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

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. 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. 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. 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.