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

Why clinicians should know about it

• Picked for Anesthesiology and Pain Medicine (top studies of the week, 20 September 2026): Opioid‑free esketamine‑dexmedetomidine vs sufentanil analgesia
• Picked for Obstetrics and Gynecology (top studies of the week, 20 September 2026): Double‑blind RCT of opioid‑free analgesia after gyn laparoscopy

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.

Abstract as published, via PubMed.