The cardiovascular effects of hyperoxia during and after CABG surgery

Although the deleterious effects of hypoxia are well known, most physicians are
less aware of the potential harmfull effect of hyperoxia. To avoid hypoxia, the
tendency to supply extra oxygen to patients is widespread. Increasing evidence
shows that hyperoxia has important circulatory effects, with decreased cardiac
output (CO) and increased systemic vascular resistance (SVR), resulting in
increased infarct size and increased mortality after myocardial infarction and
cardiac arrest. The underlying mechanisms are unknown, but could relate to
increased formation of reactive oxygen species (ROS), which not only causes
vasoconstriction, but also other untoward effects, such as reperfusion damage.
Hyperoxia is frequently, >20% of the mechanical ventilation time, encountered
in the Intensive Care. Patients who underwent a coronary bypass graft operation
(CABG) may be especially vulnerable to the detrimental cardiovascular effects
of hyperoxia because of fluctuations in cardiac function due to other causes
(such as blood loss and fluid shifts) post-surgery. However, many physicians
still feel that increased arterial oxygen pressure (PaO2) represents a salutary
oxygen reserve not only post-surgery but also during cardiopulmonary bypass
(CPB). PaO2 measurements of >200 to 300 mmHg during CPB are no exception, as
confirmed by our own pilot data. Therefore, we chose to investigate the
cardiovascular effects of hyperoxia in patients during and after CABG surgery
together with the proposed mechanisms by which hyperoxia exerts its effects. We
will compare standard patient care, using supra-normal PaO2 levels, with
oxygen levels titrated to normal physiological range.
We hypothesize that hyperoxia during and post CABG surgery has unfavourable
effects on myocardial injury, hemodynamics, microcirculation, and organ
perfusion, due to increased oxidative stress (ROS) affecting
endothelium-derived vaso-active factors.

1. To study the effect of different target PaO2's on myocardial damage,
hemodynamics, microcirculation and organ perfusion in CABG patients.
2. To study underlying mechanisms of hyperoxia by determining differences in
oxidative stress response between the hyperoxic patients and the normoxemic
groups.

Randomized, prospective clinical trial

We will investigate current practice ( 1, 2; group I) with titrated oxygen
levels (group II).
group I: target PaO2 on CBP during aortic clamp time 200 * 220 mmHg, PaO2 at
ICU of 130-150 mm Hg
group II: : After intubation FiO2 will be decreased to 40% (provided that O2
saturation remains > 96%). Target PaO2 on CBP during aortic clamp tima 130 *
150 mmHg, PaO2 at ICU 80 * 100 mmHg

The risk and burden for study subjects are small. Blood sampling is combined
with sampling for normal care of patients. SDF measurements and urine sampling
are not a burden for patients. Since the titrated oxygen levels administered to
the patients are based on the pO2 measured in blood and pulse oximetry and the
oxygen levels are within the range of normal physiological levels, we do not
expose the patients to additional risk.