Multiplying the serum aminotransferase by the acetaminophen concentration to predict toxicity following overdose

Abstract

Context. The first available predictors of hepatic injury following acetaminophen (APAP) overdose are the serum APAP and aminotransferases [AT, i.e., aspartate (AST) aminotransferase or alanine (ALT) aminotransferase]. Objective. We describe the initial value, rate of change, and interrelationship between these biomarkers in patients who develop hepatotoxicity despite treatment following acute overdose. A new parameter, the APAP × AT multiplication product, is proposed for early risk stratification. Methods. We conducted a descriptive study of individuals selected from a multicenter retrospective cohort of patients hospitalized for APAP poisoning. We selected those acute APAP overdose patients who subsequently developed AT  > 1,000 IU/L. Rising serum AT values were compared to simultaneously measured (or estimated) falling serum APAP. The APAP × AT was expressed relative to initiation of acetylcysteine therapy and grouped by time to meeting hepatotoxicity criteria. Results. In the 94 cases studied, serum APAP concentrations were still appreciable [median 570 (interquartile range (IQR) 314–983) μmol/L] at the time of the first measured AT [211 (77–511) IU/L at 15.3 (12.1–19.2) h post-ingestion], yielding an initial APAP × AT of 99,000 (52,000–240,000) μmol × IU/L². Because serum AT rose rapidly (doubling time 9.5 h ) and APAP fell slowly (half-life 4.8 h), the multiplication product remained elevated during the first 12–24 h of antidotal therapy, especially among patients who developed earlier hepatotoxicity (AT > 1,000 IU/L). Discussion and conclusions. The APAP × AT multiplication product, calculated at the time of presentation and after several h of antidotal therapy, holds promise as a new risk predictor following APAP overdose. It requires neither graphical interpretation nor accurate time of ingestion, two limitations to current risk stratification.

• Acetaminophen
• N-Acetylcysteine
• Transaminase
• Aspartate aminotransferase
• Alanine aminotransferase

Notes

Molar units are used for APAP throughout. To convert from μg/mL or mg/L to μmol/L, divide by the molecular weight of 0.15 g/mmol. Thus, the 150 μg/mL treatment line on the Rumack–Matthew nomogram corresponds to 1,000 μmol/L.