Neurogenic pulmonary edema (NPE) is a clinical condition that arises as acute respiratory distress taking place in conjunction with severe neurological damage/injury. By definition, this condition incorporates a clinical picture of a large accumulation of extra-vascular pulmonary fluid, of acute onset, always in the immediate outcome of serious central nervous system (CNS) lesions, mostly the brainstem. Shanahan first described acute neurogenic pulmonary edema in 1908.
This diagnosis necessitates the exclusion of other identifiable origins of pulmonary lesions or cardiovascular function that may accompany nervous system distress, for instance, broncho-pulmonary aspiration or ischemic, toxic or traumatic lesions of the heart and lungs.
If the standard clinical presentation is explicit, the diagnosis should be assumed when acute pulmonary edema is associated with CNS injury in the absence of primary pulmonary or cardiovascular injury; however, some ambiguity continues, particularly since the literature does not present a full comprehension of exact pathogenesis.
Any sort of acute CNS injury may trigger neurogenic pulmonary edema; however, the 3 most common triggers of this syndrome are cranial trauma (open or closed), subarachnoid hemorrhage (counting rupture of an aneurysm where it is found in more than 50% of cases), and epilepsy (generalized seizure). Neurogenic pulmonary edema has also been reported in some other pathological situations such as cervical medullary trauma, a postoperative period of intracranial surgery, and meningitis.
The occurrence of neurogenic pulmonary edema in a brain-injured patient is associated with a poor prognosis as the mortality rate is very high (60% to 100%). It is not only attributed to pulmonary involvement but also to primary brain injury.
There has been no confirmed incidence of neurogenic pulmonary edema. However, through pathological data, experts have projected that the condition is usually found in the autopsy of patients who die immediately after a seizure episode and also from those who are victims of severe head injuries. The cases of neurogenic pulmonary edema are generally rare. Only 20% of victims with serious head injury suffers from the condition.
The full understanding of the pathophysiology of neurogenic pulmonary edema is still, to an extent, a baffling puzzle. It is important to understand the essence of the theory of an association between a CNS disturbance and developing pulmonary edema.
The CNS disturbance will cause a sympathetic overflow leading to a state of systemic vasoconstriction. This will cause pooling of the blood from the systemic circulation to the pulmonary circulation, hence eliciting an increase in the pulmonary capillary hydrostatic pressure. That change of pressure will mediate the leakage of intravascular fluid to both the alveoli and the pulmonary interstitial space through 2 mechanisms: (1) change of pressure across the alveolar bed dictated by Starling forces, (2) the changes in permeability on the capillary walls.
For a more comprehensive understanding of the pathophysiology of the neurogenic pulmonary edema, it is important to understand 3 different sectors. However, it is worthy to note that this clinical condition results from the overlapping of these sectors through cause and effect. See Table 1.
Central Nervous System
Autonomic Nervous System
Cardiovascular and Pulmonary Systems
Sympathetic overflow and catecholamines-surge result in an increase of systemic resistance, venous return, and BP. Knowing this, the proposed theory of the development of neurogenic pulmonary edema falls into one of three supposed explanation:
Rapid developments characterize the early stages of neurogenic pulmonary edema. The common patients are usually children or young adults, who must have suffered an intracranial injury recently. In cases of blunt head injuries, neurogenic pulmonary edema may develop in a matter of minutes. There is no specific symptomatology of neurogenic pulmonary edema. It is most often concomitant of the trigger phase of the neurological pathology. The clinical signs boil down to classic signs of pulmonary edema with the absence of signs of left ventricular failure usually found in cardiogenic edema. For classic neurogenic pulmonary edema, the manifestation is immediate, and it could be detected clinically within 2 to 12 hours post-injury.
The symptomatology is that of any pulmonary edema with initially ventilation disorders often accompanied by systolic hypertension probably also testifying to intracranial hypertension. In patients with spontaneous ventilation, dyspnea, tachypnea, cough and rales with auscultation and tachycardia would be early signs, sometimes accompanied by pink foamy sputum or hemoptysis. More discrete symptoms of sympathetic stimulation, such as insomnia, sweating, paralytic ileus, and transient hypertension are also described. Ventilation/perfusion disorders, hypoxemia, and carbon dioxide retention will occur shortly after that.
The natural evolution leads to respiratory failure followed by cardiovascular collapse and has a high mortality, estimated at more than 60%. It is impossible to assess whether the direct cause of this mortality is pulmonary or neurological or even cardiovascular. In contrast to older descriptions, more recent publications seem to attribute mortality rather to brain causes. However, in pediatric encephalomyelitis cases, the cause of death would be mainly pulmonary and cardiovascular.
Neurogenic pulmonary edema diagnosis is clinical, based on the presence of pulmonary manifestations in the fact of CNS injury. The diagnostics aim toward exclusion of differentials:
A chest x-ray is important to differentiate between this condition and aspiration pneumonitis. With aspiration pneumonitis, the radiographic features take up to a few hours to evolve, and up to 3 weeks to resolve. This is in contrast to the alveolar infiltrates in neurogenic pulmonary edema, which occurs instantly after the injury. Rule out other pulmonary causes (e.g., lung contusion, hemothorax, pneumothorax, among others).
Electrocardiography and Echocardiography
These point out the functional and structural abnormalities of the heart if any.
The evolution of this syndrome is often favorable after 48 to 72 hours under treatment, and the prognosis is then more related to the underlying neurological pathology. However, these cases where the functional or vital prognoses are committed to justifying systematic vigilance to ensure early diagnosis and appropriate treatment.
In all cases, these are very serious situations with high mortality requiring intensive care. The suspicion of neurogenic pulmonary edema initially requires symptomatic treatment, often artificial ventilation and intensive care monitoring. It is wise to consider the benefits of continuous measurement of ICP and possibly capillary pulmonary pressure.
Management should aim for a causal treatment, often difficult in severe head trauma. The main effort during diffuse injury to the CNS will, therefore, be to reduce ICP. Then, based on the current physiopathological hypotheses, the therapy will be mainly cardiovascular and will aim at the increase of the inotropic especially by beta-adrenergic stimulation, the reduction of the pulmonary vascular resistance is essential. Nitric oxide (NO) for this purpose is only experimental but may be useful.
In the later stages of neurogenic pulmonary edema, the cardiovascular and ventilation strategies used in acute respiratory distress syndrome (ARDS) will be required. The administration of steroids remains controversial.
The diagnosis of neurogenic pulmonary edema is not easy, as it can mimic many other lung pathologies. Without a specific marker, good clinical acumen is necessary to make the diagnosis. Thus, the condition is best managed by an interprofessional team that includes an internist, cardiologist, intensivist, pulmonologist, and a nephrologist. Simply giving diuretics is not always the answer as some patients may be hypovolemic. The overall prognosis depends on the cause, comorbidity, patient age and the need for inotropic support. One always has to rule of aspiration pneumonia, pulmonary embolism, and primary cardiac dysfunction as a cause of the pulmonary edema. Because these patients are bedridden, deep vein thrombosis and pressure sore prophylaxis is also necessary. A team approach is an ideal method of managing neurogenic pulmonary edema to improve outcomes. [Level 5]
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