Effect of Esketamine on Postoperative Sleep in Postmenopausal Women
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexFemale
Age45+
SponsorZhuan Zhang
About this trial
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.
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 perioperative circadian rhythms and subsequently affect sleep, especially in postmenopausal women.
The objective of this multi-center, prospective, randomized controlled clinical trial is to investigate the effects of esketamine on postoperative sleep in postmenopausal women.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
American Society of Anesthesiologists (ASA) physical status I-III.
Aged ≥ 45 years.
Women with natural menopause (aged ≥ 45 years and postmenopause for more than 12 months without surgical or medical intervention) .
Scheduled to undergo elective lower-limb fracture surgery with an expected duration of more than 60 min under general anesthesia.
Disqualifiers
Presence of preoperative sleep-related disorders, such as obstructive sleep apnea or restless legs syndrome.
History of drug or alcohol abuse or dependence.
Known contraindications or allergies to esketamine or other anesthetic agents.
Use of psychotropic medications or sex hormones within the past 3 months.
Trial design
Design model
Parallel
Treatments tested in this trial
Esketamine
DrugParticipants in Group E are administered esketamine with an infusion dose of 0.1 ml·kg-¹·h-¹ (0.2 mg·kg-¹·h-¹, diluted with 0.9% sodium chloride in a 2 mg/mL.
Normal Saline
DrugIn Group C, 0.9% sodium chloride with a maintenance dose of 0.1 ml·kg-¹·h-¹ are administered intravenously.
Treatment groups
164 Participants
are divided into 2 treatment groupsGroup A: Esketamine Group (Group E)Experimental treatment 1 intervention
Group B: Control Group (Group C)Placebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
The incidence of postoperative sleep disturbance (PSD) on postoperative day 1.
The primary outcome is the incidence of 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.Secondary outcomes
1
Biological rhythm detection
Melatonin and cortisol rhythm profiles are analyzed using saliva samples 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, serum melatonin and cortisol concentrations are assessed on preoperative day 1, postoperative day 1 and postoperative day 3.
Time frame
From preoperative day 1 to postoperative day 3.2
Objective sleep parameters recorded by actigraphy
Objective sleep parameters are 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 night 1 to postoperative night 3.3
Subjective sleep quality
The Pittsburgh Sleep Quality Index (PSQI) is assessed on the day before surgery and 30 days postoperatively. Self-rated sleep quality is evaluated using the NRS and the AIS on the day before surgery and on postoperative days 2 and 3.
Time frame
From preoperative day 1 to postoperative day 30.4
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 3.Other outcomes
1
Possible adverse reactions
Time frame
From esketamine infusion to postoperative day 3.2
Quality of postoperative recovery
The QoR-15 score is used to assess the quality of recovery. The QoR-15 includes five dimensions: physical comfort, physical independence, emotional state, pain, and psychological support, with a total of 15 questions. Each question is scored from 0 to 10, with a higher score indicating better recovery quality.
Time frame
From postoperative day 1 to day 3.3
The length of hospital stay
Time frame
From the date of hospital admission to the date of discharge.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Zhuan Zhang
Lead sponsor
Yangzhou University
Sponsor institution
Source ClinicalTrials.gov