Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2021 Jul;17(3):241-249.
doi: 10.1007/s13181-021-00822-x. Epub 2021 Apr 21.

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

Regan A Baum  1 , Jordan A Woolum  2 , Abby M Bailey  2 , Molly M Howell  3 , Kyle A Weant  4 , LeeAnn Geraghty  5 , Sanjay Mohan  6   7 , Ashley N Webb  8 , Mark K Su  6   7 , Peter Akpunonu  8   9 ; Collaborators
Collaborators, Affiliations
Multicenter Study

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

Regan A Baum et al. J Med Toxicol. 2021 Jul.

Abstract

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.

Keywords: Acetaminophen; N-acetylcysteine; Obesity; Overdose; Toxicity.

PubMed Disclaimer

Conflict of interest statement

None.

Figures

Fig. 1
Fig. 1
Dosing of N-acetylcysteine in acetaminophen overdose. Comparison of potential total dosage received dependent on dosing strategy.
Fig. 2
Fig. 2
Highest liver enzyme levels.
See this image and copyright information in PMC

Comment in

References

    1. Mowry JB, Spyker DA, Cantilena LR, Jr, McMillan N, Ford M. 2013 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 31st Annual Report. Clin Toxicol (Phila). 2014;52(10):1032–1283. doi: 10.3109/15563650.2014.987397. - DOI - PMC - PubMed
    1. Hoffman RS, Howland MA, Lewin NA, Nelson L, Goldfrank LR, Flomenbaum N, Access Pharmacy, and Access Emergency Medicine. Goldfrank's Toxicologic Emergencies. Tenth ed. New York: McGraw-Hill; 2015.
    1. Rumack BH, Bateman DN. Acetaminophen and acetylcysteine dose and duration: past, present and future. Clin Toxicol (Phila). 2012;50(2):91–98. doi: 10.3109/15563650.2012.659252. - DOI - PubMed
    1. Vale JA, Meredith TJ, Crome P, Helliwell M, Volans GN, Widdop B, Goulding R. Intravenous N-acetylcysteine: the treatment of choice in paracetamol poisoning? Br Med J. 1979;2(6202):1435–1436. doi: 10.1136/bmj.2.6202.1435. - DOI - PMC - PubMed
    1. Smilkstein MJ, Knapp GL, Kulig KW, Rumack BH. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985) N Engl J Med. 1988;319(24):1557–1562. doi: 10.1056/NEJM198812153192401. - DOI - PubMed

Publication types