Dexmedetomidine-Esketamine Combination and Sleep Disturbances After Major Noncardiac Surgery

Phase 4

Recruiting

• Conditions: Adults; Esketamine; Major Noncardiac Surgery; Postoperative Sleep Disturbances; Dexmedetomidine
• Interventions: Drug: Dexmedetomidine-esketamine combination; Drug: Placebo

• Registration Number: NCT06859892
• Lead Sponsor: Peking University First Hospital

Brief Summary

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.

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 Timeline

• Study First Submitted: 2025-02-28
• Study First Submitted QC: 2025-02-28
• Status Verified: 2025-03
• Study First Posted: 2025-03-05
• Study Start: 2025-03-18
• Last Update Submitted: 2025-03-18
• Last Update Posted: 2025-03-19
• Primary Completion: 2026-11
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 476

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dexmedetomidine-esketamine group	Dexmedetomidine-esketamine combination	Dexmedetomidine-esketamine combination is infused during general anesthesia and used as a supplement for patient-controlled intravenous analgesia after surgery.
Placebo group	Placebo	Placebo (normal saline) is infused during general anesthesia and used as a supplement for patient-controlled intravenous analgesia after surgery.

Primary Outcome Measures

Name	Time	Method
Incidence of sleep disturbances within 3 days after surgery	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.

Secondary Outcome Measures

Name	Time	Method
Quality of recovery at 24 hours after surgery	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.
Subjective sleep quality in the first 3 nights after surgery.	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.
Pain intensity both at rest and with movement during the first 3 postoperative days	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.
Anxiety and depression on the third day after surgery	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).
Subjective sleep quality on the 30th day after surgery	On the 30th day after surgery	Subjective sleep quality is assessed with the Pittsburgh Sleep Quality Index (PSQI) on the 30th postoperative day.

Trial Locations

Locations (1)

Peking University First Hospital; 🇨🇳 Beijing, China