Effect of Flumazenil on Disturbance of Equilibrium Function Induced by Midazolam
Benzodiazepines in intravenous sedation are useful, owing to their outstanding amnesic effect when used for oral surgery as well as dental treatments on patients with intellectual disability or dental phobia. However, compared with propofol, the effect of benzodiazepine lasts longer and may impede discharge, especially when it is administered orally because of fear of injections. Although flumazenil antagonizes the effects of benzodiazepine quickly, its effect on the equilibrium function (EF) has never been tested. Since EF is more objective than other tests, the purpose of this study is to assess the sedation level and EF using a computerized static posturographic platform. The collection of control values was followed by the injection of 0.075 mg/kg of midazolam. Thirty minutes later, 0.5 mg or 1.0 mg of flumazenil was administered, and the sedation level and EF were measured until 150 minutes after flumazenil administration. Flumazenil antagonized sedation, and there was no apparent resedation; however, it failed to antagonize the disturbance in EF. This finding may be due to differences in the difficulty of assessing the sedation level and performing the EF test, and a greater amount of flumazenil may effectively antagonize the disturbance in EF.Abstract

Gravicorder GS10. As shown in this picture, subjects stood on the platform in the heel position with feet spread at an angle of approximately 30°.

Changes in the sedation level. The results are expressed as the mean ± SE (n = 8). Midazolam 0.075 mg/kg was administered intravenously, and 30 minutes later, the test drug (flumazenil 0.5 mg or 1.0 mg) was administered. The sedation level was assessed on a 4-point scale as follows: 0 - awake and alert; 1 - drowsy; 2 - sedated, arousable when spoken to; 3 - sedated, not arousable. (a) Effects of 0.5 mg of flumazenil. (b) Effects of 1.0 mg of flumazenil. C indicates control; before, before an injection of flumazenil. ** Significantly different from the control values, P < .01.

Changes in the area of CG (center of gravity). The results are expressed as the mean ± SE (n = 8). Measurement of the area of CG was performed just after the assessment of the sedation level. Subjects stood on the platform with their eyes open for 1 minute. The values were automatically calculated by the platform. (a) Effects of 0.5 mg of flumazenil. (b) Effects of 1.0 mg of flumazenil. C indicates control; before an injection of flumazenil. * Significantly different from the control values, P < .05, ** P < .01.
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