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BMC Anesthesiology
Published in: BMC Anesthesiology 1/2019

Open Access 01-12-2019 | Heart Surgery | Research article

Different dose regimes and administration methods of tranexamic acid in cardiac surgery: a meta-analysis of randomized trials

Authors: Jingfei Guo, Xurong Gao, Yan Ma, Huran Lv, Wenjun Hu, Shijie Zhang, Hongwen Ji, Guyan Wang, Jia Shi

Published in: BMC Anesthesiology | Issue 1/2019

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Abstract

Background

The efficacy of tranexamic acid (TXA) to reduce perioperative blood loss and allogeneic blood transfusion in cardiac surgeries has been proved in previous studies, but its adverse effects especially seizure has always been a problem of concern. This meta-analysis aims to provide information on the optimal dosage and delivery method which is effective with the least adverse outcomes.

Methods

We searched Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE for all relevant articles published before 2018/12/31. Inclusion criteria were adult patients undergoing elective heart surgeries, and only randomized control trials comparing TXA with placebo were considered. Two authors independently assessed trial quality and extracted relevant data.

Results

We included 49 studies with 10,591 patients into analysis. TXA significantly reduced transfusion rate (RR 0.71, 95% CI 0.65 to 0.78, P<0.00001). The overall transfusion rate was 35%(1573/4477) for patients using TXA and 49%(2190/4408) for patients in the control group. Peri-operative blood loss (MD − 246.98 ml, 95% CI − 287.89 to − 206.06 ml, P<0.00001) and re-operation rate (RR 0.62, 95% CI 0.49 to 0.79, P<0.0001) were also reduced significantly. TXA usage did not increase risk of mortality, myocardial infarction, stroke, pulmonary embolism and renal dysfunction, but was associated with a significantly increase in seizure attack (RR 3.21, 95% CI 1.04 to 9.90, P = 0.04).The overall rate of seizure attack was 0.62%(21/3378) for patients using TXA and 0.15%(5/3406) for patients in the control group.
In subgroup analysis, TXA was effective for both on-pump and off-pump surgeries. Topical application didn’t reduce the need for transfusion requirement, while intravenous delivery no matter as bolus injection alone or bolus plus continuous infusion were effective. Intravenous high-dose TXA didn’t further decrease transfusion rate compared with low-dose regimen, and increased the risk of seizure by 4.83 times. No patients in the low-dose group had seizure attack.

Conclusions

TXA was effective in reducing transfusion requirement in all kinds of cardiac surgeries. Low-dose intravenous infusion was the most preferable delivery method which was as effective as high-dose regimen in reducing transfusion rate without increasing the risk of seizure.
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Literature
1.
Faught C, Wells P, Fergusson D, Laupacis A. Adverse effects of methods for minimizing perioperative allogeneic transfusion: a critical review of the literature. Transfus Med Rev. 1998;12(3):206–25.PubMedCrossRef
2.
Henry DA, Carless PA, Moxey AJ, O’Connell D, Stokes BJ, Fergusson DA, et al. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev. 2011;(3):Cd001886.
3.
Baharoglu MI, Germans MR, Rinkel GJ, Algra A, Vermeulen M, van Gijn J, et al. Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev. 2013;(8):Cd001245.
4.
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(6):1375–83.PubMedCrossRef
5.
Murkin JM, Falter F, Granton J, Young B, Burt C, Chu M. High-dose tranexamic acid is associated with nonischemic clinical seizures in cardiac surgical patients. Anesth Analg. 2010;110(2):350–3.PubMedCrossRef
6.
Myles PS, Smith JA, Forbes A, Silbert B, Jayarajah M, Painter T, et al. Tranexamic acid in patients undergoing coronary-artery surgery. N Engl J Med. 2017;376(2):136–48.PubMedCrossRef
7.
Andersson L, Nilsoon IM, Colleen S, Granstrand B, Melander B. Role of urokinase and tissue activator in sustaining bleeding and the management thereof with EACA and AMCA. Ann N Y Acad Sci. 1968;146(2):642–58.PubMedCrossRef
8.
Soslau G, Horrow J, Brodsky I. Effect of tranexamic acid on platelet ADP during extracorporeal circulation. Am J Hematol. 1991;38(2):113–9.PubMedCrossRef
9.
Grassin-Delyle S, Tremey B, Abe E, Fischler M, Alvarez JC, Devillier P, et al. Population pharmacokinetics of tranexamic acid in adults undergoing cardiac surgery with cardiopulmonary bypass. Br J Anaesth. 2013;111(6):916–24.PubMedCrossRef
10.
Dowd NP, Karski JM, Cheng DC, Carroll JA, Lin Y, James RL, et al. Pharmacokinetics of tranexamic acid during cardiopulmonary bypass. Anesthesiology. 2002;97(2):390–9.PubMedCrossRef
11.
12.
Zhang Y, Gao X, Yuan S, Guo J, Lv H, Zhou Y, et al. Effects of tranexamic acid on short-term and long-term outcomes of on-pump coronary artery bypass grafting: randomized trial and 7-year follow-up. 2018;36(6):e12472.
13.
Mirmohammadsadeghi A, Mirmohammadsadeghi M, Kheiri M. Does topical tranexamic acid reduce postcoronary artery bypass graft bleeding? J Res Med Sci. 2018;23:6.PubMedPubMedCentralCrossRef
14.
Chaudhary FA, Pervaz Z, Ilyas S, Niaz MN. Topical use of tranexamic acid in open heart surgery. J Pak Med Assoc. 2018;68(4):538–42.PubMed
15.
16.
Shah MUA, Asghar MI, Siddiqi R, Chaudhri MS, Janjua AM, Iqbal A. Topical application of tranexamic acid reduces postoperative bleeding in open-heart surgery: myth or fact? J Coll Physicians Surg Pak. 2015;25(3):161–5.
17.
Hosseini H, Rahimianfar AA, Abdollahi MH, Moshtaghiyoon MM, Haddadzadeh M, Fekri A, et al. Evaluations of topical application of tranexamic acid on post-operative blood loss in off-pump coronary artery bypass surgery. Saudi J Anaesth. 2014;8(2):224–8.PubMedPubMedCentralCrossRef
18.
Alizadeh Ghavidel A, Totonchi Z, Chitsazan M, Dehaki MG, Jalili F, Farsad F, et al. Safety and efficacy of caproamin fides and tranexamic acid versus placebo in patients undergoing coronary artery revascularization. J Cardiovasc Thorac Res. 2014;6(3):197–202.PubMedPubMedCentralCrossRef
19.
Shi J, Ji H, Ren F, Wang G, Xu M, Xue Y, et al. Protective effects of tranexamic acid on clopidogrel before coronary artery bypass grafting: a multicenter randomized trial. JAMA Surg. 2013;148(6):538–47.PubMedCrossRef
20.
Nouraei M, Gholipour Baradari A, Ghafari R, Habibi MR, Emami Zeydi A, Sharifi N. Decreasing blood loss and the need for transfusion after CABG surgery: a double-blind randomized clinical trial of topical tranexamic acid. Turk J Med Sci. 2013;43(2):273–8.
21.
22.
23.
Hassani E, Mahoori A, Mehdizadeh H, Noroozinia H, Aghdashi MM, Saeidi M. The effects of tranexamic acid on postoperative bleeding in coronary artery bypass graft surgery. Tehran Univ Med J. 2012;70(3):176–82.
24.
25.
Aoki M, Okawa Y, Goto Y, Ogawa S, Baba H. Local administration of tranexamic acid in off-pump coronary artery bypass. Asian Cardiovasc Thorac Ann. 2012;20(6):658–62.PubMedCrossRef
26.
Ahn SW, Shim JK, Youn YN, Song JW, Yang SY, Chung SC, et al. Effect of tranexamic acid on transfusion requirement in dual antiplatelet-treated anemic patients undergoing off-pump coronary artery bypass graft surgery-a randomized controlled study. Circ J. 2012;76(1):96–101.PubMedCrossRef
27.
Hashemi J, Ghaffari Nejad MH, Baharestani B, Esfandiari R, Panahipoor A. Evaluation and comparison of use of low-dose aprotinin and tranexamic acid in CABG: a double-blind, prospective, randomized study of 150 patients. Iran Heart J. 2011;12(1):40–4.
28.
Baric D, Unic D, Rudez I, Bacic-Vrca V, Planinc M, Jonjic D, et al. Systemic usage of tranexamic acid is superior to topical: randomized placebo-controlled trial. Interact Cardiovasc Thorac Surg. 2011;12:S92.
29.
Taghaddomi RJ, Mirzaee A, Attar AS, Shirdel A. Tranexamic acid reduces blood loss in off-pump coronary artery bypass surgery. J Cardiothorac Vasc Anesth. 2009;23(3):312–5.PubMedCrossRef
30.
Later AFL, Maas JJ, Engbers FHM, Versteegh MIM, Bruggemans EF, Dion RAE, et al. Tranexamic acid and aprotinin in low- and intermediate-risk cardiac surgery: a non-sponsored, double-blind, randomised, placebo-controlled trial. Eur J Cardiothorac Surg. 2009;36(2):322–9.PubMedCrossRef
31.
Fawzy H, Elmistekawy E, Bonneau D, Latter D, Errett L. Can local application of tranexamic acid reduce post-coronary bypass surgery blood loss? A randomized controlled trial. J Cardiothorac Surg. 2009;4:25.PubMedPubMedCentralCrossRef
32.
Maddali MM, Rajakumar MC. Tranexamic acid and primary coronary artery bypass surgery: a prospective study. Asian Cardiovasc Thorac Ann. 2007;15(4):313–9.PubMedCrossRef
33.
Baric D, Biocina B, Unic D, Sutlic Z, Rudez I, Vrca VB, et al. Topical use of antifibrinolytic agents reduces postoperative bleeding: a double-blind, prospective, randomized study. Eur J Cardiothorac Surg. 2007;31(3):366–71 discussion 71.PubMedCrossRef
34.
Murphy GJ, Mango E, Lucchetti V, Battaglia F, Catapano D, Rogers CA, et al. A randomized trial of tranexamic acid in combination with cell salvage plus a meta-analysis of randomized trials evaluating tranexamic acid in off-pump coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2006;132(3):475–80 80.e1–8.PubMedCrossRef
35.
Mehr-Aein A, Sadeghi M, Madani-Civi M. Does tranexamic acid reduce blood loss in off-pump coronary artery bypass? Acta Med Iran. 2006;44(5):309–15.
36.
Abul-Azm A, Abdullah KM. Effect of topical tranexamic acid in open heart surgery. Eur J Anaesthesiol. 2006;23(5):380–4.PubMedCrossRef
37.
Diprose P, Herbertson MJ, O'Shaughnessy D, Deakin CD, Gill RS. Reducing allogeneic transfusion in cardiac surgery: a randomized double-blind placebo-controlled trial of antifibrinolytic therapies used in addition to intra-operative cell salvage. Br J Anaesth. 2005;94(3):271–8.PubMedCrossRef
38.
Casati V, Della Valle P, Benussi S, Franco A, Gerli C, Baili P, et al. Effects of tranexamic acid on postoperative bleeding and related hematochemical variables in coronary surgery: comparison between on-pump and off-pump techniques. J Thorac Cardiovasc Surg. 2004;128(1):83–91.PubMedCrossRef
39.
Andreasen JJ, Nielsen C. Prophylactic tranexamic acid in elective, primary coronary artery bypass surgery using cardiopulmonary bypass. Eur J Cardiothorac Surg. 2004;26(2):311–7.PubMedCrossRef
40.
Pleym H, Stenseth R, Wahba A, Bjella L, Karevold A, Dale O. Single-dose tranexamic acid reduces postoperative bleeding after coronary surgery in patients treated with aspirin until surgery. Anesth Analg. 2003;96(4):923–8 table of contents.PubMedCrossRef
41.
Jares M, Vanek T, Straka Z, Brucek P. Tranexamic acid reduces bleeding after off-pump coronary artery bypass grafting. J Cardiovasc Surg. 2003;44(2):205–8.
42.
Zabeeda D, Medalion B, Sverdlov M, Ezra S, Schachner A, Ezri T, et al. Tranexamic acid reduces bleeding and the need for blood transfusion in primary myocardial revascularization. Ann Thorac Surg. 2002;74(3):733–8.PubMedCrossRef
43.
Uozaki Y, Watanabe G, Kotou K, Ueyama K, Doi Y, Misaki T. Effect of tranexamic acid on blood loss reduction after cardiopulmonary bypass. Jpn J Thorac Cardiovasc Surg = Nihon Kyobu Geka Gakkai zasshi. 2001;49(5):273–8.PubMedCrossRef
44.
Kamada K, Yamakage M, Niiya T, Tsujiguchi N, Chen X, Namiki A. Celite-activated viscometer Sonoclot can measure the suppressive effect of tranexamic acid on hyperfibrinolysis in cardiac surgery. J Anesth. 2001;15(1):17–21.PubMedCrossRef
45.
Casati V, Gerli C, Franco A, Torri G, D'Angelo A, Benussi S, et al. Tranexamic acid in off-pump coronary surgery: a preliminary, randomized, double-blind, placebo-controlled study. Ann Thorac Surg. 2001;72(2):470–5.PubMedCrossRef
46.
Armellin G, Casella S, Guzzinati S, Pasini L, Marcassa A, Giron G. Tranexamic acid in aortic valve replacement. J Cardiothorac Vasc Anesth. 2001;15(3):331–5.PubMedCrossRef
47.
De Bonis M, Cavaliere F, Alessandrini F, Lapenna E, Santarelli F, Moscato U, et al. Topical use of tranexamic acid in coronary artery bypass operations: a double-blind, prospective, randomized, placebo-controlled study. J Thorac Cardiovasc Surg. 2000;119(3):575–80.PubMedCrossRef
48.
Misfeld M, Dubbert S, Eleftheriadis S, Siemens HJ, Wagner T, Sievers HH. Fibrinolysis-adjusted perioperative low-dose aprotinin reduces blood loss in bypass operations. Ann Thorac Surg. 1998;66(3):792–9.PubMedCrossRef
49.
Hardy JF, Bélisle S, Dupont C, Harel F, Robitaille D, Roy M, et al. Prophylactic tranexamic acid and epsilon-aminocaproic acid for primary myocardial revascularization. Ann Thorac Surg. 1998;65(2):371–6.PubMedCrossRef
50.
Pinosky ML, Kennedy DJ, Fishman RL, Reeves ST, Alpert CC, Ecklund J, et al. Tranexamic acid reduces bleeding after cardiopulmonary bypass when compared to epsilon aminocaproic acid and placebo. J Card Surg. 1997;12(5):330–8.PubMedCrossRef
51.
Landymore RW, Murphy JT, Lummis H, Carter C. The use of low-dose aprotinin, epsilon-aminocaproic acid or tranexamic acid for prevention of mediastinal bleeding in patients receiving aspirin before coronary artery bypass operations. Eur J Cardiothorac Surg. 1997;11(4):798–800.PubMedCrossRef
52.
Brown RS, Thwaites BK, Mongan PD. Tranexamic acid is effective in decreasing postoperative bleeding and transfusions in primary coronary artery bypass operations: a double-blind, randomized, placebo-controlled trial. Anesth Analg. 1997;85(5):963–70.PubMedCrossRef
53.
Shore-Lesserson L, Reich DL, Vela-Cantos F, Ammar T, Ergin MA. Tranexamic acid reduces transfusions and mediastinal drainage in repeat cardiac surgery. Anesth Analg. 1996;83(1):18–26.PubMedCrossRef
54.
Katsaros D, Petricevic M, Snow NJ, Woodhall DD, Van Bergen R. Tranexamic acid reduces postbypass blood use: a double-blinded, prospective, randomized study of 210 patients. Ann Thorac Surg. 1996;61(4):1131–5.PubMedCrossRef
55.
Speekenbrink RGH, Vonk ABA, Wildevuur CRH, Eijsman L. Hemostatic efficacy of dipyridamole, tranexamic acid, and aprotinin in coronary bypass grafting. Ann Thorac Surg. 1995;59(2):438–42.PubMedCrossRef
56.
Rousou JA, Engelman RM, Flack JE, Deaton DW, Owen SG. Tranexamic acid significantly reduces blood loss associated with coronary revascularization. Ann Thorac Surg. 1995;59(3):671–5.PubMedCrossRef
57.
Pugh SC, Wielogorski AK. A comparison of the effects of tranexamic acid and low-dose aprotinin on blood loss and homologous blood usage in patients undergoing cardiac surgery. J Cardiothorac Vasc Anesth. 1995;9(3):240–4.PubMedCrossRef
58.
De Peppo AP, Pierri MD, Scafuri A, De Paulis R, Colantuono G, Caprara E, et al. Intraoperative antifibrinolysis and blood-saving techniques in cardiac surgery: prospective trial of 3 antifibrinolytic drugs. Tex Heart Inst J. 1995;22(3):231–6.
59.
Ali IM, Landymore RW. The use of tranexamic acid in cardiac operations [10]. J Thorac Cardiovasc Surg. 1994;107(5):1377.PubMed
60.
Couture P, Lebon JS, Laliberte E, Desjardins G, Chamberland ME, Ayoub C, et al. Low-dose versus high-dose tranexamic acid reduces the risk of nonischemic seizures after cardiac surgery with cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 2017;31(5):1611–7.PubMedCrossRef
61.
Takagi H, Ando T, Umemoto T. Seizures associated with tranexamic acid for cardiac surgery: a meta-analysis of randomized and non-randomized studies. J Cardiovasc Surg. 2017;58(4):633–41.
62.
63.
Spegar J, Vanek T, Snircova J, Fajt R, Straka Z, Pazderkova P, et al. Local and systemic application of tranexamic acid in heart valve surgery: a prospective, randomized, double blind LOST study. J Thromb Thrombolysis. 2011;32(3):303–10.PubMedCrossRef
64.
Imtiaz A, Mujahid ul I, Ansa I, Azmat Ali S. Effects of bolus dose and continuous infusion of tranexamic acid on blood loss after coronary artery bypass grafting. J Ayub Med Coll Abbottabad 2014;26(3):371–375.
65.
Dincq AS, Michaux I, Lacrosse D, Collard E, Jamart J. High-dose versus low-dose of tranexamic acid in cardiac surgical patients receiving aspirin until surgery. J Cardiothorac Vasc Anesth. 2010;24(3):S36.CrossRef
66.
Du Y, Xu J, Wang G, Shi J, Yang L, Shi S, et al. Comparison of two tranexamic acid dose regimens in patients undergoing cardiac valve surgery. J Cardiothorac Vasc Anesth. 2014;28(5):1233–7.PubMedCrossRef
67.
Jiménez JJ, Iribarren JL, Brouard M, Hernández D, Palmero S, Jiménez A, et al. 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. J Cardiothorac Surg. 2011;6:138.PubMedPubMedCentralCrossRef
68.
Karski JM, Dowd NP, Joiner R, Carroll J, Peniston C, Bailey K, et al. 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(6):642–6.PubMedCrossRef
69.
Lambert W, Brisebois FJ, Wharton TJ, Carrier RC, Boyle D, Rowe BH. The effectiveness of low dose tranexamic acid in primary cardiac surgery. Can J Anaest = Journal canadien d'anesthesie. 1998;45(6):571–4.CrossRef
70.
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(3):590–600.PubMedCrossRef
71.
Karski JM, Teasdale SJ, Norman P, Carroll J, VanKessel K, Wong P, et al. Prevention of bleeding after cardiopulmonary bypass with high-dose tranexamic acid. Double-blind, randomized clinical trial. J Thorac Cardiovasc Surg. 1995;110(3):835–42.PubMedCrossRef
72.
Waldow T, Szlapka M, Haferkorn M, Bürger L, Plötze K, Matschke K. Prospective clinical trial on dosage optimizing of tranexamic acid in non-emergency cardiac surgery procedures. Clin Hemorheol Microcirc. 2013;55(4):457–68.PubMed
73.
Sharma V, Fan J, Jerath A, Pang KS, Bojko B, Pawliszyn J, et al. Pharmacokinetics of tranexamic acid in patients undergoing cardiac surgery with use of cardiopulmonary bypass. Anaesthesia. 2012;67(11):1242–50.PubMedCrossRef
Metadata
Title
Different dose regimes and administration methods of tranexamic acid in cardiac surgery: a meta-analysis of randomized trials
Authors
Jingfei Guo
Xurong Gao
Yan Ma
Huran Lv
Wenjun Hu
Shijie Zhang
Hongwen Ji
Guyan Wang
Jia Shi
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Anesthesiology / Issue 1/2019
Electronic ISSN: 1471-2253
DOI
https://doi.org/10.1186/s12871-019-0772-0

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