False positive acetaminophen levels associated with hyperbilirubinemia.

Serum acetaminophen determination is frequently necessary in patients with hepatic failure. We observed two patients (#1, #2) with elevated serum total bilirubin levels (26.5 mg/dL and 40.1 mg/dL) who had multiple false positive acetaminophen levels using the kinetic method of the GDS Diagnostics enzymatic acetaminophen assay (GDS Diagnostics, Elkhart, IN). We investigated the magnitude, threshold, and linearity of this effect using the GDS Diagnostics assay and an EMIT acetaminophen assay on two other hyperbilirubinemic patients (#3, #4) and a commercial solubilized bilirubin standard. Samples were diluted using fresh frozen plasma, and acetaminophen levels were analyzed twice using the kinetic method of the GDS Diagnostic acetaminophen assay and twice with the EMIT assay. The absence of acetaminophen in all samples was verified by gas chromatography/mass spectroscopy (GC/MS). The kinetic GDS assay resulted in a positive acetaminophen assay (cutoff for a positive result= 10 mg/L) with patient #3, patient #4, and in the bilirubin standard when the total bilirubin levels were 28.2 mg/dL, 22.5 mg/dL, and 18.3 mg/dL, respectively. One sample was interpolated to give a positive acetaminophen reading when diluted to a total bilirubin concentration of 15 mg/L. None of the samples tested with GC/MS or the EMIT assay resulted in any detectable acetaminophen. In conclusion, caution must be taken utilizing the GDS Diagnostic assay for the quantification of acetaminophen with concomitant hyperbilirubinemia. Alternatives such as EMIT or GC/MS should be employed to assess acetaminophen levels in such patients.