title: What dose of tranexamic acid is most effective and safe for adult patients undergoing cardiac surgery?
abstract: A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: what dose of tranexamic acid is most effective and safe for adult patients undergoing cardiac surgery? Altogether 586 papers were found using the reported search, of which 12 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Current evidence shows clinical benefit of using high-dose tranexamic acid (>80 mg/kg total dose) as opposed to low-dose tranexamic acid (<50 mg/kg total dose) in cardiac surgery with cardiopulmonary bypass. Evidence from a large randomized controlled trial shows that patients receiving high-dose tranexamic acid lose less blood postoperatively than patients receiving low-dose tranexamic acid (590 vs 820 ml, P = 0.01). Patients receiving high-dose tranexamic acid also require fewer units of blood product transfusion (2.5 units vs 4.1 units; P = 0.02) and are less likely to undergo repeat surgery to achieve haemostasis. This effect is larger in those who are at high risk of bleeding. Several prospective studies comparing doses found no difference in clinical outcomes between high- and low-dose regimens, but excluded patients at high risk of bleeding. However, data from numerous observational studies demonstrate that tranexamic acid use is associated with an increased risk of postoperative seizure; one analysis showed tranexamic acid use to be a very strong independent predictor (odds ratio = 14.3, P < 0.001). There is also evidence that this risk of seizure is dose-dependent, with the greatest risk at higher doses of tranexamic acid. We conclude that, in general, patients with a high risk of bleeding should receive high-dose tranexamic acid, while those at low risk of bleeding should receive low-dose tranexamic acid with consideration given to potential dose-related seizure risk. We recommend the regimens of high-dose (30 mg kg(-1) bolus + 16 mg kg(-1) h(-1) + 2 mg kg(-1) priming) and low-dose (10 mg kg(-1) bolus + 1 mg kg(-1) h(-1) + 1 mg kg(-1) priming) tranexamic acid, as these are well established in terms of safety profile and have the strongest evidence for efficacy.
authors.affiliation: Department of Medical Sciences, University of Oxford, Oxford, UK samcbhodgson@gmail.com.
authors.forename: Sam
authors.initials: S
authors.lastname: Hodgson
authors.affiliation: Department of Medical Sciences, University of Oxford, Oxford, UK.
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Larvin
authors.affiliation: Department of Medical Sciences, University of Oxford, Oxford, UK.
authors.forename: Charles
authors.initials: C
authors.lastname: Dearman
mesh_terms: D000328:Adult; D000789:Angina, Unstable / Q000601:surgery; D000933:Antifibrinolytic Agents / Q000008:administration & dosage; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D001026:Coronary Artery Bypass; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D019106:Postoperative Hemorrhage / Q000517:prevention & control*; D014148:Tranexamic Acid / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000933:Antifibrinolytic Agents; D014148:Tranexamic Acid
keywords: Cardiac surgery; Cardiopulmonary bypass; Dose; Review; Seizure; Tranexamic acid