# Effect of flumazenil on recovery of memory following recovery of consciousness from general anesthesia with remimazolam: a randomized, open-label, single-center controlled trial

## TL;DR

This study found that giving flumazenil after patients regain consciousness from anesthesia with remimazolam helps them recover memory faster.

## Contribution

The novel finding is that flumazenil accelerates memory recovery after remimazolam-based anesthesia, even though memory returns within 2 hours without it.

## Key findings

- Patients who received flumazenil had significantly better memory retention 1 hour after regaining consciousness.
- All patients, regardless of flumazenil use, recovered memory within 2 hours post-surgery.
- Effect-site concentration of remimazolam at consciousness recovery was similar between groups.

## Abstract

Recovery of consciousness from general anesthesia with remimazolam, an ultrashort-acting benzodiazepine, occurs rapidly. However, patients after recovery of consciousness from general anesthesia with remimazolam often experience periods of amnesia. Remimazolam can be antagonized by flumazenil. Therefore, we investigated the effect of flumazenil on the recovery of memory following the recovery of consciousness from general anesthesia with remimazolam.

This single-center randomized controlled trial was conducted from November 2023 to July 2024. Forty-four patients undergoing breast surgery were enrolled. The patients received general anesthesia with remimazolam and remifentanil and were randomized to receive flumazenil after recovery of consciousness or not. The recovery of the memory was evaluated by showing an A4-size poster (illustration) to the patients and asking them to remember the poster every 1 h. Furthermore, the effect-site concentration of remimazolam was calculated using the Masui model.

All 44 patients (22 with and 22 without flumazenil) were assessed. The percentage of patients who remembered the poster 1 h after regaining consciousness was significantly higher in the flumazenil group than in the no flumazenil group (95.5 vs 40.9%; p < 0.001). All patients could recall the poster within 2 h postoperatively. The mean effect-site concentration of remimazolam at the time of consciousness recovery was similar between the two groups (0.31 ± 0.08 µg/mL).

Flumazenil significantly accelerated the recovery of memory retention in patients who had recovered consciousness from general anesthesia with remimazolam. However, even without the administration of flumazenil, all patients successfully recovered their memory within 2 h after regaining consciousness.

This clinical trial was registered at the University Hospital Medical Information Network (UMIN) Center on November 01, 2023 (UMIN-CTR: UMIN000052659).

The online version contains supplementary material available at 10.1186/s40981-025-00825-5.