Objective: To demonstrate the efficacy of flumazenil in reversing the sedative action of midazolam in ventilated intensive care patients.
Design: Prospective, double-blind randomized study.
Setting: ICU of a tertiary, university-affiliated teaching hospital.
Patients: Thirty ICU patients requiring artificial ventilation for greater than 12 hrs were studied.
Interventions: All patients received a midazolam infusion for sedation. Twenty-nine patients received supplementary narcotics. At the end of the sedation period, either flumazenil or placebo was administered to all the patients in a double-blind, randomized fashion, and the effects were observed.
Measurements and main results: Sedation levels were measured hourly during the infusion; at the end of the infusion; and at 5, 15, 30, 60, and 120 mins after cessation of the midazolam infusion. Midazolam concentrations in serum were measured at the time of cessation of the midazolam infusion and at 30, 60, and 120 mins later. Reversal of sedation was observed in 14 of 15 patients who received flumazenil, and resedation occurred in seven of these patients. Reversal was not seen in any of the patients who received placebo. Midazolam serum concentrations were similar in both groups.
Conclusion: Flumazenil in a dose of 0.15 mg is a safe drug that reverses the sedative effect of midazolam.