What is the next step in managing elevated total bilirubin (hyperbilirubinemia)?

From the Guidelines

The next step in managing elevated total bilirubin is to determine the cause through additional testing, starting with fractionated bilirubin levels to distinguish between unconjugated and conjugated hyperbilirubinemia. This approach is crucial as it guides the subsequent diagnostic workup and management strategy. For instance, if the hyperbilirubinemia is predominantly unconjugated, the focus should be on evaluating for hemolysis with tests such as complete blood count, peripheral smear, reticulocyte count, haptoglobin, and LDH, as suggested by 1. On the other hand, if the hyperbilirubinemia is predominantly conjugated, obtaining liver function tests including ALT, AST, alkaline phosphatase, and GGT, along with hepatitis serologies and abdominal ultrasound to assess for biliary obstruction, is recommended, as indicated by 1 and 1.

Key considerations in the management of elevated total bilirubin include:

• Avoiding hepatotoxic medications and alcohol while awaiting test results
• Prompt referral to a hepatologist for severe elevations (total bilirubin >10 mg/dL) or signs of liver failure
• Reassurance for patients with Gilbert syndrome, a benign condition characterized by mild unconjugated hyperbilirubinemia, as noted in 1
• Potential need for ERCP or surgical intervention for obstructive causes, and specific treatments depending on the etiology for hepatocellular causes, as discussed in 1 and 1

The importance of identifying the underlying mechanism of bilirubin elevation cannot be overstated, as it directly influences the choice of treatment and significantly impacts patient outcomes in terms of morbidity, mortality, and quality of life. Therefore, a thorough and guided approach to diagnosing the cause of hyperbilirubinemia is essential in clinical practice, as supported by the guidelines and recommendations provided in 1, 1, and 1.

From the Research

Managing Elevated Total Bilirubin

The next step in managing elevated total bilirubin (hyperbilirubinemia) involves:

• Careful history and physical examination to identify underlying causes of jaundice 2
• Directed imaging of the biliary tree and liver to evaluate the cause of hyperbilirubinemia 2
• Assessment of bilirubin concentrations as part of routine liver function testing to determine the type of hyperbilirubinemia (unconjugated or conjugated) 3
• Consideration of laboratory error or interference from certain medications, such as naproxen or ceftriaxone, which can cause elevated bilirubin levels 4, 5

Diagnostic Considerations

Diagnostic criteria for hyperbilirubinemia include:

• Evaluation of bilirubin levels and liver function tests to determine the underlying cause of hyperbilirubinemia 2, 3
• Consideration of conditions such as Gilbert's syndrome, which can cause mildly elevated unconjugated bilirubin levels 3
• Assessment of hemolysis, biliary stasis, and hepatic dysfunction to rule out other causes of hyperbilirubinemia 4

Special Considerations

In certain populations, such as neonates, the management of hyperbilirubinemia may involve:

• Measurement of end-tidal CO levels to identify ongoing hemolysis and assess the risk of bilirubin-induced neurological dysfunction (BIND) 6
• Use of point-of-care devices to measure ETCOc levels and identify hemolysis-associated hyperbilirubinemia in newborns 6