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Extracorporeal elimination in acute valproic acid poisoning

Lookup NU author(s): Dr Ruben ThanacoodyORCiD


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Introduction. Valproic acid (VPA) is an antiepileptic drug that is now used for a variety of neurological and psychiatric indications. Clinical manifestations of severe VPA poisoning include central nervous system depression, hypotension, electrolyte and acidbase disturbances, and hyperammonemia. Although extracorporeal methods have been used to enhance VPA elimination, the indications for and effectiveness of these methods have not been fully characterized. Methods. A systematic literature search was performed, which identified 31 reports of the use of extracorporeal elimination in VPA poisoning. Results. VPA has a low molecular weight of 144 Da and a low volume of distribution, but at therapeutic concentrations, it is highly protein bound (8595). Protein-binding studies during hemodialysis demonstrate that at high VPA concentrations protein binding is saturated, allowing substantial clearance of the free VPA fraction. Case reports consistently show that during hemodialysis the elimination half-life of VPA can be reduced to around 2 h and the enhanced VPA clearance is often associated with improvement clinically. Hemoperfusion also enhances VPA elimination, but its effectiveness may be limited by column saturation. "In-series" hemodialysis and hemoperfusion have been used, but the combination offers little benefit over hemodialysis alone. Continuous renal replacement techniques are increasingly being used although continuous venovenous hemofiltration and continuous venovenous hemodiafiltration do not appear to be as effective as hemodialysis. No controlled trials are available comparing clinical outcomes with or without extracorporeal elimination in VPA poisoning. Novel techniques such as slow low-efficiency dialysis with filtration and supplementation of the dialysate with albumin are being evaluated. Indications. Extracorporeal methods of elimination should be considered in patients with features of severe VPA poisoning (coma or hemodynamic compromise) and plasma VPA concentration >850 mgL (coma is more likely to be present at concentrations >850 mgL), particularly if severe hyperammonemia and electrolyte and acidbase disturbances are present. Conclusions. Based on limited anecdotal evidence, hemodialysis appears to be the extracorporeal method of choice to enhance VPA elimination in acute poisoning. Controlled, randomized trials are required to better characterize the effect of extracorporeal treatment on clinical outcome. © 2009 Informa UK, Ltd.

Publication metadata

Author(s): Thanacoody R

Publication type: Article

Publication status: Published

Journal: Clinical Toxicology

Year: 2009

Volume: 47

Issue: 7

Pages: 609-616

ISSN (print): 1556-3650

ISSN (electronic): 1556-9519

Publisher: Informa Healthcare


DOI: 10.1080/15563650903167772

PubMed id: 19656009


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