title: Outcomes of Patients With Premature Discontinuation of the 21-h Intravenous N-Acetylcysteine Protocol After Acute Acetaminophen Overdose.
abstract: BACKGROUND
  The minimum recommended treatment duration for i.v. N-acetylcysteine (NAC) after an acute, single acetaminophen (APAP) overdose is 21 h. Some have questioned whether shorter courses may be sufficient in carefully selected cases.
  
  
  OBJECTIVE
  We sought to describe the incidence of hepatotoxicity in a cohort of acute APAP overdose patients who received <21 h of i.v. NAC for any reason.
  
  
  METHODS
  We performed a secondary analysis of a large multicenter retrospective cohort of patients hospitalized for APAP poisoning. We selected patients with a potentially toxic serum APAP concentration measured between 4 and 24 h post ingestion, in whom i.v. NAC was initiated but discontinued before completing the full 21-h course. We further characterized outcomes in these patients as a function of two novel risk-prediction tools, the psi (ψ) parameter and APAP × aminotransferase (AT) product. The ψ parameter is an estimate of the cellular burden of injury based on the area under the concentration-time curve before treatment, and calculated with respect to the APAP concentration and time to initiation of NAC.
  
  
  RESULTS
  Fifty-nine patients met inclusion criteria. Intravenous NAC was initiated a median of 11.3 h post ingestion and administered for a median of 11.0 h. Hepatotoxicity (aspartate aminotransferase [AST] or alanine aminotransferase [ALT] > 1,000 IU/L) occurred in one patient (1.7%; 95% confidence interval 0.04-9.1), and eight additional patients developed hepatic injury (AST or ALT > 100 IU/L). No fatalities occurred. A multiplication product of APAP and AT (APAP × AT) that falls below 10,000 μmol/L/IU-L, or pretreatment ψ < 5 mmol/L-h suggested a low risk of hepatic injury.
  
  
  CONCLUSIONS
  In this retrospective analysis of patients treated with < 21 h of i.v. NAC for acute APAP overdose, the incidence of hepatotoxicity and coagulopathy was low, despite delays to NAC treatment.
authors.affiliation: Department of Emergency Medicine, University of Alberta, Edmonton, Alberta, Canada; Ronald O. Perelman Department of Emergency Medicine, New York University School of Medicine, New York, New York; Poison and Drug Information Service, Alberta Health Services, Calgary, Alberta, Canada; Department of Emergency Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Scott N
authors.initials: SN
authors.lastname: Lucyk
authors.affiliation: Department of Emergency Medicine, University of Alberta, Edmonton, Alberta, Canada; Poison and Drug Information Service, Alberta Health Services, Calgary, Alberta, Canada; Department of Emergency Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada; Department of Critical Care Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Yarema
authors.affiliation: Departments of Emergency Medicine, and of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada; Ontario Poison Centre, Toronto, Ontario, Canada.
authors.forename: Marco L A
authors.initials: ML
authors.lastname: Sivilotti
authors.affiliation: Poison and Drug Information Service, Alberta Health Services, Calgary, Alberta, Canada; Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada.
authors.forename: David W
authors.initials: DW
authors.lastname: Johnson
authors.affiliation: Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada; Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada; Alberta Children's Hospital Research Institute for Child & Maternal Health, Calgary, Alberta, Canada.
authors.forename: Alberto
authors.initials: A
authors.lastname: Nettel-Aguirre
authors.affiliation: Statistics Canada, Microdata Access Division, Prairie Regional Research Data Centre, University of Calgary, MLT-116, 2500 University Dr. NW, Calgary, Alberta, Canada.
authors.forename: Charlemaigne
authors.initials: C
authors.lastname: Victorino
authors.affiliation: Division of Emergency Medicine, CHU Sainte Justine, Montreal, Quebec, Canada.
authors.forename: Benoit
authors.initials: B
authors.lastname: Bailey
authors.affiliation: Rocky Mountain Poison and Drug Center, Denver Hospital Health Authority, Denver, Colorado.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Dart
authors.affiliation: Rocky Mountain Poison and Drug Center, Denver Hospital Health Authority, Denver, Colorado.
authors.forename: Kennon
authors.initials: K
authors.lastname: Heard
authors.affiliation: Department of Emergency Medicine, Oregon Poison Center, Oregon Health & Science University, Portland, Oregon.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Spyker
authors.affiliation: Department of Pediatrics, University of Colorado School of Medicine, Denver, Colorado.
authors.forename: Barry H
authors.initials: BH
authors.lastname: Rumack
mesh_terms: D000082:Acetaminophen / Q000506:poisoning*; D000111:Acetylcysteine / Q000008:administration & dosage / Q000627:therapeutic use*; D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000082:Acetaminophen; D000111:Acetylcysteine