Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Low-dose S-ketamine and Dexmedetomidine in Combination With Opioids for Postoperative Analgesia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04791059
Recruitment Status : Recruiting
First Posted : March 10, 2021
Last Update Posted : April 19, 2021
Sponsor:
Information provided by (Responsible Party):
Dong-Xin Wang, Peking University First Hospital

Brief Summary:
Scoliosis correction surgery is followed with severe pain. Patients after scoliosis correction surgery usually require high dose opioids and long duration analgesia, which may increase side effects and even drug tolerance. S-ketamine is the pure dextrorotatory enantiomer of ketamine with stronger analgesic effect and less side effects, but mental side effects is a major concern. Dexmedetomidine can be used as an analgesic supplement; it also improves sleep quality in postoperative patients. We hypothesize that low-dose ketamine and dexmedetomidine in combination with opioids may have synergistic effect in analgesia and reduce drug-related side effects. This study aims to explore the effect of low-dose of S-ketamine and dexmedetomidine in combination with opioids for postoperative patient-controlled intravenous analgesia in patients following scoliosis correction surgery.

Condition or disease Intervention/treatment Phase
Scoliosis Correction Postoperative Analgesia S-ketamine Dexmedetomidine Sufentanil Drug: S-ketamine Drug: Dexmedetomidine Drug: Sufentanil Phase 4

Detailed Description:

Scoliosis correction surgery is followed with severe pain. The reported median pain score on the first day after surgery is median 7 (IQR 4, 8); with an incidence of persistent postoperative pain from 5% to 75%. Most patients undergoing this surgery are young and adolescents; they are sensitive to pain and usually require higher dose analgesics and a long duration analgesia. The total dose of opioids required for postoperative analgesia is about 2-4 times higher than that after other surgeries. But even with high dose opioids, the analgesic effect remains unsatisfied. Furthermore, high dose opioids may cause side effects such as respiratory depression, drowsiness, nausea, vomiting, skin itching, and even drug tolerance.

Ketamine is a noncompetitive N-methyl-D-aspartate receptor antagonist (NMDA) with analgesic and anti-hyperalgesia effects. It is widely used for anesthesia induction in critically ill patients, pediatric anesthesia and postoperative analgesia. The advantages of ketamine include mild influence on respiratory and circulatory function, and good analgesic effect. Recent guidelines recommends the use of low-dose ketamine infusion for postoperative analgesia in patients with moderate to severe pain, in order to reduce the consumption of opioids. S-ketamine is the pure dextrorotatory enantiomer of ketamine with stronger analgesic effect and lower incidence of adverse reactions.

Dexmedetomidine is a highly selective α2 receptor agonist with effects of antianxiety, sedation and analgesia. When used as a supplement, it improves analgesic effect, and reduces opioid consumption and opioid related adverse reactions. In the same time, dexmedetomidine activates the endogenous sleep pathway and improves sleep quality by prolonging total sleep time, increasing sleep efficiency, and promoting subjective sleep quality.

It is worthy to note that ketamine can produce adverse reactions such as agitation, delirium and anxiety, and increase the incidence of hallucinations and nightmares when the given dose is slightly higher; whereas the sedative effect of dexmedetomidine may help to reduce the adverse effects of ketamine. We hypothesize that low-dose ketamine and dexmedetomidine in combination with opioids may have synergistic effects in postoperative analgesia and reduce drug-related adverse reactions.

This study aims to explore the effect of low-dose of S-ketamine and dexmedetomidine in combination with opioids for postoperative patient-controlled intravenous analgesia in patients following scoliosis correction surgery.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Low-dose S-ketamine and Dexmedetomidine in Combination With Opioids for Patient-controlled Analgesia After Scoliosis Correction Surgery: a Randomized, Double-blind, Placebo-controlled Trial
Actual Study Start Date : April 9, 2021
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : April 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Combined analgesia group
Patient-controlled analgesia is established with S-ketamine 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 lock-out interval of 8 minutes and a background infusion rate at 1 ml/h.
Drug: S-ketamine
S-ketamine 50 mg is included in the mixture for patient-controlled analgesia.

Drug: Dexmedetomidine
Dexmedetomidine 200 microgram is included in the mixture for patient-controlled analgesia.

Drug: Sufentanil
Sufentanil 4 microgram/kg (maximum 250 microgram) is included in the mixture for patient-controlled analgesia.

Placebo Comparator: Control group
Patient-controlled analgesia is established with sufentanil 4 microgram/kg (maximum 250 microgram), diluted with normal saline to 200 ml, and programmed to administer 2-ml boluses with a lock-out interval of 8 minutes and a background infusion rate at 1 ml/h.
Drug: Sufentanil
Sufentanil 4 microgram/kg (maximum 250 microgram) is included in the mixture for patient-controlled analgesia.




Primary Outcome Measures :
  1. Percent of patients with moderate to severe pain within 72 hours [ Time Frame: Up to 72 hours after surgery ]
    Pain severity 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.


Secondary Outcome Measures :
  1. NRS pain score (at rest and with movement) at various timepoints after surgery [ Time Frame: Up to 72 hours after surgery ]
    Pain severity 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.

  2. Cumulative opioid consumption [ Time Frame: Up to 72 hours after surgery ]
    Cumulative opioid consumption

  3. Cumulative analgesic consumption [ Time Frame: Up to 72 hours after surgery ]
    Cumulative analgesic consumption

  4. 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).

  5. 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).

  6. 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)

  7. Length of stay in hospital after surgery [ Time Frame: Up to 30 days after surgery ]
    Length of stay in hospital after surgery

  8. Duration requiring analgesics within 30 days after surgery [ Time Frame: Up to 30 days after surgery ]
    Duration requiring analgesics within 30 days after surgery

  9. 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)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 years old, body weight ≥ 40 kg;
  • Scheduled to undergo scoliosis correction with pedicle screw fixation;
  • Planned to use patient-controlled intravenous analgesia after surgery.

Exclusion Criteria:

  • Refused to participate in the study;
  • 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 obstructive sleep apnea syndrome, or a STOP-Bang score ≥ 3 in combination with a serum HCO3- level ≥ 28 mmol/L;
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04791059


Contacts
Layout table for location contacts
Contact: Dong-Xin Wang, MD,PhD 8610-83572784 wangdongxin@hotmail.com
Contact: Fan Cui, MD 8610-83572460 cuifan_1987@163.com

Locations
Layout table for location information
China, Beijing
Peking University First Hospital Recruiting
Beijing, Beijing, China, 100034
Contact: Dong-Xin Wang, MD, PhD    8610 83572784    wangdongxin@hotmail.com   
Contact: Fan Cui, MD    8610 83572460    cuifan_1987@163.com   
Sponsors and Collaborators
Peking University First Hospital
Investigators
Layout table for investigator information
Principal Investigator: Dong-Xin Wang, MD,PhD Peking University First Hospital
Publications:

Layout table for additonal information
Responsible Party: Dong-Xin Wang, Professor and Chairman, Department of Anesthesiology and Critical Care Medicine, Peking University First Hospital
ClinicalTrials.gov Identifier: NCT04791059    
Other Study ID Numbers: 2020-465
First Posted: March 10, 2021    Key Record Dates
Last Update Posted: April 19, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Dong-Xin Wang, Peking University First Hospital:
Scoliosis correction
Postoperative analgesia
S-ketamine
Dexmedetomidine
Sufentanil
Additional relevant MeSH terms:
Layout table for MeSH terms
Scoliosis
Spinal Curvatures
Spinal Diseases
Bone Diseases
Musculoskeletal Diseases
Sufentanil
Dexmedetomidine
Ketamine
Esketamine
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Analgesics, Opioid
Narcotics