Risk of Oxygen During Cardiac Surgery Trial

Study Overview
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Brief Summary
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The investigators will recruit and randomize 200 elective cardiac surgery patients to receive physiologic oxygenation (normoxia) or hyper-oxygenation (hyperoxia) during surgery to test the hypothesis that intraoperative physiologic oxygenation decreases the generation of reactive oxygen species, oxidative damage, and postoperative organ injury compared to hyper-oxygenation.

Official Title
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Risk of Oxygen During Cardiac Surgery (ROCS) Trial

Conditions
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Cardiac Surgery

Intervention / Treatment
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* Drug: Oxygen - normoxia
* Drug: Oxygen - hyperoxia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Open-heart cardiac surgery, defined as surgery on the heart or aorta that requires sternotomy or thoracotomy. Exclusion Criteria: Current acute coronary syndrome (defined as ST elevation myocardial infarction or non-ST elevation myocardial infarction (troponin leak within 72 hours of surgery or consent +/- EKG changes consistent with myocardial ischemia)). Home supplemental oxygen use. Preoperative supplemental oxygen requirement to maintain arterial O2 sat of 92%. Right to left intracardiac shunt including atrial septal defect and ventricular septal defect with Cor Pulmonale. Carotid stenosis defined as >50% stenosis. Cardiac surgery that requires intraoperative circulatory arrest, such as aortic arch replacement. Current use of hemo- or peritoneal dialysis. Pregnancy

Ages Eligible for Study
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Minimum Age: 18 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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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Normoxia<br>Oxygen administration to maintain a hemoglobin oxygen saturation of 95-97% or arterial PaO2 80-110 mmHg during surgery. | Drug: Oxygen - normoxia<br>* Titration of FIO2 to maintain normal hemoglobin oxygen saturation (95-97%)<br>* Other names: oxygen;|
| Active Comparator: Hyperoxia<br>Fraction of inspired oxygen 1.0 during mechanical ventilation and 0.8 during cardiopulmonary bypass during surgery. | Drug: Oxygen - hyperoxia<br>* Administration of 1.0 FIO2 during ventilation and 0.8 or above during cardiopulmonary bypass<br>* Other names: oxygen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intraoperative Systemic Oxidative Damage | quantified by measuring F2-isoprostanes isofurans following separation from cardiopulmonary bypass or completion of off-pump coronary artery bypass grafting | separation from cardiopulmonary bypass or completion of off-pump coronary artery bypass grafting (approximately 3-5 hours into surgery and intervention) | 
| Acute Kidney Injury | quantified by change in serum creatinine concentration | baseline to postoperative day 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vascular Reactivity / Endothelial Function | measured by brachial artery flow mediated dilation, peripheral artery tonometry, tension wire myography from arterioles dissected from epicardial fat, and biomarkers including PAI-1 and e-selectin | up to 2 days following surgery | 
| Mitochondrial Function | in peripheral blood mononuclear cells and atrial myocardium | up to 2 days following surgery | 
| Number of People With Arrhythmia | defined as any atrial fibrillation following surgery until hospilate discharge assessed using continuous telemetry, rhythm strips, and electrocardiograms | from surgery to hospital discharge, average of 6 days following surgery | 
| Myocardial Injury or Infarction | plasma concentration of creatine kinase, myocardial band | morning of postoperative day 1 | 
| Number of People With Stroke | Defined as new deficit on neurologic exam and confirmed with radiologic evidence occurring at any point prior to hospital discharge | from surgery to hospital discharge, average of 6 days following surgery | 
| Postoperative Cognitive Dysfunction, Pain, and Depression |  | up to 18 months following surgery | 
| Respiratory Failure | reintubation | from surgery to hospital discharge, average of 6 days following surgery | 
| Chronic Kidney Disease | MAKE criteria (eGFR, dialysis, death) | up to 18 months following surgery | 
| Inflammation |  | up to 2 days following surgery | 
| Hemolysis | plasma free hemoglobin | separation from cardiopulmonary bypass or completion of off-pump coronary artery bypass grafting (approximately 3-5 hours into surgery and intervention) | 
| Reactive Oxygen Species Production | TMH and CAT1H electron spin probes, and dihydroethidium. | up to 1 day following surgery | 
| Acute Brain Dysfunction (Delirium) | The number of participants with acute brain dysfunction as assessed by the Confusion Assessment Method for the ICU (CAM-ICU) twice daily while patients are in the ICU or for first 3 postoperative days. | from surgery to hospital discharge, average of 6 days following surgery | 
| Oxygenation and Perfusion | hemoglobin O2 saturation, PaO2, brain and muscle oxygenation using NIRS, mixed venous O2 saturation, cardiac output, arterial lactate | up to 1 day following surgery | 
| Acute Kidney Injury, According to KDIGO Criteria | KDIGO acute kidney injury is defined as an increase in SCr ≥ 0.3 mg/dL (≥ 26.5 lmol/L) within 48 hours of surgery or 1.5 to 1.9 times baseline within 7 days of surgery | up to 7 days following surgery | 
| Acute Kidney Injury Estimated by Urine Concentration of TIMP-2 IGFBP7 |  | baseline to 2 days following surgery | 
| Acute Kidney Injury Estimated by Urine Concentration of NGAL |  | baseline to 2 days following surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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oxygen, hyperoxia, reactive oxygen species, oxidative stress, oxidative damage, endothelial function, vascular reactivity, mitochondrial function, surgery, anesthesia, kidney injury, renal failure, delirium, myocardial injury, arrythmia