Clinical trial NCT05132595: Esketamine vs. Ketorolac for Prevention of Postoperative Pain and Cognitive Dysfunction After Total Knee Arthroplasty
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Postoperative Pain
Postoperative Cognitive Dysfunction
Total Knee Arthroplasty
Keywords: esketamine
ketorolac
Lead sponsor: Tianjin Medical University General Hospital
Sponsor class: OTHER
First posted: 2021-11-24
Enrollment: 160
Sex: ALL
Minimum age (years): 65
Maximum age (years): 85
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Purpose:

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Cumulative opioid Consumption
timeFrame: 72 hours after surgery
Secondary outcomes:
measure: Pain Score (NRS) after movement
timeFrame: 72 hours after surgery
measure: Time of First Postoperative Analgesic Requirement
timeFrame: 1 hour after surgery
measure: Total Dose of First Postoperative Analgesic Requirement
timeFrame: 1 hour after surgery
measure: Mini-Mental State Examination (MMSE)
timeFrame: 72 hours after surgery
measure: The incidence of Side Effects
timeFrame: 72 hours after surgery
measure: The levels of TNF-a in blood
timeFrame: 72 hours after surgery
measure: The levels of chemokine CXCL1 in blood
timeFrame: 72 hours after surgery
measure: The levels of neuron specific enolase (NSE) in blood
timeFrame: 72 hours after surgery
measure: The levels of S-100 calcium-binding protein B in blood
timeFrame: 72 hours after surgery
measure: The levels of cortisol in blood
timeFrame: 72 hours after surgery
measure: Pain Score (NRS) at rest
timeFrame: 72 hours after surgery
measure: The levels of chemokine CCL7 in blood
timeFrame: 72 hours after surgery
measure: The levels of IL-18 in blood
timeFrame: 72 hours after surgery
measure: The levels of IL-23 in blood
timeFrame: 72 hours after surgery
measure: The levels of IL-17 in blood
timeFrame: 72 hours after surgery
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
Study officials:
affiliation: Tianjin Medical University General Hospital
name: Guolin Wang
role: PRINCIPAL_INVESTIGATOR
References: