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Title: Outcomes from massive paracetamol overdose: a retrospective observational study
Austin Authors: Marks, Daniel JB;Dargan, Paul I;Archer, John R H;Davies, Charlotte L;Dines, Alison M;Wood, David M;Greene, Shaun L 
Affiliation: Department of Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust and King's Health Partners, London, UK
Department of Clinical Pharmacology, University College London, London, UK
Faculty of Life Sciences and Medicine, King's College London, London, UK
Austin Toxicology Service, Austin Health, Heidelberg, Victoria, Australia
Victorian Poisons Information Centre, Austin Health, Heidelberg, Victoria, Australia
Issue Date: Jun-2017
Date: 2017-01-25
Publication information: British Journal of Clinical Pharmacology 2017; 83(6): 1263-1272
Abstract: AIMS: Treatment of paracetamol (acetaminophen) overdose with acetylcysteine is standardized, with dose determined only by patient weight. The validity of this approach for massive overdoses has been questioned. We systematically compared outcomes in massive and non-massive overdoses, to guide whether alternative treatment strategies should be considered, and whether the ratio between measured timed paracetamol concentrations (APAPpl ) and treatment nomogram thresholds at those time points (APAPt ) provides a useful assessment tool. METHODS: This is a retrospective observational study of all patients (n = 545) between 2005 and 2013 admitted to a tertiary care toxicology service with acute non-staggered paracetamol overdose. Massive overdoses were defined as extrapolated 4-h plasma paracetamol concentrations >250 mg l-1 , or reported ingestions ≥30 g. Outcomes (liver injury, coagulopathy and kidney injury) were assessed in relation to reported dose and APAPpl :APAPt ratio (based on a treatment line through 100 mg l-1 at 4 h), and time to acetylcysteine. RESULTS: Ingestions of ≥30 g paracetamol correlated with higher peak serum aminotransferase (r = 0.212, P < 0.0001) and creatinine (r = 0.138, P = 0.002) concentrations. Acute liver injury, hepatotoxicity and coagulopathy were more frequent with APAPpl :APAPt ≥ 3 with odds ratios (OR) and 95% confidence intervals (CI) of 9.19 (5.04-16.68), 35.95 (8.80-158.1) and 8.34 (4.43-15.84), respectively (P < 0.0001). Heightened risk persisted in patients receiving acetylcysteine within 8 h of overdose. CONCLUSION: Patients presenting following massive paracetamol overdose are at higher risk of organ injury, even when acetylcysteine is administered early. Enhanced therapeutic strategies should be considered in those who have an APAPpl :APAPt ≥ 3. Novel biomarkers of incipient liver injury and abbreviated acetylcysteine regimens require validation in this patient cohort.
DOI: 10.1111/bcp.13214
Journal: British Journal of Clinical Pharmacology
PubMed URL:
Type: Journal Article
Subjects: Acetylcysteine
Appears in Collections:Journal articles

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