Following induction and intubation, the anesthetic course is typically characterized by an initial period of minimal stimulation (skin preparation and drap-ing) that is frequently associated with hypotension, followed by discrete periods of intense stimulation that can produce tachycardia and hypertension. These periods of stimulation include the skin inci-sion, sternotomy and sternal retraction, opening the pericardium, and, sometimes, aortic dissection. The anesthetic agent should be adjusted appropriately in anticipation of these events.
Accentuated vagal responses resulting in marked bradycardia and hypotension may occa-sionally be seen during sternal retraction or open-ing of the pericardium, perhaps more commonly in patients who have been taking β-adrenergic block-ing agents or diltiazem.
Myocardial ischemia in the prebypass period is not always associated with hemodynamic per-turbations such as tachycardia, hypertension, or hypotension. Prophylactic infusion of nitroglycerin (1–2 mcg/kg/min) has been studied many times and continues to be used but does not appear to reduce the incidence of ischemic episodes or to alter outcomes.
Anticoagulation must be established before CPB to prevent acute disseminated intravascular coagulation and formation of clots in the CPB pump. In most centers the adequacy of anticoagula-tion will be confirmed by measuring the ACT. An ACT longer than 400–480 s is considered adequate at most centers. Heparin, 300–400 units/kg, is usu-ally given while the aortic pursestring sutures are placed before cannulation. Some surgeons prefer to administer the heparin themselves directly into the right atrium. If heparin is administered by the anesthesiologist, it should be given through a reli-able (usually central) intravenous line, and the ACT should be measured 3–5 min later. If the ACT is less than 400 s, additional heparin (100 units/kg) is given. Some drugs (eg, aprotinin) prolong the celite-activated ACT but not the kaolin-activated ACT; the kaolin-ACT should be used to assess ade-quacy of anticoagulation in these circumstances. Heparin concentration assays (see Reversal of Anticoagulation, below) measure heparin levels and not necessarily effect; these assays are therefore not reliable for measuring the degree of anticoagulation but can be used as an adjunct. A whole blood hepa-rin concentration of 3–4 units/mL is usually suffi-cient for CPB. The high-dose thrombin time (HiTT) is not influenced by aprotinin but is more compli-cated to perform than a kaolin-ACT. HiTT cannot provide a preheparin control and does not provide an index for the adequacy of reversal with protamine .
Resistance to heparin is occasionally encoun-tered; many such patients have antithrombin III deficiency (acquired or congenital). Antithrombin is a circulating serine protease that irreversibly binds and inactivates thrombin (as well as the acti-vated forms of factors X, XI, XII, and XIII). When heparin complexes with antithrombin III, the anti-coagulant activity of antithrombin III is enhanced 1000-fold. Patients with antithrombin III deficiency will achieve adequate anticoagulation following infusion of 2 units of fresh frozen plasma or anti-thrombin III concentrate. Alternatively, recombi-nant human antithrombin III may be administered. Milder forms of heparin resistance can be managed by administration of a modestly larger than normal dose of heparin.
Patients with a history of heparin-induced thrombocytopenia (HIT) require special consider-ation. These patients produce heparin-dependent (platelet factor 4) antibodies that agglutinate plate-lets and produce thrombocytopenia, sometimes associated with thromboembolism. If the history of HIT is remote and antibodies can no longer be demonstrated, heparin may safely used for CPB. Other anticoagulants should be preferred in other circumstances. When significant antibody titers are detected, alternative anticoagulants including hirudin, bivalirudin, ancrod, and argatroban may be considered, but experience with them is limited. Consultation with a hematologist may be helpful.
Bleeding prophylaxis with antifibrinolytic agents may be initiated before or after anticoagulation. Some clinicians prefer to administer antifibrinolytic agents after heparinization to reduce the possible incidence of thrombotic complications; others fear that delayed administration may reduce antifibrinolytic efficacy. Antifi brinolytic therapy may be particularly useful for patients who are undergoing a repeat operation; who refuse blood products (such as Jehovah’s Witnesses); who are at high risk for postoperative bleeding because of recent admin-istration of glycoprotein IIb/IIIa inhibitors (abcix-imab [RheoPro], eptifibatide [Integrilin], or tirofiban [Aggrastat]); who have preexisting coagulopathy; and who are undergoing long and complicated pro-cedures involving the heart or aorta. The antiplatelet effect of abciximab typically lasts 24–48 h; those of eptifibatide and tirofiban are 2–4 and 4–8 h, respec-tively. The combination of aspirin and the adenosine diphosphate receptor antagonist clopidogrel (Plavix) is also associated with excessive bleeding.
The antifibrinolytic agents currently avail-able, ε-aminocaproic acid and tranexamic acid, do not affect the ACT and only rarely induce allergic reactions. ε-Aminocaproic acid is usually adminis-tered as a 50–75 mg/kg loading dose followed by a 20–25 mg/kg/h maintenance infusion (some clini-cians use a standard 5–10 g loading dose followed by 1 g/h). Tranexamic acid is often dosed at 10 mg/kg followed by 1 mg/kg/h, although pharmacokinetic studies suggest that larger doses may more reliably maintain effective blood concentrations. Intra-operative collection of platelet-rich plasma by pheresis prior to CPB is employed by some centers; reinfusion following bypass may decrease bleeding and reduce transfusion requirements.
Placement of venous and arterial cannulas for CPB is a critical time. After heparinization, aortic cannulation is usually done first because of the hemodynamic problems frequently associated with venous cannulation and to allow convenient and rapid transfusion from the pump oxygenator. The inflow cannula is most often placed in the ascend-ing aorta. The small opening of most arterial cannu-las produces a jet stream that, when not positioned properly, can cause aortic dissection or preferential flow of blood to the innominate artery. The sys-temic arterial pressure is customarily reduced to 90–100 mm Hg systolic during placement of the aortic cannula to reduce the likelihood of dissection. Air bubbles should be absent from the arterial can-nula and inflow line, and adequacy of the connection between the arterial inflow line and the patient must be demonstrated before bypass is initiated. Failure to remove all air bubbles will result in air emboli, possibly into the coronary or cerebral circulations, whereas failure to enter the aorta may result in aor-tic dissection. Some clinicians routinely hand com-press the carotid arteries during aortic cannulation to decrease the likelihood of cerebral emboli, but the efficacy of this technique is doubtful.
One or two venous cannulas are placed in the right atrium, usually through the right atrial appendage. One cannula is usually adequate for most coronary artery bypass and aortic valve opera-tions. The single cannula used often has two por-tals (two-stage); when it is properly positioned, one opening is in the right atrium and the other is in the inferior vena cava.
Separate cannulas in the superior and inferior venae cavae are used for open-heart procedures.Hypotension from impaired ventricular filling may occur during manipulation of the venaecavae and the heart. Venous cannulation also fre-quently precipitates atrial or, less commonly, ventric-ular arrhythmias. Premature atrial contractions and transient bursts of a supraventricular tachycardia are common. Sustained paroxysmal atrial tachycardia or atrial fibrillation frequently leads to hemodynamic deterioration, which may be treated pharmacologi-cally, electrically, or by immediate initiation of bypass (provided that full anticoagulation has been con-firmed). Malpositioning of the venous cannulas can interfere with venous return or impede venous drainage from the head and neck (superior vena cava syndrome). Upon initiation of CPB, the former is manifested as inadequate volume in the venous res-ervoir, whereas the latter produces engorgement of the head and neck. Under these circumstances, cen-tral venous pressure may not increase if the tip of the central line is adjacent or very near the cannula.