Dexmedetomidine-esketamine Combined Nasal Administration and Perioperative Sleep Quality

Phase 4

Recruiting

• Conditions: Perioperative Period; Dexmedetomidine; Breast Cancer; Esketamine; Sleep Quality
• Interventions: Drug: Normal saline; Drug: Dexmedetomidine; Drug: Esketamine

• Registration Number: NCT05732064
• Lead Sponsor: Peking University First Hospital

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2023-01-29
• Study First Submitted QC: 2023-02-07
• Study First Posted: 2023-02-16
• Status Verified: 2023-05
• Study Start: 2023-05-22
• Last Update Submitted: 2023-05-23
• Last Update Posted: 2023-05-25
• Primary Completion: 2024-03
• Study Completion: 2024-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 180

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Normal saline	Normal saline	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.
Dexmedetomidine and esketamine	Dexmedetomidine	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.
Dexmedetomidine and esketamine	Esketamine	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.

Primary Outcome Measures

Name	Time	Method
Subjective sleep quality (the night of surgery)	The night on the day 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.

Secondary Outcome Measures

Name	Time	Method
Subjective sleep quality (the night before and the first night after surgery)	The night before surgery 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.
Objective sleep quality - total sleep time	The night before surgery, the night on the day of surgery, and the first night after surgery	Objective sleep quality is assessed with the actigraphy.
Objective sleep quality - sleep efficiency	The night before surgery, the night on the day of surgery, and the first night after surgery	Objective sleep quality is assessed with the actigraphy.
Objective sleep quality - sleep latency	The night before surgery, the night on the day of surgery, and the first night after surgery	Objective sleep quality is assessed with the actigraphy.
Objective sleep quality - wake-up time after falling asleep	The night before surgery, the night on the day of surgery, and the first night after surgery	Objective sleep quality is assessed with the actigraphy.
Intensity of acute pain	At 2 hours after surgery and twice daily during the first 2 postoperative days	Intensity of acute pain is assessed with the numeric rating scale, an 11-point scale where 0=no pain and 10=the worst pain.
Subjective sleep quality at 30 days	At 30 days after surgery	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.

Trial Locations

Locations (1)

Peking University First Hospital; 🇨🇳 Beijin, Bejing, China