{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:45:01Z","timestamp":1787013901243,"version":"build-2736575974"},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,1,25]],"date-time":"2017-01-25T00:00:00Z","timestamp":1485302400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2017,6]]},"abstract":"\n LINKED ARTICLE<\/jats:title>\n \n This article is commented on by Bateman DN and Dear JW. Should we treat very large paracetamol overdose differently? Br J Clin Pharmacol 2017; 83: 1163\u20135.\n https:\/\/doi.org\/10.1111\/bcp.13279<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>\n \n Aims<\/jats:title>\n \n 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\u2010massive overdoses, to guide whether alternative treatment strategies should be considered, and whether the ratio between measured timed paracetamol concentrations (APAP\n pl<\/jats:sub>\n ) and treatment nomogram thresholds at those time points (APAP\n t<\/jats:sub>\n ) provides a useful assessment tool.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n This is a retrospective observational study of all patients (\n n<\/jats:italic>\n \u00a0=\u00a0545) between 2005 and 2013 admitted to a tertiary care toxicology service with acute non\u2010staggered paracetamol overdose. Massive overdoses were defined as extrapolated 4\u2010h plasma paracetamol concentrations >250\u00a0mg\u00a0l\n \u22121<\/jats:sup>\n , or reported ingestions \u226530\u00a0g. Outcomes (liver injury, coagulopathy and kidney injury) were assessed in relation to reported dose and APAP\n pl<\/jats:sub>\n :APAP\n t<\/jats:sub>\n ratio (based on a treatment line through 100\u00a0mg\u00a0l\n \u22121<\/jats:sup>\n at 4\u00a0h), and time to acetylcysteine.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Ingestions of \u226530\u00a0g paracetamol correlated with higher peak serum aminotransferase (\n r<\/jats:italic>\n \u00a0=\u00a00.212,\n P<\/jats:italic>\n \u00a0<\u00a00.0001) and creatinine (\n r<\/jats:italic>\n \u00a0=\u00a00.138,\n P<\/jats:italic>\n \u00a0=\u00a00.002) concentrations. Acute liver injury, hepatotoxicity and coagulopathy were more frequent with APAP\n pl<\/jats:sub>\n :APAP\n t<\/jats:sub>\n \u00a0\u2265\u00a03 with odds ratios (OR) and 95% confidence intervals (CI) of 9.19 (5.04\u201316.68), 35.95 (8.80\u2013158.1) and 8.34 (4.43\u201315.84), respectively (\n P<\/jats:italic>\n \u00a0<\u00a00.0001). Heightened risk persisted in patients receiving acetylcysteine within 8\u00a0h of overdose.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n 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 APAP\n pl<\/jats:sub>\n :APAP\n t<\/jats:sub>\n \u00a0\u2265\u00a03. Novel biomarkers of incipient liver injury and abbreviated acetylcysteine regimens require validation in this patient cohort.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/bcp.13214","type":"journal-article","created":{"date-parts":[[2016,12,21]],"date-time":"2016-12-21T17:51:27Z","timestamp":1482342687000},"page":"1263-1272","source":"Crossref","is-referenced-by-count":73,"title":["Outcomes from massive paracetamol overdose: a retrospective observational study"],"prefix":"10.1111","volume":"83","author":[{"given":"Daniel J. B.","family":"Marks","sequence":"first","affiliation":[{"name":"Department of Clinical Toxicology Guy's and St Thomas\u2019 NHS Foundation Trust and King's Health Partners London UK"},{"name":"Department of Clinical Pharmacology University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul I.","family":"Dargan","sequence":"additional","affiliation":[{"name":"Department of Clinical Toxicology Guy's and St Thomas\u2019 NHS Foundation Trust and King's Health Partners London UK"},{"name":"Faculty of Life Sciences and Medicine King's College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R. H.","family":"Archer","sequence":"additional","affiliation":[{"name":"Department of Clinical Toxicology Guy's and St Thomas\u2019 NHS Foundation Trust and King's Health Partners London UK"},{"name":"Faculty of Life Sciences and Medicine King's College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte L.","family":"Davies","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison M.","family":"Dines","sequence":"additional","affiliation":[{"name":"Department of Clinical Toxicology Guy's and St Thomas\u2019 NHS Foundation Trust and King's Health Partners London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Wood","sequence":"additional","affiliation":[{"name":"Department of Clinical Toxicology Guy's and St Thomas\u2019 NHS Foundation Trust and King's Health Partners London 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