Acute pulmonary Part 3

Miscellaneous Causes of Pulmonary Edema

Neurologic insults

Pulmonary edema can occur as a result of various insults to the central nervous system, including grand mal seizures, head trauma, subarachnoid hemorrhage, intracerebral hemorrhage, and subdural hematoma. The common denominator for these CNS insults is that they are severe and occur acutely. Most often, pulmonary edema is acute, occurring minutes to hours after the CNS event. Occasionally, there may be a more delayed onset and gradual progression over several days. The patho-genesis of neurogenic pulmonary edema is not well understood. The acute form, which is more common, may result in large part from intense sympathetic activity associated with systemic hypertension and central pooling of blood volume. This combination of factors can lead to extraordinary, albeit transient, increases in pulmonary capillary pressure and a predominantly cardiogenic pattern of pulmonary edema. Increased permeability caused by pressure-induced mechanical injury to pulmonary capillaries or possibly by CNS control over pulmonary capillary permeability is also believed to play a role in neuro-genic pulmonary edema.40

Figure 3 In patients with ARDS, the number of failing organs and the patient’s age have a greater influence on mortality than does the number of days of failure.

Clinically, neurogenic pulmonary edema is usually diagnosed through its association with a rather dramatic preceding CNS insult. The major differential diagnosis is aspiration injury to the lungs. Unlike neurogenic pulmonary edema, chemical pneumonitis resulting from aspiration frequently persists for more than a few days and is often complicated by secondary bacterial infection. If the pulmonary process clears rapidly (i.e., over a few days), the likely diagnosis is neurogenic pulmonary edema. The management of neurogenic pulmonary edema is basically supportive. Diuretics should not be used in the absence of hypervolemia because of the risk of hypovolemic hypotension, which could aggravate the CNS injury in the setting of increased intracranial pressure.

Exposure to high altitude

High-altitude pulmonary edema (HAPE) has been reported to occur at heights of 2,500 to 5,000 m (8,202 to 16,404 ft), with an incidence of 0.5% to 15%; greater risk is associated with young age, male sex, more rapid ascent, heavy exertion, and cold envi-ronment.41 HAPE can also occur in persons residing at high altitude who return from a few days’ stay at a lower altitude. Persons with previous episodes of HAPE have a 60% chance of recurrence.

Symptoms are cough, which is sometimes productive of pink or bloody sputum, dyspnea on exertion, and fever; onset of symptoms is often gradual but typically occurs within 48 to 96 hours at high altitude.41 Fulminant pulmonary edema may be preceded by the less severe symptoms of acute mountain sickness. The edema may be diffuse, yet patchy, or quite asymmetrical.

The primary pathophysiologic abnormality underlying high-altitude pulmonary edema is increased capillary permeability, yet the mechanism of the increased permeability is uncertain. It has been suggested that pronounced hypoxia-induced pulmonary vasoconstriction may lead to overperfusion of the less obstructed portions of the vascular bed and subsequent en-dothelial injury that results in fluid leakage.41 Evidence for this mechanism comes in part from the observation that persons who have experienced HAPE have more exaggerated hypoxic pulmonary vasoconstriction than those who have not. Several mechanisms have been examined as contributing factors in this process. Exaggerated release of vasoconstrictors (e.g., endothe-lin-1) or impaired production of vasodilators (e.g., nitric oxide) may play a role.41,42 Edematogenic mediators released from endothelial or inflammatory cells may also be involved.41 In addition, impaired activity of alveolar NA+,K+-ATPase may contribute to slowed clearance of alveolar fluid.43

The risk of HAPE can be decreased by ascending slowly and steadily to high altitudes. In addition, nifedipine has been found to prevent HAPE in susceptible persons.32 Inhaled p-adrenergic agonists may also prevent HAPE.43 Descent to a lower altitude when symptoms of acute mountain sickness develop should also reduce the risk of pulmonary edema. Once full-blown pulmonary edema has occurred, administration of oxygen, continuous positive airway pressure, nifedipine, and prompt descent are useful treatments.41 Descending even only a few hundred meters may be beneficial. Inhalation of nitric oxide has been shown to improve arterial oxygenation and may be useful in patients who cannot be evacuated to a lower altitude.44 Persons who have experienced HAPE are at increased risk for its recurrence and should be advised to avoid high altitudes.

Reexpansion of collapsed lung

Rapid reexpansion of a collapsed lung may lead to ipsilateral or, occasionally, bilateral pulmonary edema.45 The risk of reex-pansion pulmonary edema after evacuation of a pneumothorax or pleural effusion is related to the amount of air or liquid in the pleural space, the duration of collapse, the rapidity of reexpan-sion, and the suctional pressures required to reexpand the lung. The development of highly negative pleural pressure during removal of pleural air or liquid, with resultant marked reduction in interstitial hydrostatic pressure, may be important in the pathogenesis of reexpansion pulmonary edema. The high protein concentration in the edema fluid suggests enhanced membrane permeability. This increased permeability could be caused in part by mechanical stretching and deformation of en-dothelial pores or by generation of toxic oxygen radicals during reperfusion of the rapidly expanded lung. Depletion of surfactant in the collapsed lung may play a role in the genesis of the reduction in interstitial hydrostatic pressure during reexpan-sion. The risk of reexpansion pulmonary edema is very low during evacuation of a pneumothorax that has been present for a day or less. For a pneumothorax that is thought to have been present for longer than a day, evacuation under water seal, rather than by application of negative pressure, may reduce the risk of edema. Evacuation of pleural liquid does not usually lead to pulmonary edema unless more than 1.0 to 1.5 L of liquid is removed rapidly. It has been suggested that any amount of pleural liquid can be removed safely as long as pleural pressure is maintained at a level higher than -20 cm H2O. It is not certain, however, whether this approach will always prevent reexpan-sion pulmonary edema; therefore, it is advisable to remove very large effusions gradually over several hours whenever possible. Treatment of reexpansion pulmonary edema is supportive. There is no evidence that treatment with diuretics is beneficial.

Upper airway obstruction

Pulmonary edema has been reported to occur after episodes of upper airway obstruction caused by postextubation laryn-gospasm, tumors, strangulation, or obstructive sleep apnea.46 The pathogenesis is thought to be related to the development of highly negative intrapleural pressure (-50 to -100 cm H2O) caused by vigorous inspiratory efforts against an obstructed airway (Muller maneuver). The highly negative intrapleural pressure decreases the interstitial hydrostatic pressure, increases venous return, and imposes an afterload on the left ventricle. In addition, such pressure may lead to intense sympathetic activation, systemic hypertension, and central pooling of blood volume. These factors together can lead to acute pulmonary edema by increasing the transcapillary pressure gradient (i.e., the difference between the capillary pressure and the interstitial hydrostatic pressure). The condition resolves rapidly after the obstruction is removed.

Drugs

Acute noncardiogenic pulmonary edema can occur after administration of a number of drugs [see Table 5]. Acute pulmonary edema can occur after intravenous injection of heroin or other narcotics.47 Because the edema fluid has a high protein concentration, it has been suggested that a permeability defect could be a pathogenetic factor, but this finding could result from a transient, extreme increase in capillary pressure produced by a so-called neurogenic mechanism. Onset usually occurs within a few hours after narcotic use, but occasionally, it may be delayed for as long as 24 hours. In addition to the clinical and radiographic features of pulmonary edema, typical signs of narcotic intoxication are present, such as pupillary constriction, decreased respiration, and altered mentation. Fever and leukocytosis do not necessarily indicate the presence of infection. As with neurogenic pulmonary edema, the primary differential diagnostic consideration is aspiration, because of the altered level of consciousness.

Management is supportive and should generally include intubation with mechanical ventilation, both to guarantee adequate ventilatory support and to provide airway protection against aspiration. The role of naloxone is uncertain. Certainly, a patient who has overdosed on narcotics and is experiencing life-threatening hypotension or bradycardia should be given nalox-one. Likewise, if naloxone is given to an unresponsive and hy-popneic patient who does not necessarily require mechanical ventilation for pulmonary edema, the patient may be spared intubation. In contrast, for a patient who is intubated on an emergency basis because of acute pulmonary edema and who becomes clinically stable without hemodynamic compromise, better management may be to allow the narcotic intoxication to reverse gradually rather than precipitously. There is no evidence that naloxone helps speed resolution of narcotic-induced pulmonary edema. In fact, naloxone has been reported to cause pulmonary edema.32 Furthermore, acute reversal of narcotic intoxication in a long-term addict could result in agitation, with marked sympathetic activation and a less stable clinical course.

Cocaine causes acute pulmonary edema, usually when used as free-base cocaine.48 The pathophysiology is uncertain. Like heroin, cocaine leads to a high-protein pulmonary edema that suggests endothelial cell injury and increased capillary permeability. However, as has been suggested with heroin, cocaine could lead to extreme sympathetic activation with a steep, extreme increase in capillary pressure that could produce a transient increase in protein leakage across the capillary membrane. Cocaine also causes coronary vasoconstriction, with acute my-ocardial ischemia or infarction, resulting in pulmonary edema.

Lung resection

Pulmonary edema can occur as a complication after lung resection, especially pneumonectomy. The clinical picture is consistent with acute lung injury or ARDS and occurs in approximately 6% of pneumonectomies, 3.7% of lobectomies, and 1% of minor resections. Mortality in these cases is 64.5%.49

The pathogenesis of post-lung-resection pulmonary edema is multifactorial. Perioperative fluid overload, impaired lymphatic drainage from lymph node dissection, damage from high concentrations of oxygen, and ischemia and reperfusion injury are probably involved.50

Management of post-lung-resection pulmonary edema includes mechanical ventilation, with particular attention paid to airway pressures, and fluid restriction.