Geoffrey K Isbister1,2, Michael A Downes1,2, Kylie Mcnamara2, Ingrid Berling1,2, Ian M Whyte1,2, Colin B Page1,2,3. 1. a Clinical Toxicology Research Group, University of Newcastle , Newcastle , Australia ; 2. b Department of Clinical Toxicology and Pharmacology , Calvary Mater Newcastle , Newcastle ; 3. c Emergency Department , Princess Alexandra Hospital , Queensland , Australia.
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.
CONTEXT: The current 3-phase acetylcysteine infusion for paracetamolpoisoning 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.
Authors: George P Bailey; Javad Najafi; Muhammad E M O Elamin; W Stephen Waring; Simon H L Thomas; John R H Archer; David M Wood; Paul I Dargan Journal: Br J Clin Pharmacol Date: 2016-08-10 Impact factor: 4.335
Authors: Mark Yarema; Puja Chopra; Marco L A Sivilotti; David Johnson; Alberto Nettel-Aguirre; Benoit Bailey; Charlemaigne Victorino; Sophie Gosselin; Roy Purssell; Margaret Thompson; Daniel Spyker; Barry Rumack Journal: J Med Toxicol Date: 2018-02-08