title: Extracorporeal Treatment for Salicylate Poisoning: Systematic Review and Recommendations From the EXTRIP Workgroup.
abstract: OBJECTIVE
  Salicylate poisoning is a challenging clinical entity associated with substantial morbidity and mortality. The indications for extracorporeal treatments such as hemodialysis are poorly defined. We present a systematic review of the literature along with evidence- and consensus-based recommendations on the use of extracorporeal treatment in salicylate poisoning.
  
  
  METHODS
  The Extracorporeal Treatments in Poisoning (EXTRIP) Workgroup is a multidisciplinary group with international representation whose aim is to provide evidence-based recommendations on the use of extracorporeal treatments in poisoning. We conducted a systematic literature review followed by data extraction and summarized findings, following a predetermined format. The entire work group voted by a 2-round modified Delphi method to reach consensus on voting statements, using a RAND/UCLA Appropriateness Method to quantify disagreement. Anonymous votes were compiled, returned, and discussed in person. A second vote determined the final recommendations.
  
  
  RESULTS
  Eighty-four articles met inclusion criteria, including 1 controlled clinical trial, 3 animal studies, and 80 case reports or case series, yielding an overall very low quality of evidence for all recommendations. Clinical data on 143 patients (130 sets of which could be analyzed for patient-level entry data), including 14 fatalities, were reviewed. Toxicokinetic data on 87 patients were also included. After the second round of voting, the workgroup concluded that salicylates are dialyzable by hemodialysis and hemoperfusion (level of evidence=B) and recommended extracorporeal treatment in patients with severe salicylate poisoning (1D), including any patient with altered mental status (1D), with acute respiratory distress syndrome requiring supplemental oxygen (1D), and for those in whom standard therapy is deemed to be failing (1D) regardless of the salicylate concentration. High salicylate concentrations warrant extracorporeal treatment regardless of signs and symptoms (>7.2 mmol/L [100 mg/dL] [1D]; and >6.5 mmol/L [90 mg/dL] [2D]), with lower thresholds applied for patients with impaired kidney function (>6.5 mmol/L [90 mg/dL] [1D]; >5.8 mmol/L [80 mg/dL] [2D]). Extracorporeal treatment is also suggested for patients with severe acidemia (pH ≤7.20 in the absence of other indications) (2D). Intermittent hemodialysis is the preferred modality (1D), although hemoperfusion (1D) and continuous renal replacement therapies (3D) are acceptable alternatives if hemodialysis is unavailable, as is exchange transfusion in neonates (1D).
  
  
  CONCLUSIONS
  Salicylates are readily removed by extracorporeal treatment, with intermittent hemodialysis being the preferred modality. The signs and symptoms of salicylate toxicity listed warrant extracorporeal treatment, as do high concentrations regardless of clinical status.
authors.affiliation: Departments of Medicine, Pediatrics and the Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada.
authors.forename: David N
authors.initials: DN
authors.lastname: Juurlink
authors.affiliation: Department of Emergency Medicine, Medical Toxicology Service, McGill University Health Centre, McGill University, Montréal, Quebec, Canada.
authors.forename: Sophie
authors.initials: S
authors.lastname: Gosselin
authors.affiliation: Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany.
authors.forename: Jan T
authors.initials: JT
authors.lastname: Kielstein
authors.affiliation: Department of Nephrology, Verdun Hospital, University of Montréal, Verdun, Quebec, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Ghannoum
authors.affiliation: Department of Medical Biology, Sacré-Coeur Hospital, University of Montréal, Montréal, Quebec, Canada.
authors.forename: Valéry
authors.initials: V
authors.lastname: Lavergne
authors.affiliation: Department of Pharmacy and Therapeutics and the Department of Medicine Renal Electrolyte Division, University of Pittsburgh Schools of Pharmacy and Medicine, Pittsburgh, PA.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Nolin
authors.affiliation: Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine, New York University School of Medicine, New York, NY. Electronic address: bobhoffmd@gmail.com.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Hoffman
mesh_terms: D003697:Delphi Technique; D062787:Drug Overdose / Q000628:therapy; D006801:Humans; D017410:Practice Guidelines as Topic; D006435:Renal Dialysis; D012459:Salicylates / Q000506:poisoning*
chemical_list: D012459:Salicylates