Nitroglycerin (TNG) is the drug of choice for the treatment of acute myocardial ischemia. Its action is via systemic venodilation that decreases LV preload, wall tension, M[V with dot above]O₂, and coronary arterial dilation, which is operative in both stenosed coronaries and collateral beds.⁴⁷ The evidence for the prophylactic use of TNG for prevention of either intraoperative ischemic episodes or postoperative cardiac complications is unconvincing.⁴⁸ At higher doses, TNG dilates arterial beds and may cause systemic hypotension. Compensatory tachycardia may increase heart M[V with dot above]O₂. The recommended TNG dose is 0.5 to 3 μg/kg/minute and is reduced in the presence of hepatic and/or renal disease. TNG may cause methemoglobinemia especially in patients with methemoglobin reductase deficiency; this complication is more likely when large doses are administered over a prolonged time.⁴⁹ TNG is administered via special intravenous tubing that does not adsorb the drug.

Sodium nitroprusside (SNP) decreases peripheral vascular resistance by metabolic or spontaneous reduction to nitric oxide. Similar to TNG, SNP improves ventricular compliance in the ischemic myocardium. The recommended SNP dose is 0.5 to 3 μg/kg/minute and should be reduced in the presence of hepatic and/or renal disease. Adverse effects include cyanide and thiocyanate toxicity, rebound hypertension, intracranial hypertension, blood coagulation abnormalities, increased pulmonary shunting, and hypothyroidism. In vitro findings suggest that cardiac surgical patients may be at increased risk of cyanide toxicity in response to the perioperative administration of SNP.⁵⁰ Cyanide is produced when SNP is metabolized; toxic blood levels (>100 μg/dL) occur when >1.0-mg/kg SNP is administered within 2 hours or when >0.5 mg/kg/hour is administered within 24 hours. The presenting signs of cyanide toxicity include the triad of elevated mixed venous O₂ (Pvo₂), requirements for increasing SNP dose (tachyphylaxis),
and metabolic acidosis.⁵¹ In addition, the patient may appear flushed. Greater risk of cyanide toxicity exists in patients who are nutritionally deficient in cobalamine (vitamin B₁₂ compounds) or in dietary substances containing sulfur. Measurement of blood cyanide and pH will enable detection of abnormalities in high-risk patients for whom larger than recommended amounts of SNP have been used (8 to 10 μg/kg/minute). Treatment should consist of discontinuing infusion, administering 100% O₂, administering amyl nitrate (inhaler) or intravenous sodium nitrite and intravenous thiosulfate, except in those patients with abnormal renal function, for whom hydroxocobalamin is recommended. Circulating levels of thiocyanate increase when renal function is compromised, and central nervous system abnormalities result when thiocyanate levels reach 5 to 10 μg/dL. Lowering the SNP dose requirement or, better, replacing SNP with nicardipine, metoprolol, and esmolol reduces or eliminates the consequent buildup of cyanide. Once dissolved, SNP deteriorates in the presence of light. The container, therefore, should be wrapped in aluminum foil. An unstable SNP ion in aqueous solution reacts with various substances within 3 to 4 hours, forming colored salts. Other drugs should not be infused in the same solution as SNP.

Vasoconstrictors (phenylephrine, norepinephrine, vasopressin) are useful adjuncts in the prevention and treatment of ischemia because they increase systemic blood pressure, thereby improving coronary perfusion pressure, albeit at the expense of increasing afterload and perhaps M[V with dot above]O₂. In addition, concomitant venoconstriction increases venous return and LV preload. TNG is sometimes added to counteract any increase in preload. In most situations, the increase in coronary perfusion pressure more than offsets any increase in wall tension. Peripheral vasoconstriction is indicated during episodes of systemic hypotension, especially those caused by reduced surgical stimulation or drug-induced vasodilation. No one vasoconstrictor is superior to all others. Occasionally, a combination of vasoconstrictors (e.g., norepinephrine and vasopressin) may be needed to achieve the desired blood pressure.⁵²

β-adrenergic blockade improves myocardial oxygen balance by preventing or treating tachycardia and by decreasing contractility. Any concomitant myocardial depression is counterbalanced by the anti-ischemic effects. Indications for β-blockers include treatment of sinus tachycardia not resulting from the usual causes (e.g., light anesthesia, hypovolemia); prophylaxis of, and slowing the ventricular response to, supraventricular dysrhythmias; decreasing heart rate and contractility in hyperdynamic states; and control of ventricular dysrhythmias.⁵³,⁵⁴ The use of β-blockers should aim at reducing the heart rate and increasing the diastolic filling time without, at the same time, decreasing the perfusion pressure and cardiac output. These therapy targets are even more important, since the POISE study revealed that death and stroke were side effects of β-blockers.⁵⁵,⁵⁶ Intravenous preparations include propranolol, metoprolol, labetalol, and esmolol. Propranolol is a nonselective β-blocker with an elimination half-life of 4 to 6 hours. Metoprolol is similar to propranolol but has the purported advantage of β₁-selectivity and is less likely to trigger bronchospasm in patients with reactive airway disease. Labetalol combines β-blocking properties with those of α-blockade and is useful in treating hyperdynamic and hypertensive situations. Esmolol is a short-acting β₁-blocker that is cardioselective, with a half-life of only 9.5 minutes. It is particularly useful in treating transient increases in heart rate owing to episodic sympathetic stimulation.

Calcium channel blockers are useful in slowing the ventricular response in atrial fibrillation and flutter, as coronary vasodilators, and in the treatment of perioperative hypertension.⁵⁷,⁵⁸ In vitro, all calcium entry blockers depress contractility, reduce coronary and systemic vascular tone, decrease sinoatrial node firing rate, and impede atrioventricular conduction. Unlike the β-blockers, which are similar in both structure and pharmacodynamic effect, the calcium entry blockers vary remarkably in their predominant pharmacologic action. The negative inotropic effect is greatest with verapamil and less with nifedipine, diltiazem, and nicardipine (in decreasing order). Verapamil is useful in the treatment of supraventricular tachycardia and slowing the ventricular response in atrial fibrillation and/or flutter; however, its myocardial depressant effects may limit its usefulness in some patients. In patients with reduced myocardial function, intravenous diltiazem is effective in the treatment of atrial fibrillation and flutter by slowing atrioventricular conduction with minimal myocardial depression. It is also useful in decreasing sinus rate. Calcium channel blockers have been found to have cardioprotective effects during reperfusion. Nicardipine in particular has coronary antispasmodic and vasodilatory effects more than systemic arterial vasodilatory effects.⁵⁹

Nifedipine, amlodipine, and nicardipine are prominent peripheral vasodilators, effective in the treatment of postoperative hypertension in cardiac surgical patients, with minimal side effects.⁶⁰ The newer agent clevidipine was a better antihypertensive agent than SNP or TNG and was equivalent to nicardipine.⁶¹ Magnesium has coronary artery vasodilating properties, reduces the size of myocardial infarction in the setting of acute ischemia, and decreases mortality associated with infarction.⁶² In addition, it is an antiarrhythmic and minimizes myocardial reperfusion injury. While magnesium was found to prevent atrial fibrillation in coronary artery surgery,⁶³ in patients treated with β-blockers, the addition of prophylactic iv magnesium did not reduce the incidence of atrial arrhythmias.⁶⁴

The most recent guidelines for CABG surgery have been published in 2011.⁶⁵ They recommend (i) volatile agent–based anesthetic aimed at early tracheal extubation; (ii) adequate perioperative analgesia; (iii) anesthetic care by a fellowship-trained or experienced, board-certified, TEE-trained anesthesiologist; (iv) utilization of intraoperative TEE for evaluation of acute, persistent, and life-threatening hemodynamic changes, for monitoring of ventricular function and regional wall motion abnormalities, and for concomitant valvular surgery; (v) management that augments the coronary arterial perfusion pressure to reduce the risk of perioperative myocardial ischemia and infarction; (vi) administration of β-blockers to reduce the incidence (or complications) of atrial fibrillation and cardiac mortality (particularly in patients with LVEF >30%); (vii) administration of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers perioperatively; (viii) selective use of PAC; and (ix) multimodal approach for management of perioperative bleeding and transfusion, based on use of lysine analogues, point-of-care testing, discontinuation of antiplatelet medications for at least 5 days preoperatively, among others. The reader is encouraged to consult the full document at http://circ.ahajournals.org.easyaccess1.lib.cuhk.edu.hk/content/124/23/e652.

The classic symptoms of AS are angina (35%), syncope (15%), and dyspnea (50%) and are harbingers of poor outcome (death) within 5, 3 and 2 years, respectively, unless the AV is replaced. The progressive narrowing of the AV orifice results in chronic obstruction to LV ejection. Intraventricular systolic pressure increases to preserve forward flow. “Concentric” ventricular hypertrophy, in which the LV wall gradually thickens but the cavity size remains unchanged, is the compensatory response that normalizes the concomitant increase in LV wall tension. Contractility is preserved and ejection fraction is maintained at a normal range until late in the disease process (Fig. 38-4). Signs and symptoms of AS usually occur when the AV orifice is reduced to less than 0.8 to 1.0 cm².⁶⁷

The costs of the concentric hypertrophy are decreased diastolic compliance and a precarious balance between myocardial oxygen supply and M[V with dot above]O₂. Hypertrophy-induced impairment of diastolic relaxation (“stiff” LV) impedes early LV filling, and LA contraction becomes critical for maintaining adequate ventricular filling and subsequent stroke volume. In AS, the “atrial kick” may account for up to 30% to 40% of LV end-diastolic volume. The ventricular filling pressure, as reflected by pulmonary capillary wedge pressure, may vary widely with only small changes in ventricular volume (reduced compliance).

The hypertrophied muscle mass has increased basal M[V with dot above]O₂, while demand per beat rises because of the elevated intraventricular systolic pressure. Because the capillary density is often inadequate for the hypertrophic muscle, a reduction in perfusion pressure (as when the aortic diastolic pressure is decreased and/or the ventricular filling pressure is increased) may compromise supply and total vasodilator reserve. This situation is compounded in the presence of coronary obstruction. Patients with AS often present with heart failure.

There is an inverse relationship between wall stress (afterload) and LV ejection fraction. In patients with a substantial transvalvular pressure gradient (mean >40 mm Hg), AV replacement corrects the afterload excess and improves outcome. Decreased contractility results in decreased stroke volume and a hemodynamically (and echocardiographically) decreased pressure gradient (<30 mm Hg: “Pseudo-AS” or “low-gradient AS”) despite the echocardiographic presence of AS. The response to pharmacologic intervention with dobutamine or nitroprusside will clarify the diagnosis: If the calculated AV area does not change there is true AS (therefore, AV replacement is indicated), if the stroke volume increases well out of proportion to the increase in valvular gradient there is relative AS, while little or no increase in stroke volume is diagnostic of severe LV dysfunction that carries increased operative risk. However, surgical intervention has better long term than medical management alone.⁶⁸

The ideal hemodynamic environment for the patient with AS is summarized in Table 38-3. Noncardiac surgery in patients with asymptomatic severe AS may not be associated with complications (one death in 23 patients with general anesthetic, no death in 25 patients with local anesthetic), provided that their hemodynamics are invasively monitored.⁶⁹ Subsequent larger studies in these patients present conflicting results. Some show a marked increase in perioperative death and infarction rates and others do not.⁷⁰,⁷¹ The reasons for these differences are not clear, but maintenance of adequate ventricular volume and sinus rhythm is crucial.
Hypotension must be prevented and treated promptly if it develops. Anticipation of likely hemodynamic changes is essential (e.g., expected decreases in blood pressure following spinal or epidural anesthesia); treatment should be immediate. Coronary perfusion pressure must be maintained to prevent the vicious cycle of hypotension-induced ischemia, subsequent ventricular dysfunction, and worsening hypotension. Bradycardia is a common clinical cause for hypotension in the patient with AS. Slowing the heart rate and increasing diastolic time will not increase stroke volume in the LV with concentric hypertrophy. Therefore, bradycardia will induce a fall in total cardiac output and systemic arterial pressure. This is especially pertinent in the elderly or diabetic patient, in whom sinus node disease and reduced sympathetic responses may predispose to significant bradycardia. Tachycardia must be avoided because it reduces the duration of diastolic coronary perfusion.

Ischemia may be difficult to detect because the characteristic electrocardiographic changes are often obscured by signs of LV hypertrophy and strain. Elevated LV filling pressures, although not necessarily reflecting increased volume, often require treatment to optimize coronary perfusion pressure.⁶⁸ TNG is useful in this regard, but it must be remembered that minimal reductions in ventricular volume are required. Therefore, very low doses of TNG should be used and titrated to effect. In the presence of LV dysfunction, an arterial dilator, such as nicardipine (preferred over SNP),⁷² should be carefully titrated to lower afterload without affecting ventricular volume. The utility of TEE in diagnosing and grading the severity of AS is described in Chapter 26.

The physiologic consequences of hypertrophic cardiomyopathy are similar to those detailed for AS and are depicted in Figure 38-5. A subset of patients (20% to 30%) have some degree of subvalvular obstruction (hypertrophic obstructive cardiomyopathy), which may result in an LVOT gradient from a combination of anatomic
(systolic septal bulging into the LVOT, malposition of the anterior papillary muscle) and functional (drag forces, and hyperdynamic LV contraction causing a Venturi effect) factors. The LVOT gradient is dynamic in nature, increased by any intervention that reduces the LV size (increased contractility and heart rate or decreased preload or afterload). As blood is ejected rapidly through this area, the anterior mitral valve leaflet is pulled closer to the septum (systolic anterior motion), resulting in a variable MR jet, which, in the absence of organic mitral disease, is directed posteriorly.⁷⁴

In hypertrophic cardiomyopathy the myocardial oxygen balance is tenuous, and angina during exercise occurs even in the absence of coronary artery disease, if the coronary blood flow is unable to meet the demands of the hypertrophied myocardium.

In AI, blood flows into the LV from the aorta during diastole and leads to volume and pressure overload (Fig. 38-6). In chronic AI, the LV cavity increases gradually, out of proportion to the LV wall thickness (eccentric LV hypertrophy), sometimes to massive proportions, thus increasing the LV wall stress. The LV end-diastolic pressures are usually within the normal range, evidence of a significant increase in chamber compliance. As a result, and in
contrast to AS, considerable alterations in LV volume can occur with only minimal changes in LV filling pressure. Although the LV may pump more than twice the normal cardiac output, M[V with dot above]O₂ does not increase extraordinarily because the oxygen cost for muscle shortening (volume work) is low. The diastolic runoff and the moderate vasodilation reduce the LV afterload and increase the arterial pulse pressure. Thus, patients may be relatively symptom-free even when contractility is reduced. This is important in terms of planning the anesthetic, but perhaps even more so with respect to the timing of AV replacement. Ideally, the valve should be replaced just prior to the onset of irreversible myocardial damage. The outcome is better in patients with LV ejection fraction >55% or an end-diastolic LV diameter <55 mm.⁷⁵ Therefore, continued follow-up of these patients emphasizes repeated noninvasive estimations of contractility, usually after some form of afterload stress, either pharmacologic-induced or exercise-induced.

In acute AI, the previously normal in size and compliance LV is faced with a large end-diastolic volume, and the diastolic aortic to LV pressure gradient is acutely decreased.⁷⁶ As a result, the LV end-diastolic pressure rises rapidly (along the steep portion of the diastolic pressure–volume relation), the myocardial perfusion gradient is decreased, and myocardial contractility becomes impaired with severe congestive heart failure as the cardinal clinical sign. Tachycardia and peripheral vasoconstriction are the compensatory mechanisms, but they further increase the myocardial oxygen needs. In acutely ill patients, emergent AV replacement is required, whereas in less severe circumstances, mild systemic vasodilation and inotropic support may return hemodynamics toward normal.

The main goal is to avoid further increases in LV wall stress. Full preload, mildly vasodilated, and modestly tachycardic describe the optimal cardiovascular state for patients with AI (Table 38-5). Vasodilation (with an arterial dilator: nicardipine or SNP) promotes forward flow, although additional intravascular volume may be necessary to maintain adequate preload. The ideal heart rate is somewhat controversial. Tachycardia reduces the diastolic runoff from the aorta to the LV, and the LV volume and wall tension, and increases the diastolic blood pressure and coronary perfusion gradient, thus offsetting any increase in M[V with dot above]O₂ secondary to increased heart rate. Bradycardia should be avoided as it results in ventricular distention, elevations in left atrial pressure, and pulmonary congestion.

Ventricular distention may occur with the onset of CPB if the heart rate slows or if there is unexpected ventricular fibrillation (ineffective systolic ejection). Monitoring of heart size, rate, rhythm, and ventricular filling pressure is especially important in these patients. If LV distention occurs, insertion of an LV vent or immediate cross-clamping of the aorta should alleviate the problem. The presence of moderate-to-severe AI will affect the approach to CPB. After application of the aortic cross-clamp, cardioplegic solution is normally injected into the aortic root, delivering this solution to the coronary system, producing diastolic arrest of the heart. An incompetent AV prevents delivery of cardioplegia to the coronary system. Instead, cardioplegia will fill and distend the LV, increasing the ischemic insult incurred during CPB, and diastolic arrest of the heart becomes difficult. As a result, in the presence of AI the heart is arrested by injecting cardioplegia directly into the coronary ostia (after aortotomy) or into the coronary sinus (“retrograde”).

The spectrum of physiologic disruption in patients with MS is presented in Figure 38-7. Progressive decrease of the mitral valve area (MVA) impedes the blood flow from the left atrium (LA) to the LV, resulting in a pressure gradient across the mitral valve during diastole. With worsening MS, decreased LV filling will limit LV stroke volume. Although the LV myocardium may be affected by rheumatic fever and LV contractility may be impaired, LV dysfunction is caused by the combination of decreased preload and increased afterload (from reflex vasoconstriction). Proximal to the decreased MVA, the LA pressure (LAP) is elevated. According to the formula by Gorlin and Gorlin,⁷⁸

where flow is cardiac output/diastolic filling time; pressure gradient is the difference between LAP and LVDP; and K is a hydraulic pressure constant (this calculation assumes no regurgitant flow). At a constant MVA, rearrangement of the Gorlin formula reveals the clinical variables determining the elevated LAP in MS:

Therefore, increased cardiac output or decreased diastolic filling period results in increased LAP by the square of the original changes. This explains why tachycardia or increased forward flow, seen classically with pregnancy, thyrotoxicosis, or infection, can precipitate pulmonary edema in a patient with MS. Thus, the development of atrial fibrillation causes hemodynamic deterioration, not so much because of the loss of atrial contraction and associated decrease in preload, but because of the rapid rate, which by decreasing the diastolic filling time increases the LAP pressure even more. Upstream from the LA, the persistently elevated LAP, which eventually leads to LA dilatation (and atrial fibrillation, usually the first manifestation of MS), is reflected through the pulmonary circulation (pulmonary congestion and increased work of breathing), leading to right ventricular pressure overload with compensatory right ventricular hypertrophy. The progression and severity of pulmonary hypertension is variable; further narrowing of the valve orifice causes irreversible reactive changes in the pulmonary vasculature (rales on auscultation, hemoptysis). Once pulmonary hypertension has developed the
operative risk is increased (12% vs. 3% to 8%).⁷⁹ Right ventricular dysfunction, tricuspid annular dilatation, and insufficiency (engorged neck veins) may develop as the right heart function worsens.

MS mimics left heart failure, with pulmonary congestion and decreased forward flow. The only definitive treatment is relief of obstruction with mitral valve replacement; balloon valvuloplasty and open commissurotomy are palliative maneuvers. The medical interventions should aim at decreasing the heart rate (with β- or calcium channel blockers) or treating the cause(s) responsible for the increased transmitral flow. The pulmonary capillary wedge pressure is higher than the true LVDP at least by the amount of the pressure gradient and can be used as a relative index of LV filling, even during episodes of tachycardia or increased flow.

The hemodynamic goals listed in Table 38-6 are the cornerstones of prebypass anesthetic management (Table 38-6). Avoiding tachycardia precludes episodes of LA and pulmonary hypertension with potential right ventricular dysfunction, as well as inadequate LV filling with concomitant systemic hypotension. Preoperative maintenance of rate-control and β-blocking drugs, selection of anesthetics with no propensity to increase heart rate, and attainment of anesthetic levels deep enough to suppress autonomic responses are methods to achieve these goals. Episodes of pulmonary hypertension and potential right-sided heart failure stemming from factors inducing pulmonary vasoconstriction must also be prevented including hypoxia, hypercarbia, and acidosis.

Treatment of hypotension in patients with MS can present a challenging dilemma. Although these patients normally take diuretics, hypovolemia is not usually the cause; hence, the response to volume administration is often disappointing. Use of a vasoconstrictor to offset mild peripheral vasodilation is acceptable, bearing in mind the effect of pulmonary vasoconstriction on right ventricular function. It is often prudent to select a drug with some inotropic effect such as ephedrine or epinephrine instead of relying on a pure vasoconstrictor, such as phenylephrine. In separating from CPB, attention is on avoiding right ventricular failure (discussed subsequently); more commonly, however, there is LV dysfunction. This may be because of intraoperative injury or sudden increase in flow to, and distention of, the chronically underloaded LV. After bypass, prominent v waves may be present in the pulmonary capillary wedge pressure waveform. This almost always reflects increased LV filling rather than MR provided that the cardiac output is increased when compared with preinduction values. The echocardiographic evaluation of MS is described in Chapter 26.

Volume overload similar to that described with AI is the car dinal feature of MR (Fig. 38-8). The LA acts as a low-pressure outlet during LV ejection; with the onset of ventricular systole blood is ejected retrograde (there is no isovolumetric contraction period). In MR, the total LV output consists of forward (systemic, via the aorta) and retrograde (into the LA) blood volumes. The aftermaths of MR are atrial and ventricular chamber
enlargement (due to “back-and-from” blood flow), ventricular wall hypertrophy (to compensate for the increased chamber size), and increased blood volume. The LV compliance is increased so that the large LV end-diastolic volume does not cause striking increase in pressure. There is no concomitant increase in oxygen requirements because there is little pressure development. As a result, patients may have minimal symptoms as well as normal or slightly reduced ejection fraction, despite progressive myocardial dysfunction and decreased contractility The regurgitant blood volume is related to the size of the regurgitant mitral orifice, the systolic time, the pressure gradient across the valve, and the compliance of the LA. The regurgitant orifice size, in turn, depends on the valvular defect and ventricular size. Therefore, increases in heart rate, reduction of preload, and arterial dilators are effective in reducing the regurgitation of blood volume from the LV to LA.

Repairing or replacing the mitral valve increases the LV afterload and unmasks any underlying myocardial dysfunction. Administration of inotropes and/or vasodilators, as well as judicious increase in preload, may be necessary to successfully separate from bypass.

Acute-onset MR has a different hemodynamic picture; acute LA and LV volume overload occurs in the absence of compensatory LV enlargement. Ventricular filling pressures increase dramatically, as do pulmonary pressures. Cardiac output decreases, and pulmonary edema develops. In the setting of acute myocardial infarction, contractility may be inadequate despite pharmacologic support, and intra-aortic balloon assistance and emergency surgery may be lifesaving.

Selection of anesthetics that promote vasodilation and tachycardia is ideal in the patient with MR (Table 38-8). In chronic MR, vasoactive medications are usually not necessary because of LV compensatory mechanisms. However, patients with acute MR may need aggressive pharmacologic management. In the absence of acute deterioration, pharmacologic intervention is not needed usually until the postbypass period. However, vasodilators and inotropes may lead to reoccurrence or worsening of MR when, following MV repair surgery, systolic anterior motion of the anterior mitral leaflet results in obstruction of the LVOT. The pathophysiologic and clinical picture is similar to that of hypertrophic cardiomyopathy. The risk of systolic anterior motion after repair is increased when the anterior leaflet is longer than the posterior leaflet or when there is a narrow angle between the mitral and aortic annuli. If this scenario is suspected, a trial of volume expansion and vasoconstrictors is indicated. The approach to evaluation of MR severity is described in Chapter 26.