Quality of Recovery From AnaesthesiaPhase 4NCT00164047
ENIGMA - Evaluation of Nitrous Oxide In the Gas Mixture for Anaesthesia: a Randomised Controlled Trial
A Phase 4 study testing Nitrous Oxide in people with Quality of Recovery From Anaesthesia and Effects of Nitrous Oxide Following Anaesthesia, run by Bayside Health at 1 site in Australia.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Quality of Recovery From Anaesthesia, Effects of Nitrous Oxide Following Anaesthesia, Induced Endothelial Dysfunction
- What is being tested?
- Nitrous Oxide
- How many people
- 2,070 participants
- Where
- 1 siteAustralia
- Study dates
- Apr 2003to Dec 2004
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females, age 18 years and over
- 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
Who cannot join
- Endoscopic or radiological procedures
- Cardiac surgery
- Marked impairment of gas-exchange (requiring Fi02> 0.3)
- Thoracic surgery requiring one-lung ventilation (requiring Fi02> 0.3)
- Specific circumstances where N2O is contraindicated (eg. volvulus, pulmonary hypertension, raised intracranial pressure)
- Lack of provision of N2O.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation of Nitrous Oxide In the Gas Mixture for Anaesthesia: a Randomised Controlled Trial
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.
Read the 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.
- Conditions
- Quality of Recovery From Anaesthesia, Effects of Nitrous Oxide Following Anaesthesia, Induced Endothelial Dysfunction
- Being tested
- Nitrous Oxide
- Keywords
- Nitrous Oxide, Anaesthesia, Anesthesia, Recovery, Quality
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitrous OxideDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
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 outcomes (11)
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).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2005 (estimated)
- Study startApr 2003
- Primary completionDec 2004
- Study completionDec 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Quality of Recovery From AnaesthesiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Enrolment
- 2,070 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bayside Health
- Sponsor type
- Other government
- Collaborators
- National Health and Medical Research Council, Australia, Australia: Theapeutic Goods Administration
- Investigators
- Paul S Myles, MB BS MPH MD, Principal investigator, The Alfred
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00164047
- Sponsor's protocol ID
- 204/02
- Other IDs
- NHMRC 236956
- Status last verified
- Jul 2009
- First submitted
- 13 Sep 2005
- Last updated
- 31 Jul 2009
- Results posted
- No
Publications
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. doi: 10.1177/0310057X0403200202. No abstract available.
PubMed 15957712Myles 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. doi: 10.1097/01.anes.0000270723.30772.da.
PubMed 17667565Leslie K, Myles PS, Chan MT, Paech MJ, Peyton P, Forbes A, McKenzie D; ENIGMA Trial Group. Risk factors for severe postoperative nausea and vomiting in a randomized trial of nitrous oxide-based vs nitrous oxide-free anaesthesia. Br J Anaesth. 2008 Oct;101(4):498-505. doi: 10.1093/bja/aen230. Epub 2008 Aug 5.
PubMed 18682411
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Nitrous Oxide In the Gas Mixture for Anaesthesia: a Randomised Controlled Trial
- ClinicalTrials.gov ID
- NCT00164047
- Acronym / sponsor ID
- 204/02
- Conditions
- Quality of Recovery From Anaesthesia, Effects of Nitrous Oxide Following Anaesthesia, Induced Endothelial Dysfunction
- Keywords
- Nitrous Oxide, Anaesthesia, Anesthesia, Recovery, Quality
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,070 participants (estimated)
- Lead sponsor
- Bayside HealthOther government
- Collaborators
- National Health and Medical Research Council, Australia, Australia: Theapeutic Goods Administration
- Study start
- Apr 2003
- Primary completion
- Dec 2004 (actual)
- Study completion
- Dec 2004 (actual)
- First posted
- 14 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Males and females, age 18 years and over
- 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
Key exclusion criteria (6 listed)
- Endoscopic or radiological procedures
- Cardiac surgery
- Marked impairment of gas-exchange (requiring Fi02> 0.3)
- Thoracic surgery requiring one-lung ventilation (requiring Fi02> 0.3)
- Specific circumstances where N2O is contraindicated (eg. volvulus, pulmonary hypertension, raised intracranial pressure)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nitrous Oxide | Drug | – |
Primary outcome
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
11 secondary outcomes
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).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2009.
- Background: PubMed 15957712Myles 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. doi: 10.1177/0310057X0403200202. No abstract available.
- Results publication: PubMed 17667565Myles 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. doi: 10.1097/01.anes.0000270723.30772.da.
- Derived from this study: PubMed 18682411Leslie K, Myles PS, Chan MT, Paech MJ, Peyton P, Forbes A, McKenzie D; ENIGMA Trial Group. Risk factors for severe postoperative nausea and vomiting in a randomized trial of nitrous oxide-based vs nitrous oxide-free anaesthesia. Br J Anaesth. 2008 Oct;101(4):498-505. doi: 10.1093/bja/aen230. Epub 2008 Aug 5.
Related trials for Quality of Recovery From Anaesthesia
RecruitingObservational study
The Impact of Fasting Duration on Quality of Recovery After Cesarean Section
Quality Improvement, Quality of Recovery From Anaesthesia
Recruiting
Impact of Sugammadex Versus Neostigmine on Early Postoperative Pulmonary Function
Residual Neuromuscular Block
Recruiting
Non-pharmacological Auditory and Somatosensory Stimulation in Anesthetic Emergence
General Anesthetic, Electroencephalographic
Not yet recruitingObservational study
Validation of the Setswana Translated Quality of Recovery Questionnaire in Orthopaedic Patients at a Tertiary Hospital in South Africa
Quality of Recovery (QoR-15), Quality of Recovery From Anaesthesia
Not yet recruitingObservational study
Validation of the Greek Postoperative Quality of Recovery Score 15
Postoperative Recovery, Quality of Recovery From Anaesthesia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul S Myles, MB BS MPH MD principal investigator
The Alfred
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Nitrous Oxide in people with Quality of Recovery From Anaesthesia and Effects of Nitrous Oxide Following Anaesthesia, run by Bayside Health at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jul 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00164047, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2009.