Midazolam infusion and the benzodiazepine antagonist flumazenil for sedation of intensive care patients

Abstract ICU patients often require sedation. Midazolam (M), a new imidazobenzodiazepine, features rapid onset and rapid elimination time. Flumazenil (Ro 15-1788) is a new benzodiazepine antagonist. We studied the efficacy and safety of M by continuous infusion in 28 ICU patients: 16 post major surgery, and 12 medical patients, aged 20–77 years. M was administered as a loading dose of 0.05–0.15 mg/kg per min followed by continuous infusion of 0.05-0.1 mg/kg per h titrated to maintain patients asleep but arousable. M was administered for up to 14 days in doses of 1–15 mg/h and cumulative doses of up to 1915 mg. No untoward effects were noted except for slight decreases in blood pressure following the loading dose. ACTH challenge tests performed before and 24 h or more following the start of M showed no depression of adrenal responsivity. All patients meeting weaning criteria were weaned off mechanical ventilation while still on M. In 13 patients extubation was performed immediately after M was stopped, and flumazenil (0.38 ± 0.27 mg, i.v.) given until full awakening. Patients remained awake yet calm. Vital signs remained stable after flumazenil. Midazolam by continuous infusion appears to be a safe and effective mode of sedation in ICU patients. Flumazenil may increase the flexibility and safety of this mode of sedation.