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

Tianjin Medical University General Hospital160 enrolled

Overview

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

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Enrollment

160

Conditions

Postoperative Pain Postoperative Cognitive Dysfunction Total Knee Arthroplasty

Interventions

Normal salineDRUG

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 doseDRUG

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 doseDRUG

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.

Eligibility

Sex: ALLMin age: 65 YearsMax age: 85 Years

Medical Language ↔ Plain English

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.

Locations (1)

Tianjin Medical University General Hospital

Tianjin, China

RECRUITING

Outcomes

Primary Outcomes

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

Time frame: 72 hours after surgery

Secondary Outcomes

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.

Time frame: 72 hours after surgery

Time of First Postoperative Analgesic Requirement

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

Time frame: 1 hour after surgery

Total Dose of First Postoperative Analgesic Requirement

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

Time frame: 1 hour after surgery

Mini-Mental State Examination (MMSE)

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

Time frame: 72 hours after surgery

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.

Time frame: 72 hours after surgery

The levels of TNF-a in blood

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

Central Contacts

Guolin Wang, MD

CONTACT

+8615822855556 wangguolinghad@hotmail.com

Data from ClinicalTrials.gov

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