Myxoma

Often a diagnostic challenge, myxoma, a benign, solitary neoplasm that is slowly and microscopically proliferating, resembles an organized clot, which often obscures its identity as a primary cardiac tumor. The pedunculated mass is believed to arise from undifferentiated cells in the fossa ovalis and adjoining endocardium, projecting into the left atrium (LA) and right atrium (RA) 75% and 20% of the time, respectively. However, myxomas appear in other locations of the heart, even occupying more than one chamber. The undifferentiated cells of a myxoma develop along a variety of cell lines, accounting for the multiple presentations and pathologic conditions observed. Any age group can be affected. Myxomas predominate in the 30- to 60-year-old age range, with more than 75% of the affected patients being women.

Rarely discovered by incidental echocardiography examination, myxomas may manifest a variety of symptoms. The classic triad includes embolism, intracardiac obstruction, and constitutional symptoms. Approximately 80% of individuals present with one component of the triad, yet up to 10% may be asymptomatic even with mitral myxomas, arising from both atrial and ventricular sides of the anterior mitral leaflet. The most common initial symptom, dyspnea on exertion, reflects mitral valve obstruction usually present with LA myxomas (Fig. 18-1). Because of the pedunculated nature of some myxomas, temporary obstruction of blood flow may cause hemolysis, hypotension, syncope, or sudden death. Other symptoms of mitral obstruction similar to mitral stenosis such as hemoptysis, systemic embolization, fever, and weight loss may also occur. The persistence of sinus rhythm in the presence of such symptoms may help distinguish atrial myxoma from mitral stenosis. Severe pulmonary hypertension without significant mitral valve involvement suggests obstruction of the tricuspid valve and recurrent pulmonary emboli known to occur with a myxoma in the RA or right ventricle (RV). Before echocardiography, angiography was used to identify all myxomas, but now it is only useful to confirm the diagnosis or determine coronary anatomy if considered necessary. TEE is 100% sensitive for diagnosis of myxoma. Specifically, it yields morphologic detail in the evaluation of cardiac tumors, including points of tumor attachment and degree of mobility. Computed tomography (CT) and MRI can help delineate the extent of the tumor and its relationships to surrounding cardiac and thoracic structures. MRI is especially valuable in the diagnosis of myxoma when masses are equivocal or suboptimal on echocardiography or if the tumor is atypical in presentation. Difficulty may arise in differentiating thrombus from myxoma because both are so heterogeneous.²

Figure 18-1 Transesophageal echocardiogram showing a left atrial myxoma prolapsing across and obstructing the mitral valve.

(Reprinted with permission from Shapiro LM: General cardiology cardiac tumors: Diagnosis and management. Heart 85:219, 2001. Reproduced with permission from the BMJ Publishing Group.)

The first surgical resection of an atrial myxoma was performed in 1954. Subsequently, surgical resection has been recommended even if the myxoma is discovered incidentally, primarily because of the risk of embolization. Generally, the time interval between onset of symptoms and surgical resection is about 4 months, but surgery has been delayed for 10 years. Surgery is associated with a mortality rate of 0% to 3%.

Tumors with Systemic Cardiac Manifestations

Carcinoid tumors are metastasizing tumors that arise primarily from the small bowel, occurring in 1 to 2 per 100,000 people in the population. Fewer than 5% of individuals with carcinoid tumors develop carcinoid syndrome, which is characterized by vasomotor symptoms, bronchospasm, and right-sided heart disease attributed to the release of serotonin, histamine, bradykinins, and prostaglandins, often in response to manipulation or pharmacologic stimulation. Manifestations of carcinoid syndrome occur primarily in patients with liver metastasis that impairs the ability of the liver to inactivate large amounts of vasoactive substances.

Initially described in 1952, carcinoid heart disease develops in more than 50% of patients with carcinoid syndrome and may be the initial feature. The prognosis has improved in the past 20 years for individuals with malignant carcinoid tumors, but carcinoid heart disease still causes considerable morbidity and mortality. Circulating serotonin levels have been found to be more than twice as high in persons with carcinoid syndrome who develop carcinoid heart disease. Carcinoid heart disease characteristically involves tricuspid regurgitation and pulmonic stenosis, resulting in severe right-sided heart failure. The left heart is usually spared involvement in carcinoid heart disease, possibly due to inactivation of serotonin in the lungs, but it may exist with the presence of a bronchial carcinoid or an interatrial shunt.

Without treatment, survival with carcinoid heart disease rarely exceeds 3 years. Surgery to replace both tricuspid and pulmonary valves with either bioprosthetic or mechanical valves is the only viable therapeutic option. The optimal timing to operate is uncertain, but consideration should be given to when signs of RV failure appear, in combination with steady follow-up. Perioperative mortality has been reported as high as 35%, but more recent data suggest it is below 10%. Despite surgery, RV dysfunction persists.

Dilated Cardiomyopathy

DCM is by far the most common of the four cardiomyopathies in adults (60%). It is a condition of diverse etiologies such as viral, inflammatory, toxic, or familial/genetic and is associated with many cardiac and systemic disorders that influence the prognosis.

DCM is characterized morphologically by enlargement of RV and LV cavities without an appropriate increase in the ventricular septal or free wall thickness, giving an almost spherical shape to the heart. The valve leaflets may be normal, yet dilation of the heart may cause a regurgitant lesion secondary to displacement of the papillary muscle.

With DCM, there is more impairment of systolic function even though diastolic function is affected. As contractile function diminishes, stroke volume is initially maintained by augmentation of end-diastolic volume. Despite a severely decreased ejection fraction, stroke volume may be almost normal. Eventually, increased wall stress due to marked LV dilation and normal or thin LV wall thickness, combined with probable valvular regurgitation, compromises the metabolic capabilities of heart muscle and produces overt circulatory failure. Compensatory mechanisms may allow symptoms of myocardial dysfunction to go unnoticed for an extended period of time.

Management of acute decompensated CHF continues to evolve, but the onset of overt CHF is a poor prognostic indicator for patients with DCM. Treatment revolves around management of symptoms and progression of DCM, whereas other measures are designed to prevent complications such as pulmonary thromboembolism and arrhythmias. The mainstay of therapy for DCM is vasodilators combined with digoxin and diuretics.⁴ All patients receive angiotensin-converting enzyme inhibitors (ACEIs) to reduce symptoms, improve exercise tolerance, and reduce cardiovascular mortality without a direct myocardial effect. Perhaps more important than the hemodynamic effects, ACEIs suppress ventricular remodeling and endothelial dysfunction, accounting for the improvement in mortality noted with this medication in DCM. Other afterload-reducing agents, such as selective phosphodiesterase-3 inhibitors like milrinone, may improve quality of life but do not affect mortality, so they are rarely administered in chronic situations. Spironolactone has assumed a greater role in treatment as mortality was reduced by 30% from all causes in patients receiving standard ACEIs for DCM with the addition of spironolactone in a large double-blind randomized trial. The use of β-blockers in DCM has provided not only symptomatic improvement but also substantial reductions in sudden death and progressive death in patients with New York Heart Association (NYHA) class II and III heart failure. This is especially significant because almost 50% of deaths are sudden. High-grade ventricular arrhythmias are common with DCM. Approximately 12% of all patients with DCM die suddenly, but overall prediction of sudden death in an individual with DCM is poor. The best predictor of sudden death remains the degree of LV dysfunction. Patients who have sustained ventricular tachycardia or out-of-hospital ventricular fibrillation are at increased risk for sudden death, but more than 70% of patients with DCM have nonsustained ventricular tachycardia during ambulatory monitoring. Antiarrhythmic medications are hazardous in patients with poor ventricular function owing to their negative inotropic and sometimes proarrhythmic properties. Amiodarone is the preferred antiarrhythmic agent in DCM because its negative inotropic effect is less than that of other antiarrhythmic medications and its proarrhythmic potential is lowest. Implantable defibrillators reduce the risk of sudden death as well as reducing mortality. Evidence has indicated that with previous cardiac arrest or sustained ventricular tachycardia, more benefit was gained from use of an implantable defibrillator. This was based on a 27% reduction in the relative risk of death attributed to a 50% reduction in arrhythmia-related mortality compared with treatment with amiodarone.

Patients who are resistant to pharmacologic therapy for CHF may derive benefit from dual-chamber pacing, cardiomyoplasty, or LV assist devices. Placement of LV assist devices has improved patients sufficiently to avoid heart transplantation or enable later transplantation. Transplantation can substantially prolong survival in patients with DCM, with a 5-year survival of 78% in adults.

Hypertrophic Cardiomyopathy

Referred to as idiopathic hypertrophic subaortic stenosis, hypertrophic obstructive cardiomyopathy, and asymmetric septal hypertrophy, among other names, the accepted term is now hypertrophic cardiomyopathy.⁵ In the past 40 years, advancements regarding the hemodynamics, systolic and diastolic abnormalities, electrophysiology, genetics, and clinical care of HCM have contributed to a greater understanding of this disease. HCM is the most common genetic cardiac disease, with marked heterogeneity in clinical expression, pathophysiology, and prognosis. The overall prevalence for adults in the general population is 0.2%, affecting men and women equally.

HCM is a primary myocardial abnormality with sarcomeric disarray and asymmetric LV hypertrophy. The extent of sarcomeric disarray distinguishes HCM from other conditions. The hypertrophied muscle is composed of muscle cells with bizarre shapes and multiple intercellular connections arranged in a chaotic pattern. Increased connective tissue combined with markedly disorganized and hypertrophied myocytes contributes to the diastolic abnormalities of HCM that manifest as increased chamber stiffness, impaired prolonged relaxation, and an unstable EP substrate that causes complex arrhythmias and sudden death. Diastolic abnormalities are more a function of impaired relaxation than of decreased compliance. Impaired relaxation produces a reduced rate of volume during rapid ventricular filling, with an increase in atrial systolic filling associated with atrial dilation. As the abnormal diastolic properties affect ventricular filling, the clinical manifestations of HCM become evident. In contrast to the diastolic function, systolic function in HCM is usually normal, with an increased ejection fraction that eventually diminishes in the later stages of the disease.

Besides diastolic dysfunction, the other major abnormality and fundamental characteristic of HCM is myocardial hypertrophy unrelated to increased systemic vascular resistance (SVR). This nonuniform, asymmetric hypertrophy is marked in the basal anterior ventricular septum, with a disproportionate increase in the thickness of the ventricular wall relative to the posterior free wall. The LV wall thickness is the most extensive of all cardiac conditions. Heart size may be deceptive because it may vary from normal to more than 100% enlarged. However, chamber enlargement is not responsible for the increase in ventricular mass but rather increases in wall thickness.

Symptoms of HCM are nonspecific and include chest pain, palpitations, dyspnea, and syncope. Dyspnea occurs in 90% of patients secondary to diastolic abnormalities that increase filling pressures, causing pulmonary congestion. Syncope occurs in only 20% of patients, but 50% may have presyncopal symptoms.

Two-dimensional echocardiography establishes the diagnosis of HCM easily and reliably. Classic echocardiography features are thickening of the entire ventricular septum from base to apex disproportional to that of the posterior wall, poor septal motion, and anterior displacement of the mitral valve without LV dilation (Fig. 18-2). Echocardiography has reduced the need for invasive catheterization procedures, unless coronary artery disease (CAD) or severe mitral valve disease is suspected or diagnostic problems are present. MRI has been useful in cases in which echocardiography is technically inadequate.

Figure 18-2 A, Parasternal long-axis view of a patient with hypertrophic cardiomyopathy (HCM). There is increased thickness of the septum from the base to the apex as well as the anterior free wall. The left ventricular cavity size is normal here. B, Transesophageal echocardiography in a patient with HCM for myectomy-myotomy. Early systole, demonstrating septal hypertrophy and narrowing of the left ventricular outflow tract (LVOT). C, Same patient in late systole. Systolic anterior motion of the mitral leaflets produced by a Venturi effect in the LVOT created by the high blood velocity. D, After myectomy-myotomy, the arrowheads point to the area of myocardium removed and the widened LVOT. LA = left atrium; RA = right atrium; LV = left ventricle; RV = right ventricle; VS = ventricular septum; MV = mitral valve; Ao = aorta; PW = posterior wall.

(A, reprinted with permission from Giuliani ER, Fuster V, Gersh BJ, et al: Cardiology: Fundamentals and Practice. St. Louis, Mosby, 1991; B, C, and D courtesy of Martin D. Abel, MD, Mayo Clinic, Rochester, MN.)

Two thirds of individuals with LV outflow tract obstruction become severely symptomatic and 10% die within 4 years of diagnosis. The outflow tract is narrowed from septal hypertrophy and anterior displacement of the papillary muscles and mitral leaflets, creating a dynamic LV outflow obstruction (see Fig. 18-2). Elongation of the mitral leaflets results in coaptation of the body of the leaflets instead of the tips. The part of the anterior leaflet distal to the coaptation is subjected to strong Venturi forces that provoke systolic anterior motion (SAM), mitral septal contact, and ultimately LV outflow obstruction. SAM of the anterior leaflet may also cause mitral regurgitation. The onset and duration of mitral leaflet-septal contact determine the magnitude of the gradient and the degree of mitral regurgitation. The pressure gradient between the aorta and LV is worsened by decreased end-diastolic volume, increased contractility, or decreased aortic outflow resistance (Fig. 18-3).

Figure 18-3 Interventions that change the outflow gradient in hypertrophic cardiomyopathy (HCM), with resultant change in intensity of the systolic murmur in HCM. Outflow gradient is affected by changes in afterload, preload, and contractility. Ao = aorta; LA = left atrium; MV = mitral valve; VS = ventricular septum; LV = left ventricle; PW = posterior wall.

(Reprinted with permission from Giuliani ER, Fuster V, Gersh BJ, et al: Cardiology: Fundamentals and Practice. St. Louis, Mosby, 1991. By permission of Mayo Foundation.)

Surgical correction of HCM is directed primarily at relieving symptoms of LV obstruction in the 5% of patients who are refractory to medication.⁶ In general, these are individuals with subaortic gradients more than 50 mmHg and frequently associated with severe CHF. A myotomy-myectomy through a transaortic approach relieves the obstruction. The muscle is excised from the proximal septum extending just beyond the mitral valve leaflets to widen the LV outflow tract. This is a technically challenging operation due to the limited exposure and precise area to excise the muscle. It is usually reserved for centers with considerable experience. When myectomy is successful, the outflow tract of the LV is widened and SAM, mitral regurgitation, and outflow gradient are all decreased.

Restrictive Cardiomyopathy

Restrictive cardiomyopathy (RCM) has included such entities as amyloidosis and eosinophilic endomyocardial disease. The 1995 WHO guidelines defined RCM as “restrictive filling and reduced diastolic volume of either or both ventricles with normal or near-normal systolic function and wall thickness.” Instead of being classified according to morphologic criteria, as are HCM and DCM, RCM is characterized by function. It may appear in the final stages of other cardiac conditions.

RCM may be classified as myocardial (infiltrative, noninfiltrative, and storage) or endomyocardial (Box 18-1) according to etiology. RCM may be associated with another disease entity except pericardial disease. Restrictive myocardial disorders are characteristically atypical in presentation and hemodynamics at times, complicating perioperative management.

Because one or both ventricles may be involved, symptoms may predominate as right or left sided. The elevated filling pressures that occur in early diastole of both ventricles lead to symptoms of right-sided failure manifested by elevated venous pressures and peripheral edema and ascites or of left-sided failure manifested by CHF and progressive dyspnea and orthopnea. Both groups of symptoms may occur separately or together.

Arrhythmogenic Right Ventricular Cardiomyopathy

Formerly called arrhythmogenic right ventricular dysplasia, ARVC is defined by the 1995 WHO as “progressive fibrofatty replacement of RV myocardium, initially with typical regional and later global RV and some LV involvement, with relative sparing of the septum.” Evidence of a more progressive involvement of not only the RV but also the LV with long-term follow-up convinced the WHO to classify ARVC as a “disease of the myocardium” that incorporates the many different clinical presentations and aspects of this condition.

It presents as the onset of arrhythmias ranging from premature ventricular contractions to ventricular fibrillation originating from the RV. Diagnosis has been rare in the early stages but not at autopsy. Identifying symptoms are absent even though structural changes exist in the myocardium. Postmortem examination reveals diffuse or segmental loss of myocardium, primarily in the RV, replaced with fat and fibrous tissue. The replacement of myocardium with fat and fibrous tissue creates an excellent environment for a fatal arrhythmia, possibly the first sign of ARVC. Sudden death occurs in up to 75% of patients, although it is difficult to accurately state in view of the extent of missed diagnosis. Sudden death occurs most often during sports-related exercise, primarily from ventricular tachycardia/fibrillation. Twenty percent of patients die as a result of CHF.

Anesthetic Considerations

It is important to distinguish between MVP syndrome and anatomic MVP regarding anesthetic considerations. Most individuals with MVP have an uncomplicated general anesthetic because they have MVP syndrome. These patients are usually younger than 45 years of age with few risk factors for anesthesia. Invasive monitoring is usually unnecessary. Patients may be taking β-blockers. Preoperative sedation is useful to suppress an increased sensitivity to catecholamines. Painful stimuli may exacerbate the autonomic system, possibly causing arrhythmias. Significant decreases in LV end-diastolic volume and SVR, or increased contractility and tachycardia, should be avoided because MVP may be enhanced by decreasing CO and coronary perfusion. Intraoperative arrhythmias usually resolve spontaneously or respond to standard therapy. If an arrhythmia occurs, adequate oxygenation should be confirmed and other causes of intraoperative arrhythmias investigated. If β-blockers are required perioperatively, the use of esmolol avoids the potential for prolonged blockade that might cause hemodynamically significant bradycardia. Digoxin may worsen MVP.

Anticholinergic preoperative medications are best avoided despite an increased vagal tone. A moderate anesthetic depth is desirable to minimize catecholamine levels and potential arrhythmias. Ketamine or drugs that have sympathomimetic effects must be administered with caution. These patients with MVP syndrome have been shown to possess good LV function if mitral regurgitation or CAD is absent; myocardial depression from volatile agents will be well tolerated. Narcotics such as fentanyl block sympathetic responses and promote hemodynamic stability; however, prolonged postoperative respiratory depression is a disadvantage. Shorter-acting narcotics such as alfentanil and remifentanil, as well as other intravenous agents such as propofol, are available to facilitate rapid extubation. Hypercapnia, hypoxia, and electrolyte disturbances increase ventricular excitability and should be corrected. If muscle relaxation is desired, vecuronium is an excellent choice because it does not cause tachycardia.

Patients with anatomic MVP warrant a different anesthetic approach compared with those with MVP syndrome. Patients with anatomic MVP are often in CHF and generally require cardiac surgery and CPB. The severity of mitral regurgitation strongly influences anesthetic decisions. Routine monitoring for patients undergoing cardiac surgery should be provided. TEE is placed after induction. Opioid agents provide excellent hemodynamic stability without depressing myocardial function.

Anesthesia Considerations for Pulmonary Embolectomy and Pulmonary Embolism

The first surgical embolectomy without CPB was described by Trendelenburg in 1908, and the first with CPB was described by Cooley in 1961. Its frequency has decreased, partly due to the success of thrombolytic measures for massive PE; however, thrombolysis is unsuccessful in 15% to 30% of cases. Of 3000 patients with documented PE over a 20-year period, 3% underwent pulmonary embolectomy.¹¹ In general, it has been reserved for patients with PE and refractory circulatory compromise, failed medical management, or contraindications to thrombolysis. Contraindication to thrombolysis accounts for more than one third of embolectomies. The overall mortality of pulmonary embolectomy varies between 20% and 90%. The patient’s preoperative status is predictive of survival. Preoperative cardiac arrest increases operative mortality by more than 50%. Age older than 60 years and a long history of dyspnea also increase the mortality of embolectomy. Echocardiography has greatly decreased the time to surgery by enabling a rapid and reliable diagnosis to be made without angiography. This has improved not only initial survival rate of embolectomy but also long-term survival.

Induction of anesthesia is a very hazardous period in the presence of PE and RV dysfunction that has precipitated cardiac arrest. Intraoperative monitoring should include an arterial catheter, ECG, pulse oximeter, capnograph, and CVP catheter or PA catheter. An inotrope may also be needed before induction. Individuals with massive PE have more of a “fixed” CO, which makes them extremely susceptible to decreases in volume and SVR. Cannulation of the femoral vessels under local anesthetic to initiate CPB may be advisable if the administration of anesthesia is judged too hazardous. Once the cannula is in place, positioning, skin cleansing, and draping should proceed while the patient is awake and breathing oxygen. After the patient is placed in a slightly head-down position to prevent venous pooling, an intravenous induction is performed. Anesthetic agents that increase PVR must be used cautiously in this setting. Ketamine is well known as an anesthetic agent for use in critically ill patients to maintain hemodynamics. Concerns about ketamine and increased PVR are unfounded if ventilation is maintained.

Embolectomy via right or left thoracotomy may be performed without CPB through venous inflow occlusion while clamping the proximal portion of the involved pulmonary artery to allow clot removal. Rapid institution of CPB by femoral cannulation percutaneously may be lifesaving in patients with cardiovascular collapse. If embolectomy is performed on CPB, the patient remains normothermic, the aorta is not cross-clamped, and cardioplegia is not administered. Maintenance of higher perfusion pressures reduces RV stunning. The CPB time is usually less than 30 minutes for embolectomy. Reperfusion bleeding may occur when reestablishment of pulmonary blood flow causes severely damaged capillaries of the pulmonary parenchyma to rupture. Large amounts of blood may be aspirated from the endotracheal tube (ETT). Large-bore intravenous catheters are necessary for embolectomy because rapid and massive blood loss can occur through reperfusion pulmonary hemorrhage.

Primary Pulmonary Hypertension

The essential characteristic of primary PAH is increased PVR that results in increased PAP, hypoxemia, elevated RV pressure, right-sided heart failure, and death. The National Institutes of Health registry’s criteria for primary PAH include a PAP of more than 25 mmHg at rest or more than 30 mmHg with exercise and exclusion of the causes of secondary PAH. It is a rare disorder, occurring in one or two individuals per 1 million people per year, primarily women in their third decade. The diagnosis is often delayed an average of 2 years owing to the nonspecific nature of the symptoms. Previously, even an early diagnosis yielded a median survival of 2.8 years. The introduction of intravenous epoprostenol (synthetic salt of prostacyclin) in the 1990s improved hemodynamics, functional capacity, and survival in patients with primary PAH in NYHA functional class III or IV. Treatment options have expanded as a new generation of drugs is being developed to address the pathologic arms of primary PAH.

Therapy for primary PAH is evolving but mostly remains empirical and nonspecific. Conventional therapy includes restricted activity, diuretics, anti-coagulation, digoxin, and pulmonary vasodilators. For years, calcium channel blockers have been useful to lower PAP 10% to 20% if vasoreactivity testing was positive. Otherwise, they may precipitate right-sided heart failure and even death in those with primary PAH. Pulmonary vasodilators are administered to decrease PVR, PAP, and RV afterload. Many pulmonary vasodilators have been tried, with unreliable and short-term benefit. Continuous prostaglandin therapy was found to improve hemodynamics and exercise to tolerance and to prolong survival. Because prostaglandin therapy requires continuous intravenous administration to be efficacious, alternate forms have been created: oral (beraprost), subcutaneous (treprostinil), and inhaled (iloprost). Prostaglandin therapy contains valuable anti-inflammatory properties that represent treatment for PAH directed at the various pathologic mechanisms considered responsible for PAH besides pulmonary vasodilation. Newer agents targeting thromboxane inhibition (terbogrel) and endothelin-receptor antagonism (bosentan, sitaxsentan, and ambrisentan) have been developed. A new pulmonary vasodilator, sildenafil, may act synergistically with other vasodilators by inactivating the phosphodiesterase enzymes that inactivate the second messengers for the vasodilating signals cyclic adenosine monophosphate and cyclic guanosine monophosphate in lung tissues.

Secondary Pulmonary Hypertension

In most patients, PAH is secondary to cardiac or pulmonary disease. The term “secondary” PAH is being used less because of the many therapies for PAH regardless of etiology. Secondary PAH is more common than primary PAH. Often, the underlying disease overshadows the clinical manifestations of PAH. The natural history, prognosis, and appropriate treatment of patients with secondary PAH depend on the underlying condition. Secondary PAH may be reversible. Once the etiology of PAH is identified, treatment should begin immediately because it is most effective if instituted before the onset of right-sided heart failure. Unfortunately, at the time of diagnosis, PAH has often progressed to the point that the value of any treatment is limited to palliation of incapacitating symptoms.

Anesthetic management of individuals with PAH is challenging because perioperative increases in PVR readily occur and may provoke right-sided heart failure, resulting in death. The tolerance of the RV is a major concern. The RV is acutely sensitive to increases in PVR (afterload). Factors that increase PVR, such as hypoxia, acidosis, hypercapnia, hypothermia, and α-adrenergic stimulation, should be minimized. Furthermore, a decrease in blood pressure or increase in RV pressure impairs coronary perfusion of the right side of the heart. A PA catheter allows perioperative detection and monitoring of PVR and therapy, enabling hyperventilation to reduce PVR. In general, intravenous anesthetics have less effect on hypoxic pulmonary vasoconstriction, PVR, and oxygenation than do volatile agents. Nitrous oxide has been reported to increase PVR, but it is not contraindicated in these patients. Isoflurane may be beneficial by decreasing PAP and has been frequently used during noncardiac procedures. Fentanyl may be given as an adjunct or a primary anesthetic agent in these patients because it causes little myocardial depression and excellent circulatory stability.¹³

Pulmonary endarterectomy (PEA) is the accepted treatment today for chronic thromboembolic pulmonary hypertension. The operation is not an embolectomy but rather a true endarterectomy, removing the fibrosis obstructive tissue from the pulmonary arteries. Extracorporeal circulation and periods of circulatory arrest under deep hypothermia are essential for successful endarterectomy.¹⁴

Anesthetic Considerations for Pericardial Disease

Pericardiectomy is performed for recurrent pericardial effusion and constrictive pericarditis. Pericardial dissection for effusive pericarditis is straightforward; however, pericardiectomy for constrictive pericarditis is a surgical challenge with a mortality of 5% to 15% and 5-year survival of 78%. Persistent low CO immediately after pericardiectomy is the primary cause of morbidity and mortality. In contrast to patients with cardiac tamponade, who usually improve clinically once the pericardium is opened, improvement is not always apparent initially after pericardiectomy. Instead, noticeable improvement in cardiac function may take weeks. Yet, 90% of patients ultimately experience relief of symptoms with surgery.

Median sternotomy provides excellent exposure and access for pericardiectomy, but thoracotomy in the left anterolateral position is also used. Opinions vary regarding the extent of pericardial resection for alleviation of cardiac constriction and the use of CPB. Good results have been obtained with and without CPB. Removal of adherent and scarred pericardium to release both the RV and LV involves extensive manipulation of the heart. Some have advocated routine CPB for pericardiectomy because a more complete pericardial excision and hemodynamic stability were thought possible. Yet, heparinization and CPB may exacerbate blood loss from exposed cardiac surfaces. Furthermore, prolonged CPB in debilitated patients contributes to early mortality associated with pericardiectomy.

Anesthetic goals for managing patients with constrictive pericarditis who require pericardiectomy include minimizing bradycardia and myocardial depression and minimizing decreases in afterload or preload. Monitoring considerations include arterial and central venous pressures. A dorsalis pedis or femoral arterial catheter in patients with uremic pericarditis may preserve future potential arteriovenous fistula sites in the upper extremities. One groin site should be reserved in case femoral cannulation is necessary to emergently initiate CPB. PA catheter monitoring is recommended due to the occurrence of postoperative low CO syndrome. Low CO, hypotension, and arrhythmias (atrial and ventricular) are common during chest dissection. Due to limited ventricular diastolic filling, CO is rate dependent. If myocardial function or heart rate is depressed, β-agonists or pacing improve CO. Lidocaine infusion may partially suppress arrhythmias during dissection. Catastrophic hemorrhage can occur suddenly if the atrium or ventricle is perforated, so sufficient venous access is necessary. Damage to coronary arteries may also occur during dissection; careful monitoring of the ECG for signs of ischemia is prudent. Pericardiectomy via left anterior thoracotomy requires close monitoring of oxygenation because the left lung is severely compressed during dissection. Anesthetic technique is based on achieving early extubation; however, patients who undergo pericardiectomy for constrictive pericarditis benefit from remaining intubated for at least 6 to 12 hours to assess bleeding and CO.

Cardiac Tamponade

Tamponade exists when fluid accumulation in the pericardial sac limits filling of the heart. Hemodynamic manifestations are mainly due to atrial rather than ventricular compression. Initially, with mild tamponade, diastolic filling is limited, causing reduced stroke volume that stimulates sympathetic reflexes to increase heart rate and contractility to maintain CO.¹⁵ The rising RA pressure reflexly stimulates tachycardia and peripheral vasoconstriction. Blood pressure is supported by vasoconstriction, but CO begins to fall as pericardial fluid continues to increase. Subsequently, diastolic filling begins to disappear so the jugular venous pulse has no prominent Y-descent but a prominent X-descent. Eventually, the pericardial pressure-volume curve becomes almost vertical so any additional fluid greatly restricts cardiac filling and reduces diastolic compliance. Ultimately, the RA pressure, pulmonary artery diastolic pressure, and pulmonary capillary wedge pressure equilibrate. Equilibration of pressures (within 5 mmHg of each other) merits immediate action to rule out acute tamponade. Once the blood pressure begins to fall, it is a precipitous drop that reduces coronary artery blood flow, leading to ischemia, especially subendocardially.

The classic diagnostic triad of acute tamponade consists of (1) decreasing arterial pressure, (2) increasing venous pressure, and (3) a small, quiet heart. Pulsus paradoxus may be present; this is a fall in systolic blood pressure of more than 12 mmHg during inspiration caused by reduced LV stroke volume generated by increased filling of the right heart during inspiration. It is not specific for tamponade, because it may be present in patients with obstructive pulmonary disease, RV infarction, or constrictive pericarditis. It may be absent if there is LV dysfunction, positive-pressure breathing, atrial septal defect, or severe aortic regurgitation. ECG changes with tamponade include low-voltage QRS complex, electrical alternans, and T-wave abnormalities. Sinus rhythm is usually present in tamponade. Echocardiography is the most reliable noninvasive method to detect pericardial effusion and exclude tamponade; echocardiography usually reveals an exaggerated motion of the heart within the pericardial sac in conjunction with atrial and ventricular collapse. Additionally, echocardiography is used to guide needle or catheter aspiration of pericardial effusion.

After cardiac surgery, tamponade due to hemorrhage requires immediate mediastinal exploration to determine bleeding site and stabilize hemodynamics. The numerous causes of hypotension in the postoperative cardiac surgical patient make tamponade more difficult to diagnose. Persistent poor CO with increased and equalized RA and LA pressures strongly suggests tamponade, but classic signs are often missing in the postoperative cardiac surgical patient. Arterial hypotension, pulsus paradoxus, and raised jugular venous pressures were absent in one series of cardiac surgical patients by 30%, 40%, and 50%, respectively. Although echocardiography is capable of identifying the size of pericardial effusions postoperatively, it does not necessarily reflect its likelihood to cause tamponade. Late cardiac tamponade occurs in 0.1% to 6% of patients after cardiac surgery. A delay in diagnosis contributes greatly to mortality in late cardiac tamponade.

Pericardiocentesis is indicated for life-threatening cardiac tamponade in conjunction with a fluid infusion to maintain filling pressures. Hemodynamics improve immediately after pericardiocentesis. Although it does provide immediate relief of the symptoms of tamponade, definitive therapy requires drainage of the pericardial space. Major complications of pericardiocentesis include coronary laceration, cardiac puncture, and pneumothorax. Surgical management of pericardial tamponade includes subxiphoid pericardiotomy, pericardial window through a left anterior thoracotomy, and pericardiectomy.

Anesthesia Considerations

CRF affects dosing of medications that have a large volume of distribution. Decreased serum protein concentration diminishes plasma binding, leading to higher levels of free drug to bind with receptors. Many patients with CRF are hypoalbuminemic. In general, anesthetic induction agents and benzodiazepines are safe to use in patients with CRF. A common induction agent, thiopental, is highly protein bound so the dose should be reduced accordingly. Medications that rely totally on renal excretion have a limited role. Fentanyl and sufentanil may be more effective for pain management because excretion is not as renally dependent as morphine sulfate. Currently used volatile anesthetic agents rarely cause any additional renal dysfunction even with underlying CRF unless severely prolonged duration of anesthesia occurs. Muscle relaxants and agents for antagonism of muscle paralysis have varying degrees of renal excretion.

A rapid-sequence induction with cricoid pressure is recommended in those with CRF in response to the likelihood of delayed gastric emptying. Significant extracellular volume contraction may also be present before induction of anesthesia due to a 6- to 8-hour fast before surgery and dialysis within 24 hours of surgery that may lead to hypotension on induction. Because fluid requirements are usually significant with CPB, a PA catheter is especially useful to manage fluid requirements. TEE may complement fluid management by assessment of LV volume and function. Before the initiation of CPB, fluid administration should be limited, especially if the patient is dialysis dependent. Otherwise, fluid should be given to maintain adequate urine output but avoid excessive cardiovascular filling pressures risking pulmonary edema. However, restricting fluids too aggressively in these patients may lead to acute renal failure superimposed on CRF. Low-dose dopamine has been recommended for patients with CRF, but its value is indeterminate. Fenoldopam, a new dopamine-1-receptor agonist, may reduce the incidence of renal dysfunction in patients with multiple risk factors for renal failure undergoing CPB. Patients with preoperative creatinine levels above 1.5 mg/dL were given renal-dose dopamine or fenoldopam perioperatively.¹⁷ Postoperative parameters were only improved in those receiving fenoldopam, suggesting a renal protective effect.

In general, CRF worsens after CPB in part owing to a combination of nonpulsatile flow, low renal perfusion, and hypothermia. Renal perfusion is lowered as CPB is initiated, increasing the chance for ischemia of the renal cortex. Mean arterial pressure should be kept above 80 mmHg. The stress of surgery and hypothermia may impair autoregulation so that renal vasoconstriction reduces renal blood flow. The fluid required to initiate CPB may significantly reduce the hemoglobin (Hb) and oxygen-carrying capacity in view of the preexisting anemia of CRF without the addition of red blood cells (RBCs) to the priming volume or immediately on initiation of CPB. A hematocrit of 25% should be maintained during CPB. Washed RBCs are recommended for RBC transfusion to lessen excessive potassium and glucose levels intraoperatively. Potassium plasma levels should be checked periodically. Mannitol and furosemide may prevent early oliguric renal failure. Patients with CRF often have glucose intolerance from an abnormal insulin response, so more frequent determination of serum glucose levels is advisable.

The anephric patient poorly tolerates post-CPB hypervolemia that often follows prolonged duration of CPB. Dialysis can be performed during CPB and is technically easy and effective because small molecules (uremic solutes, electrolytes) are removed. Instead of dialysis during CPB, hemofiltration (ultrafiltration) is more frequently performed, effectively clearing excess water without the hemodynamic instability of dialysis. Circulating blood passes through the hollow fibers of the hemoconcentrators that have a smaller pore size than albumin (55,000 Da), which remove water and solutes. These midsize molecules (inflammatory molecules) are small enough to pass through the pores to concentrate the blood. Potassium is eliminated, helping reduce excessive potassium concentration commonly associated with cardioplegia administration. Hemofiltration during CPB may not achieve a net reduction in the overall total fluid balance of the patient, in part because a minimum volume of fluid must be maintained in the venous reservoir of the extracorporeal circuit.

Excessive bleeding after CPB is not uncommon in those with CRF, in part due to preoperative platelet dysfunction. Antifibrinolytic medications are pharmacologic measures used to successfully reduce excessive bleeding and transfusion requirements associated with cardiac surgery. Tranexamic acid, an inexpensive, synthetic antifibrinolytic, is excreted primarily through the kidneys, so a dose reduction is required based on the preoperative creatinine level. Aprotinin, a serine protease inhibitor with anti-inflammatory as well as antifibrinolytic properties, is concentrated in the proximal renal tubules and leads to a clinically important increase in the postoperative creatinine levels. If renal insufficiency without dialysis dependence is present with a corresponding serum creatinine level greater than 2.5 mg/dL, aprotinin is contraindicated.

Antithrombin

Antithrombin (AT) and protein C are two primary inhibitors of coagulation. A delicate balance exists between the procoagulant system and the inhibitors of coagulation. AT is the most abundant and important of the coagulation pathway inhibitors. Deficiencies of AT increase the risk of thromboembolism and impact patients requiring CPB.

AT or AT III is an α₂-globulin that is produced primarily in the liver. It binds thrombin, as well as other serine proteases, factors IX, X, XI, and XII, kallikrein, and plasmin, irreversibly, which neutralizes their activity. However, only inhibition of thrombin and factor Xa by AT has physiologic and clinical significance. AT activity of less than 50% is clinically important. AT deficiency may occur as a congenital deficiency or as an acquired deficiency secondary to increased AT consumption, loss of AT from the intravascular compartment (renal failure, nephrotic syndrome), or liver disease (cirrhosis). Acquired deficiency is often associated with trauma, sepsis, and shock. Although AT deficiency may be acquired, cause and effect are difficult to prove because many factors may exist simultaneously to account for abnormal clotting.

Anticoagulation for CPB depends on AT to inhibit clotting because heparin alone has no effect on coagulation. Heparin catalyzes AT inhibition of thrombin by binding to a lysine residue on AT and altering its conformation. Thrombin actually attacks AT, disabling it, but in the process attaches AT to thrombin, forming the AT and thrombin complex. This complex has no activity and is rapidly removed. Thirty percent of AT is consumed during this process, so AT levels are reduced. AT deficiency may occur with cardiac and noncardiac operations. The “adequacy” of anticoagulation with heparin may be monitored with the activated coagulation time (ACT). If an individual has a reduced response to heparin, it is referred to as heparin resistance, which can lead to thrombus formation and serious complications.

Heparin exposure before CPB is increasingly common in cardiac surgical practice today, resulting in more cases of heparin resistance. The incidence varies among hospitals, but in 2270 cardiac cases, 3.7% were identified as heparin resistant. Although 50% more heparin may be required with heparin resistance, 30% of patients do not reach adequate ACT values despite having received 800 U/kg of heparin. Heparin anticoagulation for CPB causes further lowering of AT levels that were most likely low before surgery. AT activity falls an additional 25% to 50% with initiation of CPB, in part owing to dilution and elimination of the AT and thrombin complex. AT-deficient patients are at risk for major thrombosis if exposed to CPB, and clotting has been reported. Therefore, AT-deficient patients who require CPB should be treated aggressively. Once AT levels reach more than 80%, thrombosis is less likely. Postoperatively, AT levels continue to decline at a rate dependent on the extent of tissue disruption and hemorrhage. The nadir occurs on the third day and preoperative levels return by the fifth day.

Various blood products have been tried as an alternative to fresh frozen plasma (FFP) to rapidly raise the AT level. Cryoprecipitate and FFP have similar amounts of AT, but the infectious risk is greater for cryoprecipitate. AT concentrate preparations are derived from human plasma pools but are subjected to fractionation procedures and heating to inactivate viral contaminants. This process does not reduce biologic activity and viral transmission has not been reported. One bottle of AT contains approximately 500 units or the equivalent of 2 units of FFP and can be safely administered over 10 to 20 minutes. The baseline AT activity of the heparin-resistant patients was 56 ± 25%, which improved to 75 ± 31% after administration of AT concentrate.¹⁸

Cold Agglutinins

Cold agglutinins (CAs) are common but rarely clinically important. CAs form a complement antigen-antibody reaction on the surface of the RBC membrane that causes lysis. The degree of hemolysis is related to the circulating titer and thermal amplitude of the CAs. Thermal amplitude, the blood temperature below which the CAs react, is the key factor influencing clinical relevance. The titer and thermal amplitude are determined at various temperatures in the serum by an indirect hemagglutination test. Most people have cold autoantibodies that react at 4°C but in very low titers. Accelerated destruction of RBCs primarily occurs if the thermal amplitude is above 30°C. The higher is the thermal amplitude of the CAs, the more pathologic. Pathologic cold autoantibodies also have much higher titers at 30°C. However, thermal amplitude is more important than titer. With pathologic CAs, vascular occlusion occurs due to RBC clumping, injuring the myocardium, liver, and kidney. Microscopic RBC clumping may erroneously be attributed to other causes during hypothermic CPB unless agglutination is observed. Increasing temperature rapidly inactivates CAs.

Blood banks routinely screen for the presence of autoantibodies at 37°C, but cold antibodies, only reactive at lower temperatures, are not detected. The significance of CAs is determined by evaluating agglutination of RBCs in 20°C saline and 30°C albumin. If there is no agglutination, significant hemolysis is unlikely. Before initiation of CPB, the titer and thermal amplitude of CAs must be determined to avoid a temperature during CPB that would cause hemolysis. Intraoperatively, low-thermal-amplitude CAs can be determined by mixing cold cardioplegia with some of the patient’s blood to check for separation of cells. If there is concern about CAs after routine testing, the sample can also be diluted to simulate CPB, cooled, and inspected for RBC agglutination. The hemodilution commonly associated with CPB may weaken agglutination and hemolysis in a patient with high reactivity and titer of CAs exposed to hypothermia.

The actions of CA may be difficult to diagnose because there are many other causes for hemolysis with CPB, so some cardiac surgeons avoid hypothermia if CAs are suspected or identified preoperatively. Despite normothermic CPB, cold cardioplegia may cause RBC agglutination in small myocardial vessels. Nevertheless, hypothermic myocardial protection has been used successfully in patients with CAs. A review of 832 patients scheduled to undergo surgery and CPB identified only seven cases of CAs that were strongly positive at 4°C. The authors concluded that asymptomatic patients with nonspecific, low-titer, and low-thermal-amplitude CAs may undergo hypothermia and CPB without serious detectable sequelae. However, the possibility of subtle end-organ damage exists.

If hypothermic CPB is necessary despite the presence of CAs, the choices are preoperative plasmapheresis, standard hemodilution, and maintenance of CPB temperature above the CA thermal amplitude.¹⁹ Cold cardioplegia may be used without first undergoing plasmapheresis if normothermic CPB is used and 37°C cardioplegic solution is injected before administration of 4°C cardioplegic solution, clearing all potentially reactive cells. The risk of hemolysis is still high in patients with high-thermal-amplitude CAs. If CAs are particularly malignant, all of the patient’s blood from the venous reservoir is drained and discarded. It is replaced entirely by donor blood, unfortunately exposing the patient to allogeneic blood products. Today, normothermic CPB and antegrade or retrograde warm blood cardioplegia may be the best option. If CAs should go undetected, postoperative end-organ damage or low CO may occur. Subsequently, plasma exchange, corticosteroids, elevated urine output, and maintenance of a good CO are the best treatments.