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Valproic Acid Demonstrates Role in Status Epilepticus: Presented at AAN

By Jill Stein

HONOLULU, HI -- April 7, 2003 -- Rapid intravenous administration of valproic acid may abort episodes of status epilepticus (SE), according to data presented here April 3^rd at the 55^th Annual Meeting of the American Academy of Neurology.

Despite the availability of several new anti-epileptic medications in the last 10 years, at least one-third of cases remain refractory to standard anti-epileptic drugs (AED).

Against this background, Dr. Nita Limdi and associates at the University of Alabama in Birmingham, conducted a chart review to identify patients with SE who were treated with IV valproic acid during the last 5 years.

They stratified the 20 men and 20 women, ranging in age from 23 to 88 years, into three groups based on time to treatment -- those treated within 1 hour of seizure onset, patients treated within one to 24 hours, and patients treated after 24 hours.

Efficacy was defined as clinical and/or electroencephalographic evidence of termination of seizures and absence of a need for additional AEDs for 12 hours after the start of valproic acid treatment. Outcome was identified by noting whether patients had died or been discharged from hospital.

The three treatment groups were similar with respect to baseline demographic characteristics. The group of patients who had been treated more than 24 hours after seizure onset had more concurrent medical problems.

In the trial, valproic acid was administered undiluted in all patients, at rates ranging from 60 mg/minute in three patients to 1 g/minute in 27 patients. The dose varied from 1 g to 6 g. Post-infusion concentrations, drawn at varying time points, ranged from 56 to 278 mcg/mL.

The overall efficacy of valproic acid in aborting SE was 67%. Those who received it within 1 hour of seizure onset had 83% efficacy, those treated within 24 hours had 89% efficacy, and those treated after 24 hours had 25% efficacy.

There was only one case of hypotension, and this was in a patient treated more than 24 hours after seizure onset. Mortality was higher in those treated more than 24 hours after seizure onset (83%) compared with those treated within 1 hour (16.6%) and those treated within 24 hours (18.2%).

Dr. Limdi said that while the results are promising, more studies are needed to establish a potential role for valproic acid as the preferred initial treatment for SE.

In the U.S. about 50,000 to 200,000 cases of SE occur each year. The overall mortality rate is about 20%, and mortality is highest in elderly patients with hypoxic or ischemic central nervous system insults. Males and females are affected equally.

The study was supported by Abbott Laboratories.


[Study title: Efficacy of Rapid Intravenous Administration of Valproic Acid in the Treatment of Status Epilepticus. Abstract: S54.002]

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