- Title
- A prospective observational study of a novel 2-phase infusion protocol for the administration of acetylcysteine in paracetamol poisoning
- Creator
- Isbister, Geoffrey K.; Downes, Michael A.; McNamara, Kylie; Berling, Ingrid; Whyte, Ian M.; Page, Colin B.
- Relation
- Clinical Toxicology Vol. 54, Issue 2, p. 120-126
- Publisher Link
- http://dx.doi.org/10.3109/15563650.2015.1115057
- Publisher
- Routledge
- Resource Type
- journal article
- Date
- 2016
- Description
- 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.
- Subject
- acetaminophen; acetylcysteine; adverse reactions; hepatotoxicity; paracetamol poisoning; overdose
- Identifier
- http://hdl.handle.net/1959.13/1316074
- Identifier
- uon:23068
- Identifier
- ISSN:1556-3650
- Language
- eng
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