• The exudative phase occurs within hours after the initial pulmonary insult and usually lasts 2-7 days. Clinical findings are correlated with microscopic findings of hyaline membranes, loss of the alveolar epithelium, edema, and hemorrhage at this early stage of ARDS (see Image 5).
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• The proliferative phase, which usually occurs 7-28 days after the initial pulmonary insult, is the next phase of ARDS. In this early proliferative phase, type 2 pneumocytic proliferation is present, along with widening of the septa and interstitial fibroblast proliferation (see Image 6).
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• The late proliferative, or fibrotic, phase of ARDS is the result of cellular proliferation that leads to the deposition of collagen and proteoglycans. Extensive fibroblast proliferation with incorporation of the hyaline membranes is a characteristic finding in this stage of ARDS (see Image 7).
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• Interstitial fibrosis develops in some patients. Pulmonary vascular abnormalities are common such as microvascular thrombi and vascular remodeling.

Frequency:

• In the US: The annual incidence is reported to be 150,000 cases; however, this number is suspect because of differing definitions for ARDS. The National Institutes of Health (NIH) Acute Respiratory Distress Syndrome Network over the past 3 years has enrolled many ARDS patients into their clinical trials. Their estimate agrees with an earlier estimate by the NIH of 75 cases per 100,000 population per year.

• Internationally: The incidence is about 18 cases per 100,000 population per year for acute lung injury and 13 cases per 100,000 population per year for ARDS. These estimates are from the Acute Respiratory Failure (ARF) Study Group in Sweden, Denmark, and Iceland.

Mortality/Morbidity: Mortality in ARDS commonly is secondary to multiorgan dysfunction. Less alveolar epithelial damage indicates a better likelihood of recovering pulmonary function.

DIFFERENTIALS

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Aspiration Pneumonia
Congestive Heart Failure
Pneumonia, Atypical Bacterial
Pneumonia, Pneumocystis Carinii
Pneumonia, Typical Bacterial
Pneumonia, Viral

Other Problems to be Considered:

Diffuse pneumonia of any origin (though pneumonia can be a cause of ARDS)
Cardiogenic edema
Massive aspiration (though aspiration can be a cause of ARDS)
Pulmonary hemorrhage

Congestive heart failure (CHF) can mimic ARDS. A Swan-Ganz catheter is used to measure the left ventricular end-diastolic pressure to rule out CHF. For ARDS, the pulmonary artery wedge pressure (pulmonary artery occlusion pressure), as measured with a Swan-Ganz catheter, should be 18 mm Hg or less according to the AECC definition.

Some investigators believe that distinguishing CHF from ARDS may be difficult and arbitrary at times, and they propose a classification for permeability edema. The 4 categories are as follows: (1) hydrostatic edema, (2) permeability edema due to diffuse alveolar damage or ARDS, (3) permeability edema without diffuse alveolar damage, or (4) mixed (hydrostatic and permeability edema).

X-RAY

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Findings: CXR findings of ARDS vary widely depending on stage of disease. The most common CXR findings are bilateral predominantly peripheral, somewhat asymmetrical consolidation with air-bronchograms. Septal lines and pleural effusions are uncommon (see Images 1-4). Differential considerations include pneumonias including due to aspiration, diffuse alveolar hemorrhage, and pulmonary edema of any cause.

Early findings on the CXR include normal or diffuse alveolar opacities (consolidation), which are often bilateral and which obscure the vascular markings. Later, these progress to more extensive consolidation that is diffuse, and they are often asymmetric. Effusions and septal lines are not usually seen on CXRs, although they are commonly seen in CHF. Radiographic findings tend to stabilize (part of the clinical definition of ARDS), and if further worsening occurs after 5-7 days, another process should be considered.

CXR correlation with the pulmonary pathologic findings is useful, because, at the beginning of the fibrotic process in ARDS, steroids may be helpful. In the early exudative phase, CXRs show 3 general findings: a bilateral, whiteout appearance; asymmetric consolidations; and a central bat-wing consolidative appearance. In the fibrotic phase, CXRs may have an interstitial appearance, which is not necessarily due to fibrosis, because this finding may completely resolve in many who survive. Pathologic specimens have been analyzed, and the findings of severe lung fibrosis do not correlate with any specific portable CXR findings, including reticular patterns. CT scans provide more detailed and more reliable information in areas of consolidation and fibrosis.

If the patient survives, most radiographic abnormalities improve after 10-14 days. The speed and degree of this improvement varies widely from complete resolution before the patient's discharge from the intensive care unit (ICU) to gradual improvement over several months (see Image 1). Factors affecting the speed of recovery are not known but may be related to other medical factors (eg, patient’s age, underlying disease states) that may have caused the onset of ARDS in the first place.

Therapy for ARDS can affect the CXR appearance. To improve oxygenation, the clinician may place the patient in the prone position. However, large clinical trials have failed to prove any mortality benefit with prone positioning.

Partial liquid ventilation with perflubron has been used to treat ARDS. Perflubron carries gases such as oxygen, and it appears to improve gas exchange and promote lung recruitment. Pulmonary compliance may improve, alveolar hemorrhage may decrease, and pulmonary edema may be reduced, but some investigators question the possible effects, such as increased oxidative damage. This strategy is currently under investigation in several clinical trials, and results are pending. The initial CXR shows opacification in 60-100% of the lung fields, and the lateral image reveals a gravity dependent distribution (see Image 9). Findings of residual perflubron can linger for as long as 138 days, but its levels usually are minimal after 3 weeks.

Mechanical ventilation with positive end-expiratory pressure (PEEP) is another common therapy in ARDS. CXR findings when PEEP is applied vary from no change to apparent hyperinflation. Higher levels of PEEP may result in barotraumatic changes, which include vesicular rarefactions, pulmonary interstitial emphysema (lucent streaks toward the hilus), radiolucent halos around vessels, pneumatocele formation, subpleural emphysema manifested by blebs or lucent lines on the CXR, pneumothorax, mediastinal emphysema, and extrathoracic gas collection. When PEEP is initially applied or increased, lung opacities may appear to improve; or, if PEEP is reduced, the opacities may appear to worsen, although the clinical signs are stable or contrary to improvement or worsening of these opacities.

Many other methods of mechanical ventilation have been used to treat ARDS. Recently the ARDS-NET group has completed a trial showing a mortality benefit of using lower tidal volumes in ARDS. At least initially, physicians should be using tidal volumes of 6 mL/kg of ideal body weight rather than the larger tidal volumes used in the past. Sometimes this approach requires allowing the arterial carbon dioxide levels to increase because of hypoventilation. This is commonly called permissive hypercapnia.

The AECC definition is usually used in investigations of ARDS. Several entities can mimic ARDS, and attempts to exclude these diseases are important. Lung injury scores are sometimes used in clinical trials, and the CXR interpretation can be weighted 50% or more in these scores. For this reason, some investigators have questioned the reproducibility of CXR readings between physicians. High interobserver variability in CXR interpretations occurs, even between experts. On the other hand, the CXRs are very accurate in the diagnosis of ARDS, with rates as high as 84%. The accuracy of the CXR reading is stage dependent, and observer disagreement is highest in early disease. Accuracy is also dependent on the pathologic stage.