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Abstract
As part of a study exploring the use of oral diazepam to reduce carbon dioxide production and extend survival in a disabled submarine, intranasal flumazenil was used repeatedly over 48 hours to intermittently reverse benzodiazepine-induced sedation in six adult male subjects. Previous reports of intranasal flumazenil have been limited to pediatric pa-tients. Here we report the time course of administration of intranasal flumazenil and its effects on adult subjects, in whom flumazenil was given during sedation/reversal/re-sedation cycles. Sedation scores increased with flumazenil administra-tion in 24 of the 30 cycles, and in 100% of cases when subjects were at deeper levels of sedation.
Highlights
The U.S Food & Drug Administration has only approved intravenous administration of flumazenil, there are reports in the pediatric literature of successful intranasal [1, 2] and rectal administration [3, 4] of this competitive benzodiazepine antagonist
After the 30 intranasal administrations, OAA/S scores increased in twenty-four cases,and they remained the same in six cases; when subjects were at deeper levels of sedation (OAA/S scores less than 4), these scores increased in 100% of cases after flumazenil administration
At the 24-hour telephone follow up, the subjects still reported symptoms of sedation, while at the 72hour telephone follow up they reported that they were back to normal condition and activities. This is the first report in the medical literature of the use of intranasal flumazenil to reverse sedation in healthy adult humans
Summary
The U.S Food & Drug Administration has only approved intravenous administration of flumazenil, there are reports in the pediatric literature of successful intranasal [1, 2] and rectal administration [3, 4] of this competitive benzodiazepine antagonist. There is no report of intranasal flumazenil administration in adults in the medical literature, only an internet summary of a graduate student thesis [6]. As part of a study exploring the use of a benzodiazepine (diazepam) to reduce carbon dioxide production and extend survival in a disabled submarine, intranasal flumazenil was used repeatedly over 48 hours to intermittently reverse sedation in adult subjects [7]. We report the time course of the administration of intranasal flumazenil and its effects on young healthy adults
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