What is the management for a patient with hyperbilirubinemia?

Management of Hyperbilirubinemia

The management of hyperbilirubinemia requires fractionating bilirubin levels to determine if it is primarily conjugated or unconjugated, followed by targeted diagnostic testing and appropriate interventions based on the underlying cause. 1, 2

Initial Diagnostic Approach

• Obtain fractionated bilirubin levels to determine if hyperbilirubinemia is primarily conjugated (direct) or unconjugated (indirect) 2
• Complete liver function tests including ALT, AST, ALP, GGT, and albumin to assess liver injury and synthetic function 1
• Check prothrombin time (PT) and INR to evaluate liver synthetic capacity 1
• Measure complete blood count with differential and peripheral smear to assess for hemolysis 2
• Test for reticulocyte count, haptoglobin, and LDH to evaluate for hemolytic processes 1

Management Based on Bilirubin Type

For Unconjugated Hyperbilirubinemia:

• Calculate the proportion of conjugated bilirubin (should be less than 20-30% of total bilirubin) 1
• In neonates, use phototherapy when total serum bilirubin (TSB) reaches threshold levels based on age and risk factors 3:
  • 15 mg/dL (257 μmol/L) at 25-48 hours of age
  • 18 mg/dL (308 μmol/L) at 49-72 hours of age
  • 20 mg/dL (342 μmol/L) after 72 hours of age
• For infants receiving intensive phototherapy 3:
  • Continue feeding every 2-3 hours
  • Monitor TSB levels at intervals based on initial levels:
    • If TSB ≥ 25 mg/dL (428 μmol/L), repeat TSB within 2-3 hours
    • If TSB 20-25 mg/dL (342-428 μmol/L), repeat within 3-4 hours
    • If TSB < 20 mg/dL (342 μmol/L), repeat in 4-6 hours
  • Discontinue phototherapy when TSB < 13-14 mg/dL (239 μmol/L)

For Conjugated Hyperbilirubinemia:

• Perform abdominal ultrasonography as the initial imaging method to differentiate between extrahepatic obstructive and intrahepatic parenchymal disorders 1, 2, 4
• Consider MRI with MRCP for second-line imaging, particularly when primary sclerosing cholangitis or primary biliary cholangitis is suspected 2
• Consider ERCP for therapeutic intervention in biliary obstruction 2

Special Interventions

• For isoimmune hemolytic disease with rising TSB despite intensive phototherapy or TSB within 2-3 mg/dL (34-51 μmol/L) of exchange level, administer intravenous immunoglobulin 0.5-1 g/kg over 2 hours 3
• Consider exchange transfusion when 3:
  • TSB reaches exchange transfusion threshold based on age, risk factors, and albumin levels
  • TSB ≥ 25 mg/dL (428 μmol/L) at any time (medical emergency)
  • Signs of acute bilirubin encephalopathy are present (hypertonia, arching, retrocollis, opisthotonos, fever, high-pitched cry)
• If exchange transfusion is being considered, measure serum albumin level and use the bilirubin/albumin ratio in conjunction with TSB level 3

Hydration Management

• If infant's weight loss from birth is > 12% or there is clinical or biochemical evidence of dehydration, recommend formula or expressed breast milk 3
• In breastfed infants requiring phototherapy, continue breastfeeding if possible 3
• Supplementation with expressed breast milk or formula is appropriate if intake seems inadequate 3
• Consider intravenous fluids if oral intake is questionable 3

Monitoring and Follow-up

• Consider measuring TSB 24 hours after discontinuing phototherapy to check for rebound, depending on the cause of hyperbilirubinemia 3
• For patients with conjugated hyperbilirubinemia, monitor liver synthetic function with albumin and PT/INR 1
• Test for G6PD deficiency in patients with acute hemolysis, especially those with poor response to phototherapy 3, 1

Common Pitfalls to Avoid

• Do not rely solely on visual assessment of jaundice, as it can be inaccurate 2, 5
• Do not subtract direct bilirubin from total bilirubin when using guidelines for phototherapy and exchange transfusion 3
• Avoid delaying treatment when TSB is at or above 25 mg/dL (428 μmol/L), as this is a medical emergency requiring immediate hospitalization 3
• Be aware that standard laboratory tests for hemolysis have poor specificity and sensitivity 1
• Do not delay appropriate imaging in patients with conjugated hyperbilirubinemia 1