Evaluation of Dosing Strategies of N-acetylcysteine for Acetaminophen Toxicity in Patients Greater than 100 Kilograms: Should the Dosage Cap Be Used?

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Introduction: Acetaminophen is a commonly used analgesic and antipyretic, with the potential to cause significant injury when ingested in toxic amounts. Although the antidote n-acetylcysteine (NAC) is available, evidence supporting dose recommendations for patients weighing over 100 kg are lacking. We performed a retrospective, multi-center analysis to determine if a capped NAC dosing scheme is similar to a non-capped dosing scheme in patients weighing over 100 kg. Methods: Between January 2009 and January 2016, we identified patients presenting to 12 different centers who were evaluated for acetaminophen poisoning treatment. Patients must have weighed greater than 100 kg and were evaluated and identified as needing treatment for acetaminophen-related poisoning with NAC. The primary outcome was occurrence of hepatic injury, defined as an AST or ALT ≥ 100 IU/L. Secondary endpoints included number of drug-related adverse events, occurrence of hepatotoxicity, cumulative NAC dose, regimen cost, length of hospital and intensive care unit stays, and in-hospital mortality. Results: There were 83 patients identified as meeting the pre-specified inclusion and exclusion criteria. A capped NAC dosing scheme resulted in no difference in hepatic injury when compared to a non-capped regimen (49.4% vs 50%, p = 1.000). The capped dosage regimen was associated with a lower cumulative dose (285.2 mg/kg vs 304.6 mg/kg, p < 0.001) and cost. No other statistically significant differences were identified among the secondary endpoints. Conclusion: A capped NAC dosing scheme was not associated with higher rates of hepatic injury or hepatotoxicity in obese patients in the setting of acetaminophen poisoning when compared to a non-capped regimen. Further research is needed to verify these results.

Original languageEnglish
Pages (from-to)241-249
Number of pages9
JournalJournal of Medical Toxicology
Issue number3
StatePublished - Jul 2021

Bibliographical note

Funding Information:
Study data were collected by investigators at each site and managed using the REDCap (Research Electronic Data Capture) electronic data capture tools hosted at the University of Kentucky. This is a secure, web-based application designed to support data capture for research studies. REDCap was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant 8UL1TR000117-02. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH [].

Publisher Copyright:
© 2021, American College of Medical Toxicology.


  • Acetaminophen
  • N-acetylcysteine
  • Obesity
  • Overdose
  • Toxicity

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis


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