Eisenmenger Reaction

Cyanotic condition in which patients with an initially intracardiac (or surgically created extracardiac) left-to-right shunt show shunt reversal (i.e., now right-to-left shunting) secondary to significantly increased pulmonary vascular resistance (PVR).

Eisenmenger Disease.

The Austrian physician Viktor E. Eisenmenger was the first to describe in 1897 severe pulmonary vascular disease in a 32-year-old man with cyanosis and dyspnea since infancy secondary to an unrestricted ventricular septal defect, who died of massive pulmonary hemorrhage.

Approximately 8% of patients with congenital heart disease and 11% of those with left-to-right intracardiac shunting develop Eisenmenger reaction.

Eisenmenger reaction per se is not inherited; it is an acquired complication of a congenital cardiac lesion. No sexual predilection has been reported.

In congenital cardiac lesions with intracardiac shunting, blood initially shunts from the high-pressure systemic circulation to the low-pressure pulmonary circulation. If the defect is unrestricted and sustained, exposure of the pulmonary vascular bed to systemic arterial pressure initially results in increased pulmonary blood flow and pressure that over time triggers progressive adaptation processes in the microvasculature, including arteriolar intima proliferation, media hypertrophy, and finally capillary and/or arteriolar occlusion. Obliteration of pulmonary arterioles and capillaries may result from necrotizing arteritis. Decreased endothelium-dependent pulmonary arteriolar dilatation and increased pulmonary endothelin and plasma thromboxane B2 levels (both pulmonary vasoconstrictors) have been described; all of these factors ultimately lead to increased PVR. Once systemic and pulmonary vascular resistances and pressures approach each other, a process called shunt reversal occurs, where the blood now shunts bidirectionally or from the right (pulmonary) side to the left (systemic) side. Reduced pulmonary blood flow and right-to-left shunting explain the arterial hypoxemia. Endothelium-dependent pulmonary arteriolar relaxation is impaired, pulmonary endothelin production is increased, and plasma thromboxane B2 concentrations are elevated in patients with the Eisenmenger reaction, suggesting that endothelial dysfunction or platelet activation plays a causative role in this condition.

Dyspnea, chest pain (right ventricular ischemia), and new cyanosis in the presence of congenital heart disease. Echocardiography or cardiac catheterization (Caveat: radiographic contrast material may cause systemic arterial vasodilatation) can be used to determine the degree of pulmonary hypertension and demonstrate and quantify the shunting.

The term Eisenmenger reaction describes cyanosis secondary to severe pulmonary hypertension in the systemic range as a result of significantly increased PVR with reversed or bidirectional shunting resulting from a connection between systemic and pulmonary circulation (such as septal defects, atrioventricular canal, patent ductus arteriosus, or aortopulmonary windows). Obtain a history of cyanotic episodes, syncopes, fatigue, dyspnea, check for finger clubbing, plethora, and polycythemia, which may be associated with hyperviscosity. Exercise tolerance is significantly reduced because of the inability to increase pulmonary blood flow. Hemoptysis is a common finding and often caused by pulmonary infarction, rupture of a pulmonary artery aneurysm, or a thin-walled pulmonary arteriole. There is an increased risk of hyperuricemia (increased production and reduced renal clearance of urate), cholelithiasis, hypertrophic osteoarthropathy, cerebral abscesses, and thromboembolic events (cerebrovascular insults). Renal function may be decreased, with evidence of glomerulopathy (hematuria, proteinuria, increased serum creatinine levels) reported in these patients. Syncope, increased right-sided filling pressures, and severe hypoxemia (i.e., systemic SpO2 <85%) are associated with a poor prognosis. Sudden death as a result of arrhythmia and hypoxemia, but also pulmonary artery rupture, has been reported. Death as a result of Eisenmenger reaction usually occurs in the third decade of life. Patients with sleep apnea in association with congenital heart disease may demonstrate accelerated development of the disorder (e.g., patients with Trisomy 21).

Some studies reported a high perioperative mortality in these patients undergoing noncardiac surgery. Full clinical cardiac assessment (right parasternal heave, palpable pulmonary valve closure, right-sided fourth heart sound, and a loud pulmonic component of the second heart sound are constant findings) in combination with electrocardiography, echocardiography, chest radiograph is strongly recommended to define the degree of lesion and cardiac function. Arterial blood gas analysis may be considered. Obtain a complete blood count and consider iron replacement therapy for iron deficiency anemia. Check renal function (serum concentrations of creatinine, urea and electrolytes, and urine analysis for proteinuria and hematuria). Antiarrhythmic management for atrial arrhythmias and prophylaxis against thromboembolism should be considered. Isovolumetric hemodilution has been used to decrease the hematocrit in these patients, which not only increases cardiac output and systemic oxygen delivery but also decreases systemic vascular resistance (SVR) and improves the patient's symptoms. Avoid prolonged preoperative fasting, which may result in hypovolemia and hyperviscosity. It is recommended to start an intravenous infusion with maintenance fluid replacement at the beginning of the fasting period.

Consider suitability for local anesthesia because general anesthesia may cause systemic vasodilation aggravating the right-to-left shunt. Anesthesia should be administered by an experienced cardiac anesthetist, with the possibility of postoperative care in an intensive care unit setting. Avoid hypovolemia, which may lead to hypotension, hypoxemia, and sometimes hemoconcentration and thromboembolic events (volume expansion should be provided immediately). Avoid decreases in SVR in relation to PVR, which results in increased right-to-left shunting. Both spontaneous ventilation and controlled ventilation have been used; however, care should be taken to avoid hypercarbia, alveolar hypoxia, acidosis, and atelectasis. Avoid high airway pressures during controlled ventilation. There is a risk of paradoxical embolism throughout surgery, so careful deaeration of syringes and stop cocks is mandatory. Epidural analgesia (bupivacaine 0.125% with fentanyl 5 μg/ml) has been used successfully for laparotomy without adverse effects. Patients with Eisenmenger reaction can be eligible for heart and heart-lung transplantation.

Ketamine 1 to 2 mg/kg IV reportedly has minimal effects on PVR and SVR as long as ventilation is controlled and has been used successfully in patients with Eisenmenger reaction. Both thiopental and propofol, but also inhalational anesthetics, decrease SVR and should be used with caution and in low doses only. Prophylactic use of vasopressors (methoxamine, phenylephrine) has resulted in reflex bradycardia and increased right-to-left shunt. Vasopressors are probably best used only if increased right-to-left shunting develops. Nitrous oxide is contraindicated because it may increase PVR. Avoid nonsteroidal antiinflammatory drugs in the presence of renal failure.

Avoid confusion with Eisenmenger Complex (Eisenmenger Syndrome): Congenital cardiac lesion presenting with ventricular septal defect and overriding aorta, pulmonary hypertension with right-to-left shunt, and right ventricular hypertrophy. However, the terms Eisenmenger disease, Eisenmenger complex, and Eisenmenger syndrome are all used interchangeably in the literature and a consensus seems to be missing. In the editors' opinion, only the term “Eisenmenger reaction” clearly refers to the pathologic process of shunt reversal, which explains why we have chosen it as the title of this section.