Recovery of sedation and psychomotor and equilibrium functions following remimazolam anesthesia with or without flumazenil: a randomized, double-blind, controlled trial.

Abstract

Background: Prompt awakening and sufficient recovery of psychomotor and equilibrium functions are important for day surgery. Flumazenil accelerates recovery of consciousness after remimazolam anesthesia, but its effects on psychomotor and equilibrium functions are not well known. The purpose of this study was to determine whether flumazenil improves time to recovery, psychomotor, and equilibrium functions in subjects undergoing remimazolam anesthesia.

Methods: The design was a single-center, double-blind, randomized, controlled trial. Inclusion criteria were patients aged 18-64 years scheduled for oral surgery under remimazolam anesthesia, with American Society of Anesthesiologists physical status I or II. The predictor variable was the use of a reversal agent (flumazenil group) versus placebo (non-flumazenil group). The primary outcome variable was recovery from sedation measured using the Modified Observer's Alertness/Sedation (MOAA/S) scale for wakefulness. Secondary outcome variables were psychomotor function measured using the Trieger Dot Test (number of dots missed [NDM], maximum distance of dots missed [MDDM]), and the digit symbol substitution test (DSST), as well as equilibrium function measured using the timed up and go test (TUG), and gravimetric area and speed. Statistical analyses were performed using the Mann-Whitney U test, χ² test, Student's t-test, two-way ANOVA, and Bonferroni correction. P-values < 0.05 were considered significant.

Results: Sixty-eight subjects were included (male: 33, female: 35). The mean time from extubation to an MOAA/S score of 5 (minutes) was 6.5 (1.5-10.5) in the flumazenil group and 13.5 (6.8-19.3) in the non-flumazenil group (P = 0.01). There was no significant difference in the recovery of psychomotor and balance functions between the two groups. However, the following measurements were significantly increased compared to baseline: NDM (P < 0.001) and DSST (P < 0.001) at 30 minutes, MDDM (P < 0.001), TUG (P < 0.001), and gravimetric speed (P < 0.001) at 60 minutes, and gravimetric area (P = 0.03) at 90 minutes.

Conclusion: Administration of flumazenil after remimazolam anesthesia resulted in faster recovery of consciousness, but it did not affect the recovery of psychomotor and equilibrium functions. The time until patients were safe to return home was 120 minutes. Flumazenil did not improve the time until it was safe for patients to return home.