Re-evaluation of the role of antifibrinolytic therapy with lysine analogs during cardiac surgery in the post aprotinin era

被引:40
作者
Koster, Andreas [1 ]
Schirmer, Uwe [1 ]
机构
[1] Ruhr Univ Bochum, Inst Anesthesiol, Heart & Diabet Ctr Nordrheinwestfalen, D-32545 Bochum, Germany
关键词
hemostatic activation; hemorrhage; transfusions; BLOOD-CELL TRANSFUSION; DOSE TRANEXAMIC ACID; INCREASED MORTALITY; PHARMACOKINETICS; MORBIDITY; SAFETY; COST;
D O I
10.1097/ACO.0b013e32833ff3eb
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
Purpose of review Hemorrhage, transfusions and the need for re-exploration can have a detrimental effect on patient outcome in cardiac surgery. With the suspension of aprotinin from the market, only the antifibrinolytics tranexamic acid and epsilon-aminocaproic acid (EACA) are left as pharmacological options to reduce hemostatic activation and associated bleeding complications. In light of the aprotinin story, the need for large independent safety studies has become evident. The current review will focus on the question of how far the quality of available data allows for judging these agents with regard to safety and efficacy, as well as whether or not new trails are warranted. Recent findings Both, tranexamic acid and EACA are effective in reducing blood loss and transfusion requirements in cardiac surgery. Analysis of data is complicated as the dosing scheme, especially for tranexamic acid, varies extremely and the agents are highly overdosed in most relevant trials. Newer data indicates that in a dose-dependent fashion, tranexamic acid is associated with an increase of adverse events, particularly the observation of seizures. In these studies, however, tranexamic acid has also been highly overdosed. Summary The lysine analogs are unspecific enzyme inhibitors. Therefore, it is conceivable that an overdosing might reveal severe clinical side-effects beyond the inhibition of plasmin. Further studies re-evaluating the drug safety of tranexamic acid and EACA using the recommended and approved doses are necessary.
引用
收藏
页码:92 / 97
页数:6
相关论文
共 31 条
[1]   The blood sparing effect and the safety of aprotinin compared to tranexamic acid in paediatric cardiac surgery [J].
Breuer, Tamas ;
Martin, Klaus ;
Wilhelm, Markus ;
Wiesner, Gunther ;
Schreiber, Christian ;
Hess, John ;
Lange, Ruediger ;
Tassani, Peter .
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY, 2009, 35 (01) :167-171
[2]   Meta-analysis comparing the effectiveness and adverse outcomes of antifibrinolytic agents in cardiac surgery [J].
Brown, Jeremiah R. ;
Birkmeyer, Nancy J. O. ;
O'Connor, Gerald T. .
CIRCULATION, 2007, 115 (22) :2801-2813
[3]   Pharmacokinetics of ε-aminocaproic acid in patients undergoing aortocoronary bypass surgery [J].
Butterworth, J ;
James, RL ;
Lin, YG ;
Prielipp, RC ;
Hudspeth, AS .
ANESTHESIOLOGY, 1999, 90 (06) :1624-1635
[4]   Clinical inhibition of the seven-transmembrane thrombin receptor (PAR1) by intravenous aprotinin during cardiothoracic surgery [J].
Day, JRS ;
Punjabi, PP ;
Randi, AM ;
Haskard, DO ;
Landis, RC ;
Taylor, KM .
CIRCULATION, 2004, 110 (17) :2597-2600
[5]   Tranexamic Acid and Aprotinin in Primary Cardiac Operations: An Analysis of 220 Cardiac Surgical Patients Treated with Tranexamic Acid or Aprotinin [J].
Dietrich, Wulf ;
Spannagl, Michael ;
Boehm, Johannes ;
Hauner, Katharina ;
Braun, Siegmund ;
Schuster, Tibor ;
Busley, Raimund .
ANESTHESIA AND ANALGESIA, 2008, 107 (05) :1469-1478
[6]   Aprotinin: 1 year on [J].
Dietrich, Wulf .
CURRENT OPINION IN ANESTHESIOLOGY, 2009, 22 (01) :121-127
[7]   CU-2010-A Novel Small Molecule Protease Inhibitor with Antifibrinolytic and Anticoagulant Properties [J].
Dietrich, Wulf ;
Nicklisch, Silke ;
Koster, Andreas ;
Spannagl, Michael ;
Giersiefen, Helmut ;
van de Locht, Andreas .
ANESTHESIOLOGY, 2009, 110 (01) :123-130
[8]   Pharmacokinetics of tranexamic acid during cardiopulmonary bypass [J].
Dowd, NP ;
Karski, JM ;
Cheng, DC ;
Carroll, JA ;
Lin, YG ;
James, RL ;
Butterworth, J .
ANESTHESIOLOGY, 2002, 97 (02) :390-399
[9]   Antifibrinolytic therapy in surgery for congenital heart disease [J].
Eaton, Michael P. .
ANESTHESIA AND ANALGESIA, 2008, 106 (04) :1087-1100
[10]  
Ender J, 2010, J CARDIOTHORAC VAS S, V24, P78