Intraoperative Infusion of Methylene Blue for Prevention of Postoperative Delirium and Cognitive Dysfunction in Elderly Patients Undergoing Major Elective Noncardiac and Nonneurosurgical Surgery
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 248
- 试验地点
- 1
- 主要终点
- Incidence of postoperative delirium(POD)
研究概览
简要总结
Postoperative neurocognitive impairments often occur in elderly patients undergoing anesthesia and non-cardiac surgery, including postoperative delirium (POD) and postoperative cognitive dysfunction (POCD). These disorders are often associated with increased mortality and morbidity, prolonged length of hospital stay, functional and cognitive decline with nursing home or long-term care facility placement. Until now highly effective intervention has not been established yet. As a mitochondrial protective agent, the role of methylene blue(MB) in preventing elderly patients from POD/POCD is unknown.Therefore, investigators design this study to validate its prevention against POD/POCD and the aim of this study is to evaluate the efficacy and safety of perioperative administration of MB for POD/POCD prevention.
详细描述
Postoperative neurocognitive impairments often occur in elderly patients undergoing major surgery, including postoperative delirium(POD) characterized by an acute change in cognition with altered consciousness and impaired attention, and postoperative cognitive dysfunction(POCD) mainly manifested as reduced ability of learning and memory. POD and POCD are major complications that cause disability and distress for millions of patients annually.In 2004, there was an estimated 5-40% incidence in 7.9 million patients over 65 years who had a surgical procedure subsequently experiencing either POD or POCD.The underlying pathophysiology of Postoperative neurocognitive impairments is increasingly understood, implicating a prominent role of neuroinflammation, oxidative stress and mitochondrial dysfunction.Recent experimental evidences reveal that mitochondrial dysfunction is increasingly considered a significant contributor to the development of POD and POCD.
Methylene blue(MB) is a diaminophenothiazine with a long history of clinical use due to its minimal side effect profiles. MB currently is used for treatment of methemoglobinemia, carbon monoxide poisoning, and vasoplegic syndrome as well as for surgical staining. MB could diffuse rapidly into brain and accumulate in the cytoplasm and mitochondria of neurons. In recent years its role as a mitochondrial protective agent has elicited much of its renewed interest, especially, studies have shown that MB has established its neuroprotective effects against ischemic stroke, post-chemotherapy-induced Encephalopathy and neurodegenerative diseases caused by Alzheimer's disease(AD) and psychoses.To date, there is no trials have examined the role of intraoperative MB administration in prevention of POD and POCD in elderly patients undergoing non-cardiac surgery, who have preoperative normal neurocognitive function. Therefore, investigators design this study to evaluate the efficacy and safety of perioperative administration of MB for POD/POCD prevention. It's an entirely novel therapy for postoperative neurocognitive disorders and will have high clinical translatable value if this intervention is found to be beneficial.
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
- None
入排标准
- 年龄范围
- 60 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •aged 60-80 years old
- •planning to undergo non-cardiac and non-neurosurgical surgery (e.g..thoracic, orthopaedic, urologic and major abdominal surgeries) under general anesthesia
- •Liver and kidney function are normal
- •Patients have the ability to act in full spirit, understand and sign the informed consent, and are willing to complete the whole research process.
排除标准
- •Patients with personal history of allergy to methylene blue
- •Emergency Surgery
- •Patients have 6-phospho-glucose dehydrogenase deficiency (vicia faba disease)
- •Patients have recent drug administration that may lead to drug interactions(e.g..SSRIs, SNRIs)
- •Patient with a history of major head trauma
- •Patients with a history of drug or alcohol abuse
- •Patient has serious mental or neurological disorders
- •Patients with severe language, hearing and visual impairment
- •Patients have serious medical diseases(e.g..heart failure, acute stage of myocardial infarction or respiratory failure)
- •Illiteracy
- •Patients have participated in other clinical trials in the last 3 months.
研究组 & 干预措施
Methylene Blue
2mg/kg MB diluted with normal saline into total 50 ml volume intravenous administration after induction of anesthesia within one hour.
干预措施: Methylene Blue (Drug)
Control
normal saline in total 50 ml volume intravenous administration after induction of anesthesia within one hour.
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence of postoperative delirium(POD)
时间窗: Participants will be followed for the duration of hospital stay, an expected average of 5 days.
the effectiveness of MB in reducing the incidence of POD compared with placebo in elderly patients undergoing major elective non-cardiac surgery.
次要结局
- Oxidative Stress Biomarkers(the day before surgery and postoperative one day)
- Incidence of postoperative cognitive dysfunction (POCD)(Up to 3 month after surgery)
- Safety Assessments: incidence of perioperative adverse events(the whole perioperative period)
研究者
Jun Zhang
Principal Investigator
Huashan Hospital