Can local application of Tranexamic acid reduce post-coronary bypass surgery blood loss? A randomized controlled trial

Research article Open Access Open Peer Review Can local application of Tranexamic acid reduce post-coronary bypass surgery blood loss? A randomized controlled trial Hosam Fawzy1Email author, Elsayed Elmistekawy1, Daniel Bonneau1, David Latter1 and Lee Errett1 Journal of Cardiothoracic Surgery20094:25 https://doi.org/10.1186/1749-8090-4-25 ©  Fawzy et al; licensee BioMed Central Ltd. 2009 Received: 10 April 2009Accepted: 18 June 2009Published: 18 June 2009 Open Peer Review reports Abstract Background Diffuse microvascular bleeding remains a common problem after cardiac procedures. Systemic use of antifibrinolytic reduces the postoperative blood loss. The purpose of this study was to examine the effectiveness of local application of tranexamic acid to reduce blood loss after coronary artery bypass grafting (CABG). Methods Thirty eight patients scheduled for primary isolated coronary artery bypass grafting were included in this double blind, prospective, randomized, placebo controlled study. Tranexamic acid (TA) group (19 patients) received 1 gram of TA diluted in 100 ml normal saline. Placebo group (19 patients) received 100 ml of normal saline only. The solution was purred in the pericardial and mediastinal cavities. Results Both groups were comparable in their baseline demographic and surgical characteristics. During the first 24 hours post-operatively, cumulative blood loss was significantly less in TA group (median of 626 ml) compared to Placebo group (median of 1040 ml) (P = 0.04). There was no significant difference in the post-op Packed RBCs transfusion between both groups (median of one unit in each) (P = 0.82). Significant less platelets transfusion required in TA group (median zero unit) than in placebo group (median 2 units) (P = 0.03). Apart from re-exploration for excessive surgical bleeding in one patient in TA group, no difference was found in morbidity or mortality between both groups. Conclusion Topical application of tranexamic acid in patients undergoing primary coronary artery bypass grafting led to a significant reduction in postoperative blood loss without adding extra risk to the patient. Keywords Coronary Artery Bypass GraftingTranexamic AcidLeave Internal Mammary ArteryChest Tube DrainageAminocaproic Acid Introduction Coagulopathy remains a common problem after coronary artery bypass Grafting (CABG) using cardiopulmonary bypass (CPB). It results from many factors like thrombocytopenia, acquired platelet dysfunction, clotting factors loss, free heparin, and increased fibrinolysis [1–3]. Lemmer and Colleagues [4] found that extracorporeal circulation results in significant fibrinolysis, as reflected by increased concentrations of plasmin and fibrin degradation products (FDP), both of which have deleterious effects on platelet function. Re-exploration for bleeding following cardiac surgery with CPB was reported to be in the range of 2–7%. Of these, 50–80% was found to be medical rather than surgical bleeding [5]. Fibrinolysis was found to be responsible for 25–45% of significant post bypass bleeding [6]. Many antifibrinolytic agents have been used to diminish post-bypass bleeding. These include ε Aminocaproic acid [5], aprotinin [7], and Tranexamic acid (TA) [8]. Tranexamic acid has been found to bind to lysine binding sites of plasmin and plasminogen. Saturation of these sites displaces plasminogen from the fibrin surface thus inhibiting fibrinolysis [9]. TA has been used both systemically and topically. Intravenous TA administration increased the risk of thromoembolic complications and consequently early graft closure in coronary artery bypass grafting [10]. When used topically, TA was found effective in controlling bleeding in patients with hemorrhagic diathesis and in patients who were being treated with anticoagulants pre-operatively. Topical TA has also been successfully used in controlling bleeding in bladder, gynaecologic, oral, and otolaryngeal surgeries [11–13]. This prospective, double-blind, randomized, placebo-controlled study was designed to investigate the effect of topical TA in reducing postoperative blood loss after coronary artery bypass Grafting. Methods With institutional ethics committee approval, all patients scheduled for primary isolated elective CABG at North West Armed Forces Hospital, Tabuk, Saudi Arabia, during the period from March 2004 to November 2005, were scrutinized for eligibility enrolment. Our exclusions criteria included patients who had combined procedure; redo surgery, bleeding diathesis (Haemophilia or platelet count < 100 × 109 L-1), renal failure (Creatinine > 160 mg/dl), known allergy to TA, recent (<7 days before surgery) intake of anti-platelets (e.g. Aspirin, non-steroidal anti-inflammatory drugs) or Heparin administration within 48 hours of operation. Thirty eight patients met the requirements for inclusion, and informed consent was obtained from all of them. The patients were randomly allocated into one of the two groups. Group I (TA group) included 19 patients who received 1 gm of TA diluted in 100 ml normal saline. Group II (Placebo group) included 19 patients who received 100 ml normal saline as placebo. The solution was purred in the pericardial and mediastinal cavities before closure of the strenotomy while clamping the chest tubes. These clamps were released once the closure of the strenotomy was completed. The study was carried out as a prospective randomized, double blind investigation. Randomization was carried out with random-number tables by a research pharmacist who prepared the two solutions in two identical bottles and delivered to the operating theatre. Neither the surgeon, assistant, anaesthetist, scrub nurse nor the perfusionist knew the composition of the solution administered. Only two cardiac surgeons were responsible for the surgical haemostasis. The anaesthetic management and conduct of CPB were standardized. The patients were premedicated using Nitrozepam 0.1 mg/kg tablet the night of the operation, and morphine 0.15 mg/kg intramuscular half an hour before operation. Induction was done using Fentanyl 2–5 ug/kg, Propofol 1–2 mg/kg, and Pancronium 0.1 mg/kg. Anaesthesia was maintained by using Sevoflurane 0.5–1%, Pancronium 0.06 mg/kg, Fentanyl 1–2 ug/kg during cardiopulmonary bypass time. All patients received Heparin 300 units/Kg before CPB to achieve target activated clotting time (ACT) of ≥ 480 seconds. During CPB, extra heparin was given as needed to maintain the target ACT. After separation from CPB, heparin was reversed using protamine sulphate in the dose of 1 mg/100 units of heparin to achieve target ACT 80–120 seconds. After the patient was transferred to the intensive care unit (ICU), continuous low grade suction (10–15 cm H2O) was applied together with periodic milking of the drains. Haemoglobin level (Hb), Hematocrite value (Hct %), Platelet count, International Normalized Ratio (INR), Partial Thrombop (...truncated)