Different Dose Esketamine and Dexmedetomidine Combination for Supplemental Analgesia After Scoliosis Correction Surgery

April 7, 2026 updated by: Dong-Xin Wang, Peking University First Hospital

Efficacy of Different Dose Esketamine and Dexmedetomidine Combination for Supplemental Analgesia After Scoliosis Correction Surgery: A Randomized, Double-blind Trial

Scoliosis correction surgery is associated with severe pain. Patients after scoliosis correction surgery usually require high dose opioids and long duration analgesia, which may increase side effects and drug tolerance. In a recent trial, mini-dose esketamine and dexmedetomidine combination as a supplement to sufentanil significantly improved analgesia and subjective sleep quality after spinal correction surgery without increasing adverse events; however, the proportion of patients with moderate-to-severe pain remained high. The authors speculate that increasing esketamine dose in the combination may further improve analgesic effects.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Spinal surgery is associated with severe pain, with a median pain score of 7 (interquartile range, 4 to 8) on the first postoperative day, and requires long duration analgesia. The total dose of opioids required for postoperative analgesia is about 2-4 times that for other surgeries. However, despite high dose opioids, the analgesic effects remain unsatisfied. In a recent trial of 200 patients following scoliosis correction surgery, the proportion with moderate-to-severe pain in patients given routine analgesia was 84.6%. Severe acute pain is an important risk factor of chronic postsurgical pain and is associated with an increased risk of long-term opioid use.

Ketamine is a non-competitive N-methyl-D-aspartate receptor antagonist. Low-dose ketamine infusion is recommended for postoperative analgesia but may cause neuropsychiatric side effects. Esketamine is the S-enantiomer of racemic ketamine with approximately twice as potent as racemic ketamine in analgesia and less likely to produce side effects. Dexmedetomidine is a highly selective α2 receptor agonist and has anxiolytic, sedative, analgesic effects. When used as a supplement to opioid analgesia, dexmedetomidine improves analgesia and sleep quality but may produce sedation.

In a recent trial, mini-dose esketamine-dexmedetomidine combination as a supplement to sufentanil significantly improved analgesia and subjective sleep quality after scoliosis correction surgery; no significant adverse reactions were observed. However, the proportion of moderate-to-severe pain remained high (65.7%) in these patients, so further improvement is needed. The authors speculate that increasing esketamine dose in the esketamine-dexmedetomidine combination may further improve the analgesia. This study aims to explore the effects of different dose esketamine in the combination on acute and chronic pain in patients following spinal deformity surgery.

Study Type

Interventional

Enrollment (Estimated)

312

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Aged ≥18 years and body weight ≥40 kg;
  • Scheduled to undergo scoliosis correction with pedicle screw fixation;
  • Required patient-controlled intravenous analgesia after surgery.

Exclusion Criteria:

  • Preoperative sick sinus syndrome, severe sinus bradycardia (heart rate <50 beats/min), atrioventricular block grade II or above without pacemaker; or comorbid with congenital heart disease, arrhythmia, or other serious cardiovascular diseases with a cardiac function grade ≥III;
  • Patients with moderate and severe obstructive sleep apnea diagnosed preoperatively or according to the STOP-Bang score；
  • History of hyperthyroidism and pheochromocytoma;
  • History of schizophrenia, epilepsy, myasthenia gravis, or delirium;
  • Severe liver dysfunction (child Pugh grade C), severe renal dysfunction (preoperative dialysis), or American Society of Anesthesiologists grade ≥IV;
  • Barrier in communication;
  • Other conditions that are considered 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
Active Comparator: Low-dose group
Patient-controlled analgesia is established with esketamine 50 mg, dexmedetomidine 200 microgram, and sufentanil 4 microgram/kg (maximum 250 microgram), diluted with normal saline to 200 ml, and programmed to administer 2-ml boluses with a lockout interval of 8 minutes and a background infusion rate at 1 ml/h.
Drug: Esketamine
Different doses of esketamine in the esketamine-dexmedetomidine combination as a supplement to sufentanil for postoperative intravenous analgesia.
Experimental: Medium-dose group
Patient-controlled analgesia is established with esketamine 100 mg, dexmedetomidine 200 microgram, and sufentanil 4 microgram/kg (maximum 250 microgram), diluted with normal saline to 200 ml, and programmed to administer 2-ml boluses with a lockout interval of 8 minutes and a background infusion rate at 1 ml/h.
Drug: Esketamine
Different doses of esketamine in the esketamine-dexmedetomidine combination as a supplement to sufentanil for postoperative intravenous analgesia.
Experimental: High-dose group
Patient-controlled analgesia is established with esketamine 150 mg, dexmedetomidine 200 microgram, and sufentanil 4 microgram/kg (maximum 250 microgram), diluted with normal saline to 200 ml, and programmed to administer 2-ml boluses with a lockout interval of 8 minutes and a background infusion rate at 1 ml/h.
Drug: Esketamine
Different doses of esketamine in the esketamine-dexmedetomidine combination as a supplement to sufentanil for postoperative intravenous analgesia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pain intensity with movement and opioid consumption within 72 hours.
Time Frame: Within 72 hours after surgery
A comprehensive index of pain intensity and opioid consumption is calculated. The range of the index is -200% to +200%; values above 0 indicate increased summed area under curve (AUC) and opioid consumption (OC) compared to the all patients.
Within 72 hours after surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patients with moderate to severe pain within 72 hours.
Time Frame: Up to 72 hours after surgery.
Pain intensity is evaluated with the Numeric Rating Scale (NRS, an 11-point scale where 0 = no pain and 10 = the worst pain) twice daily (8:00-10:00 and 18:00-20:00) at rest and with movement. Moderate to severe pain is defined as any NRS pain score of 4 or higher.
Up to 72 hours after surgery.
The highest NRS pain score within 72 hours after surgery.
Time Frame: Up to 72 hours after surgery.
Pain intensity is evaluated with the Numeric Rating Scale (NRS, an 11-point scale where 0 = no pain and 10 = the worst pain) twice daily (8:00-10:00 and 18:00-20:00) at rest and with movement.
Up to 72 hours after surgery.
Area under curve of NRS pain score within 72 hours after surgery.
Time Frame: Up to 72 hours after surgery
Pain intensity is evaluated with the Numeric Rating Scale (NRS, an 11-point scale where 0 = no pain and 10 = the worst pain) twice daily (8:00-10:00 and 18:00-20:00) at rest and with movement.
Up to 72 hours after surgery
Cumulative opioid consumption within 72 hours after surgery.
Time Frame: Up to 72 hours after surgery
Cumulative opioid consumption within 72 hours after surgery.
Up to 72 hours after surgery
Requirement of supplement analgesia within 72 hours.
Time Frame: Up to 72 hours after surgery
Requirement of supplement analgesia within 72 hours.
Up to 72 hours after surgery
Subjective sleep quality during the first 5 postoperative days.
Time Frame: Up to the 5th day after surgery.
Subjective sleep quality is evaluated with the Numeric Rating Scale (NRS, an 11-point scale where 0 = the best sleep and 10 = no sleep at all) once daily (8:00-10:00).
Up to the 5th day after surgery.
Number of days requiring analgesics within 30 days after surgery.
Time Frame: Up to 30 days after surgery.
Number of days requiring analgesics within 30 days after surgery.
Up to 30 days after surgery.
Pain intensity at rest and opioid consumption within 72 hours.
Time Frame: Within 72 hours after surgery.
A comprehensive index of pain intensity and opioid consumption is calculated. The range of the index is -200% to +200%; values above 0 indicate increased summed AUC and OC compared to the all patients.
Within 72 hours after surgery.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Length of stay in hospital after surgery.
Time Frame: Up to 30 days after surgery.
Length of stay in hospital after surgery.
Up to 30 days after surgery.
Agitation and sedation score at various timepoints after surgery.
Time Frame: Up to the 5th day after surgery.
Agitation and sedation score is evaluated with the Richmond Agitation and Sedation Scale (RASS, with scores ranging from -5 [unarousable] to +4 [combative] and 0 indicates alert and calm) twice daily (8:00-10:00 and 18:00-20:00).
Up to the 5th day after surgery.
Incidence of postoperative delirium within the first 5 days.
Time Frame: Up to the 5th day after surgery.
Delirium is assessed with the Three-dimensional Confusion Assessment Method (3D-CAM) twice daily (8:00-10:00 and 18:00-20:00).
Up to the 5th day after surgery.
Depression severity at 7 days after surgery.
Time Frame: At the 7th day after surgery.
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.
At the 7th day after surgery.
Incidence of postoperative complications within 30 days
Time Frame: Up to 30 days after surgery.
Postoperative complications are defined as new-onset medical conditions that were deemed harmful and required therapeutic intervention (i.e., grade II or higher on the Clavien-Dindo classification).
Up to 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)

October 24, 2023

Primary Completion (Actual)

October 23, 2025

Study Completion (Estimated)

October 1, 2026

Study Registration Dates

First Submitted

September 25, 2023

First Submitted That Met QC Criteria

September 25, 2023

First Posted (Actual)

October 2, 2023

Study Record Updates

Last Update Posted (Actual)

April 13, 2026

Last Update Submitted That Met QC Criteria

April 7, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2023-351

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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