N-Acetylcysteine Dose and Treatment Duration in High-Risk Acetaminophen Ingestions Treated Within Eight Hours: A Retrospective Cohort Study.

Abstract

INTRODUCTION: Toxicologists may use high dose n-acetylcysteine (HD-NAC) for early-treated high-risk acetaminophen ingestions (EHRAI) given concerns over standard NAC (S-NAC) dosing’s efficacy. We utilize the novel, clinically relevant outcome of mean additional 16-hour NAC maintenance infusions (NMI) to evaluate differences in treatment duration for EHRAI patients treated with S-NAC versus HD-NAC. METHODS: Retrospective multistate poison center study from 1/1/2019-7/4/2024 of patients ≥ 13-years-old who were treated with S-NAC or HD-NAC within eight hours of a high-risk acetaminophen ingestion. The primary outcome was mean additional NMI. Secondary outcomes were NAC infusion duration, hepatotoxicity, coagulopathy, transplant, and death. Sensitivity analyses evaluated for robustness of findings. RESULTS: Of 127 included cases, 52.0% (66/127) received HD-NAC. 7.1% (9/127) had anti-peristaltic co-ingestions. HD-NAC cases received more fomepizole (23.1% versus 1.6%; difference 21.1%). Acetaminophen concentrations controlled for time since ingestion were similar (mean acetaminophen ratio for HD-NAC: 2.7, IQR: 2.3, 3.3 versus S-NAC: 2.4, IQR: 2.2, 2.7; difference − 0.3). 26.0% (33/127) received NMI solely for residual detectable serum acetaminophen. There was no difference in mean additional NMI (HD-NAC: 0.53 versus S-NAC: 0.38; p = 0.240). Median NAC infusion durations were equal across groups (21.0; IQR: 21.0, 37.0; difference 0.0) (p = 0.137). One patient per group developed hepatotoxicity; there were no transplants or deaths. Sensitivity analyses yielded similar results. CONCLUSIONS: We found no difference in mean NMI for EHRAI based on NAC dose. These findings support additional NMI as an objective, common, clinically relevant outcome for acetaminophen toxicity research.