Anesth Analg 2004;98:285-290
© 2004 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000096260.35340.C5
CARDIOVASCULAR ANESTHESIA
Heparin-Level-Based Anticoagulation Management During Cardiopulmonary Bypass: A Pilot Investigation on the Effects of a Half-Dose Aprotinin Protocol on Postoperative Blood Loss and Hemostatic Activation and Inflammatory Response
Andreas Koster, MD,
Sabine Huebler, MD,
Frank Merkle, EBCP,
Thomas Hentschel, MD,
Marcus Gründel, MD,
Thomas Krabatsch, MD,
Luc Tambeur, MD,
Michael Praus, MD,
Helmut Habazettl, MD,
Wolfgang M. Kuebler, MD, and
Hermann Kuppe, MD
From the Department of Anesthesia, Deutsches Herzzentrum, Berlin, Germany
Address correspondence and reprint requests to Andreas Koster, MD, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, 13353 Berlin. Address email to Koster{at}dhzb.de
Cardiac surgery involving cardiopulmonary bypass (CPB) leads to activation of the hemostatic/inflammatory system. We compared the influence of a half-dose aprotinin regimen on postoperative blood loss and the activation of the hemostatic/inflammatory system during CPB, when used during a heparin-level-based heparin management for cardiac surgery. Two-hundred patients (n = 100 in each group) were enrolled in this randomized prospective study. In Group I only heparin was given according to the results of the Hepcon HMS PlusTM. In Group II aprotinin was added with a bolus of 1 x 106 kallikrein inhibiting units (KIU) for the patient immediately before initiation of CPB, 1 x 106 KIU in the priming solution of the CPB, and a continuous infusion of 250,000 KIU/h during CPB. Postoperative blood loss was determined after 12 h. Heparin and antithrombin activity were evaluated by an anti-Xa assay and measurement of antithrombin III activity. Hemostatic activation was evaluated by adenosine diphosphate-stimulated platelet aggregometry and by measurements of the generation/release of ß-thromboglobulin (ß-TG), soluble P-selectin (sPS), thrombin (TAT), prothrombin 1 and 2 fragments (PTF1+2), factor XIIa (FXIIa), plasmin (PAP), and D-dimers. Inflammatory response was evaluated by measuring complement factors 5b-9 (C5b-9), interleukin (IL)-6, and neutrophil elastase (NE). There were no differences in the pre-CPB values or duration of CPB between the two groups. There were no differences in the post-CPB values for platelet count, platelet aggregation, ß-TG, sPS, TAT, PTF1+2, C5b-9, NE, or IL-6. The additional use of aprotinin resulted in a significant decrease of PAP, D-dimers, and 12 h postoperative blood loss, whereas generation of the contact factor XIIa was increased. The administration of aprotinin significantly reduced postoperative blood loss after cardiac surgery and CPB. This most likely has to be attributed to the antifibrinolytic effects of aprotinin. No effects on thrombin generation, platelet activation, inflammatory response, or clinical outcome were noted.
IMPLICATIONS: The use of half-dose aprotinin and heparin-level-based anticoagulation management during cardiopulmonary bypass leads to a significant reduction of postoperative blood loss after cardiac surgery. This effect can most likely be attributed to the antifibrinolytic effects of aprotinin, as we did not observe effects on other variables of activation of the hemostatic/inflammatory system.
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