Extracorporeal Management of Valproic Acid Toxicity: A Case Report and Review of the Literature

Abstract

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. 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.

Simultaneous, Dual Continuous Venovenous Haemodiafiltration as Salvage Therapy for Severe Sodium Valproate Intoxication

“…Moreover, CVVHDF following in-series haemodialysis and haemofiltration has been shown to prevent postdialytic rebound whilst first optimising drug clearance in a case of severe VPA toxicity [ 13 ].…”

Factors Influencing Plasma Concentrations of Valproic Acid in Pediatric Patients With Epilepsy and the Clinical Significance of CYP2C9 Genotypes in Personalized Valproic Acid Therapy

“…This emphasizes the importance of careful monitoring and dosage adjustments in the treatment of pediatric epilepsy using VPA. 47…”

“…This emphasizes the importance of careful monitoring and dosage adjustments in the treatment of pediatric epilepsy using VPA. 47 Furthermore, VPA acts as a hepatic enzyme inhibitor, and its plasma concentration can be affected by concomitant medication. Studies have shown that the concurrent use of AEDs such as CBZ, phenobarbital, phenytoin, and OXC can accelerate VPA metabolism through enzyme induction, increase its clearance rate, shorten its half-life, expand its distribution volume, and reduce its plasma concentration.…”

Rescue strategies for valproic acid overdose poisoning: Case series and literature review

“…In Case 1, the clinician urgently opened central venous access and performed CRRT+HP treatment to rapidly and stably reduce the concentration of free sodium valproate in the patient's blood. After 10 h of CRRT+HP treatment, the blood concentration of sodium valproate decreased from 635.77 mg/L to 193.00 mg/L, and the blood concentration rebounded to 263.20 mg/L after 12 h. The blood concentration of sodium valproate may rebound after one time of blood purification, 19 because drug concentration in tissues and organs is still significant, drug redistribution increases blood drug concentration again. The protein binding rate of sodium valproate is high.…”