Intraoperative Opioid-Free Anesthesia with Dexmedetomidine and Esketamine Versus Conventional General Anesthesia in Laparoscopic Cholecystectomy at 3,600 m: A Randomized Trial on Hemodynamic Stability and Postoperative Recovery

Tu, Ke, Lei Tian, Qi Zhu, Kailian Bai, Lin Li, Mengmei Fu, Mengxia Wang, Lei Zhang, Zhuo Zhan, Haoxi Li, Xiaojun Li, Ruofan Yi, Cheng Jiang, Hua Huang, and Mingming Zhang. Intraoperative opioid-free anesthesia with dexmedetomidine and esketamine versus conventional general anesthesia in laparoscopic cholecystectomy at 3,600 m: a randomized trial on hemodynamic stability and postoperative recovery. High Alt Med Biol. 27:8–16, 2026. Background: Opioid-free anesthesia (OFA) is gaining attention as an alternative to opioid-based techniques. However, its hemodynamic and clinical characteristics at high altitudes, where hypoxia and resource limitations prevail, remain unclear. Methods: In this single-blind randomized trial, 48 patients undergoing laparoscopic cholecystectomy at 3,600 m were assigned to either a conventional general anesthesia (CGA) group (sevoflurane, sufentanil, remifentanil) or an OFA group (sevoflurane, dexmedetomidine, esketamine). The primary outcome was intraoperative mean arterial pressure (MAP); secondary outcomes included heart rate (HR), awakening time, sedation level, patient satisfaction, postoperative pain, postoperative nausea and vomiting (PONV), perioperative medication use, and adverse events. Results: Compared with CGA, the OFA group maintained higher intraoperative MAP, with significant differences after induction (OFA: 87.9 ± 12.3 vs. CGA: 77.2 ± 11.7 mmHg, p < 0.005) and 10 minutes after incision (OFA: 83.5 ± 14.9 vs. CGA: 72.5 ± 9.8 mmHg, p < 0.005). The CGA group exhibited a significant MAP decline at 10 minutes postincision (72.5 ± 9.8 vs. baseline: 83.0 ± 9.1 mmHg, p < 0.001), whereas the OFA group showed a transient MAP increase after intubation (96.1 ± 16.1 vs. baseline: 85.8 ± 7.8 mmHg, p < 0.01). HR trends paralleled MAP changes. Awakening time was significantly longer with OFA (OFA: 20.4 ± 7.5 min vs. CGA: 10.6 ± 8.2 min, p < 0.001), while pain scores at 6 and 12 hours were lower ( p < 0.005). Sedation, satisfaction, PONV, and medication use were comparable. No severe adverse events occurred. Conclusions: At high altitudes, OFA with dexmedetomidine and esketamine exhibited distinct clinical characteristics compared with opioid-based anesthesia, maintaining blood pressure and postoperative analgesia but less effectively blunting intubation-induced pressor responses and prolonging awakening time. These factors should be weighed when selecting anesthesia strategies in resource-limited, high-altitude settings, particularly when managing large numbers of patients.