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

Tianjin Medical University

Status: Unknown

Conditions: Postoperative Pain; Total Knee Arthroplasty; Postoperative Cognitive Dysfunction

Treatments: Drug: Esketamine at high dose; Drug: Ketorolac at high dose; Drug: Normal saline; Drug: Esketamine at low dose; Drug: Ketorolac at low dose

Study type: Interventional

Funder types: Other

Identifiers

NCT05132595

GWang020

Details and patient eligibility

About

Purpose:

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

Full 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.

Enrollment: 160 estimated patients

Sex: All

Ages: 65 to 85 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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160 participants in 4 patient groups, including a placebo group

Normal saline in patients

Placebo Comparator group

Description:

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.

Treatment:

Drug: Normal saline

Esketamine in patients

Active Comparator group

Description:

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.

Treatment:

Drug: Esketamine at high dose

Ketorolac in patients

Active Comparator group

Description:

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.

Treatment:

Drug: Ketorolac at high dose

Esketamine and Ketorolac in patients

Active Comparator group

Description:

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.

Treatment:

Drug: Ketorolac at low dose

Drug: Esketamine at low dose