Treatment of Hyperbilirubinemia
Phototherapy is the first-line treatment for neonatal hyperbilirubinemia, with intensive phototherapy (≥30 μW/cm²/nm in the blue-green spectrum) initiated based on hour-specific bilirubin nomograms and risk factors, while exchange transfusion is reserved for severe cases (TSB ≥25 mg/dL or ≥20 mg/dL in sick/premature infants) that fail phototherapy. 1, 2
Neonatal Hyperbilirubinemia (≥35 Weeks Gestation)
Initial Management and Prevention
Promote frequent breastfeeding (8-12 times daily) during the first several days to prevent dehydration-associated hyperbilirubinemia, while continuing breastfeeding during phototherapy with supplementation only if intake is inadequate or weight loss is excessive 1, 2
Perform systematic risk assessment before discharge using clinical factors (gestational age <38 weeks, exclusive breastfeeding, bruising, cephalohematoma, family history, Asian or Black ethnicity, male sex, G6PD deficiency) to stratify infants for follow-up intensity 1
Phototherapy Indications and Implementation
Initiate intensive phototherapy when TSB reaches treatment thresholds based on the infant's age in hours and risk factors (isoimmune hemolytic disease, G6PD deficiency, asphyxia, lethargy, temperature instability, sepsis, acidosis, or albumin <3.0 g/dL) 1, 2
Position light source as close as possible to the infant's skin to maximize spectral irradiance in the blue-green spectrum (430-490 nm), ensuring ≥30 μW/cm²/nm intensity 2
Do NOT subtract direct (conjugated) bilirubin from total bilirubin when using treatment guidelines, unless direct bilirubin is ≥50% of total (in which case consult an expert) 1
Monitor TSB levels every 2-3 hours if ≥25 mg/dL, every 3-4 hours if 20-25 mg/dL, and every 4-6 hours if <20 mg/dL during intensive phototherapy 2
Exchange Transfusion
This is a medical emergency requiring immediate direct admission to a neonatal intensive care unit (not the emergency department, as this delays treatment) when: 1
- TSB ≥25 mg/dL (428 μmol/L) at any time, OR
- TSB ≥20 mg/dL (342 μmol/L) in sick infants or those <38 weeks gestation, OR
- TSB continues rising despite intensive phototherapy
Perform exchange transfusion only in a NICU with trained personnel, full monitoring, and resuscitation capabilities using modified whole blood crossmatched against the mother and compatible with the infant 1, 2
Adjunctive Therapy for Isoimmune Hemolytic Disease
Administer intravenous immunoglobulin (IVIG) 0.5-1 g/kg over 2 hours if TSB is rising despite intensive phototherapy or is within 2-3 mg/dL (34-51 μmol/L) of the exchange transfusion threshold in infants with Rh or ABO hemolytic disease (repeat in 12 hours if necessary) 1
Essential Laboratory Evaluation
When TSB requires treatment, obtain: 1
- TSB and direct bilirubin levels
- Blood type (ABO, Rh) and direct antibody test (Coombs')
- Serum albumin
- Complete blood count with differential and smear
- Reticulocyte count
- G6PD testing if suggested by ethnicity, geography, or poor phototherapy response
- Blood culture, urine culture, and CSF studies if sepsis is suspected
Follow-Up Timing
Schedule follow-up based on discharge timing: 1
- Discharged before 24 hours → seen by 72 hours
- Discharged 24-47.9 hours → seen by 96 hours
- Discharged 48-72 hours → seen by 120 hours
Delay discharge until 72-96 hours if adequate follow-up cannot be ensured in high-risk infants 1
Adult Hyperbilirubinemia
Identify and treat the underlying cause rather than the hyperbilirubinemia itself, as the approach differs fundamentally from neonatal management 2, 3
Diagnostic Approach
Measure fractionated bilirubin to confirm indirect (unconjugated) versus direct (conjugated) predominance 2, 3
For indirect hyperbilirubinemia: Check CBC, reticulocyte count, peripheral smear, haptoglobin, and LDH to exclude hemolysis 2, 4
For direct hyperbilirubinemia: Obtain right upper quadrant ultrasound; if inconclusive, proceed to CT or MRI for biliary obstruction evaluation 3
Treatment by Etiology
Gilbert syndrome (indirect bilirubin <20-30% of total, no hemolysis) requires no treatment, as this benign condition affects ~5% of Americans 2, 3, 4
Drug-induced hyperbilirubinemia: Discontinue the offending agent immediately 2, 4
Hemolytic conditions: Treat the underlying hemolysis; for antiviral-induced hemolysis causing significant anemia, modify drug choice or dose 4
Cholestatic liver diseases (PBC, PSC): Administer ursodeoxycholic acid per AASLD guidelines 3
Malignant biliary obstruction: Perform stent placement or surgical intervention based on location and nature of obstruction 3
Monitoring for Cholestatic Patients
Monitor for fat-soluble vitamin deficiencies (A, D, E, K) in chronic cholestasis 3
Attempt parenteral vitamin K supplementation to correct prolonged INR before attributing coagulopathy to liver failure 3
Repeat liver function tests to monitor treatment response, with INR rechecked within 2-5 days to confirm trajectory 3
Critical Pitfalls to Avoid
In neonates: Delayed treatment initiation, ignoring risk factors, inadequate phototherapy intensity, and unnecessarily interrupting breastfeeding all increase kernicterus risk 2, 4
In adults: Treating the bilirubin number instead of identifying the underlying cause, and performing extensive workup for Gilbert syndrome (which requires only fractionated bilirubin and exclusion of hemolysis) leads to unnecessary testing and patient anxiety 2, 3
G6PD deficiency requires intervention at lower bilirubin thresholds and can cause sudden bilirubin increases; retest at 3 months if initially normal during hemolysis 4
Exchange transfusion carries significant morbidity (apnea, bradycardia, cyanosis, vasospasm, thrombosis, necrotizing enterocolitis) in up to 5% of patients, emphasizing the importance of aggressive phototherapy to avoid this intervention 1