Clinical trial NCT03552627: Perioperative UtiLisation of SupplEmental Oxygen
Official title: Perioperative UtiLisation of SupplEmental Oxygen
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Anesthesia
Keywords: hyperoxia
oxygen
surgery
perioperative
Lead sponsor: University Hospital Southampton NHS Foundation Trust
Sponsor class: OTHER
First posted: 2018-06-12
Enrollment: 28
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Total Free Thiols
timeFrame: End of surgery
Secondary outcomes:
measure: Other oxidative stress markers
timeFrame: Within 7 days of surgery
measure: Acute cardiac events
timeFrame: Within 7 days of surgery
measure: Acute Kidney Injury
timeFrame: Within 7 days of surgery
measure: Acute Liver Injury
timeFrame: Within 7 days of surgery
measure: Post-operative Cognitive Recovery
timeFrame: 7 days after surgery
measure: Postoperative Morbidity
timeFrame: 7 days after surgery
Other outcomes:
Locations:
city: Southampton
country: United Kingdom
facility: University Hospital Southampton
state: Hampshire
Study officials:
affiliation: University Hospital Southampton NHS Foundation Trust
name: Andrew Cumpstey, BM BCh
role: PRINCIPAL_INVESTIGATOR
References: