Gas exchange occurs at the delicate interface between air and blood consisting of the alveolar epithelium and capillary endothelium. Flooding of the interstitium and alveoli with ﬂuid and solutes from the pulmonary microvascular space disrupts this interface and is an important cause of dyspnea, hypoxemia, and respiratory failure. The pathophysiologic mechanisms that cause pulmonary edema differ among the conditions that can lead to this problem. Understanding these mechanisms provides a rationale for management (see Plate 4-127).
PULMONARY EDEMA: PATHWAY OF NORMAL PULMONARY FLUID RESORPTION
The familiar Starling relationship applies to the pulmonary microvasculature as it does in other capillary beds and estimates the net ﬂuid ﬂux (Q) across the capillary membrane from the microvascular space (mv) into the perimicrovascular interstitial ﬂuid (if). The important variables are the total surface area of the microvasculature (S), the vascular permeability per unit surface area (L), and the net hydrostatic pressures across this membrane (Pmv - Pif ), offset partially by the plasma colloid oncotic pressure within the microvasculature as opposed to the somewhat lower colloid osmotic pressure in the interstitium (mv -if ). The difference in osmotic pressures across the pulmonary capillaries is less than in other capillary beds, and low albumin states alone do not cause pulmonary edema.
In the normal lung, the tight junctions of the alveolar epithelium prevent ﬂuid from entering the alveoli, so that the ﬂuid transudate enters the perimicrovascular interstitial space and then drains proximally through the pulmonary lymphatics into the venous system. The two most common perturbations that overwhelm this homeostasis are an elevation in capillary hydrostatic pressure and an increase in the permeability of the microvasculature (see Plate 4-128).
CARDIOGENIC PULMONARY EDEMA
Pulmonary edema from increased hydrostatic pressures is almost always caused by increased left atrial ﬁlling pressures from cardiac dysfunction or volume overload and is termed cardiogenic pulmonary edema. Common clinical situations are acute coronary syndromes, systolic or diastolic heart failure, valvular heart disease, and volume overload from acute or chronic renal failure. Because the permeability of the capillaries to proteins is preserved, the ﬂuid in the alveoli is low in protein. Management is focused on reducing the ﬁlling pressures with diuresis and afterload reduction, as well as speciﬁc therapies for the underlying disorder (e.g., coronary revascularization, valvular surgery, renal replacement therapy).
NONCARDIOGENIC PULMONARY EDEMA
Pulmonary edema may occur even with normal hydrostatic pressures if there is an increase in the permeability of the endothelial and epithelial membranes. As both proteins and ﬂuids leak through these altered membranes, the amount of protein in the edema ﬂuid is elevated. The most frequent cause of noncardiogenic pulmonary edema is acute lung injury (ALI) initiated by inhaled or ingested toxins or by inﬂammatory mediators released in response to pulmonary or systemic insults. ALI and adult respiratory distress syndrome (ARDS) are most frequently associated with pneumonia, aspiration of gastric contents, sepsis syndromes, pancreatitis, major trauma, and multiple blood transfusions.
The management of patients with ALI and ARDS is deﬁnitive treatment of the underlying disorder and supportive care during resolution of the lung injury. Despite the severity of the lung injury, most patients with ARDS do not die from respiratory failure but instead from the underlying illness or from complications of the complex supportive care. Ventilatory strategies for patients with ARDS now use low tidal volumes (6 mL/kg ideal body weight) so as not to damage the remaining aerated alveoli with excessive distending pressures or volumes. Noncardiogenic pulmonary edema can also be worsened by an increase in hydrostatic pressures from sepsis-associated cardiac dysfunction or overly aggressive volume resuscitation.
SPECIFIC CLINICAL CAUSES OF NONCARDIOGENIC PULMONARY EDEMA
High-altitude pulmonary edema usually occurs in individuals ascending to altitudes above 3000 m (9000 ft) above sea level even if they are athletically ﬁt. Current evidence suggests that some individuals have accentuated pulmonary vasoconstriction in response to hypoxemia, perhaps from impaired nitric oxide production or exaggerated sympathetic responses, causing high pulmonary artery pressures that tear or fracture the pulmonary capillaries. This can be fatal unless managed promptly with supplemental oxygen and prompt descent to lower altitudes.
Neurogenic pulmonary edema may occur within minutes to hours in patients with acute central nervous system injury, usually in the form of seizures, intra-cerebral or subarachnoid hemorrhage, or head trauma. The exact pathophysiology is unknown but may involve an abrupt increase in pulmonary venoconstriction from sympathetic stimulation with subsequent elevations in capillary hydrostatic pressures, pulmonary microvascular injury, or both. With supportive care and management of the underlying neurologic insult, the edema usually resolves within 48 to 72 hours.
Certain drug ingestions can cause pulmonary edema, including opiates (heroin and methadone), oral or intravenous-agonists used to manage preterm labor, and salicylates. Again, the exact mechanisms are not completely understood but may involve a combination of increased pulmonary capillary pressures and altered vascular permeability. The pulmonary edema from salicylate overdose can be exacerbated by standard overdose management with volume resuscitation and alkalinization with intravenous sodium bicarbonate.
PULMONARY EDEMA: SOME ETIOLOGIES AND HYPOTHESES OF MECHANISMS
EVALUATION OF PATIENTS WITH PULMONARY EDEMA
Patients with pulmonary edema present with the acute onset of dyspnea, tachypnea, and hypoxemia with radiographic studies showing bilateral alveolar inﬁltrates and increased interstitial markings. The history and clinical context often suggest the cause of the pulmonary edema. Symptoms consistent with an acute coronary syndrome strongly suggest cardiogenic edema, although pulmonary edema in the setting of pneumonia, an acute abdomen, or aspiration points toward ALI. Patients with seizures or intracerebral hemorrhage may have neurogenic pulmonary edema but could also have had gastric aspiration during periods of altered consciousness. Older cardiac patients often are at risk for sepsis syndromes. Thus, although the clinical history is essential, it is not always deﬁnitive as to whether the edema is cardiogenic, noncardiogenic, or a combination of both.
The physical examination may suggest cardiac disease, but ﬁndings of an S3 gallop or murmurs from valvular disorders may be difﬁcult to hear in the noisy emergency department or intensive care unit environment. Lung examination ﬁndings of inspiratory crackles are similar in both forms of pulmonary edema. Peripheral edema is not speciﬁc for cardiac disease. Ancillary studies are obviously important. The electro-cardiogram may show evidence of ischemia. Laboratory tests assess for evidence of infection, pancreatitis, or drug ingestions. Plasma levels of brain natriuretic peptide (BNP) are elevated when cardiac chambers are distended from congestive heart failure or volume overload. Low BNP levels (100 pg/mL) strongly support a noncardiogenic cause of pulmonary edema. High levels (500 pg/mL) suggest a cardiac cause, but intermediate levels are generally not helpful. Direct hemodynamic estimates of the left atrial pressures are possible with placement of a pulmonary artery catheter, but this is an invasive procedure with known complications. Use of these catheters has not been associated with improved patient outcomes.
Imaging of the chest with plain radiographs and computed tomography scans suggests cardiogenic edema if there are pleural effusions, an enlarged cardiac silhouette, widened central vascular structures, septal lines, and peribronchial cufﬁng. Absence of these features and patchy, peripheral inﬁltrates suggest noncardiogenic edema. Bedside transthoracic cardiac echocardiography can be a quick and noninvasive way to evaluate for impaired systolic function or valvular disease, but it is less sensitive for diastolic dysfunction.
The systematic approach to pulmonary edema uses history, physical exam, laboratory evaluation, and imaging. Echocardiography and, if needed, invasive hemodynamic monitoring are used in patients in whom the cause of the edema is still not certain.