The incidence of intentional or accidental valproic acid (VPA) overdose is increasing. Severe VPA toxicity may lead to coma and death. Traditionally the treatment of patients with VPA toxicity has been limited to supportive measures. ⋯ However, studies of VPA toxicokinetics indicate that at blood levels that exceed therapeutic concentrations, VPA protein binding sites become saturated, leading to increased concentration of the free unbound drug. The free unbound drug has a small molecular weight and therefore it is theoretically amenable to removal by extracorporeal means. We present a patient with VPA toxicity who was successfully treated with "in-series" hemodialysis and hemoperfusion followed by continuous venovenous hemodiafiltration (CVVHDF) and review the literature on the management of VPA toxicity using extracorporeal therapies.
Ziyad Al Aly, Praveen Yalamanchili, and Esther Gonzalez.
Division of Nephrology, Saint Louis University, St. Louis, Missouri 63110, USA. zalaly@slu.edu
Semin Dial. 2005 Jan 1; 18 (1): 62-6.
AbstractThe incidence of intentional or accidental valproic acid (VPA) overdose is increasing. Severe VPA toxicity may lead to coma and death. Traditionally the treatment of patients with VPA toxicity has been limited to supportive measures. VPA is highly protein bound and therefore it is considered not to be removable by extracorporeal means. However, studies of VPA toxicokinetics indicate that at blood levels that exceed therapeutic concentrations, VPA protein binding sites become saturated, leading to increased concentration of the free unbound drug. The free unbound drug has a small molecular weight and therefore it is theoretically amenable to removal by extracorporeal means. We present a patient with VPA toxicity who was successfully treated with "in-series" hemodialysis and hemoperfusion followed by continuous venovenous hemodiafiltration (CVVHDF) and review the literature on the management of VPA toxicity using extracorporeal therapies.