The effects of midazolam and flumazenil on psychomotor function and alertness in human volunteers

Objective To investigate the effect of midazolam and flumazenil on psychomotor function and alertness in human volunteers. Design Randomised, double-blind, cross over study. Methods Intravenous flumazenil was administered to sedated and non-sedated healthy human volunteers, in doses typical of those used clinically to induce sedation with midazolam and for reversal with flumazenil. Subjective assessment of alertness and objective measures of psychomotor function using light reaction time and the Maddox wing were made over a 1 hour period. Results Seven males and seven females each attended four experimental sessions. Psychomotor function was impaired by midazolam but there was some individual variation to this response. All sedated subjects receiving flumazenil had significantly improved alertness and psychomotor function when compared with those subjects who received placebo. Mean alertness (P < 0.01) and light reaction time (P < 0.05) showed significant improvement and returned to baseline by 60 minutes. Stability also showed significant improvement (P < 0.05) but did not return to baseline by 60 minutes. There was no significant effect on psychomotor function or alertness when the antagonist flumazenil was administered in the absence of the agonist midazolam. Conclusion An earlier discharge time based on subjective assessment of alertness is not advocated for patients whose intravenous midazolam sedation is reversed with flumazenil.