Surgery · Medical Literature
Comparative Efficacy of Dexmedetomidine and Esketamine on Postoperative Sleep Disturbances and Analgesia: A Systematic Review and Network Meta-Analysis.
Abstract
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. This review aimed to evaluate the efficacy of dexmedetomidine and esketamine in treating PSDs and providing analgesia. 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. 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. 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. 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). The primary limitation on this study is that the trials included were all conducted in China. 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.
Clinical relevance
Among adult surgical patients, do dexmedetomidine and esketamine differ in their comparative efficacy for reducing postoperative sleep disturbance (PSD) and providing analgesia, as assessed by Visual Analog Scale pain scores at 24 and 48 hours and secondary sleep-specific measures? __SNAPSHOT__ {"studyDesign":"Systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs)","setting":"Multi-database synthesis (4 electronic databases searched from inception to August 1, 2025); specific countries or institution types of included primary studies not reported in abstract","sampleSize":"Not reported in abstract; number of included RCTs not stated in abstract","population":"Adult surgical patients (age ≥18 years implied by inclusion of 'adult surgical patients'); patients with postoperative sleep disturbances or at risk thereof; specific exclusion criteria not reported in abstract","intervention":"Dexmedetomidine (alpha-2 adrenergic agonist) and/or esketamine (S-enantiomer of ketamine; NMDA receptor antagonist) administered perioperatively — dosing, route, and timing details not reported in abstract","comparator":"Control interventions (specific nature — e.g., saline placebo, standard of care — not specified in abstract); network structure permits indirect comparison of dexmedetomidine vs. esketamine via common control arms","primaryOutcome":"Postoperative pain scores assessed by the Visual Analog Scale (VAS) at 24 hours and 48 hours postoperatively","followUp":"At minimum 48 hours postoperatively for primary outcome; full follow-up duration not reported in abstract","fundingSource":"Not reported"}
Key findings
Specific quantitative results (effect sizes, mean differences, standardized mean differences, odds ratios, surface under the cumulative ranking [SUCRA] values, confidence/credible intervals, p-values, and NNT/NNH) are not reported in the available abstract. The abstract identifies VAS scores at 24 and 48 hours as the primary outcomes and states that incidence of PSD and Athens Insomnia Scale (AIS) scores are among the secondary outcomes, but no numerical results are disclosed. The abstract does not report which agent—dexmedetomidine, esketamine, or control—ranked highest for analgesia or sleep improvement, nor does it quantify between-agent comparative effect sizes. Adverse event data and safety outcomes are not mentioned in the abstract. No NNT or NNH can be calculated. NOTE: This summary is based solely on the published abstract; full results, including all primary and secondary outcome data, are available only in the complete manuscript.
Practice implications
This network meta-analysis was designed to address a clinically important and previously unresolved question: whether dexmedetomidine or esketamine is superior—or whether they are equivalent—for reducing postoperative sleep disturbance and pain in adult surgical patients. Prior pairwise meta-analyses have established that each agent individually improves postoperative sleep quality and reduces pain scores versus placebo, but head-to-head RCT data are sparse. The NMA framework is methodologically appropriate to indirectly compare these agents through common control arms. However, because only the abstract is available, the direction, magnitude, and certainty of comparative findings cannot be assessed, and no conclusions about which agent should be preferred, or in which patient populations, can be drawn from this summary alone. The clinical applicability of results will further depend on: (1) the surgical types, patient demographics, and anesthetic backgrounds of included RCTs; (2) the dosing and timing of each agent across studies; (3) the degree of network connectivity and consistency; and (4) GRADE-level certainty of evidence. Patients not adequately represented in this body of literature are likely to include those undergoing cardiac surgery, pediatric patients, patients with pre-existing sleep disorders requiring pharmacotherapy, and patients with significant hepatic or renal impairment relevant to drug metabolism. Clinicians should not change practice based on this abstract alone; the full-text findings and certainty of evidence ratings are essential before drawing practice-informing conclusions. LIMITATION NOTE: This entire interpretation is constrained by abstract-only availability. __LIMITATIONS__ Only the abstract is available; primary outcome data, effect sizes, confidence/credible intervals, heterogeneity statistics, and GRADE certainty ratings cannot be evaluated.,Network meta-analyses are subject to transitivity assumptions (i.e., comparability of patient populations, intervention protocols, and outcome definitions across trials forming the network); whether this assumption was tested and met is not assessable from the abstract.,The body of evidence in this field is heavily concentrated in studies conducted in China, which may limit generalizability to Western surgical populations with differing anesthetic practices, opioid regimens, and baseline sleep characteristics.,Significant clinical heterogeneity is expected across included RCTs with respect to surgical type, patient age and comorbidities, dosing regimen (route, dose, and timing of dexmedetomidine and esketamine), background analgesic protocols, and sleep outcome measurement tools (AIS vs. other scales).,The primary outcomes (VAS at 24 and 48 hours) are surrogate endpoints; long-term outcomes such as chronic postsurgical pain, quality of life, or durable sleep architecture improvements are not captured within this timeframe.,Sleep outcomes rely predominantly on subjective patient-reported scales (AIS, VAS for sleep); polysomnographic or actigraphy-confirmed objective sleep architecture data are likely inconsistently reported across included studies, limiting conclusions about true sleep biology.,Adverse events—including dexmedetomidine-associated bradycardia and hypotension, and esketamine-associated dizziness, dissociation, hypertension, and neuropsychiatric symptoms—are not mentioned in the abstract, raising uncertainty about the safety comparative analysis.,Funding source is not disclosed; potential for industry sponsorship bias cannot be excluded.,The abstract does not report the number of included RCTs or total participants, precluding assessment of statistical power or the reliability of network estimates. __BOTTOM_LINE_CATEGORY__ low_certainty __BOTTOM_LINE__ This PROSPERO-registered network meta-analysis (CRD420251126227) compares dexmedetomidine and esketamine for postoperative sleep disturbance and analgesia in adult surgical patients using VAS pain scores at 24 and 48 hours as primary outcomes, but no quantitative results are available in the abstract. Clinicians should not alter practice based on this abstract alone and should review the full published manuscript for effect sizes, certainty of evidence ratings, and safety data before drawing comparative conclusions about these two agents.