Utility of In Vitro Heparin and Protamine Titration for Dosing During Cardiopulmonary Bypass Surgery

Abstract

Methods used to maintain a hemostatic balance during cardiopulmonary bypass surgery include the optimization of heparin and protamine dosing. Higher heparin doses have been associated with increased bleeding, while other studies have attributed reduced blood loss and transfusion requirements to lower protamine doses. We have evaluated the use of an in vitro heparin and protamine titration system and compared it to standard dosing in patients undergoing surgery requiring cardiopulmonary bypass. Based upon the principle of the Hemochron® RxDx® system, Heparin Response Tests (HRT) and Protamine Response Tests (PRT) were performed for 40 patients undergoing cardiac surgery at three hospital centers. The Activated Clotting Time (ACT) was used to monitor adequate heparin dosing prior to placing the patient on bypass, and to monitor heparin reversal after protamine dosing. The efficacy of heparin reversal was determined using the Protamine Dose Assay (PDA-O) test. All centers used standard hospital pharmaceutical preparations of heparin and protamine. Heparin and protamine RxDx dosing was compared to standard hospital practice for each site. Based on the HRT, the average heparin dose was not different from empirical dosing; however, individual differences were as high as 11,000 units. Only a single patient required a second heparin bolus prior to initiation of bypass. On average, the protamine dose predicted by the PRT was only 67% of the empirical protamine dose. The PDA-O test identified the need for additional protamine in 13% of patients. Patients administered additional protamine at the request of the surgical team, despite the presence of a normal PDA-O test, had no further decrease in ACT. In summary, the in vitro HRT and PRT system did not alter the initial heparin dose yet significantly decreased the protamine doses administered. Based on prior clinical outcome studies, this reduction is expected to have a beneficial effect on postoperative bleeding and transfusion requirements.