Pathophysiology

Although pulmonary edema is traditionally separated into two categories according to cause (cardiogenic and noncardiogenic), the end result of both processes is a net fluid accumulation within the interstitial and alveolar spaces. Noncardiogenic pulmonary edema, in its most severe state, is also known as acute respiratory distress syndrome (ARDS) (Chapters 65 and 365).

The hydrostatic pressure and colloid osmotic (oncotic) pressure on either side of a pulmonary vascular wall, along with vascular permeability, are the forces and physical factors that determine fluid movement through the vessel wall. Baseline conditions lead to a net filtration of fluid from the intravascular space into the interstitium. This “extra” interstitial fluid is usually rapidly reabsorbed by pulmonary lymphatics. Conditions that lead to altered vascular permeability, increased pulmonary vascular pressure, and decreased intravascular oncotic pressure increase the net flow of fluid out of the vessel (Table 388-1). Once the capacity of the lymphatics for fluid removal is exceeded, water accumulates in the lung.

To understand the sequence of lung water accumulation, it is helpful to consider its distribution among 4 distinct compartments, as follows:

Etiology

The specific clinical findings vary according to the underlying mechanism (see Table 388-1).

Increases in pulmonary vascular pressure (capillary hydrostatic pressure) lead to increases in transudation of fluid. Cardiac processes that lead to myocardial dysfunction and decreased left-sided output and those that lead to mitral valve regurgitation cause increased “back-pressure” in the pulmonary vasculature. In addition, abnormalities of the pulmonary veins often obstruct venous drainage and also result in an increase in pulmonary capillary pressure.

Increased capillary permeability is usually secondary to endothelial damage. Such damage can occur secondary to direct injury to the alveolar epithelium or indirectly through systemic processes that deliver circulating inflammatory mediators or toxins to the lung. Inflammatory mediators (tumor necrosis factor, leukotrienes, thromboxanes) and vasoactive agents (nitric oxide, histamine) formed during pulmonary and systemic processes potentiate the altered capillary permeability that occurs in many disease processes, with sepsis being a common cause.

Fluid homeostasis in the lung largely depends on drainage via the lymphatics. Experimentally, pulmonary edema occurs with obstruction of the lymphatic system. Increased lymph flow and dilation of lymphatic vessels occur in chronic edematous states.

A decrease in intravascular oncotic pressure leads to pulmonary edema by altering the forces promoting fluid reentry into the vascular space. This occurs in dilutional disorders such as fluid overload with hypotonic solutions and in protein-losing states such as nephrotic syndrome and malnutrition.

The excessive negative interstitial pressure seen in upper airway diseases, such as croup and laryngospasm, may promote pulmonary edema. Aside from the physical forces present in these diseases, other mechanisms may also be involved. Theories implicate an increase in CO₂ tension, decreased O₂ tension, and extreme increases in cardiac afterload, leading to transient cardiac insufficiency.

The mechanism causing neurogenic pulmonary edema is not clear. A massive sympathetic discharge secondary to a cerebral injury may produce increased pulmonary and systemic vasoconstriction, resulting in a shift of blood to the pulmonary vasculature, an increase in capillary pressure, and edema formation.

The mechanism responsible for high-altitude pulmonary edema is unclear, but it may also be related to sympathetic outflow, increased pulmonary vascular pressures, and hypoxia-induced increases in capillary permeability.

Active ion transport followed by passive, osmotic water movement is important in clearing the alveolar space of fluid. Interindividual genetic differences in the rates of these transport processes may be important in determining which individuals are susceptible to altitude-related pulmonary edema. Although the existence of these mechanisms suggests that therapeutic interventions may be developed to promote resolution of pulmonary edema, no such therapies currently exist.

Clinical Manifestations

The clinical features depend on the mechanism of edema formation. In general, interstitial edema and alveolar edema prevent the inflation of alveoli, leading to atelectasis and decreased surfactant production. This results in diminished pulmonary compliance and tidal volume. The patient must increase respiratory effort and/or the respiratory rate in order to maintain minute ventilation. The earliest clinical signs of pulmonary edema include increased work of breathing, tachypnea, and dyspnea. As fluid accumulates in the alveolar space, auscultation reveals fine crackles and wheezing, especially in dependent lung fields. In cardiogenic pulmonary edema, a gallop may be present as well as peripheral edema and jugular venous distention.

Chest radiographs can provide useful ancillary data, although findings of initial radiographs may be normal. Early radiographic signs that represent accumulation of interstitial edema include peribronchial and perivascular cuffing. Diffuse streakiness reflects interlobular edema and distended pulmonary lymphatics. Diffuse, patchy densities, the so-called butterfly pattern, represent bilateral interstitial or alveolar infiltrates and are a late sign. Cardiomegaly is often seen with causes that involve left ventricular dysfunction. Heart size is usually normal in noncardiogenic pulmonary edema (Table 388-2). Chest tomography demonstrates edema accumulation in the dependent areas of the lung. As a result, changing the patient’s position can alter regional differences in lung compliance and alveolar ventilation.

Table 388-2 RADIOGRAPHIC FEATURES THAT MAY HELP DIFFERENTIATE CARDIOGENIC FROM NONCARDIOGENIC PULMONARY EDEMA

* The width of the vascular pedicle in adults is determined by dropping a perpendicular line from the point at which the left subclavian artery exits the aortic arch and measuring across to the point at which the superior vena cava crosses the right mainstem bronchus. A vascular-pedicle width >70 mm on a portable digital anteroposterior radiograph of the chest obtained when the patient is supine is optimal for differentiating high from normal-to-low intravascular volume.

From Ware LB, Matthay MA: Acute pulmonary edema, N Engl J Med 353:2788–2796, 2005.

Measurement of brain natriuretic peptide (BNP), often elevated in heart disease, can help differentiate cardiac from pulmonary causes of pulmonary edema. A BNP level >500 pg/mL suggests heart disease; a level <100 pg/mL suggests lung disease.

Treatment

The treatment of a patient with noncardiogenic pulmonary edema is largely supportive, with the primary goal to ensure adequate ventilation and oxygenation. Additional therapy is directed toward the underlying cause. Patients should receive supplemental oxygen to increase alveolar oxygen tension and pulmonary vasodilation. Patients with pulmonary edema of cardiogenic causes should be managed with inotropic agents and systemic vasodilators to reduce left ventricular afterload (Chapter 436). Diuretics are valuable in the treatment of pulmonary edema associated with total body fluid overload (sepsis, renal insufficiency). Morphine is often helpful as a vasodilator and a mild sedative.

Positive airway pressure improves gas exchange in patients with pulmonary edema. In tracheally intubated patients, positive end-expiratory pressure (PEEP) can be used to optimize pulmonary mechanics. Noninvasive forms of ventilation, such as mask or nasal prong continuous positive airway pressure (CPAP), are also effective. The mechanism by which positive airway pressure improves pulmonary edema is not entirely clear but is not associated with decreasing lung water. Rather, CPAP prevents complete closure of alveoli at the low lung volumes present at the end of expiration. It may also recruit already collapsed alveolar units. This leads to increased functional residual capacity (FRC) and improved pulmonary compliance, improved surfactant function, and decreased pulmonary vascular resistance. The net effect is to decrease the work of breathing, improve oxygenation, and decrease cardiac afterload (Chapter 365).

When mechanical ventilation becomes necessary, especially in noncardiogenic pulmonary edema, care must be taken to minimize the risk of development of complications from barotrauma, including pneumothorax, pneumomediastinum, and primary alveolar damage (Chapter 65.1). Lung protective strategies include setting low tidal volumes, relatively high PEEPs, and allowing for permissive hypercapnia.

High-altitude pulmonary edema (HAPE) should be managed with altitude descent and supplemental oxygen. Portable CPAP or a portable hyperbaric chamber is also helpful. Nifedipine (10 mg initially, and then 20-30 mg by slow release every 12-24 hr) in adults is also helpful. If there is a history of HAPE, nifedipine and β-adrenergic agonists (inhaled) may prevent recurrence.