Reversal of Zolpidem Intoxication By Sublingual Flumazenil

摘要

In military operational environments, fatigue induced performance decrements resulting from reduced sleep and disrupted daily rhythms may result in outcomes ranging from severe discomfort, to mission degradation, to loss of life. In the operational environment, sleep aids cannot be used to rest the warfighter because the warfighter may be called upon to act on short notice and the sleep aid might itself degrade performance resulting in the same poor outcome. However, if the sleepiness and cognitive degradation caused by the sleep aid could be reversed, the use of sleep aids could be expanded to include some operational environments. The objective of this study was to evaluate the ability of flumazenil, administered as a liquid sublingually, to quickly and safely counteract the sleep-inducing effect of zolpidem. Thirteen participants received 10 mg zolpidem or placebo, instructed to sleep 90 minutes, and were then awakened and given either 1 mg flumazenil or placebo and tested. At the beginning of the second hour after awakening, participants were given a second sublingual; 1 mg does of flumazenil or placebo and tested over the next 5 hours. The repeated-measures, double-blind design showed that flumazenil provided partial recovery from the soporific effects of zolpidem. Conclusions: 1. Sublingual flumazenil, administered immediately on awakening, was shown to reverse the cognitively degrading effects of zolpidem by 23%, restoring performance to 92.5% of placebo. 2. One to two hours after awakening, performance did not return to the level of the placebo after flumazenil administration, but rather joined the zolpidem-only decay function which continued to be approximately 20% degraded compared to placebo.