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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
213
Titration of FIO2 to maintain normal hemoglobin oxygen saturation (95-97%)
Administration of 1.0 FIO2 during ventilation and 0.8 or above during cardiopulmonary bypass
Vanderbilt University Medical Center
Nashville, Tennessee, United States
Intraoperative Systemic Oxidative Damage
quantified by measuring F2-isoprostanes isofurans following separation from cardiopulmonary bypass or completion of off-pump coronary artery bypass grafting
Time frame: 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
Time frame: baseline to postoperative day 2
Vascular Reactivity / Endothelial Function (as Measured by Flow Mediated Dilation)
brachial artery flow mediated dilation assessed when patient arrives in ICU after surgery. brachial artery flow mediated dilation is represented as the percent change in brachial artery diameter following 5 minutes of artery occlusion. The entire assessment takes place at ICU admission.
Time frame: ICU admission (immediately after arrival in ICU from operating room)
Mitochondrial Function
mitochondrial function in atrial myocardium estimated by quantifying adenylate kinase at the end of surgery and oxygen intervention
Time frame: up to 2 days following surgery
Number of People With Arrhythmia
defined as any atrial fibrillation following surgery until hospital discharge assessed using continuous telemetry, rhythm strips, and electrocardiograms
Time frame: from surgery to hospital discharge, average of 6 days following surgery
Myocardial Injury or Infarction
plasma concentration of creatine kinase, myocardial band
Time frame: morning of postoperative day 1
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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
Time frame: from surgery to hospital discharge, average of 6 days following surgery
Postoperative Cognitive Dysfunction
Median change scores at the Short Blessed Scale (SBT) administered one-year following surgery. The SBT is a validated rating scale, administered by the clinician, measuring the cognitive performance. Sum Total (range 0-28) with 0 indicating no cognitive impairment and 28 indicating severe cognitive impairment.
Time frame: up to 18 months following surgery
Respiratory Failure
reintubation
Time frame: from surgery to hospital discharge, average of 6 days following surgery
Chronic Kidney Disease
eGFR one year following surgery
Time frame: 12 months following surgery
Inflammation
Estimated by quantifying plasma concentration of plasminogen activator inhibitor-1 (PAI-1)
Time frame: up to 2 days following surgery
Hemolysis
plasma free hemoglobin
Time frame: 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 electron spin probe
Time frame: end of surgery, defined as immediately after separation from cardiopulmonary bypass or completion of off-pump coronary artery bypass grafting (approximately 3-5 hours into surgery and intervention)
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.
Time frame: from surgery to hospital discharge, average of 6 days following surgery
Oxygenation and Perfusion (Lactate)
arterial lactate measured from arterial blood collected at ICU admission (immediately after arrival in ICU from operating room)
Time frame: ICU admission (immediately after arrival in ICU from operating room)
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
Time frame: up to 7 days following surgery
Acute Kidney Injury Estimated by Urine Concentration of TIMP-2 IGFBP7
Urinary concentration of \[TIMP2\]\*\[IGFBP7\] 6 hours after ICU admission
Time frame: baseline to 2 days following surgery
Acute Kidney Injury Estimated by Urine Concentration of NGAL
Urinary concentration of neutrophil gelatinase-associated lipocalin (NGAL) 6 hours after ICU admission.
Time frame: baseline to 2 days following surgery
Reactive Oxygen Species Production
CAT1H electron spin probe
Time frame: end of surgery, defined as immediately after separation from cardiopulmonary bypass or completion of off-pump coronary artery bypass grafting (approximately 3-5 hours into surgery and intervention)
Oxygenation and Perfusion (SpO2)
hemoglobin O2 saturation summarized using SpO2 data continuously measured and recorded every minute during surgery. We calculated the median SpO2 throughout surgery using all the minute to minute values. For example, if a participant had a 5 hour (300 minutes) long surgery, the participant would have 300 SpO2 measurements. We calculated and report the median of those measurements.
Time frame: during surgery
Oxygenation and Perfusion (PaO2)
partial pressure of oxygen in arterial blood measured from blood sampled at end of surgery, defined as following separation from cardiopulmonary bypass or completion of off-pump coronary artery bypass grafting (approximately 3-5 hours into surgery and intervention)
Time frame: end of surgery, defined as separation from cardiopulmonary bypass or completion of off-pump coronary artery bypass grafting (approximately 3-5 hours into surgery and intervention)
Oxygenation and Perfusion (Cerebral Oximetry)
brain hemoglobin oxygenation using near-infrared spectroscopy (NIRS). The median percent changes from baseline (baseline measured at beginning of surgery when probes placed on forehead, prior to intervention) throughout surgery was calculated using cerebral oximetry measurements collected every minute throughout surgery. We calculated the difference between baseline and each measurement throughout surgery. For example, if a participant had a 5 hour (300 minutes) long surgery, the participant would have 300 cerebral oximetry measurements. We calculated and report the median of those measurements.
Time frame: continuously assessed throughout surgery and recorded each minute
Oxygenation and Perfusion (SvO2)
mixed venous O2 saturation, measured from blood sampled from pulmonary artery sampled at end of surgery, defined as following separation from cardiopulmonary bypass or completion of off-pump coronary artery bypass grafting (approximately 3-5 hours into surgery and intervention)
Time frame: end of surgery, defined as following separation from cardiopulmonary bypass or completion of off-pump coronary artery bypass grafting (approximately 3-5 hours into surgery and intervention)
Oxygenation and Perfusion (Cardiac Index)
cardiac output (normalized to body surface area, i.e., cardiac index)
Time frame: end of surgery, defined as immediately after separation from cardiopulmonary bypass or completion of off-pump coronary artery bypass grafting (approximately 3-5 hours into surgery and intervention)
Vascular Reactivity / Endothelial Function (Peripheral Artery Tonometry)
reactive hyperemia index measured at ICU admission (immediately after arrival in ICU from operating room). The reactive hyperemia index is a number generated by an endopat machine performing peripheral artery tonometry. The index ranges from approximately 1-3, where higher values indicate better vascular reactivity and endothelial function.
Time frame: ICU admission (immediately after arrival in ICU from operating room)
Vascular Reactivity / Endothelial Function (Tension Wire Myography, Endothelial Dependent Vasodilation, EC50)
Effective concentration for 50% dilation acetylcholine dose response, tension wire myography from arterioles dissected from epicardial fat
Time frame: tissue collected during surgery when heart is exposed approximately 2 hours into intervention
Vascular Reactivity / Endothelial Function (Tension Wire Myography, Endothelial Dependent Vasodilation, Emax)
Maximum percentage of arteriole dilation after increasing doses of acetylcholine measured using tension wire myography of arterioles dissected from epicardial fat. The fat sample was collected during surgery when heart is exposed approximately 2 hours into intervention.
Time frame: tissue collected during surgery when heart is exposed approximately 2 hours into intervention
Vascular Reactivity / Endothelial Function (Tension Wire Myography, Endothelial Independent Vasodilation, EC50)
Effective concentration for 50% dilation sodium nitroprusside dose response, tension wire myography from arterioles dissected from epicardial fat
Time frame: tissue collected during surgery when heart is exposed approximately 2 hours into intervention
Vascular Reactivity / Endothelial Function (Tension Wire Myography, Endothelial Independent Vasodilation, Emax)
Maximum percentage of arteriole dilation after increasing doses of sodium nitroprusside measured using tension wire myography of arterioles dissected from epicardial fat. The fat sample was collected during surgery when heart is exposed approximately 2 hours into intervention.
Time frame: tissue collected during surgery when heart is exposed approximately 2 hours into intervention
Vascular Reactivity / Endothelial Function (Tension Wire Myography, sGC Activation Vasodilation, EC50)
Effective concentration for 50% dilation cinaciguat dose response, tension wire myography from arterioles dissected from epicardial fat
Time frame: tissue collected during surgery when heart is exposed approximately 2 hours into intervention
Vascular Reactivity / Endothelial Function (Tension Wire Myography, sGC Activation Vasodilation, Emax)
Maximum percentage of arteriole dilation after increasing doses of cinaciguat measured using tension wire myography of arterioles dissected from epicardial fat. The fat sample was collected during surgery when heart is exposed approximately 2 hours into intervention.
Time frame: tissue collected during surgery when heart is exposed approximately 2 hours into intervention
Vascular Reactivity / Endothelial Function (PAI-1)
Plasminogen activator inhibitor 1
Time frame: end of surgery, defined as immediately after separation from cardiopulmonary bypass or completion of off-pump coronary artery bypass grafting (approximately 3-5 hours into surgery and intervention)
Vascular Reactivity / Endothelial Function (E-selectin)
E-selectin
Time frame: end of surgery, defined as immediately after separation from cardiopulmonary bypass or completion of off-pump coronary artery bypass grafting (approximately 3-5 hours into surgery and intervention)