NCT04964219

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

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

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 164 (actual)
• Sponsor: Peking University First Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

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.

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.

Conditions

• S-ketamine
• Postoperative Analgesia
• Spine Fusion

Interventions

Type	Name	Description
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.
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.

Timeline

• Start date: 2022-02-08
• Primary completion: 2025-04-01
• Completion: 2025-05-02
• First posted: 2021-07-16
• Last updated: 2025-07-30

Locations

1 site across 1 country: China