title: Implementing a Statistical Model for Protamine Titration: Effects on Coagulation in Cardiac Surgical Patients.
abstract: OBJECTIVE
  To implement a statistical model for protamine titration.
  
  
  METHODS
  Prospective randomized trial.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  Sixty (n = 30+30) patients scheduled for elective coronary artery bypass surgery were randomly assigned to 2 groups.
  
  
  METHODS
  Protamine dose calculated according to an algorithm established from a statistical model or to a fixed protamine-heparin dose ratio (1:1).
  
  
  RESULTS
  Both groups demonstrated comparable patient demographics and intraoperative data. Coagulation effects were evaluated using rotational thromboelastometry. Using the statistical model reduced (p<0.01) the protamine dose from 426±43 mg to 251±66 mg, followed by significantly (p<0.01) shorter intrinsic clotting time (208±29 seconds versus 244±52 seconds) and stronger clot firmness (p = 0.01), and effects on indices of extrinsic or fibrinogen coagulation pathways were insignificant. Test of residual heparin was negative in all patients after protamine administration, aligned with insignificant (p = 0.27) intergroup heparinase-verified clotting time differences.
  
  
  CONCLUSIONS
  The statistical model for protamine titration is clinically feasible and protects the patient from exposure to excessive doses of protamine, with advantageous effects on coagulation as measured using rotational thromboelastometry. Significance regarding clinical outcome is yet to be defined.
authors.affiliation: Department of Public Health and Clinical Medicine, Heart Centre, Umeå University, Umeå, Sweden.
authors.forename: Oskar
authors.initials: O
authors.lastname: Hällgren
authors.affiliation: Department of Public Health and Clinical Medicine, Heart Centre, Umeå University, Umeå, Sweden. Electronic address: staffan.svenmarker@umu.se.
authors.forename: Staffan
authors.initials: S
authors.lastname: Svenmarker
authors.affiliation: Department of Public Health and Clinical Medicine, Heart Centre, Umeå University, Umeå, Sweden.
authors.forename: Micael
authors.initials: M
authors.lastname: Appelblad
mesh_terms: D000368:Aged; D001777:Blood Coagulation / Q000187:drug effects* / Q000502:physiology; D006348:Cardiac Surgical Procedures / Q000639:trends; D001026:Coronary Artery Bypass / Q000639:trends*; D005260:Female; D006494:Heparin Antagonists / Q000008:administration & dosage / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D011446:Prospective Studies; D011479:Protamines / Q000008:administration & dosage / Q000097:blood*; D014914:Whole Blood Coagulation Time / Q000639:trends
chemical_list: D006494:Heparin Antagonists; D011479:Protamines
keywords: cardiac surgery; cardiopulmonary bypass; heparin; protamine; statistical model