Effect of Flumazenil on Disturbance of Equilibrium Function Induced by Midazolam

Abstract

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.

Midazolam Increases Bite Force During Intravenous Sedation

“…41,42 Although flumazenil 0.5 or 1.0 mg may antagonize the sedative effects of midazolam, it does not completely reverse the disturbance of the equilibrium function. 43 Therefore, the authors suggest that the PBR was activated by midazolam during sedation and that this activation was not reversed by flumazenil after sedation. These mechanisms may explain at least in part the sustained increase in bite force during midazolam sedation and flumazenil reversal.…”

The combined effects of midazolam and propofol sedation on muscle power

“…In addition, midazolam binds to both CBRs and PBRs, while flumazenil binds specifically to CBRs . Although 0.5–1.0 mg intravenous flumazenil antagonises the sedative effects of midazolam, it may not completely reverse the other actions of midazolam . It has been postulated that PBRs are activated by midazolam and this activation is not completely reversed by flumazenil.…”

Use of Flumazenil in Detoxification of High-Dose Benzodiazepine Users: A Mini Review of Pharmacological Basis and Clinical Studies

“…The use of Flumazenil in the detoxification of high dose abusers of BDZ is not a recent procedure as it has been applied in some clinics including in Italy for over 15 years. To date, we cannot say that this is the absolute best methodology for obtaining and, above all, maintaining over time the total abstention from BDZ in subjects who use at least 50 mg / day of diazepam-equivalent [34,35]. Certainly, the results available to date say that, compared to other methods such as progressive dose scaling or replacement with long acting agonists like clonazepam (very effective methods in therapeutic dose users), which have often proved unsuccessful in this type of patients, are often unsuccessful in high dose users [36].…”