The prevalence of sleep disturbance among postmenopausal women has been reported to reach 51.6%. Epidemiological studies consistently show that the incidence of sleep disorders increases with age and menopausal transition. Compared with premenopausal women, postmenopausal women demonstrate reduced circadian rhythm stability and a higher prevalence of sleep disturbance. In this population, levels of melatonin, total sleep time, sleep latency, N3 stage sleep, and the circadian amplitude of alertness are all diminished. Sleep disturbance can adversely affect both the mental and physical health of women and significantly impair their social functioning. Poor sleep is associated with decreased cognitive performance and heightened emotional distress, contributing to diminished quality of life. Moreover, prolonged sleep deprivation elevates the risk of developing obesity, diabetes, cardiovascular conditions, and psychiatric disorders. Circadian rhythms are endogenous physiological and behavioral cycles that oscillate over approximately 24 hours, governing critical processes such as sleep-wake cycles, hormonal fluctuations (e.g., cortisol and melatonin). These rhythms are regulated by the suprachiasmatic nucleus (SCN). Disruptions in circadian rhythms have been associated with sleep disturbances. Esketamine is the S (+) enantiomer of ketamine and has a higher affinity for the NMDA receptor than the R-enantiomer. Previous studies have demonstrated that intraoperative administration of esketamine can improve postoperative sleep quality and reduce the incidence of postoperative sleep disturbances, through its antidepressant efficacy, anti-inflammatory properties, analgesic efficacy, neurocognitive and anxiolytic effects. However, few studies have investigated whether esketamine can regulate circadian rhythms and subsequently affect sleep, especially in postmenopausal women. The objective of this two-center, prospective, randomized controlled clinical trial is to investigate the effects of esketamine on postoperative sleep in postmenopausal women.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
120
Participants in Group E are administered esketamine with a loading dose of 0.2 mg/kg (diluted to 10 ml with normal saline) and a maintenance dose of 0.2 mg·kg-¹·h-¹ .
In Group C, a loading dose of normal saline 10 ml and a maintenance dose of 10 ml/h of normal saline is given intravenously.
Jingjiang People's Hospital
Jingjiang, Jiangsu, China
The Affiliated Hospital of Yangzhou University, Yangzhou University
Yangzhou, Jiangsu, China
The incidence of postoperative sleep disturbance
The primary outcome is the incidence of postoperative sleep disturbance (PSD) , evaluated using the Numeric Rating Scale (NRS) and the Athens Insomnia Scale (AIS) on postoperative day 1. PSD is defined as an NRS score of 6 or higher or an AIS score of 6 or higher.
Time frame: Postoperative day 1.
Biological rhythm detection
Melatonin rhythm profiles are analyzed using saliva samples by measuring melatonin every 6 h for 48 h: at 10:00 PM on the night of surgery; 4:00 AM, 10:00 AM, 4:00 PM, and 10:00 PM on postoperative day 1; and 4:00 AM and 10:00 AM on postoperative day 2. Expression of core circadian clock genes (CLOCK, BMAL1, PER1, PER2, CRY1, CRY2) and blood melatonin concentrations are assessed on preoperative day 1, postoperative day 1 and postoperative day 3.
Time frame: From preoperative day 1 to postoperative day 3.
PSQI
Subjective sleep quality, sleep length, sleep latency, habitual sleep efficiency, use of sleep drugs, sleep disruptions, and daytime dysfunction are among the seven domains in which the 19 items are assessed. A scale of 0 to 3 is utilized to grade the domains, with 3 denoting serious impairment. The seven subscale scores are then added together to generate a global PSQI score, which ranged from 0 to 21 points, with a total score greater than 7 indicates poor sleep quality.
Time frame: Preoperative day 1 and postoperative day 30.
Objective sleep parameters recorded by actigraphy
Objective sleep parameters will be recorded using actigraphy.The parameters include total sleep time (TST), sleep onset latency (SOL), wake after sleep onset (WASO), proportion of WASO (WASO%), and sleep efficiency (SE%).
Time frame: From preoperative day 1 to postoperative day 3.
Anxiety and Depression assessments
Anxiety and depression are measured using the Hospital Anxiety and Depression Scale (HADS). It comprises two subscales: the Anxiety subscale (HADS-A) and the Depression subscale (HADS-D). For each item, respondents select the degree of severity, ranging from 0 to 3, representing none, mild, moderate, and severe. The total score for each subscale ranges from 0 to 21, with higher scores indicating more severe anxiety or depression symptoms. Scores of 0-7 are considered normal, 8-10 suggest the possibility of mild anxiety or depression, 11-14 indicate the possibility of moderate anxiety or depression, and 15-21 signify the possibility of severe anxiety or depression.
Time frame: From preoperative day 1 to postoperative day 30.
Frontal electroencephalography
Electroencephalogram (EEG) data is collected using the ConView Anesthesia Depth Monitoring System (ConView YY-105, Zhejiang Puke Medical Technology Co., Ltd., China). The analysis includes the power spectrum of EEG energy across various frequency bands, the peak frequencies in the α-β band, and key electrocorticogram indices such as the left α-index (Aileft), right α-index (Airight), electromyographic index (EMG), and burst suppression ratio (BSR).
Time frame: From entering the operating room to surgery ending.
Postoperative cognitive function and biomarkers
Delirium assessments is conducted twice daily on postoperative days 1, 2, and 3 with at least 6 hours between evaluations, using the Chinese version of the 3-Minute Diagnostic Confusion Assessment Method (3D-CAM). Brain-derived neurotrophic factor (BDNF) and S100β are measured from blood samples collected on preoperative day 1, postoperative day 1 and postoperative day 3.
Time frame: From preoperative day 1 to postoperative day 3.
Inflammatory markers
Inflammatory biomarkers including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-10 are measured.
Time frame: From preoperative day 1 to postoperative day 3.
Postoperative pain assessment
Pain levels, including both rest and exercise pain, are measured using the Visual Analogue Scale (VAS) at 24 hours, 48 hours, and 72 hours postoperatively. Data on the use of the Patient-Controlled Analgesia (PCIA) device, including trigger times for bolus doses within the first 24 hours post-surgery the total number of bolus presses, and the use of the rescue analgesic flurbiprofen, are documented.
Time frame: From postoperative day 1 to day 3.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.