Abstracts

Despite the introduction of several new antiepileptic drugs (AED) in the last decade, the treatment and outcome of SE remains unaltered, with 30-40% cases being refractory to conventional AED therapy. Although the initial usefulness of intravenous (I.V.) valproic acid (VPA) was limited by slow infusion rates, studies establishing the safety of rapid infusion have facilitated its use in the treatment of SE. VPA, although not approved by the FDA for the treatment of SE, is emerging as an option in the treatment of acute seizure exacerbations and SE.
The purpose of this project is to elucidate the efficacy of VPA in the treatment of SE.
We retrospectively reviewed our institutional databases and identified patients with SE who received IV VPA during the last 5 years. The following information was collected and analyzed: 1) demographics; 2) etiology of SE; 3) co-morbidities; 4) duration of SE; 5) order of AED administration; 6) dose and rate of AED administration; 7) postinfusion concentrations; 8) safety, and 9) efficacy in aborting SE. Efficacy was defined as clinical and/or EEG termination of seizures and the lack of necessity of additional AED for 12 hrs after institution of VPA treatment. Safety was defined as lack of cardiovascular adverse effects and skin reactions. Outcome was noted by identifying each patient[apos]s disposition (death or discharge).
Sixty-three patients, 30 men (average age: 57.4 years) and 33 women (average age: 50.5 years) met the criteria. Efficacy of VPA in abolishing SE was analyzed based on time to treatment and order of AED administration.
Efficacy of VPA in abolishing SE when used as the 1st AED was 50% (n=14), as the 2nd AED was 60% (n=20), as the 3rd AED was 63% (n=19), and as the 4th AED was 75% (n=8).
Time to treatment or duration of SE significantly affected efficacy. Efficacy of VPA in abolishing SE when used within 4 hours was 86.6% (n=15), within 4-24 hours was 68% (n=28) and after 24 hours was 35% (n=17).
A majority of patients (n=49) had received at least one AED prior to VPA for the treatment of SE. The dose varied from 1gm to 6gm (13mg/kg to 77mg/kg). Post infusion concentrations from 56 to 278 mcg/ml. Neither the dose nor the serum VPA levels influenced efficacy.
Higher co-morbidity adversely affected efficacy of VPA in abolishing SE and patient outcome (death or discharge).
The overall efficacy of VPA in aborting SE was 63.3%, which compares favorably with other agents. Rapid administration of undiluted VPA was tolerated without significant adverse effects.
The efficacy and safety of rapid administration of intravenous VPA in the management of SE supports its use. Importantly, VPA retains its efficacy even when used as the 2nd or 3rd AED. Further controlled trials are indicated to better define the role of VPA as a first line agent in the treatment of SE.
[Supported by: In part through a grant form Abbott Laboratories]