Seizures associated with tranexamic acid for cardiac surgery: A meta-analysis of randomized and non-randomized studies

Journal of Cardiovascular Surgery

Volumn 58, Issue 4, 2017, Pages 633-641

  Takagi, Hisato ^a   Ando, Tomo ^b   Umemoto, Takuya ^a  

^a SHIZUOKA MEDICAL CENTER   (Japan)

^b DETROIT MEDICAL CENTER   (United States)

Author keywords

Cardiac surgical procedures; Meta analysis; Seizures; Tranexamic acid

Indexed keywords

ACETYLSALICYLIC ACID; AMINOCAPROIC ACID; APROTININ; PLACEBO; TRANEXAMIC ACID; ANTIFIBRINOLYTIC AGENT;

AORTIC STENOSIS; AORTIC VALVE REPLACEMENT; CARDIOPULMONARY BYPASS; COMPUTER ASSISTED TOMOGRAPHY; CORONARY ARTERY BYPASS GRAFT; HEART SURGERY; HUMAN; LOW DRUG DOSE; META ANALYSIS; NUCLEAR MAGNETIC RESONANCE IMAGING; OBSERVATIONAL STUDY; OPERATIVE BLOOD LOSS; PROPENSITY SCORE; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SEIZURE; SENSITIVITY ANALYSIS; SYSTEMATIC REVIEW; ADOLESCENT; ADULT; ADVERSE EFFECTS; AGED; BLOOD LOSS, SURGICAL; CHEMICALLY INDUCED; CHI SQUARE DISTRIBUTION; FEMALE; MALE; MIDDLE AGED; ODDS RATIO; RISK ASSESSMENT; RISK FACTOR; TREATMENT OUTCOME; VERY ELDERLY; YOUNG ADULT;

ADOLESCENT; ADULT; AGED; AGED, 80 AND OVER; ANTIFIBRINOLYTIC AGENTS; BLOOD LOSS, SURGICAL; CARDIAC SURGICAL PROCEDURES; CHI-SQUARE DISTRIBUTION; FEMALE; HUMANS; MALE; MIDDLE AGED; OBSERVATIONAL STUDIES AS TOPIC; ODDS RATIO; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RISK ASSESSMENT; RISK FACTORS; SEIZURES; TRANEXAMIC ACID; TREATMENT OUTCOME; YOUNG ADULT;

EID: 85020442210     PISSN: 00219509     EISSN: None     Source Type: Journal    
DOI: 10.23736/S0021-9509.17.09877-9     Document Type: Review

References (39)

1. Ngaage DL, Bland JM. Lessons from aprotinin: is the routine use and inconsistent dosing of tranexamic acid prudent? Meta-analysis of randomised and large matched observational studies. Eur J Cardiothorac Surg 2010; 37:1375-83.
2. McCormack PL. Tranexamic acid: a review of its use in the treatment of hyperfibrinolysis. Drugs 2012; 72:585-617.
3. Sharma V, Katznelson R, Jerath A, Garrido-Olivares L, Carroll J, Rao V, et al. The association between tranexamic acid and convulsive seizures after cardiac surgery: a multivariate analysis in 11,529 patients. Anaesthesia 2014; 69:124-30.
4. Koster A, Börgermann J, Zittermann A, Lueth JU, Gillis-Januszewski T, Schirmer U. Moderate dosage of tranexamic acid during cardiac surgery with cardiopulmonary bypass and convulsive seizures: incidence and clinical outcome. Br J Anaesth 2013; 110:34-40.
5. Manji RA, Grocott HP, Leake J, Ariano RE, Manji JS, Menkis AH, et al. Seizures following cardiac surgery: the impact of tranexamic acid and other risk factors. Can J Anaesth 2012; 59:6-13.
6. Kalavrouziotis D, Voisine P, Mohammadi S, Dionne S, Dagenais F. High-dose tranexamic acid is an independent predictor of early seizure after cardiopulmonary bypass. Ann Thorac Surg 2012; 93:148-54.
7. Keyl C, Uhl R, Beyersdorf F, Stampf S, Lehane C, Wiesenack C, et al. High-dose tranexamic acid is related to increased risk of generalized seizures after aortic valve replacement. Eur J Cardiothorac Surg 2011; 39:e114-21.
8. Goldstone AB, Bronster DJ, Anyanwu AC, Goldstein MA, Filsoufi F, Adams DH, et al. Predictors and outcomes of seizures after cardiac surgery: a multivariable analysis of 2,578 patients. Ann Thorac Surg 2011; 91:514-8.
9. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994; 50:1088-101.
10. Egger M, Davey Smith G, Schneider M, Minder C. Bias in metaanalysis detected by a simple, graphical test. BMJ 1997; 315:629-34.
11. Myles PS, Smith JA, Forbes A, Silbert B, Jayarajah M, Painter T, et al.; ATACAS Investigators of the ANZCA Clinical Trials Network. Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery. N Engl J Med 2017; 376:136-48.
12. Faraoni D, Cacheux C, Van Aelbrouck C, Ickx BE, Barvais L, Levy JH. Effect of two doses of tranexamic acid on fibrinolysis evaluated by thromboelastography during cardiac surgery: a randomised, controlled study. Eur J Anaesthesiol 2014; 31:491-8.
13. Makhija N, Sarupria A, Kumar Choudhary S, Das S, Lakshmy R, Kiran U. Comparison of epsilon aminocaproic acid and tranexamic acid in thoracic aortic surgery: clinical efficacy and safety. J Cardiothorac Vasc Anesth 2013; 27:1201-7.
14. Jiménez JJ, Iribarren JL, Brouard M, Hernández D, Palmero S, Jiménez A, et al. Safety and effectiveness of two treatment regimens with tranexamic acid to minimize inflammatory response in elective cardiopulmonary bypass patients: a randomized double-blind, dose-dependent, phase IV clinical trial. J Cardiothorac Surg 2011; 6:138.
15. Santos AT, Kalil RA, Bauemann C, Pereira JB, Nesralla IA. A randomized, double-blind, and placebo-controlled study with tranexamic acid of bleeding and fibrinolytic activity after primary coronary artery bypass grafting. Braz J Med Biol Res 2006; 39:63-9.
16. Falana O, Patel G. Efficacy and safety of tranexamic acid versus e-aminocaproic acid in cardiovascular surgery. Ann Pharmacother 2014; 48:1563-9.
17. Martin K, Knorr J, Breuer T, Gertler R, Macguill M, Lange R, et al. Seizures after open heart surgery: comparison of e-aminocaproic acid and tranexamic acid. J Cardiothorac Vasc Anesth 2011; 25:20-5.
18. Berman M, Cardone D, Sharpies L, Vuylsteke A, Klein A, Gerrard C, et al. Safety and efficacy of aprotinin and tranexamic acid in pulmonary endarterectomy surgery with hypothermia: review of 200 patients. Ann Thorac Surg 2010; 90:1432-6.
19. Bell D, Marasco S, Almeida A, Rowland M. Tranexamic Acid in cardiac surgery and postoperative seizures: a case report series. Heart Surg Forum 2010; 13:E257-9.
20. Sander M, Spies CD, Martiny V, Rosenthal C, Wernecke KD, von Heymann C. Mortality associated with administration of high-dose tranexamic acid and aprotinin in primary open-heart procedures: a retrospective analysis. Crit Care 2010; 14:R148.
21. Martin K, Wiesner G, Breuer T, Lange R, Tassani P. The risks of aprotinin and tranexamic acid in cardiac surgery: a one-year follow-up of 1188 consecutive patients. Anesth Analg 2008; 107:1783-90.
22. Duval S, Tweedie R. Trim and fill: A simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 2000; 56:455-63.
23. Lin Z, Xiaoyi Z. Tranexamic acid-associated seizures: A meta-analysis. Seizure 2016; 36:70-3.
24. Menkis AH, Martin J, Cheng DC, Fitzgerald DC, Freedman JJ, Gao C, et al. Drug, devices, technologies, and techniques for blood management in minimally invasive and conventional cardiothoracic surgery: a consensus statement from the International Society for Minimally Invasive Cardiothoracic Surgery (ISMICS) 2011. Innovations (Phila) 2012; 7:229-41.
25. Mangano DT, Tudor IC, Dietzel C.; Multicenter Study of Perioperative Ischemia Research Group.; Ischemia Research and Education Foundation. The risk associated with aprotinin in cardiac surgery. N Engl J Med 2006; 354:353-65.
26. Karkouti K, Beattie WS, Dattilo KM, McCluskey SA, Ghannam M, Hamdy A, et al. A propensity score case-control comparison of aprotinin and tranexamic acid in high-transfusion-risk cardiac surgery. Transfusion 2006; 46:327-38.
27. Ng W, Jerath A, Wąsowicz M. Tranexamic acid: a clinical review. Anaesthesiol Intensive Ther 2015; 47:339-50.
28. Fergusson DA, Hébert PC, Mazer CD, Fremes S, MacAdams C, Murkin JM, et al.; BART Investigators. A comparison of aprotinin and lysine analogues in high-risk cardiac surgery. N Engl J Med 2008; 358:2319-31.
29. Lecker I, Wang DS, Whissell PD, Avramescu S, Mazer CD, Orser BA. Tranexamic acid-associated seizures: Causes and treatment. Ann Neurol 2016; 79:18-26.
30. Schlag MG, Hopf R, Zifko U, Redl H. Epileptic seizures following cortical application of fibrin sealants containing tranexamic acid in rats. Acta Neurochir (Wien) 2002; 144:63-9.
31. Pellegrini A, Giaretta D, Chemello R, Zanotto L, Testa G. Feline generalized epilepsy induced by tranexamic acid (AMCA). Epilepsia 1982; 23:35-45.
32. Yamaura A, Nakamura T, Makino H, Hagihara Y. Cerebral complication of antifibrinolytic therapy in the treatment of ruptured intracranial aneurysm. Animal experiment and a review of literature. Eur Neurol 1980; 19:77-84.
33. Lecker I, Wang DS, Romaschin AD, Peterson M, Mazer CD, Orser BA. Tranexamic acid concentrations associated with human seizures inhibit glycine receptors. J Clin Invest 2012; 122:4654-66.
34. Kratzer S, Irl H, Mattusch C, Bürge M, Kurz J, Kochs E, et al. Tranexamic acid impairs γ-aminobutyric acid receptor type A-mediated synaptic transmission in the murine amygdala: a potential mechanism for drug-induced seizures? Anesthesiology 2014; 120:639-49.
35. Furtmüller R, Schlag MG, Berger M, Hopf R, Huck S, Sieghart W, et al. Tranexamic acid, a widely used antifibrinolytic agent, causes convulsions by a gamma-aminobutyric acid (A) receptor antagonistic effect. J Pharmacol Exp Ther 2002; 301:168-73.
36. Hodgson S, Larvin JT, Dearman C. What dose of tranexamic acid is most effective and safe for adult patients undergoing cardiac surgery? Interact Cardiovasc Thorac Surg 2015; 21:384-8.
37. Sigaut S, Tremey B, Ouattara A, Couturier R, Taberlet C, Grassin-Delyle S, et al. Comparison of two doses of tranexamic acid in adults undergoing cardiac surgery with cardiopulmonary bypass. Anesthesiology 2014; 120:590-600.
38. Sterne JA, Egger M, Moher D, editors. Chapter 10: Addressing reporting biases. In: Higgins JP, Green S, editors. Cochrane Handbook for Systematic Reviews of Intervention Version 5.1.0 (updated March 2011). The Cochrane Collaboration; 2011. Available from: www.co-chrane-handbook.org.
39. Sutton AJ, Duval SJ, Tweedie RL, Abrams KR, Jones DR. Empirical assessment of effect of publication bias on meta-analyses. BMJ 2000; 320:1574-7.