Implementing a Statistical Model for Protamine Titration: Effects on Coagulation in Cardiac Surgical Patients.

OBJECTIVES: To implement a statistical model for protamine titration. DESIGN: Prospective randomized trial. SETTING: University hospital. PARTICIPANTS: Sixty (n = 30+30) patients scheduled for elective coronary artery bypass surgery were randomly assigned to 2 groups. INTERVENTIONS: Protamine dose calculated according to an algorithm established from a statistical model or to a fixed protamine-heparin dose ratio (1:1). MEASUREMENTS AND MAIN 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.