A Pharmacokinetic Model for Protamine Dosing After Cardiopulmonary Bypass

作者：Meesters Michael I; Veerhoek Dennis; de Jong Jan R; Boer Christa^*

来源：Journal of Cardiothoracic and Vascular Anesthesia, 2016, 30(5): 1190-1195.

DOI：10.1053/j.jvca.2016.04.021

• protamine
• heparin
• cardiac surgery
• cardiopulmonary bypass
• hemostasis
• coagulation

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 (Delta ACT) 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.

• 出版日期2016-10