SAFETY AND EFFICACY OF FLUMAZENIL IN THE REVERSAL OF BENZODIAZEPINE-INDUCED CONSCIOUS SEDATION

Objective: To determine the safety and efficacy of flumazenil when giv en for reversal of benzodiazepine-induced conscious sedation in childr en. Design: Multicenter study conducted in emergency departments and p ediatric endoscopy, bronchoscopy, or oncology suites. Patients: One hu ndred seven children (median age, 6 years; range, 1 to 17 years) who r eceived intravenous benzodiazepine for an invasive procedure. Interven tions: Flumazenil was given in increments of 0.01 mg/kg (0.2 mg maximu m) at 1-minute intervals to a maximum total dose of 0.05 mg/kg (1.0 mg maximum). Measurements: Clinical efficacy was assessed by the Clinica l Global Impression Scale and Observer's Assessment of Alertness/Sedat ion Scale. The OAA/S, vital signs, lead II electrocardiogram, and clin ical assessments were recorded at 0, 10, 30, 60, 90, and 120 minutes a fter flumazenil was given. Results: All children received midazolam (m ean total dose, 0.18 mg/kg) for sedation. One hundred (96%) patients a chieved a complete or partial response to flumazenil by 10 minutes aft er its administration, on the basis of their CGIS scores (the mean dos e of flumazenil administered at the time of the first complete respons e was 0.017 +/- 0.010 mg/kg). Seventy-one of 93 (76%) patients with a baseline OAA/S score less than or equal to 3 (1 = deep sleep, 5 = aler t) experienced an increase of greater than or equal to 2 points at 10 minutes after flumazenil administration and 81 of 93 (87%) had a score of 4 or 5 after flumazenil administration. Seven patients, all within the 1- to 5-year age range, experienced resedation after initially re sponding to flumazenil. Thirty-seven of 107 patients (35%) experienced a total of 56 adverse events, most of which were considered to be unr elated to flumazenil administration. The most frequently occurring adv erse events were abnormal crying, dizziness, nausea, fever, and headac he. There were no clinically significant changes in vital signs or ECG tracings. No adverse events resulted in premature termination of drug administration. Conclusions: Flumazenil promptly and effectively reve rses the central nervous system depressant effects of midazolam in chi ldren undergoing conscious sedation, with no significant adverse effec ts. Because of the potential for resedation, children who receive flum azenil should be monitored for 1 to 2 hours after its administration.