What is the management for high bilirubin levels?

Management of High Bilirubin Levels

Immediate Risk Stratification

The first critical step is determining whether the hyperbilirubinemia is predominantly unconjugated or conjugated by obtaining fractionated bilirubin levels, as this fundamentally directs all subsequent management. 1, 2

For Neonates (≥35 weeks gestation):

• If total serum bilirubin (TSB) ≥25 mg/dL at any time, this is a medical emergency requiring immediate hospital admission for intensive phototherapy. 1, 2
• If TSB is approaching exchange transfusion levels or the infant shows signs of acute bilirubin encephalopathy (hypertonia, arching, retrocollis, opisthotonos, fever, high-pitched cry), perform immediate exchange transfusion even if TSB is falling. 3
• Exchange transfusions must only be performed by trained personnel in a neonatal intensive care unit with full monitoring and resuscitation capabilities. 1, 2

For Adults:

• Obtain complete liver function tests including ALT, AST, alkaline phosphatase, GGT, and albumin to assess for liver injury and synthetic function. 1, 2
• Measure prothrombin time (PT) and INR to evaluate liver synthetic capacity. 1, 2
• Order complete blood count with peripheral smear if unconjugated hyperbilirubinemia is suspected to assess for hemolysis. 1

Management Based on Bilirubin Type

Unconjugated Hyperbilirubinemia:

If unconjugated bilirubin represents >70-80% of total bilirubin with normal liver enzymes, consider Gilbert's syndrome, which requires no specific treatment as it is benign. 2

• Check reticulocyte count, haptoglobin, and LDH to evaluate for hemolysis. 1
• Screen for G6PD deficiency, particularly in patients of African, Mediterranean, or Asian descent, as this can cause sudden increases in bilirubin and requires intervention at lower thresholds. 3, 1
• Critical pitfall: In the presence of active hemolysis, G6PD levels can be falsely elevated, obscuring the diagnosis—repeat testing at 3 months if strongly suspected. 3, 1

Conjugated Hyperbilirubinemia:

Perform abdominal ultrasound as the initial imaging study to evaluate for biliary obstruction (specificity 71-97%). 1, 2

• If direct bilirubin is ≥50% of total bilirubin, consultation with a hepatology expert is recommended due to limited guidance for therapy. 1
• For biliary obstruction with total bilirubin >12.8 mg/dL (218.75 μmol/L), consider preoperative biliary drainage, especially if major hepatic resection is planned. 1, 2
• If abrupt elevations in liver tests occur in patients with primary sclerosing cholangitis, evaluate for dominant stricture with magnetic resonance cholangiography or endoscopic retrograde cholangiography. 1, 2

Neonatal-Specific Management Protocol

Laboratory Evaluation Required:

• TSB and direct bilirubin levels, blood type (ABO, Rh), direct antibody test (Coombs'), serum albumin, complete blood count with differential and smear, reticulocyte count. 3, 1
• G6PD testing if suggested by ethnic/geographic origin or poor response to phototherapy. 3, 1
• If sepsis suspected: blood culture, urine culture, and cerebrospinal fluid analysis. 3

Phototherapy Guidelines:

• Intensive phototherapy can produce a 30-40% decrease in initial bilirubin level within 24 hours, with the most significant decline in the first 4-6 hours. 3
• Expose maximum surface area to phototherapy—remove diaper when bilirubin approaches exchange transfusion range. 3
• Continue breastfeeding during phototherapy when possible; supplementation with expressed breast milk or formula is appropriate if intake is inadequate or weight loss is excessive. 3
• Phototherapy should be continuous (not intermittent) when bilirubin is approaching exchange transfusion zone. 3

Isoimmune Hemolytic Disease:

• Administer intravenous immunoglobulin 0.5-1 g/kg over 2 hours (repeat in 12 hours if necessary) if TSB is rising despite intensive phototherapy or within 2-3 mg/dL of exchange level. 3, 1, 2

Exchange Transfusion Criteria:

• Use both TSB level and bilirubin/albumin (B/A) ratio in conjunction with other factors to determine need. 3, 1
• If TSB ≥25 mg/dL or ≥20 mg/dL in a sick infant or infant <38 weeks gestation, obtain type and crossmatch immediately. 3
• Critical: Do NOT subtract direct (conjugated) bilirubin from total bilirubin when making treatment decisions. 1, 2

Special Population Considerations

Infants with Conjugated Hyperbilirubinemia:

• If conjugated bilirubin >25 μmol/L, urgent referral to a pediatrician for assessment of possible liver disease is essential. 1, 2
• Check results of newborn thyroid and galactosemia screening. 3
• Perform urinalysis and urine culture; evaluate for sepsis if indicated. 3

Jaundice Persisting Beyond 3 Weeks:

• Measure total and direct/conjugated bilirubin to identify cholestasis. 3, 2
• Verify newborn thyroid and galactosemia screen results. 3

Critical Pitfalls to Avoid

• Never delay appropriate imaging in patients with conjugated hyperbilirubinemia—early identification of biliary obstruction is critical for timely intervention. 1, 2
• Do not overinterpret albumin concentrations as a marker of liver disease severity, as albumin can be reduced in sepsis, inflammatory disorders, and malnutrition. 1, 2
• Standard laboratory tests for hemolysis have poor specificity and sensitivity—clinical correlation is essential. 1, 2
• Visual estimation of bilirubin levels from degree of jaundice leads to errors, particularly in darkly pigmented infants—always measure objectively. 3

Monitoring and Follow-Up

For Neonates on Intensive Phototherapy:

• If TSB ≥25 mg/dL, repeat TSB within 2-3 hours. 3
• If TSB 20-25 mg/dL, repeat within 3-4 hours. 3
• If TSB <20 mg/dL, repeat in 4-6 hours; if continuing to fall, repeat in 8-12 hours. 3
• Discontinue phototherapy when TSB <13-14 mg/dL. 3
• Consider measuring TSB 24 hours after discharge to check for rebound, depending on the cause of hyperbilirubinemia. 3

For Adults with Drug-Induced Liver Injury:

• For suspected hepatocellular injury, repeat blood tests within 2-5 days. 2
• For suspected cholestatic injury, repeat within 7-10 days. 2