Background: Patients undergoing modified radical mastectomy (MRM) often suffer some postoperative adverse events such as acute pain, mental abnormalities, and sleep disorders. This study aim to explore the effect of esketamine as the sole intraoperative analgesic on the quality of postoperative recovery in patients undergoing MRM.Methods: Ninety-eight female patients scheduled for elective MRM were randomly divided into two groups: the esketamine group (group E) or remifentanil group (group R).

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... In group E, anesthesia was induced with etomidate, midazolam, esketamine, and rocuronium, and maintained with intravenous propofol and esketamine. In group R, anesthesia was induced with etomidate, midazolam, rocuronium, and remifentanil, and maintained with propofol and remifentanil. The scores of the Quality of Recovery (QoR-40) questionnaire, and Pittsburgh Sleep Quality Index (PSQI) were evaluated at 1 d, 3 d, 7 d, and 30 d after surgery as primary outcome and main secondary outcome respectively. Other secondary outcomes including intraoperative hemodynamics, postoperative inflammatory indicator, and the incidence of adverse events (e.g., vomiting and dizziness) during hospitalization were also recorded.Main Results: QoR-40 total scores in group E were higher than group R at 1 d [160.71±9.811 VS 146.94±7.375, P<0.001], 3 d [168.45±9.670 VS 152.90±8.089, P<0.001], 7 d [180.06±7.367 VS 175.20±6.334, P=0.001] postoperatively. The PSQI scores in group E were lower than group R at 1 d [14.18±1.740 VS 17.20±1.87, P<0.001], 3 d [11.82±1.799 VS 16.31±2.133, P<0.001], 7 d [7.71±1.814 VS 9.65±1.832, P<0.001] after surgery. Conclusion: Our research shows that esketamine has a certain effect on improving the quality of short-term recovery after MRM.Clinical Trials Registration: Clinical Trials gov: ChiCTR2200056576. registered February 8th, 2022, http://www.chictr.org.cn/index.aspx.