Midazolam treatment of acute and refractory status epilepticus

Generalized convulsive status epilepticus (GCSE) is a medical emergency req uiring prompt resolution. Acute treatment is often delayed by difficulty in obtaining intravenous (IV) access. Refractory GCSE is often difficult to t reat, and traditional therapy with barbiturates induces hypotension and res piratory depression and prolongs recovery. Midazolam is particularly useful for treating acute GCSE because it has an imidazole ring that is open at l ow pH, allowing it to be dissolved in aqueous solution for intramuscular in jection, but closed at physiologic pH, increasing lipophilicity and renderi ng good intramuscular absorption, brain penetration, and fast onset of acti on. When given intramuscularly as a 0.2 mg/kg bolus, it has efficacy at lea st equal to that of IV diazepam, is well tolerated, induces little respirat ory compromise, and has a shorter latency to onset of action. Therefore, it should be considered for the treatment of acute GCSE when IV access is pro blematic. For refractory GCSE, continuous IV midazolam infusion at 0.1-0.6 mg/kg/hr after a 0.2 mg/kg IV bolus is effective and has advantages over tr aditional therapies because it induces less hypotension and cardiorespirato ry depression and can be easily titrated. Further prospective studies are n eeded to define the role of continuous IV midazolam compared to other conte mporary therapies.