Large, Randomised, Parallel-group, Controlled Trial, With Patients Randomly Allocated to Either N2O-containing (70% N2O in Oxygen [FiO2 0.3]) or N2O-free (70% Nitrogen in Oxygen [FiO2 0.3]).
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 7,112
- 试验地点
- 1
- 主要终点
- The Primary Endpoint is a Composite of Death and Cardiovascular Events (Clinical and Silent MI, Cardiac Failure, Cardiac Arrest, Pulmonary Embolism, and Stroke) Measured at 30 Days After Surgery.
研究概览
简要总结
To investigate the safety of nitrous oxide (N2O) anaesthesia in patients with risk factors for coronary artery disease undergoing major surgery.
详细描述
Approximately 25% of patients undergoing major surgery have known coronary artery disease (CAD) or risk factors for CAD.
N2O interferes with vitamin B12 and folate metabolism. This impairs production of methionine (from homocysteine), used to form tetrahydrofolate and thymidine during DNA synthesis. It has been repeatedly demonstrated that N2O anaesthesia increases postoperative homocysteine levels. Chronic hyperhomocysteinaemia is associated with cardiovascular disease, and acute hyperhomocysteinaemia is known to cause endothelial dysfunction. One small trial has demonstrated an increased incidence of postoperative myocardial ischaemia in patients receiving N2O anaesthesia. Reducing postoperative myocardial infarction and death are important aims for those with CAD undergoing major surgery.
Our previous trial (ENIGMA) studied 2050 patients and identified some serious adverse effects, but most patients were not at risk of CAD and so we could not reliably assess serious cardiac complications. We propose a large simple randomized clinical trial of 7,000 patients to provide a definitive evaluation of the safety of N2O anaesthesia.
Updated statistical analysis plan can be found at www.enigma2.org.au.
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, Care Provider, Outcomes Assessor)
盲法说明
The treating anaesthetist will be unblinded to the allocation. All other personnel (surgeon, participant and outcome assessor are all blinded to treatment.
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 age ≥ 45 years, undergoing noncardiac surgery and general anaesthesia expected to exceed two hours.
- •At increased risk of cardiac events, defined as any of
- •history of coronary artery disease as defined by a history of any one of the following: i. angina ii. MI iii. segmental wall motion abnormality on echocardiography or a fixed defect on radionuclide imaging iv. a positive exercise stress test for cardiac ischaemia v. a positive radionuclide exercise, echocardiographic exercise, or pharmacological cardiovascular stress test for cardiac ischaemia vi. coronary revascularization (CABG or PTCA) vii. angiographic evidence of atherosclerotic stenosis > 50% of the diameter of any coronary artery viii. ECG with pathological Q waves in two contiguous leads
- •heart failure
- •cerebrovascular disease thought due to atherothrombotic disease
- •aortic or peripheral vascular disease
- •or three or more of the following risk factors:
- •age ≥70 years
- •any history of congestive heart failure
- •diabetes and currently on an oral hypoglycaemic agent or insulin therapy
- •current treatment for hypertension
- •preoperative serum creatinine >175 micro mol/L (> 2.0 mg/dl)
- •current or previous high cholesterol ≥6.2 mmol/L (> 240 mg/dl)
- •history of a transient ischemic attack (TIA) (i.e. a transient focal neurological deficit that lasted less than 24 hours and thought to be vascular in origin)
- •emergency/urgent surgery (i.e. surgery which must be undertaken within 24 hours of acute presentation to hospital)
- •high-risk type of surgery (i.e. intrathoracic or intraperitoneal)
排除标准
- •having cardiac surgery
- •marked impairment of gas-exchange expected to require Fi02> 0.5 intraoperatively
- •specific circumstances where N2O is contraindicated (eg. volvulus, pulmonary hypertension, raised intracranial pressure) or the anaesthetist plans to use supplemental oxygen (eg. colorectal surgery)
- •N2O unavailable for use.
研究组 & 干预措施
No Nitrous Oxide
General anaesthesia not containing Nitrous oxide with fraction of inspired oxygen at 30%
干预措施: No Nitrous Oxide (Other)
70% Nitrous Oxide
General anaesthesia using 70% Nitrous Oxide with fraction of inspired oxygen at 30%
干预措施: Nitrous Oxide (Other)
结局指标
主要结局
The Primary Endpoint is a Composite of Death and Cardiovascular Events (Clinical and Silent MI, Cardiac Failure, Cardiac Arrest, Pulmonary Embolism, and Stroke) Measured at 30 Days After Surgery.
时间窗: 30 days post op
次要结局
- Stroke(30 Days Post op)
- Myocardial Infarction (MI)(30 days post op)
- Cardiac Arrest(30 days)
- Pulmonary Embolism(30 Days Post op)
- Wound Infection(30 Days Post op)
- Hospital Stay (Days)(30 Days Post Op)