Safety and efficacy of flumazenil in the reversal of benzodiazepine-induced conscious sedation. The Flumazenil Pediatric Study Group.
OBJECTIVE
To determine the safety and efficacy of flumazenil when given for reversal of benzodiazepine-induced conscious sedation in children.


METHODS
Multicenter study conducted in emergency departments and pediatric endoscopy, bronchoscopy, or oncology suites.


METHODS
One hundred seven children (median age, 6 years; range, 1 to 17 years) who received intravenous benzodiazepine for an invasive procedure.


METHODS
Flumazenil was given in increments of 0.01 mg/kg (0.2 mg maximum) at 1-minute intervals to a maximum total dose of 0.05 mg/kg (1.0 mg maximum).


METHODS
Clinical efficacy was assessed by the Clinical Global Impression Scale and Observer's Assessment of Alertness/Sedation Scale. The OAA/S, vital signs, lead II electrocardiogram, and clinical assessments were recorded at 0, 10, 30, 60, 90, and 120 minutes after flumazenil was given.


RESULTS
All children received midazolam (mean total dose, 0.18 mg/kg) for sedation. One hundred (96%) patients achieved a complete or partial response to flumazenil by 10 minutes after its administration, on the basis of their CGIS scores (the mean dose of flumazenil administered at the time of the first complete response was 0.017 +/- 0.010 mg/kg). Seventy-one of 93 (76%) patients with a baseline OAA/S score < or = 3 (1 = deep sleep, 5 = alert) experienced an increase of > or = 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 responding to flumazenil. Thirty-seven of 107 patients (35%) experienced a total of 56 adverse events, most of which were considered to be unrelated to flumazenil administration. The most frequently occurring adverse events were abnormal crying, dizziness, nausea, fever, and headache. 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 reverses the central nervous system depressant effects of midazolam in children undergoing conscious sedation, with no significant adverse effects. Because of the potential for resedation, children who receive flumazenil should be monitored for 1 to 2 hours after its administration.
Shannon
M
M
Division of Emergency Medicine, Children's Hospital, Boston, Massachusetts 02115, USA.
Albers
G
G
Burkhart
K
K
Liebelt
E
E
Kelley
M
M
McCubbin
M M
MM
Hoffman
J
J
Massarella
J
J
D000293:Adolescent; D000931:Antidotes / Q000627:therapeutic use*; D001569:Benzodiazepines; D002648:Child; D002675:Child, Preschool; D016292:Procedural Sedation / Q000009:adverse effects*; D005442:Flumazenil / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D008874:Midazolam; D012189:Retrospective Studies
D000931:Antidotes; D001569:Benzodiazepines; D005442:Flumazenil; D008874:Midazolam