Objectives: To evaluate the safety and efficacy of flumazenil vs placebo in reversing fentanyl and midazolam-induced conscious sedation in ED patients undergoing a short, painful procedure.
Methods: This was a multicenter, randomized, parallel, double-blind, placebo-controlled study conducted at 9 university-affiliated teaching hospitals. Patients > 18 years of age requiring conscious sedation for a painful procedure expected to last < 20 minutes were eligible for inclusion in the study. Patients received 2 micrograms/kg of fentanyl, followed by midazolam titrated to the desired level of sedation. Patients were then randomized to receive either flumazenil or placebo in a 3:1 ratio (flumazenil:placebo). Vital signs, O2 saturation, and alertness were recorded at regular intervals. Prior to ED release, patients were asked to rate the amount of discomfort they experienced and the level of relaxation achieved on a 10-cm visual analog scale (VAS). They also were questioned about their recall for the procedure and satisfaction with the drug regimen. Physicians also rated their satisfaction with the drug regimen on a 10-cm VAS.
Results: Overall, 133 patients received flumazenil and 46 patients received placebo. Patients in the 2 groups received similar doses of midazolam. The patients who received flumazenil returned to baseline alertness earlier (11.1 min vs 24.8 min, p < 0.001) and at a faster rate than did the patients given placebo. Actual intervals from procedure completion until release from the ED did not differ between the 2 groups (98.2 +/- 3.6 min flumazenil vs 96.9 +/- 5.8 min placebo; p = 0.89). The amounts of discomfort experienced, levels of relaxation achieved, recalls for the procedure, and both patient and physician satisfactions were also similar for the 2 groups. There were no serious adverse effects related to the study drug, and minor adverse effects were similar for the 2 groups.
Conclusion: Flumazenil is safe and efficacious in reversing midazolam-induced sedation in ED patients given a combination of fentanyl and midazolam to facilitate the performance of a short, painful procedure. The patients given flumazenil returned to baseline alertness earlier and at a faster rate than did the patients given placebo. However, flumazenil did not alter the actual interval from procedure completion until ED release.