Acute Respiratory Distress Syndrome ARDS.pptx

Includes predisposing factors, risk factors, clinical features, pathophysiology, diagnosis, stages of ARDS, disease progression, prognosis, treatment and various supportive therapies related to ARDS in ICU setting

1. ARDS Dr. Nischal Karki 2 nd year MD Anesthesiology Resident Nepal Medical College and Teaching Hospital

2. Introduction a life-threatening acute onset of respiratory failure Characterized by severe dyspnea of rapid onset, hypoxemia, and diffuse pulmonary infiltrates leading to respiratory failure caused by diffuse lung injury from many underlying medical and surgical disorders

3. Predisposing Factors Direct causes of lung (pneumocytes) injury Pneumonia (60 %) Aspiration Inhaled toxins Pulmonary contusion Pulmonary vasculitis Drowning Fat embolism

4. Indirect / Systemic causes of lung (pneumocytes) injury (Systemic inflammation) Sepsis Pancreatitis TRALI Major  Trauma Severe  Burns Non-cardiogenic shock Drug overdose

5. Risk Factors Pneumonia and sepsis (40-60%) Older age Chronic alcohol abuse Smoker Pancreatitis Trauma

6. Clinical Findings Acute onset severe Dyspnoea Other s igns of respiratory distress ( laboured breathing, tachypnoea , intercostal retractions, crackles, cyanosis ) ABG - T1RF, Hypoxemia, ↑ ed A-a gradient Chest radiography – diffuse or patchy b/l infiltrates, Air bronchogram Confusion , extreme tiredness, diaphoresis Marked hypoxemia refractory to treatment with supplemental O2

7. ARDS Berlin Definition Timing Acute Onset within 1 week of a clinical insult or new / worsening respiratory symptoms Chest imaging Presence of bilateral opacities - not fully explained by effusions, lobar/lung collapse or nodules Origin of edema - Respiratory failure not fully explained by cardiac failure or fluid overload - Need for objective assessment (echocardiography) to exclude hydrostatic edema Oxygenation Impaired oxygenation, with ratio of partial pressure of oxygen in arterial blood (Pao2) to fractional concentration of inspired oxygen (Fio2) < 300 mm Hg, with PEEP ≥ 5 cm H2O.

8. Acute Hypoxemia P/F ratio < 300 Diffuse bilateral infiltrates Cardiogenic pulmonary edema ruled out Severity Mild ARDS - PaO2/FiO2 200 to 300 mmHg with PEEP ≥ 5 cmH2O Moderate ARDS - PaO2/FiO2 100 to 200 mmHg with PEEP ≥ 5 cmH2O Severe ARDS - PaO2/FiO2 ≤ 100 mmHg with PEEP ≥ 5 cmH2O

9. Diagnosis Acute Hypoxemia < 1 week ABG (PaO2/FiO2 ratio < 300) CXR – Bilateral diffuse fluffy infiltrates CT – widespread patchy or coalescent airspace opacities involving dependent portions of the lung with relative sparing of other regions Rule out cardiogenic Pulmonary edema – ECHO, BNP, Right heart catheterization

10. Differential Diagnosis Cardiogenic pulmonary edema Bilateral pneumonia Diffuse alveolar hemorrhage Acute ILD (AIP) Acute immunologic injury (hypersensitivity pneumonitis) Toxin injury (radiation pneumonitis) Neurogenic pulmonary edema A/E of IPF

11. Pathophysiology

12. Type I cell injury Alveolar fluid accumulation (exudates, proteins, immune cells) Alveolar Filling Type II cell injury ↓ ed surfactant > ↑ ed Surface tension + fluid accumulation Alveolar collapse VQ mismatch Hypoxemia Increased RR and WOB

13. Disease Progression Exudative Phase Proliferative Phase Fibrotic Phase

14. Exudative phase Injury to alveolar capillary endothelial cells and type I pneumocytes ↑ ed vascular permeability > Protein rich edematous fluid fills in interstitial and alveolar spaces of dependent portions of lung ↑ in proinflammatory cytokines + Recruitment of neutrophils Aggregation of condensed plasma proteins, ↓ ed production & activity of surfactant form hyaline membrane whorls As a result > Intrapulmonary shunting > Hypoxemia > ↑ ed RR and WOB Similarly, vascular occlusion by microthrombi and fibrocellular proliferation > Pulmonary vascular injury > reduced pulmonary arterial blood flow > Dead space, PHTN > Hypercapnia

15. Exudate also contains fibrin > progressive inflammation results in fibrin accumulation > structural remodelling and pulmonary fibrosis Clinically Onset of early non specific respiratory symptoms Dyspnoea rapid shallow breathing and an inability to get enough air Tachypnoea, ↑ ed WOB, respiratory fatigue > respiratory failure

16. Proliferative phase Day 7 to 21 signs of resolution and initiation of lung repair often evident with organization of alveolar exudates shift from neutrophil to lymphocyte predominant pulmonary infiltrates proliferation of abnormal Type II pneumocytes, fibrob lasts, myofibroblasts, collagen and inflammatory cells along alveolar basement membranes These specialized epithelial cells synthesize new pulmonary surfactant and differentiate into type I pneumocytes Many patients recover rapidly, get rid of MV Some develop Stiff / Shock lungs ( ↓ ed lung compliance) May experience dyspnea, tachypnea, hypoxemia

17. Fibrotic Phase Alveolar edema and inflammatory exudates convert to extensive alveolar duct and interstitial fibrosis Marked disruption of acinar architecture Emphysema-like changes, with large bullae Intimal fibroproliferation in the pulmonary microcirculation > progressive vascular occlusion and pulmonary hypertension ↑ ed risk of pneumothorax, reductions in lung compliance, ↑ e d pulmonary dead space Only some patients enter fibrotic phase, a/w ↑ ed mortality risk may require long-term support on MV and supplemental O2

18. Functional Lung volume in ARDS lung infiltration in ARDS is confined to dependent lung regions Only small portion of the lung is normal and participates in gas exchange – Baby Lung High ventilator volumes being delivered to a markedly reduced volume of available lung (Baby lung) can cause overdistension and rupture of the distal airspaces (barotrauma)

19. Treatment

20. Treatment Standard Supportive Therapy Treatment of predisposing factors Fluid and Hemodynamic Management Nutrition Mechanical Ventilation Lung Protective Ventilation Noninvasive Ventilation and High Flow Nasal Canula Pharmacological Therapy Rescue Therapies

21. Standard Supportive Therapy Standardized “bundled care” approaches for ICU patients prophylaxis against venous thromboembolism, GI bleeding, aspiration, excessive sedation, prolonged MV, CVC infections FASTHUGSBID Contributing factor in decline in mortality attributable to ARDS

22. Treatment of predisposing factors Appropriate treatment for any precipitating infection such as pneumonia or sepsis Timely surgical management of intraabdominal sepsis

23. Fluid and Hemodynamic Management A/c to a large, multi-centre RCT conducted by the ARDS Network liberal fluid treatment strategy (1L of fluid accumulation per day) vs. conservative fluid treatment strategy (net fluid balance of zero by day 7) no difference in mortality at 60 days BUT patients in the conservative group experienced improved oxygenation and significantly more ventilator-free days without the development of additional organ failures recommended strategy - aim for lowest IV volume that maintains adequate tissue perfusion (measured by urine output, perfusion of other vital organs, metabolic acid-base status, target CVP < 4 mm Hg, PAOP < 8 mm Hg) Target Hb > 7 g/dl

24. Nutrition Preferred route – Enteral (fewer infectious complications ) Parenteral feeding translocation of bacteria from the intestine ↑ ed circulating levels of TNF- α , glucagon, epinephrine increased febrile responses high-fat, low-carbohydrate diet - reduce duration of MV Avoid overfeeding - ↑ ed respiratory quotient Goals of Nutrition Provide adequate nutrients for the patient’s metabolism and the treatment prevention of micronutrients or macronutrients deficiencies

25. Mechanical Ventilation ARDS causes fatigue from ↑ ed work of breathing and progressive hypoxemia Patients require MV to support adequate gas exchange But MV can aggravate lung injury (VILI) Attempts to fully inflate the consolidated lung may lead to overdistention and injury to the more normal areas

26. Ventilator Induced Lung Injury Barotrauma ↑ ed alveolar pressure > ↑ ed risk of pneumothorax, pneumomediastinum Volutrauma repeated alveolar overdistention from excess TV > injure Type I and II alveolar cells > increase inflammatory mediators > more severe ARDS Atelectrauma too little pressure (less PEEP) > recurrent alveolar collapse > ↑ ed inflammation, more features of ARDS Hyperoxia high levels of FiO2 > generation of free oxygen radicals > more damage to alveoli > ↑ ed tissue destruction and worsened VQ mismatch

27. Ventilator (In General) PSV (if patient is taking spontaneous breaths) patient breathes at own RR and TV, we set PEEP and FiO2 CMV (if patient not taking spontaneous breaths) we set RR and TV Manage PCO2 and pH by altering RR and TV If PaO2 too high – ↓ PEEP or FiO2 ( derecruitment ) If PaO2 too low – ↑ PEEP or FiO2 (recruitment) High peak pressure - high airway resistance (small tube, kinked, bronchospasm, mucus plug) Low peak pressure - low airway resistance (air leak) High plateau pressure - ↓ ed lung compliance (ARDS, pneumonia, pneumothorax) or Auto PEEP (asthma, COPD) – ↓ TV to avoid barotrauma

28. Lung protective ventilation L ow TV ( < or equal to 6 mL/kg) to limit the risk of volutrauma PEEP of at least 5 cm of H2O to limit the risk of atelectrauma RR ≤ 35 bpm Target E nd-inspiratory “plateau” pressure (Ppl) ≤ 30 cm H2O Driving pressure < 15 Target PaO2 55 to 80 mm Hg Target SpO2 88 to 95 % Use NMB + sedation, analgesia - If ventilator dyssynchrony or P/F < 150

29. Permissive Hypercapnia One of the consequences of low tidal volume ventilation is a ↓ in CO2 elimination in the lungs > hypercapnia and respiratory acidosis hypercapnia is allowed to persist as long as there is no evidence of harm because of benefits of low tidal volume ventilatio n Limits - A rterial PCO2 60 to 70 mm Hg and pH levels of 7.2 to 7.25 are safe for most patients

30. Noninvasive Ventilation and HFNC NIV shown to improve oxygenation and prevented the need for intubation in children with ARDS Role of NIV in adults still unclear Some studies show lower rates of intubation and mortality with use of NIV and HFNC in those who do not have a severe oxygenation defect, hemodynamic instability, or altered mental status

31. Pharmacological Therapies N o specific pharmacologic therapy for ARDS Sedation To avoid dyssynchrony Midazolam, Propofol NMB re served for patients with severe ARDS and refractory hypoxemia Cisatracurium @ 37.5 mg/ hr for first 48 hours – improved mortality and more ventilator free days

32. Corticosteroids Early severe ARDS (PaO2/FIO2 <200 mm Hg, PEEP 10 cm H2O) Methylprednisolone IV loading dose of 1 mg/kg over 30 minutes > Then 1 mg/kg/day for 14 days > Then gradually taper over next 14 days Unresolving ARDS (start in initial stage of fibrinoproliferation ) Methylprednisolone IV loading dose of 2 mg/kg over 30 minutes > Then 2 mg/kg/day for 14 days > 1 mg/kg/day for the next 7 days > Then gradually taper and discontinue at 2 weeks after extubation A recent (2020) RCT of early Dexamethasone use in ARDS resulted in a substantial increase in ventilator-free days (4.8 days) and a 15.3% reduction in mortality 1st dose within 30 hours of ARDS onset 20 mg once daily IV from day 1 to 5 > 10 mg once daily IV from day 6 to 10 Treatment continued until day 10 or until extubated if before day 10

33. Rescue Therapies ARDS with profound and refractory hypoxemia despite best possible treatment ↑ sedation and neuromuscular paralysis Recruitment Prone positioning ECMO HFOV iNO

34. Prone Positioning PROSEVA Trial – 28 day mortality 32.8 % in supine group, 16 % in prone group 12-18 hours a day associated with improvements in oxygenation Indication - Moderate to severe ARDS with refractory hypoxemia (P/F ratio < 150) even after 12-24 hours of optimization on the ventilator C ontraindications – Thoracic / Abdominal surgery, Pregnancy, unstable fractures, Cardiac abnormalities Proning improves outcome by following mechanisms Relief of mediastinal compression R ecruitment of atelectatic alveoli Homogenous distribution of ventilation Better VQ matching

35. Extubation Spontaneous Breathing Trial (NHLBI ARDS network protocol) Conduct daily SBT if FiO2 < 40 % and PEEP < 8 cm of H2O FiO2 < 50 % & PEEP < 5 cm of H2O & FiO2 values ↓ ing Patient has acceptable breathing efforts SBP > 90 mm Hg without vasopressor support No NMB agent Evidence of SBT tolerance SpO2 > 90 % of PaO2 > 60 % Spontaneous TV > 4 ml/kg, RR < 35/min pH > 7.3 No signs of respiratory distress

36. Complications Barotrauma ( pneumothorax, pneumomediastinum, pneumatocele, or subcutaneous emphysema ) Pulmonary Hypertension Nosocomial pneumonia Ventilator associated Pneumonia (pseudomonas, S. aureus, MRSA) longer the intubation, higher the risk Ventilator Induced Lung Injury (VILI) Multi Organ System Dysfunction Neuromuscular weakness

37. Prognosis ARDS mortality with low TV ventilation is around 30% ( ARDSnet ) Trauma associated ARDS - better prognosis (mortality ~ 20%) If associated with sepsis, non pulmonary organ failure (mortality ~ 80%) Poor prognosis Older age, chronic immunosuppression, chronic liver disease Sepsis, chronic alcohol abuse ARDS d/t direct lung injury Failure to improve in the 1 st week of treatment Residual abnormalities restrictive or obstructive lung defects Diminished health-related, pulmonary disease–specific quality of life Exercise limitation, muscle wasting, weakness and fatigue PTSD, Depression

38. References The ICU Book, Paul L. Marino, 4 th edition Textbook of Critical Care, Jean Louis Vincent, 8 th edition Harrison’s principles of Internal Medicine, 21 st Edition