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

Postoperative Pain Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05132595
• Other study ID #: GWang020
• Status: Recruiting
• Phase: N/A
• Start date: November 30, 2021
• Est. completion date: July 30, 2022

Study information

• Verified date: April 2022
• Source: Tianjin Medical University General Hospital
• Contact: Guolin Wang, MD
• Phone: +8615822855556
• Email: wangguolinghad[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Purpose:

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: July 30, 2022
• Est. primary completion date: July 15, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Pain, Postoperative
• Postoperative Cognitive Complications
• Postoperative Cognitive Dysfunction
• Postoperative Pain
• Total Knee Arthroplasty

Intervention

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.
• 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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
China	Tianjin Medical University General Hospital	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Tianjin Medical University General Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cumulative opioid Consumption	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	72 hours after surgery
Secondary	Pain Score (NRS) after movement	The pain score after movement was evaluated by pain 11-point numerical rating scale (NRS): 0 = no pain, 10 = greatest imaginable pain.	72 hours after surgery
Secondary	Time of First Postoperative Analgesic Requirement	First postoperative pain (NRS=5) is initially controlled by titration of sufentanyl.	1 hour after surgery
Secondary	Total Dose of First Postoperative Analgesic Requirement	First postoperative pain (NRS=5) is initially controlled by titration of sufentanyl.	1 hour after surgery
Secondary	Mini-Mental State Examination (MMSE)	Cognitive performance was assessed with 0-30 points Mini-Mental State Examination (MMSE) scale. Greater scores means better outcome.	72 hours after surgery
Secondary	The incidence of Side Effects	The number of patients with post-operative side effects including nausea, vomiting, dizziness, headache, shivering, and pruritus was recorded 72 hours after surgery.	72 hours after surgery
Secondary	The levels of TNF-a in blood	Blood samples are collected to measure the levels of cytokine TNF-a using ELISA kits.	72 hours after surgery
Secondary	The levels of chemokine CXCL1 in blood	Blood samples are collected to measure the levels of chemokine CXCL1 using ELISA kits.	72 hours after surgery
Secondary	The levels of neuron specific enolase (NSE) in blood	Blood samples are collected to measure the levels of neuron specific enolase (NSE) using electrochemilumiscence kit.	72 hours after surgery
Secondary	The levels of S-100 calcium-binding protein B in blood	Blood samples are collected to measure the levels of S-100 calcium-binding protein B using electrochemilumiscence kit.	72 hours after surgery
Secondary	The levels of cortisol in blood	Blood samples are collected to measure the levels of cortisol using electrochemilumiscence kit.	72 hours after surgery
Secondary	Pain Score (NRS) at rest	The pain score at rest was evaluated by pain 11-point numerical rating scale (NRS): 0 = no pain, 10 = greatest imaginable pain.	72 hours after surgery
Secondary	The levels of chemokine CCL7 in blood	Blood samples are collected to measure the levels of chemokine CCL7 using ELISA kits.	72 hours after surgery
Secondary	The levels of IL-18 in blood	Blood samples are collected to measure the levels of cytokine IL-18 using ELISA kits.	72 hours after surgery
Secondary	The levels of IL-23 in blood	Blood samples are collected to measure the levels of cytokine IL-23 using ELISA kits.	72 hours after surgery
Secondary	The levels of IL-17 in blood	Blood samples are collected to measure the levels of cytokine IL-17 using ELISA kits.	72 hours after surgery