Cardiogenic pulmonary edema (CPE)

Introduction
Background
Pulmonary edema refers to extravasation of fluid from the pulmonary vasculature into the interstitium and alveoli of the lung. The formation of pulmonary edema may be caused by 4 major pathophysiologic mechanisms: (1) imbalance of Starling forces (ie, increased pulmonary capillary pressure, decreased plasma oncotic pressure, increased negative interstitial pressure), (2) damage to the alveolar-capillary barrier, (3) lymphatic obstruction, and (4) idiopathic or unknown mechanism.
Cardiogenic pulmonary edema (CPE) is defined as pulmonary edema due to increased capillary hydrostatic pressure secondary to elevated pulmonary venous pressure. CPE reflects the accumulation of fluid with a low-protein content in the lung interstitium and alveoli, when pulmonary veins and left atrium venous return exceeds left ventricular (LV) output.
Increased hydrostatic pressure leading to pulmonary edema may result from many causes, including excessive intravascular volume administration, pulmonary venous outflow obstruction (eg,mitral stenosis or left atrial myxoma), or LV failure secondary to systolic or diastolic dysfunction of the LV. CPE leads to progressive deterioration of alveolar gas exchange and respiratory failure. Without prompt recognition and treatment, a patient's condition can deteriorate rapidly.

Pathophysiology
CPE is caused by elevated pulmonary capillary hydrostatic pressure leading to transudation of fluid into the pulmonary interstitium and alveoli. Increased left atrial pressure increases pulmonary venous pressure and pressure in the lung microvasculature, resulting in pulmonary edema.
Mechanism of CPE
Pulmonary capillary blood and alveolar gas are separated by the alveolar-capillary membrane, which consists of 3 anatomically different layers: (1) the capillary endothelium; (2) the interstitial space, which may contain connective tissue, fibroblasts, and macrophages; and (3) the alveolar epithelium. Exchange of fluid normally occurs between the vascular bed and the interstitium. Pulmonary edema occurs when the net flux of fluid from the vasculature into the interstitial space is increased. The Starling relationship determines the fluid balance between the alveoli and the vascular bed.
Net flow of fluid across a membrane is determined by applying the following equation:
Q = K (P cap -P is) - l(Pcap - Pis),

where Q is net fluid filtration; K is a constant called the filtration coefficient; P cap is capillary hydrostatic pressure, which tends to force fluid out of the capillary; P is is hydrostatic pressure in the interstitial fluid, which tends to force fluid into the capillary; l is the reflection coefficient, which indicates the effectiveness of the capillary wall in preventing protein filtration; Pcap is the colloid osmotic pressure of plasma, which tends to pull fluid into the capillary; and Pis is the colloid osmotic pressure in the interstitial fluid, which pulls fluid out of the capillary.


The net filtration of fluid may increase with changes in different parameters of the Starling equation. CPE predominantly occurs secondary to left atrial outflow impairment or LV dysfunction. For pulmonary edema to develop secondary to increased pulmonary capillary pressure, the pulmonary capillary pressure must rise to a level higher than the plasma colloid osmotic pressure. Pulmonary capillary pressure is normally 8-12 mm Hg, and colloid osmotic pressure is 28 mm Hg. High pulmonary capillary wedge pressure (PCWP) may not always be evident in established CPE because the capillary pressure may have returned to normal when the measurement is performed.
Lymphatics
The lymphatics play an important role in maintaining an adequate fluid balance in the lungs by removing solutes, colloid, and liquid from the interstitial space at a rate of approximately 10-20 mL/h. An acute rise in pulmonary arterial capillary pressure (ie, to >18 mm Hg) may increase filtration of fluid into the lung interstitium, but the lymphatic removal does not increase correspondingly. In contrast, in the presence of chronically elevated left atrial pressure, the rate of lymphatic removal can be as high as 200 mL/h, which protects the lungs from pulmonary edema.
Stages
The progression of fluid accumulation in CPE can be identified as 3 distinct physiologic stages.
In stage 1, elevated left atrial pressure causes distention and opening of small pulmonary vessels. At this stage, blood gas exchange does not deteriorate, or it may even be slightly improved.
In stage 2, fluid and colloid shift into the lung interstitium from the pulmonary capillaries, but an initial increase in lymphatic outflow efficiently removes the fluid. The continuing filtration of liquid and solutes may overpower the drainage capacity of the lymphatics. In this case, the fluid initially collects in the relatively compliant interstitial compartment, which is generally the perivascular tissue of the large vessels, especially in the dependent zones. The accumulation of liquid in the interstitium may compromise the small airways, leading to mild hypoxemia. Hypoxemia at this stage is rarely of sufficient magnitude to stimulate tachypnea. Tachypnea at this stage is mainly the result of the stimulation of juxtapulmonary capillary (J-type) receptors, which are nonmyelinated nerve endings located near the alveoli. J-type receptors are involved in reflexes modulating respiration and heart rates.
In stage 3, as fluid filtration continues to increase and the filling of loose interstitial space occurs, fluid accumulates in the relatively noncompliant interstitial space. The interstitial space can contain up to 500 mL of fluid. With further accumulations, the fluid crosses the alveolar epithelium in to the alveoli, leading to alveolar flooding. At this stage, abnormalities in gas exchange are noticeable, vital capacity and other respiratory volumes are substantially reduced, and hypoxemia becomes more severe.
Pathophysiologic considerations
CPE usually occurs secondary to left atrial outflow impairment or LV dysfunction. Left atrial outflow impairment may be acute or chronic. Causes of chronic impairment include mitral stenosis or left atrial tumors. Increased heart rate, which may occur secondary to atrial fibrillation, leads to pulmonary edema because of reduced LV filling. Acute mitral-valve regurgitation secondary to papillary muscle dysfunction or ruptured chordae tendineae increases LV end-diastolic pressure and is another cause of pulmonary edema.
LV dysfunction can be systolic or diastolic or combined. It can also be associated with LV volume overload or LV outflow obstruction. Systolic dysfunction, a common cause of CPE, is defined as decreased myocardial contractility that reduces cardiac output. The fall in cardiac output stimulates sympathetic activity and blood volume expansion by activating the renin-angiotensin-aldosterone system, which causes deterioration by decreasing LV filling time and increasing capillary hydrostatic pressure, respectively.
Diastolic dysfunction signals a decrease in LV diastolic distensibility (compliance). Therefore, a heightened diastolic pressure is required to achieve the similar stroke volume. Despite normal LV contractility, the reduced cardiac output in conjunction with excessive end-diastolic pressure generates hydrostatic pulmonary edema. Diastolic abnormalities can also be caused by constriction and restriction.
LV volume overload occurs in a variety of cardiac or noncardiac conditions. Cardiac conditions are ventricular septal rupture, acute or chronic aortic insufficiency, and acute or chronic mitral regurgitation. The noncardiac condition is volume overload. These conditions cause elevation of LV end-diastolic pressure and left atrial pressure, leading to pulmonary edema. LV outflow obstruction, such as aortic stenosis, produces increased end-diastolic filling pressure, increased left atrial pressure, and increased pulmonary capillary pressures. Cardiac tamponade results in elevation of left atrial (pulmonary capillary pressure), and right atrial pressure resulting in pulmonary and peripheral edema, respectively.
After pulmonary edema begins to develop, a self-perpetuating cycle of events occurs in the cardiopulmonary system. The cycle begins when LV systolic dysfunction decreases myocardial contractility and cardiac output, activating the renin-angiotensin-aldosterone system and stimulating catecholamine production. As a result, systemic vascular resistance increases leading to increased myocardial wall tension, myocardial ischemia, and worsening LV function and cardiac output, all of which perpetuate the cycle. The increase in myocardial wall tension also leads to concurrent diastolic dysfunction, which increases pulmonary artery and pulmonary capillary pressures. When the pulmonary capillary hydrostatic pressure exceeds the pulmonary interstitial pressure, transudation of fluid in the pulmonary interstitium and alveoli occurs. If the cycle is not aborted promptly with appropriate treatment, pulmonary edema rapidly develops.
Mortality/Morbidity
• In-hospital mortality rates are difficult to assign because the causes and the severity vary considerably. In a high-acuity setting, in-hospital death rates are as high as 15-20%.
• Severe hypoxia may result in myocardial ischemia or infarction. Mechanical ventilation may be required if medical therapy is delayed or unsuccessful. Endotracheal intubation and mechanical ventilation are associated with their own risks, including aspiration (during intubation), mucosal trauma (more common with nasotracheal intubation than orotracheal intubation), and barotrauma.
Clinical
History
Patients with CPE present with the dramatic clinical features of left heart failure. Patients develop a sudden onset of extreme breathlessness, anxiety, and feelings of drowning.
• Clinical manifestations of acute CPE reflect evidence of hypoxia and increased sympathetic tone (increased catecholamine outflow).
• Patients most commonly complain of shortness of breath and profuse diaphoresis.
• Patients with symptoms of gradual onset (eg, over 24 h) often report dyspnea on exertion, orthopnea, and paroxysmal nocturnal dyspnea.
• Cough is a frequent complaint that may provide an early clue to worsening pulmonary edema in patients with chronic LV dysfunction. Pink, frothy sputum may be present in patients with severe disease. Occasionally, hoarseness may be present as a result of recurrent laryngeal nerve palsy from mitral stenosis or pulmonary hypertension (Ortner sign).
• Chest pain should alert the physician to the possibility of acute myocardial ischemia/infarction, or aortic dissection with acute aortic regurgitation as the precipitant of pulmonary edema.
Physical
• Physical findings in patients with CPE are notable for tachypnea and tachycardia.
• Patients may be sitting upright, they may demonstrate air hunger, and they may become agitated and confused.
• Patients usually appear anxious and diaphoretic.
• Hypertension is often present because of the hyperadrenergic state. Hypotension indicates severe LV systolic dysfunction and the possibility of cardiogenic shock. Cool extremities may indicate low cardiac output and poor perfusion.
• Auscultation of the lungs usually reveals fine crepitant rales, but rhonchi or wheezes may also be present. Rales are usually heard at the bases first; as the condition worsens, they progress to the apices.
• Cardiovascular findings are usually notable for S 3 , accentuation of pulmonic component of S 2 and jugular venous distension.
o Auscultation of murmurs can help in the diagnosis of acute valvular disorders manifesting with pulmonary edema.
o Aortic stenosis is associated with a harsh crescendo-decrescendo systolic murmur, which is heard best at the upper sternal border and radiating to the carotid arteries.
o In contrast, acute aortic regurgitation is associated with a short, soft diastolic murmur.
o Acute mitral regurgitation produces a loud systolic murmur heard best at the apex or lower sternal border. In the setting of ischemic heart disease, this may be a sign of acute myocardial infarction (MI) with rupture of mitral valve chordae.
o Mitral stenosis typically produces a loud S 1 , opening snap, and diastolic rumble at the cardiac apex.
• Another notable physical finding is skin pallor or mottling resulting from peripheral vasoconstriction, low cardiac output, and shunting of blood to the central circulation in patients with poor LV function and substantially increased sympathetic tone. Skin mottling at presentation is an independent predictor of an increased risk of in-hospital mortality.
• Patients with concurrent right ventricular (RV) failure may present with hepatomegaly, hepatojugular reflux, and peripheral edema.
• Severe CPE may be associated with a change in mental status, which may be the result of hypoxia or hypercapnia. Although CPE is usually associated with hypocapnia, hypercapnia with respiratory acidosis may be seen in patients with severe CPE or underlying COPD.
Causes
• Atrial outflow obstruction: This can be due to mitral stenosis or, in rare cases, atrial myxoma, thrombosis of a prosthetic valve, or a congenital membrane in the left atrium (eg, cor triatriatum). Mitral stenosis is usually a result of rheumatic fever, after which it may gradually cause pulmonary edema. Therefore, other causes of CPE often accompany mitral stenosis in acute CPE; an example is decreased LV filling because of tachycardia in arrhythmia (eg, atrial fibrillation) or fever.
• LV systolic dysfunction: Chronic LV failure is usually the result of congestive heart failure (CHF) or cardiomyopathy. Causes of acute exacerbations include the following:
o Acute MI or ischemia
o Patient noncompliance with dietary restrictions (eg, dietary salt restrictions)
o Patient noncompliance with medications (eg, diuretics)
o Severe anemia
o Sepsis
o Thyrotoxicosis
o Myocarditis
o Myocardial toxins (eg, alcohol, cocaine, chemotherapeutic agents such as doxorubicin [Adriamycin], trastuzumab [Herceptin])
o Chronic valvular disease, aortic stenosis, aortic regurgitation, and mitral regurgitation
• LV diastolic dysfunction, nonischemic acute mitral regurgitation (ruptured chordae tendineae), and acute aortic insufficiency (endocarditis, aortic dissection): This can cause acute, severe systemic hypertension (diastolic dysfunction), resulting in CPE.
o Constrictive pericarditis and pericardial tamponade are other etiologies that mainly compromise LV diastolic function.
o Ischemia and infarction may cause LV diastolic dysfunction in addition to systolic dysfunction. With a similar mechanism, myocardial contusion induces systolic or diastolic dysfunction.
• Dysrhythmias: New-onset rapid atrial fibrillation and ventricular tachycardia can be responsible for CPE.
• LVH and cardiomyopathies: These can increase LV stiffness and end-diastolic pressure, leading to pulmonary edema by increasing capillary hydrostatic pressure.
• LV volume overload
o Some sodium retention may occur in association with LV systolic dysfunction. However, in some situations, such as primary renal disorders, sodium retention and volume overload may play a primary role. CPE can occur in patients with hemodialysis-dependent renal failure, often as the result of noncompliance with dietary restrictions or noncompliance with hemodialysis sessions.
o Valvular diseases, especially aortic regurgitation and mitral regurgitation, may be associated with volume overload. Endocarditis, aortic dissection, traumatic rupture, rupture of a congenital valve fenestration and iatrogenic causes are the most important etiologies of acute aortic regurgitation that may lead to pulmonary edema.
• MI: One of the mechanical complications of MI can be the rupture of ventricular septum or papillary muscle. These mechanical complications substantially increase volume load in the acute setting and therefore may cause pulmonary edema.
• LV outflow obstruction
o Acute stenosis of the aortic valve can cause pulmonary edema. However, aortic stenosis due to a congenital disorder, calcification, prosthetic valve dysfunction, or rheumatic disease usually has a chronic course and is associated with hemodynamic adaptation of the heart. This adaptation may include concentric LV hypertrophy, which itself can cause pulmonary edema by way of LV diastolic dysfunction.
o Hypertrophic cardiomyopathy is a cause of dynamic LV outflow obstruction.
o Elevated systemic BP can be considered an etiology of LV outflow obstruction because it increases systemic resistance against the pump function of the LV
Differential Diagnoses
Other Problems to Be Considered
CPE should be differentiated from pulmonary edema associated with injury to the alveolar-capillary membrane caused by diverse etiologies. Damage to alveolar capillary barrier can be seen in various direct lung injuries (pneumonia, aspiration pneumonitis, toxin inhalation, pulmonary contusion, radiation, drowning and fat emboli) or indirect lung injuries (sepsis, shock and multiple transfusions, acute pancreatitis, anaphylactic shock).
In addition, several conditions related to noncardiogenic pulmonary edema (NCPE) primarily affect Starling forces rather than the alveolar-capillary barrier. These conditions include decreased oncotic pressure of the plasma due to various etiologies and increased negativity of interstitial pressure due to rapid removal of pneumothorax. Lymphatic insufficiency (eg, lymphangitic carcinomatosis, fibrosing lymphangitis, lung transplantation) is another important pathophysiologic mechanism of NCPE.
Several features may differentiate CPE from NCPE. In CPE, a history of an acute cardiac event is usually present. Physical examination shows a low-flow state, an S3 gallop, jugular venous distention, and crackles on auscultation. Patients with NCPE have a warm periphery, a bounding pulse, and no S3 gallop or jugular venous distention. Definite differentiation is based on PCWP measurements. The PCWP is generally >18 mm Hg in CPE and <18 mm Hg in NCPE, but superimposition of chronic pulmonary vascular disease can make this distinction difficult.
Workup
Laboratory Studies
• Blood count: The CBC with differential helps in assessing for severe anemia and may suggest sepsis or infection if a markedly elevated WBC count or bandemia is present.
• Serum electrolyte measurements
o Patients with chronic CHF often use diuretics. Therefore, they are predisposed to have electrolyte abnormalities, especially hypokalemia and hypomagnesemia.
o Patients with chronic renal failure are at high risk for hyperkalemia, especially when they are noncompliant with hemodialysis sessions.
• BUN and creatinine determinations: These tests help in assessing for renal failure and the anticipated response to diuretics. In low-output states, such as systolic dysfunction, decreased BUN and creatinine levels may be secondary to hypoperfusion of the kidneys.
Imaging Studies
• Chest radiography is helpful in distinguishing CPE from other pulmonary causes of severe dyspnea.
• An enlarged heart, inverted blood flow, Kerley lines, basilar edema (vs diffuse edema), absence of air bronchograms, and presence of pleural effusion (particularly bilateral and symmetrical pleural effusions) are features that suggest CPE versus NCPE and other lung pathologies.
• Chest radiography is somewhat limited in patients with CPE of abrupt onset because the classic radiographic abnormalities may not appear for as long as 12 hours after dyspnea begins.
• Echocardiography: A bedside echocardiogram in a patient with decompensated CHF is an important diagnostic tool in determining the etiology of pulmonary edema. Echocardiography can evaluate LV systolic and diastolic function, valvular function, and assess for pericardial disease. It is especially helpful in identifying a mechanical etiology for pulmonary edema (eg, acute papillary muscle rupture, acute ventricular septal defect [VSD], cardiac tamponade, contained LV rupture, valvular vegetation with resulting acute severe mitral, aortic regurgitation).
Other Tests
• Arterial blood gas analysis
o This test is more accurate than pulse oximetry for measuring oxygen saturation.
o The decision to start mechanical ventilation is mainly based on clinical findings and rarely arterial blood gas results.
• Pulse oximetry
o Pulse oximetry is useful in assessing hypoxia and, therefore, the severity of CPE.
o It is also useful for monitoring the patient's response to supplemental oxygenation and other therapies.
• Electrocardiography
o Left atrial enlargement and LV hypertrophy are sensitive, though nonspecific, indicators of chronic LV dysfunction.
o The ECG may suggest an acute tachydysrhythmia or bradydysrhythmia as the cause of CPE.
o The ECG may suggest acute myocardial ischemia or infarction as the cause of CPE.
Plasma brain-type natriuretic peptide (BNP) and NT-proBNP testing
Both BNP and NT-proBNP are derived from pre-proBNP, a 134-amino-acid precursor synthesized by cardiac myocytes. A number of triggers including wall stretch, ventricular dilation, and/or increased pressures stimulate a 26-amino-acid signal peptide sequence to be cleaved from the precursor’s N-terminus to produce proBNP (108-amino-acid). This hormone is further cleaved by a membrane-bound serine protease (corin) into the inactive N-terminal fragment (NT-proBNP) and the active BNP (32-amino-acid) fragment. Both NT-proBNP and BNP testing are clinically available and have exhibited parallel changes across broad ranges of age, ejection fraction, diastolic CHF, and renal function.
• NT-proBNP testing
o Ventricular myocytes secrete proBNP in response to muscle-wall tension.
o NT-proBNP has a longer half-life (120 min) than that of BNP (20 min)
o NT-proBNP is less studied than BNP, but its levels are well correlated with BNP levels.
o The cutoff value of NT-proBNP >450 pg/mL in patients younger than 50 years correlates to values of BNP >100 pg/mL. NT-proBNP is less accurate than BNP in patients older than 65 years.
• BNP testing
o CHF is the most common form of CPE.
o Several observational studies and clinical trials have shown the important diagnostic value of BNP measurements in differentiating heart failure from pulmonary causes of dyspnea.
o BNP testing decreases the total cost of treatment and the length of hospitalization. This is a cost-effective diagnostic test in this setting.
o Although reports differ, a cutoff value of 100 pg/mL is generally accepted. By using this cutoff value, measurement of BNP has a high negative predictive value. That is, in patients with BNP value of <100 pg/mL, heart failure is unlikely.
o The level of BNP increases with age and is slightly higher in women than men. BNP levels also tend to be lower in obese patients.
o In a recent study, a cutoff point of 250 pg/mL was the most accurate for elderly patients (mean age, 80 y).
o Renal dysfunction may be associated with a significantly increased level of BNP.
o In the Breathing Not Properly Multinational Study, the mean BNP level in patients without heart failure and with a glomerular filtration rate (GFR) below normal was 300 pg/mL.
o Although the predictive value of BNP measures with cutoff value of 100 pg/mL is high, its positive predictive value is not as high as its negative predictive value. This means that mildly to moderately elevated levels of BNP should be interpreted in accordance to the patient's clinical status and other diagnostic results.
o Values of 100-400 pg/mL may be related to various pulmonary conditions, such as cor pulmonale, COPD, and pulmonary embolism.
o Atrial fibrillation is another factor that may mildly increase the cutoff value of BNP in diagnosing heart failure. Important information to know is the patient's baseline heart function. Patients with chronic heart failure and BNP values of  400 pg/mL may have pulmonary causes of dyspnea without an exacerbation of their CHF.
o Until additional studies establish the precise cutoff values for different conditions, the threshold of 100 pg/mL is recommended, with the exceptions noted above. This cutoff value has an accuracy of 80-85%, a sensitivity of 90%, and a specificity of about 75% along with other appropriate clinical and laboratory findings.
o One study of ICU patients who required invasive hemodynamic monitoring showed that they had markedly elevated BNP values, but the correlation between BNP values and PCWP was weak.
Procedures
• PCWP can be measured by using a pulmonary arterial catheter (Swan-Ganz catheter). This method helps in differentiating CPE from NCPE.
o NCPE occurs secondary to injury to the alveolar-capillary membrane rather than to alteration in Starling forces.
o A PCWP exceeding 18 mm Hg in a patient not known to have chronically elevated left atrial pressure indicates CPE.
o In patients with chronic pulmonary capillary hypertension, capillary wedge pressures exceeding 30 mm Hg are required to overcome the pumping capacity of the lymphatics and produce pulmonary edema.
• Large V waves are sometimes observed in the PCWP tracing with acute mitral regurgitation because large volumes of blood regurgitate into a poorly compliant left atrium.
o This condition raises pulmonary venous pressure and causes acute pulmonary edema.
o The pulmonary artery waveform appears falsely elevated because of the large V wave reflected back from the left atrium through the compliant pulmonary vasculature.
o The Y descent of the waveform is rapid, as the overdistended left atrium quickly empties.
• Cardiogenic shock is the result of a severe depression in myocardial function.
o Cardiogenic shock is hemodynamically characterized by a systolic BP <80 mm Hg, a cardiac index <1.8 L/min/m2, and a PCWP >18 mm Hg.
o This form of shock can occur from a direct insult to the myocardium (large acute MI, severe cardiomyopathy) or from a mechanical problem that overwhelms the functional capacity of the myocardium (acute severe mitral regurgitation, acute ventricular septal defect). Although the pulmonary artery catheter is commonly used in ICU patients with severe acute decompensated CHF, it is not clear whether this technique improves mortality rate and clinical outcome. The results of the recent ESCAPE trial showed no mortality benefit or decrease in the number of hospitalized days in the group of patients who underwent PAC insertion.1 This matter needs further investigation.

Follow-up
Further Inpatient Care
• When the patient's condition is initially stabilized, further inpatient care depends on the underlying cause of the episode of CPE.
• Admit patients to a telemetry unit to monitor for acute dysrhythmias. Pay strict attention to the patient's fluid balance and closely monitor fluid input and output. Maintain a negative fluid balance in patients who are fluid-overloaded by using diuretics or hemodialysis (in patients with renal failure).
• Check cardiac enzyme levels to evaluate for MI. Stress testing can also be performed during hospitalization to evaluate for reversible ischemia as the cause of pulmonary edema.
• Consider ECG to evaluate for evidence of acute valvular dysfunction and wall-motion abnormalities and to assess the patient's ejection fraction. Patients with poor ejection fractions or severe dilated cardiomyopathies are often given digoxin.
• In general, begin with oral vasodilator therapy, most commonly ACE inhibitors. If the patient was initially treated with inotropic medications, wean the patient off of these as soon as his or her condition is stable to minimize adverse effects.
• Patients in whom pulmonary edema is due to dietary factors or medication noncompliance need strict counseling and education to help prevent recurrences.
Inpatient & Outpatient Medications
• See Treatment and Mdication.
Transfer
• Transfer of patients to a tertiary receiving hospital is generally indicated if the initial hospital lacks adequate resources to care for the patient. Most patients with CPE can be treated well at community hospitals. However, if definitive surgery is required to stabilize the cause of CPE, transfer is often indicated.
• Examples of patients who may require transfer include the following:
o Patients with CPE due to acute valvular dysfunction requiring urgent valve replacement.
o Patients with acute MI that results in cardiogenic shock manifesting as CPE with hypotension (thrombolysis may be attempted at the initial hospital, but outcomes are generally poor without percutaneous coronary intervention or coronary artery bypass surgery.)
o Patients with CPE who require inotropic support or hemodialysis beyond the capabilities of the initial hospital.
o In severe cases of refractory cardiogenic shock, consider early transfer of appropriate patients to a tertiary medical center where, if clinically indicated, more advanced treatments such as left ventricular assist device and or cardiac transplantation may be performed.
Complications
• The major complication associated with CPE is respiratory fatigue and failure.
• Prompt diagnosis and treatment usually prevent this complication, but the physician must be prepared to provide assisted ventilation if the patient begins to show signs of respiratory fatigue (eg, lethargy, fatigue, diaphoresis, worsening anxiety).
• Sudden cardiac death secondary to cardiac arrhythmia is another concern and continues monitoring of heart rhythm is helpful in prompt diagnosis of dangerous arrhythmias.
Prognosis
• In general, the inpatient mortality rate for patients with CPE is 15-20%.
• CPE associated with acute MI is associated with a mortality rate of at least 40%. The mortality rate approaches 80% if the patient is also hypotensive.
Patient Education
• To help prevent recurrence, counsel and educate patients in whom pulmonary edema is due to dietary causes or medication noncompliance.
Miscellaneous
Medicolegal Pitfalls
• Failure to rapidly recognize CPE and distinguish this entity from other pulmonary diseases
• Failure to rapidly initiate medical therapy for CPE
• Failure to obtain an early ECG and failure to rapidly diagnose and treat MI and ischemia
• Failure to rapidly and aggressively treat intractable hypoxia with mechanical ventilation

Acknowledgments
The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors, Ari M Perkins, MD, Michael E Zevitz, MD, Sat Sharma, MD, and Amal Mattu, MD, to the development and writing of this article.
Multimedia

Media file 1: Radiograph shows acute pulmonary edema in a patient who was admitted with acute anterior myocardial infarction. Findings are vascular redistribution, indistinct hila, and alveolar infiltrates.

Radiograph shows acute pulmonary edema in a patient who was admitted with acute anterior myocardial infarction. Findings are vascular redistribution, indistinct hila, and alveolar infiltrates.

Media file 2: Radiograph shows acute pulmonary edema in a patient known to have ischemic cardiomyopathy. Findings are Kerley B lines (1 mm thick and 1 cm long) in lower lobes and Kerley A lines in the upper lobes.

Radiograph shows acute pulmonary edema in a patient known to have ischemic cardiomyopathy. Findings are Kerley B lines (1 mm thick and 1 cm long) in lower lobes and Kerley A lines in the upper lobes.

Media file 3: Radiograph demonstrates cardiomegaly, bilateral pleural effusions, and alveolar opacities in a patient with pulmonary edema.

Radiograph demonstrates cardiomegaly, bilateral pleural effusions, and alveolar opacities in a patient with pulmonary edema.

Media file 4: Radiograph shows interstitial pulmonary edema, cardiomegaly, and left pleural effusion presenting at an earlier stage of pulmonary edema.

Radiograph shows interstitial pulmonary edema, cardiomegaly, and left pleural effusion presenting at an earlier stage of pulmonary edema.

Media file 5: Lateral chest radiograph shows prominent interstitial edema and pleural effusions.