Esketamine vs. Ketorolac for Prevention of Postoperative Pain and Cognitive Dysfunction After Total Knee Arthroplasty in Patients: a Randomized Double-blind Controlled Trial
试验速览
- 阶段
- 不适用
- 入组人数
- 160
- 试验地点
- 1
- 主要终点
- Cumulative opioid Consumption
研究概览
简要总结
Purpose:
To compare esketamine and ketorolac separately and in combination to prevent postoperative pain and cognitive dysfunction after total knee arthroplasty
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 65 Years 至 85 Years（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: Ketorolac at low dose (Drug)
结局指标
主要结局
Cumulative opioid Consumption
时间窗: 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
次要结局
- 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)
研究者
Guolin Wang
Professor
Tianjin Medical University General Hospital