Esketamine Linked to Less Day-3 Sleep Disruption After Oocyte

Key Takeaways

• Among women undergoing transvaginal oocyte retrieval under intravenous anesthesia, esketamine was associated with significantly less day-3 sleep disturbance than saline.
• Day-1 sleep disturbance and postoperative anxiety and depression scores did not differ significantly between groups.
• Pain at 30 minutes, intraoperative hypotension, and movement were lower with esketamine.
• Dreaming was more frequent with esketamine, while full alertness and postanesthesia care unit stay took longer.

Women undergoing retrieval were enrolled in Ma and colleagues' randomized trial of esketamine and sleep after oocyte retrieval at the First Affiliated Hospital of Zhengzhou University in China. The prospective, single-center, double-blind, placebo-controlled trial ran from July through November 2025 and randomized 196 women aged 18–50, with 98 per arm.

Eligible women had American Society of Anesthesiologists (ASA) physical status I–II; a recent Athens Insomnia Scale (AIS) score ≥6 excluded participation. Before induction, women received intravenous esketamine 0.2 mg/kg or equal-volume saline, followed in both groups by ciprofol and remifentanil. The prespecified day-3 composite was AIS ≥6 or sleep numerical rating scale (NRS) ≥6; day-1 sleep, pain, mood, and anesthesia satisfaction were secondary measures.

Seven women did not complete all follow-up assessments. All randomized women remained in the intention-to-treat (ITT) analysis, which used multiple imputation for missing outcomes. The per-protocol (PP) sensitivity analysis included 189 women (94 esketamine, 95 saline).

In the prespecified ITT analysis, pooled estimated risks of day-3 composite sleep disturbance after multiple imputation were 13% with esketamine versus 24.9% with saline. The absolute risk difference was −11.84 percentage points (95% confidence interval [CI] −22.98 to −0.69). For this estimated ITT finding, the relative risk was 0.52 (95% CI 0.28–0.99; P=0.047).

In the PP sensitivity analysis, observed day-3 composite events occurred in 12/94 (12.8%) esketamine recipients versus 23/95 (24.2%) saline recipients. The risk difference was −11.44 percentage points (95% CI −22.39 to −0.50). The PP relative risk was 0.53 (95% CI 0.28–0.99; P=0.043).

Day-1 sleep disturbance and adjusted AIS, anxiety, depression, and postoperative-day pain comparisons did not differ significantly. Pain at 30 minutes was lower with esketamine; intraoperative hypotension and movement were less frequent. Anesthesia satisfaction and willingness to repeat anesthesia were comparable.

Dreaming occurred in 21.4% of esketamine recipients versus 11.2% of saline recipients. Most other measured adverse events did not differ significantly. Median time to full alertness was 12 versus 11 minutes, and median postanesthesia care unit (PACU) stay was 34 versus 31 minutes, respectively.

The investigators noted that sleep was self-reported rather than objectively measured and assessed only on days 1 and 3, leaving its intervening course and persistence beyond day 3 unknown. Hormonal and circadian parameters were not measured, so the trial did not establish a sleep mechanism. Applicability remains confined to relatively young ASA I–II women at one Chinese center undergoing this procedure with this anesthetic regimen; the nonsignificant day-1 finding does not establish equivalence.

The investigators characterized the association between a single esketamine bolus and less day-3 sleep disturbance as short-term, alongside more dreaming and modest recovery delays. They called for larger multicenter confirmation.

Clinician Questions

How was full alertness defined after intravenous anesthesia for oocyte retrieval?

For women undergoing transvaginal oocyte retrieval with intravenous anesthesia, time to full alertness ran from the last anesthetic administration to the first of three consecutive Modified Observer’s Assessment of Alertness/Sedation scores of 5.