Midazolam treatment of acute and refractory status epilepticus

Generalized convulsive status epilepticus (GCSE) is a medical emergency requiring prompt resolution. Acute treatment is often delayed by difficulty in obtaining intravenous (i.v.) access. Refractory GCSE is often difficult to treat, and traditional therapy with barbiturates induces hypotension and respiratory depression and prolongs recovery. Midazolam is particularly useful for treating acute GCSE because it has an imidazole ring that is open at low pH, allowing it to be dissolved in aqueous solution for intramuscular injection, but closed at physiologic pH, increasing lipophilicity and rendering good intramuscular absorption, brain penetration, and fast onset of action. When given intramuscularly as a 0.2 mg/kg bolus, it has efficacy at least equal to that of i.v. diazepam, is well tolerated, induces little respiratory compromise, and has a shorter latency to onset of action. Therefore, it should be considered for the treatment of acute GCSE when i.v. access is problematic. For refractory GCSE, continuous i.v. midazolam infusion at 0.1-0.6 mg/kg/hr after a 0.2 mg/kg i.v. bolus is effective and has advantages over traditional therapies because it induces less hypotension and cardiorespiratory depression and can be easily titrated. Further prospective studies are needed to define the role of continuous i.v. midazolam compared to other contemporary therapies.