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

Not Applicable

• Conditions: Postoperative Pain; Postoperative Cognitive Dysfunction; Total Knee Arthroplasty
• Interventions: Drug: Normal saline; Drug: Esketamine at high dose; Drug: Ketorolac at high dose; Drug: Esketamine at low dose; Drug: Ketorolac at low dose

• Registration Number: NCT05132595
• Lead Sponsor: Tianjin Medical University General Hospital

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.

Study Timeline

• Study First Submitted: 2021-10-28
• Study First Submitted QC: 2021-11-12
• Study First Posted: 2021-11-24
• Study Start: 2021-11-30
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-08
• Last Update Posted: 2022-04-15
• Primary Completion: 2022-07-15
• Study Completion: 2022-07-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 160

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Normal saline in patients	Normal saline	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.
Esketamine in patients	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.
Ketorolac in patients	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.
Esketamine and Ketorolac in patients	Esketamine at low dose	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.
Esketamine and Ketorolac in patients	Ketorolac at low dose	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.
Time of First Postoperative Analgesic Requirement	1 hour after surgery	First postoperative pain (NRS≥5) is initially controlled by titration of sufentanyl.
Total Dose of First Postoperative Analgesic Requirement	1 hour after surgery	First postoperative pain (NRS≥5) is initially controlled by titration of sufentanyl.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
The levels of cortisol in blood	72 hours after surgery	Blood samples are collected to measure the levels of cortisol using electrochemilumiscence kit.
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.

Trial Locations

Locations (1)

Tianjin Medical University General Hospital; 🇨🇳 Tianjin, China