Dual benefit of esketamine-based opioid-free anesthesia on postoperative pain and mental health outcomes in patients undergoing bariatric surgery: a randomized controlled trial

Patients with morbid obesity are at a high risk of comorbid depressive and anxiety symptoms. While bariatric surgery is an effective treatment, conventional opioid-based anesthesia carries significant perioperative risks. Opioid-free anesthesia (OFA) presents a safer alternative. Esketamine, known for its dual analgesic and rapid antidepressant effects, is a promising component of OFA. However, clinical evidence supporting its simultaneous benefits for both physical and psychological recovery in bariatric patients remains limited. In this double-blind, randomized clinical trial, patients scheduled for laparoscopic sleeve gastrectomy were randomly assigned (1:1) to receive either esketamine-based anaesthesia or opioid-based anaesthesia with remifentanil during surgery. The co-primary outcomes were postoperative pain intensity within the first 24 h and mental health status at three months after surgery. Secondary outcomes included pharmacokinetics of esketamine and adverse events. A total of 84 patients were randomized, with 42 allocated to each group. Seventy-four participants (88.1%) completed the 3-month follow-up. Patients in the esketamine group experienced significantly lower postoperative pain intensity ( P < 0.01) and a reduced incidence of moderate-to-severe pain ( P < 0.05) within 24 h after surgery. Mental health outcomes at 3 months were also significantly better in the esketamine group, and adverse events rate did not differ significantly. Pharmacokinetic analysis showed that plasma esketamine concentrations increased rapidly during infusion, with early formation of the active metabolite (S)-norketamine. Compared to opioid-based anaesthesia, esketamine-based opioid-free anaesthesia was associated with improved postoperative analgesia and better mental health outcomes in morbidly obese patients undergoing bariatric surgery, without increasing adverse events.