Comparative Study of Tranexamic Acid Dosing in Cardiac Surgery

Excessive bleeding and blood transfusions are common in patients undergoing cardiac surgery. Antifibrinolytic therapy reduces the risk of blood loss and transfusion among patients undergoing cardiac surgery. Tranexamic acid is an antifibrinolytic agent that forms a reversible complex with plasminogen. Guidelines for the management of bleeding in patients recommend the routine use of tranexamic acid for cardiac surgery in adults. However, there is no consensus regarding the dosage regimen of tranexamic acid that should be administered. More specifically, several dosage regimens have been studied in the literature. Although higher doses of tranexamic acid achieve a marginal reduction in postoperative bleeding, they increase the risk of drug-related postoperative complications. Based on a recent 2021 meta -analysis, it appears that lower doses of tranexamic acid (eg 20 mg / kg or 10mg/kg followed by 1mg kg-1 h-1) are safe and effective. In the literature, the duration of inhibition of fibrinolysis after the administration of tranexamic acid has been studied using the point of care test ClotPro (a thromboelastometry analyzer) in relatively large dosages (total dose: 50 mg / kg), while there are no relevant randomized clinical studies. Lower doses of tranexamic acid have been shown to be effective and safe, although their duration of action has not been studied using the viscoelastic Clot Pro-TPA test and their correlation with blood tranexamic acid concentration.

The present study aims to evaluate different dosages of tranexamic acid in cardiac surgery using cardiopulmonary bypass. The primary outcome is the duration of inhibition of fibrinolysis as measured by the ClotPro test and the correlation of imprinting with tranexamic blood concentration.

Methods:

Perioperative management will follow standard department practice. Patients for elective cardiac surgery using cardiopulmonary bypass will be randomized to receive tranexamic acid after induction of anesthesia at three different doses of 30 mg / kg , 20 mg / kg or 10 mg / kg followed by 1 mg / kg / h until the end of the surgery. All patients will sign an informed consent prior to their inclusion in the study.

Data collection:

During pre-operative evaluation, age, weight, height, sex, BSA, ASA classification, Euroscore II, standard perioperative laboratory testing results, medication and co-morbidities will be documented.

Intraoperatively, the duration of anesthesia, the type and duration of surgery, the cardiopulmonary bypass and aortic cross clamping time will be documented, as well as drugs administered and related adverse events.

At specified time points (during induction of anesthesia and before administration of the drug, after the completion of the single administration, after the end of the cardiopulmonary bypass, six and twelve hours after the administration of the drug and then twelve hours until the values ML and LT in the TPA test to be greater than 50% and less than 2100 sec respectively) blood samples will be taken from the arterial line placed in the patient. The purpose will be to perform viscoelastic tests (ClotPro , TPA test), to detect successful fibrinolysis inhibition and measure tranexamic acid levels in the patient's blood. In case the ML and LT values are as above before or at the six-hour sample, the patient will be given an additional 10 mg/kg and the measurements will be repeated.

Also, the total administration of blood and products, the administration of coagulation factors intraoperatively and during the ICU stay, as well as the total postoperative bleeding in the first 24 hours are recorded. The need for reoperation due to postoperative bleeding, seizures, and all serious adverse events related to surgery and general anesthesian and/or the tranexamic acid administration in the postoperative period are also recorded.

Postoperatively, the duration of mechanical ventilation and sedation in the Cardiac Surgery ICU, the length of stay in the Cardiac Surgery ICU, the length of stay in the Hospital before surgery and after discharge from the Cardiac Surgery ICU, and all - cause in hospital mortality will be recorded.

The present study aims to evaluate different dosages of tranexamic acid in cardiac surgery using cardiopulmonary bypass. It is a prospective, randomized, comparative study. The primary outcome is the duration of inhibition of fibrinolysis as measured by the ClotPro test and the correlation of imprinting with tranexamic blood concentration. Secondary outcomes are blood and blood product transfusion, need of coagulation factors administration, postoperative bleeding, time of mechanical ventilation, length of stay in the Intensive Care Unit (ICU), total length of hospitalization and all - cause in hospital mortality. Also, secondary outcomes include the correlation of tranexamic acid dosage with the postoperative incidence of seizures and thrombotic complications.

• transfusion of blood and products [Time frame: Ιntraoperatively and during the first 24 hours postoperatively]
• need of administration of coagulation factors [Time frame: intraoperatively and during the first 24 hours postoperatively]
• Postoperative bleeding [Time frame: During the first 24 hours postoperatively]
• reoperation [Time frame: From the end of surgery until the patient's discharge from the hospital or death (up to 1 year)]
• Mechanical ventilation [Time frame: From the end of surgery until the patient's extubation, or patient's death if not extubated. (up to 1 year)]
• Length of stay in the Intensive Care Unit [Time frame: From the end of surgery until the patient's discharge from the ICU, or patient's death if not discharged. (up to 1 year)]
• Length of hospitalization [Time frame: From the day of surgery until the patient's discharge from the hospital, or patient's death if not discharged. (up to 1 year)]
• All cause in-hospital mortality [Time frame: From the day of surgery until the patient's discharge from the hospital (up to 1 year)]
• postoperative incidence of seizures [Time frame: From the administration of tranexamic acid until the patient's discharge from the hospital (up to 1 month)]
• thrombotic episodes [Time frame: From the administration of tranexamic acid until the patient's discharge from the hospital. (up to one month)]