Effect of estazolam plus remimazolam on attenuating preoperative anxiety and remifentanil-induced postoperative hyperalgesia in elective gynecological laparoscopic surgery: a randomized clinical trial.

Abstract

Background: Preoperative anxiety is closely related to opioid-induced hyperalgesia, and high levels of preoperative anxiety have the potential to aggravate opioid-induced hyperalgesia. We aimed to estimate the effect of estazolam, remimazolam, and their combination on preoperative anxiety and opioid-induced hyperalgesia in patients undergoing elective gynecological laparoscopic surgery.

Methods: We carried out a randomized, double-blind, placebo-controlled experiment between October 2020 and April 2021. Starting on 9, October 2020,a total of 108 patients were split into four groups: (1 mg estazolam or starch was taken orally on the evening before surgery; 0.1 mg/kg remimazolam or normal saline was administered intravenously after entering the operating room) Group E received estazolam and normal saline; Group R received starch and remimazolam; participants in Group ER were given not only estazolam but also remimazolam; participants in Group C were given starch and normal saline. We recorded pain intensity at rest at 24 hours postoperatively as the primary outcome and measured pain intensity, sufentanil consumption, and adverse events within 72 hours postoperatively.

Results: The mean anxiety scores were significantly lower in Groups E, R, and ER than in Group C before surgery. Compared with Group C, mean pain scores were significantly lower in Group ER at 0.5, 1, 4, 8, 24, 48, and 72 hours after surgery and lower in Groups R or E at 4, 8, and 24 hours after surgery. The mean pain scores in Group E (at 8 and 24 hours postoperatively) and Group R (at 8 hours postoperatively) were both significantly higher than those in Group ER. Moreover, the mean cumulative sufentanil consumption was significantly lower in Group ER at 0.5, 1, 4, 8, 24, 48, and 72 hours after surgery and lower in Groups E or R at 0.5 hours after surgery, compared with Group C.

Conclusions: The preoperative application of estazolam, remimazolam, and their combination can relieve preoperative anxiety and postoperative pain for patients undergoing gynecological laparoscopic surgery. Moreover, the preoperative combination can also significantly reduce postoperative sufentanil consumption.