Effects of an Esketamine-Containing Induction Regimen on Postoperative Sleep, Analgesia, and Postpartum Depression in Parturients with Sleep Disorders Undergoing Cesarean Section Under General Anesthesia: A Double-Blind Randomized Trial.

Background: Preoperative sleep disturbances in parturients undergoing cesarean section correlate with exacerbated postoperative pain and an elevated risk of postpartum depression. Although esketamine demonstrates analgesic and antidepressant benefits in the general cesarean population, its combined effects on sleep, analgesia, and mood remain poorly characterized in patients with pre-existing sleep impairment. This study investigated the efficacy of an esketamine‑containing induction regimen on postoperative sleep quality, analgesia, and early depressive symptoms in parturients with PSQI‑defined preoperative sleep disorders scheduled for elective cesarean section under general anesthesia. Methods: We conducted a randomized, double-blind, placebo-controlled trial involving 90 parturients scheduled for elective cesarean section under general anesthesia. Participants were randomly allocated in a 1:1 ratio to receive either an esketamine-containing induction regimen (esketamine 0.25 mg/kg plus propofol 1.0 mg/kg; n=45) or a standard induction regimen (saline plus propofol 2.0 mg/kg; n=45). All 90 participants were included in the intention-to-treat analysis (missing data imputed), and 84 (41 vs 43) were included in the complete-case sensitivity analysis. The primary outcome was sleep quality on postoperative day (POD) 1, assessed using an 11-point sleep Numerical Rating Scale (NRS; 0=best, 10=worst; 24-hour recall). Secondary outcomes included sleep NRS scores on POD 3 and POD 42, and the Pittsburgh Sleep Quality Index (PSQI) on POD 42 (exploratory); Visual Analog Scale (VAS) pain scores at 2, 12, 24, and 48 hours, and rescue analgesic consumption over 72 hours; and Edinburgh Postnatal Depression Scale (EPDS) scores on POD 3 and POD 42 (≥13 indicating a positive result). Results: The esketamine regimen significantly improved the primary outcome (sleep NRS on POD 1; mean difference [MD] = 3.0, 95% CI: 2.0 to 4.0; P < 0.001). Exploratory secondary outcomes showed early pain benefits and reduced rescue analgesia (risk ratio [RR] = 3.33, 95% CI: 0.98 to 11.32; absolute risk difference = 15.5%, 95% CI: 0.7% to 30.21%), but these differences were small with wide intervals. Continuous EPDS scores were lower on POD 3 (P = 0.004), while the exploratory binary analysis (EPDS ≥ 13) was not significant (RR = 1.22, 95% CI: 0.56 to 2.66; P = 0.613). No serious adverse events occurred; however, the trial was not powered for safety outcomes. Conclusion: An esketamine-containing induction regimen was associated with improved early sleep quality on POD 1 in parturients with preoperative sleep disorders undergoing cesarean delivery under general anesthesia. However, because the trial was not powered for secondary outcomes or safety, and the differing propofol doses prevent isolation of esketamine's specific effect, these secondary findings are exploratory. Further adequately powered trials are required to confirm these results and evaluate safety. Trial Registration: Chinese Clinical Trial Registry, ChiCTR2300078490.