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Title: Paracetamol metabolite concentrations following low risk overdose treated with an abbreviated 12-h versus 20-h acetylcysteine infusion.
Austin Authors: Wong, Anselm Y ;Homer, Natalie;Dear, James W;Choy, Kay Weng;Doery, James;Graudins, Andis 
Affiliation: Monash Toxicology Unit and Emergency Medicine Service, Monash Health, Victoria, Australia
Department of Medicine, School of Clinical Sciences, Monash University, Victoria, Australia
Monash Pathology, Monash Health, Victoria, Australia
Austin Toxicology Service, Austin Health, Heidelberg, Victoria, Australia
Edinburgh Clinical Research Facility, Queen's Medical Research Institute, Edinburgh, UK
Pharmacology, Toxicology and Therapeutics, University/BHF Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, UK
Issue Date: 2019 2018-11-19
Publication information: Clinical toxicology (Philadelphia, Pa.) 2019; 57(5): 312-317
Abstract: To compare degree of liver injury and paracetamol metabolite concentrations after treatment with standard of care (20-h) vs. abbreviated (12-h) acetylcysteine regimens used in paracetamol overdose (NACSTOP trial). Timed blood samples from a cohort of subjects enrolled in the cluster-controlled NACSTOP trial evaluating a 12-h acetylcysteine regimen (200 mg/kg over 4 h, 50 mg/kg over 8 h) were assayed for paracetamol metabolites as a pilot study, using liquid chromatography/mass spectrometry. Control group subjects received a 20-h course of acetylcysteine (200 mg/kg over 4 h, 100 mg/kg over 16 h). The intervention group received a 12-h acetylcysteine regimen (stopped after at least 12 h of treatment). Positive control groups not in the trial with acute liver injury (ALI) or hepatotoxicity were also studied. One hundred and forty-one blood samples were collected from 40 patients receiving acetylcysteine after paracetamol overdose. Median ALT after 20 h of acetylcysteine was 12 U/L (IQR 8.14) in the abbreviated regimen group, compared to the control group 16 U/L (IQR 11.21) (p = .46). There was no significant difference in median metabolite concentrations on presentation and after 20 h of acetylcysteine between these two groups (p > .05). Presentation median sum CYP-metabolite/total metabolite percentages were 2.5 and 3.0 in the abbreviated and control NACSTOP groups, respectively. An abbreviated 12-h acetylcysteine regimen for paracetamol overdose used in the NACSTOP trial had similar circulating metabolite concentrations compared to a 20-h regimen in selected subjects with low risk of hepatotoxicity. This suggests that further acetylcysteine may not be needed in the abbreviated group at time of cessation.
DOI: 10.1080/15563650.2018.1517881
ORCID: 0000-0002-6817-7289
PubMed URL: 30453788
Type: Journal Article
Subjects: Acetaminophen
Appears in Collections:Journal articles

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