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Adducts Post Acetaminophen Overdose Treated with a 12-Hour vs 20-Hour Acetylcysteine Infusion

  • Anselm WongEmail author
  • Kennon Heard
  • Andis Graudins
  • Richard Dart
  • Marco L. A. Sivilotti
Original Article

Abstract

Introduction

Acetaminophen protein adducts in the circulation are a specific biomarker of acetaminophen oxidation, and may be a more sensitive measure of impending hepatic injury following overdose than alanine transaminase (ALT). We performed an exploratory analytical substudy of adducts during a clinical trial (NACSTOP) of abbreviated (12-hour) versus control (20-hour) acetylcysteine to identify any signal of diminished antidotal effectiveness with shortened therapy.

Methods

We measured adducts at 0, 12, and 20 hours from a convenience sample of subjects enrolled in the cluster-controlled NACSTOP trial evaluating a 12-hour (“abbreviated”; 200 mg/kg over 4 hours, 50 mg/kg over 8 hours) vs 20-hour acetylcysteine regimen (“control”; 200 mg/kg over 4 hours, 100 mg/kg over 16 hours). Adducts were assayed using high-performance liquid chromatography/mass spectrometry.

Results

Median ALT 20 hours after the initiation of acetylcysteine was 12 U/L (IQR 8,14) in the abbreviated 12-hour regimen group (N = 8), compared with the control group 16 U/L (IQR 11,21; N = 21) (p = 0.46). Adduct concentrations were similarly low in both groups: abbreviated [(0.005 μmol/L, IQR (0,0.14)] and control [(0.005 μmol/L, IQR (0,0.05)] (p = 0.61).

Conclusions

There were minimal to no acetaminophen protein adducts detected. These findings further support discontinuing acetylcysteine when acetaminophen concentrations are low and liver function tests normal after 12 hours of treatment.

Keywords

Acetaminophen Paracetamol NAC Acetylcysteine Poisoning 

Notes

Compliance with Ethical Standards

Fully informed consent from participants was obtained to participate in the study. Ethics approval was obtained from the Monash Health Ethics Research Committee.

Conflicts of Interest

None.

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Copyright information

© American College of Medical Toxicology 2020

Authors and Affiliations

  1. 1.School of Clinical Sciences, Department of MedicineMonash UniversityMelbourneAustralia
  2. 2.Centre for Integrated Critical CareUniversity of MelbourneMelbourneAustralia
  3. 3.Victorian Poisons Information Centre and Austin Toxicology Service, Austin HospitalHeidelbergAustralia
  4. 4.Rocky Mountain Poison and Drug Center, Denver Health and HospitalsDenverUSA
  5. 5.Section of Medical Pharmacology and Toxicology, Department of Emergency MedicineUniversity of ColoradoAuroraUSA
  6. 6.Monash Toxicology Service, Monash Health, School of Clinical Sciences, Department of MedicineMonash UniversityMelbourneAustralia
  7. 7.Rocky Mountain Poison and Drug Center, Denver Health and Hospital AuthorityDenverUSA
  8. 8.Departments of Emergency Medicine, and of Biomedical & Molecular SciencesQueen’s UniversityKingstonCanada

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