title: Extracorporeal treatment for acetaminophen poisoning: recommendations from the EXTRIP workgroup.
abstract: BACKGROUND
  The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup was created to provide evidence-based recommendations on the use of extracorporeal treatments (ECTR) in poisoning and the results are presented here for acetaminophen (APAP).
  
  
  METHODS
  After a systematic review of the literature, a subgroup selected and reviewed the articles and summarized clinical and toxicokinetic data in order to propose structured voting statements following a pre-determined format. A two-round modified Delphi method was chosen to reach a consensus on voting statements, and the RAND/UCLA Appropriateness Method was used to quantify disagreement. Following discussion, a second vote determined the final recommendations.
  
  
  RESULTS
  Twenty-four articles (1 randomized controlled trial, 1 observational study, 2 pharmacokinetic studies, and 20 case reports or case series) were identified, yielding an overall very low quality of evidence for all recommendations. Clinical data on 135 patients and toxicokinetic data on 54 patients were analyzed. Twenty-three fatalities were reviewed. The workgroup agreed that N-acetylcysteine (NAC) is the mainstay of treatment, and that ECTR is not warranted in most cases of APAP poisoning. However, given that APAP is dialyzable, the workgroup agreed that ECTR is suggested in patients with excessively large overdoses who display features of mitochondrial dysfunction. This is reflected by early development of altered mental status and severe metabolic acidosis prior to the onset of hepatic failure. Specific recommendations for ECTR include an APAP concentration over 1000 mg/L if NAC is not administered (1D), signs of mitochondrial dysfunction and an APAP concentration over 700 mg/L (4630 mmol/L) if NAC is not administered (1D) and signs of mitochondrial dysfunction and an APAP concentration over 900 mg/L (5960 mmol/L) if NAC is administered (1D). Intermittent hemodialysis (HD) is the preferred ECTR modality in APAP poisoning (1D).
  
  
  CONCLUSIONS
  APAP is amenable to extracorporeal removal. Due to the efficacy of NAC, ECTR is reserved for rare situations when the efficacy of NAC has not been definitively demonstrated.
authors.affiliation: Department of Emergency Medicine, Medical Toxicology Service, McGill University Health Centre, McGill University , Montréal, QC , Canada.
authors.forename: S
authors.initials: S
authors.lastname: Gosselin
authors.forename: D N
authors.initials: DN
authors.lastname: Juurlink
authors.forename: J T
authors.initials: JT
authors.lastname: Kielstein
authors.forename: M
authors.initials: M
authors.lastname: Ghannoum
authors.forename: V
authors.initials: V
authors.lastname: Lavergne
authors.forename: T D
authors.initials: TD
authors.lastname: Nolin
authors.forename: R S
authors.initials: RS
authors.lastname: Hoffman
mesh_terms: D000082:Acetaminophen / Q000097:blood / Q000506:poisoning*; D000111:Acetylcysteine / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy*; D062787:Drug Overdose / Q000188:drug therapy*; D006801:Humans; D064887:Observational Studies as Topic; D016032:Randomized Controlled Trials as Topic; D006435:Renal Dialysis / Q000592:standards*
chemical_list: D000082:Acetaminophen; D000111:Acetylcysteine
keywords: Acetaminophen; Dialysis; Extracorporeal; Guidelines