Effect of Remimazolam on Pain Perception and Opioid-Induced Hyperalgesia in Patients Undergoing Laparoscopic Urologic Surgery—A Prospective, Randomized, Controlled Study

Abstract

Background and Objectives: The effects of midazolam, a benzodiazepine, on pain perception are complex on both spinal and supraspinal levels. It is not yet known whether remimazolam clinically attenuates or worsens pain. The present study investigated the effect of intraoperative remimazolam on opioid-induced hyperalgesia (OIH) in patients undergoing general anesthesia. Materials and Methods: The patients were randomized into three groups: group RHR (6 mg/kg/h initial dose followed by 1 mg/kg/h remimazolam and 0.3 μg /kg/min remifentanil), group DHR (desflurane and 0.3 μg /kg/min remifentanil) or group DLR (desflurane and 0.05 µg/kg /min remifentanil). The primary outcome was a mechanical hyperalgesia threshold, while secondary outcomes included an area of hyperalgesia and clinically relevant pain outcomes. Results: Group RHR had a higher mechanical hyperalgesia threshold, a smaller hyperalgesia postoperative area at 24 h, a longer time to first rescue analgesia (p = 0.04), lower cumulative PCA volume containing morphine postoperatively consumed for 24 h (p < 0.01), and lower pain intensity for 12 h than group DHR (p < 0.001). However, there was no significant difference in OIH between groups RHR and DLR. Conclusions: Group RHR, which received remimazolam, attenuated OIH, including mechanically evoked pain and some clinically relevant pain outcomes caused by a high dose of remifentanil. Further research is essential to determine how clinically meaningful and important the small differences observed between the two groups are.

Quality of Postoperative Recovery in Total Intravenous Anesthesia between Remimazolam and Propofol for Intraoperative Neurophysiological Monitoring: A Prospective Double-Blind Randomized Controlled Trial

“…Remifentanil consumption during surgery was notably higher in group R compared to group P. Despite concerns about opioid-induced hyperalgesia (OIH), our study showed that group R experienced less pain intensity compared with group P while resting in the PACU. This discrepancy is likely attributed to the effects of remimazolam on GABA receptors, potentially affecting pain perception [36]. While one might anticipate delayed recovery time, increased pain intensity due to OIH, and frequent use of rescue analgesics in group R, which received higher doses of remifentanil, the remimazolam group remarkably exhibited more favorable outcomes in these aspects in this study.…”