S-ketamine Prevents Tibial Fracture-associated Postoperative Pain and Cognitive Dysfunction After Orthopedic Surgery in Patients: a Randomized Double-blind Controlled Trial
试验速览
- 阶段
- 不适用
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Mechanical hyperalgesia threshold on the palms of feet
研究概览
简要总结
Purpose:
To explore effects of S-ketamine on postoperative pain and cognitive dysfunction after tibial fracture and orthopedic surgery.
To evaluate and examine the incidence of adverse effects with the purpose of selecting the optimum dose.
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. Also, existing treatments of opioids and non-steroidal anti-inflammatory drugs have potential drawbacks, which may in turn interfere with bone healing. Therefore, prophylaxis of fracture-associated 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, we 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 Delirium, gibberish and agitation. It is clarified that S-ketamine has lower side effects than ketamine and that antinociception of S-ketamine is stronger than ketamine. The following study is carried out to evaluate whether S-ketamine can prevent postoperative pain and cognitive impairment after tibial fracture and orthopedic surgery 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
- Double (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 tibial fracture with orthopedic surgery 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 S-ketamine.
- •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)
S-ketamine at low dose in patients
After the induction of anesthesia, S-ketamine is intravenously injected at 0.2mg/kg, and then a continuous infusion of 0.2mg/kg/h S-ketamine until starting skin suture.
干预措施: S-ketamine (low-dose) (Drug)
S-ketamine at high dose in patients
After the induction of anesthesia, S-ketamine is intravenously injected at 0.4mg/kg, and then a continuous infusion of 0.4mg/kg/h S-ketamine until starting skin suture.
干预措施: S-ketamine (high-dose) (Drug)
结局指标
主要结局
Mechanical hyperalgesia threshold on the palms of feet
时间窗: 48 hours after surgery
The mechanical hyperalgesia threshold was defined as the lowest force (g) necessary to bend a Von Frey filament, which was perceived to be painful by the patient and measured by Von Frey filament.
次要结局
- Pain Score (NRS)(48 hours after surgery)
- Mechanical Hyperalgesia Threshold on the Dominant Inner Forearm(48 hours after surgery)
- Time of First Postoperative Analgesic Requirement(1 hour after surgery)
- Total Dose of First Postoperative Analgesic Requirement(1 hour after surgery)
- Cumulative Sufentanyl Consumption(48 hours after surgery)
- Occurrence of Side Effects(48 hours after surgery)
- Mini-Mental State Examination (MMSE)(48 hours after surgery)
研究者
Guolin Wang
Professor
Tianjin Medical University General Hospital