1. Pediatric ARDS: Understanding It and Managing It James D. Fortenberry, MD Medical Director, Pediatric and Adult ECMO Medical Director, Critical Care Medicine Children’s Healthcare of Atlanta at Egleston

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

3. ARDS: New Definition Criteria  Acute onset  Bilateral CXR infiltrates  PA pressure < 18 mm Hg  Classification  Acute lung injury - P a O 2 : F 1 O 2 < 300  Acute respiratory distress syndrome - P a O 2 : F 1 O 2 < 200 - 1994 American - European Consensus Conference

4. Clinical Disorders Associated with ARDS

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

6. ARDS - Pathogenesis Instigation Endothelial injury: increased permeability of alveolar - capillary barrier Epithelial injury : alveolar flood, loss of surfactant, barrier vs. infection Proinflammatory mechanisms

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

9. ARDS - Pathophysiology Decreased compliance Alveolar edema Heterogenous “Baby Lungs”

10. ARDS:CT Scan View

11. Phases of ARDS Acute - exudative, inflammatory (0 - 3 days) Subacute - proliferative (4 - 10 days) Chronic - fibrosing alveolitis ( > 10 days)

13. 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 %

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

15. Therapies for ARDS Innovations: NO PLV Proning Surfactant Anti- Inflammatory Mechanical Ventilation Gentle ventilation: Permissive hypercapnia Low tidal volume Open-lung HFOV ECMO IVOX IV gas exchange AVCO 2 R Total Implantable Artificial Lung ARDS Extrapulmonary Gas Exchange

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

17. compliance intrapulmonary shunt FiO 2 WOB inflammatory response The Dangers of Atelectasis

18. Atelectasis “Sweet Spot” Overdistention Lung Injury Zones

19. ARDS: George 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 pCO 2

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

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

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

24. 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

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

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

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

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

29. High Frequency Oscillatory Ventilation

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

32. HFOV: Benefits Vs. Conventional Ventilation

33. - Arnold et al, CCM, 1994 * HFOV vs. CMV in Pediatric Respiratory Failure

34. Surfactant in ARDS ARDS:  surfactant deficiency  surfactant present is dysfunctional Surfactant replacement improves physiologic function

35. Surfactant in Pediatric ARDS Current randomized multi-center trial Placebo vs calf lung surfactant (Infasurf) Children’s at Egleston is a participating center-study closed, await results

36. Steroids in Unresolving ARDS Randomized, double-blind, placebo- controlled trial Adult ARDS ventilated for > 7 days without improvement Randomized:  Placebo  Methylprednisolone 2 mg/kg/day x 4 days, tapered over 1 month Meduri et al, JAMA 280:159, 1998

37. Steroids in Unresolving ARDS * * p<.01 * - Meduri et al., JAMA, 1998

38. Steroids in Unresolving ARDS Randomized, double-blind, placebo- controlled trial ARDSNetwork-180 adults Randomized:  Placebo  Methylprednisolone  No mortality difference  Decreased ventilator-free days but only if started 7-14 days Steinberg, NEJM, 354:1671,2006

39. Inhaled Nitric Oxide in Respiratory Failure Neonates  Beneficial in term neonates with PPHN  Decreased need for ECMO Adults/Pediatrics  Benefits - lowers PA pressures, improves gas exchange  Randomized trials: No difference in mortality or days of ventilation

41. Inhaled NO and HFOV In Pediatric ARDS Dobyns et al., J Peds, 2000 *

42. Partial Liquid Ventilation

43. Mechanisms of action oxygen reservoir recruitment of lung volume alveolar lavage redistribution of blood flow anti-inflammatory

44. Liquid Ventilation Pediatric trials started in 1996 Partial: FRC (15 - 20 cc/kg) Study halted 1999 due to lack of benefit Adult study (2001): no effect on outcome

45. ARDS- “Mechanical” Therapies Prone positioning- Unproven outcome benefit Low tidal volumes- Outcome benefit in large study Open-lung strategy- Outcome benefit in small study HFOV-Outcome benefit in small study ECMO- Proven in neonates unproven in children

46. Pharmacologic Approaches to ARDS: Randomized Trials Glucocorticoids Fibrosing alveolitis- lowered mortality, small study Surfactant- possible benefit in children Inhaled NO- no benefit Partial liquid ventilation- no benefit

47. “…We must discard the old approach and continue to search for ways to improve mechanical ventilation. In the meantime, there is no substitute for the clinician standing by the ventilator…” - Martin J. Tobin, MD