Overdose pattern and outcome in paracetamol-induced acute severe hepatotoxicity |
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Authors: | Craig Darren G N Bates Caroline M Davidson Janice S Martin Kirsty G Hayes Peter C Simpson Kenneth J |
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Institution: | 1Scottish Liver Transplantation Unit, Royal Infirmary of Edinburgh, Little France, Edinburgh EH16 4SA, UK;2Division of Clinical and Surgical Sciences, University of Edinburgh, Edinburgh, UK |
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Abstract: | AIMSParacetamol (acetaminophen) hepatotoxicity is the commonest cause of acute liver failure (ALF) in the UK. Conflicting data regarding the outcomes of paracetamol-induced ALF resulting from different overdose patterns are reported.METHODSUsing prospectively defined criteria, we have analysed the impact of overdose pattern upon outcome in a cohort of 938 acute severe liver injury patients admitted to the Scottish Liver Transplantation Unit.RESULTSBetween 1992 and 2008, 663 patients were admitted with paracetamol-induced acute severe liver injury. Of these patients, 500 (75.4%) had taken an intentional paracetamol overdose, whilst 110 (16.6%) had taken an unintentional overdose. No clear overdose pattern could be determined in 53 (8.0%). Unintentional overdose patients were significantly older, more likely to abuse alcohol, and more commonly overdosed on compound narcotic/paracetamol analgesics compared with intentional overdose patients. Unintentional overdoses had significantly lower admission paracetamol and alanine aminotransferase concentrations compared with intentional overdoses. However, unintentional overdoses had greater organ dysfunction at admission, and subsequently higher mortality (unintentional 42/110 (38.2%), intentional 128/500 (25.6%), P < 0.001). The King''s College poor prognostic criteria had reduced sensitivity in unintentional overdoses (77.8%, 95% confidence intervals (CI) 62.9, 88.8) compared with intentional overdoses (89.9%, 95% CI 83.4, 94.5). Unintentional overdose was independently predictive of death or liver transplantation on multivariate analysis (odds ratio 1.91 (95% CI 1.07, 3.43), P= 0.032).CONCLUSIONSUnintentional paracetamol overdose is associated with increased mortality compared with intentional paracetamol overdose, despite lower admission paracetamol concentrations. Alternative prognostic criteria may be required for unintentional paracetamol overdoses. |
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Keywords: | acute drug-induced liver injury hepatic encephalopathy liver failure liver transplantation |
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