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


RESULTS
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.


CONCLUSIONS
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.
Koster
Andreas
A
Institute of Anesthesiology, Heart and Diabetes Center Nordrheinwestfalen, Bad Oeynhausen, Ruhr University of Bochum, Bochum, Germany. akoster@hdz-nrw.de
Schirmer
Uwe
U
D015119:Aminocaproic Acid / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000933:Antifibrinolytic Agents / Q000627:therapeutic use*; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass; D006801:Humans; D019106:Postoperative Hemorrhage / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic; D014148:Tranexamic Acid / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
D000933:Antifibrinolytic Agents; D014148:Tranexamic Acid; D015119:Aminocaproic Acid