ArticleJournal of medical toxicology : official journal of the American College of Medical Toxicology2020
Adducts Post Acetaminophen Overdose Treated with a 12-Hour vs 20-Hour Acetylcysteine Infusion.
Article in Journal of medical toxicology : official journal of the American College of Medical Toxicology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
5 authors at 4 institutions in 3 countries.
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No grant is acknowledged in the PubMed record.
Abstract
introductionAcetaminophen 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.
methodsWe 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.
resultsMedian 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).
conclusionsThere 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.
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