Esketamine improves postoperative sleep quality in women undergoing gynecological laparoscopy: A prospective, randomized, double-blind, and controlled trial.

BACKGROUND: Postoperative sleep disturbance is prevalent in patients undergoing gynecological surgeries. This study is to evaluate the application of esketamine regimen for improving sleep quality after gynecological laparoscopy and explore the possible underlying mechanisms. METHODS: A total of 150 patients undergoing elective laparoscopic total hysterectomy or myomectomy were randomly allocated 1:1:1 to Group E1, esketamine loading dose 0.15 mg/kg plus maintenance dose 0.15 mg·kg -1 ·h -1 ; Group E2, esketamine loading dose 0.3 mg/kg plus maintenance dose 0.3 mg·kg -1 ·h -1 ; and Group C, saline 5 mL followed by continuous saline infusion 10 mL/h. The primary outcome was postoperative sleep quality assessed by an actigraphy (the night before surgery, the 1st and 2nd postoperative nights) and was analyzed using intention-to-treat (ITT) and per-protocol (PP) principle. Secondary outcomes, analyzed using PP principle, included perioperative changes of melatonin, brain-derived neurotrophic factor (BDNF), interleukin (IL)-6, and IL-10, intraoperative medication and hemodynamic parameters, postoperative recovery, adverse effects, and pain scales. Sensitivity analyses were performed to confirm robustness of the findings. RESULTS: Compared with Group C, Group E1 and E2 showed statistically significant but not clinically proven improvements in sleep quality, including increased total sleep time (TST: E1 +6 min, E2 +11 min on the 1st postoperative night; E1 +15 min, E2 +20 min on the 2nd postoperative night), higher sleep efficiency (SE: E1 +1.3 %, E2 +2.2 %; then E1 +1.6 %, E2 +2.2 %), and reduced wake after sleep onset (WASO%: E1 -1.7 %, E2 -2.0 %; then E1 -3.9 %, E2 -3.6 %). They also showed significantly higher melatonin, BDNF, and IL-10 concentrations; lower IL-6 concentration; lower visual analog scale pain scores; less remedial analgesia postoperatively; and lower intraoperative remifentanil consumption (P < 0.05 for all). Most of these changes were more significant in Group E2 than Group E1. CONCLUSION: Both esketamine regimens, 0.15 mg/kg + 0.15 mg·kg -1 ·h -1 and 0.3 mg/kg + 0.3 mg·kg -1 ·h -1 , produced statistically significant, but not clinically proven, improvements in postoperative sleep quality in patients undergoing gynecological laparoscopy, with the higher-dose regimen producing better effects. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05715671.