The effect on blood loss of topical and intravenous tranexamic acid in cardiac surgery patients: a randomized placebo-controlled trial

Antifibrinolytic drugs are used to reduce blood loss and exposure to
transfusion in patients undergoing cardiac surgery. Tranexamic acid is
indicated for blood conservation, to reduce total blood loss and decrease the
number of patients who require blood transfusion during cardiac surgery
procedures (class 1A evidence: recommendation that procedure or treatment is
useful/effective, sufficient evidence from multiple randomized trials or
meta-analyses). In our department (Amphia Hospital, Breda, the Netherlands),
during cardiac surgery 2 gr TA are administrated intravenously after induction
of anesthesia and 2 gr TA post cardiopulmonary bypass.
Patients with an increased incidence of thromboembolic events have an increased
risc of side effects by administration of topical TA. Patients with increased
or decreased bleeding tedency (see exclusion criteria), will not be included
In addition to systemic TA, a number of randomized studies have shown that
topical application of TA resulted in reduction in blood loss and blood
component transfusion. However, only one randomized controlled trial combined
intravenous TA with topical TA. Spegar et al. showed no difference in
post-operative blood loss, although, their patients required less fresh frozen
plasma, concluding that larger studies are needed.
The study by Bonis et al have shown that there is no systemic absortion of
tranexamic acid by topical administration.
The aim of this study is to determine whether the application of TA reduces
the12 hours post-operative blood loss by 25% after cardiac surgery on
cardiopulmonary bypass, whereby intravenous TA is administrated.

Primary Objective: the objective of this study is to determine whether the
application topical TA into the pericardial cavity just before sternal closure
reduces the 12 hours post-operative blood loss by 25% after cardiac surgery
patients on cardiopulmonary bypass, whereby intravenous TA is administrated.

Secondary Objective(s): in addition, this study is designed to compare the
amount of blood component transfusion (packed red blood cells, platelet
concentrate, Octoplas®, haemocomplettan®, cofact®), routine coagulation tests
variables (INR, aPTT, number of platelets, fibrinogen level, Hb/Ht) between the
three groups.
Furthermore the risk of thrombo-embolic events will be monitored between the
topical administration of TA with placebo. In addition, the secondary objective
of this study is to determine whether pericardial lavage with NaCl gives an
improvement in haemostasis, compared with no pericardial lavage, resulting in a
reduction of surgical re-explorations en post-operative 12-hour blood loss.

Design of the study is a randomized placebo-controlled trial. According to the
anaesthetic protocol, 2 gr of intravenous TA is given pre- and post
cardiopulmonary bypass in cardiac surgery patients. The dose range of topical
TA that has been administrated in earlier studies, is between 1 and 2.5 gr
diluted in 100 to 250 ml of saline. By means of a computer-generator 1:1:1
randomization table, one group receives pericardial lavage with 2 gr TA in 200
ml normothermic saline solution (NaCl 0.9%), the second group receives
pericardial lavage with 200 ml normothermic saline solution without TA and the
third group (control group) receives no pericardial lavage. The study solution
is for 1 minute administrated into the pericardial cavity and spread over
mediastinal tissues, to which it is then removed by the waste sucker.

By means of randomisation, subjects are divided into three groups:one group
receives pericardial lavage with 2 gr TA in 200 ml normothermic saline solution
(NaCl 0.9%), the second group receives pericardial lavage with 200 ml
normothermic saline solution without TA and the third group (control group)
receives no pericardial lavage. Study solution is topically applied after
surgical hemostasis, and just before closure metallic sternal suturing. The
study solution is for 1 minute administrated into the pericardial cavity and
spread over mediastinal tissues, to which it is then removed by the waste
sucker. The mediastinal and pleural tubes are suctioned at -15 cmH2O.

The burden and risks associated with participation on the study are none.
Patients with an increased incidence of thromboembolic events have an increased
risc of side effects by administration of topical TA. Patients with increased
or decreased bleeding tedency (see exclusion criteria), will not be included.
The study by Bonis et al have shown that there is no systemic absortion of
tranexamic acid by topical administration.
The number of blood samples, the number of site visits and other examinations
are equal in all groups. No additional tests will be performed as in standard
care.