Dexmedetomidine-esketamine Combined Nasal Administration and Perioperative Sleep Quality
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 4 |
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 Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Dexmedetomidine and esketamine Dexmedetomidine 0.5 microgram/kg (100 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
Dexmedetomidine 0.5 microgram/kg (100 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.
Drug: Esketamine
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.
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Placebo Comparator: 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. |
Drug: Normal saline
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.
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Outcome Measures
Primary Outcome Measures
- 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
- 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.
Other Outcome Measures
- Use of supplemental analgesics [Within the first 2 days after surgery]
Include opioids and non-opioid analgesics.
- Severity of anxiety [Before hospital discharge]
Anxiety is assessed with the Generalized Anxiexy Disorde-7 (GAD-7). GAD-7 contains 7 items assessing the core symptoms of anxiety. Patients rate their frequency of symptoms within the last two weeks on a four-point scale ranging from "not at all" to "almost every day". Scores range from 0 to 21, with higher scores indicating more severe anxiety.
- Severity of depression [Before hospital discharge]
Depression is assessed with the Patient Health Questionnaire-9 (PHQ-9). The PHQ-9 includes 9-item requiring responses of 0 (not at all) to 3 (nearly every day) to assess the occurrence of depressive symptoms over the last two weeks. It has 8 items on depressive symptoms and 1 focused on suicidal ideation. Total scores range from 0 to 27, with higher score indicating more severe symptoms.
- Length of hospital stay after surgery [Up to 30 days after surgery]
Length of hospital stay after surgery
- Occurrence of postoperative complications [Up to 30 days after surgery]
Postoperative complications are defined as new-onset medical events that are deemed harmful and required therapeutic intervention, that is grade II or higher on the Clavien-Dindo classification.
- Occurrence of Chronic Postoperative Pain [At 3 months after surgery]
Chronic Postoperative Pain (CPSP) is defined as pain persisted for at least three months after surgery, that was not present before surgery or that had different characteristics, and other possible causes of the pain were excluded (e.g., cancer recurrence, infection).
- Severity of chronic pain [At 3 months after surgery]
Severity of chronic pain is assessed with the Brief Pain Inventory (BPI). The BPI gives two main scores: a pain severity score and a pain interference score. The pain severity score is calculated from the four items about pain intensity. Each item is rated from 0, no pain, to 10, pain as bad as you can imagine, and contributes with the same weight to the final score, ranging from 0 to 40.
- Interference of chronic pain [At 3 months after surgery]
Interference of chronic pain is assessed with the Brief Pain Inventory (BPI). The BPI gives two main scores: a pain severity score and a pain interference score. The pain interference score corresponds to the item on pain interference. The seven subitems are rated from 0, does not interfere, to 10, completely interferes, and contributes with the same weight to the final score, ranging from 0 to 70.
- Life quality assessed with the EORTC QLQ-BR53 (part of EORTC-C30) [At 3 months after surgery]
Quality of life is assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Breast Cancer 53 (EORTC QLQ-BR53), including European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC-C30) and EORTC-BR23. EORTC QLQ-C30 contains 30 items (items 29 and 30 are classified into 7 degrees regarding to patients' response, scoring from 1 to 7; remaining items are divided into 4 degrees, including "Not at all", "A little", "Quite a bit", and "Very much", with a score from 1 to 4). All patient rated scores are linearly converted into a scale from 0 to 100 for analysis. Higher scores represent worse QoL on symptom aspects, whereas higher scores on functional interference correlate with better function.
- Life quality assessed with the EORTC QLQ-BR53 (part of EORTC-BR23) [At 3 months after surgery]
Quality of life is assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Breast Cancer 53 (EORTC QLQ-BR53), including European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC-C30) and EORTC-BR23. EORTC QLQ-BR23 contains 23 items. Each item used a 4-point Likert scale (i.e. "not at all", "a little", "quite a bit", and "very much"). All patient rated scores are linearly converted into a scale from 0 to 100 for analysis. Higher scores represent worse QoL on symptom aspects, whereas higher scores on functional interference correlate with better function.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Aged 50 years or older;
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Diagnosed with breast cancer and scheduled for surgical resection;
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Signed the informed consent form.
Exclusion Criteria:
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Not suitable for nasal administration because of nasal cavity diseases (rhinitis, nasal polyps, or nasal membrane congestion by any reason);
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History of schizophrenia, epilepsy, Parkinson's disease, or myasthenia gravis;
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Unable to communicate due to coma, delirium, severe dementia, or language barrier before surgery;
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History of intracranial injury or neurosurgery;
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Taking sedative/hypnotics for sleep in the last month;
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Preoperative sleep apnea (diagnosed with sleep apnea, or at high risk of sleep apnea according to STOP-Bang assessment);
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History of hyperthyroidism and pheochromocytoma;
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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;
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Severe liver dysfunction (Child-Pugh C classification), severe renal dysfunction (dialysis before surgery), or Amercian Society of Anesthesiologists classification ≥IV;
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Allergic to dexmedetomidine and/or esketamine, or other conditions that are considered unsuitable for study participation;
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Body mass index >30 kg/m2;
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Enrolled in other clinical studies.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Peking University First Hospital
Investigators
- Principal Investigator: Dong-Xin Wang, MD, PhD, Peking University First Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
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