Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/22448
Title: Adducts Post Acetaminophen Overdose Treated with a 12-Hour vs 20-Hour Acetylcysteine Infusion.
Austin Authors: Wong, Anselm Y ;Heard, Kennon;Graudins, Andis ;Dart, Richard;Sivilotti, Marco L A
Affiliation: Section of Medical Pharmacology and Toxicology, Department of Emergency Medicine, University of Colorado, Aurora, CO, USA
Austin Toxicology Service, Austin Health, Heidelberg, Victoria, Australia
Departments of Emergency Medicine, and of Biomedical & Molecular Sciences, Queen's University, Kingston, Ontario, Canada
Victorian Poisons Information Centre, Austin Health, Heidelberg, Victoria, Australia
Rocky Mountain Poison and Drug Center, Denver Health and Hospitals, Denver, CO, USA
Monash Toxicology Service, Monash Health, School of Clinical Sciences, Department of Medicine, Monash University, Melbourne, Victoria, Australia
Rocky Mountain Poison and Drug Center, Denver Health and Hospital Authority, Denver, CO, USA
School of Clinical Sciences, Department of Medicine, Monash University, Melbourne, Victoria, Australia
Centre for Integrated Critical Care, University of Melbourne, Melbourne, Victoria, Australia
Issue Date: Apr-2020
metadata.dc.date: 2020-01-14
Publication information: Journal of medical toxicology 2020; 16(2): 188-194
Abstract: 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. 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. 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). 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.
URI: http://ahro.austin.org.au/austinjspui/handle/1/22448
DOI: 10.1007/s13181-020-00757-9
ORCID: 0000-0002-6817-7289
PubMed URL: 31939054
Type: Journal Article
Subjects: Acetaminophen
Acetylcysteine
NAC
Paracetamol
Poisoning
Appears in Collections:Journal articles

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