A comparison of 3 routes of flumazenil administration to reverse benzodiazepine-induced desaturation in an animal model.
OBJECTIVE
The purpose of this study was to examine intralingual (IL) and submucosal (SM) delivery offlumazenil as viable alternatives to immediate intravenous (IV) administration for reversing benzodiazepine sedation in an animal model.


METHODS
A dog animal model was chosen based upon comparable body weight to children (12-17 kg) and the ease of oral access in this species. Research design was a nonrandomized matched pair study. This type of "before-and-after study" allowed the dogs to receive 3 different routes of flumazenil administration (IV, IL, and SM) following an initial dose of midazolam (0.5 mg/kg IV). Blood samples were obtained (at 0, 2, 4, 8, 15, and 30 minutes) for high performance liquid chromatography (HPLC) analysis of flumazenil and midazolam, and oxygen saturation values were recorded.


RESULTS
Both IL and SM delivery of flumazenil were determined to be viable alternatives to immediate IV administration for reversing benzodiazepine-induced oxygen saturation (SaO2) desaturation. For flumazenil to be able to reverse the SaO2 desaturation, the plasma levels must be greater than 5 ng/ml, which was exceeded by IL and SM drug delivery.


CONCLUSIONS
In a benzodiazepine-induced desaturation, the submucosal and intralingual routes are viable alternatives to intravenous administration of flumazenil in an animal model.
Unkel
John H
JH
Department of Pediatric Dentistry, Virginia Commonwealth University, Richmond,
Brickhouse
Tegwyn H
TH
Sweatman
Trevor W
TW
Scarbecz
Mark
M
Tompkins
William P
WP
Eslinger
Chad S
CS
D000284:Administration, Oral; D000818:Animals; D001569:Benzodiazepines / Q000037:antagonists & inhibitors*; D004285:Dogs; D005442:Flumazenil / Q000008:administration & dosage*; D018757:GABA Modulators / Q000008:administration & dosage* / Q000037:antagonists & inhibitors*; D007275:Injections, Intravenous; D008297:Male; D008874:Midazolam / Q000037:antagonists & inhibitors*; D023421:Models, Animal; D010100:Oxygen / Q000097:blood*
D018757:GABA Modulators; D001569:Benzodiazepines; D005442:Flumazenil; D008874:Midazolam; D010100:Oxygen