title: A prospective observational study of a novel 2-phase infusion protocol for the administration of acetylcysteine in paracetamol poisoning.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: a Clinical Toxicology Research Group, University of Newcastle , Newcastle , Australia ;|b Department of Clinical Toxicology and Pharmacology , Calvary Mater Newcastle , Newcastle ;
authors.forename: Geoffrey K
authors.initials: GK
authors.lastname: Isbister
authors.affiliation: a Clinical Toxicology Research Group, University of Newcastle , Newcastle , Australia ;|b Department of Clinical Toxicology and Pharmacology , Calvary Mater Newcastle , Newcastle ;
authors.forename: Michael A
authors.initials: MA
authors.lastname: Downes
authors.affiliation: b Department of Clinical Toxicology and Pharmacology , Calvary Mater Newcastle , Newcastle ;
authors.forename: Kylie
authors.initials: K
authors.lastname: Mcnamara
authors.affiliation: a Clinical Toxicology Research Group, University of Newcastle , Newcastle , Australia ;|b Department of Clinical Toxicology and Pharmacology , Calvary Mater Newcastle , Newcastle ;
authors.forename: Ingrid
authors.initials: I
authors.lastname: Berling
authors.affiliation: a Clinical Toxicology Research Group, University of Newcastle , Newcastle , Australia ;|b Department of Clinical Toxicology and Pharmacology , Calvary Mater Newcastle , Newcastle ;
authors.forename: Ian M
authors.initials: IM
authors.lastname: Whyte
authors.affiliation: a Clinical Toxicology Research Group, University of Newcastle , Newcastle , Australia ;|b Department of Clinical Toxicology and Pharmacology , Calvary Mater Newcastle , Newcastle ;|c Emergency Department , Princess Alexandra Hospital , Queensland , Australia.
authors.forename: Colin B
authors.initials: CB
authors.lastname: Page
mesh_terms: D000082:Acetaminophen / Q000506:poisoning*; D000111:Acetylcysteine / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D062787:Drug Overdose / Q000188:drug therapy; D005260:Female; D006760:Hospitalization; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D000082:Acetaminophen; D000410:Alanine Transaminase; D000111:Acetylcysteine
keywords: Acetaminophen; acetylcysteine; adverse reactions; hepatotoxicity; overdose; paracetamol poisoning