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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Normal saline in patients | Placebo Comparator | 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. |
|
| Esketamine in patients | Active Comparator | 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. |
|
| Ketorolac in patients | Active Comparator | 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. |
|
| Esketamine and Ketorolac in patients | Active Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Normal saline | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Time of First Postoperative Analgesic Requirement |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Guolin Wang, MD | Contact | +8615822855556 | wangguolinghad@hotmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Guolin Wang | Tianjin Medical University General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Tianjin Medical University General Hospital | Recruiting | Tianjin | 300052 | China |
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| Esketamine at high dose | Drug | 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 | Drug | 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 | Drug | 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 | Drug | 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. |
|
|
First postoperative pain (NRS≥5) is initially controlled by titration of sufentanyl.
| 1 hour after surgery |
| Total Dose of First Postoperative Analgesic Requirement | First postoperative pain (NRS≥5) is initially controlled by titration of sufentanyl. | 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. | 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. | 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. | 72 hours after surgery |
| 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 |
| 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 |
| 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 |
| The levels of cortisol in blood | Blood samples are collected to measure the levels of cortisol using electrochemilumiscence kit. | 72 hours after surgery |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| ID | Term |
|---|---|
| D010149 | Pain, Postoperative |
| D000079690 | Postoperative Cognitive Complications |
| ID | Term |
|---|---|
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D060825 | Cognitive Dysfunction |
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D000077330 | Saline Solution |
| D012965 | Sodium Chloride |
| D020911 | Ketorolac Tromethamine |
| ID | Term |
|---|---|
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |
| D007213 | Indomethacin |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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