Dexmedetomidine-esketamine Combined Nasal Administration and Perioperative Sleep Quality

July 29, 2025 updated by: Dong-Xin Wang, Peking University First Hospital

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

180

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Bejing
      • Beijin, Bejing, China, 100034
        • Peking University First Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Experimental: Dexmedetomidine and 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.
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.
Drug: Dexmedetomidine
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Subjective sleep quality (the night of surgery)
Time Frame: 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.
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)
Time Frame: 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.
The night before surgery and the first night after surgery
Objective sleep quality - total sleep time
Time Frame: 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.
The night before surgery, the night on the day of surgery, and the first night after surgery
Objective sleep quality - sleep efficiency
Time Frame: 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.
The night before surgery, the night on the day of surgery, and the first night after surgery
Objective sleep quality - sleep latency
Time Frame: 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.
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
Time Frame: 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.
The night before surgery, the night on the day of surgery, and the first night after surgery
Intensity of acute pain
Time Frame: 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.
At 2 hours after surgery and twice daily during the first 2 postoperative days
Subjective sleep quality at 30 days
Time Frame: 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.
At 30 days after surgery

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Length of hospital stay after surgery
Time Frame: Up to 30 days after surgery
Length of hospital stay after surgery
Up to 30 days after surgery
Use of supplemental analgesics
Time Frame: Within the first 2 days after surgery
Include opioids and non-opioid analgesics.
Within the first 2 days after surgery
Severity of anxiety
Time Frame: 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.
Before hospital discharge
Severity of depression
Time Frame: 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.
Before hospital discharge
Occurrence of postoperative complications
Time Frame: 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.
Up to 30 days after surgery
Occurrence of Chronic Postoperative Pain
Time Frame: 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).
At 3 months after surgery
Severity of chronic pain
Time Frame: 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.
At 3 months after surgery
Interference of chronic pain
Time Frame: 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.
At 3 months after surgery
Life quality assessed with the EORTC QLQ-BR53 (part of EORTC-C30)
Time Frame: 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.
At 3 months after surgery
Life quality assessed with the EORTC QLQ-BR53 (part of EORTC-BR23)
Time Frame: 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.
At 3 months after surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking University First Hospital

Investigators

  • Principal Investigator: Dong-Xin Wang, MD, PhD, Peking University First Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 22, 2023

Primary Completion (Actual)

April 20, 2025

Study Completion (Actual)

July 26, 2025

Study Registration Dates

First Submitted

January 29, 2023

First Submitted That Met QC Criteria

February 7, 2023

First Posted (Actual)

February 16, 2023

Study Record Updates

Last Update Posted (Actual)

July 31, 2025

Last Update Submitted That Met QC Criteria

July 29, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2022-761

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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