A prospective observational study of a novel 2-phase infusion protocol for the administration of acetylcysteine in paracetamol poisoning

Abstract

Context: The current 3-phase acetylcysteine infusion for paracetamol poisoning delivers half the dose over 15–60 min and frequently results in adverse reactions. Objective: We aimed to determine adverse reaction frequency with a modified 2-phase infusion protocol with a longer initial infusion. Materials and methods: A prospective observational study of a modified 2-phase acetylcysteine protocol was undertaken at two hospitals. Acetylcysteine was commenced on admission and ceased if paracetamol concentrations were low-risk (below the nomogram line). The first infusion was 200 mg/kg over 4–9 h based on ingestion time or 4 h for staggered/chronic ingestions. The second infusion was 100 mg/kg over 16 h. Pre-defined outcomes were frequency of adverse reactions (systemic hypersensitivity reactions or gastrointestinal); proportion with alanine transaminase (ALT) > 1000 U/L or abnormal ALT. Results: 654 paracetamol poisonings were treated with the new protocol; median age 29 y (15–98 y); 453 females; 576 acute and 78 staggered/chronic ingestions. In 420 (64%) acetylcysteine was stopped for low-risk paracetamol concentrations. An adverse reaction occurred in 229/654 admissions (35%; 95% CI: 31–39%): 173 (26.5%; 95% CI: 23–30%) only gastrointestinal, 50 (8%; 95% CI: 6–10%) skin only systemic hypersensitivity reactions; and three severe anaphylaxis (0.5%; 95% CI: 0.1–1.5%; all hypotension). Adverse reactions occurred in 111/231 (48%) receiving full treatment compared to 116/420 (28%) in whom the infusion was stopped early (absolute difference 20%; 95% CI: 13–28%; p < 0.0001). In 200 overdoses < 10 g, one had toxic paracetamol concentrations, but 53 developed reactions. Sixteen patients had an ALT > 1000 U/L and 24 an abnormal ALT attributable to paracetamol; all but one had treatment commenced >12 h post-ingestion. Conclusion: A 2-phase acetylcysteine infusion protocol results in a fewer reactions in patients with toxic paracetamol concentrations, but is not justified in patients with low-risk paracetamol concentrations.

Keywords:

• Acetaminophen
• acetylcysteine
• adverse reactions
• hepatotoxicity
• paracetamol poisoning
• overdose

This article is referred to by:

New regimens for intravenous acetylcysteine, where are we now?

Acknowledgements

We acknowledge Dr. Iain McNeil at Princess Alexandra Hospital and the assistance of the medical and nursing staff at the Calvary Mater Newcastle and Princess Alexandra Hospital emergency departments.

Disclosure statement

The authors report no conflicts of interest.

Funding information

The study was supported in part by an NHMRC Program Grant 1055176. Geoff Isbister is funded by an NHMRC Senior Research Fellowship ID1061041. Colin Page is funded by a Queensland Emergency Medicine Research Foundation research fellowship.