Chapter 7: Acute Respiratory Distress Syndrome

1. Chapter 7: Acute Respiratory Distress Syndrome James D. Fortenberry, MD, FCCM, FAAP Medical Director, Critical Care Medicine and Pediatric/Adult ECMO Children’s Healthcare of Atlanta at Egleston

2. ARDS: What Is It? Term first introduced in 1967 Acute respiratory failure with non-cardiogenic pulmonary edema, capillary leak after diverse insult Adult RDS defined to differentiate from neonatal surfactant deficiency Problems with definition troubled literature Murray score 1988: CXR, PEEP, Hypoxemia, Compliance Synonyms • Shock lung • Da Nang Lung • Traumatic wet lung

3. New and Improved Adult Respiratory Distress Syndrome Acute Respiratory Distress Syndrome

4. ARDS: New Definition Criteria • Acute onset • Bilateral CXR infiltrates • PA pressure < 18 mm Hg • Classification • Acute lung injury - PaO2 : F1O2< 300 • Acute respiratory distress syndrome - PaO2 : F1O2< 200 -1994 American - European Consensus Conference

5. ARDS - Epidemiology New criteria allow better estimate of incidence • 1994 criteria in Sweden: ALI 17.9/100,000; 13.5/100,000 ARDS • US: may be closer to 75/1000,000 • Prospective data pending • Incidence in children appears similar • 5-9% of PICU admissions

6. Clinical Disorders Associated with ARDS

7. The Problem: Lung Injury Davis et al., J Peds 1993;123:35 Non-infectious Pneumonia 14% Cardiac Arrest 12% Infectious Pneumonia 28% Hemorrhage 5% Trauma 5% Other 4% Septic Syndrome 32%

8. ARDS - Pathogenesis Instigation • Endothelial injury: increased permeability of alveolar - capillary barrier • Epithelial injury : alveolar flood, loss of surfactant, barrier vs. infection • Pro-inflammatory mechanisms

9. ARDS Pathogenesis: Resolution Phase Equally important • Alveolar edema - resolved by active sodium transport • Alveolar type II cells - re-epithelialize • Neutrophil clearance needed

11. ARDS - Pathophysiology • Capillary leak:non-cardiogenic pulmonary edema • Inflammatory mediators • Diminished surfactant activity and airway collapse • Reduced lung volumes • Heterogeneous • “Baby Lungs” • Altered pulmonary hemodynamics

12. ARDS:CT Scan View

13. ARDS - Pathophysiology: Diminished Surfactant Activity • Surfactant production and composition altered in ARDS: low lecithin-sphingomyelin ratio • Components of edema fluid may inactivate surfactant

14. ARDS - Pathophysiology: Diminished Surfactant Activity • Surfactant product of Type II pneumocytes • Importance of surfactant: • P = 2T/r (Laplace equation; P: trans-pulmonary pressure, T: surface tension, r: radius) • Surfactant proportions surface tension to surface area: thus

17. ARDS - Pathophysiology: Lung Volumes • Reduced lung volumes, primarily reduced FRC • FRC = ? Nl = • Low FRC-large intrapulmonary shunt, hypoxemia • Implies • lower compliance = flatter PV curve • marked hysteresis • PV curve concave above FRC and inflection point at volume > FRC • closing volume in range of tidal volume • resistance increased primarily due to mechanical unevenness (vs. airway R): high flow rates helpful

21. ARDS - Pathophysiology: Lung Volumes • FRC = Volume of gas in lungs at end of normal tidal expiration; outward recoil of chest wall = inward recoil of lungs • Normal FRC = • FRC decreased by 20-40% in ARDS • FRC decreased by 20-30% when supine: elevate head!

22. ARDS - Pathophysiology: Mediators • Massive literature • Mediators involved but extent of cause/effect unknown • Cellular: • neutrophils-causative: depletion in models can obliterate lesion; ARDS can occur in neutropenic patient; direct endothelial injury, release radicals, proteolytic enzymes • macrophages-release cytokines

23. ARDS - Pathophysiology: Mediators • Humoral: • Complement • Cytokines: TNF, IL-1 • PAF, PGs, leukotrienes • NO • Coagulant pathways

24. ARDS - Pathophysiology:Pulmonary Edema • Non-cardiogenic pulmonary edema-Starling formula • What changes in ARDS? • Q = K(Pc - Pis) -  (pl - is) • Q = • K = • Pc = ; Pis = •  = • pl = ; is =

26. Phases of ARDS • Acute - exudative, inflammatory: capillary congestion, neutrophil aggregation, capillary endothelial swelling, epithelial injury; hyaline membranes by 72 hours (0 - 3 days) • Sub-acute - proliferative: proliferation of type II pneumocytes (abnormal lamellar bodies with decreased surfactant), fibroblasts-intra-alveolar, widening of septae (4 - 10 days) • Chronic - fibrosing alveolitis: remodeling by collagenous tissue, arterial thickening, obliteration of pre-capillary vessels; cystic lesions ( > 10 days)

28. ARDS - Outcomes • Most studies - mortality 40% to 60%; similar for children/adults • Death is usually due to sepsis/MODS rather than primary respiratory • Mortality may be decreasing 53/68 % 39/36 %

29. ARDS - Principles of Therapy • Provide adequate gas exchange • Avoid secondary injury

31. Therapies for ARDS Mechanical Ventilation Innovations: NO PLV Proning Surfactant Anti-Inflammatory Gentle ventilation: Permissive hypercapnia Low tidal volume Open-lung HFOV ARDS Extrapulmonary Gas Exchange Total Implantable Artificial Lung IVOX IV gas exchange AVCO2R ECMO

32. The Dangers of Overdistention • Repetitive shear stress • Injury to normal alveoli • inflammatory response • air trapping • Phasic volume swings: volume trauma

33. The Dangers of Atelectasis • compliance • intrapulmonary shunt • FiO2 • WOB • inflammatory response

34. Lung Injury Zones Overdistention “Sweet Spot” Atelectasis

35. ARDS: George H. W. Bush Therapy • “Kinder, gentler” forms of ventilation: • Low tidal volumes (6-8 vs.10-15 cc/kg) • “Open lung”: Higher PEEP, lower PIP • Permissive hypercapnia: tolerate higher pCO2

37. Lower Tidal Volumes for ARDS • Multi-center trial, 861 adult ARDS • Randomized: Tidal volume 12 cc/kg Plateau pressure < 50 cm H2O vs Tidal volume 6 cc/kg Plateau pressure < 30 cm H2O ARDS Network, NEJM, 342: 2000

38. Lower Tidal Volumes for ARDS 22% decrease * * ARDS Network, NEJM, 342: 2000 * p < .001

39. Is turning the ARDS patient “prone” to be helpful?

40. Prone Positioning in ARDS • Theory: let gravity improve matching perfusion to better ventilated areas • Improvement immediate • Uncertain effect on outcome

42. Prone Positioning in Adult ARDS • Randomized trial • Standard therapy vs. standard + prone positioning • Improved oxygenation • No difference in mortality, time on ventilator, complications • Gattinoni et al., NEJM, 2001

43. Prone Positioning in Pediatric ARDS:Longer May Be Better • Compared 6-10 hrs PP vs. 18-24 hrs PP • Overall ARDS survival 79% in 40 pts. • Relvas et al., Chest 2003

44. Brief vs. Prolonged Prone Positioning in Children * ** Oxygenation Index (OI) * - Relvas et al., Chest 2003

45. High Frequency Oscillation:A Whole Lotta Shakin’ Goin’ On

46. It’s not absolute pressure, but volume or pressure swings that promote lung injury or atelectasis. - Reese Clark

47. High Frequency Ventilation • Rapid rate • Low tidal volume • Maintain open lung • Minimal volume swings

48. High Frequency Oscillatory Ventilation

50. HFOV is the easiest way to find the ventilation “sweet spot”