Perioperative Transfusion Study (PETS): does a liberal transfusion protocol improve outcome in high-risk cardiovascular patients undergoing non-cardiac surgery?

Myocardial infarction and ischemic cardiac complications are very common after
noncardiac surgery. Studies show that the incidence of perioperative myocardial
infarction varies roughly between 2 and 15%. A major concern is that in around
60% of the patients, ischemic cardiac events occur without symptoms and that
these patients therefore do not receive adequate treatment.
Although the majority of peri-operative myocardial infarctions present within
the first 4 days of surgery, and nearly 90% by 7 days, the range of
presentation is throughout the entire hospital admission.
In patients with significant coronary artery disease, perioperative myocardial
ischemia may be caused by a sustained myocardial supply/demand imbalance due to
tachycardia and increased myocardial contractility. This supply/demand
imbalance can be exaggerate by anemia. Some studies suggest that preoperative
anemia as well as a restrictive transfusion strategy might adversely affect
outcome in patients at a high risk for postoperative cardiovascular
complications
Apart from the CBO guidelines, no studies are available with regard to
optimization of postoperative hemoglobin levels in high risk cardiovascular
patients. However, one recently published pilot study shows promising results
from a more liberal transfusion regime in patients with recent myocardial
ischemia. In a randomized pilot study a more liberal transfusion regime was
tested in patients with myocardial infarction, unstable angina and stable
coronary artery disease undergoing cardiac catheterization. In the liberal
transfusion group a more than 50% reduction in the primary outcome (death,
myocardial infarction or unscheduled revascularization) was seen.
It is unsure whether the same preventive effect can be seen in the
perioperative phase. We therefore plan to undertake a pilot study

The primary objective of this study is to assess whether a liberal (6.5 mmol/l)
transfusion strategy compared to a restrictive (6.0 mmol/l) transfusion
strategy lowers the incidence of major adverse cardiac events (MACE). MACE is
defined as a composite endpoint of all-cause mortality, myocardial infarction
or unscheduled coronary revascularization up to 30 days after randomization.

PETS will be a set up a non-blinded randomised controlled (pilot) study
including 100 patients.

Patients who have provided written informed consent will be randomized to the
liberal transfusion or restrictive transfusion strategy once their hemoglobin
level has fallen below the upper limit of the liberal transfusion threshold
(i.e. 6.5 mmol/l) . Preoperative hemoglobin levels will be drawn as part of
standard care the day before surgery. If a patient has a hemoglobin level below
the transfusion threshold preoperatively, the patient is allowed to receive a
preoperative transfusion to raise the hemoglobin above the lower limit of
chosen transfusion strategy. Patients randomly allocated to the restrictive
transfusion strategy are permitted to receive transfusions above the
restrictive transfusion threshold if patients develop symptoms of anemia, but
will be marked as protocol violation. The assigned transfusion strategy is
followed until the third postoperative day or discharge from hospital. Each
unit transfused is administered one unit at a time followed by hemoglobin
measurement.

Patients who included in the study will beexposed to additional bloodsampeling;
no more than once a day 15 ml up to 3 days consecutively.
After each blood transfusion a possible transfusion reaction may develeop. The
chance of having tranfusion reaction will be minimized by prior to transfusion
to carry out a cross-matching in all patients.