State-of-the-Art Review: Optimal Anticoagulation in Cardiovascular Surgery

Despite current developments in anticoagulant drugs, unfractionated heparin has remained the drug of choice for anticoagulation during cardiopulmonary bypass surgical procedures. The use of heparin has been associated with problems. Heparin-induced thrombocytopenia, intra- and postoperative bleeding, heparin resistance, and heparin rebound after heparin neutralization are the major complications. The complexity of hemostatic control during cardiopulmonary bypass (CPB) must be emphasized. The protocol for anticoagulation during CPB has varied greatly from institution to institution. With the use of the activated clotting time (ACT) and the heparin analyzer, control of anticoagulation has become more uniform and neutralization of heparin with protamine more accurate. The preferred initial dose of heparin is controversial. It varies from 200 U/kg to 450 U/kg. In our institution the initial dose used is 200 U/kg. During cardiopulmonary bypass the ACT is maintained above 400 s. Several doses of 2,000-3,000 U of heparin are added to the oxygenator, if needed, to maintain that level. Monitoring anticoagulation with the ACT and the heparin analyzer has convinced us that the lower dose is safe and the higher dose unnecessary. Once CPB is discontinued, the dose of protamine for heparin reversal is calculated with the use of the Hepcon heparin analyzer. The total dose is divided into two: 75% is given once the lines have been removed, and the other 25% is administered once the blood from the oxygenator and the cell saver has been reinfused into the patient. With this method heparin rebound is prevented. The large surface of the extracorporeal circulation apparatus acts as a massive thrombotic stimulus. The early reactions that lead to activation of the contact system of plasma proteins, white cells, fibrinolysis, platelets, and complement are not inhibited because heparin acts near the end of the coagulation cascade. The consequences of these early reactions are potential bleeding, thrombotic complications, and inflammatory reactions associated with cardiopulmonary bypass. The introduction of aprotinin has decreased perioperative bleeding by inhibiting the inflammatory cascades associated with contact activation and by acting as an antifibrinolytic agent. Newly developed anticoagulants, such as r-hirudin, peptides, plasma-derived agents, and glycoprotein targeting drugs, may be useful as a adjunct to or replacement for heparin.