Cardiogenic Pulmonary Edema

Updated: Jul 23, 2020
Author: Ali A Sovari, MD, FACP, FACC; Chief Editor: Gyanendra K Sharma, MD, FACC, FASE 



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 as a result of cardiac dysfunction (see the image below). (See Etiology.)

Radiograph shows acute pulmonary edema in a patien 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.

Pulmonary edema can be caused by the following major pathophysiologic mechanisms:

  • Imbalance of Starling forces - ie, increased pulmonary capillary pressure, decreased plasma oncotic pressure, increased negative interstitial pressure

  • Damage to the alveolar-capillary barrier

  • Lymphatic obstruction

  • Idiopathic (unknown) mechanism

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 [LA] myxoma), and LV failure secondary to systolic or diastolic dysfunction of the left ventricle. CPE leads to progressive deterioration of alveolar gas exchange and respiratory failure. Without prompt recognition and treatment, a patient's condition can deteriorate rapidly. (See Etiology, Prognosis, Presentation, Workup, Treatment, and Medication.)


The major complications associated with CPE are respiratory fatigue and failure. Prompt diagnosis and treatment usually prevent these complications, 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). (See Prognosis and Treatment.)

Sudden cardiac death secondary to cardiac arrhythmia is another concern, and continuous monitoring of heart rhythm is helpful in prompt diagnosis of dangerous arrhythmias.

Patient education

To help prevent recurrence of CPE, counsel and educate patients in whom pulmonary edema is due to dietary causes or medication noncompliance.


CPE is caused by elevated pulmonary capillary hydrostatic pressure leading to transudation of fluid into the pulmonary interstitium and alveoli. Increased LA 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 three 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(Pcap - Pis) - l(Pcap - Pis),

where Q is net fluid filtration; K is a constant called the filtration coefficient; Pcap is capillary hydrostatic pressure, which tends to force fluid out of the capillary; Pis 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; the second Pcap is the colloid osmotic pressure of plasma, which tends to pull fluid into the capillary; and the second 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 LA 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.


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 LA pressure, the rate of lymphatic removal can be as high as 200 mL/h, which protects the lungs from pulmonary edema.


The progression of fluid accumulation in CPE can be identified as three distinct physiologic stages.

Stage 1

In stage 1, elevated LA 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.

Stage 2

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.

Stage 3

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 500mL 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.

Cardiac disorders manifesting as CPE

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. 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

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.

Chronic LV failure is usually the result of congestive heart failure (CHF) or cardiomyopathy. Causes of acute exacerbations include the following:

  • Acute myocardial infarction (MI) or ischemia

  • Patient noncompliance with dietary restrictions (eg, dietary salt restrictions)

  • Patient noncompliance with medications (eg, diuretics)

  • Severe anemia

  • Sepsis

  • Thyrotoxicosis

  • Myocarditis

  • Myocardial toxins (eg, alcohol, cocaine, chemotherapeutic agents such as doxorubicin [Adriamycin], trastuzumab [Herceptin])

  • Chronic valvular disease, aortic stenosis, aortic regurgitation, and mitral regurgitation

LV diastolic dysfunction

Ischemia and infarction may cause LV diastolic dysfunction in addition to systolic dysfunction. With a similar mechanism, myocardial contusion induces systolic or diastolic dysfunction.

Diastolic dysfunction signals a decrease in LV diastolic distensibility (compliance). Because of this decreased compliance, a heightened diastolic pressure is required to achieve a 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 constrictive pericarditis and tamponade.


New-onset rapid atrial fibrillation and ventricular tachycardia can be responsible for CPE.

LV hypertrophy and cardiomyopathies

These can increase LV stiffness and end-diastolic pressure, with pulmonary edema resulting from increased capillary hydrostatic pressure.

LV volume overload

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. 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.

Ventricular septal rupture, aortic insufficiency, and mitral regurgitation cause elevation of LV end-diastolic pressure and LA pressure, leading to pulmonary edema. LV outflow obstruction, such as that caused by aortic stenosis, produces increased end-diastolic filling pressure, increased LA pressure, and increased pulmonary capillary pressures.

Some sodium retention may occur in association with LV systolic dysfunction. However, in certain conditions, 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 a result of noncompliance with dietary restrictions or noncompliance with hemodialysis sessions.

Myocardial infarction

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

Acute obstruction 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. Hypertrophic cardiomyopathy is a cause of dynamic LV outflow obstruction.

Elevated systemic blood pressure can be considered an etiology of LV outflow obstruction because it increases systemic resistance against the pump function of the left ventricle.


In-hospital mortality rates for patients with CPE are difficult to assign because the causes and severity of the disease vary considerably. In a high-acuity setting, in-hospital death rates are as high as 15-20%.

Myocardial infarction, associated hypotension, and a history of frequent hospitalizations for CPE generally increase the mortality risk.

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 with orotracheal intubation), and barotrauma.




Patients with cardiogenic pulmonary edema (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 and 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 compression of the recurrent laryngeal nerve palsy from an enlarged left atrium, such as in mitral stenosis (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 Examination

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 S3, accentuation of the pulmonic component of S2, and jugular venous distention. Auscultation of murmurs can help in the diagnosis of acute valvular disorders manifesting with pulmonary edema.

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. In contrast, acute aortic regurgitation is associated with a short, soft diastolic murmur.

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 MI with rupture of mitral valve chordae. (See the image below.)

Radiograph shows acute pulmonary edema in a patien 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.

Mitral stenosis typically produces a loud S1, 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 can be caused by hypoxia or hypercapnia. Although CPE is usually associated with hypocapnia, hypercapnia with respiratory acidosis may be seen in patients with severe CPE or underlying chronic obstructive pulmonary disease (COPD).



Diagnostic Considerations

Cardiogenic pulmonary edema (CPE) should be differentiated from pulmonary edema associated with injury to the alveolar-capillary membrane, caused by diverse etiologies. Damage to the alveolar-capillary barrier can be seen in various direct lung injuries (from pneumonia, aspiration pneumonitis, toxin inhalation, pulmonary contusion, radiation, drowning, or fat emboli) and indirect lung injuries (from sepsis, shock and multiple transfusions, acute pancreatitis, or anaphylactic shock).

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, from lymphangitic carcinomatosis, fibrosing lymphangitis, or lung transplantation) is another important etiologic 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 pulmonary capillary wedge pressure (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 to assess.

Conditions to consider in the differential diagnosis of CPE include the following:

  • Pneumothorax

  • High-altitude pulmonary edema

  • Neurogenic pulmonary edema

  • Pulmonary embolism

  • Respiratory failure

Differential Diagnoses



Approach Considerations

Laboratory studies used in the evaluation of patients with cardiogenic pulmonary edema (CPE) include the following:

  • Complete blood count - The complete blood count (CBC) with differential helps in assessing for severe anemia and may suggest sepsis or infection if a markedly elevated white blood cell (WBC) count or bandemia is present

  • Serum electrolyte measurements - Patients with chronic CHF often use diuretics and are therefore predisposed to electrolyte abnormalities, especially hypokalemia and hypomagnesemia; patients with chronic renal failure are at high risk for hyperkalemia, especially when they are noncompliant with hemodialysis sessions

  • Blood urea nitrogen (BUN) and creatinine determinations - These tests help in assessing patients 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

  • Pulse oximetry - Pulse oximetry is useful in assessing hypoxia and, therefore, the severity of CPE; it is also useful for monitoring the patient's response to supplemental oxygenation and other therapies

  • Arterial blood gas analysis - This test is more accurate than pulse oximetry for measuring oxygen saturation; the decision to start mechanical ventilation is based mainly on clinical findings, but in rare instances, arterial blood gas results are taken into account


LA enlargement and LV hypertrophy are sensitive, although nonspecific, indicators of chronic LV dysfunction. The electrocardiogram (ECG) may suggest acute tachydysrhythmia or bradydysrhythmia or acute myocardial ischemia or infarction as the cause of CPE.

Computed tomography (CT) scanning

Chest CT scanning may be a useful tool for differentiating CPE from acute respiratory distress syndrome (ARDS) in the emergency department setting, with an overall 88.5% accuracy of diagnosis.[1] Chest CT scan features with a high positive predictive value (PPV) and moderate negative predictive value (NPV) for CPE appear to include the presence of ground glass attenuation predominantly in the upper lobe or central region as well as central-airspace consolidation. CT scan characteristics with relatively high PPVs and NPVs for ARDS include left-dominant pleural effusion and small, ill-defined opacities.[1]

Plasma BNP and NT-proBNP Testing

Brain-type natriuretic peptide (BNP) and N -terminal proBNP (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 (which has a 108 ̶ amino acid sequence). This hormone is further cleaved by a membrane-bound serine protease (corin) into the inactive NT-proBNP fragment and the active BNP (32 ̶ amino acid sequence) fragment.[2]

NT-proBNP and BNP testing are clinically available and have exhibited parallel changes across broad ranges of patient age, ejection fraction, diastolic CHF, and renal function.

BNP testing

CHF is the most common form of CPE. Several observational studies and clinical trials have shown the important diagnostic value of BNP measurements in differentiating heart failure from pulmonary causes of dyspnea.

Characteristics of BNP and points to consider in BNP testing include the following:

  • BNP testing decreases the total cost of treatment and the length of hospitalization; this is a cost-effective diagnostic test in this setting

  • 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 under 100 pg/mL, heart failure is unlikely

  • The level of BNP increases with age and is slightly higher in women than in men; BNP levels also tend to be lower in obese patients

  • In one study, a value of 400 pg/mL and above in patients aged 60-75 years was considered equal to a value of 800 pg/mL and above in patients older than 75 years to guide heart failure therapy[3]

  • Renal dysfunction may be associated with a significantly increased level of BNP

  • 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[4]

  • The levels of BNP are generally higher in critically ill patients who are in the intensive care unit (ICU) due to some of the common acute diseases in these patients, such as sepsis and acute lung injury. Elevated BNP levels in critically ill patients may be a sign of relatively poorer prognosis; however, this should be carefully considered in the context of the patient’s clinical condition.[5]

Although the predictive value of a BNP measurement with a 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 with the patient's clinical status and other diagnostic results.

Values of 100-400 pg/mL may be related to various pulmonary conditions, such as cor pulmonale, COPD, and pulmonary embolism. Atrial fibrillation is another factor that may mildly increase the BNP cutoff value in diagnosing heart failure. It is important to know the patient's baseline heart function. Patients with chronic heart failure and BNP values of less than or equal to 400 pg/mL may have pulmonary causes of dyspnea without exacerbation of their CHF.

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.

NT-proBNP testing

Ventricular myocytes secrete proBNP in response to muscle-wall tension. NT-proBNP has a longer half-life (120 min) than that of BNP (20 min). Although NT-proBNP is less studied than BNP, its levels are well correlated with BNP levels.

The cutoff value for NT-proBNP of greater than 450 pg/mL in patients younger than 50 years correlates to BNP values of greater than 100 pg/mL. NT-proBNP is less accurate than BNP in patients older than 65 years.

Radiography and Ultrasonography


Chest radiography is helpful in distinguishing CPE from other pulmonary causes of severe dyspnea. Features that suggest CPE rather than NCPE and other lung pathologies include the following (see the images below):

  • Enlarged heart

  • Inverted blood flow

  • Kerley lines

  • Basilar edema (vs diffuse edema)

  • Absence of air bronchograms

  • Presence of pleural effusion (particularly bilateral and symmetrical pleural effusions, more common in acute on chronic heart failure)

    Radiograph shows acute pulmonary edema in a patien Radiograph shows acute pulmonary edema in a patient known to have ischemic cardiomyopathy. Findings are Kerley B lines (1mm thick and 1cm long) in the lower lobes and Kerley A lines in the upper lobes.
    Radiograph shows interstitial pulmonary edema, car Radiograph shows interstitial pulmonary edema, cardiomegaly, and left pleural effusion presenting at an earlier stage of pulmonary edema.
    Radiograph demonstrates cardiomegaly, bilateral pl Radiograph demonstrates cardiomegaly, bilateral pleural effusions, and alveolar opacities in a patient with pulmonary edema.
    Lateral chest radiograph shows prominent interstit Lateral chest radiograph shows prominent interstitial edema and pleural effusions.

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.


In cases in which there is a moderate to high pretest probability of acute CPE, ultrasonography can be useful in strengthening a working diagnosis. Findings of B-lines on ultrasonography have been reported to have a sensitivity of 94.1% and a specificity of 92.4% for acute CPE.[6, 7]

Transthoracic lung ultrasonography may also be useful for differentiating between chronic obstructive pulmonary disease and chronic heart failure as causes of exacerbation of chronic dyspnea.[8]

In a prospective study of 134 patients, Sekiguchi et al found that combined cardiac and thoracic critical care ultrasonography (CCUS) assists in early bedside differential diagnosis of CPE, acute respiratory distress syndrome (ARDS), and other causes of acute hypoxemic respiratory failure (AHRF). Analysis of CCUS findings revealed that a low B-line ratio was predictive of miscellaneous cause vs CPE or ARDS. In the further differentiation of CPE from ARDS, moderately or severely decreased left ventricular function, left-sided pleural effusion (> 20 mm), and a large inferior vena cava minimal diameter (> 23 mm) were predictive of CPE.[9]


A bedside echocardiogram in a patient with decompensated CHF is an important diagnostic tool in determining the etiology of pulmonary edema. Echocardiography can be used to evaluate LV systolic and diastolic function, as well as valvular function, and to assess for pericardial disease. New wall-motion abnormalities may suggest acute myocardial infarction. It is especially helpful in identifying a mechanical etiology for pulmonary edema, such as the following:

  • Acute papillary muscle rupture

  • Acute ventricular septal defect

  • Cardiac tamponade

  • Contained LV rupture

  • Valvular vegetation with resulting acute severe mitral, aortic regurgitation

Pulmonary Arterial Catheter

PCWP can be measured with a pulmonary arterial catheter (Swan-Ganz catheter). This method helps in differentiating CPE from NCPE; NCPE occurs secondary to injury to the alveolar-capillary membrane rather than from alteration in Starling forces.

A PCWP exceeding 18 mm Hg in a patient not known to have chronically elevated LA pressure indicates CPE. 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. This condition raises pulmonary venous pressure and causes acute pulmonary edema. The pulmonary artery waveform appears falsely elevated because of the large V wave reflected back from the left atrium through the compliant pulmonary vasculature. 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. Cardiogenic shock is hemodynamically characterized by a systolic blood pressure of less than 80mm Hg, a cardiac index of less than 1.8 L/min/m2, and a PCWP of more than 18 mm Hg. 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).

The pulmonary artery catheter is sometimes 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 Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial showed no mortality benefit or decrease in the number of hospitalized days in the group of patients who underwent PAC insertion.[10] This matter needs further investigation.



Approach Considerations

The initial management of patients with cardiogenic pulmonary edema (CPE) should address the ABCs of resuscitation, that is, airway, breathing, and circulation. Oxygen should be administered to all patients to keep oxygen saturation at greater than 90%. Any associated arrhythmia or MI should be treated appropriately.

Methods of oxygen delivery include the use of a face mask, noninvasive pressure-support ventilation (which includes bilevel positive airway pressure [BiPAP] and continuous positive airway pressure [CPAP]), and intubation and mechanical ventilation. Which method is used depends on the presence of hypoxemia and acidosis and on the patient's level of consciousness. For example, intubation and mechanical ventilation may become necessary in cases of persistent hypoxemia, acidosis, or altered mental status.[11, 12]  The use of noninvasive pressure support ventilation in acidotic patients with severe acute cardiogenic pulmonary edema does not appear to be associated with adverse outcomes (early mortality and intubation rates) in these patients.[13]

Following initial management, medical treatment of CPE focuses on 3 main goals: (1) reduction of pulmonary venous return (preload reduction), (2) reduction of systemic vascular resistance (afterload reduction), and, in some cases, (3) inotropic support. Preload reduction decreases pulmonary capillary hydrostatic pressure and reduces fluid transudation into the pulmonary interstitium and alveoli. Afterload reduction increases cardiac output and improves renal perfusion, which allows for diuresis in the patient with fluid overload.

Patients with severe LV dysfunction or acute valvular disorders may present with hypotension. These patients may not tolerate medications to reduce their preload and afterload. Therefore, inotropic support is necessary in this subset of patients to maintain adequate blood pressure.

Patients who remain hypoxic despite supplemental oxygenation and patients who have severe respiratory distress require ventilatory support in addition to maximal medical therapy.


Ultrafiltration is a fluid removal procedure that is particularly useful in patients with renal dysfunction and expected diuretic resistance.

Intra-aortic balloon pumping

Intra-aortic balloon pumping (IABP) can be employed to achieve hemodynamic stabilization in the patient before definitive therapy. The IABP decreases afterload as the pump deflates; during diastole, the pump inflates to improve coronary blood flow.


Patients admitted with heart failure or pulmonary edema should be given a low-salt diet to minimize fluid retention. Closely monitor their fluid balance.

Ventilatory Support

Noninvasive pressure-support ventilation

Consider noninvasive pressure-support ventilation (NPSV) early when treating patients with severe CPE.

In NPSV, the patient breathes through a face mask against a continuous flow of positive airway pressure. NPSV maintains the patency of the fluid-filled alveoli and prevents them from collapsing during exhalation. As a result, the patient saves energy that would have been spent trying to reopen collapsed alveoli. NPSV improves pulmonary air exchange, and it increases intrathoracic pressure with reduction in preload and afterload.

Several studies suggest that NPSV is associated with decreased length of stay in the ICU, decreased need for mechanical ventilation, and decreased hospital costs. A few clinical trials showed that in patients with CPE—mainly defined as having severe dyspnea, oxygen saturation of less than 90%, and basal rales—early and prehospital NPSV treatment by paramedics is safe and associated with faster improvement of oxygen saturation.[14, 15] However, the mortality and the need for intensive care did not differ between the patients who were treated with NPSV and those who were treated with a Venturi face mask in most of those studies. Indeed, a more recent study that evaluated the safety and efficacy of implementing prehospital CPAP for the treatment of acute (CPE) and acute exacerbations of chronic obstructive pulmonary disease (AECOPD) found no benefit in morbidity, mortality, and length of hospital stay.[16]  


Two types of NPSV are CPAP and BiPAP. In CPAP, a single airway pressure is maintained throughout all phases of the respiratory cycle. In BiPAP, high pressures can be applied during inspiration and low pressures, during expiration, increasing the patient's comfort.[11]

A randomized trial comparing CPAP, noninvasive intermittent positive pressure ventilation (NIPPV), and standard oxygen therapy in 1069 patients with acute cardiogenic pulmonary edema demonstrated no mortality benefit from noninvasive ventilation, but improvements were seen in symptomatology and oxygenation.[17]

Although CPAP improves the condition of patients with cardiogenic pulmonary edema and has been associated with a reduced need for tracheal intubation, its use fails to reduce short-term mortality in this setting.[18]

In one small study, researchers compared CPAP with BiPAP and found that BiPAP was associated with more rapid improvement in vital signs but also with an increased rate of MIs.[19] Moreover, patients who received BiPAP initially had more chest pain than did patients who received CPAP. Other randomized clinical trials, however, did not show an increased rate of MI in patients who received CPAP or BiPAP compared with those who received oxygen by means of a face mask.

As of now, the data are insufficient to compare the efficacy and safety of BiPAP with those of CPAP. Therefore, the authors suggest that CPAP be the preferred method employed when NPSV is used unless the patient has obstructive airway disease.

Mechanical ventilation

In general, use endotracheal intubation and mechanical ventilation when patients with CPE remain hypoxic despite maximal noninvasive supplemental oxygenation, when patients have evidence of impending respiratory failure (eg, lethargy, fatigue, diaphoresis, worsening anxiety), or when patients are hemodynamically unstable (eg, hypotensive, severely tachycardic).

Mechanical ventilation maximizes myocardial oxygen delivery and ventilation. Positive end-expiratory pressure is generally recommended to increase alveolar patency and to enhance oxygen delivery and carbon dioxide exchange.

Preload Reduction


Nitroglycerin (NTG) is the most effective, predictable, and rapidly-acting medication available for preload reduction. Several studies demonstrated greater efficacy and safety and a faster onset of action with NTG than with furosemide or morphine sulfate. The use of sublingual NTG is associated with preload reduction within 5 minutes and with some afterload reduction.

Topical NTG may be as effective as sublingual NTG in most patients with CPE, but it should be avoided in patients with severe LV failure, because of poor skin perfusion (manifesting as skin pallor or mottling) and resultant poor absorption.

Intravenous (IV) NTG at high dosages provides rapid and titratable preload and afterload reduction and is excellent monotherapy for patients with severe CPE. IV NTG can be started with 10mcg/min and then rapidly uptitrated to more than 100mcg/min. The other alternative is NTG given as 3 mg IV boluses every 5 minutes.

The antianginal dose of NTG of 0.4 mg every 5 minutes has the bioequivalence of an NTG IV infusion of less than 80 mcg/min. Therefore, the dosage of NTG for patients with CPE is higher than the standard antianginal dosage would be.

Considering the short half-life of nitrates, physicians should be comfortable with the high dosage for CPE, especially in most patients with CPE, who present with a hyperadrenergic state and moderately elevated blood pressure. However, nitrates should not be used in hypotensive patients, and they should be used with extreme caution in patients with aortic stenosis and pulmonary hypertension.


Loop diuretics have been considered the cornerstone of CPE treatment for many years. Furosemide is used most commonly. Loop diuretics are presumed to decrease preload through 2 mechanisms: diuresis and direct vasoactivity (venodilation).

In most patients, diuresis does not occur for at least 20-90 minutes; therefore, the effect is delayed. Loop diuretics affect the ascending loop of Henle; therefore, the diminished renal perfusion in CPE may delay the onset of effects of loop diuretics.

Many patients with CPE do not have fluid overload. Continued use of diuretics in these patients after their acute symptoms have resolved may be associated with adverse outcomes, including electrolyte derangements, hypotension, and worsening renal function (GFR) as a result of tubuloglomerular feedback.

The presumption that these medications have a direct vasoactive (venodilating) effect has been questioned. Some studies demonstrated initial adverse hemodynamic consequences (eg, elevations of PCWP, LV filling pressure, heart rate, and systemic vascular resistance) after the administration of IV furosemide, perhaps due to direct neurohormonal stimulation.

Premedication with drugs that decrease preload (eg, NTG) and afterload (eg, angiotensin-converting enzyme [ACE] inhibitors) before the administration of loop diuretics can prevent potential adverse hemodynamic changes.

Morphine sulfate

The use of morphine sulfate in CPE for preload reduction has been commonplace for many years, but good evidence supporting a beneficial hemodynamic effect is lacking. Data suggest that morphine sulfate may contribute to a decrease in cardiac output and that it may be associated with an increased need for ICU admission and endotracheal intubation.

Adverse effects (eg, nausea and vomiting, local or systemic allergic reactions, respiratory depression) may outweigh any potential benefit, especially given the availability of medications that are more effective than morphine in reducing preload (eg, NTG).

Any beneficial hemodynamic effect from morphine is probably due to anxiolysis, with a resulting decrease in catecholamine production and a decrease in systemic vascular resistance. An alternative can be low-dose benzodiazepines (eg, lorazepam 0.5mg IV) in patients who are extremely anxious. This alternative reduces the risk of respiratory depression in patients whose condition responded to initial therapy.


Nesiritide is recombinant human BNP that decreases PCWP, pulmonary artery pressure, RA pressure, and systemic vascular resistance while increasing the cardiac index and stroke volume index. Therapy with nesiritide has decreased plasma renin, aldosterone, norepinephrine, and endothelin-1 levels and has reduced ventricular ectopy and ventricular tachycardia. Heart-rate variability also improves with nesiritide.[20, 21, 22]

Most of the beneficial effects of nesiritide were shown in the landmark Vasodilation in the Management of Acute Congestive Heart Failure (VMAC) study. Investigators compared IV nesiritide with IV NTG. IV nesiritide was associated with some hypotension but was otherwise well tolerated.

However, the VMAC study also showed a trend toward increased mortality in the IV nesiritide group compared with the patients receiving IV NTG, although the difference was not statically significant (90-day mortality, 19% for nesiritide vs 13% for NTG). The most important limitation of this study was the use of suboptimal dosages of IV NTG (mean 30-40 mcg/min) because the dosage was based on physician's decision and not on a protocol.

A later meta-analysis of 3 randomized trials of 485 patients receiving nesiritide and 377 patients not receiving nesiritide showed a 7.2% 30-day mortality with nesiritide versus 4% without nesiritide.[23]

In most large clinical trials nesiritide has not had a significant effect on renal function. In one of the largest studies of nesiritide to date, the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND HF), nesiritide had a neutral effect on survival and rehospitalization and a small effect on dyspnea when used in combination with other treatments.[24] In the study, which was powered to show the effects of the drug on survival and renal function, no association was found between use of nesiritide and deteriorating renal function, although use of this agent was associated with a slight increase in hypotension. The investigators recommended against the routine use of nesiritide in the broad population of patients with acute heart failure.[24]

Afterload Reduction

ACE inhibitors

ACE inhibitors are generally considered the cornerstones for treating chronic CHF, and studies have demonstrated excellent results with ACE inhibitors for the treatment of acute decompensated CHF and CPE. The use of ACE inhibitors in CPE is associated with reduced admission rates to ICUs and decreased endotracheal intubation rates and length of ICU stay.

The hemodynamic effects of ACE inhibitors include reduced afterload, improved stroke volume and cardiac output, and a slight reduction in preload. The last effects happen when renal perfusion improves after cardiac output improves and diuresis occurs.

Enalapril 1.25 mg IV or captopril 25 mg, given sublingually, result in hemodynamic and subjective improvements within 10 minutes. Improvements occur much more slowly with the oral route.

Angiotensin II receptor blockers

Angiotensin II receptor blockers (ARBs) have comparable beneficial effects in heart failure. Studies have proposed a role for ACE inhibitors and ARBs in preventing structural and electrical remodeling of the heart, resulting in a reduced incidence of arrhythmias.

The Valsartan Heart Failure Trial (Val-HeFT) showed that valsartan reduces the incidence of atrial fibrillation (AF) by 37%. (BNP level and advanced age were the strongest independent predictors for AF occurrence.)[25] Similarly, the Candesartan in Heart Failure: Assessment in Reduction of Mortality and Morbidity (CHARM) trial showed a reduction in the onset of AF in patients who were treated with Candesartan compared with placebo, with a median follow-up period of 37.7 months.[26]


Nitroprusside results in simultaneous preload and afterload reduction by causing direct smooth-muscle relaxation, with an increased effect on afterload. Afterload reduction is associated with increased cardiac output. The potency and rapidity of onset and offset of effect make this an ideal medication for patients who are critically ill. It may induce precipitous falls and labile fluctuations in blood pressure; intra-arterial blood pressure monitoring is often recommended.

Nitroprusside should generally be avoided in the setting of acute MI. Its use is associated with the shunting of blood away from ischemic myocardium toward healthy myocardium (ie, coronary steal syndrome), which potentiates ischemia.

If nitroprusside is used, convert therapy to oral or alternative IV vasodilator therapy as soon as possible, because prolonged high-dose use is associated with thiocyanate and cyanide toxicity, particularly in patients with significant hepatic or renal dysfunction. Use in pregnancy is associated with fetal thiocyanate toxicity. Prolonged infusion can induce tolerance, and reflex tachycardia may occur.


Inotropic support is usually used when preload- and afterload-reduction strategies are not successful or when hypotension precludes the use of these strategies. Two main classes of inotropic agents are available: catecholamine agents and phosphodiesterase inhibitors (PDIs). Calcium-sensitizer agents are a new class of medications that have notably beneficial effects in acute decompensated heart failure; these drugs are under investigation.


Dobutamine, a catecholamine agent, mainly serves as a beta1-receptor agonist, though it has some beta2-receptor and minimal alpha-receptor activity. IV dobutamine induces significant positive inotropic effects, with mild chronotropic effects. It also induces mild peripheral vasodilation (decrease in afterload). The combination effect of increased inotropy with decreased afterload significantly increases cardiac output. Combination use with IV NTG may be ideal for patients with MI and CPE and mild hypotension to simultaneously reduce preload and increase cardiac output. In general, avoid dobutamine in patients with moderate or severe hypotension (eg, systolic BP < 80 mm Hg), because of the peripheral vasodilation.


The vascular and myocardial receptor effects of dopamine, a catecholamine agent, are dose dependent. Low dosages of 0.5-5 mcg/kg/min stimulate dopaminergic receptors in the renal and splanchnic vascular beds, causing vasodilation and increasing diuresis. Moderate dosages of 5-10 mcg/kg/min stimulate beta-receptors in the myocardium, increasing cardiac contractility and heart rate.

High dosages of 15-20 mcg/kg/min stimulate alpha-receptors, resulting in peripheral vasoconstriction (increased afterload), increased blood pressure, and no further improvement in cardiac output.

Moderate and high dosages are arrhythmogenic and increase myocardial oxygen demand (with the potential for myocardial ischemia). Therefore, use these dosages only in patients with CPE who cannot tolerate dobutamine because of severe hypotension (eg, systolic blood pressure 60-80 mm Hg)


Norepinephrine, a catecholamine agent, primarily stimulates alpha receptors, significantly increasing afterload (and the potential for myocardial ischemia) and reducing cardiac output. Norepinephrine is generally reserved for patients with profound hypotension (eg, systolic blood pressure < 60 mm Hg). After blood pressure is restored, add other medications to maintain cardiac output.

Phosphodiesterase inhibitors

PDIs increase the level of intracellular cyclic adenosine monophosphate (cAMP) by preventing the breakdown of cAMP to 5'AMP. This results in a positive inotropic effect on the myocardium, in peripheral vasodilation (decreased afterload), and in a reduction in pulmonary vascular resistance (decreased preload). Unlike the catecholamine inotropes, PDIs do not depend on adrenoreceptor activity. Therefore, patients are less likely to develop tolerance to PDIs than they are to other medications. (Tolerance to catecholamine inotropes can rapidly develop by means of a down-regulation of adrenoreceptors.)

PDIs are less likely than catecholamine inotropes to cause the adverse effects that are typically associated with adrenoreceptor activity (eg, increased myocardial oxygen demand, myocardial ischemia).

Several direct comparisons of PDIs (milrinone) to dobutamine in patients with CPE demonstrated that milrinone produced equal or greater improvements in stroke volume, cardiac output, PCWPs (preload), and systemic vascular resistance (afterload). However, milrinone was associated with the same or more tachycardia and with an increased incidence of tachyarrhythmias.

Furthermore, the use of milrinone in the Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF) study did not reduce hospital length of stay and was associated with a significant increase in adverse events compared with placebo.[27]

All known IV inotropic agents are associated with an increased long-term mortality compared with placebo and therefore should be reserved for patients with heart failure and a markedly depressed cardiac index and stroke volume.

Calcium sensitizers

Levosimendan is a calcium sensitizer that is used in several European countries to manage moderate to severe heart failure. It has inotropic, metabolic, and vasodilatory effects. Levosimendan increases contractility by binding to troponin C. It does not increase myocardial oxygen demand, and it is not a proarrhythmogenic agent.[28, 29, 30]

Levosimendan opens potassium channels sensitive to adenosine triphosphate (ATP), causing peripheral arterial and venous dilatation. It also increases coronary flow reserve. Moreover, studies have shown levosimendan to have an anti-inflammatory effect.

Overall, levosimendan has been an effective and safe alternative to dobutamine. The most common adverse effects of levosimendan treatment are hypotension and headache. A randomized clinical study—the Survival of Patients With Acute Heart Failure in Need of Intravenous Inotropic Support (SURVIVE) trial—demonstrated no mortality benefit from levosimendan in comparison with dobutamine in patients with acute decompensated CHF.[31]


Tolvaptan is an oral vasopressin V2-receptor antagonist that was evaluated in a large (4133 patients), randomized, double-blind, placebo-controlled trial in patients with acute clinically decompensated CHF. This study, the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST), demonstrated no mortality or CHF hospitalization benefit at a median follow-up of 9.9 months. However, patients randomized to tolvaptan demonstrated early (1-7 d) improvements in body weight, dyspnea, serum sodium, and edema, as compared with placebo.[32, 33]

Intra-Aortic Balloon Pumping

Kantrowitz initially described intra-aortic balloon pumping (IABP) in 1953, but IABP was first used clinically in 1969 in a patient with cardiogenic shock. Since the 1980s, IABP has been increasingly applied in various clinical situations as a life-saving intervention to achieve hemodynamic stabilization before definitive therapy. The IABP decreases afterload as the pump deflates, and it improves coronary blood flow as it inflates during diastole.

The intra-aortic balloon pump is inserted percutaneously through the femoral artery using a modified Seldinger technique. The distal end of the pump is placed just distal to the aortic knob and the origin of the left subclavian artery. Fluoroscopy may be used for correct positioning of the balloon, and a subsequent radiograph should be obtained to document satisfactory placement of the balloon. Helium, a low-density gas with minimal water solubility, is used to inflate the balloon.

Proper timing of counterpulsation is necessary for maximum hemodynamic support. The timing of balloon inflation and deflation are best evaluated and adjusted at a pump ratio of 1:2. Inflation of the balloon should occur in early diastole, just after the aortic valve closes, and it should correspond to the dicrotic notch of the aortic pressure waveform. Balloon deflation should occur in early systole, just before the aortic valve opens.

Proper inflation leads to an assisted peak diastolic pressure higher than the unassisted peak systolic arterial pressure. Proper deflation results in assisted aortic end-diastolic pressure of approximately 10mm Hg lower than the unassisted end-diastolic pressure.

Diastolic augmentation enhances perfusion of the coronary circulation and carotid arteries. The reduction in end-diastolic pressure decreases aortic impedance (afterload) and augments systole.

By reducing aortic impedance and systolic pressure, IABP leads to a 15-25% reduction in LV wall stress. This level of afterload reduction improves LV volume, LV emptying, and myocardial oxygen consumption.

Diastolic aortic pressure augmentation improves myocardial perfusion and coronary blood flow. The effects on coronary blood flow may be variable but generally consist of a boost of 10-20% in the ischemic territories.

IABP decreases LV filling pressures by 20-25% and improves cardiac output by 20% in patients with cardiogenic shock. Therefore, IABP substantially reduces myocardial oxygen demand, although increased oxygen supply to the myocardium may also be a beneficial effect in some clinical situations.

IABP is effective in providing temporary support to patients in cardiogenic shock and end-stage cardiomyopathy while definite therapies, such as angioplasty, cardiac bypass surgery, mechanical circulatory support, or cardiac transplantation, are undertaken. In this case, the use of IABP is considered a bridge to a definitive revascularization procedure or implementation of an LV-assist device.

IABP is effective in stabilizing patients with unstable angina refractory to medical therapy before a definitive revascularization procedure.

IABP may be a life-saving intervention in patients with acute mitral regurgitation secondary to papillary muscle rupture or in patients with ventricular septal defect as a complication of MI. IABP reduces afterload and thereby reduces the severity of mitral regurgitation. It enhances forward cardiac output, reduces LA pressure, and improves pulmonary edema. Furthermore, IABP decreases LV afterload and improves cardiac output.

IABP can also provide hemodynamic support in the perioperative and postoperative period in high-risk patients, such as those with severe coronary disease, severe LV dysfunction, or recent MI.


Absolute contraindications for IABP counterpulsation are a dissecting aortic aneurysm, severe aortic regurgitation, a large arteriovenous shunt, and severe coagulopathy. Relative contraindications are severe peripheral vascular disease, recent thrombolytic therapy, bleeding diathesis, and descending aortic and peripheral vascular grafts.


IABP can cause several complications, which should be monitored while the patient is receiving IABP support. In general, the patient’s platelet counts are mildly reduced; however, the counts usually do not fall below 100 x 109/L.

Complications also may occur during cannulation of the femoral artery. These include perforation, laceration, or dissection of the artery (1-6%). Thrombosis of the iliofemoral artery and distal emboli may also occur (1-7%), and limb ischemia is reported in up to 40% of patients. Limb ischemia is reversible by removing the intra-aortic balloon pump, unless thrombosis develops; if thrombosis does occur, embolectomy is required to save the limb.

The other complications are localized bleeding (3-5%), infection (2-4%), thrombocytopenia (< 1%), and intestinal ischemia (< 1%).


Ultrafiltration (UF) is a method of fluid removal that is particularly useful in patients with renal dysfunction and expected diuretic resistance.

The randomized Ultrafiltration Versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated Heart Failure (UNLOAD) trial demonstrated that ultrafiltration was superior to the use of IV diuretics in controlling net fluid loss and rehospitalization in hypervolemic patients with heart failure.[34] These results indicated that UF should be considered in patients with volume overload and acute CHF who have not responded well to moderate to large doses of diuretic treatment or in whom the adverse effects of such treatment (eg, renal dysfunction) do not allow initiation or continuation of the therapy. 

Use of ultrafiltration in patients with decompensated heart failure and worsening renal function compared to conventional stepwise pharmacotherapy (consisting of diuretics and inotropic agents) is associated with similar diuresis but more impaired renal function at 96 hours following the initiation of treatment.[35]  Therefore, use of ultrafiltration is generally considered after failure of pharmacologic options or when it is known in a particular patient that the clinical response to drugs will be inadequate.    

Inpatient Care

After the patient's condition has been 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 or cardiac catheterization can also be performed during hospitalization to evaluate for reversible ischemia as the cause of pulmonary edema.

Consider echocardiography 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.

Cortellaro et al studied the potential role of lung ultrasound (LUS) in monitoring CPE response to therapy, by evaluating the clearance of interstitial syndrome within the first 24 hours after emergency department admission in 41 patients. LUS allowed the investigators to assess the clearance of interstitial syndrome and its distribution in the early hours of treatment of CPE, thereby representing a potential tool to guide therapy titration. At final evaluation (T24), 75% of apical regions were cleared and only 38% of basal regions were cleared.[36]

Patients in whom pulmonary edema is due to dietary factors or medication noncompliance need strict counseling and education to help prevent recurrences.


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:

  • Patients with CPE due to acute valvular dysfunction requiring urgent valve replacement

  • 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)

  • Patients with CPE who require inotropic support or hemodialysis beyond the capabilities of the initial hospital

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 implantation of a left ventricular assist device may be performed.


Consultations with subspecialists depend on the underlying cause of the episode of CPE. If the acute episode is attributed to an acute MI, acute cardiac ischemia, or an acute dysrhythmia, consultation with a cardiologist is often warranted.

If the episode is attributed to fluid overload in a patient with renal failure, consultation with a nephrologist is indicated for emergency or urgent hemodialysis.

If CPE results from acute valvular dysfunction, consultation with a cardiothoracic surgeon (including a cardiologist) for urgent valve replacement may be indicated, depending on the integrity of the valve.

In patients who develop cardiogenic shock, consultation with a cardiologist and/or critical care specialist is generally indicated to assist with titrating inotropic medication and, in some cases, to place an intra-aortic balloon pump as a temporizing measure before surgery (eg, valve replacement or coronary revascularization).



Medication Summary

Loop diuretics have long been the cornerstone of cardiogenic pulmonary edema (CPE) treatment, with furosemide being the most commonly used of these drugs. Premedication with drugs that decrease preload (eg, nitroglycerin [NTG]) and afterload (eg, angiotensin-converting enzyme [ACE] inhibitors) before the administration of loop diuretics can prevent adverse hemodynamic changes.

Nesiritide is recombinant human brain-type natriuretic peptide (BNP); it reduces pulmonary capillary wedge pressure (PCWP), pulmonary artery pressure, RA pressure, and systemic vascular resistance while increasing the cardiac index and stroke volume index. Therapy with nesiritide has decreased plasma renin, aldosterone, norepinephrine, and endothelin-1 levels and reduced ventricular ectopy and ventricular tachycardia. Heart-rate variability also improves with nesiritide. However, owing to the lack of positive outcomes data (ASCEND-HF) from the use of nesiritide, nesiritide cannot be recommended for routine use in the broad population of patients with acute heart failure.

Inotropic support is usually used following unsuccessful attempts at preload and afterload reduction or when hypotension precludes the use of these strategies. The two main classes of inotropic agents that are available are catecholamine agents and phosphodiesterase inhibitors (PDIs).

Preload Reducers

Class Summary

Reduced pulmonary venous return decreases pulmonary capillary hydrostatic pressure and reduces fluid transudation into the pulmonary interstitium and alveoli. Preload reducers include NTG (eg, Deponit, Minitran, Nitro-Bid IV, Nitro-Bid ointment, Nitrodisc, Nitro-Dur, Nitrogard, Nitroglyn, Nitrol, Nitrolingual, Nitrong, Nitrostat, Transdermal-NTG, Transderm-Nitro, Tridil) and furosemide (eg, Lasix).

Nitroglycerin IV (Nitro-Bid, Minitran, Nitrostat)

NTG is the drug of choice (DOC) for patients who are not hypotensive. It provides excellent and reliable preload reduction, and high dosages provide mild afterload reduction. NTG has rapid onset and offset (both within minutes), allowing for rapid clinical effects and rapid discontinuation of effects in adverse reactions.

Furosemide (Lasix)

Furosemide is the most commonly used loop diuretic. It increases the excretion of water by interfering with the chloride-binding cotransport system, inhibiting sodium and chloride reabsorption in the ascending loop of Henle and distal renal tubule. Furosemide reduces preload by diuresis in 20-60 minutes. It may contribute to hastened preload reduction with a direct vasoactive mechanism, but this is controversial.

As many as 50% of patients with CPE have total-body euvolemia. Although furosemide is generally administered to all patients with CPE, it is probably most useful in patients with total-body fluid overload.

The oral form of furosemide has a relatively slow onset of action and, therefore, is generally not appropriate in CPE.

Afterload Reducers

Class Summary

Reduced systemic vascular resistance increases cardiac output and improves renal perfusion, allowing for diuresis.


Captopril prevents the conversion of angiotensin I to angiotensin II. It is a potent vasodilator that lowers aldosterone secretion. It is an option in patients who are unable to tolerate NTG (eg, concurrent use of sildenafil). Hemodynamic (improved afterload and cardiac output) and subjective (decreased dyspnea) improvements occur in 10-15 minutes. Although captopril is not specifically formulated for sublingual (SL) use, the tablet can be wetted before it is placed under the patient's tongue to achieve the desired effect.

Enalapril (Vasotec)

Enalapril is a competitive ACE inhibitor. It reduces angiotensin II levels, decreasing aldosterone secretion. The use of IV captopril to treat decompensated heart failure and pulmonary edema not been studied as well as SL captopril has.

In 1993, Varriale evaluated patients with severe CHF and mitral regurgitation; he observed improved preload, afterload, cardiac output, and magnitude of regurgitation. In 1996, Annane evaluated patients with acute CPE and found improvements in preload and afterload. There was no demonstrated effect on cardiac output. Both studies showed an excellent safety profile.

Nitroprusside (Nitropress)

Nitroprusside is a potent, direct smooth muscle–relaxing agent that primarily reduces afterload but can mildly reduce preload. It improves cardiac output but can precipitously decrease blood pressure. Intra-arterial blood pressure monitoring is strongly recommended. Nitroprusside is excellent for use in critically ill patients because of its rapid onset and offset of action (within 1-2 min). It is excellent for use against pulmonary edema associated with severe hypertension that is unresponsive to other agents.

Inotropic Agents

Class Summary

These agents produce vasodilation and increase the inotropic state. At high dosages, they may increase the patient's heart rate, exacerbating myocardial ischemia. Conversely, phosphodiesterase enzyme inhibitors or bipyridine-positive inotropic agents have little chronotropic activity. They differ from digitalis glycosides and catecholamines in their mechanism of action.


Dobutamine is a synthetic catecholamine that mainly has beta1-receptor activity but also has some beta2- and alpha-receptor activity. It is commonly used in CPE and mild hypotension (systolic blood pressure 90-100 mm Hg). Dobutamine has a combination of beneficial hemodynamic effects (eg, positive inotropism, decreased afterload due to mild vasodilation, increased cardiac output).


Dopamine is a naturally occurring catecholamine that acts as a precursor to norepinephrine. It stimulates adrenergic and dopaminergic receptors. Dopamine's hemodynamic effect is dose dependent. A low dose is associated with dilation in renal and splanchnic vasculature, enhancing diuresis. Moderate doses enhance cardiac contractility and heart rate. High doses increase afterload due to peripheral vasoconstriction. The use of dopamine in CPE is generally reserved for patients with moderate hypotension (eg, systolic blood pressure 70-90 mm Hg). Moderate to high doses are usually used.

Norepinephrine (Levophed)

Norepinephrine is a naturally occurring catecholamine with potent alpha-receptor and mild beta-receptor activity. It stimulates beta1- and alpha-adrenergic receptors, increasing myocardial contractility, heart rate, and vasoconstriction. Norepinephrine increases blood pressure and afterload; it may decrease cardiac output and increase myocardial oxygen demand and cardiac ischemia. This agent is generally reserved for patients with severe hypotension (eg, systolic blood pressure < 70 mm Hg) or hypotension unresponsive to other medication.


Milrinone is a positive inotropic agent and vasodilator. It reduces afterload and preload and increases cardiac output. In several comparisons, milrinone improved preload, afterload, and cardiac output more than dobutamine, without significantly increased myocardial oxygen consumption.


Questions & Answers


What is cardiogenic pulmonary edema (CPE)?

What are the pathophysiologic mechanisms that cause cardiogenic pulmonary edema (CPE)?

What causes increased hydrostatic pressure in cardiogenic pulmonary edema (CPE)?

What are major complications of cardiogenic pulmonary edema (CPE)?

How is recurrence of cardiogenic pulmonary edema (CPE) prevented?

What causes cardiogenic pulmonary edema (CPE)?

What is the pathophysiology of cardiogenic pulmonary edema (CPE)?

What is the role of lymphatics in the pathophysiology of cardiogenic pulmonary edema (CPE)?

What are the stages of fluid accumulation in the pathogenesis of cardiogenic pulmonary edema (CPE)?

What is the role of atrial outflow obstruction in the etiology of cardiogenic pulmonary edema (CPE)?

What is the role of LV systolic dysfunction in the etiology of cardiogenic pulmonary edema (CPE)?

What is the role of LV diastolic dysfunction in the etiology of cardiogenic pulmonary edema (CPE)?

What is the role of dysrhythmias in the etiology of cardiogenic pulmonary edema (CPE)?

What is the role of LV hypertrophy and cardiomyopathy in the etiology of cardiogenic pulmonary edema (CPE)?

What is the role of LV volume overload in the etiology of cardiogenic pulmonary edema (CPE)?

What is the role of myocardial infarction in the etiology of cardiogenic pulmonary edema (CPE)?

What is the role of LV outflow obstruction in the etiology of cardiogenic pulmonary edema (CPE)?

What is the prognosis of cardiogenic pulmonary edema (CPE)?


What are the signs and symptoms of cardiogenic pulmonary edema (CPE)?

Which physical findings are characteristic of cardiogenic pulmonary edema (CPE)?

Which cardiovascular findings are characteristic of cardiogenic pulmonary edema (CPE)?

Which physical findings are characteristic of severe cardiogenic pulmonary edema (CPE)?


How is cardiogenic pulmonary edema (CPE) differentiated from noncardiogenic pulmonary edema (NCPE)?

Which conditions should be included in the differential diagnoses of cardiogenic pulmonary edema (CPE)?

What are the differential diagnoses for Cardiogenic Pulmonary Edema?


What is the role of lab studies in the evaluation of cardiogenic pulmonary edema (CPE)?

What is the role of electrocardiography in the evaluation of cardiogenic pulmonary edema (CPE)?

What is the role of CT scanning in the evaluation of cardiogenic pulmonary edema (CPE)?

What is brain-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) testing, and why is it performed in the workup of cardiogenic pulmonary edema (CPE)?

How is brain-type natriuretic peptide (BNP) testing used in the evaluation of cardiogenic pulmonary edema (CPE)?

What are the cutoff values for brain-type natriuretic peptide (BNP) testing in the evaluation of cardiogenic pulmonary edema (CPE)?

How is N-terminal proBNP (NT-proBNP) testing used in the evaluation of cardiogenic pulmonary edema (CPE)?

What is the role of radiography in the workup of cardiogenic pulmonary edema (CPE)?

What is the role of ultrasonography in the workup of cardiogenic pulmonary edema (CPE)?

What is the role of electrocardiography in the workup of cardiogenic pulmonary edema (CPE)?

What is the role of a pulmonary arterial catheter in the workup of cardiogenic pulmonary edema (CPE)?


What is the initial treatment for cardiogenic pulmonary edema (CPE)?

What are the goals of medical treatment for cardiogenic pulmonary edema (CPE)?

What is the role of ultrafiltration in the treatment of cardiogenic pulmonary edema (CPE)?

When is intra-aortic balloon pumping (IABP) indicated in the treatment of cardiogenic pulmonary edema (CPE)?

What dietary restrictions are needed during the treatment of cardiogenic pulmonary edema (CPE)?

What is the role of noninvasive pressure-support ventilation (NPSV) in the treatment of cardiogenic pulmonary edema (CPE)?

What are the noninvasive pressure-support ventilation (NPSV) options for the treatment of cardiogenic pulmonary edema (CPE)?

What is the role of mechanical ventilation in cardiogenic pulmonary edema (CPE)?

What is the role of nitroglycerin (NTG) in the treatment of cardiogenic pulmonary edema (CPE)?

What is the role of diuretics in the treatment of cardiogenic pulmonary edema (CPE)?

What is the role of morphine in the treatment of cardiogenic pulmonary edema (CPE)?

What is the role of nesiritide in the treatment of cardiogenic pulmonary edema (CPE)?

What is the role of ACE inhibitors in the treatment of cardiogenic pulmonary edema (CPE)?

What is the role of angiotensin II receptor blockers (ARBs) in the treatment of cardiogenic pulmonary edema (CPE)?

What is the role of nitroprusside in the treatment of cardiogenic pulmonary edema (CPE)?

Which medications are used for inotropic support in cardiogenic pulmonary edema (CPE)?

What is the role of dobutamine in the treatment of cardiogenic pulmonary edema (CPE)?

What is the role of dopamine in the treatment of cardiogenic pulmonary edema (CPE)?

What is the role of norepinephrine in the treatment of cardiogenic pulmonary edema (CPE)?

What is the role of phosphodiesterase inhibitors (PDIs) in the treatment of cardiogenic pulmonary edema (CPE)?

What is the role of calcium sensitizers in the treatment of cardiogenic pulmonary edema (CPE)?

What is the role of tolvaptan in the treatment of cardiogenic pulmonary edema (CPE)?

How does intra-aortic balloon pumping (IABP) stabilize hemodynamically unstable patients with cardiogenic pulmonary edema (CPE)?

How is intra-aortic balloon pumping (IABP) performed in the management of cardiogenic pulmonary edema (CPE)?

What is the efficacy of intra-aortic balloon pumping (IABP) for cardiogenic pulmonary edema (CPE)?

What are contraindications for intra-aortic balloon pumping (IABP) for cardiogenic pulmonary edema (CPE)?

What are possible complications of intra-aortic balloon pumping (IABP) for cardiogenic pulmonary edema (CPE)?

What is the role of ultrafiltration (UF) for the treatment of cardiogenic pulmonary edema (CPE)?

What is included in inpatient care for cardiogenic pulmonary edema (CPE)?

When is transfer of patients with cardiogenic pulmonary edema (CPE) indicated?

Which specialist consultations are needed for the treatment of cardiogenic pulmonary edema (CPE)?


Which medications are used for the treatment of cardiogenic pulmonary edema (CPE)?

Which medications in the drug class Inotropic Agents are used in the treatment of Cardiogenic Pulmonary Edema?

Which medications in the drug class Afterload Reducers are used in the treatment of Cardiogenic Pulmonary Edema?

Which medications in the drug class Preload Reducers are used in the treatment of Cardiogenic Pulmonary Edema?