Esketamine vs. Ketorolac for Prevention of Postoperative Pain and Cognitive Dysfunction After Total Knee Arthroplasty in Patients: a Randomized Double-blind Controlled Trial
Overview
- Phase
- Not Applicable
- Enrollment
- 160
- Locations
- 1
- Primary Endpoint
- Cumulative opioid Consumption
Overview
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 65 Years to 85 Years (Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Subject is scheduled to undergo total knee arthroplasty under a short general anesthesia of less than 2 hours
- •Subject's American Society of Anesthesiologists physical status is I-II.
- •The subject's parent/legally authorized guardian has given written informed consent to participate.
Exclusion Criteria
- •Subject has a diagnosis of bronchial asthma, coronary heart disease, severe hypertension, renal failure or liver failure.
- •Subject has a diagnosis of Insulin dependent diabetes.
- •Subject is allergy and contraindication to esketamine or ketorolac.
- •Subject has a history of chronic pain, a history of alcohol or opioid abuse, pre- existing therapy with opioids.
- •Subject has any contraindication for the use of patient-controlled analgesia (PCA).
- •Subject is pregnant or breast-feeding.
- •Subject is obese (body mass index \>30kg/m\^2).
- •Subject is incapacity to comprehend pain assessment and cognitive assessment.
Arms & Interventions
Normal saline in patients
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.
Intervention: Normal saline (Drug)
Esketamine in patients
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.
Intervention: Esketamine at high dose (Drug)
Ketorolac in patients
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.
Intervention: Ketorolac at high dose (Drug)
Esketamine and Ketorolac in patients
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.
Intervention: Esketamine at low dose (Drug)
Esketamine and Ketorolac in patients
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.
Intervention: Ketorolac at low dose (Drug)
Outcomes
Primary Outcomes
Cumulative opioid Consumption
Time Frame: 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 Outcomes
- Pain Score (NRS) after movement(72 hours after surgery)
- Time of First Postoperative Analgesic Requirement(1 hour after surgery)
- Total Dose of First Postoperative Analgesic Requirement(1 hour after surgery)
- Mini-Mental State Examination (MMSE)(72 hours after surgery)
- The incidence of Side Effects(72 hours after surgery)
- The levels of TNF-a in blood(72 hours after surgery)
- The levels of chemokine CXCL1 in blood(72 hours after surgery)
- The levels of IL-18 in blood(72 hours after surgery)
- The levels of IL-23 in blood(72 hours after surgery)
- The levels of IL-17 in blood(72 hours after surgery)
- Pain Score (NRS) at rest(72 hours after surgery)
- The levels of neuron specific enolase (NSE) in blood(72 hours after surgery)
- The levels of S-100 calcium-binding protein B in blood(72 hours after surgery)
- The levels of cortisol in blood(72 hours after surgery)
- The levels of chemokine CCL7 in blood(72 hours after surgery)
Investigators
Guolin Wang
Professor
Tianjin Medical University General Hospital