What is the management approach for a patient with elevated total bilirubin (hyperbilirubinemia)?

From the Guidelines

The management approach for a patient with elevated total bilirubin (hyperbilirubinemia) should prioritize identifying and treating the underlying cause while monitoring bilirubin levels, with phototherapy being a key intervention for severe cases, particularly in neonates, as recommended by the most recent guidelines 1.

Key Considerations

• Initial evaluation should include fractionation of bilirubin into direct (conjugated) and indirect (unconjugated) components, along with liver function tests, complete blood count, and imaging studies like ultrasound or CT scan as appropriate.
• For unconjugated hyperbilirubinemia, treatment may include phototherapy for severe cases, addressing hemolysis if present, or discontinuing medications that impair bilirubin conjugation, with the timing of intervention guided by serial measurements of total serum/plasma bilirubin (TSB) concentrations and screening for the presence of intrinsic risk factors for bilirubin neurotoxicity 1.
• For conjugated hyperbilirubinemia, management focuses on treating the underlying liver disease, biliary obstruction, or infection, which may involve endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC) to relieve biliary obstruction, or specific treatments for autoimmune hepatitis or primary biliary cholangitis.

Phototherapy Guidelines

• Phototherapy is prescribed for treating neonatal hyperbilirubinemia and is performed by exposing newborn infants to light in the blue-green wavelength range, preferably at an optimal peak of 478 nm and at an irradiance of 25 to 35 mW/cm2/nm to at least 1 surface of the body (ventral or dorsal) 1.
• Intensive phototherapy is recommended at the thresholds based on gestational age, neurotoxicity risk factors, and age of the infant in hours, with the decision to discontinue phototherapy individualized based on the TSB level at which phototherapy was initiated, the cause of the hyperbilirubinemia, and the risk of rebound hyperbilirubinemia 1.

Supportive Care

• Supportive care includes maintaining hydration and nutritional support, with some infants who are admitted with high bilirubin levels and are mildly dehydrated potentially benefiting from supplemental fluid intake to correct their dehydration, using a milk-based formula to inhibit the enterohepatic circulation of bilirubin 1.
• Monitoring for complications like hepatic encephalopathy is also crucial, with serial bilirubin measurements obtained to assess treatment response, and the frequency determined by the severity of elevation and clinical condition.

From the Research

Management Approach for Elevated Total Bilirubin

The management approach for a patient with elevated total bilirubin (hyperbilirubinemia) involves several strategies, including:

• Phototherapy: a common treatment for neonatal jaundice, which helps to reduce the levels of bilirubin in the blood 2
• Exchange transfusion: a procedure that involves replacing the baby's blood with donor blood to reduce the levels of bilirubin 3, 2
• Pharmacological therapies: such as metalloporhyrins, clofibrate, bile salts, laxatives, and bilirubin oxidase, which may help to decrease the plasma concentration of unconjugated bilirubin (UCB) 3
• Monitoring: regular monitoring of bilirubin levels and assessment of risk factors for bilirubin-related neurotoxicity 2, 4

Risk Factors and Prevention

Certain risk factors can increase the likelihood of kernicterus, a serious complication of hyperbilirubinemia, including:

• Premature birth: premature infants are at higher risk of kernicterus due to their immature liver and higher levels of bilirubin 4, 5
• Hemolytic diseases: conditions such as Rh disease can lead to high levels of bilirubin and increase the risk of kernicterus 5
• Low birth weight: infants with low birth weight are at higher risk of kernicterus due to their smaller liver and higher levels of bilirubin 5

Diagnostic Methods

Several analytical methods are available for measuring bilirubin and its metabolites in serum, urine, and feces, including:

• Diazo transfer reaction: the gold-standard method for measuring serum bilirubin 6
• High-performance liquid chromatography (HPLC): a method that can separate and quantify different types of bilirubin 6
• Oxidative, enzymatic, and chemical methods: alternative methods for measuring bilirubin levels 6
• Direct spectrophotometry: a method that measures the absorption of light by bilirubin 6
• Transcutaneous methods: non-invasive methods that measure bilirubin levels through the skin 6