IV Valproic Acid vs Phenytoin: Old Standby or the New Challenger?

Kandula, Padmaja
December 2008
Neurology Alert;Dec2008, Vol. 27 Issue 4, p26
HISTORICALLY, THE BENZODIAZEPINES AND PHENYTOIN have been used as first-line therapy in aborting status epilepticus (SE). The rationale for use of these two agents mainly rests on the 1998 results of the Veterans Affairs Cooperative Trial. The greatest response rate was seen in those patients who received benzodiazepines in addition to phenytoin (PHT), rather than PHT alone. Although the intravenous formulation of valproic acid (VPA) was officially approved by the FDA in 1996, the agent was not included in the Veterans Affairs Cooperative Trial and still has not received approval by the FDA for use in SE. Nevertheless, despite the lack of FDA approval, IV VPA continues to be used off-label by clinicians. Therefore, papers such as this one by Gilad et al are critical in defining the exact role of VPA in both acute repetitive seizures (ARS) and SE. Seventy-four adult patients with either ARS or SE older than age 18 were included in this open-label study. Patients with baseline abnormal liver function tests or previous toxic serum levels of VPA were excluded from the study. For this study, SE was defined as greater than 30 minutes of continuous seizure activity or two or more sequential seizures without clinical recovery. ARS was defined as two or more repetitive seizures with clinical recovery between seizures during a 5- to 6-hour period. The primary endpoint was cessation of clinical seizure activity within 20 minutes of either VPA or PHT infusion, without rescue medication intervention. The secondary endpoint was assessment of infusion tolerability over the subsequent 24 hours. The IV VPA patient group received 30 mg/kg given over 20 minutes. The PHT patient group received an infusion of 18 mg/kg also given over 20 minutes. Patients were treated randomly in the emergency room in a 2:1 ratio of either VPA or PHT infusion. If seizure control was not achieved by infusion of the first study drug, then patients were treated with the other study drug. Patients who failed both study drug infusions were then treated with IV midazolam at a dosage of 0.2 mg/kg and were then subsequently transferred to the intensive care unit. Electroencephalography was performed in select cases of clinically suspected nonconvulsive status where patients did not regain consciousness. Forty-nine patients were treated with IV VPA and 25 patients were treated with PHT. Nearly two-thirds of patients in the study experienced breakthrough seizures secondary to subtherapeutic anti-epileptic drug levels or non-compliance. Post-stroke epilepsy made up approximately 25% of patients. Twelve percent of both the IV VPA and IV PHT groups required rescue medication. No significant side effects were found in the VPA group. One patient in the PHT group (no prior cardiac history) experienced ventricular premature beats during the infusion, one experienced vertigo, and one was noted to develop hyponatremia.


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