International Substudy Enigma2 on Postoperative Cognitive Disorders (ISEP)

University Hospitals (UH)

Status and phase

Terminated

Phase 4

Conditions

Delirium, Dementia, Amnestic, Cognitive Disorders

Anesthesia

Treatments

Drug: Nitrous Oxide

Other: Placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT02489097

NAC 08-021

Enigma II nested NCT00430989 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment

140 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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),

Exclusion criteria

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