A COMPARISON OF 4 TREATMENTS FOR GENERALIZED CONVULSIVE STATUS EPILEPTICUS

Background and Methods Although generalized convulsive status epilepti cus is a life-threatening emergency, the best initial drug treatment i s uncertain. We conducted a five-year randomized, double-blind, multic enter trial of four intravenous regimens: diazepam (0.15 mg per kilogr am of body weight) followed by phenytoin (18 mg per kilogram), lorazep am (0.1 mg per kilogram), phenobarbital (15 mg per kilogram), and phen ytoin (18 mg per kilogram). Patients were classified as having either overt generalized status epilepticus (defined as easily visible genera lized convulsions) or subtle status epilepticus (indicated by coma and ictal discharges on the electroencephalogram, with or without subtle convulsive movements such as rhythmic muscle twitches or tonic eye dev iation). Treatment was considered successful when all motor and electr oencephalographic seizure activity ceased within 20 minutes after the beginning of the drug infusion and there was no return of seizure acti vity during the next 40 minutes. Analyses were performed with data on only the 518 patients with verified generalized convulsive status epil epticus as well as with data on all 570 patients who were enrolled. Re sults Three hundred eighty-four patients had a verified diagnosis of o vert generalized convulsive status epilepticus. In this group, lorazep am was successful in 64.9 percent of those assigned to receive it, phe nobarbital in 58.2 percent, diazepam and phenytoin in 55.8 percent, an d phenytoin in 43.6 percent (P=0.02 for the overall comparison among t he four groups). Lorazepam was significantly superior to phenytoin in a pairwise comparison (P=0.002). Among the 134 patients with a verifie d diagnosis of subtle generalized convulsive status epilepticus, no si gnificant differences among the treatments were detected (range of suc cess rates, 7.7 to 24.2 percent). In an intention-to-treat analysis, t he differences among treatment groups were not significant, either amo ng the patients with overt status epilepticus (P=0.12) or among those with subtle status epilepticus (P=0.91). There were no differences amo ng the treatments with respect to recurrence during the 12-hour study period, the incidence of adverse reactions, or the outcome at 30 days. Conclusions As initial intravenous treatment for overt generalized co nvulsive status epilepticus, lorazepam is more effective than phenytoi n. Although lorazepam is no more efficacious than phenobarbital or dia zepam and phenytoin, it is easier to use. (N Engl J Med 1998;339:792-8 .) (C) 1998, Massachusetts Medical Society.