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氨甲环酸在接受冠状动脉手术患者中的应用
Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery


Paul S. Myles ... 心脑血管疾病 • 2017.01.12
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• 氨甲环酸真的是产科救命药吗

摘要


背景

氨甲环酸降低行心脏外科手术患者的出血危险,但目前尚不清楚这是否会导致结局的改善。而且,也有对氨甲环酸可能有促血栓和促抽搐作用的担心。


方法

在一项2×2析因设计的试验中,我们把预定接受冠状动脉手术并且有围手术期并发症风险的患者随机分配至阿司匹林或安慰剂组和氨甲环酸或安慰剂组。本文报道了氨甲环酸比较的结果。主要结局是复合指标手术后30日内的死亡和血栓并发症(非致死性心肌梗死、卒中、肺栓塞、肾衰竭或肠梗死)。


结果

在入选并提供知情同意书的4,662例患者中,4,631例经历了手术并有结局数据;2,311例被分配至氨甲环酸组,2,320例被分配至安慰剂组。氨甲环酸组中的386例患者(16.7%)和安慰剂组中的420例患者(18.1%)发生了主要结局事件(相对危险度为0.92;95%置信区间为0.81~1.05;P=0.22)。住院治疗期间输注的血液制品单位总数氨甲环酸组为4,331,安慰剂组为7,994(P<0.001)。氨甲环酸组和安慰剂组中分别有1.4%和2.8%的患者发生了严重出血或心脏压塞导致的再次手术(P=0.001),而惊厥的发生率分别为0.7%和0.1%(Fisher精确检验P=0.002)。


结论

在经历冠状动脉手术的患者中,氨甲环酸治疗与安慰剂相比具有更低的出血危险,手术后30日内的死亡或血栓并发症危险并没有更高。氨甲环酸与术后惊厥危险更高相关(由澳大利亚国家卫生和医学研究委员会[Australian National Health and Medical Research Council]等资助;ATACAS澳大利亚新西兰临床试验注册号为ACTRN12605000557639)。





作者信息

Paul S. Myles, M.P.H., M.D., Julian A. Smith, F.R.A.C.S., Andrew Forbes, Ph.D., Brendan Silbert, M.B., B.S., Mohandas Jayarajah, M.B., B.S., Thomas Painter, M.B., Ch.B., D. James Cooper, M.D., Silvana Marasco, Ph.D., John McNeil, Ph.D., Jean S. Bussières, M.D., Shay McGuinness, M.B., Ch.B., Kelly Byrne, M.B., Ch.B., Matthew T.V. Chan, M.B., B.S., Ph.D., Giovanni Landoni, M.D., and Sophie Wallace, M.P.H., for the ATACAS Investigators of the ANZCA Clinical Trials Network*
From the Alfred Hospital (P.S.M., D.J.C., S. Marasco, S.W.) and Monash University (P.S.M., J.A.S., A.F., D.J.C., S. Marasco, J.M., S.W.), Melbourne, VIC, St. Vincent’s Hospital, Fitzroy, VIC (B.S.), and the Royal Adelaide Hospital, Adelaide, SA (T.P.) — all in Australia; South West Cardiac Centre, Derriford Hospital, Plymouth, United Kingdom (M.J.); Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec, Canada (J.S.B.); Auckland City Hospital, Auckland (S. McGuinness), and Waikato Hospital, Hamilton (K.B.) — both in New Zealand; the Chinese University of Hong Kong, Hong Kong (M.T.V.C.); and Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele and Vita-Salute San Raffaele University, Milan (G.L.). Address reprint requests to Dr. Myles at the Department of Anaesthesia and Perioperative Medicine, Alfred Hospital, Commercial Rd., Melbourne, VIC 3004, Australia, or at p.myles@alfred.org.au. *A list of participating centers and investigators in the Aspirin and Tranexamic Acid for Coronary Artery Surgery (ATACAS) trial of the Australian and New Zealand College of Anaesthetists (ANZCA) Clinical Trials Network is provided in the Supplementary Appendix, available at NEJM.org

 

参考文献

1. Robich MP, Koch CG, Johnston DR, et al. Trends in blood utilization in United States cardiac surgical patients. Transfusion 2015;55:805-814

2. Biancari F, Mikkola R, Heikkinen J, Lahtinen J, Airaksinen KE, Juvonen T. Estimating the risk of complications related to re-exploration for bleeding after adult cardiac surgery: a systematic review and meta-analysis. Eur J Cardiothorac Surg 2012;41:50-55

3. Ranucci M, Bozzetti G, Ditta A, Cotza M, Carboni G, Ballotta A. Surgical reexploration after cardiac operations: why a worse outcome? Ann Thorac Surg 2008;86:1557-1562

4. Henry DA, Carless PA, Moxey AJ, et al. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev 2011:CD001886-CD001886

5. Ker K, Edwards P, Perel P, Shakur H, Roberts I. Effect of tranexamic acid on surgical bleeding: systematic review and cumulative meta-analysis. BMJ 2012;344:e3054-e3054

6. Alderman EL, Levy JH, Rich JB, et al. Analyses of coronary graft patency after aprotinin use: results from the International Multicenter Aprotinin Graft Patency Experience (IMAGE) trial. J Thorac Cardiovasc Surg 1998;116:716-730

7. Mangano DT, Tudor IC, Dietzel C. The risk associated with aprotinin in cardiac surgery. N Engl J Med 2006;354:353-365

8. Risch A, Dorscheid E, Stein G, Seyfert UT, Grundmann U. The effect of aprotinin and tranexamic acid on fibrinolysis and thrombin generation during cardiopulmonary bypass Anaesthesist 2000;49:279-285. (In German.)

9. Dentz ME, Slaughter TF, Mark JB. Early thrombus formation on heparin-bonded pulmonary artery catheters in patients receiving epsilon aminocaproic acid. Anesthesiology 1995;82:583-586

10. Garg J, Pinnamaneni S, Aronow WS, Ahmad H. ST elevation myocardial infarction after tranexamic acid: first reported case in the United States. Am J Ther 2014;21:e221-4

11. Stief TW. Tranexamic acid triggers thrombin generation. Hemost Lab 2009;2:73-82

12. 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;37:1375-1383

13. 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;110:350-353

14. Tsementzis SA, Meyer CH, Hitchcock ER. Cerebral blood flow in patients with a subarachnoid haemorrhage during treatment with tranexamic acid. Neurochirurgia (Stuttg) 1992;35:74-78

15. Baharoglu MI, Germans MR, Rinkel GJ, et al. Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev 2013:CD001245-CD001245

16. Myles PS, Smith J, Knight J, et al. Aspirin and Tranexamic Acid for Coronary Artery Surgery (ATACAS) Trial: rationale and design. Am Heart J 2008;155:224-230

17. Myles PS, Smith JA, Forbes A, et al. Stopping vs. continuing aspirin before coronary artery surgery. N Engl J Med 2016;374:728-737

18. Dowd NP, Karski JM, Cheng DC, et al. Pharmacokinetics of tranexamic acid during cardiopulmonary bypass. Anesthesiology 2002;97:390-399

19. Sharma V, Katznelson R, Jerath A, et al. The association between tranexamic acid and convulsive seizures after cardiac surgery: a multivariate analysis in 11 529 patients. Anaesthesia 2014;69:124-130

20. Manji RA, Grocott HP, Leake J, et al. Seizures following cardiac surgery: the impact of tranexamic acid and other risk factors. Can J Anaesth 2012;59:6-13

21. Keyl C, Uhl R, Beyersdorf F, 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

22. Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. Circulation 2012;126:2020-2035

23. Thielmann M, Massoudy P, Schmermund A, et al. Diagnostic discrimination between graft-related and non-graft-related perioperative myocardial infarction with cardiac troponin I after coronary artery bypass surgery. Eur Heart J 2005;26:2440-2447

24. Mohammed AA, Agnihotri AK, van Kimmenade RR, et al. Prospective, comprehensive assessment of cardiac troponin T testing after coronary artery bypass graft surgery. Circulation 2009;120:843-850

25. Fransen EJ, Diris JH, Maessen JG, Hermens WT, van Dieijen-Visser MP. Evaluation of “new” cardiac markers for ruling out myocardial infarction after coronary artery bypass grafting. Chest 2002;122:1316-1321

26. Grassin-Delyle S, Tremey B, Abe E, et al. Population pharmacokinetics of tranexamic acid in adults undergoing cardiac surgery with cardiopulmonary bypass. Br J Anaesth 2013;111:916-924

27. Fergusson DA, Hébert PC, Mazer CD, et al. A comparison of aprotinin and lysine analogues in high-risk cardiac surgery. N Engl J Med 2008;358:2319-2331

28. Sigaut S, Tremey B, Ouattara A, et al. Comparison of two doses of tranexamic acid in adults undergoing cardiac surgery with cardiopulmonary bypass. Anesthesiology 2014;120:590-600

29. Goldstone AB, Bronster DJ, Anyanwu AC, et al. Predictors and outcomes of seizures after cardiac surgery: a multivariable analysis of 2,578 patients. Ann Thorac Surg 2011;91:514-518

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