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

NCT04964219 | Completed Phase 4 DMC

• 1 other identifier: 2021-272
• Study Type: interventional
• Target: 164
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

S-ketamine; Postoperative Analgesia; Spine Fusion

Keywords

S-ketamine; Postoperative Analgesia; Spine Fusion

Outcome Measures

Primary Outcomes (1)

• The percentage of patients with moderate-to-severe pain in the first 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 Outcomes (11)

• Opioid consumption during anesthesia

  From induction to end of anesthesia

• Cumulative opioid consumption after surgery

  From end of anesthesia to the 5th day after surgery

• NRS pain score at rest and with movement

  Up to postoperative day 5

• The percentage of using rescue analgesics

  Up to postoperative day 5

• Subjective sleep quality

  Up to postoperative day 5

Other Outcomes (5)

• Sedation or agitation level

  Up to 5 days after surgery

• The incidence of postoperative nausea and vomiting

  Up to 5 days after surgery

• The incidence of delirium

  Up to 5 days after surgery

Study Arms (2)

S-ketamine group

EXPERIMENTAL

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

Control group

PLACEBO COMPARATOR

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

Interventions

S-ketamine DRUG

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.

S-ketamine group

Placebo DRUG

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.

Control group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Peking University First Hospital: lead

Study Sites (1)

Beijing University First Hospital

Beijing, Beijing Municipality, 100034, China

Location

Related Publications (17)

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• Nielsen RV, Fomsgaard JS, Siegel H, Martusevicius R, Nikolajsen L, Dahl JB, Mathiesen O. Intraoperative ketamine reduces immediate postoperative opioid consumption after spinal fusion surgery in chronic pain patients with opioid dependency: a randomized, blinded trial. Pain. 2017 Mar;158(3):463-470. doi: 10.1097/j.pain.0000000000000782.

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• Brinck ECV, Maisniemi K, Kankare J, Tielinen L, Tarkkila P, Kontinen VK. Analgesic Effect of Intraoperative Intravenous S-Ketamine in Opioid-Naive Patients After Major Lumbar Fusion Surgery Is Temporary and Not Dose-Dependent: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Anesth Analg. 2021 Jan;132(1):69-79. doi: 10.1213/ANE.0000000000004729.

  PMID: 32167978 BACKGROUND

MeSH Terms

Interventions

Esketamine

Study Officials

• Dong-Xin Wang, MD, PhD

  Peking University First Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 6, 2021
• First Posted: July 16, 2021
• Study Start: February 8, 2022
• Primary Completion: April 1, 2025
• Study Completion: May 2, 2025
• Last Updated: July 30, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)