TRICS-III: Transfusion Requirements in Cardiac Surgery. An international, multi-centre, randomized controlled trial to assess transfusion thresholds in patients undergoing cardiac surgery

Acute anemia is associated with increased mortality likely due to impaired
oxygen delivery and tissue hypoxia. Since hemoglobin contributes to more than
99% of blood oxygen content, severe anemia leads to inadequate tissue oxygen
delivery, resulting in tissue hypoxia, organ failure, and death. In acute
anemia the increase in mortality is proportional to the reduction in
hemoglobin. During cardiopulmonary bypass (CPB), the acute hemodilution that
occurs has been shown to reduce oxygenation in the brain, heart, kidney,
intestine, and muscle, although the critical hemoglobin concentration that
would lead to inadequate oxygen delivery during CPB has not been determined.
There are a number of complications related to transfusion that are associated
with considerable morbidity and mortality. Non-infectious risks from
transfusion such as TRALI, which tends to occur more frequently in patients
having cardiac surgery,has a high case fatality rate, 5 to 13%. Additionally,
administrative errors resulting in hemolytic transfusion reactions can be
life-threatening. Pulmonary edema, due to the volume of red cells transfused,
has also been shown to occur more frequently in patients with critical illness
and cardiovascular disease who were transfused at a hemoglobin concentration of
100 g/L compared to a hemoglobin concentration of 70 g/L. Although the risk of
acquiring the human immune deficiency virus and hepatitis C virus is low, new
emerging pathogens constantly threaten the blood supply. Unnecessary
transfusions also have an impact on the care of patients. Optimum utilization
of blood components is essential as there is a continuous strain on blood
systems because of increased blood utilization. Additionally, increased blood
utilization results in increased resource utilization and cost of blood is
increasing. In an era where there are new emerging pathogens and blood
shortages, it is essential that these patients be transfused appropriately.
There is a critical need to determine the appropriate threshold for red cell
transfusion in patients undergoing cardiac surgery. While restrictive
transfusion strategies have been shown to reduce transfusion in other patient
populations, it may be inappropriate and unsafe to extrapolate these findings
to cardiac surgery. This clinical uncertainty is reflected in the tremendous
inter-physician and inter-hospital variability in transfusion practice, which
are unrelated to patient risk factors. This has prompted the recommendation by
the expert panel of the NHLBI to classify a trial such as this as one of the
most important trials required. If our trial demonstrates the safety of a
restrictive strategy, the risks and costs attributable to unnecessary
transfusions will be reduced. Alternatively, if restrictive transfusion is
found to be inferior, risks of complications related to untreated perioperative
anemia will be reduced. Our multicentre international study will thus provide
high-quality generalizable data to guide transfusion practice worldwide,
regardless of its eventual results.

A lower hemoglobin concentration for red cell transfusion (restrictive
transfusion strategy) will be non-inferior to a liberal strategy in terms of
vital organ function (heart, brain and kidney) and mortality.

An international, multi-centre, open-label, randomized controlled trial of two
commonly used transfusion strategies, using a non-inferiority trial design.

Study participants will be randomized to one of the following transfusion
strategies in a 1:1 manner: * Restrictive transfusion strategy: patients will
receive a red cell transfusion if their hemoglobin is <75 g/L (<7.5 g/dL; <4.7
mmol/L) intraoperatively and/or postoperatively * Liberal transfusion strategy:
patients will receive a red cell transfusion if their hemoglobin concentration
is <95 g/L (<9.5 g/dL; <5.9 mmol/L) intraoperatively or postoperatively in the
intensive care unit; or <85 g/L (<8.5 g/dL; <5.3 mmol/L) on the ward. When the
appropriate hemoglobin trigger is reached, patients in each group will have one
unit of red cells administered at a time followed by repeat determination of
the hemoglobin concentration. Each group will be transfused only if their
hemoglobin concentration falls below the transfusion threshold.

It is an obligation of the site Investigator to obtain informed consent
from every study patient by means of a dated and signed informed consent form
before any study related procedure is performed. *Informed consent* also
implies individual discussion with the patient about the nature of study
interventions to be conducted in a language that is easy to comprehend, which
will take about 10 to 15 minutes. At 6 months, a telephone follow-up will occur
and the following clinical outcomes will be collected based on patient or
caregiver report, since hospital discharge/postoperative day 28: * Death (and
reason for death) * MI * Stroke * Surgical or non-surgical coronary
revascularization * New renal dialysis status at 6 months which will take about
5 to 10 minutes. risks: There are a number of complications related to
transfusion that are associated with considerable morbidity and mortality and
on the other hand acute anemia is associated with increased mortality.