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

Abstract

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

Acknowledgments

We would like to acknowledge the tremendous work of our dedicated translators: Marcela Covica, Alexandra Angulo, Ania Gresziak, Samantha Challinor, Monique Cormier, Martine Blanchet, Gunel Alpman, Joshua Pepper, Lee Anderson, Andreas Betz, Tetsuya Yamada, Nathalie Eeckhout, Matthew Fisher, Ruth Morton, Denise Gemmellaro, Nadia Bracq, Olga Bogatova, Sana Ahmed, Christiane Frasca, Katalin Fenyvesi, Timothy Durgin, Helen Johnson, Martha Oswald, Ewa Brodziuk, David Young, Akiko Burns, Anna Lautzenheiser, Banumathy Sridharan, Charlotte Robert, Liliana Ionescu, Lucile Mckay, Vilma Etchart, Valentina Bartoli, Nathan Weatherdon, Marcia Neff, Margit Tischler, Sarah Michel, Simona Vairo, Mairi Arbuckle, Luc Ranger, Nerissa Lowe, Angelina White, Salih Topal, John Hartmann, Karine Mardini, Mahala Bartle Mathiassen, Anant Vipat, Gregory Shapiro, Hannele Marttila, and Kapka Lazorova. We also acknowledge the important contribution from our librarians and administrative aides: Marc Lamarre, David Soteros, Salih Topal, Henry Gaston, and Brenda Gallant.

Support and financial disclosure declaration

Funding: Funding for EXTRIP was obtained from industry in the form of unrestricted educational grants. These funds were used solely for expenses related to literature retrieval, translation of publications, and for reimbursement of conference calls and travel expenses for attendance at EXTRIP meetings. A list of EXTRIP sponsors can be found on www.extrip-workgroup.org. There was no industry input into meeting organization, scientific content, development, or publication of the recommendations. Furthermore, industry presence at meetings was not allowed, nor was industry awareness or comment on the recommendations sought or accepted.

Declaration of interests

The authors declare that they have no conflict of interest financial or otherwise related to this work. Complete financial disclosure for each EXTRIP member can be found on www.extrip-workgroup.org.

Supplementary material available online

Supplementary Tables 1 and 2.