Analgesic Effects of Low-dose S-ketamine in Major Spine Fusion Surgery

July 28, 2025 updated by: Dong-Xin Wang, Peking University First Hospital

Analgesic Effects of Low-dose S-ketamine in Patients Undergoing Major Spine Fusion Surgery: A Double-blinded, Randomized Controlled Trial

Despite opioid-based multimodal analgesia, moderate-to-severe pain remains a big problem in patients following multi-segment spinal fusion. As a N-methyl-D-aspartate receptor antagonist, S-ketamine has prominent analgesic effects through activating receptors both in the brain and in the spinal cord, inhibiting the excitatory postsynaptic potential, and thus blunting nociception transmission.

This randomized controlled trial is designed to investigate whether perioperative S-ketamine infusion can decrease pain intensity after major spine fusion surgery.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Multi-segment spinal fusion usually lasts long and produces significant trauma. Patients following this surgery are at high risk of developing moderate-to-severe pain. In a large sample size cohort study investigating pain severity following 179 kinds of surgical procedures, multi-segment spinal fusion ranked the third with a median pain score of 6.6 (assessed with an 11-point scale, where 0=no pain and 10= the worst pain) and a median morphine consumption of 27 mg during the first postoperative day.

High-dose opioids are associated with adverse effects including respiratory depression, sedation, nausea and vomiting, pruritus, and constipation, which are harmful for early postoperative recovery. A previous study showed that about 50% of patients are taking opioids for chronic pain at 3 months after spinal fusion surgery. Chronic pain is considered to be a result of poorly controlled acute postoperative pain. Thus, multimodal analgesia aiming at improving analgesia while decreasing opioid consumption is advocated to control acute postsurgical pain, in order to promote perioperative recovery and prevent chronic pain.

Racemic ketamine, a commonly used N-methyl-D-aspartate receptor antagonist, is a mixture of equal parts of two optical isomers including R-(-)-ketamine and S-(+)-ketamine. It has prominent analgesic effects through activating receptors both in the brain and in the spinal cord, inhibiting the excitatory postsynaptic potential, and thus blunting nociception transmission. Additionally, studies also showed that, when used within the appropriate time, ketamine reduces pain-related sensitization that aggravates postoperative pain. Thus, ketamine is recommended as a part of a multimodal analgesia regimen in clinical practice, especially for patients undergoing major orthopedic surgery. However, the reported psychotropic side effects limit the clinical use of racemic ketamine.

S-ketamine, an S-isomer of ketamine, is twice as potent as the racemic mixture in analgesia, and produces fewer side effects than the racemic ketamine. How, there are only a few studies exploring analgesic effect of S-ketamine in spine fusion surgery. In opioid-dependent patients, Nielsen et al. reported that intraoperative S-ketamine infusion reduced opioid consumption within 24 hours and relieved back pain intensity at 6 months, it also decreased the daily opioid use at 1 year after spinal surgery. On the other hand, the study of Brinck et al. did not found any superiority of intraoperative S-ketamine in reducing oxycodone consumption within 48 hours after lumbar fusion surgery in opioid-naive patients.

Considering these inconsistent results, the effects of S-ketamine in spinal surgery require further clarification. This trial is designed to investigate the analgesic effect of S-ketamine infused both intraoperatively and postoperatively in patients undergoing multi-segment spine infusion surgery.

Study Type

Interventional

Enrollment (Actual)

164

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
      • Beijing, Beijing, 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

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients aged between 18 and 80 years.
  • Scheduled to undergo multi-segment (≥2) spine fusion surgery.
  • Agreed to receive postoperative patient-controlled analgesia.

Exclusion Criteria:

  • Refused to participant in this trial.
  • Poor blood pressure control in those with hypertension (BP >160/100 mmHg in the ward).
  • Previous history of hyperthyroidism or pheochromocytoma.
  • Previous history of schizophrenia, epilepsy or Parkinson disease.
  • History of sick sinus syndrome, bradycardia (HR <50 beat per min), or atrioventricular block of grade II or higher without pacemaker.
  • Severe heart dysfunction (New York Heart Association functional classification 4), hepatic insufficiency (Child-Pugh grade C), renal insufficiency (serum creatinine of 442 μmol/L or above, or requirement of renal replacement therapy), or ASA classification IV or above.
  • Unable to complete preoperative assessment due to severe dementia or language barrier.
  • Any other conditions that were considered unsuitable for the 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: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: S-ketamine group

After anesthesia induction, a bolus of 0.15 mg/kg S-ketamine is injected intravenously about 30 min before incision; this is followed by a continuous infusion at a rate of 0.15 mg/kg/h until 1 hour before the end of surgery.

After surgery, patient-controlled analgesia is provided. The pump is established with S-ketamine 25 mg, dexmedetomidine 100 microgram, and sufentanil 100 microgram, diluted with normal saline to 100 ml. The pump is programmed to deliver 2-ml boluses with a background infusion rate at 1 ml /h and a 10-min lockout interval.
Drug: S-ketamine

After anesthesia induction, a bolus of 0.15 mg/kg S-ketamine is injected intravenously about 30 min before incision; this is followed by a continuous infusion at a rate of 0.15 mg/kg/h until 1 hour before the end of surgery.

After surgery, patient-controlled analgesia is provided. The pump is established with S-ketamine 25 mg, dexmedetomidine 100 microgram, and sufentanil 100 microgram, diluted with normal saline to 100 ml. The pump is programmed to deliver 2-ml boluses with a background infusion rate at 1 ml /h and a 10-min lockout interval.
Placebo Comparator: Control group

After anesthesia induction, a bolus of placebo (normal saline) in the same volume is injected intravenously about 30 min before incision; this is followed by a continuous infusion of placebo at the same rate until 1 hour before the end of surgery.

After surgery, patient-controlled analgesia is provided. The pump is established with placebo, dexmedetomidine 100 microgram and sufentanil 100 microgram, diluted with normal saline to 100 ml. The pump is programmed to deliver 2-ml boluses with a background infusion rate at 1 ml /h and a 10-min lockout interval.
Drug: Placebo

After anesthesia induction, a bolus of placebo (normal saline) in the same volume is injected intravenously about 30 min before incision; this is followed by a continuous infusion of placebo at the same rate until 1 hour before the end of surgery.

After surgery, patient-controlled analgesia is provided. The pump is established with placebo, dexmedetomidine 100 microgram and sufentanil 100 microgram, diluted with normal saline to 100 ml. The pump is programmed to deliver 2-ml boluses with a background infusion rate at 1 ml /h and a 10-min lockout interval.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The percentage of patients with moderate-to-severe pain in the first 48 hours after surgery.
Time Frame: Up to 48 hours after surgery
Moderate-to-severe pain is defined as a numeric rating scale (NRS; an 11-point scale where 0=no pain and 10=the worst pain) pain score ≥4.
Up to 48 hours after surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Opioid consumption during anesthesia
Time Frame: From induction to end of anesthesia
Opioid consumption in equivalent-dose of sufentanil
From induction to end of anesthesia
Cumulative opioid consumption after surgery
Time Frame: From end of anesthesia to the 5th day after surgery
Opioid consumption in equivalent-dose of sufentanil
From end of anesthesia to the 5th day after surgery
NRS pain score at rest and with movement
Time Frame: Up to postoperative day 5
Pain is assessed with a numeric rating scale (NRS; an 11-point scale where 0=no pain and 10=the worst pain)
Up to postoperative day 5
The percentage of using rescue analgesics
Time Frame: Up to postoperative day 5
The percentage of using rescue analgesics
Up to postoperative day 5
Subjective sleep quality
Time Frame: Up to postoperative day 5
Subjective sleep quality is assessed with NRS scale (0 indicates the best sleep and 10 indicates the worst sleep)
Up to postoperative day 5
Time to first ambulation
Time Frame: Up to 30 days after surgery
Time to first ambulation
Up to 30 days after surgery
Quality of recover after surgery
Time Frame: On the third day after surgery
Quality of recover is assessed with the Quality of Recovery scale, a 15-item Q-15 questionnaire with score ranges from 0 to 150, with higher score indicating better recovery.
On the third day after surgery
The percentage of taking oral analgesics
Time Frame: On the 30th day after surgery
The percentage of taking oral analgesics
On the 30th day after surgery
The severity of anxiety and depression
Time Frame: On the 30th day after surgery
The severity of anxiety and depression is assessed with the Hospital Anxiety and Depression Scale, a 14-item questionnaire with scores range from 0 to 21 for either anxiety or depression. Higher score indicates more severe symptom.
On the 30th day after surgery
The incidence of postoperative complications and mortality
Time Frame: Up to 30 days after surgery
The incidence of postoperative complications and mortality
Up to 30 days after surgery

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sedation or agitation level
Time Frame: Up to 5 days after surgery
Sedation or agitation was assessed using the Richmond Agitation Sedation Scale (RASS), with scores ranging from -5 (unarousable) to +4 (combative) and 0 indicates alert and calm
Up to 5 days after surgery
The incidence of postoperative nausea and vomiting
Time Frame: Up to 5 days after surgery
The incidence of postoperative nausea and vomiting
Up to 5 days after surgery
The incidence of delirium
Time Frame: Up to 5 days after surgery
The incidence of delirium
Up to 5 days after surgery
The incidence of other adverse events (dizziness, nightmares, hallucination and etc.)
Time Frame: Up to 5 days after surgery
Other adverse events include dizziness, nightmares, hallucination, and others
Up to 5 days after surgery
The percentage of adverse events requiring therapeutic intervention
Time Frame: Up to 5 days after surgery
The percentage of adverse events requiring therapeutic intervention
Up to 5 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)

February 8, 2022

Primary Completion (Actual)

April 1, 2025

Study Completion (Actual)

May 2, 2025

Study Registration Dates

First Submitted

July 6, 2021

First Submitted That Met QC Criteria

July 6, 2021

First Posted (Actual)

July 16, 2021

Study Record Updates

Last Update Posted (Actual)

July 30, 2025

Last Update Submitted That Met QC Criteria

July 28, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2021-272

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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