title: A Pharmacokinetic Model for Protamine Dosing After Cardiopulmonary Bypass.
abstract: 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.
  
  
  METHODS
  Retrospective case-control study.
  
  
  METHODS
  Tertiary university hospital.
  
  
  METHODS
  Patients undergoing elective cardiac surgery with cardiopulmonary bypass.
  
  
  METHODS
  In 56 patients, protamine was dosed in a fixed ratio (CD), while 62 patients received protamine based on the PK model.
  
  
  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.
authors: Departments of Anesthesiology.
authors: Michael I
authors: MI
authors: Meesters
authors: Cardio-thoracic Surgery, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.
authors: Dennis
authors: D
authors: Veerhoek
authors: Departments of Anesthesiology.
authors: Jan R
authors: JR
authors: de Jong
authors: Departments of Anesthesiology. Electronic address: c.boer@vumc.nl.
authors: Christa
authors: C
authors: Boer
mesh_terms: D000368:Aged; D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests / Q000706:statistics & numerical data; D006348:Cardiac Surgical Procedures; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006494:Heparin Antagonists / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D011182:Postoperative Care / Q000379:methods*; D011479:Protamines / Q000493:pharmacokinetics*; D012189:Retrospective Studies; D013916:Thrombelastography / Q000187:drug effects
chemical_list: D006494:Heparin Antagonists; D011479:Protamines
keywords: cardiac surgery; cardiopulmonary bypass; coagulation; hemostasis; heparin; protamine