What are the treatment options for elevated bilirubin (hyperbilirubinemia)?

Treatment of Elevated Bilirubin

Treatment of elevated bilirubin depends critically on whether the patient is a neonate or adult, and whether the hyperbilirubinemia is unconjugated or conjugated—with phototherapy being the definitive treatment for neonatal unconjugated hyperbilirubinemia and biliary decompression being the primary intervention for obstructive conjugated hyperbilirubinemia in adults. 1, 2

Initial Diagnostic Approach

Before initiating treatment, determine the type of hyperbilirubinemia:

• Obtain fractionated bilirubin levels to distinguish conjugated from unconjugated hyperbilirubinemia 1, 2
• Order complete liver function tests (ALT, AST, ALP, GGT, albumin) to assess hepatocellular injury versus cholestasis 1, 2
• Measure PT/INR to evaluate synthetic liver function 1, 2
• Check complete blood count with peripheral smear if unconjugated hyperbilirubinemia suggests hemolysis 1

Treatment for Neonates (Unconjugated Hyperbilirubinemia)

Intensive Phototherapy

Initiate intensive phototherapy immediately if total serum bilirubin (TSB) ≥25 mg/dL at any time—this is a medical emergency requiring immediate admission. 1, 2

Phototherapy technique:

• Use blue-green light at 460-490 nm wavelength (optimal peak 478 nm) with irradiance of 25-35 mW/cm²/nm 3
• Position fluorescent tubes within 10 cm of the infant in a bassinet (not incubator) to maximize spectral irradiance 4
• Maximize exposed body surface area (35-80%) by removing the diaper when bilirubin approaches exchange levels and changing position every 2-3 hours 4, 3
• Apply phototherapy continuously when bilirubin approaches exchange transfusion levels—intermittent therapy has no scientific rationale 4, 1
• Line bassinet sides with aluminum foil or white cloth when bilirubin levels are extremely high to increase surface area exposure 4

Expected response:

• A 30-40% decline in bilirubin within 24 hours is expected with intensive phototherapy 1, 3
• The most significant decline occurs in the first 4-6 hours, with decreases of 0.5-1 mg/dL per hour when TSB >30 mg/dL 4, 3
• Discontinue phototherapy when serum bilirubin falls below 13-14 mg/dL 3

Adjunctive Pharmacologic Treatment

Administer intravenous immunoglobulin (IVIG) 0.5-1 g/kg over 2 hours if TSB continues rising despite intensive phototherapy in isoimmune hemolytic disease (ABO or Rh incompatibility). 1, 2

Exchange Transfusion

Perform exchange transfusion only by trained personnel in a neonatal ICU with full monitoring and resuscitation capabilities when TSB reaches exchange transfusion thresholds despite intensive phototherapy. 1, 2

• Use the bilirubin/albumin ratio as an additional factor when determining need for exchange transfusion, but not in lieu of TSB level 1, 2
• Perform immediate exchange transfusion for any infant showing signs of intermediate to advanced acute bilirubin encephalopathy even if TSB is falling 3

Monitoring During Treatment

• Repeat TSB within 2-3 hours if TSB ≥25 mg/dL 3
• Repeat within 3-4 hours if TSB 20-25 mg/dL 3
• Repeat in 4-6 hours if TSB <20 mg/dL 3
• Continue feeding every 2-3 hours during phototherapy to maintain adequate hydration 3
• Measure TSB 24 hours after discharge to check for rebound hyperbilirubinemia, especially in hemolytic disease 3

Treatment for Adults (Conjugated Hyperbilirubinemia)

Biliary Obstruction Management

Perform abdominal ultrasound immediately as the first-line imaging study to detect biliary obstruction (specificity 71-97%). 1, 2

For confirmed biliary obstruction:

• Perform ERCP with plastic stent placement for choledocholithiasis with dilated ducts, suspected sclerosing cholangitis, and malignant common bile duct obstruction 1
• Use percutaneous transhepatic biliary drainage (PTBD) as second-line when ERCP fails or is not technically feasible 1
• Use PTBD as first-line for hilar biliary obstruction from malignancy 1
• Consider preoperative biliary drainage if total bilirubin >12.8 mg/dL and major hepatic resection is planned 1, 2

Medical Management

Ursodeoxycholic acid may improve quality of life in primary sclerosing cholangitis but lacks definitive survival benefit. 1

Critical Pitfalls to Avoid

• Never subtract direct (conjugated) bilirubin from total bilirubin when making treatment decisions in neonates 1, 2
• Do not overinterpret albumin levels as a marker of liver disease severity—albumin can be reduced in sepsis and malnutrition 2
• Do not delay imaging in conjugated hyperbilirubinemia—early identification of biliary obstruction is critical 1, 2
• Recognize that standard hemolysis tests have poor sensitivity and specificity, and G6PD levels may be falsely elevated during active hemolysis 1, 2
• Do not position halogen phototherapy lamps closer than manufacturer recommendations due to burn risk 4

Red Flags Requiring Urgent Intervention

• TSB ≥25 mg/dL in neonates at any time requires immediate admission for intensive phototherapy 1, 2
• Failure of bilirubin to decrease during phototherapy suggests ongoing hemolysis requiring further evaluation 1, 2
• Signs of acute liver failure (encephalopathy, coagulopathy) accompanying hyperbilirubinemia require urgent hepatology consultation 2
• Conjugated bilirubin >25 μmol/L in infants requires urgent pediatric referral for liver disease evaluation 1, 2