Risk of Oxygen During Cardiac Surgery Trial

Risk of Oxygen During Cardiac Surgery (ROCS) Trial

Status

Completed

Phases

Phase 2Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02361944

Acronym

ROCS

Enrollment

213

Registered

2015-02-12

Start date

2016-04-05

Completion date

2021-01-08

Last updated

2024-02-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cardiac Surgery

Keywords

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

Brief summary

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.

Interventions

DRUGOxygen - normoxia

Titration of FIO2 to maintain normal hemoglobin oxygen saturation (95-97%)

DRUGOxygen - hyperoxia

Administration of 1.0 FIO2 during ventilation and 0.8 or above during cardiopulmonary bypass

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

DOUBLE (Subject, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
Number of People With Arrhythmia	from surgery to hospital discharge, average of 6 days following surgery	defined as any atrial fibrillation following surgery until hospital discharge assessed using continuous telemetry, rhythm strips, and electrocardiograms
Myocardial Injury or Infarction	morning of postoperative day 1	plasma concentration of creatine kinase, myocardial band
Number of People With Stroke	from surgery to hospital discharge, average of 6 days following surgery	Defined as new deficit on neurologic exam and confirmed with radiologic evidence occurring at any point prior to hospital discharge
Postoperative Cognitive Dysfunction	up to 18 months following surgery	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.
Respiratory Failure	from surgery to hospital discharge, average of 6 days following surgery	reintubation
Chronic Kidney Disease	12 months following surgery	eGFR one year following surgery
Inflammation	up to 2 days following surgery	Estimated by quantifying plasma concentration of plasminogen activator inhibitor-1 (PAI-1)
Hemolysis	separation from cardiopulmonary bypass or completion of off-pump coronary artery bypass grafting (approximately 3-5 hours into surgery and intervention)	plasma free hemoglobin
Reactive Oxygen Species Production	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)	TMH electron spin probe
Acute Brain Dysfunction (Delirium)	from surgery to hospital discharge, average of 6 days following surgery	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.
Oxygenation and Perfusion (Lactate)	ICU admission (immediately after arrival in ICU from operating room)	arterial lactate measured from arterial blood collected at ICU admission (immediately after arrival in ICU from operating room)
Acute Kidney Injury, According to KDIGO Criteria	up to 7 days following surgery	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
Acute Kidney Injury Estimated by Urine Concentration of TIMP-2 IGFBP7	baseline to 2 days following surgery	Urinary concentration of \[TIMP2\]\*\[IGFBP7\] 6 hours after ICU admission
Acute Kidney Injury Estimated by Urine Concentration of NGAL	baseline to 2 days following surgery	Urinary concentration of neutrophil gelatinase-associated lipocalin (NGAL) 6 hours after ICU admission.
Vascular Reactivity / Endothelial Function (as Measured by Flow Mediated Dilation)	ICU admission (immediately after arrival in ICU from operating room)	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.
Oxygenation and Perfusion (PaO2)	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)	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)
Oxygenation and Perfusion (Cerebral Oximetry)	continuously assessed throughout surgery and recorded each minute	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.
Oxygenation and Perfusion (SvO2)	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)	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)
Oxygenation and Perfusion (Cardiac Index)	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)	cardiac output (normalized to body surface area, i.e., cardiac index)
Vascular Reactivity / Endothelial Function (Peripheral Artery Tonometry)	ICU admission (immediately after arrival in ICU from operating room)	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.
Vascular Reactivity / Endothelial Function (Tension Wire Myography, Endothelial Dependent Vasodilation, EC50)	tissue collected during surgery when heart is exposed approximately 2 hours into intervention	Effective concentration for 50% dilation acetylcholine dose response, tension wire myography from arterioles dissected from epicardial fat
Vascular Reactivity / Endothelial Function (Tension Wire Myography, Endothelial Dependent Vasodilation, Emax)	tissue collected during surgery when heart is exposed approximately 2 hours into intervention	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.
Vascular Reactivity / Endothelial Function (Tension Wire Myography, Endothelial Independent Vasodilation, EC50)	tissue collected during surgery when heart is exposed approximately 2 hours into intervention	Effective concentration for 50% dilation sodium nitroprusside dose response, tension wire myography from arterioles dissected from epicardial fat
Vascular Reactivity / Endothelial Function (Tension Wire Myography, Endothelial Independent Vasodilation, Emax)	tissue collected during surgery when heart is exposed approximately 2 hours into intervention	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.
Vascular Reactivity / Endothelial Function (Tension Wire Myography, sGC Activation Vasodilation, EC50)	tissue collected during surgery when heart is exposed approximately 2 hours into intervention	Effective concentration for 50% dilation cinaciguat dose response, tension wire myography from arterioles dissected from epicardial fat
Vascular Reactivity / Endothelial Function (Tension Wire Myography, sGC Activation Vasodilation, Emax)	tissue collected during surgery when heart is exposed approximately 2 hours into intervention	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.
Vascular Reactivity / Endothelial Function (PAI-1)	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)	Plasminogen activator inhibitor 1
Vascular Reactivity / Endothelial Function (E-selectin)	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)	E-selectin
Oxygenation and Perfusion (SpO2)	during surgery	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.
Mitochondrial Function	up to 2 days following surgery	mitochondrial function in atrial myocardium estimated by quantifying adenylate kinase at the end of surgery and oxygen intervention

Countries

United States

Participant flow

Pre-assignment details

213 patients signed consent. 12 participants were withdrawn prior to randomization. 201 were randomized.

Participants by arm

Arm	Count
Normoxia Oxygen administration to maintain a hemoglobin oxygen saturation of 95-97% or arterial PaO2 80-110 mmHg during surgery. Oxygen - normoxia: Titration of FIO2 to maintain normal hemoglobin oxygen saturation (95-97%)	100
Hyperoxia Fraction of inspired oxygen 1.0 during mechanical ventilation and 0.8 during cardiopulmonary bypass during surgery. Oxygen - hyperoxia: Administration of 1.0 FIO2 during ventilation and 0.8 or above during cardiopulmonary bypass	100
Total	200

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	surgery cancellation	0	1

Baseline characteristics

Characteristic	Normoxia	Hyperoxia	Total
Age, Continuous	66 years	64 years	66 years
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants	1 Participants	4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	97 Participants	99 Participants	196 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants	0 Participants	1 Participants
Race (NIH/OMB) Asian	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Black or African American	7 Participants	5 Participants	12 Participants
Race (NIH/OMB) More than one race	1 Participants	2 Participants	3 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	91 Participants	92 Participants	183 Participants
Region of Enrollment United States	100 participants	100 participants	200 participants
Serum Creatinine	1.04 mg/dl	1.08 mg/dl	1.06 mg/dl
Sex: Female, Male Female	26 Participants	34 Participants	60 Participants
Sex: Female, Male Male	74 Participants	66 Participants	140 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	2 / 100	0 / 100
other Total, other adverse events	80 / 100	80 / 100
serious Total, serious adverse events	8 / 100	11 / 100

Outcome results

Primary

Acute Kidney Injury

quantified by change in serum creatinine concentration

Time frame: baseline to postoperative day 2

Arm	Measure	Value (MEDIAN)
Normoxia	Acute Kidney Injury	-0.01 mg/dl
Hyperoxia	Acute Kidney Injury	0.01 mg/dl

Primary

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)

Arm	Measure	Value (MEDIAN)
Normoxia	Intraoperative Systemic Oxidative Damage	69 pg/ml
Hyperoxia	Intraoperative Systemic Oxidative Damage	83 pg/ml

Secondary

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

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Normoxia	Acute Brain Dysfunction (Delirium)	16 Participants
Hyperoxia	Acute Brain Dysfunction (Delirium)	22 Participants

Secondary

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

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Normoxia	Acute Kidney Injury, According to KDIGO Criteria	21 Participants
Hyperoxia	Acute Kidney Injury, According to KDIGO Criteria	21 Participants

Secondary

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

Arm	Measure	Value (MEDIAN)
Normoxia	Acute Kidney Injury Estimated by Urine Concentration of NGAL	6.9 ng/ml
Hyperoxia	Acute Kidney Injury Estimated by Urine Concentration of NGAL	4.8 ng/ml

Secondary

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

Arm	Measure	Value (MEDIAN)
Normoxia	Acute Kidney Injury Estimated by Urine Concentration of TIMP-2 IGFBP7	0.224 (ng/ml) squared
Hyperoxia	Acute Kidney Injury Estimated by Urine Concentration of TIMP-2 IGFBP7	0.187 (ng/ml) squared

Secondary

Chronic Kidney Disease

eGFR one year following surgery

Time frame: 12 months following surgery

Population: eGFR assessed in participants available for long-term follow-up

Arm	Measure	Value (MEDIAN)
Normoxia	Chronic Kidney Disease	63.0 ml/min/1.73 meters squared
Hyperoxia	Chronic Kidney Disease	60.4 ml/min/1.73 meters squared

Secondary

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)

Arm	Measure	Value (MEDIAN)
Normoxia	Hemolysis	388,030 ng/ml
Hyperoxia	Hemolysis	433,274 ng/ml

Secondary

Inflammation

Estimated by quantifying plasma concentration of plasminogen activator inhibitor-1 (PAI-1)

Time frame: up to 2 days following surgery

Arm	Measure	Value (MEDIAN)
Normoxia	Inflammation	31.08 ng/ml
Hyperoxia	Inflammation	36.62 ng/ml

Secondary

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

Population: Analyzed in subjects with tissue available

Arm	Measure	Value (MEDIAN)
Normoxia	Mitochondrial Function	1884 Absorbance Units (AU)
Hyperoxia	Mitochondrial Function	1936 Absorbance Units (AU)

Secondary

Myocardial Injury or Infarction

plasma concentration of creatine kinase, myocardial band

Time frame: morning of postoperative day 1

Arm	Measure	Value (MEDIAN)
Normoxia	Myocardial Injury or Infarction	27.2 ng/ml
Hyperoxia	Myocardial Injury or Infarction	24.5 ng/ml

Secondary

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

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Normoxia	Number of People With Arrhythmia	37 Participants
Hyperoxia	Number of People With Arrhythmia	46 Participants

Secondary

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

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Normoxia	Number of People With Stroke	1 Participants
Hyperoxia	Number of People With Stroke	2 Participants

Secondary

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)

Arm	Measure	Value (MEDIAN)
Normoxia	Oxygenation and Perfusion (Cardiac Index)	2.56 liters/min/meter squared
Hyperoxia	Oxygenation and Perfusion (Cardiac Index)	2.48 liters/min/meter squared

Secondary

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

Arm	Measure	Value (MEDIAN)
Normoxia	Oxygenation and Perfusion (Cerebral Oximetry)	-7.2 percentage change from baseline
Hyperoxia	Oxygenation and Perfusion (Cerebral Oximetry)	6.0 percentage change from baseline

Secondary

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)

Arm	Measure	Value (MEDIAN)
Normoxia	Oxygenation and Perfusion (Lactate)	1.5 mmol/liter
Hyperoxia	Oxygenation and Perfusion (Lactate)	1.8 mmol/liter

Secondary

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)

Arm	Measure	Value (MEDIAN)
Normoxia	Oxygenation and Perfusion (PaO2)	99 mmHg
Hyperoxia	Oxygenation and Perfusion (PaO2)	377 mmHg

Secondary

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

Arm	Measure	Value (MEDIAN)
Normoxia	Oxygenation and Perfusion (SpO2)	97 percent saturation
Hyperoxia	Oxygenation and Perfusion (SpO2)	100 percent saturation

Secondary

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)

Arm	Measure	Value (MEDIAN)
Normoxia	Oxygenation and Perfusion (SvO2)	68 percent saturation
Hyperoxia	Oxygenation and Perfusion (SvO2)	78 percent saturation

Secondary

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

Population: Assessed in participants available for long-term follow-up who were able to complete cognitive assessments

Arm	Measure	Value (MEDIAN)
Normoxia	Postoperative Cognitive Dysfunction	3 score on a scale
Hyperoxia	Postoperative Cognitive Dysfunction	2 score on a scale

Secondary

Reactive Oxygen Species Production

CAT1H electron spin probe

Arm	Measure	Value (MEDIAN)
Normoxia	Reactive Oxygen Species Production	17,300 Absorbance Units (AU)
Hyperoxia	Reactive Oxygen Species Production	17,040 Absorbance Units (AU)

Secondary

Reactive Oxygen Species Production

TMH electron spin probe

Arm	Measure	Value (MEDIAN)
Normoxia	Reactive Oxygen Species Production	165,000 Absorbance Units (AU)
Hyperoxia	Reactive Oxygen Species Production	180,100 Absorbance Units (AU)

Secondary

Respiratory Failure

reintubation

Time frame: from surgery to hospital discharge, average of 6 days following surgery

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Normoxia	Respiratory Failure	5 Participants
Hyperoxia	Respiratory Failure	1 Participants

Secondary

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)

Arm	Measure	Value (MEDIAN)
Normoxia	Vascular Reactivity / Endothelial Function (as Measured by Flow Mediated Dilation)	4.50 percentage change
Hyperoxia	Vascular Reactivity / Endothelial Function (as Measured by Flow Mediated Dilation)	4.71 percentage change

Secondary

Vascular Reactivity / Endothelial Function (E-selectin)

E-selectin

Arm	Measure	Value (MEDIAN)
Normoxia	Vascular Reactivity / Endothelial Function (E-selectin)	16.4 ng/ml
Hyperoxia	Vascular Reactivity / Endothelial Function (E-selectin)	16.2 ng/ml

Secondary

Vascular Reactivity / Endothelial Function (PAI-1)

Plasminogen activator inhibitor 1

Arm	Measure	Value (MEDIAN)
Normoxia	Vascular Reactivity / Endothelial Function (PAI-1)	31.2 ng/ml
Hyperoxia	Vascular Reactivity / Endothelial Function (PAI-1)	36.6 ng/ml

Secondary

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)

Arm	Measure	Value (MEDIAN)
Normoxia	Vascular Reactivity / Endothelial Function (Peripheral Artery Tonometry)	1.41 index
Hyperoxia	Vascular Reactivity / Endothelial Function (Peripheral Artery Tonometry)	1.23 index

Secondary

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