title: Extracorporeal Treatment in Phenytoin Poisoning: Systematic Review and Recommendations from the EXTRIP (Extracorporeal Treatments in Poisoning) Workgroup.
abstract: The Extracorporeal Treatments in Poisoning (EXTRIP) Workgroup conducted a systematic literature review using a standardized process to develop evidence-based recommendations on the use of extracorporeal treatment (ECTR) in patients with phenytoin poisoning. The authors reviewed all articles, extracted data, summarized findings, and proposed structured voting statements following a predetermined format. A 2-round modified Delphi method was used to reach a consensus on voting statements, and the RAND/UCLA Appropriateness Method was used to quantify disagreement. 51 articles met the inclusion criteria. Only case reports, case series, and pharmacokinetic studies were identified, yielding a very low quality of evidence. Clinical data from 31 patients and toxicokinetic grading from 46 patients were abstracted. The workgroup concluded that phenytoin is moderately dialyzable (level of evidence = C) despite its high protein binding and made the following recommendations. ECTR would be reasonable in select cases of severe phenytoin poisoning (neutral recommendation, 3D). ECTR is suggested if prolonged coma is present or expected (graded 2D) and it would be reasonable if prolonged incapacitating ataxia is present or expected (graded 3D). If ECTR is used, it should be discontinued when clinical improvement is apparent (graded 1D). The preferred ECTR modality in phenytoin poisoning is intermittent hemodialysis (graded 1D), but hemoperfusion is an acceptable alternative if hemodialysis is not available (graded 1D). In summary, phenytoin appears to be amenable to extracorporeal removal. However, because of the low incidence of irreversible tissue injury or death related to phenytoin poisoning and the relatively limited effect of ECTR on phenytoin removal, the workgroup proposed the use of ECTR only in very select patients with severe phenytoin poisoning.
authors.affiliation: Campus Stuivenberg, Emergency Medicine, Antwerpen, Belgium.
authors.forename: Kurt
authors.initials: K
authors.lastname: Anseeuw
authors.affiliation: Indiana University Health, Indiana Poison Center, Indianapolis, IN.
authors.forename: James B
authors.initials: JB
authors.lastname: Mowry
authors.affiliation: LIM 12, Division of Nephrology, University of Sao Paulo Medical School, Sao Paulo, Brazil.
authors.forename: Emmanuel A
authors.initials: EA
authors.lastname: Burdmann
authors.affiliation: Department of Nephrology, Verdun Hospital, University of Montreal, Verdun, QC, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Ghannoum
authors.affiliation: Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine, New York University School of Medicine, New York, NY.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Hoffman
authors.affiliation: Department of Emergency Medicine, Medical Toxicology Division, McGill University Health Centre & Department of Medicine, McGill University, Montreal, QC, Canada.
authors.forename: Sophie
authors.initials: S
authors.lastname: Gosselin
authors.affiliation: Department of Medical Biology, Sacre-Coeur Hospital, University of Montreal, Montreal, QC, Canada.
authors.forename: Valery
authors.initials: V
authors.lastname: Lavergne
authors.affiliation: Department of Pharmacy and Therapeutics, University of Pittsburgh Schools of Pharmacy and Medicine, Pittsburgh, PA; Renal Electrolyte Division, Department of Medicine, University of Pittsburgh Schools of Pharmacy and Medicine, Pittsburgh, PA. Electronic address: nolin@pitt.edu.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Nolin
mesh_terms: D003128:Coma / Q000139:chemically induced / Q000175:diagnosis / Q000628:therapy; D004493:Education / Q000379:methods / Q000592:standards*; D006801:Humans; D010672:Phenytoin / Q000506:poisoning*; D017410:Practice Guidelines as Topic / Q000592:standards*; D006435:Renal Dialysis / Q000379:methods / Q000592:standards*; D016896:Treatment Outcome
chemical_list: D010672:Phenytoin
keywords: EXTRIP (Extracorporeal Treatments in Poisoning); Phenytoin; dialyzability; extracorporeal treatment (ECTR); hemodialysis; hemoperfusion; indications; pharmacokinetics; poisoning; recommendations; renal replacement therapy (RRT); toxicity; toxicokinetics