Dexmedetomidine-esketamine Combined Nasal Administration and Perioperative Sleep Quality

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.

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.

Eligibility Criteria:
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.