I. Prime: fluid contained within the CPB tubing. a. Normally crystalloid solutions are used and allows the CPB prime to acienve similar osmolarity and electrolyte composition as blood. b. Other solutions added to prime.i. Albumin: to decrease postoperative edemaii. Mannitol: to promote diuresisiii. Electrolytes: calcium to prevent hypocalcemia due to citrate in transfused bloodiv. Heparin to ensure a safe level of anticoagulationc. Many institutions use a standard volume prime for all adult patients, and others use a minimum volume based on body weight or body surface area ( the average prime volume is about 1,500 mL)d. Lowest hematocrit on CPB is debated, but hematocrits of 17% are well tolerated. II. Anticoagulationa. Contact between the patients blood and components of the CPB circuit initiates activation of the coagulation cascade. b. To prevent thrombosis of the CPB circuit, systemic anticoagulation is required prior to insertion of cannulae and initiation of CPB. c. Anticoagulant of choice is heparin. d. Following IV injection, the peak onset of heparin is 1,000 fold. h. By inhibiting thrombin, AT prevents formation of fibrin clot via both the intrinsic and extrinsic pathways, in addition to inhibiting factors 9,10a,11a, 12a, kallekrein, and plasmin. i. With those who experience deficiency of AT we can administer exogenous AT.i. Keep in mind that heparin rebound and subsequent bleeding may be a concern following the administration of exogenous AT. j. Partial thrombopalstin time is not used in cardiac surgery to measure heparin action. This is due to the fact that modern partial throboplastin time assays are so sensitive that heparin levels far lower than those used for safe initiation of CPB cause the sample blood to become almost unclottable within the time fram of the test. k. The 2 methods used for determining adequate heprinization are measurement of the activated clotting time.i. ACT test conissits of adding blood t otubes containing either diatomaceious earth (celite) or kaolin, warming and rotating the tube and then recoring the time required for clot formation. 1. Generally, ACTs>480 seconds are considered acceptable for the initiation of CPB. ii. Or blood-heparin concenctrations. 1. Known doses of protamine are added to heparinized sample of blood sequentially, until the optimum dose of protamine that produces a clot in the shortes amount of time is determine.d 2. By knowning the neurtralizition ration of heparin and protamine ( usually 1mg to 100U of heparin)m, the heparin concentration in the sample can ebe determined. l. Allergies to heparin are rare; more commonly, patients may present with a history of heparin-induced thrombocytopenia (HIT). i. There are 2 subtypes:ii. The 1st is generally mild and consists of a transient decrease in platelet count following the administration of heparin a few days following surgery. iii. The 2nd type is more severe, characterized by autoimmune-mediated decreasein the platelet count due to the formation of antigenic heparin compounds (Anti-PF4) that activate platelets in the face of endothelial injury. This predisposes toe platelet clumping and microvascular thrombosis. This thrombosis may occur anywhere in the body and cause bowel or limb ischemia to name a fe.iv. In patients with HIT who require systemic anticoagulation, heparin alternative should be used instead. Ex: defibrinogenating agents, hirudin, bivalirudin, and factor 10 inhibitors. III. Blood conservation in cardiac surgerya. Intraoperative autologous hemodilution is a well-described method of removing whole blood from a patient prior to systemic heparinization and CPB. i. Returning this blood following the separation from CPB returns RBS, active platelets, and functional coagulation factors that may mitigate surgical bleeding. ii. CI to intraoperative autologous blood donation include preoperative anemia, unstable angina/ high grade left main coronary artery disease, and AS.b. Blood salvage is another key method of intraoperative blood conservation in cardiac surgery.i. Following processing, units of shed blood may have hematrocrits of 70%. ii. As PLTs and coagualation factors are removed in the washing process, reinfusion of shed blood may worsen the CPB-associated coagulopathy by promting a dilutional thrombocytopenia and reduction of clotting factors. iii. CI to the use of intraoperative cell salvage incude infection, malignancy, and the use of topical hemostatic agetnsc. Antifibrinolytic use in cardiac surgery is the standard in most cardiac centers, with E-aminocaproic acid being the primary agent used in the US. The lsine analoguese-aminocaproic and tranexamic acid bind to plasminiogen and block it ability to bind at lysine resideues of fibrinogen. This prevents the lysis of firbin clots. i. Administration of these antibirbinolytics decreases bleeding after CPB and reduces the risk of blood transfusion. d. Aprotinin, a naturally occurring fibrinolytic , inhibits kallekrein, preserves platelet glycoprotein receoptros, inhibits the proinflammatory cytokine release associated with CPB, as well as the inhibition of plasmin and protein C. until recelntly it was used in repoperation, aortic srurgyer, and whenever major bleeding was expected. Questions regarding safety are raised. Can cause RF, increase patient mortality. No longer used. Higher 30 day mortality when compared to aminocaproice. Hemodilution is due to the CPB prime is one undesired byproduct of extracorporeal circulation. One method that has been ued with success to avoid excess hemodilution and reduce the need for blood transfusion is retrograde autologous priming. (RAP). In RAP, the cruystalloid prime contained within the CPB circuit is drained prior to the initiation of CPB and replaced by blood drained retrogreade via the arterial cannula. RAP reduces hemodilution and diminishes the drop in systemic vascular resistance associated with the initiation of CPB. f. Ultrafiltration is another technique used in conjuction with CPB to reduce postoperative bleeding and transfusion needs. i. During ultrafiltration (hemoconcentration), plasma water is separated from low-molecular weight solutes, intravascular cell components, and plasma proteins with a semipermeable membrane, using a hydrostatic pressure differential created by external suction. Advantages of hemoconcentration include a reduction in free water, increase in hemoglobin and hematocrit, preservation of hemostasis, and a decrease in levels of circulating inflammatory mediators. IV. Myocardial protection:via hypothermiaa. Most common method of myocardial protection used today is that of intermittent hyperkalemic cold cardioplegia and moderate systemic hypothermia. b. Systemic hypothermia is beneficial for both myocardial and neurologic protection during cardiac surgery. c. The benefits of hypothermia area a reduction in metabolic rate and oxygen consumption, preservation of high-energy phosphate substrates, and a reduction in excitatory neurotransmitter release. d. For each degree centigrade reduction in temperature, there is an 8% reduction in metabolic rate, so that at 28* C there is an approximate reduction in metabolic reate of 50%. e. Moderate systemic hypothermia can be achieved with either passive or active cooling. Using passive cooling, the patients core temperature is allowed to equalize with the ambient temperature. This may be a slow or rapid process depending on variables such as patients body surface area exposed and ambient temperature. f. Most patients undergoing cardiac surgery are actively colled and then rewarmed using a heat exchanger. g. Cold cardioplegia is that a cold solution (10-15*C) of either blood or cystalloid with a supranormal concenctration of potassium is injected in to the coronary artiers or veins to induce diastolic electrical arrest. h. Cardioplegia may be employed via an anterograde, a retrograde, or a combination of the two routes.