Drug Des Devel Ther. 2026 Oct 14;20:630545. doi: 10.2147/DDDT.S630545. eCollection 2026.
ABSTRACT
PURPOSE: Postoperative sleep disturbance (PSD) is a common complication after oocyte retrieval under intravenous anesthesia. This study aimed to evaluate whether a subanesthetic dose of esketamine reduces the incidence of PSD.
PATIENTS AND METHODS: This randomized, double-blind, placebo-controlled trial included 196 women undergoing oocyte retrieval under intravenous anesthesia. Participants were randomly assigned to the esketamine or control group. During anesthesia induction, the esketamine group received an intravenous bolus of esketamine 0.2 mg/kg, whereas the control group received an equivalent volume of normal saline. The primary analysis was conducted according to the intention-to-treat principle, with missing outcome data handled using multiple imputation; 189 participants (95 in the control group and 94 in the esketamine group) were included in the per-protocol sensitivity analysis. The primary outcome was the incidence of PSD on postoperative day (POD) 3, defined using a composite criterion of an Athens Insomnia Scale (AIS) score ≥6 or a numerical rating scale (NRS) score ≥6. Secondary outcomes included the incidence of PSD on POD 1, postoperative pain scores, postoperative anxiety and depression scores, and patient satisfaction with the anesthetic technique.
RESULTS: In the intention-to-treat analysis with multiple imputation, the estimated incidence of PSD on POD 3 was lower in the esketamine group than in the control group (13.06% vs 24.90%; risk difference, -11.84 percentage points [95% CI, -22.98 to -0.69]; relative risk [RR], 0.52 [95% CI, 0.28-0.99]; P = 0.047). The per-protocol (PP) sensitivity analysis yielded similar results (12.8% vs 24.2%; RR, 0.53 [95% CI, 0.28-0.99]; P = 0.043). PSD on POD 1 did not differ between the groups. No between-group differences in postoperative anxiety or depression scores were noted. Postoperative pain scores at 30 minutes were significantly lower in the esketamine group (P < 0.001). Dreaming was more frequent in the esketamine group (21.4% vs 11.2%; P = 0.048), and the time to full alertness (12 [10-14] vs 11 [9-13] minutes; P = 0.002) and postanesthesia care unit (PACU) stay (34 [30-37] vs 31 [29-34] minutes; P = 0.005) were modestly longer.
CONCLUSION: A single subanesthetic dose of esketamine was associated with a lower incidence of short-term PSD on POD 3 in women undergoing oocyte retrieval under intravenous anesthesia. Larger multicenter studies are warranted to confirm these findings.
TRIAL REGISTRATION: China Clinical Trial Registry Identifier: ChiCTR2500105998.
PMID:42894628 | PMC:PMC13676867 | DOI:10.2147/DDDT.S630545
