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

3. 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: Clinical features

4.  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: Common risk factors

5. 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

6. 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 (eg, echocardiography) to exclude hydrostatic pulmonary edema is required if no risk factors for ARDS are present. The diagnosis of ARDS requires that all of the following criteria be present

7. Hypoxemia must be present on minimal ventilator settings, as defined by the ratio of arterial oxygen tension to fraction of inspired oxygen (PaO 2 /FiO 2 ). The severity of the hypoxemia defines the severity of the ARDS. Mild ARDS exists when the PaO 2 /FiO 2 is >200 mmHg, but ≤300 mmHg, on invasive or non-invasive ventilator settings that include a positive end-expiratory pressure (PEEP) or continuous positive airway pressure (CPAP) ≥5 cm H 2 O. Moderate ARDS exists when the PaO 2 /FiO 2 is >100 mmHg, but ≤200 mmHg, on ventilator settings that include a PEEP ≥5 cm H 2 O. Severe ARDS exists when the PaO 2 /FiO 2 is ≤100 mmHg on ventilator settings that include a PEEP ≥5 cm H 2 O. The diagnosis of ARDS requires that all of the following criteria be present

9. 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: Pathophysiology

10.  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

11.  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 ARDS: Clinical presentation Portable chest radiograph in a patient with ARDS. The condition evolved over approximately 1 week.

12. 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). HRCTscan in a patient with ARDS. This image demonstrates a small right pleural effusion, consolidation with air-bronchograms, and some ground- glass-appearing opacities. The findings indicate an alveolar process, in this case, alveolar damage.

13.  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

14.  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: Clinical course

15.  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.  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. ARDS: Diagnostic evaluation

16. 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

17. 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.  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). ARDS: Diagnostic evaluation

18. Flexible bronchoscopy:  Flexible bronchoscopy can obtain lower respiratory samples for microscopic analysis and culture if the noninvasive techniques are unsuccessful.  Identify abnormalities that may not be detected with noninvasive  A reasonable next step if noninvasive sampling is non-diagnostic. Lung biopsy: Surgical lung biopsy may be considered when alternative causes of acute hypoxemic respiratory failure cannot be excluded on the basis of the clinical context, symptoms, signs, and bronchoscopy ARDS: Diagnostic evaluation

19. 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 ARDS: Differential diagnosis

20. 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

21.  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

22.  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

23.  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: Differential diagnosis