Perioperative esketamine and postoperative sleep quality: a systematic review and meta-analysis of randomized trials

Abstract

Postoperative sleep disturbance (PSD) is common among surgical patients and adversely affects recovery. The benefits of perioperative esketamine on sleep remain incompletely defined. Randomized controlled trials (RCTs) comparing ketamine or esketamine with saline or other drugs for postoperative sleep quality were identified through a systematic search of PubMed, Embase, Web of Science, and the Cochrane Library until 6 September 2025. The primary outcome was postoperative sleep quality scores, and effect sizes were calculated using the ratio of means (ROM). Secondary outcomes included incidence of PSD, postoperative pain and depression scores, and adverse events. Twenty-three trials including 2868 participants met inclusion criteria. Esketamine improved sleep quality on postoperative day (POD) 1 (ROM, 0.85; 95% CI, 0.80 to 0.90; P  < 0.001; I 2  = 84%; 21 studies), POD 2 (ROM, 0.73; 95% CI, 0.57 to 0.93; P  = 0.01; I 2  = 92%; 8 studies), POD 3 (ROM, 0.94; 95% CI, 0.90 to 0.99; P  = 0.02; I 2  = 25%; 12 studies), and POD 7 (ROM, 0.89; 95% CI, 0.82 to 0.95; P  = 0.001; I 2  = 36%; 8 studies); no benefit was observed at 1 month. The incidence of PSD was reduced on PODs 1 through 3 (RRs, 0.71, 0.70, and 0.61, respectively; all P  ≤ 0.01), with no effect on POD 7. Esketamine also lowered postoperative pain and depression scores. However, it increased drowsiness (RR, 12.64; 95% CI, 6.04 to 26.46; P  < 0.001; I 2  = 21%). Perioperative esketamine is associated with short-term improvements in postoperative sleep quality and a lower incidence of PSD, alongside reductions in pain and depressive symptoms. However, these benefits are accompanied by an increased risk of drowsiness, and the current evidence does not yet support routine clinical use. Larger multinational trials are warranted.