Blender Biomarkers: A BLENDER Sub-study to Evaluate the Effect of Oxygen Dose on Oxidative Stress and Organ Injury

Study Overview
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Brief Summary
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To compare the impact of liberal vs conservative oxygen doses on markers of oxidative stress in patients enrolled in the BLENDER trial.

Detailed Description
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Extracorporeal membrane oxygen (ECMO) is a heart lung support device used for patients with severe and cardiac and respiratory failure and carries an increased risk of exposure to very high oxygen tensions. Hyperoxia (arterial oxygen >100mmHg) can lead to the production of reactive oxygen species (ROS). Excess production of ROS and depletion of antioxidant compounds is referred to as oxidative stress and results in inflammation, tissue injury and cell death. The inter-relationship between the production of ROS and end organ dysfunction is complicated and remain unclear. A more detailed assessment of the timing of changes in markers of oxidative stress, inflammatory mediators and tissue injury is warranted to understand the processes and potentially identify therapeutic targets. The BLENDER Trial is a multicentre trial in ECMO patients to determine whether a conservative oxygen strategy during ECMO reduces ICU length of stay and improves patient outcomes compared to a liberal oxygen strategy. Currently there have been no studies that look at the underlying pathophysiological changes that occur in patients on ECMO when subjected to different oxygen concentrations. As such The BLENDER study represents a unique opportunity to understand the mechanisms by which hyperoxia may cause tissue injury in patients receiving ECMO. This nested study seeks to elucidate whether exposure to hyperoxia during ECMO results in increased oxidative stress and whether this is correlated with increased risk of tissue injury and organ dysfunction. A better understanding of the mechanism of hyperoxia induced tissue injury may allow treatment to be optimised for patients exposed to hyperoxia as part of their treatment.

Official Title
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Blender Biomarkers: A BLENDER Sub-study to Evaluate the Effect of Oxygen Dose on Oxidative Stress and Organ Injury

Conditions
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Cardiac Failure, Critical Illness

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients receiving venoarterial (VA) ECMO Enrolled in the BLENDER trial Exclusion Criteria: Not enrolled in the BLENDER trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Super oxide dismutase levels U/ml | Plasma levels of superoxide dismutase in patients exposed to either a liberal or conservative oxygen strategy during VA-ECMO | Within 24 hours of ECMO commencement | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Marker of Cardiac Injury | Troponin ng/ml This will be determined by analysing blood samples routinely collected daily from patient receiving ECMO | Day 3 of ECMO | 
| Marker of Cardiac Injury | Troponin I ng/ml This will be determined by analysing blood samples routinely collected daily from patient receiving ECMO | Day 7 of ECMO | 
| Markers of Liver Injury | ALT and AST (IU/L) This will be determined by analysing blood samples routinely collected daily from patient receiving ECMO | Day 3 of ECMO | 
| Markers of Liver Injury | ALT and AST (IU/L) This will be determined by analysing blood samples routinely collected daily from patient receiving ECMO | Day 7 of ECMO | 
| Marker of Neurological Injury | Neuron Specific Enolase (microg/L) This will be determined by analysing blood samples routinely collected daily from patient receiving ECMO | Day 3 of ECMO | 
| Marker of Neurological Injury | Neuron Specific Enolase (microg/L) This will be determined by analysing blood samples routinely collected daily from patient receiving ECMO | Day 7 of ECMO | 
| Coagulation Parameters | APTT This will be determined by analysing blood samples routinely collected daily from patient receiving ECMO | Day 3 of ECMO | 
| Coagulation Parameters | APTT This will be determined by analysing blood samples routinely collected daily from patient receiving ECMO | Day 7 of ECMO | 
| Immune Markers | IL-6, TNFa, IL-10, IL-1B (pg/ml) | Day 3 of ECMO | 
| Immune Markers | IL-6, TNFa, IL-10, IL-1B (pg/ml) | Day 7 of ECMO | 
| Other Markers of Oxidative Stress | Malondialdehyde, Vitamin C | Day 3 of ECMO | 
| Other Markers of Oxidative Stress | Malondialdehyde, Vitamin C | Day 7 of ECMO | 
| Superoxide dismutase levels U/ml | Plasma levels of superoxide dismutase in patients exposed to either a liberal or conservative oxygen strategy during VA-ECMO | On Day 3 following ECMO commencement | 
| Superoxide dismutase levels | Plasma levels of superoxide dismutase in patients exposed to either a liberal or conservative oxygen strategy during VA-ECMO | On Day 7 following ECMO commencement | 
| Markers of Kidney Injury | Creatinine (micromol/L) | Day 3 of ECMO | 
| Markers of Kidney Injury | Creatinine (micromol/L) | Day 7 of ECMO | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ECMO, V-A ECMO, Oxidative stress, Oxygen, Hyperoxia