Augmenting the sensitivity for hepatotoxicity prediction in acute paracetamol overdose: combining psi (ψ) parameter and paracetamol concentration aminotransferase activity multiplication product

Abstract

Introduction: While factors like high serum paracetamol (acetaminophen) concentration and delayed acetylcysteine treatment increase hepatotoxicity risk, existing predictive tools, such as the paracetamol concentration aminotransferase activity multiplication product and the psi (ψ) parameter, lack definitive accuracy. This study evaluated the paracetamol psi parameter multiplication product addition against the psi parameter and the paracetamol concentration aminotransferase activity multiplication product for predicting hepatotoxicity following an acute paracetamol overdose. Methods: A retrospective analysis of patients with acute paracetamol overdose from January 2007 to December 2016 was conducted. The paracetamol psi parameter multiplication product addition, calculated by summing the psi parameter (mmol/L × h) and the paracetamol concentration aminotransferase activity multiplication product (g U/L2), was used. Hepatotoxicity was defined as aspartate or alanine aminotransferase activities ≥1,000 U/L. Diagnostic accuracy was assessed through sensitivity, specificity, the area under the receiver operating characteristic curve, and their corresponding 95% CI, with the optimal cutoff determined using the maximum Youden index method. Results: The study comprised 421 patients, mostly female (82.9%) with a median age of 23 years. Hepatotoxicity occurred in 13.5% (57 patients). The paracetamol psi parameter multiplication product addition showed an area under the receiver operating characteristic curve of 0.989 (95% CI: 0.974–0.997), with an optimal cutoff at 9.723, providing 96.5% sensitivity and 97.3% specificity. The paracetamol psi parameter multiplication product addition demonstrated superior performance in area under the receiver operating characteristic curve compared to the individual assessments of the psi parameter (0.916; 95% CI: 0.885–0.941) and the paracetamol concentration aminotransferase activity multiplication product (0.901; 95% CI: 0.868–0.928). Discussion: The paracetamol psi parameter multiplication product addition appears to be a more effective diagnostic tool than the psi parameter or the paracetamol concentration aminotransferase activity multiplication product alone. Conclusion: Incorporating the paracetamol psi parameter multiplication product addition into clinical protocols could improve paracetamol overdose management by enabling precise identification of individuals at heightened risk for hepatotoxicity, thereby facilitating the customization of treatment approaches.