Use of midazolam in the treatment of refractory status epilepticus

Status epilepticus is an epileptic seizure that lasts at least 30 minutes or is repeated at sufficiently brief intervals to produce a continued epileptic condition lasting a total of 30 minutes without the patient fully regaining consciousness. Various combinations of anticonvulsant agents, including benzodiazepines, phenytoin, and phenobarbital, have been used to manage this condition. However, at least 9% of patients with generalized convulsive status epilepticus do not respond to conventional first-line agents, and additional intervention is required. Refractory status epilepticus refers to sustained seizures that do not respond to initial drug therapy and persist longer than 60 minutes. Reports on the response to first- and second-line agents suggest that the incidence of refractory status epilepticus is between 2000 and 6000 cases per year in the United States. Refractory status epilepticus is a major medical and neurologic emergency that requires immediate treatment to avoid significant morbidity and mortality. The anticonvulsive agent midazolam has proved to be effective, well tolerated, and fast acting when used to treat refractory status epilepticus in both adults and children. Its pharmacodynamic effects can be seen within 1 to 5 minutes of administration, and its anticonvulsive effects are apparent as early as 5 to 15 minutes after administration. This article reviews the pharmacology of midazolam and recent clinical reports on the drug's tolerability and effectiveness in the treatment of patients with refractory status epilepticus.