Decreasing blood loss and the need for transfusion after CABG surgery: a double-blind randomized clinical trial of topical tranexamic acid

Turkish Journal of Medical Sciences Turk J Med Sci (2013) 43: 273-278 © TÜBİTAK doi:10.3906/sag-1206-37 http://journals.tubitak.gov.tr/medical/ Research Article Decreasing blood loss and the need for transfusion after CABG surgery: a double-blind randomized clinical trial of topical tranexamic acid 1 2, 1 Mahmoud NOURAEI , Afshin GHOLIPOUR BARADARI *, Rahman GHAFARI , 2 3 2 Mohammad Reza HABIBI , Amir EMAMI ZEYDI , Narges SHARIFI 1 Department of Surgery, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran 2 Department of Anesthesia and Critical Care, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran 3 Department of Nursing, Faculty of Nursing and Midwifery, Mazandaran University of Medical Sciences, Sari, Iran Received: 10.06.2012 Accepted: 07.08.2012 Published Online: 15.03.2013 Printed: 15.04.2013 Aim: Reopening sternotomy to control bleeding after coronary artery bypass grafting surgery (CABG) has been reported in 2%–7% of cases. Platelet dysfunction and activation of fibrinolytic cascade are the common causes of bleeding after on-pump CABG. Different antifibrinolytic drugs have been used to reduce bleeding. In this study, we aimed to investigate the efficacy of topical tranexamic acid in reducing postoperative mediastinal bleeding after CABG. Materials and methods: This was a double-blind placebo-controlled randomized clinical trial on 40 patients as the control and another 40 patients as the study group. On completion of CABG before sternotomy wound closure, tranexamic acid (2 g/20 mL) or placebo (20 mL of saline) was diluted in 500 mL of warm saline (37 °C), poured into the pericardial cavity, and left for 5 min. Results: There was no significant difference in baseline demographic data and laboratory results between the 2 groups (P > 0.05). Mediastinal bleeding and packed red cell transfusion requirements were significantly lower in the study group (P ≤ 0.01). There were no complications related to topical tranexamic such as mortality, myocardial infarction, cerebrovascular accident, seizure, or renal failure. Conclusion: Topical tranexamic acid can reduce mediastinal bleeding and packed red cell transfusion requirements after CABG. Key words: Bypass surgery, coronary artery, tranexamic acid, postoperative hemorrhage 1. Introduction Today, coronary artery diseases (CADs) are the most common causes of morbidity and mortality (1) and coronary artery bypass graft (CABG) surgery is a common intervention annually performed in more than 800,000 cases worldwide (2). Bleeding is a common complication after CABG. Excessive bleeding and blood transfusion play an important role in post-CABG mortality and morbidity (3–5). Patients undergoing cardiac surgery still receive more blood transfusions than in other surgical procedures, consuming 20% of blood bank reserves (6). Reopening sternotomy to control bleeding has been reported in 2%–7% of cases (7). Blood transfusion can cause infection and immunological reactions and increase hospital length stay and cost, which justifies all efforts to reduce bleeding after CABG (4). Activation of fibrinolytic cascade and platelet dysfunction have proven to have a major role in on-pump * Correspondence: CABG mediastinal bleeding (3). Fibrinolysis plays a major role in 25% to 45% of cases (7). Tranexamic acid is an antifibrinolytic agent that is substituted for more expensive drugs like aprotinin in recent years (3,4). It can be used both systemically and topically (5). Tranexamic acid binds to lysine binding sites of plasmin and plasminogen. Saturation of these sites displaces plasminogen from the fibrin surface, thus inhibiting fibrinolysis (7). Intravenous tranexamic acid can increase risk of thromboembolism and early graft occlusion (7). This drug has been used topically in patients with a bleeding tendency and in patients taking anticoagulation medication to reduce bleeding after surgery. Tranexamic acid also has been used topically in bladder, gynecology, and ear, nose, and throat operations successfully (7). Systemic complications and the higher expense of its intravenous use prompted us to investigate the efficacy of topical tranexamic acid to reduce blood loss after CABG surgery. 273 NOURAEI et al. / Turk J Med Sci 2. Materials and methods This was a double-blind placebo-controlled clinical trial on 80 patients undergoing CABG at the Mazandaran Heart Center, Sari, Iran. The study was approved by the ethics committee of the Mazandaran University of Medical Sciences (approval number: 8411) and registered in the Iranian Registry of Clinical Trials Database (IRCT138901243646N2). After giving informed consent, patients were randomly assigned to 2 equal groups of study and control by a third party. Patient inclusion criteria were first time on-pump elective CABG surgery with left ventricular ejection fraction of more than 35% and use of the left internal mammary artery with or without venous graft. Exclusion criteria include age of more than 75 years; advanced liver, kidney, lung, or severe peripheral vascular disease; internal carotid artery narrowing of >50%; recent myocardial infarction, New York Heart Association class 3 and 4; CABG with valve operation; insulin-dependent diabetes mellitus; reexploration; history of seizure disorder; hemoglobin (Hb) levels of <10 g/dL or hematocrit (Hct) levels of <30%; and anticoagulation usage 5 days before surgery. Anesthetic protocol, surgical procedures, and cardiopulmonary bypass management were similar in both groups. Patients were premedicated with promethazine (25 mg) and morphine (5 mg) intramuscular injections 1 h before entering the operating room. Anesthesia in all patients was based on moderate doses of fentanyl (20 to 30 µg/kg) and midazolam (0.05 to 0.15 mg/kg), supplemented with isoflurane (<1%) or propofol (hourly rate of 2.5 to 4.0 mg/kg) during cardiopulmonary bypass (CPB). Muscle relaxation was maintained with cisatracurium. Median sternotomy was performed in all patients, and CPB was instituted through cannulation of the ascending aorta and the right atrium. Aortic palpation was used to detect atherosclerosis and, if it was present, to select an appropriate site for cannulation and clamping. Heparin was given at an initial dose of 300 IU/kg to achieve an activated clotting time (ACT) of >480 s, and at the end of CPB it was reversed with a full dose of protamine chloride to achieve an ACT of <120 s. In all patients, blood-based St. Thomas’ Hospital cardioplegic (BSTH1) solutions at 12 °C were used for myocardial protection. Distal coronary anastomoses were completed with the proximal aorta cross-clamped and the heart arrested. For proximal aortic anastomoses, the aorta was partially clamped and the heart was beating. The CPB circuit lines were not heparin-coated and included a roller pump (Stöckert Instrumente, Munich, Germany), a hollow-fiber membrane oxygenator (Medtronic Inc., Minneapolis, USA), and a 34-µm scr (...truncated)