Pulmonary edema can be defined as an abnormal accumulation of extravascular fluid in the lung parenchyma. This process leads to diminished gas exchange at the alveolar level, progressing to potentially causing respiratory failure. Its etiology is either due to a cardiogenic process with the inability to remove sufficient blood away from the pulmonary circulation or non-cardiogenic precipitated by injury to the lung parenchyma. It is an important pathologic feature in many disease processes, and hence learning the underlying disease process is crucial to guide its management. Clinical features include progressive worsening dyspnea, rales on lung auscultation, and worsening hypoxia.

Edema is the accumulation of excess water in the tissues. It is most common in the soft tissues of the extremities. The physiological causes of edema include water leakage from blood capillaries. Edema is almost always caused by an underlying medical condition, by the use of certain therapeutic drugs, by pregnancy, by localized injury, or by an allergic reaction. In the limbs, the symptoms of edema include swelling of the subcutaneous tissues, an increase in the normal size of the limb, and stretched, tight skin. One quick way to check for subcutaneous edema localized in a limb is to press a finger into the suspected area. Edema is likely if the depression persists for several seconds after the finger is removed (which is called “pitting”).

Pulmonary edema is excess fluid in the air sacs of the lungs, a common symptom of heart and/or kidney failure. People with pulmonary edema likely will experience difficulty breathing, and they may experience chest pain. Pulmonary edema can be life threatening, because it compromises gas exchange in the lungs, and anyone having symptoms should immediately seek medical care.

In pulmonary edema resulting from heart failure, excessive leakage of water occurs because fluids get “backed up” in the pulmonary capillaries of the lungs, when the left ventricle of the heart is unable to pump sufficient blood into the systemic circulation. Because the left side of the heart is unable to pump out its normal volume of blood, the blood in the pulmonary circulation gets “backed up,” starting with the left atrium, then into the pulmonary veins, and then into pulmonary capillaries. The resulting increased hydrostatic pressure within pulmonary capillaries, as blood is still coming in from the pulmonary arteries, causes fluid to be pushed out of them and into lung tissues.

Other causes of edema include damage to blood vessels and/or lymphatic vessels, or a decrease in osmotic pressure in chronic and severe liver disease, where the liver is unable to manufacture plasma proteins (Figure). A decrease in the normal levels of plasma proteins results in a decrease of colloid osmotic pressure (which counterbalances the hydrostatic pressure) in the capillaries. This process causes loss of water from the blood to the surrounding tissues, resulting in edema.

Figure. Edema An allergic reaction can cause capillaries in the hand to leak excess fluid that accumulates in the tissues. (credit: Jane Whitney)

Mild, transient edema of the feet and legs may be caused by sitting or standing in the same position for long periods of time, as in the work of a toll collector or a supermarket cashier. This is because deep veins in the lower limbs rely on skeletal muscle contractions to push on the veins and thus “pump” blood back to the heart. Otherwise, the venous blood pools in the lower limbs and can leak into surrounding tissues.

Medications that can result in edema include vasodilators, calcium channel blockers used to treat hypertension, non-steroidal anti-inflammatory drugs, estrogen therapies, and some diabetes medications. Underlying medical conditions that can contribute to edema include congestive heart failure, kidney damage and kidney disease, disorders that affect the veins of the legs, and cirrhosis and other liver disorders.

Therapy for edema usually focuses on elimination of the cause. Activities that can reduce the effects of the condition include appropriate exercises to keep the blood and lymph flowing through the affected areas. Other therapies include elevation of the affected part to assist drainage, massage and compression of the areas to move the fluid out of the tissues, and decreased salt intake to decrease sodium and water retention.

Pulmonary edema can be broadly classified into cardiogenic and noncardiogenic pulmonary edema.

Cardiogenic or volume-overload pulmonary edema arises due to a rapid elevation in the hydrostatic pressure of the pulmonary capillaries. This is typically seen in disorders involving left ventricular systolic and diastolic function (acute myocarditis including other etiologies of non-ischemic cardiomyopathy, acute myocardial infarction), valvular function (aortic/mitral regurgitation and stenosis in the moderate to the severe range), rhythm (atrial fibrillation with a rapid ventricular response, ventricular tachycardia, high degree, and third-degree heart block).

Noncardiogenic pulmonary edema is caused by lung injury with a resultant increase in pulmonary vascular permeability leading to the movement of fluid, rich in proteins, to the alveolar and interstitial compartments. Acute lung injury with severe hypoxemia is referred to as acute respiratory distress syndrome (ARDS) and is seen in various conditions directly affecting the lungs, such as pneumonia, inhalational injury, or indirectly, such as sepsis, acute pancreatitis, severe trauma with shock, multiple blood transfusions.

In addition to a thorough history and physical examination, electrocardiogram assists in diagnosing cardiac ischemia or myocardial infarction. It is a quick, inexpensive, and relatively less specialized test that can be done at the bedside.

Following are a variety of diagnostic tools utilized to help diagnose pulmonary edema and, more importantly, differentiate between its different types. 

Laboratory Testing

Brain-type natriuretic peptide (BNP) is secreted by the cardiac myocytes of the left ventricles in response to stretching caused by increased ventricular blood volume or increased intracardiac pressures. Elevated BNP levels correlate with left ventricular end-diastolic pressure as well as pulmonary occlusion pressure and can be seen in patients with congestive heart failure. BNP levels less than 100 pg/ml suggest heart failure is less likely, and levels greater than 500 pg/ml suggest a high likelihood of heart failure. Levels between 100 and 500 pg/ml do not help in the diagnosis of heart failure and are often seen in critically ill patients. 

Troponin elevation is commonly noted in patients with damage to myocytes, such as acute coronary syndrome. They, however, are also noted to be elevated in patients with severe sepsis.

Hypoalbuminemia (≤3.4 g/dL) is an independent marker of increased in-hospital and post-discharge mortality for patients presenting in acute decompensated heart failure. Low albumin in isolation does not lead to pulmonary edema as there is a concurrent drop in pulmonary interstitial and plasma albumin levels preventing the creation of a transpulmonary oncotic pressure gradient.

Obtaining serum electrolyte levels, including renal function, serum osmolarity, toxicology screening, help in patients with pulmonary edema due to toxic ingestion. Obtaining lipase and amylase levels help diagnose acute pancreatitis.  

Radiographic Testing

Both posteroanterior and lateral views in standard imaging or anteroposterior views in portable imaging are utilized. Cardiogenic pulmonary edema is characterized by the presence of central edema, pleural effusions, Kerley B septal lines, peribronchial cuffing, and enlarged heart size. In noncardiogenic etiologies, the edema pattern is typically patchy and peripheral that can demonstrate the presence of ground-glass opacities and consolidations with air bronchograms. Pleural effusions are more commonly seen in the cardiogenic type.

Echocardiography 

Assists in the diagnosis of left ventricular systolic dysfunction and valvular dysfunction. Through modalities, including tissue Doppler imaging of the mitral annulus, the presence and degree of diastolic dysfunction can be assessed.

Lung Ultrasound

A newer technique that is non-invasive and does not involve radiation exposure. It is most commonly used in intensive care units, emergency rooms, and operating rooms. It helps detect the accumulation of extravascular lung water (EVLW) ahead of the clinical manifestations.

Pulmonary Artery Catheterization

Often considered a gold standard in the determination of the etiology of pulmonary edema, it is an invasive test that helps monitor systemic vascular resistance, cardiac output, and filling pressures. An elevated pulmonary artery occlusion pressure over 18 mm Hg is helpful in the determination of cardiogenic pulmonary edema.

Transpulmonary Thermodilution

It is an invasive testing modality performed in patients typically undergoing major cardiac, vascular, or thoracic surgeries. They are also used in septic shock and monitors several hemodynamic indices such as cardiac index, mixed venous oxygen saturation, stroke volume index, and EVLW.

Therapeutic goals in patients with pulmonary edema include alleviation of symptoms and treatment of the underlying pathologic condition.

Diuretics remain the mainstay of treatment, and furosemide being the most commonly used medication. Higher doses are associated with more improvement in dyspnea; however, also associated with transient worsening of renal function.

Vasodilators can be added as an adjuvant therapy to the diuretics in the management of pulmonary edema. IV nitroglycerin (NTG) is the drug of choice, and it lowers preload and pulmonary congestion. NTG should only be used when the systolic blood pressure (SBP) is > 110 mm Hg. Nesiritide is a recombinant brain natriuretic peptide that has vasodilatory properties. It has been shown to reduce pulmonary capillary wedge pressure (PCWP) and filling pressures significantly, but no subsequent improvement in dyspnea has been noted. Newer drugs like serelaxin, a recombinant human form of relaxin, induced nitric oxide activation, which causes vasodilation. Clevidipine is an ultra-short-acting calcium channel blocker, initiated very early in the presentation, has been associated with reduced length of stay, improved dyspnea, and less frequent ICU admission. 

Nifedipine has been utilized in the prophylaxis and treatment of high altitude pulmonary edema (HAPE). This calcium channel blocker counteracts the hypoxia-mediated vasoconstriction of the pulmonary vasculature. This leads to the lowering of the pulmonary arterial pressure with subsequent improvements in gas exchange, exercise capability, and chest radiography. Nifedipine is only used as a prophylactic strategy when altitude acclimatization cannot be achieved in high-risk individuals and situations, including a rapid rate of ascent, extreme physical exertion, recent respiratory tract infection, and low altitude of native place of residence.

Inotropes, such as dobutamine and dopamine, are used in the management of pulmonary congestion when associated with low SBP and signs of tissue hypoperfusion. Significant adverse events include tachyarrhythmias, ischemia, and hypotension. Milrinone is an IV inotrope with vasodilatory properties but is associated with an increase in post-discharge mortality. Morphine reduces systemic vascular resistance and acts as an analgesic and anxiolytic. It has been used in the management of pulmonary edema secondary to acute coronary syndrome. However, it may cause respiratory depression needing intubation, and generally not recommended.

Ventilatory support, both noninvasive and invasive, is used to improve oxygenation, direct alveolar and interstitial fluids back into the capillaries, improve hypercarbia and hence reverse respiratory acidosis, and lastly, tissue oxygenation. It also aims at reducing the work of breathing. The decision to provide ventilatory support is based on clinical improvement with a trial of the above-mentioned drugs, patient's mental status, overall energy, or lack of such. In patients on invasive mechanical ventilation, continuous monitoring of hemodynamics is essential as a reduction in preload can lead to reduced cardiac output and thus a fall in SBP. Noninvasive mechanical ventilation, when initiated early in the management of pulmonary edema, has been associated with lower occurrences of respiratory muscle fatigue and, thus, reduction in invasive ventilation.

Prognosis

Pulmonary edema is an acutely decompensated state due to either cardiac or noncardiac etiologies. Temporizing measures such as supplemental oxygenation, diuretics, nitrates, and morphine help manage dyspnea, hypoxemia. However, definitive management of the underlying causes is necessary to prevent its recurrences. Prognostic predictions are difficult to quantify, given the vast number of cardiogenic and non-cardiogenic etiologies of pulmonary edema and their individual mortality data. Pulmonary edema's advanced state in ARDS has had progressively improved outcomes. Hospital mortality has decreased from 60% from 1967 through 1981 to the range of 30% to 40% in the 1990s. Furthermore, analysis of ARDS mortality studies demonstrated a decline in overall mortality of about 1.1% per year from 1994 to 2006. Prognosis utilizing mortality data is largely variable and depends on the precipitating process of ARDS.

Complications

Since pulmonary edema is a result of complex physiologic derangements, be it cardiac, hepatic, multiorgan system involvement, toxic stimuli, the complications arising from it are generally secondary to the aforementioned pathophysiologic processes. Cardiogenic pulmonary edema can progress to respiratory failure requiring the utilization of a mechanical ventilator. ARDS is a complication of acute lung injury with progressive hypoxemia, also requiring intubation and mechanical ventilation.

Deterrence and Patient Education

Patients with a history of ischemic or valvular cardiac disease must be educated on the symptoms of pulmonary edema on every clinic visit with their doctors. Counseling on a low salt diet, regular exercise, and medication compliance must be emphasized.

Enhancing Healthcare Team Outcomes

Pulmonary edema can be a result of multiorgan involvement, and hence the involvement of an interprofessional team such as internists, cardiology, pulmonology early in the course is recommended for timely initiation of targeted therapy to improve patient outcomes. Education to the nurses, medical students, nursing students on the signs of respiratory failure must be provided regularly for earlier identification of patients with an impending respiratory decompensation. Good history-taking skills must be practiced to identify factors such are medication non-compliance, a poor socioeconomic situation, illicit drug use to avoid recurrences or readmissions.