Heparin management protocol for cardiopulmonary bypass influences postoperative heparin rebound but not bleeding

A group of 63 adult patients undergoing cardiac surgical procedures requiring cardiopulmonary bypass (CPB) were studied to examine the relationship between heparin doses administered and postoperative bleeding. Patients were randomly assigned either to receive heparin 200 U/kg and additional heparin as needed to reach and maintain an activated clotting time (ACT) > 400 s for CPB (group A, n = 30), or to receive heparin 400 U/kg and additional heparin as needed to reach and maintain a whole blood heparin concentration > 4.0 U/ml for CPB (group H, n = 33). Groups were compared for the amount of postoperative bleeding, heparin rebound, homologous transfusion requirements, and standard laboratory coagulation tests. In the last 33 patients studied, additional tests of platelet aggregation and plasma levels of β thromboglobulin (BTG), antithrombin III, and several markers of fibrinolysis were measured and compared by group. The mean heparin dose was 28,000 ± 4,800 U for group A and 57,000 ± 10,700 U for group H (P < 0.05 for group A vs. group H). At 8 and 24 h postoperatively, mediastinal drainage did not differ significantly between groups (mean 24-h drainage ± SD = 901 ± 414 ml in group A, 1035 ± 501 ml in group H), nor did the incidence of transfusion with homologous blood products. Defining heparin rebound as a > 10% increase in ACT, patients in group H had a larger incidence of postoperative heparin rebound (26 of 31 patients [84%] vs. 16 of 30 [53%] patients in group A, P = 0.005) and of requiring supplemental protamine treatment for heparin rebound (8 patients in group H, 1 patient in group A, P = 0.01) in the first 8 h postoperatively. Because heparin rebound was treated with protamine only if excessive bleeding was present, patients in group H had a greater incidence of clinically significant heparin rebound. Overall, the occurrence of heparin rebound did not significantly influence the amount of postoperative blood loss, possibly because its occurrence was aggressively treated whenever bleeding was excessive. Platelet aggregation response to adenosine diphosphate and thrombin did not differ between groups before, during, or after CPB, but collagen-mediated platelet aggregation was significantly more impaired during CPB in group H (P = 0.01). Biochemical markers of fibrinolysis suggested ongoing fibrinolysis during and shortly after CPB, but the degree of activation was similar in both groups. Antithrombin III levels were significantly less in group H (P = 0.03) during CPB rewarming. In conclusion, the use of smaller versus larger doses of heparin for CPB did not significantly influence postoperative blood loss or transfusion requirements, although the larger doses of heparin used in group H increased the incidence of postoperative heparin rebound.