Antifibrinolytic Therapy in Pediatric Congenital Heart Surgery

Chapter

Abstract

For decades, aprotinin was the standard antifibrinolytic drug used in adult and pediatric major surgery [1]. Numerous studies showed that the perioperative loss of blood, and thus the use of homologous blood, could be limited by administering aprotinin. Other antifibrinolytic-acting substances, such as e-aminocapronic acid (EACA) or tranexamic acid (TXA), tended to be misfits in routine clinical practice.

Keywords

Placebo Hydrolysis Toxicity Catheter Ischemia 

References

  1. 1.
    Levy JH, Ramsay JG, Guyton RA. Aprotinin in cardiac surgery. N Engl J Med. 2006;354:1953–7.PubMedCrossRefGoogle Scholar
  2. 2.
    Mangano DT, Tudor IC, Dietzel C. The risk associated with aprotinin in cardiac surgery. N Engl J Med. 2006;354:353–65.PubMedCrossRefGoogle Scholar
  3. 3.
    Fergusson DA, Hebert PC, Mazer CD, Fremes S, MacAdams C, Murkin JM, et al. A comparison of aprotinin and lysine analogues in high-risk cardiac surgery. N Engl J Med. 2008;358:2319–31.PubMedCrossRefGoogle Scholar
  4. 4.
    Andrew M, Vegh P, Johnston M, Bowker J, Ofosu F, Mitchell L. Maturation of the hemostatic system during childhood. Blood. 1992;80:1998–2005.PubMedGoogle Scholar
  5. 5.
    Monagle P. Thrombosis in pediatric cardiac patients. Semin Thromb Hemost. 2003;29:547–55.PubMedCrossRefGoogle Scholar
  6. 6.
    Monagle P, Barnes C, Ignjatovic V, Furmedge J, Newall F, Chan A, et al. Developmental haemostasis. Impact for clinical haemostasis laboratories. Thromb Haemost. 2006;95:362–72.PubMedGoogle Scholar
  7. 7.
    Monagle P, Ignjatovic V, Savoia H. Hemostasis in neonates and children: pitfalls and dilemmas. Blood Rev. 2010;24:63–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Monagle P, Massicotte P. Developmental haemostasis: secondary haemostasis. Semin Fetal Neonatal Med. 2011;16:294–300.PubMedCrossRefGoogle Scholar
  9. 9.
    Albisetti M. The fibrinolytic system in children. Semin Thromb Hemost. 2003;29:339–48.PubMedCrossRefGoogle Scholar
  10. 10.
    van Oeveren W, Jansen NJ, Bidstrup BP, Royston D, Westaby S, Neuhof H, et al. Effects of aprotinin on hemostatic mechanisms during cardiopulmonary bypass. Ann Thorac Surg. 1987;44:640–5.PubMedCrossRefGoogle Scholar
  11. 11.
    Royston D. Aprotinin therapy. Br J Anaesth. 1994;73:734–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Royston D. High-dose aprotinin therapy: a review of the first five years’ experience. J Cardiothorac Vasc Anesth. 1992;6:76–100.PubMedCrossRefGoogle Scholar
  13. 13.
    Verstraete M. Clinical application of inhibitors of fibrinolysis. Drugs. 1985;29:236–61.PubMedCrossRefGoogle Scholar
  14. 14.
    Green D, Ts’ao CH, Cerullo L, Cohen I, Ruo TI, Atkinson Jr AJ. Clinical and laboratory investigation of the effects of epsilon-aminocaproic acid on hemostasis. J Lab Clin Med. 1985;105:321–7.PubMedGoogle Scholar
  15. 15.
    Ratnoff OD. Epsilon aminocaproic acid–a dangerous weapon. N Engl J Med. 1969;280:1124–5.PubMedCrossRefGoogle Scholar
  16. 16.
    Zonis Z, Seear M, Reichert C, Sett S, Allen C. The effect of preoperative tranexamic acid on blood loss after cardiac operations in children. J Thorac Cardiovasc Surg. 1996;111:982–7.PubMedCrossRefGoogle Scholar
  17. 17.
    Andersson L, Nilsson IM, Liedberg G, Nilsson L, Rybo G, Eriksson O, et al. Antifibrinolytic drugs. Comparative studies on trans-4-(aminomethyl)-cyclohexane carbonic acid, aminocapronic acid and p-aminomethylbenzoic acid. Arzneimittelforschung. 1971;21:424–9.PubMedGoogle Scholar
  18. 18.
    Andersson L, Nilsson IM, Olow B. Fibrinolytic activity in man during surgery. Thromb Diath Haemorrh. 1962;7:391–403.PubMedGoogle Scholar
  19. 19.
    Soslau G, Horrow J, Brodsky I. Effect of tranexamic acid on platelet ADP during extracorporeal circulation. Am J Hematol. 1991;38:113–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Davies MJ, Allen A, Kort H, Weerasena NA, Rocco D, Paul CL, et al. Prospective, randomized, double-blind study of high-dose aprotinin in pediatric cardiac operations. Ann Thorac Surg. 1997;63:497–503.PubMedCrossRefGoogle Scholar
  21. 21.
    Williams GD, Ramamoorthy C, Pentcheva K, Boltz MG, Kamra K, Reddy VM. A randomized, controlled trial of aprotinin in ­neonates undergoing open-heart surgery. Paediatr Anaesth. 2008;18:812–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Carrel TP, Schwanda M, Vogt PR, Turina MI. Aprotinin in pediatric cardiac operations: a benefit in complex malformations and with high-dose regimen only. Ann Thorac Surg. 1998;66:153–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Murugesan C, Banakal SK, Garg R, Keshavamurthy S, Muralidhar K. The efficacy of aprotinin in arterial switch operations in infants. Anesth Analg. 2008;107:783–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Schouten ES, van de Pol AC, Schouten AN, Turner NM, Jansen NJ, Bollen CW. The effect of aprotinin, tranexamic acid, and aminocaproic acid on blood loss and use of blood products in major pediatric surgery: a meta-analysis. Pediatr Crit Care Med. 2009;10:182–90.PubMedCrossRefGoogle Scholar
  25. 25.
    Pasquali SK, Li JS, He X, Jacobs ML, O’Brien SM, Hall M, et al. Comparative analysis of antifibrinolytic medications in pediatric heart surgery. J Thorac Cardiovasc Surg. 2012;143:550–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Chauhan S, Bisoi A, Kumar N, Mittal D, Kale S, Kiran U, et al. Dose comparison of tranexamic acid in pediatric cardiac surgery. Asian Cardiovasc Thorac Ann. 2004;12:121–4.PubMedCrossRefGoogle Scholar
  27. 27.
    Levin E, Wu J, Devine DV, Alexander J, Reichart C, Sett S, et al. Hemostatic parameters and platelet activation marker expression in cyanotic and acyanotic pediatric patients undergoing cardiac surgery in the presence of tranexamic acid. Thromb Haemost. 2000;83:54–9.PubMedGoogle Scholar
  28. 28.
    van der Staak FH, de Haan AF, Geven WB, Festen C. Surgical repair of congenital diaphragmatic hernia during extracorporeal membrane oxygenation: hemorrhagic complications and the effect of tranexamic acid. J Pediatr Surg. 1997;32:594–9.PubMedCrossRefGoogle Scholar
  29. 29.
    Bulutcu FS, Ozbek U, Polat B, Yalcin Y, Karaci AR, Bayindir O. Which may be effective to reduce blood loss after cardiac operations in cyanotic children: tranexamic acid, aprotinin or a combination? Paediatr Anaesth. 2005;15:41–6.PubMedCrossRefGoogle Scholar
  30. 30.
    Schindler E, Photiadis J, Sinzobahamvya N, Dores A, Asfour B, Hraska V. Tranexamic acid: an alternative to aprotinin as antifibrinolytic therapy in pediatric congenital heart surgery. Eur J Cardiothorac Surg. 2011;39:495–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Edmunds Jr LH. Blood-surface interactions during cardiopulmonary bypass. J Card Surg. 1993;8:404–10.PubMedCrossRefGoogle Scholar
  32. 32.
    Despotis GJ, Joist JH. Anticoagulation and anticoagulation reversal with cardiac surgery involving cardiopulmonary bypass: an update. J Cardiothorac Vasc Anesth. 1999;13:18–29.PubMedGoogle Scholar
  33. 33.
    Edmunds Jr LH, Colman RW. Thrombin during cardiopulmonary bypass. Ann Thorac Surg. 2006;82:2315–22.PubMedCrossRefGoogle Scholar
  34. 34.
    Chan AK, Leaker M, Burrows FA, Williams WG, Gruenwald CE, Whyte L, et al. Coagulation and fibrinolytic profile of paediatric patients undergoing cardiopulmonary bypass. Thromb Haemost. 1997;77:270–7.PubMedGoogle Scholar
  35. 35.
    Mangano DT, Miao Y, Vuylsteke A, Tudor IC, Juneja R, Filipescu D, et al. Mortality associated with aprotinin during 5 years following coronary artery bypass graft surgery. JAMA. 2007;297:471–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Szekely A, Sapi E, Breuer T, Kertai MD, Bodor G, Vargha P, et al. Aprotinin and renal dysfunction after pediatric cardiac surgery. Paediatr Anaesth. 2008;18:151–9.PubMedCrossRefGoogle Scholar
  37. 37.
    Backer CL, Kelle AM, Stewart RD, Suresh SC, Ali FN, Cohn RA, et al. Aprotinin is safe in pediatric patients undergoing cardiac surgery. J Thorac Cardiovasc Surg. 2007;134:1421–6.PubMedCrossRefGoogle Scholar
  38. 38.
    Brown JR, Birkmeyer NJ, O’Connor GT. Meta-analysis comparing the effectiveness and adverse outcomes of antifibrinolytic agents in cardiac surgery. Circulation. 2007;115:2801–13.PubMedCrossRefGoogle Scholar
  39. 39.
    Breuer T, Martin K, Wilhelm M, Wiesner G, Schreiber C, Hess J, et al. The blood sparing effect and the safety of aprotinin compared to tranexamic acid in paediatric cardiac surgery. Eur J Cardiothorac Surg. 2009;35:167–71.PubMedCrossRefGoogle Scholar
  40. 40.
    Fodstad H. Convulsive seizures following subdural application of fibrin sealant containing tranexamic acid in a rat model. Neurosurgery. 2001;49:479–80.PubMedGoogle Scholar
  41. 41.
    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.CrossRefGoogle Scholar
  42. 42.
    Jaquiss RD, Ghanayem NS, Zacharisen MC, Mussatto KA, Tweddell JS, Litwin SB. Safety of aprotinin use and re-use in pediatric cardiothoracic surgery. Circulation. 2002;106:I90–4.PubMedGoogle Scholar
  43. 43.
    Furtmuller 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.PubMedCrossRefGoogle Scholar
  44. 44.
    Williams-Johnson JA, McDonald AH, Strachan GG, Williams EW. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2) a randomised, placebo-controlled trial. West Indian Med J. 2010;59:612–24.PubMedGoogle Scholar

Copyright information

© Springer-Verlag London 2013

Authors and Affiliations

  1. 1.Department for Pediatric AnesthesiologyGerman Pediatric Heart Center, Asklepios Klinik Sankt AugustinSankt AugustinGermany

Personalised recommendations