Opioid-free analgesia with esketamine-dexmedetomidine versus opioid-based analgesia after gynaecological laparoscopic surgery: a double-blind, randomized, controlled trial

Abstract

Abstract Background Postoperative opioid-based analgesia after gynecological laparoscopic surgery often causes dizziness, nausea and vomiting, with limited benefit for mood and sleep. We tested whether opioid-free analgesia combining dexmedetomidine and esketamine was non-inferior to sufentanil-based opioid analgesia for pain control and superior for postoperative recovery quality. Methods Adult ASA I–III patients undergoing elective gynecological laparoscopic surgery were randomized 1:1. The opioid-free group received patient-controlled intravenous analgesia (PCIA) with esketamine 1 mg kg-1 plus dexmedetomidine 3 μg kg-1; the opioid group received sufentanil 2 μg kg-1. The primary non-inferiority endpoint was the area under the curve (AUC) of numerical rating scale (NRS) pain scores during coughing within 48 h postoperatively; the primary superiority endpoint was the mean quality of recovery (QoR)-15 score on postoperative days 1 and 2. Results Of 134 randomized patients, 132 were analyzed per intention-to-treat. Pain control was non-inferior in the opioid-free group (AUC 175 [47] vs 169 [37]; mean difference 6, 95%CI −8 to 20; non-inferiority margin 24, p = 0.008). The mean QoR-15 score was significantly higher in the opioid-free group (116 [10] vs 108 [12]; mean difference 8, 95%CI 4–12; p < 0.001), driven by better physical comfort and emotional state domain scores, with comparable pain domain scores. No serious adverse events occurred. Conclusions Postoperative opioid-free analgesia with dexmedetomidine and esketamine provides analgesia non-inferior to sufentanil-based opioid analgesia and significantly improves postoperative quality of recovery, and may serve as a promising alternative strategy for postoperative analgesia in this population. Trial registration: This trial was registered at the Chinese Clinical Trial Registry (identifier: ChiCTR2300078569) on 12 December 2023 before patient recruitment.