Dexmedetomidine-esketamine Combined Nasal Administration and Perioperative Sleep Quality

Study Overview
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Brief Summary
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Breast cancer patients often have sleep disturbances during the perioperative period. Dexmedetomidine is a highly selective alpha 2-adrenoceptor agonist with sedative, anxiolytic, and analgesic effects. Previous studies showed that night-time low-dose dexmedetomidine infusion improved sleep quality. Esketamine is a N-methyl-D-aspartic acid receptor antagonist and has been used as an anesthetic and analgesic. Recent studies showed that low-dose esketamine has anti-depressive and sleep-promoting effects. The investigators suppose that low-dose dexmedetomidine-esketamine combined nasal administration at night can improve perioperative sleep quality in patients scheduled for breast cancer surgery.

Detailed Description
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Normal sleep is important for maintaining both physical and mental health. Patients who are scheduled for breast cancer surgery often have sleep disturbances during the perioperative period. Patients with persistent sleep disturbances have increased sensitivity to pain and are at increased risk of developing chronic postsurgical pain. Dexmedetomidine is a highly selective alpha 2-adrenoceptor agonist with sedative, anxiolytic, and analgesic effects. Previous studies showed that night-time low-dose dexmedetomidine infusion improves sleep quality. Nasal administration of dexmedetomidine has been used in children as a premedication and in adults to reduce emergence agitation. Esketamine is a N-methyl-D-aspartic acid receptor antagonist and has been used as an anesthetic and analgesic. Recent studies showed that low-dose esketamine has anti-depressive and sleep-promoting effects. Nasal administration of esketamine has been used in children to relieve pain and in adults for treatment-resistant depression. This randomized trial is designed to test the hypothesis that combined nasal administration of low-dose dexmedetomidine-esketamine at night can improve perioperative sleep quality in patients scheduled for breast cancer surgery.

Official Title
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Effects of Low-dose Dexmedetomidine-esketamine Combined Nasal Administration at Night on Perioperative Sleep Quality in Breast Cancer Patients: a Randomized, Double-blind, Placebo-controlled Trial

Conditions
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Breast Cancer, Perioperative Period, Dexmedetomidine, Esketamine, Sleep Quality

Intervention / Treatment
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* Drug: Dexmedetomidine
* Drug: Esketamine
* Drug: Normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 50 years or older; Diagnosed with breast cancer and scheduled for surgical resection; Signed the informed consent form. Exclusion Criteria: Not suitable for nasal administration because of nasal cavity diseases (rhinitis, nasal polyps, or nasal membrane congestion by any reason); History of schizophrenia, epilepsy, Parkinson's disease, or myasthenia gravis; Unable to communicate due to coma, delirium, severe dementia, or language barrier before surgery; History of intracranial injury or neurosurgery; Taking sedative/hypnotics for sleep in the last month; Preoperative sleep apnea (diagnosed with sleep apnea, or at high risk of sleep apnea according to STOP-Bang assessment); History of hyperthyroidism and pheochromocytoma; Preoperative LVEF<30%; sick sinus syndrome, severe sinus bradycardia (heart rate<50 beats/min), or atrioventricular block of degree II or higher without pacemaker; use vasopressors with systolic blood pressure <90 mmHg; Severe liver dysfunction (Child-Pugh C classification), severe renal dysfunction (dialysis before surgery), or Amercian Society of Anesthesiologists classification ≥IV; Allergic to dexmedetomidine and/or esketamine, or other conditions that are considered unsuitable for study participation; Body mass index >30 kg/m2; Enrolled in other clinical studies.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dexmedetomidine and esketamine<br>Dexmedetomidine 0.5 microgram/kg (300 microgram/ml) and esketamine 0.2 mg/kg (25 mg/ml) are administered via nasal cavity at 20:00 pm the day before surgery, the day of surgery, and the first day after surgery. | Drug: Dexmedetomidine<br>* Dexmedetomidine 0.5 microgram/kg (300 microgram/ml) is administered via nasal cavity at 20:00 pm the day before surgery, the day of surgery, and the first day after surgery.<br>Drug: Esketamine<br>* Esketamine 0.2 mg/kg (25 mg/ml) is administered via nasal cavity at 20:00 pm the day before surgery, the day of surgery, and the first day after surgery.<br>|
| Placebo Comparator: Normal saline<br>Same volumes of normal saline are administered via nasal cavity at 20:00 pm the day before surgery, the day of surgery, and the first day after surgery. | Drug: Normal saline<br>* Normal saline of same volume is administered via nasal cavity at 20:00 pm the day before surgery, the day of surgery, and the first day after surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective sleep quality (the night of surgery) | Subjective sleep quality is assessed with the Richards-Campbell Sleep Questionnaire (RCSQ). RCSQ is a self-reported measure that evaluated perception of nighttime sleep in five items, including sleep depth, sleep latency, number of awakenings, returning to sleep, and overall sleep quality. Each item was assessed with a 100-millimeter visual analog scale (score ranges from 0 to 100, with higher scores representing better sleep). The mean score of the five items represents the overall RCSQ score. | The night on the day of surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective sleep quality (the night before and the first night after surgery) | Subjective sleep quality if assessed with the RCSQ. RCQS is a self-reported measure that evaluated perception of nighttime sleep in five items, including sleep depth, sleep latency, number of awakenings, returning to sleep, and overall sleep quality. Each item was assessed with a 100-millimeter visual analog scale (score ranges from 0 to 100, with higher scores representing better sleep). The mean score of the five items represents the overall RCSQ score. | The night before surgery and the first night after surgery | 
| Objective sleep quality - total sleep time | Objective sleep quality is assessed with the actigraphy. | The night before surgery, the night on the day of surgery, and the first night after surgery | 
| Objective sleep quality - sleep efficiency | Objective sleep quality is assessed with the actigraphy. | The night before surgery, the night on the day of surgery, and the first night after surgery | 
| Objective sleep quality - sleep latency | Objective sleep quality is assessed with the actigraphy. | The night before surgery, the night on the day of surgery, and the first night after surgery | 
| Objective sleep quality - wake-up time after falling asleep | Objective sleep quality is assessed with the actigraphy. | The night before surgery, the night on the day of surgery, and the first night after surgery | 
| Intensity of acute pain | Intensity of acute pain is assessed with the numeric rating scale, an 11-point scale where 0=no pain and 10=the worst pain. | At 2 hours after surgery and twice daily during the first 2 postoperative days | 
| Subjective sleep quality at 30 days | Subjective sleep quality at 30 days is assessed with the Pittsburgh Sleep Quality Index (PSQI). PSQI is a 7-item questionnaire consisting 19 self-rated questions that assesses sleep quality over the last month, each weighted equally on a 0-3 scale; higher scores indicate worse sleep quality. | At 30 days after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, Perioperative period, Dexmedetomidine, Esketamine, Sleep quality