Outcomes of Acetaminophen Poisoned Patients Treated with and Without Fomepizole: A ToxIC Core Registry Study

Introduction: Acute acetaminophen poisoning remains the leading cause of acute hepatic failure in the country. Fomepizole has been suggested to improve outcomes in case reports involving acetaminophen-poisoned patients. The purpose of this study is to evaluate if fomepizole impacts mortality and other clinical outcomes in acetaminophen-poisoned patients seen at the bedside by medical toxicology physicians. Methods: This was a secondary analysis of cases reported to the Toxicology Investigators Consortium (ToxIC) Core Registry between January 1, 2010, and October 28, 2024. Mono-substance, acetaminophen-poisoned patients managed with NAC therapy were identified. Patients were excluded if they were reported to have a chronic or parenteral acetaminophen exposure or did not receive NAC therapy. Patients were then stratified into two groups: NAC therapy alone (NAC), or NAC therapy in combination with fomepizole (NAC+4MP). The primary outcome of the study was in-hospital mortality. Other secondary clinical endpoints were also collected. Results: Cases of acute acetaminophen poisoning managed with NAC therapy (n = 3789) were identified and divided into two cohorts: the NAC cohort (n = 3665) and the NAC+4MP cohort (n = 124). Overall, mortality was higher with combination therapy compared with NAC monotherapy (OR 3.59, P = 0.01 [95% CI (1.23, 8.67)]). Metabolic acidosis, AST/ALT > 1000, coagulopathy, vitamin K use, vasopressor use, transfusion, and renal replacement therapy use were also more common in the combination group. Conclusion: In this large observational database study of acetaminophen poisoning, use of fomepizole and NAC therapy was not associated with improved mortality.