Non-cardiogenic pulmonary edema (Proceedings)

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.