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

Article · Ren Y, Li YT, Yin QL, Li HP, Zhang PJ, Cao JH, Yu B, Yang XL, Yang ZZ, Kong H

- Archive id: doi:10.1080/07853890.2026.2732292
- Published: 2026-09-16
- Venue: Annals of medicine
- DOI: https://doi.org/10.1080/07853890.2026.2732292
- PMID: 42745658
- PMCID: PMC13587535
- Citations: 0
- Source URL: https://doi.org/10.1080/07853890.2026.2732292
- PDF: https://europepmc.org/articles/PMC13587535/pdf
- Provenance: europepmc

## 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 reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Novel Psychiatric Therapeutics](https://space-kitty.com/topics/psychiatric-therapeutics)

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