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NCT00164047 Clinical Trial

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

Effects of Nitrous Oxide Following Anaesthesia Clinical Trial

Official title:
Evaluation of Nitrous Oxide In the Gas Mixture for Anaesthesia: a Randomised Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data
NCT number NCT00164047
Other study ID # 204/02
Secondary ID NHMRC 236956
Status Completed
Phase Phase 4
First received September 13, 2005
Last updated July 29, 2009
Start date April 2003
Est. completion date December 2004

Study information
Verified date July 2009
Source Bayside Health
Contact n/a
Is FDA regulated No
Health authority Australia: National Health and Medical Research CouncilAustralia: TGAAustralia: Monash University
Study type Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility
Status Completed
Enrollment 2070
Est. completion date December 2004
Est. primary completion date December 2004
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility 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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

Intervention

Drug:
• Nitrous Oxide

Locations
Country Name City State
Australia Alfred Hospital Melbourne Victoria

Sponsors (3)
Lead Sponsor Collaborator
Bayside Health Australia: Theapeutic Goods Administration, National Health and Medical Research Council, Australia

Country where clinical trial is conducted

Australia, 

References & Publications (2)

Myles PS, Leslie K, Chan MT, Forbes A, Paech MJ, Peyton P, Silbert BS, Pascoe E; ENIGMA Trial Group. Avoidance of nitrous oxide for patients undergoing major surgery: a randomized controlled trial. Anesthesiology. 2007 Aug;107(2):221-31. — View Citation

Myles PS, Leslie K, Silbert B, Paech MJ, Peyton P. A review of the risks and benefits of nitrous oxide in current anaesthetic practice. Anaesth Intensive Care. 2004 Apr;32(2):165-72. Review. — View Citation

Outcome
Type Measure Description Time frame Safety issue
Primary 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 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:
Secondary Wound infection - if associated with purulent discharge or a positive microbial culture (46)
Secondary Myocardial infarction - confirmed by ECG and/or troponin or CK-MB enzyme rise
Secondary Venous thromboembolism - symptomatic DVT or PE, confirmed by venography, duplex ultrasonography, V-Q scan or spiral CT, or autopsy
Secondary Stroke - a new neurological deficit persisting for 24 hours, confirmed by neurologist assessment and/or CT scan or MRI
Secondary Awareness - postoperative recollection of intraoperative events
Secondary Blood transfusion - any red cell transfusion within 30 days of surgery
Secondary 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
Secondary Severe vomiting - at least 2 episodes >6 hrs apart, or if requiring >2 doses of antiemetic medication
Secondary 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.
Secondary 30-day mortality - for safety analysis only (study not powered for this rare event).