EFFICACY OF A HEPARIN REMOVAL DEVICE IN COMPARISON WITH PROTAMINE AFTER HYPOTHERMIC CARDIOPULMONARY BYPASS

To reduce the risks of protamine reactions after cardiopulmonary bypas s (CPB), a heparin removal device (HRD) with plasma separation and pol y-l-lysine (PLL) affinity adsorption was developed. To compare the eff icacy of HRD with that of protamine, blood coagulation variables were evaluated in a swine model of CPB. Female Yorkshire swine were randoml y divided into the HRD group (n = 6, weight 79.7 +/- 7.0 kg) and the p rotamine group (n = 6, weight 79.3 +/- 6.8 kg), and subjected to 60 mi n of right atrium-to-aortic, hypothermic (28 degrees C) CPB. After wea ning from CPB, the right atrium was recannulated with a two-stage, dua l lumen cannula in the HRD group. Blood flow was drained from the infe rior vena cava, through the plasma separation chamber of the HRD where heparin was bound to PLL, and re-infused into the right atrium. The H RD run time was determined by an established mathematical model of fir st-order exponential depletion targeted to 90% heparin removal. In the protamine group, protamine was given in a 100 U heparin to 1 mg prota mine ratio after CPB in a slow intravenous infusion. Hemodynamics, act ivated clotting time (ACT), activated partial thromboplastin time (APT T), and heparin concentration were obtained before, every 5 min during , and after the use of the HRD or before and after protamine administr ation, and 1 and 3 hours after HRD or protamine. Heparin concentration immediately after CPB was 4.90 +/- 0.19 U/ml in the HRD group and 3.9 4 +/- 0.63 U/ml in the protamine group, respectively (p > 0.05 between groups). The ACT was 994 +/- 7 sec in the HRD group and 768 +/- 55 se c in the protamine group, and APTT was greater than 150 sec in both gr oups (p > 0.05 between groups). In the HRD group, the HRD run time was determined to be 31.5 +/- 2.4 min for the targeted 90% heparin remova l, and the plasma heparin concentration followed first-order depletion kinetics. In the protamine group, the full dose of protamine was admi nistered over 15 min. Immediately after the HRD run or protamine admin istration, plasma heparin concentration decreased to 0.48 +/- 0.09 U/m l in the HRD group and 0.13 +/- 0.02 U/ml in the protamine group (p < 0.01 between groups); likewise, ACT decreased to 188 +/- 25 sec in the HRD group and 101 +/- 5 in the protamine group (p < 0.01 between grou ps). The APTT was not significantly different between the groups at an y time during the experiment. Plasma heparin concentration and ACT wer e not significantly different three hours after the HRD run or protami ne administration. The authors conclude that the HRD is capable of pre dictable reversal of systemic heparinization after CPB, and is an alte rnative to achieve heparin clearance in subjects who may develop adver se reactions to protamine.