Extracorporeal treatment for valproic acid poisoning: systematic review and recommendations from the EXTRIP workgroup

Clin Toxicol (Phila). 2015 Jun;53(5):454-65. doi: 10.3109/15563650.2015.1035441.


Background: The EXtracorporeal TReatments In Poisoning (EXTRIP) workgroup presents its systematic review and clinical recommendations on the use of extracorporeal treatment (ECTR) in valproic acid (VPA) poisoning.

Methods: The lead authors reviewed all of the articles from a systematic literature search, extracted the data, summarized the key findings, and proposed structured voting statements following a predetermined 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. Anonymous votes were compiled, returned, and discussed in person. A second vote was conducted to determine the final workgroup recommendations.

Results: The latest literature search conducted in November 2014 retrieved a total of 79 articles for final qualitative analysis, including one observational study, one uncontrolled cohort study with aggregate analysis, 70 case reports and case series, and 7 pharmacokinetic studies, yielding a very low quality of evidence for all recommendations. Clinical data were reported for 82 overdose patients while pharmaco/toxicokinetic grading was performed in 55 patients. The workgroup concluded that VPA is moderately dialyzable (level of evidence = B) and made the following recommendations: ECTR is recommended in severe VPA poisoning (1D); recommendations for ECTR include a VPA concentration > 1300 mg/L (9000 μmol/L)(1D), the presence of cerebral edema (1D) or shock (1D); suggestions for ECTR include a VPA concentration > 900 mg/L (6250 μmol/L)(2D), coma or respiratory depression requiring mechanical ventilation (2D), acute hyperammonemia (2D), or pH ≤ 7.10 (2D). Cessation of ECTR is indicated when clinical improvement is apparent (1D) or the serum VPA concentration is between 50 and 100 mg/L (350-700 μmol/L)(2D). Intermittent hemodialysis is the preferred ECTR in VPA poisoning (1D). If hemodialysis is not available, then intermittent hemoperfusion (1D) or continuous renal replacement therapy (2D) is an acceptable alternative.

Conclusions: VPA is moderately dialyzable in the setting of overdose. ECTR is indicated for VPA poisoning if at least one of the above criteria is present. Intermittent hemodialysis is the preferred ECTR modality in VPA poisoning.

Keywords: Anticonvulsant; Extracoporeal treatments; Poisoning; Recommendations; Valproic acid.

Publication types

  • Practice Guideline
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Anticonvulsants / blood
  • Anticonvulsants / pharmacokinetics
  • Anticonvulsants / poisoning*
  • Drug Overdose / blood
  • Drug Overdose / diagnosis
  • Drug Overdose / mortality
  • Drug Overdose / therapy*
  • Hemoperfusion / standards*
  • Humans
  • Poisoning / blood
  • Poisoning / diagnosis
  • Poisoning / mortality
  • Poisoning / therapy*
  • Renal Dialysis / standards*
  • Treatment Outcome
  • Valproic Acid / blood
  • Valproic Acid / pharmacokinetics
  • Valproic Acid / poisoning*


  • Anticonvulsants
  • Valproic Acid