Dexmedetomidine-Esketamine Combination and Sleep Disturbances After Major Noncardiac Surgery

March 18, 2025 updated by: Mo Li, Peking University First Hospital

Effect of Dexmedetomidine-esketamine Combination on Sleep Disturbances After Major Noncardiac Surgery: a Single-center, Randomised, Double-blind, Placebo-controlled Trial

Sleep disturbances are common early after major surgery, and are associated with delayed recovery. A previous study showed that dexmedetomidine-esketamine combination as a supplement to patient-controlled intravenous analgesia improved postoperative analgesia and subjective sleep quality in patients after scoliosis correction surgery. The purpose of this trial is to test the hypothesis that dexmedetomidine-esketamine combination used as a supplement during general anesthesia and postoperative intravenous analgesia may reduce sleep disturbances in adult after major noncardiac surgery.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Sleep disturbances after surgery is usually manifested as sleep deprivation, altered circadian rhythm, and disturbed sleep structure. The reported incidence of sleep disturbances was 31.4% after gynecologic surgery, 31.9% after urologic surgery, and 35.9% after spine surgery. The occurrence of sleep disturbances is associated with worse perioperative outcomes, including aggravated pain intensity, increased delirium, higher risk of cardiovascular events, and delayed hospital discharge.

Dexmedetomidine is a high-specific alpha 2-adrenergic agonist with anxiolytic, sedative, and analgesic effects. When used during general anesthesia and for postoperative analgesia, dexmedetomidine is associated with improved analgesia and sleep quality. The effect of dexmedetomidine is dose-dependent. However, even commonly used dosage increases bradycardia and hypotension.

Ketamine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist. Esketamine is the S-enantiomer of racemic ketamine with a higher affinity for NMDA receptors and is approximately twice as potent as racemic ketamine in analgesia. When used during general anesthesia and for postoperative analgesia, esketamine improves analgesia and reduces opioid consumption, but psychiatric symptoms may occur.

The sedative effect of dexmedetomidine is helpful to relieve psychiatric side effects of ketamine/esketamine. A previous study showed that dexmedetomidine-esketamine combination as a supplement to patient-controlled intravenous analgesia improved postoperative analgesia and subjective sleep quality in patients after scoliosis correction surgery.

This trial is designed to test the hypothesis that dexmedetomidine-esketamine combination used as a supplement during general anesthesia and postoperative intravenous analgesia may reduce sleep disturbances in adult after major noncardiac surgery.

Study Type

Interventional

Enrollment (Estimated)

476

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 Contact

Study Locations

  • China
      • Beijing, China, 100034
        • Recruiting
        • Peking University First Hospital
        • Contact:
          • Mo Li, MD, PhD

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Aged ≥18 years.
  2. Scheduled for major noncardiac surgery (≥60 minutes) under general anesthesia with an expected end of surgery no later than 18:00 pm.
  3. Required patient-controlled intravenous analgesia after surgery.

Exclusion Criteria:

  1. Emergency surgery, transurethral surgery, organ transplantation.
  2. Pregnant or lactating women.
  3. Patients who need hypnotics for sleep disturbance or antidepressants for depression prior to surgery.
  4. History of schizophrenia, epilepsy, Parkinson's disease, or myasthenia gravis.
  5. Inability to communicate due to coma, severe dementia, or speech disorders, endured hypoxic encephalopathy or traumatic brain injury, or after neurosurgery.
  6. Comorbid with hyperthyroidism and pheochromocytoma.
  7. Preoperative left ventricular ejection fraction <30%, sick sinus syndrome, severe sinus bradycardia (heart rate <50 beats/min), atrioventricular block of degree II or higher without pacemaker implantation, or systolic blood pressure below 90 mmHg despite use of vasopressors.
  8. Diagnosed as sleep apnea, or judged to be at high risk of moderate-to-severe sleep apnea as assessed by STOP-Bang.
  9. Severe hepatic dysfunction (Child-Pugh class C), severe renal dysfunction (on dialysis), or ASA classification ≥IV.
  10. Hypersensitive to dexmedetomidine and/or esketamine.
  11. Other conditions that are deemed unsuitable for study participation.

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
Experimental: Dexmedetomidine-esketamine group
Dexmedetomidine-esketamine combination is infused during general anesthesia and used as a supplement for patient-controlled intravenous analgesia after surgery.
Drug: Dexmedetomidine-esketamine combination
Dexmedetomidine 0.4 μg/kg and esketamine 0.2 mg/kg is infused over 10 minutes before anesthesia induction. Dexmedetomidine 0.20 μg/kg/h and esketamine 0.10 mg/kg/h is then infused until 60 minutes before the expected end of surgery. Patient-controlled intravenous analgesia is established with 100 μg dexmedetomidine, 50 mg esketamine, and 100 μg sufentanil, diluted to 100 mL with normal saline, and programmed to deliver 2-mL boluses with a lock-out interval of 8 minutes and background infusion rate at 1 mL/h for up to 72 hours after surgery.
Placebo Comparator: Placebo group
Placebo (normal saline) is infused during general anesthesia and used as a supplement for patient-controlled intravenous analgesia after surgery.
Drug: Placebo
Placebo (normal saline) is administered in the same rate and volume as that in the dexmedetomidine-esketamine group. Patient-controlled intravenous analgesia is established with 100 μg sufentanil, diluted to 100 mL with normal saline, and programmed to deliver 2-mL boluses with a lock-out interval of 8 minutes and background infusion rate at 1 mL/h for up to 72 hours after surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of sleep disturbances within 3 days after surgery
Time Frame: Up to 3 days after surgery
Sleep disturbances are defined as Richards-Campbell Sleep Questionnaire (RCSQ) score below 50, based on assessments conducted daily between 8:00 am and 10:00 am during postoperative days 1 to 3.
Up to 3 days after surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pain intensity both at rest and with movement during the first 3 postoperative days
Time Frame: Up to 3 days after surgery
Pain intensity is assessed with the numeric rating scale (NRS; an 11-point scale where 0=no pain and 10=the worst pain) twice daily (8:00 am to 10:00 am, and 18:00 pm to 20:00 pm) both at rest and with movement during the first 3 postoperative days.
Up to 3 days after surgery
Anxiety and depression on the third day after surgery
Time Frame: On the third day after surgery
Postoperative anxiety and depression are assessed using the Hospital Anxiety and Depression Scale (HADS), with scores categorized as follows: 0-7 (negative), 8-10 (mild), 11-14 (moderate), and 15-21 (severe).
On the third day after surgery
Subjective sleep quality on the 30th day after surgery
Time Frame: On the 30th day after surgery
Subjective sleep quality is assessed with the Pittsburgh Sleep Quality Index (PSQI) on the 30th postoperative day.
On the 30th day after surgery
Quality of recovery at 24 hours after surgery
Time Frame: At 24 hours after surgery
Quality of recovery is assessed using the Quality of Recovery-15 (QoR-15) scale at 24 hours after surgery. The total QoR-15 scores are evaluated based on physical comfort (five items), emotional state (four items), psychological support (two items), physical independence (two items), and pain (two items) for QoR-15 questionnaire. Each item is scored from 0 to 10, and the possible total score ranges from 0 to 150, with higher scores representing better recovery quality after operation.
At 24 hours after surgery
Subjective sleep quality in the first 3 nights after surgery.
Time Frame: Up to 3 days after surgery.
Subjective sleep quality is assessed daily (8:00 am to 10:00 am) using the Richards-Campbell Sleep Questionnaire (RCSQ) during the first 3 postoperative days. Richards-Campbell Sleep Questionnaire (RCSQ) comprises five items: sleep depth, sleep latency, awakenings, returning to sleep, and sleep quality. Each item is assessed with a 100-mm visual analog scale. The scores range from 0, indicating the worst possible sleep, to 100, indicating the best possible sleep. The total RCSQ sleep score is derived by summing up the individual scores on the five sleep items and dividing it by 5.
Up to 3 days after surgery.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to extubation after surgery
Time Frame: On the day of surgery
Time interval from end of surgery to extubation.
On the day of surgery
Incidence of emergence agitation after surgery
Time Frame: Up to 2 hours after extubation
Emergence agitation was defined as a Richmond Agitation-Sedation Scale (RASS) score ≥ +2 at any time point from tracheal extubation to discharge from the post-anesthesia care unit (PACU)
Up to 2 hours after extubation
Cumulative opioid consumption within 48 hours after surgery
Time Frame: Within 48 hours after surgery
Cumulative opioid consumption from end of surgery to 48 hours after surgery.
Within 48 hours after surgery
Length of hospital stay after surgery
Time Frame: Up to 30 days after surgery.
Time interval from end of surgery to hospital discharge.
Up to 30 days after surgery.
Incidence of postoperative complications
Time Frame: Up to 30 days after surgery
Postoperative complications are defined as new onset conditions that are deemed harmful and and require therapeutic intervention, i.e., class II or above on the Clavien-Dindo classification.
Up to 30 days after surgery
All-cause 30-day mortality
Time Frame: Up to 30 days after surgery
All-cause death within 30 days after surgery.
Up to 30 days after surgery
Proportion of patients requiring rescue analgesia within 48 hours after surgery
Time Frame: Within 48 hours after surgery
Rescue analgesia indicates any analgesics in addition to patient-controlled intravenous analgesia.
Within 48 hours after surgery
Agitation and sedation levels during the first 3 postoperative days
Time Frame: Up to 3 days after surgery
Agitation and sedation levels are assessed using the Richmond Agitation-Sedation Scale (RASS) twice daily (8:00 am to 10:00 am, and 18:00 pm -20:00) during the first 3 postoperative days.
Up to 3 days after surgery

Collaborators and Investigators

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

Sponsor

Peking University First Hospital

Investigators

  • Study Chair: Dong-Xin Wang, 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)

March 18, 2025

Primary Completion (Estimated)

November 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

February 28, 2025

First Submitted That Met QC Criteria

February 28, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 18, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024-729

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

product manufactured in and exported from the U.S.

Yes

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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