1. Adult Respiratory Distress Syndrome
Prof.Dr Yaşar Küçükardalı
İç Hastalıkları ve Yoğun Bakım Uzmanı

4. The age-adjusted incidence was 86 per 100,000 person-years for individuals with an arterial oxygen tension to fraction of inspired oxygen (PaO2/FiO2) ratio ≤300 mmHg and 64 per 100,000 person-years for individuals with a PaO2/FiO2 ≤200 mmHg.
●The incidence increased with patient age from 16 per 100,000 person-years among individuals 15 to 19 years of age to 306 per 100,000 person-years among individuals 75 to 84 years of age.

5. definition
ARDS is an acute, diffuse, inflammatory lung injury that leads to
increased pulmonary vascular permeability,
increased lung weight,
a loss of aerated tissue

6. Clinical hallmarks of ARDS are hypoxemia and bilateral radiographic opacities,
Pathological hallmark is diffuse alveolar damage
alveolar edema with or without focal hemorrhage
acute inflammation of the alveolar walls
hyaline membranes

7. Clinical presentation
 The clinical features of ARDS usually appear within 6 to 72 hours of an inciting event and worsen rapidly

8. Patients typically present with dyspnea, cyanosis (ie, 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.

9. 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.

10. A conservative estimate of normal A–a gradient is less than [age in years/4] + 4

15. 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,
disseminated intravascular coagulation (DIC).

22. Long Term
Chronic Respiratory Disease
Muscle Fatigue
Muscle Wasting
Weakness

23. 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.
Some patients, however, have persistent, severe hypoxemia and remain ventilator-dependent. 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 is characterized radiographically by progression from airspace opacification to a more coarsely reticular pattern of lung infiltration. These changes within the lung parenchyma are often 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.

24. Complications Patients with ARDS are at high risk for complications.
Some complications are related to mechanical ventilation
pulmonary barotrauma,
nosocomial pneumonia,
while others are related to critical illness and being in the intensive care unit
delirium,
deep venous thrombosis,
gastrointestinal bleeding due to stress ulceration,
catheter-related infections.

25. Other complications
 Other complications that frequently occur during the hospital course of patients with ARDS include the following:
Deep venous thrombosis
Gastrointestinal bleeding due to stress ulceration
Poor nutrition
Catheter-related infections

26. DIAGNOSTIC EVALUATION
Excluding cardiogenic pulmonary edema 
An absence of cardiac exam abnormalities (eg, an S3 or S4 gallop, new or changed murmur),
elevated right-sided filling pressures (eg, elevated jugular venous pressure),
certain radiographic abnormalities (eg, 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:

27. Brain natriuretic peptide (BNP)
A plasma BNP level below 100 pg/mL favors ARDS, but higher levels neither confirm heart failure nor exclude ARDS . This derives from an observational study of patients with ARDS (n = 33) or cardiogenic pulmonary edema (n = 21) . The study found that a plasma BNP level less than 100 pg/mL identified ARDS with a sensitivity, specificity, positive predictive value, and negative predictive value of 27, 95, 90, and 44 percent, respectively.

28. Echocardiography
Many clinicians use transthoracic echocardiography as the first-line diagnostic test if cardiogenic pulmonary edema cannot be excluded by clinical evaluation and measurement of the BNP level. While severe aortic or mitral valve dysfunction, severe diastolic dysfunction, or a severely reduced left ventricular ejection fraction favors cardiogenic pulmonary edema, the latter is insufficient to confirm primary cardiogenic pulmonary edema because some precipitants of ARDS (eg, septic shock) can cause an acute, severe cardiomyopathy that develops concomitantly with ARDS.

29. Right heart catheterization
There is evidence that there is generally no value to routine right heart catheterization for either the diagnosis or management of ARDS . However, pulmonary artery catheterization may be considered if primary cardiogenic pulmonary edema cannot be excluded on the basis of the clinical evaluation, plasma BNP measurement, and echocardiogram.

30. Excluding other causes of hypoxemic respiratory failure
Noninvasive respiratory sampling – The lower respiratory tract can be sampled via tracheobronchial aspiration or mini-bronchoalveolar lavage (mini-BAL).
Regardless of the technique, the specimen that is obtained may be evaluated via microscopic analysis (eg, Gram stain, cytology) and microbiologic culture; these studies may identify pneumonia or rapidly progressive cancer as the correct diagnosis

31. Flexible bronchoscopy – Flexible bronchoscopy can obtain lower respiratory samples for microscopic analysis and microbiologic culture if the noninvasive techniques are unsuccessful. It can also identify abnormalities that may not be detected with noninvasive sampling. Therefore, flexible bronchoscopy is a reasonable next step whenever noninvasive sampling is nondiagnostic.

32. 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 . The safety of lung biopsy in selected patients with hypoxemic respiratory failure was demonstrated by a retrospective study of 57 patients with ARDS who underwent open lung biopsy . The patients had a mean ratio of arterial oxygen tension to fraction of inspired oxygen (PaO2/FiO2) of 145 mmHg and the rate of major complications was 7 percent, with no deaths attributed to the biopsy. Although the complication rate was 39 percent, most were tolerable (eg, persistent air leaks).
The results of the biopsy resulted in the addition of specific therapy in 60 percent of patients and the withdrawal of unnecessary therapy in 37 percent.

33. DIAGNOSTIC CRITERIA
Berlin definition — ARDS can be diagnosed once cardiogenic pulmonary edema and alternative causes of acute hypoxemic respiratory failure and bilateral infiltrates have been excluded. The Berlin Definition of ARDS requires that all of the following criteria be present to diagnose ARDS

34. DIAGNOSTIC CRITERIA
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.

35. ●A moderate to severe impairment of oxygenation must be present, as defined by the ratio of arterial oxygen tension to fraction of inspired oxygen (PaO2/FiO2). The severity of the hypoxemia defines the severity of the ARDS:
•Mild ARDS – The PaO2/FiO2 is >200 mmHg, but ≤300 mmHg, on ventilator settings that include positive end-expiratory pressure (PEEP) or continuous positive airway pressure (CPAP) ≥5 cm H2O.
•Moderate ARDS – The PaO2/FiO2 is >100 mmHg, but ≤200 mmHg, on ventilator settings that include PEEP ≥5 cm H2O.
•Severe ARDS – The PaO2/FiO2 is ≤100 mmHg on ventilators setting that include PEEP ≥5 cm H2O.

36. DIFFERENTIAL DIAGNOSIS
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

37. Cardiogenic pulmonary edema
Cardiogenic pulmonary edema is usually due to left ventricular systolic or diastolic dysfunction, but may also be due to fluid overload, severe hypertension, renal artery stenosis, or severe renal disease. Its presentation is nearly identical to ARDS, except there may be evidence of cardiac dysfunction (eg, an S3 or S4 gallop, new or changed murmur), elevated right-sided filling pressures (eg, elevated jugular venous pressure), or related radiographic abnormalities (eg, pulmonary venous congestion, Kerley B lines, cardiomegaly, and pleural effusions). Distinguishing cardiogenic pulmonary edema from ARDS can be aided by measurement of a brain natriuretic peptide (BNP) level, echocardiography, and, less often, right heart catheterization

38. An acute exacerbation of idiopathic pulmonary fibrosis
An acute exacerbation of idiopathic pulmonary fibrosis or other chronic interstitial lung diseases can closely resemble ARDS in both clinical presentation and chest radiographic abnormalities. Like ARDS, the pathological findings are dominated by diffuse alveolar damage, but the prognosis is substantially worse. This diagnostic possibility is easily overlooked in patients whose underlying interstitial lung disease is unknown or mild or moderate in severity. The diagnosis is suggested by careful review of previous chest radiographic images, by discovery of subpleural reticular changes intermixed with alveolar opacities on a chest CT scan obtained shortly after onset of ARDS, or by surgical lung biopsy.

39. Diffuse alveolar hemorrhage
Diffuse alveolar hemorrhage may be associated with a large, otherwise unexplained drop in the hemoglobin concentration and hematocrit. While hemoptysis may be minimal or absent, bronchoscopy often reveals frothy bloody secretions throughout the airways and invariably detects an increasing amount of red blood cells in serial bronchoalveolar lavage specimens.
The recovery of hemosiderin-laden macrophages from bronchoalveolar lavage fluid is strongly suggestive of diffuse alveolar hemorrhage.

40. Idiopathic acute eosinophilic pneumonia
Idiopathic acute eosinophilic pneumonia (IAEP) 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 [

41. Cryptogenic organizing pneumonia
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 most common features at presentation are a persistent nonproductive cough, dyspnea with exertion, and weight loss. Bronchoalveolar lavage usually contains a smaller proportion of macrophages and higher proportions of lymphocytes, neutrophils, and eosinophils than healthy patients. This "mixed pattern" of increased cellularity is thought to be characteristic of COP. The diagnosis is made by ruling out infectious causes of pneumonia and documenting typical pathologic changes in tissue obtained by open lung biopsy

42. Acute interstitial pneumonia
Acute interstitial pneumonia (Hamman-Rich syndrome) is a rare and fulminant form of diffuse lung injury that has a presentation similar to ARDS. Many people consider acute interstitial pneumonia 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.

43. Cancer
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.

44. MANAGEMENT OF HYPOXEMIA 
— By definition, patients with ARDS are severely hypoxemic. Options available for improving arterial oxygen saturation (SaO2) include:
●Use of high fractions of inspired oxygen (FiO2)
●Decrease oxygen consumption
●Improve oxygen delivery
●Manipulate mechanical ventilatory support

45. Treatment Medications
• Medications directed at the underlying cause of ARDS are indicated
• Intravascular volume should be maintained at the lowest level required to maintain adequate cardiac output
• Diuretics may be needed to reduce pulmonary capillary wedge pressure and improve oxygenation
• Cardiac output that falls when PEEP is used may be improved by reducing the level of PEEP or by the judicious use of inotropic drugs (eg, norepinephrine)
• Achieving supranormal oxygen delivery through the use of inotropes and blood transfusion is not clinically useful and may be harmful
• Sedatives, analgesics, and antipyretics may be used to decrease oxygen consumption
• Systemic corticosteroids have not been shown to reliably improve outcomes

46. Therapeutic Procedures
• Intubation and mechanical ventilation are usually required to treat hypoxemia
• Use the lowest levels of PEEP and Fio2 needed to maintain Pao2 > 55 mm Hg (7.13 kPa) or the Sao2 above 88%
• Mechanical ventilation with small tidal volumes (6 mL/kg of ideal body weight) has been shown to reduce mortality by 10% in a multicenter trial
•• Prone positioning may improve oxygenation in selected patients

49. Supine Ventilation
± 40% lung volume under heart, especially patients with large hearts

50. Prone Ventilation