ARDS

2. ARDS Definition and Epidemiology.

3. Vietnam war ARDS Ashbaughet al. Acute respiratorydistress in adults. Lancet 1967 .

4. ALI/ARDS • acute onset • bilateral CXR infiltrates • P/F ratio <200 (ALI <300) • pulmonary artery occlusion pressure < 18 mm Hg • or absence of clinical evidence of left atrial hypertension AECC 1994

5. DEFINITION Esteban A et al. Ann Intern Med. 2004 In a series of autopsy patients, the accuracy of the American-European Consensus Conference definition of ARDS was only moderate.

8. incidence ALI: 20 to 50 cases per 100,000 ARDS: 3 to 8 cases per 100,000 recent study ARDS and ALI: 22 cases/100,000 Rubenfeld GD et al. NEJM 2005

12. Hugeeconomicalburden in the survivors

13. ARDS How can we improve the diagnosis and assess the risk of death.

14. This meta-analysis provides a unique ranking of plasma biomarkers according to their strength of association with ARDS diagnosis or mortality. The relative performance of biomarkers among studies shown in this ranking may help to improve acute respiratory distress syndrome diagnosis and outcome prediction Critical Care Medicine 2014

15. ARDS: diagnosis Critical Care Medicine 2014

16. ARDS: prognosis Critical Care Medicine 2014

17. Rationale: PaO₂/Fio₂ may increase when Fio2 is raised from moderate to high levels, suggesting that patients with similar PaO₂/Fio₂ ratios but different Fio₂ levels have different risks of mortality Conclusions: the addition of baseline Fio2 to PaO₂/Fio₂ could be used to identify subsets of patients with low or high mortality

19. ARDS How can we decrease mortality

20. ARDS How can we decrease mortality: New drugs New management strategies New ventilatory strategies

31. Pulmonary vascular leakage occurs early in acute respiratory distress syndrome (ARDS). Mortality is high (35-45%), but no effective pharmacotherapy exists. Production of anti-inflammatory adenosine by ecto-5'-nucleotidase (CD73) helps maintain endothelial barrier function. We tested whether interferon-beta-1a (IFN-beta-1a), which increases CD73 synthesis, can reduce vascular leakage and mortality in patients with ARDS.

34. Conclusions: FP-1201 up-regulates human lung CD73 expression, and is associated with a reduction in 28-day mortality in patients with ARDS. Our findings need to be substantiated in large, prospective randomised trials, but suggest that FP-1201 could be the first effective, mechanistically targeted, disease-specific pharmacotherapy for patients with ARDS

35. ARDS How can we decrease mortality: New drugs New management strategies New ventilatory strategies New ventilatory options

39. ARDS How can we decrease mortality: New drugs New management strategies New ventilatory strategies New ventilatory options

40. Ventilator-induced lung injury

41. VILI: lung edema RATS Dreyfuss D et al. Am Rev RespirDis 1988

42. VILI: biotrauma RATS Tremblay L et al. JCI 1997

43. RABBITS Low TV high PEEP=noninjurious vs High TV low PEEP=injurious

45. Ventilator-induced lung injury Imai Y. Crit Care Med 2005; 33:S129–S134

46. the search of a new “DOGMA” HOW TO VENTILATE TO PREVENT VILI

47. NEJM 2000;342:1301-8

48. 861 PATIENTS WITH ALI/ARDS * (p = 0.007) 12 ml/Kg 6 ml/Kg NIH ARDS network, NEJM 2000; 342: 1301-1308

49. Plasma Cytokine Levels Stuber F, Putensen C et al: Intensive Care Med 2003

50. Avoidrecruitment and derecruitment Keeping VT low and PEEP high