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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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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.

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Acknowledgements

Collaborators:

A. J. Dugan, L. Atchison, K. M. DeWitt, M. K. Doolin, M. A. Howland, E. Lingenfelter, T. Neitzel, C. Sloan, P. Wong

Funding

REDCap used in this study 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. There was no additional funding to support this study.

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Authors and Affiliations

  1. Department of Pharmacy Services, University of Kentucky HealthCare, 800 Rose Street, H112, Lexington, KY, 40536-2093, USA

    Regan A. Baum, Jordan A. Woolum & Abby M. Bailey

  2. Pharmacy Department, Eskenazi Health, 720 Eskenazi Avenue, Indianapolis, IN, 46202, USA

    Molly M. Howell

  3. Department of Clinical Pharmacy and Outcome Sciences, College of Pharmacy, University of South Carolina, Columbia, South Carolina 715 Sumter Street – CLS, Columbia, SC, 29208, USA

    Kyle A. Weant

  4. Department of Pharmacy, Norton Cancer Institute, 676 South Floyd Street, Louisville, Kentucky, 40202, USA

    LeeAnn Geraghty

  5. Ronald O. Perelman Department of Emergency Medicine, New York University Grossman School of Medicine, 462 First Avenue, Room A340A, New York, NY, 10016, USA

    Sanjay Mohan & Mark K. Su

  6. Kentucky Poison Control Center, Norton Children’s Hospital, PO Box 35070, Louisville, KY, 40232-5070, USA

    Ashley N. Webb & Peter Akpunonu

  7. New York City Poison Control Center, 455 1st Avenue, Room 123, New York, NY, 10016, USA

    Sanjay Mohan & Mark K. Su

  8. Department of Emergency Medicine, University of Kentucky-Chandler Medical Center, 800 Rose Street, Lexington, KY, USA

    Peter Akpunonu

Authors
  1. Regan A. Baum
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  2. Jordan A. Woolum
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  4. Molly M. Howell
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  7. Sanjay Mohan
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  8. Ashley N. Webb
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Consortia

Collaborators

  • Adam J. Dugan
  • , Leanne Atchison
  • , Kyle M. DeWitt
  • , Meagan K. Doolin
  • , Mary Ann Howland
  • , Erin Lingenfelter
  • , Tara Neitzel
  • , Cole Sloan
  •  & Paul Wong

Contributions

• All authors contributed to the study conception and design.

• Material preparation, data collection, and analysis were performed by Regan Baum, Abby Bailey, Molly Howell, Kyle Weant, Sanjay Mohan, LeeAnn Geraghty, Leanne Atchison, Kyle DeWitt, Meagan Doolin, Adam Dugan, Erin Lingenfelter, Sanjay Mohan, Tara Neitzel, Cole Sloan, and Paul Wong.

• The first draft of the manuscript was written by Regan Baum, LeeAnn Geraghty, Ashley Webb, Molly Howell Abby Bailey, Kyle Weant, and Peter Akpunonu.

• All authors commented on previous versions of the manuscript. Formatting, feedback, and revisions are performed by Regan Baum, Abby Bailey, Kyle Webb, Jordan Woolum, Sanjay Mohan, Mark Su, and Peter Akpunonu.

All authors read and approved the final manuscript.

Corresponding author

Correspondence to Regan A. Baum.

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Supervising Editor: Maryann Amirshahi, PharmD, MD, MPH, PhD

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Baum, R.A., Woolum, J.A., Bailey, A.M. et al. Evaluation of Dosing Strategies of N-acetylcysteine for Acetaminophen Toxicity in Patients Greater than 100 Kilograms: Should the Dosage Cap Be Used?. J. Med. Toxicol. 17, 241–249 (2021). https://doi.org/10.1007/s13181-021-00822-x

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  • DOI: https://doi.org/10.1007/s13181-021-00822-x

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