Intravenous Sodium Valproate(Depakine(R)):Antiepileptic Effect and Safety Assessment During the Postoperative Seven Days in Neurosurgical Patients

ABSTRACT

Diphenylhydantoin(DPH) has been used intravenously as a drug of choice in conditions which seizure patients are incapable of oral feeding or in a state of status epilepticus. However, its clinical use has limitations because of its serious side effects of cardiac depression or systemic hypotension. In Western countries, the recently developed intravenous sodium valproate has been reported as safe and effective for seizure control in such patients. To assess the safety and effectiveness in seizure control, we investigated the serum levels of the drug at 24 hours, 48 hours, and 7 days after intravenous administration of sodium valproate(Depakine(R)), occurrence of seizures in the perioperative period, and the side effects of the drugs in 30 neurosurgical patients older than 3 years of age. The mean serum concentrations of valproic acid after bolus injection of 15mg/kg followed by continuous infusion with the rate of 0.5mg/kg/hour, were over 45.0 microgram/ml;45.0+/-16.3 microgram/ml at 24 hours, 50.4+/-21.0 microgram/ml at 48 hours, and 58.9+/-20.7 microgram/ml at 7 days after the start of the administration. All the patients whose serum valproic acid level was within the therapeutic range(40-100 microgram/ml), had never experienced an episode of seizure attack during the perioperative days. There was no evidence of elevated liver enzyme activity, but there were evidence of some tendency of decreased platelet count in the peripheral blood at 2 days after the administration of intravenous valproic acid. Four patients experienced episodes of mild nausea and/or vomiting. In conclusion, perioperative intravenous administration of valproic acids in neurosurgical patients was safe and effective in seizure control. However, it must be used precauciously in the patients with compromised coagulation system.