The ENIGMA II Trial:Nitrous Oxide Anaesthesia and Cardiac Morbidity After Major Surgery: a Randomised Controlled Trial
Condition: Coronary Artery Disease
MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
Intervention: Nitrous Oxide; No Nitrous Oxide
Intervention description: General anaesthesia with the inclusion of Nitrous Oxide at 70%; General anaesthesia with no use of Nitrous Oxide
Intervention MeSH terms: Nitrous Oxide
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: international, randomised, assessor-blinded trial in patients aged at least 45 years with known or suspected coronary artery disease having major non-cardiac surgery.
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Masking description: The treating anaesthetist will be unblinded to the allocation. All other personnel (surgeon, participant and outcome assessor are all blinded to treatment.
Enrollment: 7112.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Anaesthesia; Major Surgery; Coronary artery disease; Nitrous oxide; Effects of Nitrous Oxide following Anaesthesia; Anaesthesia and coronary artery disease

Summary:

      To investigate the safety of nitrous oxide (N2O) anaesthesia in patients with risk factors
      for coronary artery disease undergoing major surgery.
    

Eligibility criteria:

        Inclusion Criteria

          1. Adult males and females age ≥ 45 years, undergoing noncardiac surgery and general
             anaesthesia expected to exceed two hours.

          2. At increased risk of cardiac events, defined as any of

               1. 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

               2. heart failure

               3. cerebrovascular disease thought due to atherothrombotic disease

               4. aortic or peripheral vascular disease

               5. 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)

        Exclusion Criteria

          1. having cardiac surgery

          2. marked impairment of gas-exchange expected to require Fi02> 0.5 intraoperatively

          3. specific circumstances where N2O is contraindicated (eg. volvulus, pulmonary
             hypertension, raised intracranial pressure) or the anaesthetist plans to use
             supplemental oxygen (eg. colorectal surgery)

          4. N2O unavailable for use.