Safety and Effectiveness of two treatment regimes with tranexamic acid to minimize inflammatory response in elective cardiopulmonary bypass patients: A randomized double-blind, dose-dependent, phase IV clinical trial

Journal of Cardiothoracic Surgery

Volumn 6, Issue 1, 2011, Pages

  Jiménez, Juan J ^a   Iribarren, José L ^a   Brouard, Maitane ^a   Hernández, Domingo ^b   Palmero, Salomé ^a   Jiménez, Alejandro ^a   Lorente, Leonardo ^a   Machado, Patricia ^a   Borreguero, Juan M ^a   Raya, José M ^a   Martín, Beatriz ^a   Pérez, Rosalía ^a   Martínez, Rafael ^a   Mora, María L ^a  

^a HOSPITAL UNIVERSITARIO DE CANARIAS   (Spain)

^b HOSPITAL REGIONAL UNIVERSITARIO DE MÁLAGA   (Spain)

Author keywords

Bleeding; Cardiac surgery; Cardiopulmonary bypass; Fibrinolysis; Inflammatory response; Tranexamic acid

Indexed keywords

EID: 80053999848     PISSN: None     EISSN: 17498090     Source Type: Journal    
DOI: 10.1186/1749-8090-6-138     Document Type: Article

References (32)

1. Munoz JJ, Birkmeyer NJ, Birkmeyer JD, O'Connor GT, Dacey LJ. Is epsilon-aminocaproic acid as affective as aprotinin in reducing bleeding with cardiac surgery? A meta-analysis. Circulation 1999, 99:81-89.
2. Dunn CJ, Goa KL. Tranexamic acid: a review of its use in surgery and other indications. Drugs 1999, 57:1005-1032. 10.2165/00003495-199957060-00017, 10400410.
3. Robson SC, Shephard EG, Kirsch RE. Fibrin degradation product D-dimer induces the synthesis and release of biologically active IL-1 beta, IL-6 and plasminogen activator inhibitors from monocytes in vitro. Br J Haematol 1994, 86:322-326. 10.1111/j.1365-2141.1994.tb04733.x, 8199021.
4. Laffey JG, Boylan JF, Cheng DC. The systemic inflammatory response to cardiac surgery: implications for the anesthesiologist. Anesthesiology 2002, 97:215-252. 10.1097/00000542-200207000-00030, 12131125.
5. Greilich PE, Brouse CF, Whitten CW, Chi L, Dimaio JM, Jessen ME. Antifibrinolytic therapy during cardiopulmonary bypass reduces proinflammatory cytokine levels: a randomized, double-blind, placebo-controlled study of epsilon-aminocaproic acid and aprotinin. J Thorac Cardiovasc Surg 2003, 126:1498-1503. 10.1016/S0022-5223(03)00946-2, 14666025.
6. Jimenez JJ, Iribarren JL, Lorente L, Rodriguez JM, Hernandez D. Tranexamic acid attenuates inflammatory response in cardiopulmonary bypass surgery through blockade of fibrinolysis: a case control study followed by a randomized double-blind controlled trial. Critical Care 2007, 11:R117. 10.1186/cc6173, 2246206, 17988379.
7. Koster A, Schirmer U. Re-evaluation of the role of antifibrinolytic therapy with lysine analogs during cardiac surgery in the post aprotinin era. Curr Opin Anaesthesiol 2011, 24:92-97. 10.1097/ACO.0b013e32833ff3eb, 20881484.
8. Sander M, Spies CD, Martiny V, Rosenthal C, Wernecke KD, 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. 10.1186/cc9216, 2945131, 20682059.
9. Martin K, Wiesner G, Breuer T, Lange R, Tassani P. The risk of aprotinin and tranexamic acid in cardiac surgery: a one-year follow-up of 1188 consecutive patients. Anesth Analg 2008, 107:1783-1790. 10.1213/ane.0b013e318184bc20, 19020118.
10. Murkin JM, Falter F, Granton J, Young B, Burt C, Chu M. High-Dose tranxamic acid is associated with nonischemic clinical seizures in cardiac surgical patients. Anesth Analg 2010, 110:350-353. 10.1213/ANE.0b013e3181c92b23, 19996135.
11. Moher D, Schulz KF, Altman DG. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials. Lancet 2001, 357:1191-1194. 10.1016/S0140-6736(00)04337-3, 11323066.
12. Karski JM, Dowd NP, Joiner R, Carroll J, Peniston C, Bailey K, Glynn MF, Teasdale SJ, Cheng DC. The effect of three different doses of Tranexamic acid on blood loss after cardiac surgery with mild systemic hypothermia (32 degrees C). J Cardiothorac Vasc Anesth 1998, 12:642-646. 10.1016/S1053-0770(98)90235-X, 9854660.
13. Horrow JC, Van Riper DF, Strong MD, Grunewald KE, Parmet JL. The dose-response relationship of Tranexamic acid. Anesthesiology 1995, 82:383-392. 10.1097/00000542-199502000-00009, 7856897.
14. Dowd NP, Karski JM, Cheng DC, Carroll JA, Lin Y, James RL, Butterworth J. Pharmacokinetics of Tranexamic acid during cardiopulmonary bypass. Anesthesiology 2002, 97:390-399. 10.1097/00000542-200208000-00016, 12151929.
15. Bellomo R, Kellum JA, Ronco C. Defining and classifying acute renal failure: from advocacy to consensus and validation of the RIFLE criteria. Intensive Care Medicine 2007, 33:409-413. 10.1007/s00134-006-0478-x, 17165018.
16. Meng QH, Zhu S, Sohn N, Mycyk T, Shaw SA, Dalshaug G, Krahn J. Release of cardiac biochemical and inflammatory markers in patients on cardiopulmonary bypass undergoing coronary artery bypass grafting. J Card Surg 2008, 23:681-687.
17. Roth-Isigkeit A, Hasselbach L, Ocklitz E, Brückner S, Ros A, Gehring H, Schmucker P, Rink L, Seyfarth M. Inter-individual differences in cytokine release in patients undergoing cardiac surgery with cardiopulmonary bypass. Clin Exp Immunol 2001, 125:80-88. 10.1046/j.1365-2249.2001.01521.x, 1906109, 11472429.
18. Jansen PM, Boermeester MA, Fischer E, de Jong IW, van der Poll T, Moldawer LL, Hack CE, Lowry SF. Contribution of interleukin-1 to activation of coagulation and fibrinolysis, neutrophil degranulation, and the release of secretory-type phospholipase A2 in sepsis: studies in nonhuman primates alter interleukin-1 alpha administration and during lethal bacteremia. Blood 1995, 86:1027-1034.
19. Reinartz J, Hansch GM, Kramer MD. Complement component C7 is a plasminogen-binding protein. J Immunol 1995, 154:844-850.
20. Syrovets T, Jendrach M, Rohwedder A, Schule A, Simmet T. Plasmin-induced expression of cytokines and tissue factor in human monocytes involves AP-1 and IKKbeta-mediated NFkappaB activation. Blood 2001, 97:3941-3950. 10.1182/blood.V97.12.3941, 11389038.
21. Li Q, Laumonnier Y, Syrovets T, Simmet T. Plasmin Triggers Cytokine Induction in Human Monocyte-Derived Macrophages. Arterioscler Thromb Vasc Biol 2007, 27:1383-1389. 10.1161/ATVBAHA.107.142901, 17413040.
22. Bouter H, Schippers EF, Luelmo SA, Versteegh MI, Ros P, Guiot HF, Frölich M, van Dissel JT. No effect of preoperative selective gut decontamination on endotoxemia and cytokine activation during cardiopulmonary bypass: a randomized, placebo-controlled study. Crit Care Med 2002, 30:38-43. 10.1097/00003246-200201000-00006, 11905407.
23. Neri M, Cerretani D, Fiaschi AI, Laghi PF, Lazzerini PE, Maffione AB, Micheli L, Bruni G, Nencini C, Giorgi G, D'Errico S, Fiore C, Pomara C, Riezzo I, Turillazzi E, Fineschi V. Correlation between cardiac oxidative stress and myocardial pathology due to acute and chronic norepinephrine administration in rats. J Cell Mol Med 2007, 11:156-170. 10.1111/j.1582-4934.2007.00009.x, 17367510.
24. Wan S, LeClerc JL, Vincent JL. Cytokine Responses to Cardiopulmonary Bypass: Lessons Learned From Cardiac Transplantation. Ann Thorac Surg 1997, 63:269-276. 10.1016/S0003-4975(96)00931-9, 8993291.
25. Hennein HA, Ebba H, Rodriguez JL, Merrick SH, Keith FM, Bronstein MH, Leung JM, Mangano DT, Greenfield LJ, Rankin JS. Relationship of the proinflammatory cytokines to myocardial ischemia and dysfunction after uncomplicated coronary revascularization. J Thorac Cardiovasc Surg 1994, 108:626-635.
26. Mebazaa A, Pitsis AA, Rudiger A, Toller W, Longrois D, Ricksten SE, Bobek I, De Hert S, Wieselthaler G, Schirmer U, von Segesser LK, Sander M, Poldermans D, Ranucci M, Karpati PC, Wouters P, Seeberger M, Schmid ER, Weder W, Follath F. Clinical review: practical recommendations on the management of perioperative heart failure in cardiac surgery. Crit Care 2010, 14:201. 10.1186/cc8153, 2887098, 20497611.
27. Levy B, Perez P, Perny J, Thivilier C, Gerard A. Comparison of norepinephrine-dobutamine to epinephrine for hemodynamics, lactate metabolism, and organ function variables in cardiogenic shock. A prospective, randomized pilot study. Crit Care Med 2011, 39:450-455. 10.1097/CCM.0b013e3181ffe0eb, 21037469.
28. Kuepper F, Dangas G, Mueller-Chorus A, Kulka PM, Zenz M, Wiebalck A. Fibrinolytic activity and bleeding after cardiac surgery with cardiopulmonary bypass and low-dose aprotinin therapy. Blood Coagul Fibrinolysis 2003, 14:147-153. 10.1097/00001721-200302000-00005, 12632024.
29. Beattie WS, Karkouti K. The post-BART anti-fibrinolytic dilemma?. J Cardiothorac Vasc Anaesth 2011, 25:3-5.
30. 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. 10.1159/000115131, 6893025.
31. Furtmuller R, Schlag MG, Berger M, Hopf R, Huck S, Sieghart W, Redl H. Tranexamic acid, a widely used antifibrinolytic agent, causes convulsions by a gamma-aminobutiric acid(A) receptorantagonistic effect. J Pharmacol Exp Ther 2002, 301:168-73. 10.1124/jpet.301.1.168, 11907171.
32. Oakes DA, Mangano CT. Cardiopulmonary bypass in 2009: Achieving and circulating best practices. Anaesth Analg 2009, 108:1368-1370.