Maurizio Cereda, M.D. Dept. of Anesthesiology and Critical Care University of Pennsylvania

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1 Maurizio Cereda, M.D. Dept. of Anesthesiology and Critical Care University of Pennsylvania

2 Disclosures Conflicts of interest: I wish.

3 Goals Definitions Morphology Gas exchange Respiratory mechanics Ventilator Associated Lung Injury Alveolar recruitment

4 What ARDS is about Diffuse alveolar damage Acute onset Fibrotic evolution Multiple causes Matthay MA, Zimmerman GA Am J Respir Cell Mol Biol. 2005;33:319-27

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6 Acute Lung Injury/ARDS AECC 1994 Definitions Bilateral Radiological Infiltrates No evidence of cardiogenic edema ALI: PaO 2 /FiO 2 ratio <300 ARDS: PaO2/FiO2 ratio <200

7 The Berlin Definition The ARDS Definition Task ForceJAMA. 2012;307(23):

8 Response to Ventilator Settings predicts Outcomes 41 ARDS pts screened at baseline and with standardized ventilator settings (PEEP 10, FiO2 1.0) 24 did not meet ARDS criteria with the new settings = 12.5% PaO 2 /FiO 2 = 52.9% Niall D. Ferguson et al. Intensive Care Med (6):1111-6

9 ARDS mortality is decreasing and we are doing a great job PROSEVA Matthay MA et al. J Clin Invest. 2012;122(8):

10 Two-year mortality in Baltimore Needham et al. BMJ Apr 5;344:e2124

11 Goals Definitions Morphology Gas exchange Respiratory mechanics Ventilator Associated Lung Injury Alveolar recruitment

12 Pattern of Gas Distribution in ARDS Alveolar flooding/consolidation Atelectasis Fan, E. et al. JAMA 2005;294:2889

13 Gravity related alveolar collapse

14 Compression Atelectasis NORMAL ARDS All volumes noted at ZEEP Puybasset, Slutsky & Robin AJRCCM 158: 1998

15 Compressive Mechanisms Rouby, JJ et al. Anesthesiology 2004; 101:228

16 Goals Definitions Morphology Gas exchange Respiratory mechanics Ventilator Associated Lung Injury Alveolar recruitment

17 Mechanisms of Gas Exchange Impairment Intrapulmonary Shunt V/Q scatter or mismatch Alveolar dead space Diffusion impairment

18 Gas-Blood Interface O2 CO2

19 V/Q distribution and alveolar gases PCO 2 (mmhg) SHUNT IDEAL 1 V D,alv PO 2 (mmhg)

20 Causes of Intrapulmonary Shunt Alveolar flooding Alveolar debris Atelectasis

21 Effect of shunt on arterial oxygenation FiO 2 =1.0 SO PO

22 Response to 1.0 FiO 2 in ALI and in COPD COPD ALI Time Santos et al. Am. J. Respir. Crit. Care Med.2000, 161 : 26

23 Distribution of Water and Perfusion in Patients with ARDS Water Blood flow Schuster et al. J Nucl Med 2002; 43: 863

24 Why does proning work? Tissue density Blood Flow Schuster et al. J Nucl Med 2002? Gattinoni et al. AJRCCM 2000

25 Effect of Position on V/Q Distribution in Surfactant Deficient Animals Perfusion Ventilation Perfusion Ventilation Perfusion & Ventilation Perfusion & Ventilation Richter et al. Am J Respir Crit Care Med. 2005;172:480

26 Alveolar Dead Space P E CO 2 = 25 P A CO 2 = 50 P A CO 2 = 0 P a CO 2 = 50

27 Dead Space in Acute Respiratory Failure Pulmonary vessel thrombosis Tissue remodeling Pulmonary vasoconstriction Alveolar hyperinflation Arteriole P ALV Venule Decreases efficiency of ventilation Associated with increased mortality Nuckton, T. J. et al. N Engl J Med 2002;346:1281

28 Goals Definitions Radiological morphology Gas exchange pathophysiology Respiratory mechanics Ventilator Associated Lung Injury Alveolar recruitment

29 Basic respiratory mechanics Resistive compartment: resistance Elastic compartment: compliance = ΔV/ ΔP ALV Elastance = ΔP ALV / ΔV Transpulmonary pressure = P ALV - P PL V Paw P plat P PL P ALV

30 Respiratory mechanics in ARDS Low lung capacity Pelosi et al. AJRCCM 1995

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32 Respiratory mechanics in ARDS Stiff lung Stiff chest Pelosi et al. AJRCCM 1995

33 Effect of chest wall on lung distension

34 Pplat does not predict transpulmonary pressure Talmor et al. Crit Care Med 2006 Vol. 34, No

35 Goals Definition Morphology Gas exchange Respiratory mechanics Ventilator Induced Lung Injury Alveolar recruitment

36 Ventilator Induced Lung Injury (VILI)

37 Ventilator Induced Lung Injury (VILI) 0 20 Lung strain/overdistension Atelectrauma Mechano-signaling Inflammatory cascade Local Injury Extrapulmonary injury (?)

38 Barotrauma or volotrauma?

39 Lung strain Inspired volume/lung capacity Mechano-signaling Inflammatory cascade Protti et al. Am J Respir Crit Care Med; 183: , 2011

40 Low vs. high tidal volume in ARDS 50 P= Mortality (Percent) ml/kg IBW 12 ml/kg IBW ARDSnet, NEJM 2000

41 Why we use ideal body weight to set TV Males IBW (kg) = [height (cm) 152.4] Females IBW (kg) = [height (cm) 152.4]

42 Tidal hyperinflation during lung protective ventilation Terragni et. Al. Am J Respir Crit Care Med Vol 175. pp , 2007

43 Is there a 100% safe level of Pplat? 30 cmh2o 30 cmh2o 30 cmh2o

44 Mortality when Pplat is low Brower et al. Am J Respir Crit Care Med 2002;166:

45 The business of recruitment.. Hedenstierna G. Clinical Physiology and Functional Imaging 23 (3),

46 Tidal changes of lung aeration Black: non-aerated Red: poorly aerated White: normo-aeraed

47 The concept of atelectrauma J Halter et al. AJRCC 2002; 167:1620-6

48 Lung aeration and metabolic activity after unilateral surfactant depletion Gas Fraction 18 FDG Uptake DeProst et al. J Appl Physiol 111: , 2011

49 Open up the lung and keep it open!

50 Lost in Translation: Clinical Trials on Alveolar Recruitment ALVEOLI EXPRESS LOV

51 Recruit this!

52 Meta-analysis of three studies on high PEEP Briel M, Meade M, Mercat A, et al. JAMA. 2010;303(9):

53 Prone Positioning in Severe Acute Respiratory Distress Syndrome Guérin C et al. N Engl J Med 2013;368:

54 Standard ventilatory management of ARDS Tidal volume 4-6 ml/kg IBW Pplat < 30 cmh 2 O Accept high PaCO 2 PEEP according to ARDSnet nomograms Goal PaO mmhg/spo % P plat

55 Alveolar recruitability and outcomes in ARDS Gattinoni et al. N Engl J Med 2006;354: Gattinoni L et al. N Engl J Med 2006;354:

56 Open lung ventilation: increased overdistension and strain? Malhotra A. N Engl J Med 2007;357:

57 Lung strain in ARDS Inspired volume/functional residual capacity Harmful threshold Chiumello et al. Am J Respir Crit Care Med 178: , 2008

58 Andreas Güldner, Anesthesiology 2015; 123:00-00

59 Do you choose atelectasis or overdistention?

60 Recruitment comes with a price

61 PEEP and right ventricle Vieillard-Baron Curr Op Crit Care 2003

62 How to individualize ventilator settings?

63 How to individualize ventilator settings?

64 How to individualize ventilator settings?

65 The concept of Driving Pressure Strain TV/FRC CCCCCCCCCC = TT/ΔP Δ P CCCCCCCCCC f(fff) Strain TV/Compliance ΔP

66 Driving Pressure and Survival in the Acute Respiratory Distress Syndrome Marcelo Amato et al. N Engl J Med 2015;372:

67 Driving Pressure and Survival in the Acute Respiratory Distress Syndrome Marcelo Amato et al. N Engl J Med 2015;372:

68 Sepsis increases the sensitivity of the lung to strain PEEP 0 cmh 2 O,VT 30 ml/kg

69 Lung Inhomogeneity in Patients with Acute Respiratory Distress Syndrome Cressoni, Cadringher et al. Am J Respir Crit Care Med, 2014

70 Lung protective ventilation in non- ARDS patients Serpa Neto et al. JAMA. 2012;308(16):

71 A Trial of Intraoperative Low-Tidal Volume Ventilation in Abdominal Surgery Futier et al. N Engl J Med 2013;369:

72 Neil M. Goldenberg, et al. Anesthesiology 2014; 121:

73 Conclusions ARDS is a homogeneous disease with non homogeneous distribution Lung mechanics alterations are related to loss of gas volume ARDS lung should be treated with gentle inflations proportionate to the amount of viable lung tissue Clinical management should be individualized to physiology

74 Influence of VT vs. PEEP on alveolar strain Albaiceta and Blanch Critical Care 2011, 15:304

75 Regional Lung Derecruitment and Inflammation during 16 Hours of Mechanical Ventilation Tucci et al. Anesthesiology 2013; 119:156-65

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80 Do we need more research on VILI?

81 Unresolved mysteries J Appl Physiol published online 12 July 2012 Gerald C. Smaldone and Wayne Mitzner

82 Do we need more research on atelectasis and VILI?

83 High Metabolic Activity in Healthy Parenchyma in ARDS Bellani et al. Am J Respir Crit Care Med , 2011

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