Repeated intranasal flumazenil administration in adult subjects during prolonged benzodiazepine-induced sedation

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 patients. 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 administration in 24 of the 30 cycles, and in 100% of cases when subjects were at deeper levels of sedation.