 & displaces o th e r structu re s • Brain tissue: IC H , neoplasm, in farct, D K A (young and new d x t risk) • CSF: C N S infection, vasculitis, hydrocephalus, pseu do tum or cerebri ■ Blood: Hem orrhage (TBI, ru p tu re d AVM , o th e r vascular anomalies) • Mixed: D K A -> cerebral edema (cytotoxic.va sog e nic.o r ¡nterst¡dal),TBI (see TBI sección) C lin ic a l M a n ife s ta tio n s • N e uro: ¿MS, irritab ility, bulging fontanelle, H A , lethargy -> coma, retinal hem orrhage, dilated pupil (usually on side o f lesión), C N palsy (esp III, IV,VI), ¡ncontinence, d ecorticace/decerebrate poscuring • C a rd io resp irato ry: Cushing tria d (LATE - bradyeardia, H T N , irregular respirations), Cheyne-S tokes breathing, apneusis • Gl: V om iting D ia g n o stic E va lu atio n • Careful neurologic exam & fundoscopic exam; imaging: Head C T • Labs: CMP (hypo- o r hypernatremia), coags (bleeding can cause D IC , and fo r therapeutic intervención), CBC, and type and screen • EKG: C erebral T waves (deep T wave irwersions) • LP: G enerally n o t recom m ended ¡f concern fo r increased ICP. T re a t em pirically

17-10 - TlCP PICU

T r e a t m e n t (Pedialr C rit C nrc Med 2003:565; • Goals: M inim ize ICP and maintain CPP • A void 2 injury:avoid hypoxia, hypercarbia, H o T N , hypo/hyperglycemia, hypertherm ia • Is t-lin e therapy • ABCs: Intubate if needed (GCS 40 f o r >30 min Tre atm e n ts for A cute H ern iatio n T re a tm e n t

M ech an ism

N o te s

M a n n ito l: 0.5-1 g/kg IV over 20 min q6-8h fo r goal sOsm 300-310 mOsm/L

t sOsm -> net flow of water o u t of brain along gradient

Hyperosmolarity, profound osmotic diuresis —> hypovolemia, abn lytes.ARF.

H y p e rv e n tila tio n

i PaCC >2 -> cerebral vasoconstrict - t i CBF

Risk o f cerebral ischemia ( i CPP)

3% norm al saline Goal Na 155-160 Acute herniation: 2 cc/kg oyer 20 min o r 50 cc of 23.4% saline if >40 kg

T sOsm -> net flow o f water out o f brain along gradient

Risk of hyperosmolality. central pontine myelinolysis

P entobarbital com a (refractory cases)

¿ cerebral metabolic rate -» dec CBF

Risk o f HoTN, need continuous EEG

Decompressive craniectom y

Abs indications: Refractory ICP o r ICP >40 fo r >30 min.

Dosages are suggestions and d o n o t replace clinical ju d g m c n t.F o llo w institu cion al guidelines w h e re available.

P ro g n o s is (J Pediatr 2002:141:793) • M o rta lity: Severe TBI 8%, severe TBI w / e ith e r H o T N , hypoxia, o r hypercarbia -55% • O th e r p o o r prognostic signs: Hyper-/hypoglycemia (TBI), T B U N , GCS < 7, P C O 2 < 22 (D K A ), hypoxia,hypercarbia,each episode o f H o T N leads to w o rse neurologic disability P e d ia tric B ra in D e a th C r it e r i a (Crit. Care Med 2011:39:2139) • D e finition : A bsent neurological fxn w / kn ow n irreversible cause o f coma and apnea • Prerequisites: H o T N , hypothermia and metabolic abn corrected; sedatives, N M blockers, anti-convulsants d/c’d fo r reasonable duration p rio r to exam. Exam 24—48 hr after resuscitadon o r acute brain injury • C rite ria • 2 neuro exams (2 d iff attendings) 1 2-24 h r apart w /: Coma (LO C , unresponsive to noxious stim .n o purposeful m vm t),absent brain stem reflexes (no pupillary resp [C N II], absent corneal resp),Absent gag, cough, sucking, ro o ting reflexes (C N IX, X), absent oculovestibuiar reflex (C N XIII; coid w a te r caloric testing w /o eye deviation o r nystagmus), absent facial m vm t (C N VII, no grim acc w / deep pressure at supraorbital ridge). flaccid tone (w / exception o f spinal cord reflexes) • Apnea testing x2 (can be the same provider); begin by ventilation/oxygenation to nml parameters. Cease support and PaCCh must rise 20 mm Hg (>60 mm Hg abs) w /o resp effort; termínate test if desat o r pt destabilizes. Can sub ancillary testing fo r apnea • A ncilla ry testing: N o t necessary; EEG, N M sean, cerebral bloo d flow, angiography; these can be substituted fo r apnea testing b u t does n o t replace neuro exam

RAPID SEQU ENCE INTUBATION P r e p a r a tio n • SOAPME: S uction, O xygen, A irw a y equipm ent, Pharmacology, M o n ito rin g E quipm ent E T T Size (m m ) = (age in y r/4 ) + 4 A ge

B irth

6 mo

1 yr

2 yr

3 yr

4 yr

5 yr

6 yr

8 yr

10 y r

12 y r

14 y r

A d u lt

Average weight (kg)

3.5

7

10

12

14

16

18

20

20

30

40

50

70

Blade

0-1 Miller

1 Miller

1 Miller

2 Miller

2

2

2

2

2-3

2-3

2-3

3

3

ETT size

2.5—3.5 uncuffed

3.5—4 uncuffed

4 uncuffed

4.5 uncuffed

4.5-5 uncuffed

5 uncuffed

5-5.5 uncuffed

5.5 uncuffed

6 Uncuffed

6-6.5 uncuffed

7

7.5

8

ETT length at lip (cm)

1 kg = 7 cm 2 kg = 8 cm 3 kg = 9 cm

10

11

12

13

14

14.5

15

16

17

18

19

20

LMA size

1

1.5

2

2

2

2

2

2.5

2.5

3

3

4

4

LMA Max cuff volume (mL)

4

7

10

10

10

10

10

14

14

20

20

30

30

Adapted from 2002 B rosclow Pediatric Resuscitation Tape, modifced from Hazinski MF, ed. Manual o f Pediatric Critical C are 1999.

u-n isa ■nDid

P h a rm a c o lo g y ¡n o r d e r g iv e n f o r RSI (see che cables below) • P r e m e d ic a tio n : Oxygen, lidocaine, acropine, defasciculacing dose N M blocker, sedación, analgesia = fencanyl, N M b locker P r e t r e a t m e n t M e d ic a tio n s A gent

Dose

U se ful in

A d ve rse Events

Lidocaine

1.5 mg/kg IV

TBI (blunts ICP response, cough, dysrhythmia)

Seizure, brady/HOTN

Fentanyl

2-5 mcg/kg IV

TBI (may blunt ICP response)

Resp depression, l HR. laryngospasm, rigidity, N/V

Atropine

0.02 mg/kg IV min: 0.1 mg;