The safety of rapid valproic acid infusion

Purpose: The recommended rate of administration of valproic acid injection is 20 mg/min. Drug delivery at this rate may be inadequate for expeditious control of seizures. The safety of rapid infusion of valproic acid has not been established, and this study was designed to explore the effects of rapid infusion in patients with acute seizures. Methods: Twenty patients with acute repetitive seizures received 20 mg/kg loading doses of valproic acid. Infusion rates ranged from 33.3 to 555 mg/min (median, 200 mg/min). Sixteen patients had received previous or concomitant antiepileptic drugs, with inadequate seizure control. Heart rate, blood pressure, and respiratory rate were measured before infusion and at frequent intervals for 1 hour after infusion. Patients were also observed for changes in level of alertness and signs of local irritation. Results: No patient exhibited a decline in level of consciousness or respiratory function. Two patients with significant contributing factors exhibited declines in blood pressure requiring vasopressors. No significant local irritation was reported. Although efficacy was not a measured end point, seizures were abolished in all patients. Conclusions: Infusion of valproic acid at rates between 33 and 555 mg/min is well tolerated. No serious adverse effects attributable to the rapid infusion of valproic acid were encountered, although valproic acid, along with other factors, may have contributed to the hypotension in two patients. Intravenous valproic acid is an option for the control of acute seizures.