Pain Physician. 2026 Jul;29(5):E325-E336.
ABSTRACT
BACKGROUND: Postoperative sleep disturbance (PSD) is a complication that often follows surgery. The condition is closely associated with impaired recovery, heightened pain sensitivity, and increased risk of chronic postsurgical pain. While pharmacological interventions like dexmedetomidine and esketamine have been reported to improve perioperative sleep quality, their comparative efficacy-particularly in the realm of analgesia-remains uncertain.
OBJECTIVES: This review aimed to evaluate the efficacy of dexmedetomidine and esketamine in treating PSDs and providing analgesia.
STUDY DESIGN: We conducted a systematic review and network meta-analysis of randomized controlled trials (RCTs) that compared the effects of dexmedetomidine, esketamine, and control interventions on adult surgical patients.
SETTING: Comprehensive literature searches were performed in 4 electronic databases from their inception to August 1st, 2025. The protocol was previously registered in the PROSPERO database under the registration number CRD420251126227.
METHODS: The primary outcomes were postoperative pain scores assessed using the Visual Analog Scale (VAS) at 24 and 48 hours. Secondary outcomes included the incidence of PSD, Athens Insomnia Scale (AIS) scores, and sleep quality measured on the Numerical Rating Scale (NRS). Subjective sleep outcomes were synthesized using a Bayesian network meta-analysis. Additionally, a supplementary traditional meta-analysis was performed on studies that used polysomnography (PSG) to evaluate objective sleep architecture.
RESULTS: Ten RCTs involving 645 patients were included in the study. Esketamine demonstrated significantly superior analgesic efficacy, substantially reducing VAS pain scores both at rest and during movement at 24 and 48 hours postoperatively. Compared to the control, both esketamine and dexmedetomidine showed a tendency to reduce the incidence of PSD on the first postoperative day (esketamine: risk ratio [RR] = 0.655, 95% credible interval [CrI]: 0.517-0.798; dexmedetomidine: RR = 0.773, 95% CrI: 0.434-1.23) and improved AIS and NRS scores. A supplementary meta-analysis of 4 PSG studies (n = 182 patients) indicated that dexmedetomidine increased the percentage of stage N2 sleep (mean difference [MD] = 13.0%, 95% confidence interval [CI]: -5.2 to 31.2) and the odds of experiencing stage N3 sleep, although the latter finding was not statistically significant (odds ratio [OR] = 2.99, 95% CI: 0.61 to 14.66).
LIMITATIONS: The primary limitation on this study is that the trials included were all conducted in China.
CONCLUSIONS: Both dexmedetomidine and esketamine improve postoperative sleep quality effectively. Esketamine demonstrates superior analgesic efficacy and has the higher probability being the optimal treatment for reducing early PSD incidence. In contrast, dexmedetomidine appears to objectively improve sleep architecture by promoting N2 sleep. The superior analgesic profile of esketamine likely underpins its enhanced subjective sleep benefits.
PMID:42550519
