A Pharmacokinetic Model for Protamine Dosing After Cardiopulmonary Bypass.

OBJECTIVE: This study investigated postoperative hemostasis of patients subjected to conventional protamine dosing compared with protamine dosing based on a pharmacokinetic (PK) model following cardiopulmonary bypass.

DESIGN: Retrospective case-control study.

SETTING: Tertiary university hospital.

PARTICIPANTS: Patients undergoing elective cardiac surgery with cardiopulmonary bypass.

INTERVENTIONS: In 56 patients, protamine was dosed in a fixed ratio (CD), while 62 patients received protamine based on the PK model.

MEASUREMENTS AND MAIN RESULTS: There was no difference in heparin administration (414±107 mg (CD) v 403±90 mg (PK); p = 0.54), whereas protamine dosing was considerably different with a protamine-to-heparin dosing ratio of 1.1±0.3 for the CD group and 0.5±0.1 for the PK group (p<0.001). The changes in activated coagulation time (ΔACT) values (ACT after protamine minus preoperative ACT;+17±77 s v+6±15 s; p = 0.31) were equal between groups. Yet, the thromboelastometric intrinsically activated coagulation test clotting time (CT; 250±76 s v 203±44 s; p<0.001) and intrinsically activated coagulation test without the heparin effect CT (275±105 v 198±32 s; p<0.001) were prolonged in the CD group. Median packed red blood cell transfusion (0 [0-2] v 0 [0-0]), fresh frozen plasma transfusion (1 [0-2] v 0 [0-0]), and platelet concentrate transfusion (0 [0-1] v 0 [0-0]) were different between the fixed ratio and PK group, respectively (all p<0.001).

CONCLUSIONS: This study showed that patient-tailored protamine dosing based on a PK model was associated with a reduction in protamine dosing, with better hemostatic test results when compared with fixed-ratio protamine dosing.