Dexmedetomidine-esketamine Combination and Chronic Postsurgical Pain After Spinal Surgery

April 13, 2026 updated by: Dong-Xin Wang, Peking University First Hospital

Effect of Perioperative Use of Dexmedetomidine-esketamine Combination on Incidence of Chronic Postsurgical Pain After Spinal Surgery: a Randomized Controlled Trial

Spinal surgery is generally followed by severe postoperative pain, and poor pain control may cause adverse outcomes such as cardiovascular events, neurocognitive disorders, and chronic postsurgical pain (CPSP). In previous studies, perioperative use of dexmedetomidine or esketamine is each associated with improved analgesia after surgery. Recent studies suggest that combined use of dexmedetomidine and esketamine may produce synergetic effects in improving analgesia. This trial is designed to test the hypothesis that perioperative combined use of dexmedetomidine and esketamine may reduce CPSP in patients after spinal surgery.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Spinal surgery is generally followed by severe pain due to extensive trauma. The reported rate of moderate-to-severe pain ranged from 30% to 63%. Uncontrolled postoperative pain is associated with worse outcomes including cardiovascular events, neurocognitive complications, and chronic postsurgical pain (CPSP). Opioids are the main stay of analgesia after spinal surgery. However, high dose opioids provoke side effects such as nausea and vomiting, delirium, and even respiratory depression. Multimodel analgesia is suggested for these patients.

Dexmedetomidine is a highly selective alpha 2 adrenergic receptor agonist with sedative, analgesic, and anxiolytic effects. A meta-analysis suggest that, for patients undergoing spinal surgery, intraoperative dexmedetomidine improved early postoperative analgesia, but the effect did not persist beyond 6 hours. Ketamine is a noncompetitive N-Methyl-D-aspartic acid (NMDA) receptor antagonist and has been used as an anesthetic and analgesic for decades. Esketamine is the S-enantiomer of ketamine and has an analgesic potent of approximately 2 times of that of ketamine. Small sample size studies in patients undergoing spinal surgery showed that intra- or postoperative use of subanesthetic dose esketamine improved analgesia and reduced rescue analgesics.

The analgesic effects of dexmedetomidine and esketamine are dose-dependent. However, routine dose dexmedetomidine may increase bradycardia and hypotnsion, and even subanethetic dose esketamine may produce neuropsychiatric symptoms. Combined use of dexmedetomdine and esketamine may augment analgesic and sedative effects while decreasing side effects. In a previous study, using low-dose dexmedetomidine (1 ug/ml) and esketamine (0.25 mg/ml) as supplements to self-controlled sufentanil analgesia improved pain relief and sleep quality after spinal surgery, but the rate of moderate-to-severe pain remained high. In a recent study, when used as a supplement to sufentanil analgesia, increasing esketamine dose to 0.5 mg/ml did not significantly improve analgesia, whereas increasing esketamine dose to 0.75 mg/ml increased nausea and vomiting.

In available studies, use of dexmedetomidine and/or esketamine were mostly limited to either intra- or postoperative period. Introperative use of the combination only improve early postoperative analgesia. Whereas postoperative use of the combination did not have effects on peak intraoperative stress. It is reasonable to hypothesize that using dexmedetomidine-esketamine combination during both the intra- and postoperative periods may provide better analgesia and decrease CPSP in patients after spinal surgery.

Study Type

Interventional

Enrollment (Estimated)

274

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:

  1. Aged >= 40 years and < 80 years;
  2. Scheduled to undergo elective posterior cervical, thoracic or lumbar spine surgery under general anesthesia, with an expected operative duration >= 2 hours;
  3. Requirement for patient-controlled intravenous analgesia (PCIA) postoperatively.

Exclusion Criteria:

  1. Severe uncontrolled hypertension preoperatively (baseline ward blood pressure: SBP > 180 mmHg or DBP > 110 mmHg);
  2. Severe bradycardia (heart rate <= 50 bpm), sick sinus syndrome, atrioventricular block of grade II or higher without pacemaker implantation, or a history of myocardial infarction within one year, severe heart failure (NYHA class >= III), or rapid ventricular arrhythmia;
  3. Preoperative history of schizophrenia, epilepsy, Parkinson's disease, myasthenia gravis, or intracranial hypertension;
  4. Preoperative history of hyperthyroidism or pheochromocytoma;
  5. Inability to communicate preoperatively due to coma, severe dementia, or language impairment;
  6. Severe cardiac insufficiency (preoperative LVEF < 30% or NYHA class IV), severe hepatic dysfunction (Child-Pugh class C), severe renal dysfunction (preoperative dialysis), or ASA physical status >= grade IV;
  7. Other conditions deemed inappropriate for study participation by the investigator or attending physician.

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: Combined dexmedetomidine-esketamine group

During anesthesia, a loading dose (0.2 ml/kg) of dexmedetomidine-esketamine (DEX-ESK) combination (DEX 2 ug/ml; ESK 1 mg/ml) will be infused after anesthesia induction (DEX 0.4 ug/kg; ESK 0.2 mg/kg), followed by a continuous infusion at 0.1 ml/kg/h (DEX 0.2 ug/kg/h; ESK 0.1 mg/kg/h) until 1 hour before the expected end of surgery.

After surgery, patient-controlled intravenous analgesia will be established with dexmedetomidine (DEX 1.5 ug/ml), esketamine (ESK 0.5 mg/ml), and sufentanil (1.25 ug/ml), programmed to deliver 2-ml boluses (DEX 3.0 ug, ESK 1 mg, and sufentanil 2.5 ug) with a 8-10-minute lockout interval and a 1-ml/h (DEX 1.5 ug/h, ESK 0.5 mg/h, and 1.25 ug/h sufentanil) background infusion, and used for up to 48 hours.
Drug: Combined dexmedetomidine-esketamine administration

During anesthesia, a loading dose (0.2 ml/kg) of dexmedetomidine-esketamine (DEX-ESK) combination (DEX 2 ug/ml; ESK 1 mg/ml) will be infused after anesthesia induction (DEX 0.4 ug/kg; ESK 0.2 mg/kg), followed by a continuous infusion at 0.1 ml/kg/h (DEX 0.2 ug/kg/h; ESK 0.1 mg/kg/h) until 1 hour before the expected end of surgery.

After surgery, patient-controlled intravenous analgesia will be established with dexmedetomidine (DEX 1.5 ug/ml), esketamine (ESK 0.5 mg/ml), and sufentanil (1.25 ug/ml), programmed to deliver 2-ml boluses (DEX 3.0 ug, ESK 1 mg, and sufentanil 2.5 ug) with a 8-10-minute lockout interval and a 1-ml/h (DEX 1.5 ug/h, ESK 0.5 mg/h, and 1.25 ug/h sufentanil) background infusion, and used for up to 48 hours.

Other Names:
  • Dexmedetomidine and esketamine
Placebo Comparator: Placebo group

During anesthesia, a loading dose (0.2 ml/kg) of normal saline will be infused after anesthesia induction, followed by a continuous infusion at 0.1 ml/kg/h until 1 hour before the expected end of surgery.

After surgery, patient-controlled intravenous analgesia will be established with sufentanil (1.25 ug/ml), programmed to deliver 2-ml boluses (sufentanil 2.5 ug) with a 8-10-minute lockout interval and a 1-ml/h (1.25 ug/h sufentanil) background infusion, and used for up to 48 hours.
Drug: Placebo administration

During anesthesia, a loading dose (0.2 ml/kg) of normal saline will be infused after anesthesia induction, followed by a continuous infusion at 0.1 ml/kg/h until 1 hour before the expected end of surgery.

After surgery, patient-controlled intravenous analgesia will be established with sufentanil (1.25 ug/ml), programmed to deliver 2-ml boluses (sufentanil 2.5 ug) with a 8-10-minute lockout interval and a 1-ml/h (1.25 ug/h sufentanil) background infusion, and used for up to 48 hours.

Other Names:
  • Placebo (normal saline)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of chronic pain at 3 months after surgery
Time Frame: Up to 3 months after surgery.

Chronic post-spinal surgery pain is a specific type of Chronic Postsurgical Pain (CPSP), defined as pain lasting >=3 months postoperatively after exclusion of other known causes. The presence of persistent pain beyond the postoperative recovery period is confirmed if any one of the following three criteria is met (either alone or in combination):

  1. Any additional lumbar spine surgery within 3 months after the index surgery;
  2. At least one pain-related physician visit within 3 months after the index surgery;
  3. Any other surgical intervention for pain management at any time after surgery (not limited to 24 months), such as neuromodulation or implantation of a drug delivery system.
Up to 3 months after surgery.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of chronic pain at 6 months after surgery
Time Frame: Up to 6 months after surgery.

Chronic post-spinal surgery pain is a specific type of Chronic Postsurgical Pain (CPSP), defined as pain lasting >=3 months postoperatively after exclusion of other known causes. The presence of persistent pain beyond the postoperative recovery period is confirmed if any one of the following three criteria is met (either alone or in combination):

  1. Any additional lumbar spine surgery between 3 and 6 months after the index surgery;
  2. At least one pain-related physician visit within between 3 and 6 months after the index surgery;
  3. Any other surgical intervention for pain management at any time after surgery (not limited to 24 months), such as neuromodulation or implantation of a drug delivery system.
Up to 6 months after surgery.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pain scores (Numerical Rating Scale, NRS) at 3 and 6 months after surgery
Time Frame: Up to 6 months after surgery.
Assesses pain intensity at 3 and 6 months post-surgery via the NRS scale (0=no pain, 10=worst imaginable pain), with patients rating pain at rest and during activity through telephone follow-up.
Up to 6 months after surgery.
Incidence of neurocognitive disorders at 3 and 6 months postoperatively
Time Frame: Up to 6 months after surgery.
Postoperative neurocognitive disorder was defined as a decrease in T-MoCA score of >= 1 standard deviation (SD) from baseline.
Up to 6 months after surgery.
Oswestry Disability Index (ODI) at 3 and 6 months postoperatively
Time Frame: Up to 6 months after surgery.
Evaluates spinal-related functional impairment at 3 and 6 months post-surgery via the ODI scale (0-100%), with patients rating disability from back/leg pain across 10 daily life domains; higher scores mean greater functional impairment (assessed by telephone follow-up).
Up to 6 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 (Estimated)

April 1, 2026

Primary Completion (Estimated)

November 1, 2027

Study Completion (Estimated)

December 1, 2027

Study Registration Dates

First Submitted

April 6, 2026

First Submitted That Met QC Criteria

April 6, 2026

First Posted (Actual)

April 13, 2026

Study Record Updates

Last Update Posted (Actual)

April 16, 2026

Last Update Submitted That Met QC Criteria

April 13, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2026-0136-LT

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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