The Goal dIrected perFusion Trial, a multi-center, prospective, randomized, controlled study.

Previous studies (1-5) have demonstrated that oxygen delivery (DO2) and carbon
dioxide production (VCO2) during cardiopulmonary bypass (CPB) are associated
with renal outcome in cardiac surgery. The critical value for DO2 is around 262
* 272 mL/min/m2, and the correspondent critical value of DO2/VCO2 ratio is
around 5.0.
Patients with nadir DO2 and DO2/VCO2 ratio below these critical levels have an
increased incidence of acute kidney injury (AKI) after cardiac operations.
These observations offer an interpretation for the well-known deleterious
effects of excessive hemodilution during CPB, supported by many studies where
an association between nadir hematocrit (HCT) on CPB and bad outcomes
(especially renal) was found (6-8). It is reasonable to hypothesize that a low
oxygen delivery may determine an ischemic damage to the kidney, that due to its
peculiar circulation is particularly susceptible to a decrease in the oxygen
supply.
However, there is no evidence that a strategy directed towards the specific
goal of avoiding critical values of DO2 during CPB may actually decrease the
postoperative AKI rate.

The present study is designed to verify the hypothesis that a strategy based on
a goal-directed perfusion, aimed to avoid a nadir DO2 below the critical
threshold, is effective in limiting the postoperative AKI rate.

Multicenter, international, prospective, randomized and controlled study.

Patients will be randomly allocated to the Control or the GDP group.
Randomization will be performed locally at each participating Institution,
using computer-generated schemes. The patients in control Group will be treated
according to the local standards. The patients in GDP group will be treated
according to the GDP.

Details of the GDP protocol:
The main intervention to achieve the target value of DO2 is increasing the pump
flow. Additional interventions include hemofiltration to increase the HCT.

Transfusion protocol:
1. During CPB: Transfusions are mandatory below a HCT of 18%. Transfusions are
generally prohibited for an HCT > 21%. However, based on the individual
judgement that the patient is actually in need for packed red cells,
transfusions are allowed between an HCT of 22% and 24%. In this case, this will
be considered as a protocol violation, but the patient will not be withdrawn.
Transfusions are always prohibited for an HCT > 24%.
2. After CPB:
HCT < 18%: packed red cells are mandatory
HCT between 19% and 23%: packed red cells are allowed
HCT between 24% and 30%: packed red cells generally prohibited, but
admitted based on physician*s judgement. This represents a protocol
violation. In this case, this will be considered as a protocol violation,
but the patient will not be withdrawn.
HCT > 30%: packed red cells are prohibited.

Perfusion by the heart-lung machine based on the oxygen supply levels does not
involve any risk for the patient. The intervention takes place while the
patient is under anesthesia, which is therefore not associated with a burden
for the patient.