ENIGMA - Evaluation of Nitrous Oxide In the Gas Mixture for Anaesthesia: a Randomised Controlled Trial

Phase 4

Completed

• Conditions: Quality of Recovery From Anaesthesia; Effects of Nitrous Oxide Following Anaesthesia; Induced Endothelial Dysfunction

• Registration Number: NCT00164047
• Lead Sponsor: Bayside Health

Brief Summary

We aim to investigate the effectiveness and safety of nitrous oxide (N2O) in anaesthesia.

Hypothesis In patients undergoing anaesthesia for major surgery, avoidance of N2O will reduce hospital length of stay when compared with otherwise identically managed surgical patients receiving N2O as a component of their anaesthesia.

Detailed Description

There are some compelling reasons to question the routine use of nitrous oxide (N2O), also known as "laughing gas". Despite being the first anaesthetic drug introduced, and still widely used, 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, increased hospital length of stay and healthcare expenditure), and will be more likely in longer surgery. The extent of wound infection and cardiac morbidity associated with N2O is not known.

Large outcome trial data are lacking. When considering its widespread use in about 90% of all surgery around the world, small differences in outcome would have major implications for healthcare delivery. A large randomised controlled trial is necessary to answer this question.

We have recruited 2000 patients from about 25 centres around the world (mostly Australasia), who are undergoing major surgery.

Study Timeline

• Study Start: 2003-04
• Primary Completion: 2004-12
• Study Completion: 2004-12
• Study First Submitted: 2005-09-13
• Study First Submitted QC: 2005-09-13
• Study First Posted: 2005-09-14
• Status Verified: 2009-07
• Last Update Submitted: 2009-07-29
• Last Update Posted: 2009-07-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 2070

Inclusion Criteria

1. Males and females, age 18 years and over
2. Planned general anaesthesia for surgery that includes a skin incision and expected to exceed two hours, and the patient is expected to be in hospital for at least three days

Exclusion Criteria

1. Endoscopic or radiological procedures
2. Cardiac surgery
3. Marked impairment of gas-exchange (requiring Fi02> 0.3)
4. Thoracic surgery requiring one-lung ventilation (requiring Fi02> 0.3)
5. Specific circumstances where N2O is contraindicated (eg. volvulus, pulmonary hypertension, raised intracranial pressure)
6. Lack of provision of N2O.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
The primary endpoint is hospital length of stay (LOS), defined from the start of surgery until actual hospital discharge. Patients transferred to another hospital will be tracked until final discharge to home (or other final destination). LOS is likely

Secondary Outcome Measures

Name	Time	Method
Secondary endpoints will be detected by a research assistant who will be masked to Group identity, using chart review up to 30 days postoperatively; confirmation of each will be sought by an independent member of the Endpoint Committee:
Wound infection - if associated with purulent discharge or a positive microbial culture (46)
Myocardial infarction - confirmed by ECG and/or troponin or CK-MB enzyme rise
Venous thromboembolism - symptomatic DVT or PE, confirmed by venography, duplex ultrasonography, V-Q scan or spiral CT, or autopsy
Stroke - a new neurological deficit persisting for 24 hours, confirmed by neurologist assessment and/or CT scan or MRI
Awareness - postoperative recollection of intraoperative events
Blood transfusion - any red cell transfusion within 30 days of surgery
Pneumothorax, atelectasis, or pneumonia - confirmed by chest x-ray; for pneumonia: also 2 or more of temp> 38oC, white cell count >12,000/ml, positive sputum culture
Severe vomiting - at least 2 episodes >6 hrs apart, or if requiring >2 doses of antiemetic medication
Quality of recovery on the morning after surgery -using the validated QoR Score instrument (14), a 9-item patient-orientated measure of early postoperative health status. This is associated with patient satisfaction.
30-day mortality - for safety analysis only (study not powered for this rare event).

Trial Locations

Locations (1)

Alfred Hospital; 🇦🇺 Melbourne, Victoria, Australia