Esketamine improves postoperative sleep quality in thoracic surgery patients with preoperative sleep disturbance: a randomized controlled trial.

Objective: To investigate the effect of multiple intraoperative subanesthetic doses of esketamine on postoperative sleep quality in non-cardiac thoracic surgery patients with preoperative sleep disturbance. Methods: This was a prospective single-center, double-blind placebo-randomized controlled trial of 100 patients undergoing elective non-cardiac thoracic surgery under general anesthesia with preoperative sleep disturbance who were given 0.25 mg/kg esketamine at induction of anesthesia and cutaneous suture compared with placebo to prevent the occurrence of postoperative sleep disturbance. Primary outcomes were the incidence of postoperative sleep disturbance on postoperative day 1, as assessed by Numeric Rating Scale, Athens Insomnia Scale and RCSQ. Secondary outcomes included the incidence of postoperative sleep disturbance on postoperative day 3 and 5,sleep duration, proportion of deep sleep, proportion of rapid eye movement sleep, postoperative pain score, postoperative anxiety score and depression score, intraoperative hemodynamic parameters and blood biomarkers (IL-6,IL-10, and brain-derived neurotrophic factor). Result: A total of 100 patients were randomized to the control group and the esketamine group. The incidence of postoperative sleep disturbance in the esketamine group was significantly lower than in the control group on POD 1 (50%vs 82%; odds ratio [OR], 0.2 [95% CI, 0.1-0.5]; P = 0.001) and POD 3 (22%vs 42%; OR, 0.4 [95% CI, 0.2-0.9]; P = 0.032). And there were significant differences in sleep duration, proportion of deep sleep and proportion of REM sleep (Based on exploratory Fitbit-derived estimates) on postoperative day 1 and 3. By POD 5, the difference was no longer statistically significant. Postoperative pain scores at rest and during movement were significantly lower in the esketamine group immediately after surgery and on postoperative day 1 compared with the control group, with no significant differences on postoperative days 3 and 5. Anxiety and depression scores (HADS) were significantly lower in the esketamine group on postoperative days 1, 3, and 5. Intraoperative hemodynamic parameters demonstrated higher systolic and mean arterial pressures in the esketamine group during anesthesia induction (T2) and lower pressures and heart rate during extubation (T6), indicating attenuated hypotension at induction and blunted stress response at extubation. Intraoperative sufentanil consumption was significantly lower in the esketamine group. Compared with preoperative levels, serum IL-6 concentrations increased in both groups on POD 1, 3, and 5; however, the esketamine group exhibited lower IL-6 levels than the control group on POD one and POD 3, with the difference attenuating by POD 5. Serum IL-10 levels were elevated on POD 1, 3, and five in the esketamine group and were significantly higher than those in the control group at all three time points. Serum BDNF concentrations were increased relative to baseline on POD 1, 3, and five in both groups, and were consistently higher in the esketamine group than in the control group across all postoperative assessments. Subgroup analyses demonstrated that intraoperative esketamine consistently reduced the incidence of postoperative sleep disturbance across predefined subgroups stratified by age, sex, PSQI score, and ASA classification, with no significant interaction effects observed. Conclusion: Multiple intraoperative infusion of 0.25 mg/kg esketamine can effectively improve the postoperative sleep quality of non-cardiac thoracic surgery patients with preoperative sleep disturbance, reduce the incidence of postoperative sleep disturbance, reduce the use of opioids, reduce the occurrence of intraoperative hypotension events, reduce the stress response during extubation, maintain the stability of intraoperative hemodynamics, reduce postoperative pain, and relieve adverse emotions. Moreover, esketamine decreased the level of the pro-inflammatory cytokine IL-6, increased the level of the anti-inflammatory cytokine IL-10, attenuated the postoperative inflammatory response, and promoted the release of BDNF. Clinical Trial Registration: https://www.chictr.org.cn/bin/project/edit?pid=248681, identifier ChiCTR2500096036.