ADULT RESPIRATORY DISTRESS SYNDROME Dr. M. SOFI MD; FRCP (London); FRCPEdin; FRCSEdin

ARDS: Clinical features Acute respiratory distress syndrome (ARDS) is characterized by the development of acute dyspnea and hypoxemia within hours to days of an inciting event, such as trauma, sepsis, drug overdose, massive transfusion, acute pancreatitis, or aspiration. Clinical hallmarks of ARDS are hypoxemia and bilateral radiographic opacities. Pathological hallmark is diffuse alveolar damage (i.e., alveolar edema with or without focal hemorrhage, acute inflammation of the alveolar walls, and hyaline membranes). Most common risk factors: Sepsis Massive trauma with shock and multiple transfusions Hypovolaemic shock Pneumonia Gastric aspiration

ARDS: Common risk factors Smoke inhalation Burns Sepsis Near drowning Diabetic ketoacidosis Pregnancy Eclampsia Amniotic fluid embolus Drugs - paraquat, heroin, aspirin Massive transfusions Acute pancreatitis Disseminated intravascular coagulation (DIC) Head injury/raised intracranial pressure (ICP) Fat emboli Transfusions of blood products Heart/lung bypass Tumor lysis syndrome Pulmonary contusion

ARDS: Pathophysiology Three pathologic stages: The initial exudative stage, of diffuse alveolar damage. 7 – 10 days later proliferative stage develops - resolution of pulmonary edema, type II alveolar cell proliferation, squamous metaplasia, interstitial infiltration and early deposition of collagen. Some progress to a fibrotic stage - obliteration of normal lung architecture, diffuse fibrosis, and cyst formation.

ARDS: Pathophysiology Increased permeability of pulmonary microvasculature causes leakage proteinaceous fluid across the alveolar capillary membrane. This may be one manifestation of a more generalized disruption of endothelium, resulting in hypoxia and multiple organ failure. There is also evidence of inflammation in the lung tissue which can be seen on metabolic imaging methods interrupted by lung injury, causing excess fluid in both the interstitium and alveoli. Consequences include impaired gas exchange, decreased compliance, and increased pulmonary arterial pressure.

ARDS: Clinical presentation The clinical features of ARDS usually appear within 6 to 72 hours of an inciting event and worsen rapidly. Patients typically present with dyspnea, cyanosis (i.e., hypoxemia), and diffuse crackles. Respiratory distress is usually evident, including tachypnea, tachycardia, diaphoresis, and use of accessory muscles of respiration. A cough and chest pain may also exist. Arterial blood gases reveal hypoxemia, which is often accompanied by acute respiratory alkalosis and an elevated alveolar-arterial oxygen gradient. High concentrations of supplemental oxygen are generally required to maintain adequate oxygenation.

ARDS: Clinical presentation The initial chest radiograph typically has bilateral alveolar infiltrates, while computed tomography (CT) usually reveals widespread patchy or coalescent airspace opacities that are usually more apparent in the dependent lung zones The infiltrates do not have to be diffuse or severe, as bilateral infiltrates of any severity are sufficient 

Clinical findings related to the precipitant may also exist at presentation. As an example, in patients with ARDS due to sepsis, there may be fever, hypotension, leukocytosis, lactic acidosis, and disseminated intravascular coagulation (DIC). ARDS due to sepsis after pneumococcal pneumonia.

ARDS: Clinical course The first several days of ARDS are characterized by hypoxemia requiring a moderate to high concentration of inspired oxygen. The bilateral alveolar infiltrates and diffuse crackles are persistent during this period and patients may be tenuous due to severe hypoxemia. Most patients who survive this initial course begin to exhibit better oxygenation and decreasing alveolar infiltrates over the next several days. This may permit the amount of ventilatory support to be decreased and weaning to begin. Some will have severe hypoxemia and remain ventilator-dependent.

ARDS: Clinical course Pulmonary proliferative changes and fibrosis may progressively replace the pathological findings of diffuse alveolar damage as early as ten days after the onset of the respiratory failure. The fibroproliferative phase of ARDS radiographically shows progression from airspace opacification to a more coarsely reticular pattern of lung infiltration. These changes are accompanied by persistent hypoxemia, low lung compliance, high dead space, and sometimes by progressive pulmonary hypertension. The course may become dominated by persistent ventilator dependence and various complications.

ARDS: Diagnostic evaluation Eosinophilic pneumonia and diffuse alveolar hemorrhage associated with collagen vascular diseases are not. Cardiogenic pulmonary edema is the primary alternative that needs to be excluded because it is common and can be clinically indistinguishable from ARDS. The diagnostic evaluation is aimed at identifying specific causes of ARDS that are amenable to treatment and excluding other conditions that also present with acute hypoxemia, bilateral alveolar infiltrates, and respiratory distress. Viral or diffuse bacterial pneumonia and acute inhalational injuries are included.

ARDS: Diagnostic evaluation Excluding cardiogenic pulmonary edema:  An absence of cardiac exam abnormalities (e.g., an S3 or S4 gallop, new or changed murmur), elevated right-sided filling pressures (e.g., elevated jugular venous pressure), and certain radiographic abnormalities (e.g., pulmonary venous congestion, Kerley B lines, cardiomegaly, and pleural effusions), helps distinguish ARDS from cardiogenic pulmonary edema. Several additional diagnostic tests may also be helpful, including measurement of plasma brain natriuretic peptide levels, echocardiography, and right heart catheterization

ARDS: Diagnostic evaluation If such conditions cannot be identified on the basis of the clinical context additional diagnostic testing should be performed: Tracheobronchial aspiration : The lower respiratory tract can be sampled via tracheobronchial aspiration or mini-bronchoalveolar lavage (mini-BAL). Excluding other causes of hypoxemic respiratory failure: Potentially treatable causes of ARDS and alternative forms of acute hypoxemic respiratory failure with bilateral infiltrates should be considered once cardiogenic pulmonary edema has been excluded.

ARDS: Diagnostic evaluation If such conditions cannot be identified on the basis of the clinical context additional diagnostic testing should be performed: Tracheobronchial aspiration : The lower respiratory tract can be sampled via tracheobronchial aspiration or mini-bronchoalveolar lavage (mini-BAL). Excluding other causes of hypoxemic respiratory failure: Potentially treatable causes of ARDS and alternative forms of acute hypoxemic respiratory failure with bilateral infiltrates should be considered once cardiogenic pulmonary edema has been excluded.

ARDS: Differential diagnosis Cardiogenic pulmonary edema: Distinguishing cardiogenic pulmonary edema from ARDS can be aided by measurement of a brain natriuretic peptide, echocardiography, and, less often, right heart catheterization. Acute exacerbation of idiopathic pulmonary fibrosis or other chronic interstitial lung diseases can closely resemble ARDS in both clinical presentation and chest radiographic abnormalities Diffuse alveolar hemorrhage may be associated with a large, otherwise unexplained drop in the hemoglobin concentration and hematocrit. The recovery of hemosiderin-laden macrophages from bronchoalveolar lavage fluid is strongly suggestive of diffuse alveolar hemorrhage.

ARDS Differential diagnosis Aspiration Pneumonitis and Pneumonia Bacterial Pneumonia Bacterial Sepsis Goodpasture Syndrome Hemorrhagic Shock Hypersensitivity Pneumonitis Multiple Organ Dysfunction Syndrome in Sepsis Toxicity, Heroin Transfusion Reactions Tumor Lysis Syndrome Nosocomial and Healthcare-Associated Pneumonia Pneumocystis jiroveci Pneumonia Pulmonary Eosinophilia Respiratory Failure Septic Shock Toxic Shock Syndrome Ventilation, Mechanical Ventilation, Noninvasive Ventilator-Associated Pneumonia Viral Pneumonia

ARDS: Differential diagnosis Idiopathic acute eosinophilic pneumonia occurs in previously healthy individuals and is characterized by cough, fever, dyspnea, and sometimes chest pain. Bronchoalveolar lavage specimens always contain a large number of eosinophils, typically 35 to 55 percent of all recovered cells. Peripheral eosinophilia may or may not be present . Cryptogenic organizing pneumonia (COP) often mimics community-acquired pneumonia with an onset that is heralded by a flu-like illness with fever, malaise, fatigue, and cough. The diagnosis is made by ruling out infectious causes of pneumonia and documenting typical pathologic changes in tissue obtained by open lung biopsy

ARDS: Differential diagnosis Acute interstitial pneumonia (Hamman-Rich syndrome) is a rare and fulminant form of diffuse lung injury that has a presentation similar to ARDS. Many consider AIP a subset of idiopathic ARDS since its clinical manifestations are similar and both demonstrate diffuse alveolar damage on histopathology. The distinguishing characteristic is that ARDS is often associated with a known risk factor, whereas acute interstitial pneumonia is not

ARDS: Differential diagnosis Cancer can disseminate through the lungs so rapidly that the ensuing respiratory failure may be mistaken for ARDS. This is most often due to lymphoma or acute leukemia, but lymphangitic spread of solid tumors occasionally behaves this way. Cytological preparation of bronchoscopic specimens (eg, brushings, lavage) may reveal malignant cells.

ARDS: SUMMARY The diagnosis of acute respiratory distress syndrome (ARDS) requires that all of the following criteria be present : Respiratory symptoms must have begun within one week of a known clinical insult, or the patient must have new or worsening symptoms during the past week. Bilateral opacities consistent with pulmonary edema must be present on a chest radiograph or computed tomographic (CT) scan. These opacities must not be fully explained by pleural effusions, lobar collapse, lung collapse, or pulmonary nodules. The patient’s respiratory failure must not be fully explained by cardiac failure or fluid overload. An objective assessment (e.g., echocardiography) to exclude hydrostatic pulmonary edema is required if no risk factors for ARDS are present.

ARDS: SUMMARY ARDS is a diagnosis of exclusion. Therefore, the diagnostic evaluation is aimed at excluding other causes of acute hypoxemic respiratory failure with bilateral alveolar infiltrates. Cardiogenic pulmonary edema is the primary alternative that needs to be excluded. This may require diagnostic testing (e.g., brain natriuretic peptide [BNP] levels, echocardiography, and/or right heart catheterization). Alternative causes of acute hypoxemic respiratory failure with bilateral infiltrates should be considered once cardiogenic pulmonary edema has been excluded and, if such diseases cannot be excluded on the basis of the clinical context and accompanying symptoms and signs, additional diagnostic testing should be performed. This may include noninvasive respiratory sampling, flexible bronchoscopy, and/or lung biopsy.

ARDS: SUMMARY A variety of alternative conditions may present as acute hypoxemic respiratory failure with bilateral alveolar infiltrates and, therefore, should be considered whenever ARDS is suspected. They include: Cardiogenic pulmonary edema Diffuse alveolar hemorrhage Idiopathic acute exacerbation of pre-existing interstitial lung disease Acute eosinophilic pneumonia Cryptogenic organizing pneumonia Acute interstitial pneumonia Rapidly disseminating cancer