Optimized Heparin Regimen in Vascular Surgery
Condition: Peripheral Revascularisation
Study type: Interventional

Summary: 
      Hypothesis: Optimal anticoagulation defined as an Activated Clotting Time (ACT) of 300 to 350
      seconds obtained by weight-adjusted doses of unfractionated heparin (UFH) will improve the
      hemostatic environment downstream from the vascular clamp, provide better blood flow in the
      distal bed following peripheral revascularization surgery.

      Objectives: This study is designed to assess the effects of an optimized regimen of UFH on
      the hemostatic environment downstream from the vascular clamp in major vascular surgery.
    

Detailed description: 
      Peripheral revascularization surgery is usually performed in high-risk patients, suffering
      from major comorbidities. Complications associated with vascular surgery include coronary
      problems, arrhythmias, failure of revascularization and thrombosis. In order to prevent these
      complications and possible re-interventions it is essential to optimize the intraoperative
      path.

      Unfractionated heparin is commonly used during arterial vascular surgery to prevent
      thrombosis and accumulation of thrombi at the surgical site. UFH is administered before
      clamping and blood flow interruption. However, the best heparin regimen to achieve optimal
      anticoagulation for peripheral revascularization remains unknown, with current
      recommendations based on data from the coronary literature and guidelines. Few studies have
      assessed the effect of vascular clamping and blood flow interruption on the anticoagulation
      in the distal vascular bed.

      Perioperative monitoring of coagulation is important to diagnose potential causes of
      hemorrhage and guide hemostatic therapies. Routine laboratory-based coagulation tests such as
      prothrombin time (PT), International Normalized Ratio (INR), activated partial thromboplastin
      time (aPTT) and platelet count are used to assess the patient's coagulation status. However,
      the value of these tests has been questioned in the acute perioperative setting for the
      following reasons: substantial delays between blood sampling and results, tests performed on
      plasma rather than whole blood and lack of information on platelet function.

      The activated clotting time (ACT) is used to monitor anticoagulation and, indirectly,
      concentrations of UFH. The ACT is measured on whole blood in cuvettes containing high
      concentrations of activators, typically celite or kaolin. Modern methods are completely
      automated. ACT measurement with point-of-care devices is used during procedures requiring
      anticoagulation, such as cardiopulmonary bypass, interventional cardiology and hemodialysis.
      In vascular surgery, the target ACT is not clearly defined and therefore not systematically
      monitored.

      Thromboelastography (TEG) is a bedside coagulation test that enables evaluation of all
      components of hemostasis. An advantage of TEG over conventional tests of hemostasis is that
      it is performed on whole blood, taking into consideration the role of interacting blood
      elements. The TEG can also be adapted to different clinical situations. Activators such as
      tissue factor, celite and thrombin can be added to whole blood to accelerate the analysis.
      TEG cups coated with heparinase can also be used to degrade heparin without affecting other
      coagulation parameters.

      Ankle-brachial (ABI) and toe-brachial (TBI) indexes are currently used to evaluate patients
      with peripheral arterial disease. These non-invasive tests provide information about
      peripheral blood flow. The ankle-brachial index is the ratio of the systolic blood pressure
      at the ankle to that measured at the brachial artery. The diagnostic limits of the ABI have
      been confirmed in several large-scale studies. Conditions associated with medial
      calcifications, such as diabetes, chronic kidney disease or advanced age, can lead to false
      results due to vessel stiffness. The toe vessels are less susceptible to vessel stiffness,
      which makes the TBI useful.

      Methods:

      Monitoring and postoperative analgesia will be left to the discretion of the attending
      anesthesiologist. Surgery will be performed under general or regional anesthesia. For safety
      reasons, patients under regional anesthesia will automatically be assigned to receive a fixed
      dose of heparin.

      UFH will be administered 2 minutes prior to vascular clamping according to randomization.
      Blood samples will be collected at the following time points for ACT and TEG analysis:
      following induction of anesthesia, 30 minutes after heparin administration, and on arrival in
      the recovery room. Heparin will be neutralized with protamine if needed.

      Intraoperative blood losses will be recorded. Administration of crystalloids, colloids and
      blood products during surgery will be noted. Blood samples to assess cardiac troponin levels
      will be collected in the recovery room and on the day following surgery. Ankle-brachial and
      toe-brachial indexes will be measured preoperatively and postoperatively in the recovery
      room. The occurrence of cardiovascular complications will be noted during the hospital stay.
      The incidence of vascular re-interventions will be noted 30 days following surgery.
    

Intervention name(s): ACT; TEG; Ankle-brachial index; Toe-brachial index; Heparin
Intervention type(s): Procedure; Procedure; Procedure; Procedure; Drug
Intervention description(s): Blood samples for ACT will be collected following induction of anesthesia, 30 minutes after heparin administration, and on arrival in the recovery room.; Blood samples for TEG will be collected following induction of anesthesia, 30 minutes after heparin administration, and on arrival in the recovery room.; Peripheral blood flow will be assessed prior and after surgery using the ankle-brachial and toe-brachial indexes.; Peripheral blood flow will be assessed prior and after surgery using the ankle-brachial and toe-brachial indexes.; Heparin doses will be administered according to the assigned group.
Other intervention name(s): Activated clotting time; Thromboelastography; Unfractionated heparin
Intervention MeSH terms: Heparin; Calcium heparin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment