PICU Morbidity

Khlaire D. Pioquinto, M.D.

Objectives

• To present a case of an infant with jaundice.• To discuss the probable treatable causes of

acute liver failure in infancy.

General Patient Information

• CC• 2 months old• Male• Date of Admission: January 2, 2014

Vomiting

Chief Complaint

History of Present Illness

• Product of IVF, no consanguinity• Born full term via NSD to a 36 y.o. G1P1 (1001) at 37

1/7 weeks AOG• BW 2655g, BL 47, HC 31cm, MT 38 weeks, AGA, AS 9,9• Stayed in the NICU for hypoglycemia (Hgt 12 mg/dL),

hyperbilirubinemia sec. to ABO incompatibility, clinical sepsis (blood culture negative), completed 7-day course of IV Ampicillin and Cefotaxime

• Sent home on the 8th day of life stable with decreased jaundice

History of Present Illness

History of Present Illness

ER Consult

Maternal History

• In-vitro fertilization – 2x, worked up for TORCH infection – told to have normal results

• Regular prenatal check-up• No infection• OGCT – normal• No BP elevations• HBsAg nonreactive• No intake of teratogenic drugs

Past Medical History

• Normal newborn screen

Family History

• Maternal side: (+) hypertension, diabetes, psoriasis

At the ER

• T 36.8C HR 140 RR 40 BP 80/50• Wt 3.8kg (z-score = 0.5)• Generalized jaundice• Icteric sclerae, pink conjunctivae• HC 39cm; flat, patent fontanelles• Nonsunken eyeballs, moist lips• Clear breath sounds• Regular cardiac rhythm• Soft abdomen, distended, AC 38cm• Scrotal mass, (+) transillumination, right• Full pulses, no cyanosis

Hyperbilirubinemia, etiology to be determinedVomiting, unspecified

Hydrocoele, right

Assessment

PlansDiagnostics

– CBCPC– Urinalysis– Bilirubin levels– ALT, AST– Hgt– Whole abdominal

ultrasound

Therapeutics• IVF: D5IMB at

maintenance rate

URINALYSIS

RBC 17

WBC 2

EPITHELIAL CELLS 4

CASTS 0

BACTERIA 32

CBC hgb hct wbc neu lym mono eos plt

1/3/14 113 36 16.1 48 47 05 2 264

Total Bilirubin(0.20-1.19)

39.76

Direct Bilirubin(0-50)

23.93

Indirect Bilirubin (0.20-0.70)

16.11

SGPT (0-55 u/l)

297 u/l

SGOT (5-34 u/l)

737 u/lHgt = 84 mg/dL

Ultrasound of the abdomen

• Mildly prominent-sized kidneys, may be due to mild inflammation changes or may still be normal.

• Unremarkable liver, pancreas and spleen. • Partially contracted gallbladder. • Negative biliary ectasia. • Negative for mass ascites.

SUBJECTIVE OBJECTIVE ASSESSMENT

AfebrilePoor activity(+) tea-colored urineNo vomitingNo cough

LethargicHR 100 RR 44 T 36.4 02 83%(+) generalized jaundiceClear breath sounds, (+) shallow subcostal retractionsDistended abdomen AC: 38cm39cmLiver edge not palpable, (+) splenomegaly(+) hydrocoele, rightFull Pulses, (+) clubbing

Neonatal hepatitis

Hepatic encephalopathy

Hydrocele, right

3rd Hospital Day

PLANDiagnostics Therapeutics

Chest XrayCMV of mother and patientVDRL or RPRTotal Protein, albumin, globulinNa, K, iCaSerum ammoniaPT, PTT

Referral to GI specialistReferral to InfectiousReferral to Surgery

Ampicillin IV 105mkdayAmikacin IV 57mkdayVitamin K 4mg/SIVPRanitidine 4mg/IV q 825% Albumin infusionFurosemide 4mg/SIVPLactulose Suspension 4mL until 5-6 stools/day02 5lpm via face maskNGT inserted

PICU Transfer

Creatinine (0.34-0.54 mg/dl)

0.31 mg/dl

BUN (8.96 – 20.73mg/dl)

4.76 mg/dl

Ammonia (30.6-122)

212.8ug/dL

Na (136-145mmol/L)

126 mmol/l

K (3.5-5.10 mmol/L)

2.5 mmol/l

iCa (1.12-1.32 mmol/l)

1.16 mmol/l

PT

Pt 53.8

Control 13.3

%Activity 0.13

INR 5.76

APTT

Pt 94.1

Control 30.9

Lactulose q6

Corrected via with proper IVF

with K incorporation

Vitamin K 1mkdose SIVP, ODN-Acetylcysteine

Total Protein(6.40-8.30 g/dL)

5g/dl

A/G Ratio(1.21-1.52)

2.85

Globulin(2.90-3.30 g/dl)

1.3 g/dl

Albumin(3.50-5g/dl)

3.70 g/dl

RBS 69.92 mg/dl

25% albumin transfusion

Chest X ray

Normal

Scrotal Ultrasound

Hydrocoele, right, probably communicating

VDRL Nonreactive

Plans

Therapeutics• Hypokalemia and

Hyponatremia correction• Acetylcysteine 500mg/IV

every 4 hours• Spironolactone 25mg/tab,

6mg pptab/NGT BID (1.5mkdose)

• Vit A, D, E, K, UDCA, Zinc

Diagnostics• Daily AC monitoring• Referral to a Geneticist for

metabolic genetic workup of hepatic failure– Urinary organic acid profile

• Referral Hepatobiliary Surgeon

Family conference

• Discussed the diagnosis of CMV hepatitis and hepatic failure

• Acquisition of CMV infection– Patient probably acquired infection via transmission

transplacentally from the mother (1-3 mos of pregnancy)• Plan– Confirm CMV infection (test mother)– Metabolic work-up: test liver parameters to monitor for

prognostication purposes– Liver biopsy – cannot be done yet

• Option:– Ultimately, liver transplant– Supportive treatment:

• Nutrition, Vitamins, UDCA, Spironolactone, Albumin transfusion, Lactulose

• Goals:– Decrease jaundice– Normalize PT, PTT

• Prognosis• Prevalence

Family conference

3rd Hospital day

PT 1/3 1/4

Pt 53.8 40.1

Control 13.3 13.3

%Activity 0.13 0.19

INR 5.76 3.98

APTT

Pt 94.1 30.9

Control 84.9 30

Ampicillin IV 105mkdayAmikacin IV 57mkdayVitamin ADEKUDCA SpironolactoneN-AcetylcysteineLactuloseRanitidine 4mg/IV q 8

Subjective Objective AssessmentNo vomitingImproving oral intake

Improved sensoriumHR 100 RR 44 T 37BP 86/51 mmHg 02 100%

Neonatal hepatitisHepatic encephalopathyHydrocele, right

SUBJECTIVE OBJECTIVE

AfebrileImproved feeding5-6x BMUO 6.3mL/kg/hr

Awake, more alertHR 106 RR 48 T 37BP 80/50 mmHg 02 100%(+) generalized jaundiceClear breath sounds, Good air entry, no retractionsDistended abdomen (+) splenomegaly(+) hydrocoele, rightFull Pulses, (+) clubbing

4th Hospital DayNH4

(30.67-122.70 ug/dl)

212.8 141.36 ug/dl

GGT (12-64 u/l) 50 u/l

PTPt 40.1 44.7Control 13.3 13.3

%Activity 0.19 0.16

INR 3.98 4.51APTT

Patient 84.9 108.5Control 30 28.1

CMV (Patient)

IgG Positive

IgM Positive

CMV (mother)IgG PositiveIgM Negative

Organic Acid and Amino Acid Analysis

Negative

AFP (0.89-8.78 ng/ml)

136,500 ng/ml

CBC hgb hct wbc neu lym mono eos plt

1/6/14 100 29 7.80 29 64 05 02 160

Total Bilirubin(0.20-1.19)

39.76 35.41

Direct Bilirubin(0-0.5 mg/dL)

23.93 21.54

Indirect Bilirubin (0.20-0.70)

16.11 14.11

4th Hospital DayAssessment Plant

CMV Hepatitis in Hepatic Failure

Ampicillin IV 105mkdayAmikacin IV 57mkdayVitamin ADEKUDCA Spironolactone N-AcetylcysteineLactuloseRanitidine 4mg/IV q 8Propranolol 4mg 3x/dayTransferred to

regular room on the 6th Hospital Day

Treatable cause of acute liver failure in infancy

• Cytomegalovirus infection• Petechiae or purpura (79%), hepatosplenomegaly

(74%), jaundice (63%), prematurity and blueberry muffin spots consistent with extramedullary �hematopoiesis. • Laboratory abnormalities: elevated hepatic

transaminase and bilirubin levels (as much as half is conjugated), anemia, and thrombocytopenia.• Hyperbilirubinemia persists beyond the period of

physiologic jaundice.

Treatable cause of acute liver failure in infancy

• Cytomegalovirus infection

CMV (Patient)

IgG Positive

IgM Positive

CMV (mother)IgG PositiveIgM Negative

CMV PCR: 298 copies/mL

Treatable cause of acute liver failure in infancy

• Hepatitis B– Mother and patient: HBsAg negative

• Galactosemia– newborn screen negative, no diarrhea on

exclusive breastfeeding • Hereditary fructose intolerance– no intake of fructose yet

• Congenital syphilis– Both mother and patient are VDRL negative

Treatable cause of acute liver failure in infancy

• Neuroblastoma – Ultrasound liver normal in size with homogenous

parenchymal echopattern, smooth contour, no discrete focal mass lesion, no intrahepatic bile duct dilatation, portal vein normal in caliber, gall bladder partially contracted 2.6 x 0.62 cm, visualized common bile duct 0.26 cm in diameter

Treatable cause of acute liver failure in infancy

• Hereditary tyrosinemia– urine organic acid, succinylacetate screen negative

• Mitochondrial defects– serum lactate normal at 11.8 mg/dl (NV 4.5-19.82)

• HIV– Mother negative in her IVF work up

Treatable cause of acute liver failure in infancy

• Neonatal hemochromatosis– serum ferritin slightly increased at 413 ng/ml (NV

8.7-71– Transferrin saturation 68% (NV 15-55%)– Reticulocyte count normal at 0.006( NV 0.005-

0.15) – Liver biopsy not done as INR has been >3.5 despite

Vitamin K daily. – No active bleeding.

11th Hospital DaySUBJECTIVE OBJECTIVE

AfebrileGood appetite and activityNo vomitingSleeps wellGood urine output

Awake and alertHR 118 RR 44 T 36.5(+) generalized jaundice and icteric scleraeClear breath sounds, Soft abdomen(+) splenomegaly(+) hydrocoele, rightFull Pulses, (+) clubbing

Discharged

Acute Liver Failure probably secondary to Severe Neonatal HepatitisHepatic Encephalopathy

Final Diagnosis

Home Medications

• Multivitamins• Vit ADEK• UDCA• Zinc• N-Acetylcysteine 500mg/IV every 4 hours• Propranolol 10mg/tab, 4mg/pptab 3x a day• Spironolactone 4mg/pptab 2x a day• Oral KCl 5meq BID

Update

• 4months old• Currently in Singapore where the patient is

continuously being worked up pending possible liver transplant

Galactosemia

• Most common metabolic cause of liver disease in the neonate.• Inherited as an autosomal recessive trait and develops because

of the deficiency of galactose-1-phosphate uridyl transferase (GALT).

• Clinical manifestations: jaundice, hepatosplenomegaly, feeding difficulties and vomiting, hypoglycemia, lethargy, irritability, seizures, cataracts.

• Delayed diagnosis results in cirrhosis and mental retardation• Management consists of substituting a lactose-free formula

for breast-feeding or for a standard formula, and, later, a galactose-free diet.

Cloherty J. Eichenwald E., Hansen A., Manual of Neonatal Care, 7th edition

Hereditary Fructose Intolerance

• deficiency of the enzyme aldolase B• asymptomatic until they ingest fructose,

sucrose, or sorbitol• Clinical manifestations: hypoglycemia,

jaundice, hepatomegaly, vomiting, lethargy, irritability, seizures, and abnormal LFTs

• Management is done by elimination of sucrose, fructose, and sorbitol from the diet

Cloherty J. Eichenwald E., Hansen A., Manual of Neonatal Care, 7th edition

Hereditary Tyrosinemia

• A low protein diet may be required in the management of tyrosinemia. Recent experience with NTBC has shown to be very effective. The most effective treatment in patients with tyrosinemia type I seems to be full or partial liver transplant.

Hereditary hemochromatosis

• a common autosomal recessive disorder that results in excessive iron deposition in the liver as well as in extrahepatic sites

• Also known as neonatal iron storage disease• frequently are premature or are small for

gestational age• features of liver failure with hypoalbuminemia,

hypoglycemia, coagulopathy, low fibrinogen, and, frequently, thrombocytopenia and anemia.

• Liver dysfunction. Galactosemia is the most common metabolic cause of liver disease in the neonate. Hepatomegaly with hypoglycemia and seizures suggest glycogenosis type I or III, gluconeogenesis defects, or hyperinsulinism. Hereditary fructose intolerance (when there is ingestion of fructose or sucrose, in the neonate usually a soy formula), tyrosinemia type I, neonatal hemochromatosis, and mitochondrial diseases can also present predominantly with liver dysfunction in the neonate. Cholestatic jaundice with failure to thrive is observed primarily in alpha-1-antitrypsin deficiency, Byler disease, and Niemann-Pick disease type C.