Antifibrinolíticos e cirurgia cardíaca com circulação extracorpórea / Antifibrinolytics and cardiac surgery with cardiopulmonary bypass

JUSTIFICATIVA E OBJETIVOS: A cirurgia cardíaca é a especialidade cirúrgica que com mais freqüência está associada a sangramento, coagulopatia e necessidade de derivados de sangue. Os agentes farmacológicos aprotinina, ácido epsilon-aminocapróico e ácido tranexâmico são os mais utilizados para auxiliar na hemostasia dos pacientes submetidos à circulação extracorpórea. O objetivo deste trabalho foi apresentar a fisiopatologia do sangramento em cirurgia cardíaca e a atual situação dos antifibrinolíticos quanto à sua eficácia e complicações quando usados nesses procedimentos, dando maior ênfase ao ácido tranexâmico e à aprotinina. CONTEUDO: São discutidos os mecanismos pelos quais a circulação extracorpórea provoca alteração na hemostasia e de que maneira os antifibrinolíticos agem para diminuir o sangramento e o uso de sangue alogênico em cirurgia cardíaca. É dada ênfase ao problema do tromboembolismo que pode ocorrer com o emprego desses antifibrinolíticos, com revisão da literatura. CONCLUSÃO: A fibrinólise é um dos principais fatores relacionados com o aumento do sangramento em cirurgia cardíaca com circulação extracorpórea. A inibição da fibrinólise, juntamente com a preservação da função plaquetária, é, provavelmente, o mecanismo pelo qual os antifibrinolíticos diminuem o sangramento. O emprego desses fármacos reduz o sangramento em cirurgia cardíaca com circulação extracorpórea num percentual que pode chegar a 50 por cento. Com relação à preocupação com o tromboembolismo, os ácidos tranexâmico e epsilon-aminocapróico são opções que oferecem maior segurança que a aprotinina.

BACKGROUND AND OBJECTIVES: Cardiac surgery is the surgical subspecialty most often associated with bleeding, bleeding disorders, and the need of blood products. Agents such as aprotinin, episilon-aminocaproic acid, and tranexamic acid are frequently used to aid the hemostasis of patients undergoing cardiopulmonary bypass. The objective of this report is to present the physiopathology of bleeding during cardiac surgeries and the current role of antifibrinolytics regarding their efficacy and complications when used in those procedures, with emphasis on tranexamic acid and aprotinin. CONTENTS: The mechanisms of changes in hemostasis caused by cardiopulmonary bypass, how antifibrinolytics decrease bleeding, and the use of alogenic blood in cardiac surgery are discussed. A review of the literature emphasizes the thromboembolism secondary to the use of those antifibrinolytics. CONCLUSION: Fibrinolysis is one of the main factors related with increased bleeding during cardiac surgery with cardiopulmonary bypass. Inhibition of fibrinolysis associated with the preservation of platelet function is, probably, the mechanism by which anti-fibrinolytics decrease bleeding. Those agents reduce bleeding in up to 50 percent in cardiac surgeries with cardiopulmonary bypass. Tranexamic acid and episilon-aminocaproic acid are safer than aprotinin in the prevention of thromboembolism.

JUSTIFICATIVA Y OBJETIVOS: La cirugía cardiaca es la especialidad quirúrgica que más frecuentemente está asociada al sangramiento, cuagulopatía y con necesidad de derivados de sangre. Los agentes farmacológicos aprotinina, ácido epsilon-aminocapróico y el ácido tranexámico son los más utilizados para auxiliar en la hemostasia de los pacientes sometidos a la circulación extracorpórea. El objetivo de este trabajo fue presentar la fisiopatología del sangramiento en cirugía cardiaca y la actual situación de los antifibrinolíticos en cuanto a su eficacia y complicaciones cuando usados en estos procedimientos dando más énfasis al ácido tranexámico y a la aprotinina. CONTENIDO: Son discutidos los mecanismos por los cuales la circulación extracorpórea provoca alteración en la hemostasia y de que manera los antifibrinolíticos actúan para disminuir el sangramiento y el uso de sangre alogénica en cirugía cardiaca. Se le da énfasis al problema del trombo embolismo que puede ocurrir con el uso de esos antifibrinolíticos, con revisión de la literatura. CONCLUSIONES: La fibrinólisis es uno de los principales factores relacionados con el aumento del sangramiento en cirugía cardiaca con circulación extracorpórea. La inhibición de la fibrinólisis, conjuntamente con la preservación de la función plaquetaria es probablemente el mecanismo por el cual los antifibrinolíticos disminuyen el sangramiento. El uso de esos fármacos reduce el sangramiento en cirugía cardiaca con circulación extracorpórea en un porcentaje que puede alcanzar el 50 por ciento. Con relación a la preocupación con el trombo embolismo, el ácido tranexámico y el ácido epsilon-aminocapróico son opciones que ofrecen una mayor seguridad que la aprotinina.

Effect of epsilon-aminocaproic acid on fibrinolysis in patients undergoing open heart surgery with cardioulmonary bypass / 中华麻醉学杂志

Objective To investigate the dynamic changes in the fibrinolytic system during and after open heart surgery performed with cardiopulmonary bypass (CPB) and the effect of epsilon-aminocaproic acid (EACA) on fibrinolysis, postoperative blood loss and transfusion requirements.Methods Forty patients (24 males, 16 females) aged 17-43 yr undergoing valve replacement with CPB were randomized to receive EACA 200 mg?kg-1 (group A) or normal saline (group B) added to the priming solution. The patients were premedicated with intramuscular morphine 0.2 mg?kg-1 and scopolamine 0.3 mg. Anesthesia was induced with midazolam 0.2 mg ? kg, fentanyl 10 ?g?kg-1 and vecuronium 0.1 mg?kg-1 and maintained with isoflurane inhalation and intermittent i.v. boluses of fentanyl and vecuronium. The patients were mechanically ventilated (VT = 10 ml?kg-1 , RR = 10-12 bpm, I:E = 1:2) after tracheal intubation. Blood samples were taken before skin incision (baseline) , 8 and 30 min on CPB, 10 min after protamine administration and 2 h after operation for determination of tissue type plasminogen activator (t-PA) activity, plasminogen activator inhibitor (PAI) activity, plasmin (Plm) activity and D-dimer. The amount of blood drained from chest and bank blood infused within 24 h after operation were recorded.Results (1) Group B (control group): PAI activity was maintained stable perioperatively. The t-PA activity and t-PA/PAI ratio increased significantly during operation but returned to the baseline value 2 h after operation. D-dimer level also significantly increased during and after operation. The Plm activity increased significantly at 8h on CPB and 10 min after protamine administration compared to the baseline value. (2) The t-PA activity and t-PA /PAI ratio were significantly lower in group A than in group B. The D-dimer level and Plm activity were also significantly lower in group A than in group B during and after operation. The amount of blood loss and bank blood infused within 24 h after operation was 40% and 37% less than that in group B.Conclusion Fibrinolytic system is activated during CPB as shown by the increase in plasminogen and t-PA/PAI ratio. EACA is effective in reducing postoperative blood loss and blood transfusion through inhibition of the activation of fibrinolytic system.