Safety of rapid intravenous infusion of valproate loading doses in epilepsy patients

IV valproate may be given to patients requiring rapid elevation of serum valproate or for patients unable to take oral medication. Previously we established the loading dose of IV valproate needed to achieve serum concentrations of > 100 ug/ml. This study evaluated the safety of rapid infusion of valproate to achieve high therapeutic levels. Twenty-four infusions of IV valproate were carried out electively in twenty-one patients with epilepsy (ages 2-54 years). The dose ranged from 21-28 mg/kg (mean 24.2 mg/kg). Target infusion rates were 3 or 6 mg/kg per min, yielding an infusion duration of 4.17 or 8.34 min. ECG was monitored; blood pressure was measured before and after infusion. Post infusion serum valproate concentrations were 64-204.1 ug/ml (mean 132.6). There were no significant changes in blood pressure and no ECG abnormalities observed. Transient pain occurred at the site of injection in five patients, associated with redness in two. This appeared to related to the concentration of valproic acid in the infusion fluid. We conclude that a loading dose of IV valproate can be administered safely and rapidly. This finding enables further studies evaluating IV valproate as a non-sedative anticonvulsant in the management of status epilepticus.