Patients with respiratory distress are often frail and excessive stress may progress to respiratory arrest. Non-invasive techniques
are essential to avoid exacerbation of tenuous circumstances. One must rely upon abridged and fragmented physical examinations
in the most serious cases, accurate historical information, and noninvasive diagnostics. Emergency interventions may be required
such as oxygen supplementation, obtaining thoracic radiographs, medication administration, thoracocentesis, thoracostomy tube
placement, tracheostomy, or even intubation. As the clinician is working to stabilize the animal, reasonable differential
diagnoses are pursued.
Non-cardiogenic pulmonary edema (NCPE) is a differential that can be overlooked due to the infrequency it is diagnosed. It
may also be known as neurogenic pulmonary edema. The pathophysiology of the syndrome is not well understood. Multiple disease
processes can lead to a similar pulmonary response. Head trauma, electrocution, upper airway obstruction, and seizures are
the more common underlying conditions in veterinary medicine. Others reported in human medicine include subarachnoid hemorrhage,
intracerbral hemorrhage, cerebral vascular events, post operative intracranial surgery, and meningitis. Pulmonary edema in
patients suffering from NCPE may be of low or high protein content. Two different mechanisms (hemodynamic and inflammatory)
seem to exist either independent or simultaneously within any given patient; they are triggered by sudden increase in intracranial
pressure (ICP) with subsequent decrease in brain perfusion, or a localized ischemic insult to the vasomotor center.
1. Hemodynamic mechanisms induce intense pulmonary vasoconstriction which is the effect of an adrenergic response to the insult.
There is a dramatic increase in pulmonary hydrostatic pressures followed by an increase in pulmonary capillary permeability.
In the 'blast injury' theory an increased ICP induces a sudden and dramatic α-adrenergic response. There is a dramatic increase
in both pulmonary and systemic vasoconstriction. This leads to alterations of the Starling forces and shift of fluid into
the pulmonary interstitium and alveoli. Mechanical lesions can result as elevated hydrostatic edema may cause injury to the
pulmonary capillary endothelium, basement membrane, and finally the alveolar epithelium resulting in leakage of plasma proteins
and red blood cells. There may also be simultaneous cardiac insult with increased cardiac work load. A poorly functional myocardial
reserve increases the risk of pulmonary edema.
2. Inflammatory mechanism also induces an increase in pulmonary capillary permeability. A major cerebral insult causes local
inflammatory reaction with the cytokines tumor necrosis factor-α (TNFα), interlukin-1 β (IL-1 β), and IL-6 being produced
in the injured brain. They gain access to the systemic circulation and cause stimulation of target cells in the periphery.
Experimental work has also identified substance P and neurokinin A from the frontal cortex that may cause bronchoconstriction
and bronchial edema as well as increased pulmonary capillary permeability, pulmonary edema, and leukocyte activation. The
sympathetic storm resulting from a cerebral insult may initiate the stimulation of cytokines expression and an inflammatory
process in the lungs caused by the severe change in pressure. The resulting elevated levels of IL-1 β and IL-6 tend to affect
all peripheral organs, while TNF-α seems to affect predominantly the lung.
The diagnosis of NCPE is non-specific. Variable levels of tachypnea and respiratory distress will be apparent dependent upon
the extent & severity of pulmonary injury. Increased brochovesicular sounds and/or crackles may be present predominantly in
the caudodorsal lung fields which are most often affected. Tachycardia is often present due to hypoxemia. Careful examination
may reveal burns supporting electrical shock. Obvious signs of head trauma may not be evident; diligent examination of boney
protuberances and finding abrasions may raise the level of concern for head trauma. Careful questioning might reveal history
of choke. Animals that had not been well supervised just prior to illness seizure activity should be considered as the seizure(s)
may have gone unwitnessed and the patient completely recovered. Thoracic radiographs may reveal a classical caudodorsal alveolar
pulmonary pattern without findings of significant cardiac disease such as cardiomegaly or pulmonary vessel enlargement. Variable
patterns have been reported and the pattern may be diffuse, asymmetrical, or involve only one quadrant. Careful consideration
of the diagnosis of NCPE is challenging in these instances. Assessment of oxygenation with arterial blood gas and/or pulse
oximetry is useful to determine level of hypoxemia, and also response to therapy and a trend over time. Clinicopathologic
findings are non-specific and may be related to the underlying etiology; however hyperglycemia has been reported in nearly
half of veterinary patients with NCPE.
Treatment of NCPE is directed at the underlying etiologic process. Patients with airway obstruction should be intubated and
the underlying disease process treated. Supplemental oxygen is provided in a non-stressful manner and nasal oxygen is avoided
patients with seizures or head trauma as nasal cannula often induces sneezing which increases intracranial pressure. Fluid
therapy is carefully titrated to target euvolemia and avoid fluid overload. Hypertonic saline is very useful fluid for resuscitating
patients with head trauma. The use of synthetic colloids is controversial in pulmonary disease including NCPE. Concerns with
colloids are they may help maintain vascular volume, or they may leak into the pulmonary parenchyma and exacerbate pulmonary
edema. Seizures should be treated aggressively with anticonvulsants. The use of diuretics is controversial. The author rarely
uses diuretics due to the theory that pulmonary edema in cases of NCPE resulted from a vasoconstrictive process with elevated
pulmonary hydrostatic pressure that was transient and typically resolved by time of presentation; further diuretics will contribute
to hypovolemia. Bronchodilators may be beneficial in cases of refractory hypoxemia; methylxanthines have the added benefit
of supporting diaphragmatic contractility. Corticosteroids and antimicrobials are not indicated in cases of NCPE.
The prognosis for patients suffering from NCPE will hinge upon the underlying diagnosis. With control of the underlying disease
process, pulmonary clearance of NCPE is typically prompt with significantly improved oxygenation and radiographs within 24-48
hours. With early recognition and diagnosis, appropriate therapy, and committed clients, cases of NCPE are often rewarding.
References available upon request.