Intracoronary administration of levosimendan in acute coronary syndrome with decreased left ventricular ejection fraction: a case series

Abstract

Introduction. Protamine has intrinsic anticoagulant properties and protamine dosing based on a fixed dosing ratio to heparin might overdose protamine impairing patient hemostasis. This study compared hemostasis of fixed ratio protamine dosing to protamine dosing based on a novel computerized pharmacokinetic (PK) model of heparin.Methods. This case-control study included 109 patients undergoing elective cardiac surgery with CPB. In 56 patients protamine was dosed in a fixed ratio, while 63 patients received protamine based on the PK-model. Study parameters included delta activated clotting time (ΔACT ¼ ACT after protamine minus preoperative ACT), aPTT, rotational thromboelastometry (INTEM and HEPTEM), blood loss and blood transfusion. Data was analysed by Student's T-test or Mann Witney test.Results. There was no difference in the amount of heparin administrated (414 Ϯ 107 mg (fixed ratio group) vs. 403 Ϯ 90 mg (PK-group); n.s.), whereas protamine dosing was considerably different with a protamine:heparin-ratio of 1.1 Ϯ 0.3 for the fixed dosing ratio and 0.5 Ϯ 0.1 for the PK-group, po0.001. The ΔACT values were not different (þ17 Ϯ 77 s for the fixed ratio group and þ6 Ϯ 15 s for the PK-dosed group). Postoperative aPTT values were similar (42 Ϯ 13 s vs. 43 Ϯ 5 s; n.s.). Thromboelastometric data were prolonged in the routine practice group compared to the PK group, INTEM clotting time (CT) 250 Ϯ 76 s vs. 198 Ϯ 32 s and HEPTEM CT 275 Ϯ 105 vs. 198 Ϯ 32 s (both Po0.001). Median packed red blood cell transfusion ((0 (0-2) vs. 0(0-0)), fresh frozen plasma transfusion ((1 (0-2) vs. 0 (0-0)) and platelet concentrate transfusion (0 (0-1) vs. 0 (0-0)) were different between the fixed ratio and PK group, respectively (all Po0.001). Although postoperative hemostasis differed 24-hour postoperative blood loss did not differ between the fixed ratio and PK group, (389 (293-548) ml vs. 340 (243-525) ml; n.s.). Conclusion. Patient-tailored protamine dosing based on a pharmacokinetic model resulted in a significant reduction of protamine dosing with better hemostasis and fewer blood product transfusion when compared to fixed ratio protamine dosing.