Perioperative esketamine for prevention of postoperative sleep disturbance after anesthesia: a systematic review and meta-analysis of randomized controlled trials.

TL;DR: A meta-analysis of 22 randomized controlled trials found that perioperative esketamine reduced postoperative sleep disturbance on days 1-3 after surgery, with moderate certainty of evidence . Effects did not persist by day 7, and long-term impacts remain unknown.

What the Study Found

Postoperative sleep disturbance affects a substantial portion of patients recovering from general anesthesia. Poor sleep in the immediate postoperative period is linked to slower recovery, increased pain perception, and worse overall outcomes. Researchers conducted a systematic review and meta-analysis to evaluate whether esketamine, a dissociative anesthetic agent, could prevent this common complication when given during the perioperative window.

The analysis pooled data from 22 randomized controlled trials comparing perioperative esketamine to placebo or standard care. The primary focus was the incidence of postoperative sleep disturbance across different timepoints: postoperative days 1, 2, 3, and 7. Across these trials, esketamine showed a dose-dependent benefit early on: the incidence of sleep disturbance dropped by 42% on postoperative day 1 (risk ratio = 0.58), 60% on day 2 (RR = 0.40), and 45% on day 3 (RR = 0.55). These effects were statistically significant and robust across sensitivity analyses. However, by postoperative day 7, the difference between esketamine and control groups narrowed and was no longer statistically significant (RR = 0.77), suggesting the benefit does not extend into the second week of recovery.

The certainty of evidence for early outcomes was rated as moderate, meaning the findings are reasonably reliable but not definitive. Statistical heterogeneity across studies was low, indicating consistent results, though the researchers acknowledged clinical heterogeneity: the trials differed in surgical types, patient populations, esketamine dosing regimens, and how sleep disturbance was measured. Subgroup analyses generally confirmed the early benefit pattern, though results stratified by preoperative sleep status require cautious interpretation. No statistically significant differences emerged in the analyzed adverse events, though the researchers emphasized that safety data remain limited and further monitoring is warranted.

A critical limitation: most included trials used subjective, binary assessments of sleep disturbance rather than objective measures like polysomnography or actigraphy. The meta-analysis captured whether patients reported poor sleep, not the actual architecture or quality of sleep. Effects on objective sleep parameters, circadian rhythm recovery, and long-term sleep outcomes remain uncertain.

What This Means for You

If you are scheduled for surgery under general anesthesia, this research provides suggestive evidence that esketamine during the perioperative period could reduce the likelihood of poor sleep in the first few nights after your operation. The benefit appears strongest on days 1 and 2. However, the findings have practical limits:

This is not a reason to request esketamine solely for sleep prevention, but if your anesthesia team proposes it for other perioperative benefits (pain, postoperative nausea, delirium prevention), the sleep benefit would be a secondary upside. Standard postoperative sleep hygiene practices, such as maintaining cool room temperature, minimizing light and noise, and managing pain effectively, remain foundational regardless of pharmacologic interventions.

Study Details

Sources

PubMed: 42318333