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

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ClinicalTrials.gov Identifier: NCT04964219
Recruitment Status : Not yet recruiting
First Posted : July 16, 2021
Last Update Posted : July 22, 2021
Sponsor:
Information provided by (Responsible Party):
Dong-Xin Wang, Peking University First Hospital

Tracking Information
First Submitted Date  ICMJE July 6, 2021
First Posted Date  ICMJE July 16, 2021
Last Update Posted Date July 22, 2021
Estimated Study Start Date  ICMJE September 2021
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 6, 2021)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 15, 2021)
  • Opioid consumption during anesthesia [ Time Frame: From induction to end of anesthesia ]
    Opioid consumption in equivalent-dose of sufentanil
  • Cumulative opioid consumption after surgery [ Time Frame: From end of anesthesia to the 5th day after surgery ]
    Opioid consumption in equivalent-dose of sufentanil
  • 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)
  • The percentage of using rescue analgesics [ Time Frame: Up to postoperative day 5 ]
    The percentage of using rescue analgesics
  • 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)
  • Time to first ambulation [ Time Frame: Up to 30 days after surgery ]
    Time to first ambulation
  • 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.
  • Length of hospital stay after surgery [ Time Frame: Up to 30 days after surgery ]
    Length of hospital stay after surgery
  • The percentage of taking oral analgesics [ Time Frame: On the 30th day after surgery ]
    The percentage of taking oral analgesics
  • 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.
  • The incidence of postoperative complications and mortality [ Time Frame: Up to 30 days after surgery ]
    The incidence of postoperative complications and mortality
Original Secondary Outcome Measures  ICMJE
 (submitted: July 6, 2021)
  • Sufentanil consumption during anesthesia [ Time Frame: From induction to end of anesthesia ]
    Sufentanil consumption during anesthesia
  • Cumulative sufentanil consumption after surgery [ Time Frame: From end of anesthesia to the 5th day after surgery ]
    Cumulative sufentanil consumption 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)
  • The percentage of using rescue analgesics [ Time Frame: Up to postoperative day 5 ]
    The percentage of using rescue analgesics
  • 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)
  • Time to first ambulation [ Time Frame: Up to 30 days after surgery ]
    Time to first ambulation
  • 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.
  • Length of hospital stay after surgery [ Time Frame: Up to 30 days after surgery ]
    Length of hospital stay after surgery
  • The percentage of taking oral analgesics [ Time Frame: On the 30th day after surgery ]
    The percentage of taking oral analgesics
  • 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.
  • The incidence of postoperative complications and mortality [ Time Frame: Up to 30 days after surgery ]
    The incidence of postoperative complications and mortality
Current Other Pre-specified Outcome Measures
 (submitted: July 6, 2021)
  • 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
  • The incidence of postoperative nausea and vomiting [ Time Frame: Up to 5 days after surgery ]
    The incidence of postoperative nausea and vomiting
  • The incidence of delirium [ Time Frame: Up to 5 days after surgery ]
    The incidence of delirium
  • 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
  • The percentage of adverse events requiring therapeutic intervention [ Time Frame: Up to 5 days after surgery ]
    The percentage of adverse events requiring therapeutic intervention
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Analgesic Effects of Low-dose S-ketamine in Major Spine Fusion Surgery
Official Title  ICMJE Analgesic Effects of Low-dose S-ketamine in Patients Undergoing Major Spine Fusion Surgery: A Double-blinded, Randomized Controlled Trial
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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • S-ketamine
  • Postoperative Analgesia
  • Spine Fusion
Intervention  ICMJE
  • 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.

Study Arms  ICMJE
  • 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.

    Intervention: Drug: S-ketamine
  • 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.

    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: July 6, 2021)
164
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2023
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Dong-Xin Wang, MD, PhD +8610-83572784 wangdongxin@hotmail.com
Contact: Xue Li, MD 18810527114 3999165@163.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04964219
Other Study ID Numbers  ICMJE Peking UFH
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Dong-Xin Wang, Peking University First Hospital
Study Sponsor  ICMJE Peking University First Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Dong-Xin Wang, MD, PhD Peking University First Hospital
PRS Account Peking University First Hospital
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP