Postoperative Cognitive Dysfunction, Postoperative Pain, Total Knee Arthroplasty
Conditions
Keywords
esketamine, ketorolac
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.
Interventions
DRUGNormal 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.
DRUGEsketamine 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.
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.
DRUGKetorolac 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.
DRUGKetorolac 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.
Sponsors
Tianjin Medical University General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to 85 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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) 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. |
| The levels of cortisol in blood | 72 hours after surgery | Blood samples are collected to measure the levels of cortisol 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 chemokine CCL7 in blood | 72 hours after surgery | Blood samples are collected to measure the levels of chemokine CCL7 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 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. |
Countries
China
Contacts
Primary ContactGuolin Wang, MD
Outcome results
None listed