Should Standard On-Pump Protamine Dosing Formulas Be Recalculated for Off-Pump Coronary Artery Bypass Grafting?

  • Y. Joseph Woo
  • Pavan Atluri
  • Todd J. Grand
  • Vivian Hsu
  • Timothy J. Gardner


Background: Since 1994 at the authors' institution, approximately 9000 cardiac surgical procedures were performed using activated clotting time (ACT)-monitored heparin anticoagulation for cardiopulmonary bypass and protamine administration calculated from a standard unchanged formula. This formula incorporates physiologic consequences of bypass pump-induced dilutional coagulopathy, platelet dysfunction, and coagulation/fibrinolytic cascade component activation, and thus may overcorrect in a subset of off-pump coronary artery bypass graft (OPCAB) patients who may in fact manifest a relative perioperative hypercoagulability state. This study evaluated a strategy of decreased protamine dosing in OPCAB.

Methods: Eighty consecutive OPCAB patients who underwent surgery performed by a single surgeon at a single institution over a 12-month period were retrospectively analyzed. Patients underwent a mean of 2.91 ± 0.1 OPCAB grafts with full heparinization and 50% of the calculated protamine dose was administered. ACT, partial thromboplastin times, thoracostomy tube outputs, transfusions, and clinical outcomes were assessed.

Results: Of 80 patients, 76 (95%) returned to baseline ACT values with 50% protamine dosing. All patients demonstrated intraoperative clinical evidence of hemostasis. Mean 8- and 24-hour thoracostomy tube outputs were 424 ± 24 mL and 806 ± 38 mL, respectively. A mean of 1.7 ± 0.2 packed red blood cell transfusions/patient was administered. There were no transfusions of platelets, fresh frozen plasma, or cryoprecipitate; no reexplorations; and no mortalities. Patients were discharged a mean of 4.4 ± 0.1 days postoperatively. Conclusion: A standard protamine dosing formula adequate for on-pump cardiac surgical procedures significantly overestimates protamine requirements for OPCAB. Patients treated with decreased protamine do not appear to have adverse outcomes.


Ascione R, Williams S, Lloyd CT, Sundaramoorthi T, Pitsis AA, Angelini GD. 2001. Reduced postoperative blood loss and transfusion requirement after beating-heart coronary operations: a prospective randomized study. J Thorac Cardiovasc Surg 121:689-96.\nCasati V, Gerli C, Franco A, et al. 2001. Activation of coagulation and fibrinolysis during coronary surgery. Anesthesiology 95:1103-9.\nChan AK, Leaker M, Burrows FA, et al. 1997. Coagulation and fibrinolytic profile of paediatric patients undergoing cardiopulmonary bypass. Thromb Haemost 77:270-7.\nDespotis GJ, Avidan MS, Hogue CW. 2001. Mechanisms and attenuation of hemostatic activation during extracorporeal circulation. Ann Thor Surg 72:S1821-31.\nDespotis GJ, Gravlee G, Filos K, Levy J. 1999. Anticoagulation monitoring during cardiac surgery: a review of current and emerging techniques. Anesthesiology 91:1121-51.\nGatti G, Pugliese P. 2002. Heparin reversal in off-pump coronary artery bypass surgery: complete, partial, or no reversal? Cardiovasc Surg 10:245-50.\nGreilich PE, Brouse CF, Beckham J, Jessen ME, Matin EJ, Marcus ME. 2002. Reductions in platelet contractile force correlate with duration of cardiopulmonary bypass and blood loss in patients undergoing cardiac surgery. Thromb Res 105:523-29.\nGrossman R, Babin-Ebell J, Misoph M, et al. 1996. Changes in coagulation and fibrinolytic parameters caused by extracorporeal circulation. Heart Vessels 11:310-7.\nHunt BJ, Parratt RN, Segal HC, Sheik S, Kallis P, Yacoub M. 1998. Activation of coagulation and fibrinolysis during cardiothoracic operations. Ann Thor Surg 65:712-8.\nLevy JH, Tanaka KA. 2003. Inflammatory response to cardiopulmonary bypass. Ann Thor Surg 75:S715-20.\nMariani MA, Gu YJ, Boonstra PW, Grandjean JG, Van Oeveren W, Ebels T. 1999. Procoagulant activity after off-pump coronary operation: is the current anticoagulation adequate? Ann Thor Surg 67:1370-5.\nPorsche R, Brenner ZR. 1999. Allergy to protamine sulfate. Heart Lung 28:418-28.\nPuskas JD, Williams WH, Duke PG, et al. 2003. Off-pump coronary artery bypass grafting provides complete revascularization with reduced myocardial injury, transfusion requirements, and length of stay: a prospective randomized comparison of two hundred unselected patients undergoing off-pump versus conventional coronary artery bypass grafting. J Thorac Cardiovasc Surg 125:797-808.\nQuigley RL, Fried DW, Pym J, Highbloom RY. 2003. Off-pump coronary artery bypass surgery may produce a hypercoagulable patient. Heart Surg Forum 6:94-8.\nRay MJ, Marsh NA, Hawson GA. 1994. Relationship of fibrinolysis and platelet function to bleeding after cardiopulmonary bypass. Blood Coagul Fibrinolysis 5:679-85.\nSaatvedt K, Lindberg H, Michelsen S, Pedersen T, Geiran OR. 1995. Activation of the fibrinolytic, coagulation and plasma kallikrein-kinin systems during and after open heart surgery in children. Scand J Clin Lab Invest 55:359-67.\nSlaughter TF, Sreram G, Sharma AD, El-Moalem H, East CJ, Greenberg CS. 2001. Reversible shear mediated platelet dysfunction during cardiac surgery as assessed by the PFA-100 platelet function analyzer. Blood Coagul Fibrinolysis 12:85-93.\n
How to Cite
Woo, Y. J., Atluri, P., Grand, T. J., Hsu, V., & Gardner, T. J. (2005). Should Standard On-Pump Protamine Dosing Formulas Be Recalculated for Off-Pump Coronary Artery Bypass Grafting?. The Heart Surgery Forum, 7(1), E43-E45.