2. “ فإذا سويته ونفخت فيه من روحي فقعوا له ساجدين“ ص ۷۲

3. Mechanical Ventilation Strategies in ARDS Nabil Abouchala, MD Consultant Pulmonary & Critical Care Medicine abouhani@yahoo.com

4. Case presentation A 45-year-old man develops ARDS after sustaining multiple broken bones in an automobile accident. The man weighs 70 kg. Mechanical ventilation is initiated in the AC mode with the following settings: (PEEP), 10 cm H2O; (FiO2), 70%; respiration rate, 12/min. The most appropriate Tidal volume at this point: –(A)1000 ml –(B)420 ml –(C)500 ml –(D)560 ml –(E)700 ml

5. Definitions The 1994 North American-European Consensus Conference (NAECC) criteria: –Onset - Acute and persistent –Radiographic criteria - Bilateral pulmonary infiltrates consistent with the presence of edema –Oxygenation criteria - Impaired oxygenation regardless of the PEEP concentration, with a Pao2/Fio2 ratio  300 torr (40 kPa) for ALI and  200 torr (27 kPa) for ARDS –Exclusion criteria - Clinical evidence of left atrial hypertension or a pulmonary-artery catheter occlusion pressure of  18 mm Hg. Bernard GR et al., Am J Respir Crit Care Med 1994

6. Stratification System of Acute Lung Injury GOCA LetterMeaningScaleDefinition G Gas exchange (to be combined with the numeric descriptor) 0123ABCD0123ABCD Pao 2 /Fio 2  301 Pao 2 /Fio 2 200 -300 Pao 2 /Fio 2 101 – 200 Pao 2 /Fio 2  100 Spontaneous breathing, no PEEP Assisted breathing, PEEP 0-5 cmH 2 O Assisted breathing, PEEP 6-10 cmH 2 O Assisted breathing, PEEP  10 cmH 2 O OOrgan failure ABCDABCD Lung only Lung + 1 organ Lung + 2 organs Lung +  3 organs CCause 123123 Unknown Direct lung injury Indirect lung injury A Associated diseases 012012 No coexisting disease that will cause death within 5 yr Coexisting disease that will cause death within 5 yr but not within 6 mo Coexisting disease that will cause death within 6 mo Artigas A, et al. Am J Respir Crit Care Med. 1998.

7. ARDSFocalPatchyDiffuse Chest x-ray (zero PEEP) Focal heterogeneous loss of aeration in caudal and dependent lung region Bilateral and diffuse x- ray densities respecting lung apices Bilateral and diffuse hyperdensities “White lungs” Chest CT scan (zero PEEP) Loss of aeration Upper lobes normally aerated despite a regional excess of lung tissue – Lower lobes poorly or non aerated Lower lobes massively nonaerated – The loss of aeration involves partially the upper lobes Massive, diffuse and bilateral non- or poorly aerated lung regions – No normally aerated lung region Response to PEEP ± PEEP <10-12 cmH 2 O ++++ Lung recruitment curve Open lung concept Risk of overinflation of the aerated lung regions ++++ ± Recruitment of non aerated lung unit Low potential for recruitment High potential for recruitment Rouby JJ, et al. Eur Respir J. 2003. Rouby JJ, et al. Anesthesiology. 2004. The ARDS Lung

8. Early phases of ARDS Direct insult of the lung Primary pulmonary ARDS “Indirect” insult of the lung Secondary extrapulmonary ARDS Pathologic changes Lung tissue consolidation Severe intra-alveolar damage (Edema, fibrin, collagen neutrophil aggregates, red cells) Microvascular congestion Interstitial edema Alveolar collapse Less severe alveolar damage End-expiratory lung volume EELV  Static elastance of the total respiratory system Est,rs  Static elastance of the chest wall Est,w / Static lung elastance Est,L  /  /  Intra-abdominal pressure  Response to PEEP Est,rs  [Est,L >> Est,w] Stretching phenomena Est,rs  [Est,L  Est,w] Recruitment of previously closed alveolar spaces Lung recruitment±++++ Gattinoni L, et al. Am J Respir Crit Care Med. 1998. The ARDS Lung

10. FTFT Stress distribution: homogeneous system min max Mead J et al. J. Appl. Physiol. 28(5):596-608 1970 L. Gattinoni, 2003

11. min max Stress distribution: high stiffness zone Mead J et al. J. Appl. Physiol. 28(5):596-608 1970 L. Gattinoni, 2003

12. Copyright ©2008 Canadian Medical Association or its licensors Gattinoni, L. et al. CMAJ 2008;178:1174-1176 Ventilator-induced lung injury is initiated by the application of excessive stress

13. NEJM 2000;342:1334-1349

15. ARDS

16. Ventilator Strategy

17. Ventilator-induced Lung Injury (VILI) Barotrauma Volutrauma Atelectrauma Biotrauma Over Distension Collapse

18. Ventilation-Induced Lung Injury (VILI) Atelectrauma: Repetitive alveolar collapse and reopening of the under- recruited alveoli Volutrauma: Over-distension of normally aerated alveoli due to excessive volume delivery *Dreyfuss: J Appl Physiol 1992 Cytokines, complement, prostanoids, leukotrienes, O 2 - Proteases Biotrauma:

19. Healthy subject In normal healthy volunteers, the P/V curve explore the mechanical properties of the respiratory system (lung + chest wall) ARDS RV, Residual volume; FRC, Functional residual capacity; TLC, Total lung capacity; UIP, Upper inflection point; LIP, Lower inflection point. The critical opening pressure above which most of the collapsed units open up and may be recruited - CLIN Compliance of the intermediate, linear segment of the P/V curve Maggiore SS, et al. Eur Respir J. 2003. Rouby JJ, et al. Eur Respir J. 2003. Respiratory Pressure/Volume (P/V) Curve

20. Ventilator-induced Lung Injury (VILI) Upper Deflection point Lower Inflection point

21. Pressure Volume Normal Early ARDS Late ARDS ARDS: Pressure Volume Curves

22. Courtesy of Dr Neil Macintyre PEEP = 5 mbar Pinsp = 40 mbar

23. Muscedere JG et al. Am J Respir Crit Care Med 1994;149:1327-1334

24. The PEEP Effect NEJM 2006;354:1839-1841

25. Barotrauma

26. Multiple Organ Failure!

27. ARDS: Baby lungs

28. Preventing Overdistention and Collapse Injury “Lung Protective” Ventilation VOLUMEVOLUME VOLUMEVOLUME Pressure Limit Distending Pressure Add PEEP Limit VT

29. Lung Protective Ventilator Protective VenLung Protective Ventilator Strategies Strategies Courtesy of Dr Neil Macintyre P "safe" window zone of overdistension V atelectrauma volutrauma LIP UIP zone of derecruitment and atelectasis DON’T EVEN THINK OF PARKING HERE

30. ARMA TrialInterventionControl TV (4-6 ml/Kg) PEEP 8.5 TV (10-12 ml/Kg) PEEP 8.6

31. Balancing need for support vs distending pressures/FiO2 Crs also better in the HIGH Vt group

32. ARDS Network, 2000: Multicenter, randomized 861 patients Lung-protective ventilation Conventional ventilation Tidal Volume (ml/kg) 612 P plateau <30<50 PEEPProtocolProtocol Actual PEEP 8.19.1 Result (p<0.001) 31.0%39.8% Principle for FiO2 and PEEP Adjustment FiO20.30.40.50.60.70.80.91.0 PEEP55-88-101010-141414-1818-24 NEJM 2000; 342: 1301-1308 Lung-Protective Ventilation

33. Result: –Lower 22% mortality (31% vs 39.8%) –Increase ventilator-free days Lung-Protective Ventilation NEJM 2000; 342: 1301-1308

34. Concerns when using lung- protective strategy… Heterogeneous distribution Hypercapnia Auto-PEEP Sedation and paralysis Patient-ventilator dyssynchrony Increased intrathoracic pressure Maintenance of PEEP

35. What next? Prone position Inhaled nitric oxide High-frequency oscillation ECMO

36. Other Ventilator Strategies Lung recruitment maneuvers Prone positioning High-frequency oscillatory ventilation (HFOV) ECMO

37. Lung Recruitment To open the collapsed alveoli A sustained inflation of the lungs to higher airway pressure and volumes –Ex.: PCV, Pi = 45 cmH2O, PEEP = 5 cmH2O, RR = 10 /min, I : E = 1:1, for 2 minutes NEJM 2006; 354: 1775-1786

38. Lung Recruitment NEJM 2006; 354: 1775-1786

39. Lung Recruitment NEJM 2006; 354: 1775-1786

40. Potentially recruitable (PEEP 5  15 cmH2O) –Increase in PaO2:FiO2 –Decrease in PaCO2 –Increase in compliance The effect of PEEP correlates with the percentage of potentially recruitalbe lung The percentage of recruitable lung correlates with the overall severity of lung injury Lung Recruitment Sensitivity : 71% Specificity : 59% NEJM 2007; 354: 1775-1786

41. The percentage of potentially recruitable lung: –Extremely variable, –Strongly associated with the response to PEEP Not routinely recommended Lung Recruitment

42. Prone Position

43. Mechanisms to improve oxygenation: –Increase in end- expiratory lung volume –Better ventilation- perfusion matching –More efficient drainage of secretions

44. Prone Position Improved gas exchange More uniform alveolar ventilation Recruitment of atelectasis in dorsal regions Improved postural drainage Redistribution of perfusion away from edematous, dependent regions

45. Prone Positioning

46. Prone Position NEJM 2001;345:568-573

47. Prone Position NEJM 2001;345:568-573

48. Improve oxygenation in about 2/3 of all treated patients No improvement on survival, time on ventilation, or time in ICU Might be useful to treat refractory hypoxemia Optimum timing or duration ? Routine use is not recommended Prone Position

49. High-Frequency Oscillatory Ventilation (HFOV)

50. HFV - the “ultimate” lung protective strategy? Over-distended Protected Under-recruit

51. HFOV Frequency: 180-600 breaths/min (3-10Hz)

52. Effect of HFOV on gas exchange in ARDS patients AJRCCM 2002; 166:801-8

53. Survival difference of ARDS patients treated with HFOV or CMV 30-day: P=0.057 90-day: P=0.078 AJRCCM 2002; 166:801-8

54. HFOV Complications: –Recognition of a pneumothorax –Desiccation of secretions –Sedation and paralysis –Lack of expiratory filter Failed to show a mortality benefit Combination with other interventions ? Chest 2007; 131:1907-1916

55. Acute Lung injury Decreased lung compliance results in high airway pressures Low tidal volume 6-8 ml/kg ideal body weight Maintain IPP  30 cm H 2 O PEEP to improve oxygenation

56. Conclusions The only treatment that shows mortality benefit: –lung-protective ventilation strategy –Low tidal volume (6ml/Kg), high PEEP, adequate Pplat (<30 cmH2O) Modalities to improve oxygenation: –Prone position, steroid, fluid treatment, steroid, HFOV, NO Combining other treatments: –Activated protein C, antibiotics, EGDT…etc