Perioperative/Postoperative Complications Clinical Trial
Official title:
Haemostasis Management of Patients Undergoing Abdominal Aortic Procedures Associated With High Bleeding Risk
Comparative study on efficacy of haemostatic therapy guided either by standard laboratory
coagulation parameters or point-of-care testing in patients undergoing vascular surgical
procedures. We investigate the amount of perioperative bleeding and the number of blood
product used.
Inclusion criteria Patients scheduled for elective and acute open aorta surgery or undergoing
acute aorta surgery with minimally invasive techniques and were provided treatment in the
operating theatre and/or ICU attached to perioperative care, they must be at least 18 years
of age and written informed consent was obtained from the patient or his/her legal
representative.
Randomisation technique Patients will be randomly assigned to each of two treatment groups
using sealed envelopes. In group 1 (G1) haemostasis strategy guided by conventional
coagulation tests, while in group 2 (G2) transfusion algorithms guided by point-of-care (POC)
tests will be carried out.
Sampling techniques and measurements
For assessment of monitored parameters shall be used arterial or venous blood depending on
the catheter placed preoperatively. In case of the above mentioned vascular surgical
procedures, all patients will receive arterial cannula routinely, and, depending on the
extension of procedure, as appropriate, a central venous catheter will be inserted as well.
Sampling in the patient groups shall be performed as follows:
- pre- and postoperative evaluation of standard laboratory parameters in all patients
- evaluation of standard laboratory parameters and arterial Astrup test during and after
surgery in group 1, if the blood loss volume reaches 1,5 ml/kg/minute during 20 minutes
- in case of elective surgery: thromboelastometry and arterial Astrup test during and
after surgery in group 2 if the blood loss volume reaches 1,5 ml/kg/minute during 20
minutes
- in case of acute surgery: thromboelastometry and arterial Astrup test before, during and
after surgery in group 2
- in case of positive anamnesis, preoperative platelet aggregation test in both groups
Besides the above samplings, routine lab tests (blood gas, blood count, sodium (Na),
potassium (K), parameters of renal and liver function, clotting and inflammation, lactic
acid, blood sugar) will be performed every day as usual during intensive therapy.
Despite the fact that interventional therapy of vascular lesions (endovascular and hybrid
procedures) is becoming more and more common, angioplasties involving major vessels have to
be still managed as surgical procedures associated with extreme high demand for transfusion,
this applies especially to acute rupture of aortic aneurysm, aortic dissection,
aortobifemoral bypass and certain elective procedures where conventional open surgery is the
only therapeutic option. Due the generalised atherosclerosis typical for most vascular
surgical patients as well as the vulnerability of vessel wall, major blood loss has to be
taken in account even during elective surgeries with minimally invasive techniques. In the
event that excessive bleeding would occur, conversion to open surgery may be necessary, for
this reason the preparation and perioperative care of patients undergoing interventional
surgery have to be performed in the same manner as its is prescribed for open aorta
operations.
The bleeding risk associated with the above surgical procedures is increased by the fact that
the majority of patients affected are on a single or in some cases on double antiplatelet
therapy, and/or receive prolonged anticoagulation treatment. Discontinuation of the
treatments is expensive and, in case of indication for acute surgery, may not always be
carried out.
Previous bleeding history, current drug therapy, evaluation of coagulation status
(prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen) and
blood count screening using conventional laboratory tests are part of preoperative
preparations. Control of platelet function is always indicated in case of positive anamnesis
(inherited or acquired thrombocytopathy, anamnestic information on bleeding complication,
skin symptoms suggesting haemophilia), but is not performed routinely. Preoperative
normalization of possible abnormalities as well as optimalization of drugs affecting
haemostasis, so the reduction of bleeding risk to the minimum are of essential importance,
however, we do not always have enough time for it. In cardiovascular surgery, withdrawal of
aspirin and/or clopidogrel therapy increases the risk of thrombosis; continuation of aspirin
and/or clopidogrel therapy increases the risk of bleeding. In our own practice, in case of
elective vascular surgical procedures, aspirin therapy will be continued, but clopidogrel
will be stopped 5-7 days prior to surgery, according to the European recommendations. When a
patient with prolonged anticoagulant therapy is at high risk for embolism, his medication
will be switched to low molecular weight heparin. In case the surgery is performed under
ongoing antiplatelet therapy, transfusion of thrombocyte concentrate may also be necessary.
In the European guidelines, the application of transfusion algorithms and protocols
incorporating predefined intervention triggers to guide haemostatic intervention during
preoperative bleeding are recommended, as well as viscoelastic point-of-care tests (POCT). In
lack of the latter, the Hungarian recommendation suggests the application of conventional
monitoring assays, however, they give an poor assessment picture with associated with
significant time delay, therefore have to be considered inadequate in case of excessive
bleeding.
At first, it has to be definitely cleared whether the blood loss is caused by haemostatic or
surgical source. In the meantime, however, maintenance of normothermia, prevention of
acidosis and normalisation of ionized calcium level are of significant importance. In case of
active bleeding the targeted value of systolic blood pressure is 80-100 mmHg, that of
haemoglobin concentration 7-9 g/dl. The restrictive transfusion strategy is aimed at
decreasing the number of allogeneic transfusions which are regarded as a form of tissue
transplantation to the possible minimum.
The first step for optimal restoration of the function of haemostasis system has to be the
regulation of the concentration of fibrinogen in the blood plasma, using either conventional
laboratory tests or point-of-care testing. Fibrinogen is synthesized in the liver and will
not be stored; it has the highest concentration among all coagulation factors (3 g/l). During
blood loss, its concentration decreases and reaches the crucial level (<2 g/l) most rapidly.
It is essential that besides erythrocyte (RBC) concentrate fresh frozen plasma (FFP) has also
to be given (RBC:FFP=2:1) in a timely manner, in a fixed proportion. In case of excessive
blood loss and transfusion, administration of thrombocyte concentrate is also necessary.
Aim of the study Comparative study on efficacy of haemostatic therapy guided either by
standard laboratory parameters or point-of-care testing in patients undergoing vascular
surgical procedures.
Study design Prospective randomised clinical trial
Patients Inclusion criteria Patients scheduled for elective and acute open aorta surgery or
undergoing acute aorta surgery with minimally invasive techniques and were provided treatment
in the operating theatre and/or ICU attached to perioperative care, they must be at least 18
years of age and written informed consent was obtained from the patient or his/her legal
representative.
Randomisation technique:
Patients will be randomly assigned to each of two treatment groups using sealed envelopes:
- Patient group 1: haemostasis strategy guided by conventional coagulation tests.
- Patient group 2: transfusion algorithm guided by viscoelastic POC tests and algorithms.
Exclusion criteria:
- patients under 18 years of age
- informed consent not provided
- congenital coagulation factor deficiency
- congenital thrombocytopathy
Discontinuation criteria:
- death of patient
- withdrawal of consent by the patient or his/her relative
Assessment of parameters Conventional coagulation laboratory tests In the preanalytical phase
consisting of steps within and outside the laboratory we have to face a great number of
influence factors which can be of critical importance concerning the result of the lab test
(e.g. quality of blood sampling tube, method of sampling, appropriate amount of sample,
haemolysis, lipaemia). The time-consuming nature of these tests may cause problems primarily
in case of massive bleeding. It is not the same blood that circulates in the patient's
organism by the time we receive the result. Another disadvantage is that only a few steps of
coagulation cascade are investigated. The tests are performed using the plasma separated by
centrifugation of blood. Information regarding reactions on the surface of activated
platelets, fibrin polymerisation, clot firmness and fibrinolysis cannot be obtained.
Routinely monitored parameters:
- Prothrombin time (PT)/ International normalized ratio (INR): extrinsic coagulation
pathway and final common pathway.
- Activated partial thromboplastin time (aPTT): intrinsic coagulation pathway and final
common pathway.
- Thrombin Time (TI): reflects the speed of conversion of fibrinogen to fibrin.
- Fibrinogen: amount of fibrinogen in the blood plasma.
- Blood count (platelet number ) Point-of-care methods Point-of-care tests using whole
blood provide information within a short time, including the patient's haemostatic
status. These benefits are associated with many advantageous features such as small
place demand, simply use, no need of maintenance; centrifugation is not required, the
reagents are ready to use, some tests can be stored at room temperature.
Viscoelastic tests Viscoelastic tests used for global haemostasis assays are
thromboelastography (TEG) and rotational thromboelastometry (ROTEM). The original method has
been developed by Harter in 1948 in Heidelberg, initially for analysis of not anticoagulated
blood. Viscoelastic tests provide information on primary haemostasis (platelet adhesion and
aggregation), thrombin generation, thrombus formation and fibrinolysis, thus, on every steps
of haemostasis. Informative analysis in case of patients who are on prolonged heparin therapy
can also be accomplished.
Disadvantages of viscoelastic coagulation POC tests include indirectly obtained information
on the platelet function, furthermore, the role of endothelium is not recognizes and the
characteristics of blood flow are disregarded.
During TEG/ROTEM analysis a pin is dipped into a sample of whole blood - to be given in a
cuvette of not physiological surface - and the coagulation becomes activated. Cuvette and
sensor move relative to each other. In TEG, the movement is initiated from the cup, in ROTEM
the pin is oscillated and the cuvette remains fixed. Increasing viscosity of blood and
enhancing stability of clot being formed induce a change of elasticity. This process affects
the motion of the sensor that is detected by light reflection changes. The two methods are
equivalent and can be considered as mutual alternatives.
The tested parameters provide information on the starting time of clotting process, the clot
formation, stabilisation and quality as well as fibrinolysis.
The efficacy of viscoelastic POC tests have been confirmed by several clinical studies,
primarily in the field of cardiac surgery, liver transplantation, and traumatology. As per
the published data, the number of allogeneic transfusions and postoperative blood loss
decreased significantly.
Parameters of ROTEM analysis:
- Clotting time (CT): Time elapsed from beginning of test until the starting time of
clotting.
- Clot formation time (CFT): Time to reach 20 mm amplitude from the starting time of
clotting.
- Maximum clot firmness (MCF): Provides information on firmness of clot.
- Maximum lysis (ML): Provides information on loss of clot firmness.
Analysis of platelet aggregation Platelet aggregation inhibitors (e.g. aspirin
[acetylsalicylic acid], ticlopidine, clopidogrel), significantly decrease the aggregation
ability of platelets or may even completely terminate it. During examination, several
platelet aggregation agents will be added to the platelet-rich plasma prepared appropriately
and the aggregation induced this way will be measured using an impedance aggregometer. The
device measures the change of electric resistance between the two electrodes dipped into the
blood sample in relation to time.
Most commonly it is applied for adjustment of antiplatelet therapy and monitoring the
efficacy of the substance. It is suitable for highly sensitive detection of aspirin,
clopidogrel, prasugrel and IIb/IIIa-receptor antagonists.
Now there are literary data also in respect of its efficacy in respect of predicting the
probability of coronary stent thrombosis, as well as that of bleeding and the need of
transfusion in cardiac surgery. Still, it is not recommended to routinely use this device in
the perioperative care of any and all patients. At the same time, however, in case of
patients at risk (e.g. positive bleeding anamnesis, treatment with platelet-aggregation
inhibiting drugs) it is able to identify and to help diagnose a possible platelet
disfunction.
Routinely monitored parameter:
• Area Under the Curve (AUC): Indication of platelet activity. The results calculated by the
software are the mean values of data of the several curves.
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