False-Positive Elevation of Blood Gas Bilirubin in a Patient With Mixed Drug Overdose Involving Pregabalin and Diazepam Abuse

Bilirubin measurements are commonly performed using a blood gas analyzer and are particularly useful in managing neonatal hyperbilirubinemia. This report presents a case of a white British man in his 40s who was treated for a mixed drug overdose involving cocaine, mirtazapine, fentanyl, codeine, methadone, morphine, and diazepam. His bilirubin levels measured on the blood gas analyzer were elevated at 63 µmol/L, whereas the normal range is 1.71-20.5 µmol/L. However, a formal laboratory bilirubin test returned a normal value of 21 µmol/L. Given the absence of jaundice or signs of liver disease, the unexpectedly high bilirubin reading on the blood gas analyzer prompted further investigation. Laboratory analysis involved scanning the absorbance of three serum samples received on the same day and comparing them with the absorbance of the blood gas analyzer. A significant peak at approximately 400 nm was detected in the first sample, corresponding to the wavelengths used for blood gas bilirubin measurement. Native bilirubin exhibits a broad absorbance spectrum between 350 and 500 nm, overlapping with the absorbance spectra of diazepam and pregabalin. This interference likely contributed to the false-positive bilirubin elevation. Currently, little is known about the relationship between false-positive bilirubin elevations and drugs of abuse. This case highlights potential causes of isolated bilirubin elevation, particularly interference from substances with overlapping absorbance spectra. While the interference is suspected, it has not been definitively proven. The findings underscore the limitations of arterial blood gas analysis and the potential for interference from other substances, particularly drugs of abuse. Clinicians should exercise caution when interpreting blood gas bilirubin concentrations in patients with a history of substance misuse. Consulting the laboratory is advisable when encountering unexpected discrepancies in bilirubin levels.