Impact of Perioperative Dexmedetomidine and Esketamine on Postoperative Quality of Recovery

April 8, 2026 updated by: Dong-Xin Wang, Peking University First Hospital

Impact of Perioperative Dexmedetomidine and Esketamine on Postoperative Quality of Recovery in Patients Undergoing General Anesthesia and Surgery: A 2×2 Factorial Randomized Trial

For patients after surgery, quality of recovery has significant impacts on the prognosis, quality of life, and rational allocation of medical resources. Dexmedetomidine and esketamine have each been used during the perioperative period and improved postoperative analgesia and subjective sleep quality. This 2x2 factorial trial is designed to explore the effects of dexmedetomidine, esketamine, and their combination on the quality of recovery in patients recovering from surgery under general anesthesia.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Surgical operation is an important therapeutic modality for surgical patients; quality of postoperative recovery has significant impacts on the prognosis, quality of life, and rational allocation of medical resources. Postoperative recovery is a complex process involving return of patients from surgery to baseline physiological and psychological status. Traditional indicators evaluating postoperative recovery mainly focus on physiological markers, length of hospital stay (LOS), and incidences of adverse events and complications. Recently, the quality of recovery (QoR) is increasingly used. QoR is subjectively reported by patients and includes multidimensional assessments on postoperative pain, cognitive function, sleep quality, and emotional stability.

Dexmedetomidine, a highly selective α2-adrenergic receptor agonist, has anxiolytic, sedative, and analgesic effects. By activing α2-adrenergic receptors in the locus coeruleus, it activates the endogenous sleep pathways, and produce a state mimicking non-rapid eye movement (NREM) sleep. Clinical studies showed that perioperative use of low-dose dexmedetomidine improves sleep architecture, increases sleep efficiency, and prolongs total sleep time in non-mechanically ventilated patients. Furthermore, when used as an analgesic adjuvant, dexmedetomidine improves analgesia, reduces opioid consumption, and reduces opioid-related adverse events.

Ketamine, a non-competitive N-Methyl-D-aspartic (NMDA) receptor antagonist, exerts analgesic and anti-hyperalgesic effects by reducing transmission of noxious stimuli to the spinal cord. It is characterized by minimal respiratory and circulatory depression and excellent analgesic efficacy. In recent years, multiple studies confirmed that ketamine has antidepressant properties. Ketamine is a racemic mixture composed of S-ketamine (esketamine) and R-ketamine. Esketamine exhibits a stronger affinity for the NMDA receptor, with an effect approximately twice that of racemic ketamine. In clinical practice, esketamine has stronger analgesic effects and a lower incidence of adverse psychomimetic reactions. When used in combination with opioids, esketamine improved postoperative analgesia.

Previous studies showed that combined use of dexmedetomidine and esketamine might produce synergetic effects in improving sedation and analgesia. A recent trial found that low-dose dexmedetomidine-esketamine combination improved pain relief and subjective sleep quality in patients after scoliosis corrective surgery, without increasing side effects. It is therefore hypothesized that co-administration of dexmedetomidine and esketamine may enhance efficacy and optimize the quality of postoperative recovery. This 2x2 factorial trial is designed to explore the effects of dexmedetomidine, esketamine, and their combination on the quality of recovery in patients recovering from surgery under general anesthesia.

Study Type

Interventional

Enrollment (Estimated)

316

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 Contact Backup

Study Locations

  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100034

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:

  • Aged 18 years or over;
  • Scheduled to undergo surgery under general anesthesia, with an expected surgical duration of at least 1 hour;
  • Required patient-controlled intravenous analgesia after surgery.

Exclusion Criteria:

  • Unable to communicate preoperatively due to visual, auditory, or verbal barriers or other reasons;
  • Severe bradycardia (heart rate <50 bpm), sick sinus syndrome, or grade 2 or higher atrioventricular block without pacemaker;
  • History of hyperthyroidism or pheochromocytoma;
  • History of schizophrenia, epilepsy, Parkinson's disease, myasthenia gravis, or intracranial hypertension;
  • Intracranial tumor or neurosurgery;
  • Severe liver dysfunction (Child-Pugh class C), renal failure (requiring renal replacement therapy), or American Society of Anesthesiologists class IV or higher;
  • 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: Factorial Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dexmedetomidine

A loading dose of dexmedetomidine (0.2 ug/kg) is administered after anesthesia induction, followed by a continuous infusion of dexmedetomidineat a rate of 0.2 ug/kg/h until 30 minutes before the end of surgery.

Self-controlled analgesia is established with dexmedetomidine 100 ug and sufentanil 100 ug, diluated with normal saline to 100 ml, and programmed to deliver 2-ml boluses with a lock-out interval of 10 minutes and a background infusion rate at 1 ml/h for a duration of 48 hours.
Drug: Dexmedetomidine

A loading dose of dexmedetomidine (0.2 ug/kg) is administered after anesthesia induction, followed by a continuous infusion of dexmedetomidineat a rate of 0.2 ug/kg/h until 30 minutes before the end of surgery.

Self-controlled analgesia is established with dexmedetomidine 100 ug and sufentanil 100 ug, diluated with normal saline to 100 ml, and programmed to deliver 2-ml boluses with a lock-out interval of 10 minutes and a background infusion rate at 1 ml/h for a duration of 48 hours.
Experimental: Esketamine

A loading dose of esketamine (0.1 mg/kg) is administered after anesthesia induction, followed by a continuous infusion of esketamineat a rate of 0.1 mg/kg/h until 30 minutes before the end of surgery.

Self-controlled analgesia is established with esketamine 50 mg and sufentanil 100 ug, diluated with normal saline to 100 ml, and programmed to deliver 2-ml boluses with a lock-out interval of 10 minutes and a background infusion rate at 1 ml/h for a duration of 48 hours.
Drug: Esketamine

A loading dose of esketamine (0.1 mg/kg) is administered after anesthesia induction, followed by a continuous infusion of esketamineat a rate of 0.1 mg/kg/h until 30 minutes before the end of surgery.

Self-controlled analgesia is established with esketamine 50 mg and sufentanil 100 ug, diluated with normal saline to 100 ml, and programmed to deliver 2-ml boluses with a lock-out interval of 10 minutes and a background infusion rate at 1 ml/h for a duration of 48 hours.
Experimental: Dexmedetomidine-esketamine

A loading dose of dexmedetomidine (0.2 ug/kg) and esketamine (0.1 mg/kg) is administered after anesthesia induction, followed by a continuous infusion of dexmedetomidine at a rate of 0.2 ug/kg/h and esketamine at a rate of 0.1 mg/kg/h until 30 minutes before the end of surgery.

Self-controlled analgesia is established with dexmedetomidine 100 ug, esketamine 50 mg, and sufentanil 100 ug, diluated with normal saline to 100 ml, and programmed to deliver 2-ml boluses with a lock-out interval of 10 minutes and a background infusion rate at 1 ml/h for a duration of 48 hours.
Drug: Dexmedetomidine-esketamine

A loading dose of dexmedetomidine (0.2 ug/kg) and esketamine (0.1 mg/kg) is administered after anesthesia induction, followed by a continuous infusion of dexmedetomidine at a rate of 0.2 ug/kg/h and esketamine at a rate of 0.1 mg/kg/h until 30 minutes before the end of surgery.

Self-controlled analgesia is established with dexmedetomidine 100 ug, esketamine 50 mg, and sufentanil 100 ug, diluated with normal saline to 100 ml, and programmed to deliver 2-ml boluses with a lock-out interval of 10 minutes and a background infusion rate at 1 ml/h for a duration of 48 hours.
Placebo Comparator: Control

A loading dose of placebo (normal saline) is administered after anesthesia induction, followed by a continuous infusion of placebo at a rate same as above until 30 minutes before the end of surgery.

Self-controlled analgesia is established with sufentanil 100 ug, diluated with normal saline to 100 ml, and programmed to deliver 2-ml boluses with a lock-out interval of 10 minutes and a background infusion rate at 1 ml/h for a duration of 48 hours.
Drug: Placebo

A loading dose of placebo (normal saline) is administered after anesthesia induction, followed by a continuous infusion of placebo at a rate same as above until 30 minutes before the end of surgery.

Self-controlled analgesia is established with sufentanil 100 ug, diluated with normal saline to 100 ml, and programmed to deliver 2-ml boluses with a lock-out interval of 10 minutes and a background infusion rate at 1 ml/h for a duration of 48 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quality of recovery-15 (QoR-15) score
Time Frame: At 24 hours after surgery
A 15-item scale that evaluate quality of recovery in five dimensions: pain, physiological comfort, physiological independence, psychological support, and emotional state. Scores range from 0 to 150 , with higher scores indicating better recovery quality.
At 24 hours after surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quality of recovery-15 (QoR-15) score
Time Frame: At 72 hours after surgery
QoR is a 15-item scale that evaluate quality of recovery in five dimensions: pain, physiological comfort, physiological independence, psychological support, and emotional state. Scores range from 0 to 150 , with higher scores indicating better recovery quality.
At 72 hours after surgery
Postoperative delirium (POD) within 4 days
Time Frame: Up to 4 days after surgery
Delirium will be assessed twice daily (8:00-10:00 and 18:00-20:00) using the 3-minute diagnostic interview for confusion assessment method-defined delirium (3D-CAM) or the confusion assessment method for the intensive care unit (CAM-ICU).
Up to 4 days after surgery
Incidence of delayed neurocognitive recovery at 5 days
Time Frame: Up to 5 days after surgery
Cognitive function will be assessed with the telephone-administered Montreal Cognitive Assessment (T-MoCA) at baseline and at 5 days or before hospital discharge after surgery. A decline of T-MoCA score of 1 standard deviation (SD) or more from baseline is defined as delayed neurocognitive recovery.
Up to 5 days after surgery

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
All-cause 30-day mortality
Time Frame: Up to 30 days after surgery
All-cause 30-day mortality
Up to 30 days after surgery
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
Area under curve of pain intensity after surgery
Time Frame: Up to 4 days after surgery
Pain intensity will be assessed at 1 hour and then twice daily (8:00-10:00 and 18:00-20:00) after surgery using the numeric rating scale (an 11-point scale where 0=no pain and 10=the worst pain).
Up to 4 days after surgery
Cumulative subjective sleep quality score after surgery
Time Frame: Up to 4 days after surgery
Subjective sleep quality will be assessed once daily (8:00-10:00) after surgery using the numeric rating scale (an 11-point scale where 0=the best sleep and 10=the worst sleep).
Up to 4 days after surgery
Incidence of postoperative complications within 30 days
Time Frame: Up to 30 days after surgery
Postoperative complications are generally defined as new-onset medical conditions that are deemed harmful and required therapeutic intervention, i.e., grade 2 or higher on the Clavien-Dindo classification.
Up to 30 days after surgery
Incidence of delayed neurocognitive recovery at 30 days
Time Frame: At 30 days after surgery
Cognitive function will be assessed with the telephone-administered Montreal Cognitive Assessment (T-MoCA) at baseline and at 30 days after surgery. A decline of T-MoCA score of 1 standard deviation (SD) or more from baseline is defined as delayed neurocognitive recovery.
At 30 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

  • 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)

January 5, 2026

Primary Completion (Estimated)

March 1, 2027

Study Completion (Estimated)

April 1, 2027

Study Registration Dates

First Submitted

December 15, 2025

First Submitted That Met QC Criteria

December 17, 2025

First Posted (Actual)

December 30, 2025

Study Record Updates

Last Update Posted (Actual)

April 13, 2026

Last Update Submitted That Met QC Criteria

April 8, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2025-0455

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.

Clinical Trials on Surgery

Clinical Trials on Dexmedetomidine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Spain

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe