Neurogenic pulmonary edema (NPE) is a relatively rare form of pulmonary edema caused by an increase in pulmonary interstitial and alveolar fluid. Neurogenic pulmonary edema develops within a few hours after a neurologic insult, and diagnosis requires exclusion of other causes of pulmonary edema (eg, high-altitude pulmonary edema).
The pathogenesis of neurogenic pulmonary edema (NPE) is not completely understood.[1] Because the most common neurological events are associated with increased intracranial pressure, intracranial hypertension is considered a key etiologic factor.
Within the central nervous system, the sites responsible for the development of neurogenic pulmonary edema are not fully elucidated. Animal studies suggest that hypothalamic lesions, stimulation of the vasomotor centers of the medulla, elevated intracranial pressure, and activation of the sympathetic system have potential roles.[2, 3] Cervical spinal cord nuclei also may have a role. Both hypothalamic lesions (paraventricular and dorsomedial nuclei) and stimulation of the vasomotor centers of the medulla (A1 and A5, nuclei of solitary tract, and area postrema, medial reticulated nucleus, and the dorsal motor vagus nucleus in the medulla oblongata) can increase output along the sympathetic trunk. Neurogenic pulmonary edema trigger zones may exist in these structures, with specific neurologic foci or centers producing massive sympathetic discharges that lead to neurogenic pulmonary edema.[4]
The medulla is believed to activate sympathetic components of the autonomic nervous system. Experimentally, bilateral lesions of the nuclei in the medulla produce profound pulmonary and systemic hypertension and pulmonary edema. Alpha-adrenergic blockade (with phentolamine) and spinal cord transection at the C7 level prevent the formation of neurogenic pulmonary edema, suggesting an important role for sympathetic activation.
An acute neurological crisis, accompanied by a marked increase in intracranial pressure, may stimulate the hypothalamus and the vasomotor centers of the medulla. This, in turn, initiates a massive autonomic discharge mediated by preganglionic centers within the cervical spine.
A central nervous system event produces a dramatic change in Starling forces, which govern the movement of fluid between capillaries and the interstitium. Both hemodynamic (cardiogenic) and nonhemodynamic (noncardiogenic) components contribute to edema formation. Factors leading to the development of edema in patients with subarachnoid hemorrhage are illustrated in the flowchart below; however, these can be extrapolated to other types of central nervous system insults.
View Image | Factors leading to the development of neurogenic pulmonary edema in patients with subarachnoid hemorrhage. |
Alterations in pulmonary vascular pressures appear to be the most likely Starling force to influence the formation of neurogenic pulmonary edema. Experimental observations suggest the following mechanisms by which pulmonary capillary hydrostatic pressures can be increased acutely:
An increase in capillary permeability can result in neurogenic pulmonary edema without elevation of pulmonary capillary hydrostatic pressure, because causative hemodynamic alteration is inconsistent. However, evidence shows that alpha-adrenergic blockade can protect against neurogenic pulmonary edema. Epinephrine, norepinephrine, and even a release of secondary mediators may directly increase pulmonary vascular permeability. Whether the capillary leak is produced by pressure-induced mechanical injury because of the elevated capillary hydrostatic pressure or because of some direct nervous system control over the pulmonary capillary permeability remains uncertain.
An initial and rapid rise in pulmonary vascular pressure due to pulmonary vasoconstriction or pulmonary blood flow can lead to pulmonary microvascular injury. Consequently, an increase in vascular permeability results in edema formation, as suggested by the frequent observation of pulmonary hemorrhage in neurogenic pulmonary edema (ie, blast theory).[5, 6, 7]
United States
Importantly, recognize that neurogenic pulmonary edema is an underdiagnosed condition. Patients with neurologic events often have multiple other comorbidities, which may obscure or mimic the diagnosis of neurogenic pulmonary edema. The lack of a standardized definition for neurogenic pulmonary edema also makes defining its epidemiology difficult.
As many as one third of patients with status epilepticus may have evidence of neurogenic pulmonary edema.[8] More than half the patients with severe, blunt, or penetrating head injury have associated neurogenic pulmonary edema. Approximately 71% of fatal cases of subarachnoid hemorrhage are complicated by neurogenic pulmonary edema. Neurogenic pulmonary edema may complicate subarachnoid and intercerebral hemorrhage in 30-70% of patients and may recur after initial resolution.[9, 10]
A series of 457 patients with subarachnoid hemorrhage reported a 6% prevalence of severe neurogenic pulmonary edema.[11] Solenski et al reported in 1995 that increased age and a worse clinical grade of subarachnoid hemorrhage were associated with neurogenic pulmonary edema.
International
No data suggest differences in the international incidence of neurogenic pulmonary edema compared with the experience in the United States. However, note that epidemiologic data on this entity in general are very sparse because of the difficulties in recognition and diagnosis and lack of a standardized definition.
Data regarding morbidity and mortality following neurogenic pulmonary edema (NPE) have not been well documented, given the relatively low prevalence and likely underdiagnosis. Overall, patient outcome is usually determined by the underlying neurological insult that led to neurogenic pulmonary edema. Morbidity related to neurogenic pulmonary edema is reported to be in the range of 40-50%, and reported mortality from neurogenic pulmonary edema is low, at approximately 7%.
No ethnic predisposition has been noted for neurogenic pulmonary edema.
The individual’s sex is not associated with the development of neurogenic pulmonary edema.
Age is not a specific risk factor for neurogenic pulmonary edema, other than the increased risk for neurologic events and cardiovascular abnormalities associated with increasing age.
Neurogenic pulmonary edema (NPE) characteristically presents within minutes to hours of a severe central nervous system insult.
Sudden onset of dyspnea is the most common symptom; mild hemoptysis also may occur.
Physical findings include the following:
Major causes
Minor causes
No specific laboratory study confirms the diagnosis of neurogenic pulmonary edema (NPE). Cardiac injury enzyme levels are elevated in patients with neurologic injury, especially subarachnoid hemorrhage. The magnitude of elevation often correlates with the severity of the neurologic event and its effect on cardiac function.
Chest radiographs demonstrate a bilateral alveolar filling process and a normal-sized heart. This may mimic congestive heart failure with cephalization of blood flow, although other features of heart failure, such as septal Kerley B lines, are usually not evident. See the images below.
View Image | Neurogenic pulmonary edema in a patient with a subdural hematoma. |
View Image | Progression of neurogenic pulmonary edema in the same patient in the image above, with subdural hematoma (day 2). |
No specific test confirms the diagnosis of neurogenic pulmonary edema.
Hemodynamic measurements with right-sided heart catheterization (ie, Swan-Ganz catheter) may be necessary to differentiate neurogenic pulmonary edema from hydrostatic or cardiogenic pulmonary edema. Systemic blood pressure, cardiac output, and pulmonary capillary wedge pressure are usually normal by the time neurogenic pulmonary edema is diagnosed clinically.
No specific histologic findings confirm the diagnosis of neurogenic pulmonary edema.
Neurologic disorder and neurogenic pulmonary edema (NPE)
General supportive care for neurogenic pulmonary edema
Pharmacological therapy for neurogenic pulmonary edema: Pharmacological agents are not used routinely in the treatment of neurogenic pulmonary edema. Several agents, such as alpha-adrenergic antagonists, beta-adrenergic blockers, dobutamine, and chlorpromazine, are advocated by some authors, but assessment of their effectiveness is difficult because neurogenic pulmonary edema is usually a self-limited condition that resolves spontaneously.
Surgical management is directed at the neurologic insult (eg, intracerebral hemorrhage, subdural hematoma) because neurogenic pulmonary edema has no direct surgical treatment.
Consultations may include the following:
No specific dietary recommendations are needed for patients with neurogenic pulmonary edema.
Patients with neurogenic pulmonary edema usually have limited mobility as a result of their neurologic condition. No specific restrictions on activity are needed, except those required for treatment of the neurologic condition, especially patients undergoing neurologic surgery. Early ambulation and rehabilitation are crucial for recovery.
No targeted or specific medications treat neurogenic pulmonary edema (NPE), other than those that have been discussed in Medical Care. These include alpha-adrenergic antagonists (eg, phentolamine) and Beta-adrenergic agonists (eg, dobutamine, dopamine, norepinephrine).
No specific recommendations for outpatient follow up are needed for persons who have been treated for neurogenic pulmonary edema. Patients who recover should probably follow up with a physician in an outpatient setting as clinically indicated; however, no specific guidelines are available regarding the appropriate time interval following discharge from the hospital. In general, patients with neurogenic pulmonary edema do not present as outpatients and should not be treated in an outpatient setting.
Neurological insults severe enough to cause neurogenic pulmonary edema (NPE) always warrant admission to hospital. Most patients require close cardiac monitoring, requiring initial admission to a monitored bed. A telemetry unit or step-down unit bed may suffice for less severe cases. Intensive care admission may be required if patients develop increasingly severe hypoxemia or respiratory distress, or if invasive monitoring is required.
No specific recommendations for outpatient medications are needed for neurogenic pulmonary edema. See Medical Care.
Patients with neurogenic pulmonary edema generally have multiple comorbidities that dictate the setting in which they are receiving care. Transfer between levels of acute care (ie, ICU to transitional care units, and subsequently to general medical/surgical ward) is influenced by a variety of factors. The most important of these is likely the underlying neurological insult that led to the development of pulmonary edema. Once this is managed and stabilized, further transitions between level of care are dictated by clinical circumstances. These include an ongoing need for mechanical ventilation, hemodynamic parameters, and the need for regular neurologic monitoring.
Prevention is primarily aimed at interventions that help avoid or relieve the neurological insults that subsequently lead to pulmonary edema. Current understanding is limited as to which patients are likely to develop pulmonary edema as a result of neurological injury. Given this lack of understanding, predicting who will develop pulmonary edema and determining what measures can then be undertaken to prevent its occurrence are difficult.
Complications include but are not limited to the following:
Neurogenic pulmonary edema usually is generally well tolerated by the patient, although some patients require ventilatory support. The neurogenic pulmonary edema usually resolves within 48-72 hours. Prognosis is determined more by the course of the underlying neurological problem than by the neurogenic pulmonary edema, unless significant respiratory complications develop.
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