1. What Is New in ARDS ? Lluis Blanch MD PhD Senior Critical Care Center Scientific Director Corporació Parc Taulí Universitat Autónoma de Barcelona Sabadell, Spain 11 th Annual Congress Turkish Thoracic Society Belek-Antalya. April 23 – 27, 2008

2. What Is New in ARDS ? Definition Types Therapy Mechanical Ventilation Practice & Organization Aim of the talk: Aim of the talk: To reveal novel solutions for problems during mechanical ventilation and supportive therapy in ARDS.

3. What Is New in ARDS ? Definition Types Therapy Mechanical Ventilation Practice & Organization

4. Fan E, et al. JAMA 2005;294:2889-96 Diagnostic Criteria for ARDS

5. The definitions of ARDS and ALI require the use of standard ventilator settings to ensure that patients with consistent levels of lung injury are properly classified as having ARDS or ALI In 170 pts meeting ARDS criteria (PaO 2 /FiO 2 < 200 mmHg ) diferent combinations of FiO 2 & PEEP at VT 7 ml/kg were obtained in Day 0 and in Day 1. PaO 2 /FiO 2 156 mmHg PaO 2 /FiO 2 247 mmHg PaO 2 /FiO 2 370 mmHg

6. Nuckton TJ et al. N Engl J Med 2002; 346:1281. Observed Mortality According to the Quintile of Dead-Space Fraction in 179 Patients with ARDS Mechanisms: 1- Injury of pulmonary capillaries by thrombotic and inflammatory factors. 2- Obstruction of pulmonary blood flow in pulmonary circulation. 3- Lung areas with high V/Q ratio (impaired CO 2 excretion)

7. Exhaled Volume PCO2 Phase I Phase II Phase III PaCO2 PetCO2 Effective Alveolar Ventilation 0.2 0.4 0.5 0.6 0.7 0.3 Adm48 h24 h * * ns p<0.05 V AE /V T S D SS 73% SP 93%

8. What Is New in ARDS ? Definition Types Therapy Mechanical Ventilation Practice & Organization

9. Severe intra-alveolar infiltrates, deposition of hyaline membranes, vascular congestion and microthrombi. Human ARDS Matute-Bello G, et al. http://www.thoracic.org LPS inhaled OAI i.v. CLP sepsis Models of ARDS

10. American–European Consensus Conference Definition and Sensitivity, Specificity, and Likelihood Ratios Assessed in Patients Who Died in the Intensive Care Unit Reference Standard: Diffuse Alveolar Damage at Autopsy The accuracy of the American–European Consensus Conference definition of ARDS was only moderate. The definition was more accurate for patients with extrapulmonary risk factors than for patients with pulmonary risk factors.

11. Mortality in Relation to the Percentage of Potentially Recruitable Lung PRL: difference between non-aerated tissue between 5 and 45 cmH 2 O PEEP

13. DirectIndirectPulmonaryExtrapulmonaryMedicalSurgicalPrimarySecondary Human ARDS ?

14. What Is New in ARDS ? Definition Types Therapy Mechanical Ventilation Practice & Organization

15. Effects of NO on Mortality

16. Effects of NO on PaO2/FiO2 Effects of NO on Renal Dysfunction

17. Day 28 Ventilator-free days Mortality % CMV 13  9 15 Low dose PLV group 7  9* 26 High dose PLV group 10  9* 19 311 pts with ARDS At Randomization: VT 9 ml/kg, PEEP 14 cmH 2 O Pplat 30 cmH 2 O

18. Rationale: Persistent ARDS is characterized by ongoing inflammation, parenchymal-cell proliferation and disordered deposition of collagen all of which may be responsive to corticosteroid therapy.

19. Main Outcome Variables

20. Prolonged methylprednisolone treatment of greater than 1 week’s duration after removing patients randomized after day 14. Steroid Treatment in ARDS Meduri GU Intensive Care Med 2008; 34:61-69 Correct use of prolonged glucocorticoid treatment is associated with a substantial and significant improvement in meaningful patient-centered outcome variables. Surveillance measures: 1)intensive infection vigilance 2)avoidance of paralytic agents 3)avoidance of rebound inflammation with premature discontinuation of treatment

21. Pulmonary Edema Formation in Congestive Heart Failure & ARDS Piantadosi CA, Schwartz DA. Ann Intern Med 2004; 141:460-470.

22. can B-agonists can enhance alveolar fluid clearance through the up-regulation of sodium transport mechanisms located on the alveolar epithelial cells. Objective & Methods: manipulation of alveolar fluid clearance with B-agonists can accelerate the resolution of alveolar edema. 40 pts.with ALI/ARDS were randomized to treatment with intravenous salbutamol (15 g kg -1 h -1 ) or placebo for 7 d. Results: Patients in the salbutamol group had lower extravascular lung water, plateau pressure and LIS at day 7 compared with placebo group.

24. Main Outcome Variables

25. Prone Positioning in Critically Ill Patients

26. Am J Resp Crit Care Med 2006;173:1233-39 ARDS patients FiO2 0.85, VT 8 ml/kg, PEEP 12 SAPS 38 – 42 & Diffuse Infiltrates Enrolled 48 h Prone 20 h/day A total of 718 turning procedures were done and PP was applied for a mean of 17 h/day. A total of 28 complications were reported, most rapidly reversible.

27. Probability of Survival 10 20 30 40 50 60 Days After Randomization 0 20 40 60 80 100 SUPINE PRONE p= 0.27 Spanish Trial: Kaplan-Meier Estimates of ICU Survival (up to 60 days) 25% ↓ Mortality in Prone

28. What Is New in ARDS ? Definition Types Therapy Mechanical Ventilation Practice & Organization

29. ARDSNet: V T 6 ml/kg & Pplat < 30 cm H 2 O P a O 2 /F i O 2 149±34102±240,009 Pplat25,5±0.528,9±0.90,006 PEEP9,3±2.312,6±2.50,005 Days off MV 7±81±20,01 More Protected (n=20)Less Protected (n=10)

30. JAMA, Feb.13, 2008;209:646-55 ALI pts. (n=767) Minimal Distension (n=382): - VT 6 ml/kg PBW - PEEP 5 – 9 cmH 2 O Increased Recruitment (n=385) - VT 6 ml/kg PBW - PEEP to reach Pplat 28-30 cmH 2 O Mortality: MD 31.2%, IR 27.8 %, p=.31 Vent. Free Days: MD 3, IR 7, p=.04 Organ Failure Free Days: MD 2, IR 6, p=.04 IR assocaited with better PaO2, Crs, less adjunctive therapies and larger fluid requir.

31. JAMA, Feb.13, 2008;209:637-45 ALI pts. & PaO 2 < 250 mmHg (n=983) Control Ventilation (n=508): - VT 6 ml/kg PBW, Pplat < 30 cmH 2 O, - PEEP mean 9.8 cmH 2 O -Table- Lung Open Ventilation (n=475) - VT 6 ml/kg PBW, Pplat < 40 cmH 2 O - PEEP mean 14.6 cmH 2 O -Table- & RMs. Mortality: CV 40.4%, LOV 36.4%, p=.19 Refractory Hipoxemia: CV 10%, LOV 5% p=.01 Rescue Therapies: CV 13%, LOV 8%, p=.05 RM associated with a complication in 22.1% of p.

32. What Is New in ARDS ? Definition Types Therapy Mechanical Ventilation Practice & Organization

33. Assessing practice changes 1998 (1.383 p.) 2004 (1.675 p.)

35. Thank You lblanch@tauli.cat