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

Hongwei Zhang·Feng Yin·Lantao Li·Xuefei Li·Weiwei Xu·Yi Zhou·Liang Jin·Hongyan Lin·Xihua Lu·Jianjun Yang·Hai Yu
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Abstract

BACKGROUND: 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. METHODS: In this double-blinded, multicenter randomized controlled trial, patients scheduled for elective McKeown esophagectomy were allocated to esketamine (0.25&#x2009;mg/kg loading dose and 0.125&#x2009;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. RESULTS: A total of 198 patients were analyzed (esketamine, n&#x2009;=&#x2009;98; placebo, n&#x2009;=&#x2009;100). Intraoperative esketamine significantly improved QoR-15 scores on POD 2 (116.9&#x2009;&#xb1;&#x2009;9.4 vs. 110.2&#x2009;&#xb1;&#x2009;9.8, p&#x2009;<&#x2009;0.001) and POD 3 (123.6&#x2009;&#xb1;&#x2009;7.2 vs. 116.8&#x2009;&#xb1;&#x2009;8.4, p&#x2009;<&#x2009;0.001) compared with placebo. HADS-A and HADS-D scores were lower in the esketamine group on POD 1 to 3 (all p&#x2009;<&#x2009;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&#x2009;<&#x2009;0.001). There were no significant between-group differences in safety outcomes. CONCLUSIONS: Intraoperative low-dose esketamine improved early, patient-reported recovery after MIE by enhancing analgesia and reducing postoperative anxiety and depression without increasing adverse events. TRIAL REGISTRATION: Chinese Clinical Trial Register (identifier: ChiCTR2400088916).

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HumansEsophagectomyPostoperative PainDouble-Blind MethodFemaleMaleAgedMiddle AgedMinimally Invasive Surgical ProceduresAnxietyPain MeasurementDepressionAnalgesicsTreatment OutcomeKetamineEsketamineminimally invasive esophagectomyquality of recoveryJournal ArticleMulticenter StudyRandomized Controlled TrialResearch Support, Non-U.S. Gov't

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Hongwei Zhang, Feng Yin, Lantao Li, Xuefei Li, Weiwei Xu, Yi Zhou, Liang Jin, Hongyan Lin, Xihua Lu, Jianjun Yang, Hai Yu. 2026-07-22. Effects of low-dose esketamine on early quality of recovery following minimally invasive esophagectomy: a multicenter, randomized controlled study.. https://doi.org/10.1080/07853890.2026.2704297

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