Perioperative UtiLisation of SupplEmental Oxygen

Study Overview
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Brief Summary
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The World Health Organisation recommends that all patients having a general anaesthetic for surgery should be given 80% oxygen as this might reduce their risk of getting an infection after their operation. However there remains a lot of uncertainty about how much oxygen patients should be given whilst undergoing surgery. In other areas of medicine evidence is slowly emerging to suggest that giving less oxygen may be as safe or even safer than giving high amounts of oxygen (e.g. after a heart attack, patients unnecessarily given oxygen seem to do worse than those given air). The amount of oxygen currently given to patients having surgery varies widely; in a recent study of almost 400 procedures across 29 hospitals, we found values ranged from below 30% to almost 100% oxygen. The aim of this research is to explore if giving less oxygen will generate less strain on parts of the body, particularly the lungs as they are always exposed to all of the oxygen that enters the body. Participants undergoing major elective surgical procedures will be randomised to receive either 80%, 55% or 30% throughout their general anaesthetic and levels of inflammation, oxidative stress and perioperative recovery will all be measured for upto 7 days after surgery.

Detailed Description
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Over 3 million patients receive oxygen (O2) during general anaesthesia (GA) in the UK annually, and a large number of these also have co-morbid respiratory diseases such as Asthma or COPD. The World Health Organisation (WHO) recently recommended that all surgical patients receive 80% O2 throughout GA and for 6 hours in recovery to reduce Surgical Site Infections (SSIs). However, a recent Cochrane systematic review found no evidence of benefit from this approach and some evidence that harm could be increased (including mortality). Excess oxygen has been associated with worse outcomes in many areas of medicine (including acute respiratory illnesses), possibly due to increased Reactive Oxygen Species (ROS) production: ROS can cause oxidative stress and damage proteins, DNA, and lipids. Observational data from our group shows most surgical patients currently receive nearer 55% O2 under GA. The effect of intraoperative O2 concentration on other surgical outcomes remains unknown. This project will determine whether giving lower concentrations of oxygen to surgical patients during anaesthesia can reduce levels of oxidative stress during surgery (particularly in the lungs); investigate how this affects other organs; and evaluate the feasibility of performing a large (multi-centre) effectiveness study to define 'safe' oxygen administration concentrations during surgery. Patient undergoing elective major surgery will be randomised to receive 80% (WHO's recommendation); 55% (current usual care) or 30% oxygen (intervention) throughout anaesthesia. Endotracheal aspirates will be sampled along with paired central venous and arterial blood samples throughout surgery to monitor levels of oxidative stress and organ function. Patients will be followed up for 7 days after surgery.

Official Title
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Perioperative UtiLisation of SupplEmental Oxygen

Conditions
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Anesthesia

Intervention / Treatment
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* Drug: Oxygen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥16yrs - no upper limit Undergoing elective surgical procedure Planned for placement of arterial line and central venous catheter as part of routine anaesthetic delivery Written informed consent Exclusion Criteria: Withdrawal of written consent or unable to give informed written consent Pregnant at time of enrolment Neurosurgery, cardiothoracic surgery or any other operation involving 1 lung ventilation at any point during procedure Baseline SpO2 < 90% Severe COPD (3 or 4 on GOLD criteria), Interstitial lung disease or other severe respiratory inflammatory co-morbidity (including already on home oxygen) BMI > 35 Assessed as having a potentially difficult airway or being difficult to ventilate (defined as concern documented at anaesthetic assessment) Participating in another research trial with similar interventions or outcomes. Sickle cell disease Thalassemia Major Under custody

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 80% Oxygen<br>Patients will receive 80% oxygen throughout anaesthesia in accordance with current World Health Organisation Recommendations | Drug: Oxygen<br>* Medical Oxygen<br>|
| Active Comparator: 55% Oxygen<br>Patients will receive 55% oxygen throughout anaesthesia in accordance with current UK clinical practice | Drug: Oxygen<br>* Medical Oxygen<br>|
| Experimental: 30% Oxygen<br>Patients will receive 30% oxygen throughout anaesthesia in accordance with this research's hypothesis that lowering intraoperative oxygen concentrations may benefit patients | Drug: Oxygen<br>* Medical Oxygen<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Free Thiols | A measure of (Anti)oxidant capacity | End of surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Other oxidative stress markers | A panel of other markers of oxidative stress | Within 7 days of surgery | 
| Acute cardiac events | Elevations in troponin levels | Within 7 days of surgery | 
| Acute Kidney Injury | Elevations in creatinine or NGAL-1 | Within 7 days of surgery | 
| Acute Liver Injury | Elevations in ALT | Within 7 days of surgery | 
| Post-operative Cognitive Recovery | PQRS score | 7 days after surgery | 
| Postoperative Morbidity | Post Operative Morbidity Survey score | 7 days after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hyperoxia, oxygen, surgery, perioperative