Effects of low-dose esketamine on early quality of recovery following minimally invasive esophagectomy: a multicenter, randomized controlled study

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Patients undergoing minimally invasive esophagectomy (MIE) frequently experience moderate-to-severe postoperative pain and anxiety-depressive symptoms, compromising postoperative quality of recovery (QoR). Esketamine is a promising adjunct for analgesia and anxiolysis; however, the effect of low-dose esketamine on patient-centered recovery outcomes in MIE remains unclear. In this double-blinded, multicenter randomized controlled trial, patients scheduled for elective McKeown esophagectomy were allocated to esketamine (0.25 mg/kg loading dose and 0.125 mg/kg/h continuous infusion during surgery) or placebo (equivalent volume and rate of saline). The primary outcome was the QoR-15 score on postoperative day (POD) 2. Secondary outcomes included QoR-15 scores on POD 1, 3, 7 and 30. Hospital Anxiety and Depression Scale - Anxiety Subscale (HADS-A) and Depression Subscale (HADS-D) scores, numeric rating scale (NRS) pain scores, and the Brief Pain Inventory (BPI) scores on POD 1 to 3, and safety evaluations. A total of 198 patients were analyzed (esketamine, n = 98; placebo, n = 100). Intraoperative esketamine significantly improved QoR-15 scores on POD 2 (116.9 ± 9.4 vs. 110.2 ± 9.8, p < 0.001) and POD 3 (123.6 ± 7.2 vs. 116.8 ± 8.4, p < 0.001) compared with placebo. HADS-A and HADS-D scores were lower in the esketamine group on POD 1 to 3 (all p < 0.001). Additionally, esketamine recipients reported significantly lower NRS scores at rest and during movement and BPI scores for pain severity and pain interference items (all p < 0.001). There were no significant between-group differences in safety outcomes. Intraoperative low-dose esketamine improved early, patient-reported recovery after MIE by enhancing analgesia and reducing postoperative anxiety and depression without increasing adverse events. Chinese Clinical Trial Register (identifier: ChiCTR2400088916). Patients undergoing minimally invasive esophagectomy often experience poor quality of recovery due to postoperative pain, anxiety, and depression. Effective analgesia and psychological support are essential to improving postoperative recovery in these patients.No prior studies have specifically examined the effect of low-dose esketamine on patient-centered recovery outcomes in patients undergoing minimally invasive esophagectomy.Low-dose esketamine (0.25 mg/kg loading dose and 0.125 mg/kg/h continuous infusion during surgery) improved early, patient-reported recovery after minimally invasive esophagectomy by enhancing analgesia and reducing postoperative anxiety and depression, without increasing adverse events. Patients undergoing minimally invasive esophagectomy often experience poor quality of recovery due to postoperative pain, anxiety, and depression. Effective analgesia and psychological support are essential to improving postoperative recovery in these patients. No prior studies have specifically examined the effect of low-dose esketamine on patient-centered recovery outcomes in patients undergoing minimally invasive esophagectomy. Low-dose esketamine (0.25 mg/kg loading dose and 0.125 mg/kg/h continuous infusion during surgery) improved early, patient-reported recovery after minimally invasive esophagectomy by enhancing analgesia and reducing postoperative anxiety and depression, without increasing adverse events.

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