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

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: . 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: < 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.