What is the treatment for elevated bilirubin levels?

Treatment for Elevated Bilirubin

Treatment of elevated bilirubin depends critically on whether the patient is a neonate or adult, and whether hyperbilirubinemia is conjugated or unconjugated—with neonates requiring immediate intensive phototherapy when total serum bilirubin (TSB) reaches ≥25 mg/dL, while adults need urgent imaging to identify biliary obstruction. 1

Initial Diagnostic Framework

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, alkaline phosphatase, 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 (≥35 Weeks Gestation)

Intensive Phototherapy

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

• Use intensive phototherapy with irradiance in the blue-green spectrum (430-490 nm) of at least 30 μW/cm²/nm delivered to as much of the infant's surface area as possible 3
• Apply phototherapy continuously when bilirubin approaches exchange transfusion levels 3
• Expect a 30-40% decline in bilirubin within 24 hours with intensive phototherapy 3, 1
• Remove the diaper when bilirubin levels approach exchange transfusion range to maximize surface area exposure 3
• Line bassinet sides with aluminum foil or white material when TSB approaches exchange transfusion levels to increase exposed surface area 3

Hydration and Feeding

• Provide adequate hydration with milk-based formula if the infant is dehydrated, as formula inhibits enterohepatic circulation of bilirubin 3, 1
• Feed every 2-3 hours (breast or bottle) during phototherapy 3
• Continue breastfeeding if possible during phototherapy, though temporarily substituting formula is an option to enhance phototherapy efficacy 3

Intravenous Immunoglobulin (IVIG)

• Administer IVIG 0.5-1 g/kg over 2 hours if TSB continues rising despite intensive phototherapy in isoimmune hemolytic disease 1, 2

Exchange Transfusion

• Perform exchange transfusion only by trained personnel in a neonatal ICU with full monitoring and resuscitation capabilities 1, 2
• Use the bilirubin/albumin ratio as an additional factor (not in lieu of TSB) when determining need for exchange transfusion 3, 1
• Immediate exchange transfusion is required in any jaundiced infant manifesting signs of intermediate to advanced acute bilirubin encephalopathy (hypertonia, arching, retrocollis, opisthotonos, fever, high-pitched cry) 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
• Discontinue phototherapy when TSB falls to <13-14 mg/dL 3
• Consider measuring TSB 24 hours after discharge to check for rebound, depending on the cause 3

Treatment for Adults

Obstructive Causes (Conjugated Hyperbilirubinemia)

Perform abdominal ultrasound immediately as the first-line imaging study to detect biliary obstruction 1

Endoscopic Intervention

• ERCP with plastic stent placement is the procedure of choice for:
  • Choledocholithiasis with dilated ducts 1
  • Suspected sclerosing cholangitis 1
  • Malignant common bile duct obstruction 1

Percutaneous Drainage

• Use percutaneous transhepatic biliary drainage (PTBD) as second-line when ERCP fails or is not technically feasible 1
• PTBD is first-line for hilar biliary obstruction from malignancy 1

Preoperative Management

• Consider preoperative biliary drainage if total bilirubin >12.8 mg/dL (218.75 μmol/L) and major hepatic resection is planned 1, 2

Medical Management

• Ursodeoxycholic acid may improve quality of life but lacks definitive survival benefit in primary sclerosing cholangitis 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, as albumin can be reduced in sepsis and malnutrition 1, 2
• Avoid delaying imaging in conjugated hyperbilirubinemia, as this can lead to preventable complications 1, 2
• Be aware that standard hemolysis tests have poor sensitivity and specificity, and G6PD levels may be falsely elevated during active hemolysis 1, 2

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