Acute respiratory distress syndrome (ARDS) is characterized by acute lung injury and hypoxemia caused by a profound inflammatory response and diffuse alveolar damage. ARDS has an incidence of 5-71 per 100,000 people and costs $5 billion annually to treat in the US. Standard treatment focuses on treating the underlying cause, maintaining adequate oxygen levels through ventilator support using lung-protective strategies, and considering approaches like prone positioning to improve oxygenation. While mortality was historically high, outcomes have improved with application of evidence-based protocols, though ARDS still carries significant morbidity and risk of long-term complications.

1. ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS) Timothy G. Janz, MD Department of Emergency Medicine Pulmonary/Critical Care Division Department of Internal Medicine

2. ARDS Definitions Acute Lung Injury 150 – 200 mmHg < PaO 2 /FIO 2 < 250 – 300 mmHg ARDS PaO 2 /FIO 2 < 150 – 200 mmHg

3. ARDS Epidemiology Incidence: 5 – 71 per 100,000 Financial cost: $5,000,000,000 per annum

4. ARDS Pathophysiology Profound inflammatory response Diffuse alveolar damage acute exudative phase (1-7days) proliferative phase (3-10 days) chronic/fibrotic phase (> 1-2 weeks)

5. ARDS Acute Exudative Phase Basement membrane disruption Type I pneumocytes destroyed Type II pneumocytes preserved Surfactant deficiency inhibited by fibrin decreased type II production Microatelectasis/alveolar collapse

6. ARDS Acute Exudative Phase

7. ARDS Acute Exudative Phase

8. ARDS Acute Exudative Phase

9. ARDS Proliferative Phase Type II pneumocyte proliferate differentiate into Type I cells reline alveolar walls Fibroblast proliferation interstitial/alveolar fibrosis

10. ARDS Proliferative Phase

11. ARDS Fibrotic Phase Characterized by: local fibrosis vascular obliteration Repair process: resolution vs fibrosis

12. ARDS Pathophysiology Interstitial/alveolar edema Severe hypoxemia due to intra-pulmonary shunt (V/Q = 0) shunt ~ 25% - 50% Increased airway resistance

13. ARDS Pathophysiology High ventilatory demands high metabolic state increased V D /V T decreased lung compliance Pulmonary HTN neurohumoral factors, hypoxia, edema

14. ARDS Etiology

15. ARDS Etiology Hospital-acquired infection/sepsis massive blood transfusions gastric aspiration Community-acquired trauma pneumonia drugs/aspiration/inhalations

16. ARDS Clinical Phases I. Injury Phase II. Latent/Lag Phase III. ARF Phase IV. Recuperative/Terminal Phase

17. ARDS Clinical Features Acute dyspnea/tachypnea rales/rhonchi/wheezing Resistant hypoxemia PaO 2 /FIO 2 < 150 – 200 mmHg CXR diffuse, bilateral infiltrates No evidence of LV failure (PAWP < 18 mmHg)

18. ARDS Clinical Features: CXR

19. ARDS Clinical Features: CXR

20. ARDS Differential Diagnosis CARDIOGENIC PULMONARY EDEMA Bronchopneumonia Hypersensitivity pneumonitis Pulmonary hemorrhage Acute interstitial pneumonia (Hamman-Rich Syndrome)

21. ARDS Diagnosis Resistant hypoxemia PaO 2 /FIO 2 < 150 – 200 mmHg CXR diffuse, bilateral infiltrates No evidence of LV failure (PAWP < 18 mmHg)

22. ARDS Diagnosis

23. ARDS Diagnosis Based on clinical criteria no diagnostic tests Confirmatory tests: PA catheter PAWP = normal/reduced [bronchial secretion protein]:[serum protein] ratio > 70% - 80%

24. ARDS Treatment: Standard Rx underlying cause Adequate oxygenation/ventilation PaO 2 > 60 mmHg; SaO 2 > 90% PEEP usually needed to meet O 2 goals Prevents/corrects alveolar collapse converts: (V/Q = 0) to V/Q mismatch

25. ARDS “Open-Lung “ Approach to PEEP Amato , Am J Respir Crit Care Med 1995; 152:1835

26. ARDS Treatment: PEEP “Open-lung” approach Not practical Does not improve outcomes Optimal PEEP ??? Most cases: PEEP ~ 15 – 20 cmH 2 O

27. ARDS Optimal PEEP Maximize lung compliance Crs = Vt/(P plateau – PEEP) Maximize O 2 delivery DO 2 = 10 x CO x (1.34 x Hgb x SaO 2 ) Lowest PEEP to oxygenate @ FIO 2 < .60 Empiric approach: PEEP = 16 cmH 2 O and Vt = 6 ml/kg

28. ARDS Optimal PEEP ARDS Network protocol FIO 2 - 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 PEEP - 5 5-8 8-10 10 10-14 14 14-18 18-22 ARDS Network, N Engl J Med 2000; 342:1301 www.ardsnet.org

29. ARDS Ventilator-Induced Lung Injury

30. ARDS Treatment:Lung-Protective Ventilation ARDS Network, N Engl J Med 2000; 342:1301 ardsnet.org

31. ARDS Treatment: Lung-Protective Ventilation V T = 6 mL/kg Limit plateau pressures < 30 cmH 2 O Volume controlled ventilation Limit peak airway pressures < 40 cmH 2 O Pressure controlled ventilation

32. ARDS Treatment: Lung-Protective Ventilation V T = 6 mL/kg Limit peak airway pressures < 40 cmH 2 O Limit plateau pressures < 30 cmH 2 O

33. ARDS Treatment: Lung-Protective Ventilation Complications: (derecruitement) Elevated PaCO 2 Limit: pH > 7.20 –7.25 Worsening hypoxemia Correction: Recruitement maneuver increasing PEEP

34. ARDS Treatment: Mechanical Ventilation (MV) Pressure controlled ventilation Controlled airway pressures Controlled inspiratory times Patient comfort Effectiveness: PCV = VCV

35. ARDS Treatment: Alternate Modes of MV Inverse-ratio ventilation Airway pressure-release ventilation Bilevel airway pressure ventilation Proportional-assist ventilation High-frequency ventilation ECMO Tracheal gas insufflation

36. ARDS Treatment: Prone Positioning Chatte, Am J Respir Crit Care Med 1997; 25:1539

37. ARDS Treatment: Prone Positioning

38. ARDS Treatment: Prone Positioning 65% responders Multiple proposed mechanisms Improved oxygenation Difficult to implement No improvement in outcomes

39. ARDS Treatment: Partial Liquid Ventilation Lungs filled to FRC with perflubron 17 times more O 2 dissolved than water Low surface tension Gravitates to dependent areas of lungs Nontoxic Minimally absorbed Eliminated by evaporation

40. ARDS Treatment: Partial Liquid Ventilation Used as lavage + conventional MV Multiple proposed mechanisms Improves oxygenation No improvement in outcomes

41. ARDS Treatment: Vasodilators Gerlach, Eur J Clin Invest 1993; 23:499

42. ARDS Treatment: Vasodilators NO has 83% response rate Problems: Special equipment Rebound phenomenon No improvements in outcomes Prostacyclin may be better agent

43. ARDS Treatment: Other Modalities Antiinflammatory agents Steroids may have a role Antioxidants Surfactant replacement Increased alveolar fluid removal Effect sodium channels Activate Na + -K + -ATPase pump

44. ARDS Prognosis Mortality 30% - 50% Death from respiratory failure = 15% - 18% Most common cause of death - sepsis/infection Outcomes Majority have near-normal lung function Small % develop pulmonary fibrosis Neuropsychiatric sequelae – may be high

45. The End