Esketamine vs. Ketorolac for Prevention of Postoperative Pain and Cognitive Dysfunction After Total Knee Arthroplasty

Sponsor
Tianjin Medical University General Hospital (Other)
Overall Status
Recruiting
CT.gov ID
NCT05132595
Collaborator
(none)
160
1
4
8
20.1

Study Details

Study Description

Brief Summary

Purpose:

To compare esketamine and ketorolac separately and in combination to prevent postoperative pain and cognitive dysfunction after total knee arthroplasty

Condition or Disease Intervention/Treatment Phase
  • Drug: Normal saline
  • Drug: Esketamine at high dose
  • Drug: Esketamine at low dose
  • Drug: Ketorolac at high dose
  • Drug: Ketorolac at low dose
N/A

Detailed Description

With the increase in human life span, orthopedic injuries and subsequent repair surgery have become a major health problem which impairs the life quality of patients and burdens healthcare systems worldwide. Poor post-surgical pain control is a leading factor that hinders the physical rehabilitation and musculoskeletal functional recovery, and causes acute cognitive impairment and chronic pain syndrome. Therefore, prophylaxis of postoperative pain is indispensable to postoperative comfort and satisfaction. There is no denying the fact that pathologic pain is related to central glutaminergic system and N-methyl-d-aspartate (NMDA) receptor activation induced central sensitization. Also, it is previously reported that neuroinflammation is associated with pain development and cognitive dysfunction. Ketamine, a NMDA receptor antagonist, is effective in reversing NMDA receptor activation underlying pain states. But the side effects of ketamine limit its clinical application, such as gibberish and agitation. It is clarified that esketamine has lower side effects than ketamine and that antinociception of esketamine is stronger than ketamine. The following study is carried out to evaluate whether esketamine and ketorolac can prevent postoperative pain and cognitive impairment after total knee arthroplasty in patients.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
160 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
Esketamine vs. Ketorolac for Prevention of Postoperative Pain and Cognitive Dysfunction After Total Knee Arthroplasty in Patients: a Randomized Double-blind Controlled Trial
Actual Study Start Date :
Nov 30, 2021
Anticipated Primary Completion Date :
Jul 15, 2022
Anticipated Study Completion Date :
Jul 30, 2022

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Normal saline in patients

After the induction of anesthesia, normal saline is intravenously injected in a volume of 2ml, and then a continuous infusion of 20 ml/h normal saline until starting skin suture.

Drug: Normal saline
After the induction of anesthesia, normal saline is intravenously injected in a volume of 2ml, and then a continuous infusion of 20ml/h normal saline until starting skin suture.
Other Names:
  • 0. 9% Sodium Chloride Injection
  • Active Comparator: Esketamine in patients

    After the induction of anesthesia, esketamine is intravenously injected at 0.4mg/kg, and then a continuous infusion of 0.4mg/kg/h esketamine until starting skin suture.

    Drug: Esketamine at high dose
    After the induction of anesthesia, esketamine is intravenously injected at 0.4mg/kg, and then a continuous infusion of 0.4mg/kg/h esketamine until starting skin suture.
    Other Names:
  • Esketamine Hydrochloride Injection
  • Active Comparator: Ketorolac in patients

    After the induction of anesthesia, ketorolac is intravenously injected at 0.4mg/kg, and then a continuous infusion of 0.4mg/kg/h ketorolac until starting skin suture.

    Drug: Ketorolac at high dose
    After the induction of anesthesia, Ketorolac is intravenously injected at 0.4mg/kg, and then a continuous infusion of 0.4mg/kg/h Ketorolac until starting skin suture.
    Other Names:
  • Ketorolac Tromethamine
  • Active Comparator: Esketamine and Ketorolac in patients

    After the induction of anesthesia, 0.2mg/kg esketamine and 0.2mg/kg ketorolac are intravenously injected, and then a continuous infusion of 0.2mg/kg/h esketamine and 0.2mg/kg/h ketorolac until starting skin suture.

    Drug: Esketamine at low dose
    After the induction of anesthesia, esketamine is intravenously injected at 0.2mg/kg, and then a continuous infusion of 0.2mg/kg/h esketamine until starting skin suture.
    Other Names:
  • Esketamine Hydrochloride Injection
  • Drug: Ketorolac at low dose
    After the induction of anesthesia, Ketorolac is intravenously injected at 0.2mg/kg, and then a continuous infusion of 0.2mg/kg/h Ketorolac until starting skin suture.
    Other Names:
  • Ketorolac Tromethamine
  • Outcome Measures

    Primary Outcome Measures

    1. Cumulative opioid Consumption [72 hours after surgery]

      Each patient was administered analgesics using a PCA (Patient-controlled analgesia) pump containing sufentanil in normal saline after leaving PACU (Postanesthesia care unit). Sufentanyl cumulative consumption is recorded 72 hours postoperatively

    Secondary Outcome Measures

    1. Pain Score (NRS) after movement [72 hours after surgery]

      The pain score after movement was evaluated by pain 11-point numerical rating scale (NRS): 0 = no pain, 10 = greatest imaginable pain.

    2. Time of First Postoperative Analgesic Requirement [1 hour after surgery]

      First postoperative pain (NRS≥5) is initially controlled by titration of sufentanyl.

    3. Total Dose of First Postoperative Analgesic Requirement [1 hour after surgery]

      First postoperative pain (NRS≥5) is initially controlled by titration of sufentanyl.

    4. Mini-Mental State Examination (MMSE) [72 hours after surgery]

      Cognitive performance was assessed with 0-30 points Mini-Mental State Examination (MMSE) scale. Greater scores means better outcome.

    5. The incidence of Side Effects [72 hours after surgery]

      The number of patients with post-operative side effects including nausea, vomiting, dizziness, headache, shivering, and pruritus was recorded 72 hours after surgery.

    6. The levels of TNF-a in blood [72 hours after surgery]

      Blood samples are collected to measure the levels of cytokine TNF-a using ELISA kits.

    7. The levels of chemokine CXCL1 in blood [72 hours after surgery]

      Blood samples are collected to measure the levels of chemokine CXCL1 using ELISA kits.

    8. The levels of neuron specific enolase (NSE) in blood [72 hours after surgery]

      Blood samples are collected to measure the levels of neuron specific enolase (NSE) using electrochemilumiscence kit.

    9. The levels of S-100 calcium-binding protein B in blood [72 hours after surgery]

      Blood samples are collected to measure the levels of S-100 calcium-binding protein B using electrochemilumiscence kit.

    10. The levels of cortisol in blood [72 hours after surgery]

      Blood samples are collected to measure the levels of cortisol using electrochemilumiscence kit.

    11. Pain Score (NRS) at rest [72 hours after surgery]

      The pain score at rest was evaluated by pain 11-point numerical rating scale (NRS): 0 = no pain, 10 = greatest imaginable pain.

    12. The levels of chemokine CCL7 in blood [72 hours after surgery]

      Blood samples are collected to measure the levels of chemokine CCL7 using ELISA kits.

    13. The levels of IL-18 in blood [72 hours after surgery]

      Blood samples are collected to measure the levels of cytokine IL-18 using ELISA kits.

    14. The levels of IL-23 in blood [72 hours after surgery]

      Blood samples are collected to measure the levels of cytokine IL-23 using ELISA kits.

    15. The levels of IL-17 in blood [72 hours after surgery]

      Blood samples are collected to measure the levels of cytokine IL-17 using ELISA kits.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    65 Years to 85 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Subject is scheduled to undergo total knee arthroplasty under a short general anesthesia of less than 2 hours

    2. Subject's American Society of Anesthesiologists physical status is I-II.

    3. The subject's parent/legally authorized guardian has given written informed consent to participate.

    Exclusion Criteria:
    1. Subject has a diagnosis of bronchial asthma, coronary heart disease, severe hypertension, renal failure or liver failure.

    2. Subject has a diagnosis of Insulin dependent diabetes.

    3. Subject is allergy and contraindication to esketamine or ketorolac.

    4. Subject has a history of chronic pain, a history of alcohol or opioid abuse, pre- existing therapy with opioids.

    5. Subject has any contraindication for the use of patient-controlled analgesia (PCA).

    6. Subject is pregnant or breast-feeding.

    7. Subject is obese (body mass index >30kg/m^2).

    8. Subject is incapacity to comprehend pain assessment and cognitive assessment.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Tianjin Medical University General Hospital Tianjin China 300052

    Sponsors and Collaborators

    • Tianjin Medical University General Hospital

    Investigators

    • Principal Investigator: Guolin Wang, Tianjin Medical University General Hospital

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Guolin Wang, Professor, Tianjin Medical University General Hospital
    ClinicalTrials.gov Identifier:
    NCT05132595
    Other Study ID Numbers:
    • GWang020
    First Posted:
    Nov 24, 2021
    Last Update Posted:
    Apr 15, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Guolin Wang, Professor, Tianjin Medical University General Hospital
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Apr 15, 2022