Safety of high intravenous valproate loading doses in epilepsy patients

Parenteral antiepileptic drugs (AEDs) are required in patients needing emergent treatment or unable to take oral medication. In the two United States trials of IV valproate, only low therapeutic serum levels were achieved. This study evaluated the safety of high loading doses to achieve therapeutic levels rapidly. Twenty-five epilepsy patients without active seizures received a single loading dose of IV valproate (Depacon) based on body weight and infused over 1 hour. Ages were 4–39 years (mean: 13.1 ± 8.6 years). Electrocardiogram (ECG) and electroencephalogram (EEG) were monitored throughout infusion; blood pressure was measured before and after. Serum valproate was measured 10 minutes postinfusion. The IV valproate dose range was 15–44 mg/kg (mean: 28.3 ± 7.4 mg/kg); infusion rates were 0.25–0.73 mg/ kg/minute (mean: 0.47 ± 0.1 mg/kg/minute). Postinfusion serum valproate concentrations were 71–277 μg/ml (mean: 135.3 ± 59.5 μg/ml). There were no significant changes in blood pressure, no redness or tenderness at the IV site, and no ECG abnormalities. One patient with serum valproate ⩾ 200 μg/ml had mild sedation (resolving in 24 hours). We concluded that serum valproate concentrations of ⩾ 100 μg/ml can be achieved rapidly and safely parenterally, a finding with important implications for the treatment of status epilepticus.