Evaluating the Incidence and Association Between Nitrous Oxide and Postoperative Cognitive Disorders in Anaesthesia
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 140
- 试验地点
- 2
- 主要终点
- Memory, Executive function, Attention and psychomotor speed testing battery
研究概览
简要总结
The study is a substudy of the Enigma2 trial (NCT00430989) which aims at investigating the effectiveness and safety of nitrous oxide (N2O) in anaesthesia.The substudy focus is on postoperative cognitive disorders.
Substudy Hypothesis: In patients undergoing anaesthesia for major surgery, administration of N2O will reduce postoperative cognitive disorders when compared with otherwise identically managed surgical patients not receiving N2O as a component of their anaesthesia.
详细描述
Numerous studies questioned the routine use of nitrous oxide (N2O), the oldest anaesthetic agent used since the development of anaesthesia care. Despite its wide use, there is sufficient doubt as to the risk-benefit profile.
There is strong evidence that N2O is a major risk factor for postoperative nausea and vomiting. It is clear that (even) brief exposure to N2O impairs methionine synthetase, an enzyme required for DNA production, red and white blood cell formation. Tissue hypoxia may be more common. These adverse effects are enhanced in "sick" patients (ie. those at highest risk, with increased hospital length of stay and healthcare expenditure), and will be more likely in longer surgery. At the same time, observational studies and subgroup analysis of published trials suggest that N2O may have beneficial effects in preventing pain and postoperative cognitive disorders
Outcome trial data on postoperative cognitive disorders are lacking in this area for an anaesthetic gas used in more than 90% of all surgery around the world. The enigma2 substudy as a nested study of the large Enigma2 randomised controlled trial aims at answering this question.
The investigators aim at recruiting 420 patients in 2 of the 25 centres participating to the Enigma 2 trials, who are undergoing major surgery.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult males and females aged ≥ 45 years, undergoing noncardiac surgery and general anaesthesia that exceeds two hours.
- •At increased risk of cardiac events, defined as any of:
- •history of coronary artery disease (angina, MI, Coronary revascularisation-Coronary Artery Bypass Graft (CABG) and Percutaneous Transluminal Coronary Angiography ( PTCA)-, positive stress testing, angiography/other imaging, Q waves on ECG)
- •heart failure
- •cerebrovascular disease due to atherothrombotic disease
- •aortic or peripheral vascular disease
- •three or more of the following risk factors: age ≥70 years, history of heart failure, diabetes (medicated), hypertension (medicated), preoperative serum creatinine >175 mmol/L, cholesterol ≥6.2 mmol/L, history of a transient ischemic attack (TIA),
排除标准
- •Dementia (MMS test≤24)
- •Parkinson Disease
- •Patients taking regularly (>2 weeks) tricyclic antidepressants or neuroleptics
- •Patients suffering from Alcohol Dependency (WHO CRITERIA )
- •Patients suffering from severe hypoacusis or visual loss or any other reason hindering the CANTAB battery testing process
- •Patients with untreated deficit in Vitamin B6, B12 and folic acid
- •Patients with marked impairment of gas-exchange requiring Fi02> 0.5 intraoperatively
- •Patients with specific circumstances where N2O is contraindicated (eg. volvulus, pulmonary hypertension, raised intracranial pressure) or the use of supplemental oxygen is planned (eg. colorectal surgery)
- •N2O unavailable
研究组 & 干预措施
Nitrous Oxide
Receives a mixture of 70% Nitrous Oxide in 30% Oxygen
干预措施: Nitrous Oxide (Drug)
Air/Oxygen (placebo)
Receives a mixture of 70% Air in 30% Oxygen
干预措施: Placebo (Other)
结局指标
主要结局
Memory, Executive function, Attention and psychomotor speed testing battery
时间窗: Baseline before surgery
Validated Computerized testing battery developed by the University of Cambridge for cognitive testing (CANTAB). Patients are tested for baseline cognitive function before surgery
Memory, Executive function, Attention and psychomotor speed using CANTAB Cognitive testing battery at 7days following surgery
时间窗: First assessment (7 days)
Validated Computerized testing battery developed by the University of Cambridge for cognitive testing (CANTAB). Patients are tested for changes from the baseline cognitive function (before surgery) at 7 days after surgery
Memory, Executive function, Attention and psychomotor speed using CANTAB Cognitive testing battery at 3 months following surgery
时间窗: Second assessment (3 months)
Validated Computerized testing battery developed by the University of Cambridge for cognitive testing (CANTAB). Patients are tested for changes from the baseline cognitive function (before surgery) at 3 months after surgery
次要结局
- Hospital stay(up to a maximum of 3 months)
- Quality of life(3 months)
- ICU stay(up to a maximum of 3 months)
研究者
Dr Guy Haller
Staff Anaesthetist
University Hospital, Geneva