- Title
- Efficacy of a two bag acetylcysteine regimen to treat paracetamol overdose (2NAC study)
- Creator
- Wong, Anselm; Isbister, Geoff; Graudins, Andis; McNulty, Richard; Isoardi, Katherine; Harris, Keith; Chiew, Angela; Greene, Shaun; Gunja, Naren; Buckley, Nicholas; Page, Colin
- Relation
- NHMRC.1061041 http://purl.org/au-research/grants/nhmrc/106104
- Relation
- EClinicalMedicine Vol. 20, Issue March 2020, no. 100288
- Publisher Link
- http://dx.doi.org/10.1016/j.eclinm.2020.100288
- Publisher
- The Lancet Publishing Group
- Resource Type
- journal article
- Date
- 2020
- Description
- Background: Previous studies of paracetamol overdose treatment show that a 2-bag, 20-h intravenous (IV) acetylcysteine regimen decreased the incidence of non-allergic anaphylactic reactions compared to the 3-bag, 21 h IV regimen, but have not examined efficacy of the 20-h 2 bag regimen. Methods: This was a multi-centre observational study of paracetamol overdose presentations treated with a 2-bag IV acetylcysteine regimen (200 mg/kg over 4 h, 100 mg/kg over 16 h) compared to a 3-bag regimen, performed from 2009 to 2019. Patients were referred from the emergency department to the inpatient toxicology units for continued management. For the primary non-inferiority analysis: subjects had single, acute ingestions, a serum paracetamol-concentration performed 4 to 8-h post-ingestion. The primary outcome was development of acute liver injury (ALI), defined as peak ALT>150 U/L; and > double admission baseline ALT (for presentations within 24 h post-overdose). Secondary outcomes included adverse reactions to acetylcysteine (cutaneous and systemic). Finding: Out of 6419 paracetamol overdoses, 2763 received acetylcysteine. For the primary analysis, 1003 received the 2-bag and 783 the 3-bag acetylcysteine regimen. When presentation bloods were performed 4 to 8-h post-overdose, 21 (3.1%) developed ALI with the 2-bag regimen vs 16 (2.9%) with the 3-bag regimen (Difference: 0.2%, 95%CI:-1.6 to 2.2). The incidence of hepatotoxicity was: 1.2% (n = 8) with the two-bag regimen and 1.6% (n = 9) with the three-bag regimen (Difference -0.4%, 95%CI -1.75, 0.91). When presentation bloods were performed 8 to 24-h post-overdose, 70 (21%) developed ALI with the 2-bag regimen vs 46 (23%) with the 3-bag regimen (Difference: -2%, 95%CI -9.12 to 5.36). There were significantly less cutaneous and systemic non-allergic anaphylactic reactions recorded after treatment with the two-bag than the three-bag regimen (1.3% [n = 17] and 7.1% [n = 65], Difference: -5.8%, 95%CI -7.6 to -4.0, p < 0.0001), respectively. Interpretation: A two-bag intravenous acetylcysteine regimen was found to be non-inferior to the three-bag regimen with regards to efficacy in preventing acute liver injury for early presentations of paracetamol overdose. No important differences were seen for any other presentations. The two-bag regimen also decreased the incidence of both non-allergic anaphylactic reactions and gastrointestinal adverse events from acetylcysteine treatment.
- Subject
- acetaminophen; poisoning; n-acetylcysteine
- Identifier
- http://hdl.handle.net/1959.13/1456835
- Identifier
- uon:45267
- Identifier
- ISSN:25895370
- Rights
- 5370/© 2020PublishedbyElsevierLtd.ThisisanopenaccessarticleundertheCCBY-NC-NDlicense.(http://creativecommons.org/licenses/by-nc-nd/4.0/)
- Language
- eng
- Full Text
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