Acetaminophen psi parameter: a useful tool to quantify hepatotoxicity risk in acute acetaminophen overdose

Abstract

Context.The risk of hepatotoxicity secondary to acute acetaminophen overdose is related to serum acetaminophen concentration and lag time from ingestion to N-acetylcysteine (NAC) therapy. Psi (Greek letter ψ) is a toxicokinetic parameter that takes the acetaminophen level at 4 h post-ingestion ([APAP]4 h)and the time-to-initiation of NAC (tNAC) into account and was found to be significantly predictive of hepatotoxicity in Canadian patients with acetaminophen overdose treated with intravenous NAC. Objective. We report the relationship of psi and hepatotoxicity in a Thai population with acute acetaminophen overdose. Methods. This is a retrospective study of patients with acute paracetamol overdose during January 2004 to June 2009 at Siriraj Hospital. Patients were treated with the standard 21-h intravenous NAC regimen. Univariate analyses were performed with logistic regression to assess the relationships of psi, [APAP]4 h, and tNAC, and hepatotoxicity. Results. A total of 127 patients were enrolled. The median (interquartile range; IQR) of [APAP]4 h was 267.8 (196.0-380.0) mg/L. The median (IQR) of tNAC was 8.5 (6.2-12.0) h. Thirteen patients (10.2%) developed hepatotoxicity. Univariate analysis revealed [APAP]4 h, tNAC, and psi as statistically significant predictors of hepatotoxicity. Discussion and conclusion. The psi parameter is a reliable prognostic tool to predict hepatotoxicity secondary to acute acetaminophen overdose treated with intravenous NAC. Our evidence shows that psi may be a more superior tool than either acetaminophen level or time-toinitiation of NAC at predicting hepatotoxicity.