Citation

Marks DJ, Dargan PI, Archer JR, Davies CL, Dines AM, Wood DM, Greene SL. Br. J. Clin. Pharmacol. 2016; 83(6): 1263-1272.

Affiliation

Austin Toxicology Service and Victorian Poisons Information Centre, Austin Hospital, Victoria, Australia.

Copyright

(Copyright © 2016, John Wiley and Sons)

DOI

10.1111/bcp.13214

PMID

28002875

Abstract

AIM: Treatment of paracetamol (acetaminophen) overdose with acetylcysteine is standardised, 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: Retrospective observational study of all patients (n = 545) between 2005-2013 admitted to a tertiary care toxicology service with acute non-staggered paracetamol overdose. Massive overdoses were defined as extrapolated 4-hour plasma paracetamol concentrations >250 mg/L, 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 at 4 hours), 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 hours 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. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Language: en