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

Bayside Health

Status and phase: Completed; Phase 4

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

Treatments: Drug: Nitrous Oxide

Study type: Interventional

Funder types: Other

Identifiers

NCT00164047

204/02

NHMRC 236956

Details and patient eligibility

About

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.

Full 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.

Enrollment: 2,070 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind