CEEA 2015, Kosice Luciano Gattinoni, MD, FRCP Università di Milano Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico Milan, Italy

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1 ARDS and VILI CEEA 2015, Kosice Luciano Gattinoni, MD, FRCP Università di Milano Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico Milan, Italy

2

3 VILI 3

4 VILI What is due to the ventilator/ventilation: Tidal Volume Pressure change Flow rate Respiratory rate Energy Power What is due to the lung: Lung inhomogeneity Stress risers

5 Chest wall elastance Stiff Soft Soft Stiff ELL Ew ELL Ew 25 5 cmh 2 O E tot E tot

6 Driving pressure Drive the lungs Drive the chest wall On the ventilator Transpulmonary pressure Pleural pressure Paw = P L + Ppl

7 How to measure the pleural pressure

8 Esophageal and gastric baloon

9 Anatomical section of a frozen cadaver between the thoracic vertebra 8 and 9 Bo WJ, Wolfman NT, Krueger WA, Meschan I Basic Atlas of Sectional Anatomy with Correlated Imaging. 2nd edition; WB Saunders Co. page 99

10 PES and Ppl Ppl 1 Ppl 2 Ppl 3 Non dependent middle dependent Ppl (cmh 2 O) PES (cmh 2 O) Inspiratory Expiratory 6 dogs, oleic acid Pelosi et al. Am J Respir Crit Care Med pp , 2001

11 Stress and Strain F b L 0 DL a S=a*b Stress Strain s=f/s e=dl/l 0 Transpulmonary pressure V T /EELV

12 Clinical equivalents Stress PL transpulmonary pressure Strain V T / FRC The linkage is the specific elastance PL E = lspec * V T FRC Barotrauma Volotrauma

13 DTranspulmonary Pressure (cm H 2 O) Specific lung elastance in ARDS is normal Control subjects (30) 26 ALI/ARDS patients (50) Lung Strain

14 DTranspulmonary plateau pressue (cmh 2 O) A Surgical control group Medical control group B ALI patients ARDS patients Airway plateau pressure (cmh 2 O) Airway plateau pressure (cmh 2 O) Chiumello et al, Am J Respir Crit Care Med. 2008

15 %Total Lung Capacity Percentage Resting Biotrauma Stress at rupture 3V ALI/ARDS 30 Healthy sbj 20 2V Specific Lung Elastance 12 (cmh 2 O) V Transpulmonary pressure (PL cmh 2 O)

16 Peripheral FRC 80% TLC

17 AS =alveolar sac P=pleura V=blood vessel Continuum of elastin fiber network (scale bar 200 μm) Elastin fiber network in the outer surface of the pleura (scale bar 10 μm) Elastin fiber network in the respiratory bronchioli (RB) and in the alveolar duct (AD) (scale bar 200 μm) Toshima et al. Arch Histol Cytol. 67(1):31-40 (2004)

18 Collagen fiber network in rat lung Collapsed Inflated AE =alveolar entrances (scale bar 100 μm) Toshima et al. Arch Histol Cytol. 67(1):31-40 (2004)

19 Time course of ventilator induced lung injury DLung Weight (g) Strain (Vt/FRC) Hours of mechanical ventilation 0.5 Protti A. et al. Am J Respir Crit Care Med Feb 4.

20 Stress-strain curve of healthy pigs Stress (PL, cmh2o) Specific Lung Elastance 5.8 cmh 2 O Strain (dvgas/vgas0) Protti A. et al. Am J Respir Crit Care Med Feb 4.

21 Volumes and Pressures FRC [ml] TLC [ml] TLC/FRC Espec [cmh 2 O] PL to TLC [cmh 2 O] MICE ?? RATS PIGS MEN

22 Lung Volume TLC FRC VT 100% V PEEP 0% VT 75% V PEEP 25% VT 50% V PEEP 50% VT 25% V PEEP 75% Protti et al. Crit Care Med Feb 4.

23 Tidal Strain P*ΔV = Energy Input Dissipated Surface Tension Sliding EM Opening and Closing Undissipated Elastic System Continuous Strain PEEP *ΔV = Energy Input = 0

24 ZEEP 600 Total Inspiratory Volume Volume EXAPLES OF ENERGY COMPUTATIONS AT DIFFERENT PRESSURES 0 ZEEP Peak Pressure Pressure Total Inspiratory Volume LOW PEEP Total Inspiratory Volume HIGH PEEP PEEP Volume Volume 600 PEEP Volume Volume PEEP Peak Pressure 0 PEEP Peak Pressure Pressure Pressure

25 76 PIGS 10 Total Peak Power SURVIVED Total Peak Power DEAD Dynamic Peak Power SURVIVED Dynamic Peak Power DEAD 8 Power (Watt) SURVIVED DEAD SURVIVED DEAD SURVIVED DEAD LOW INTERMEDIATE HIGH

26 Tidal volume 38 ml/kg Plateau pressure 27 cmh 2 O Lethal in 54 hours 15 breaths/min but RESPIRATORY RATE - 3 breaths/min - 6 breaths/min - 9 breaths/min - 12 breaths/min - 15 breaths/min

27 Baseline

28 After 12 hours

29 After 45 hours

30 After 50 hours!

31 Whole lung edema One-field edema Isolated densities Baseline Delivered dynamic transpulmonary energy load (J/min)

32 Volume (ml) Volume (ml) RR3 RR6 RR9 RR12 RR15 Paw (cmh 2 O) Start End Paw (cmh 2 O)

33 Therefore VILI arises from mechanical power: PL TV RR

34 VILI What is due to the ventilator/ventilation: Tidal Volume Pressure change Flow rate Respiratory rate Energy Power What is due to the lung: Lung inhomogeneity Stress risers

35 f=f/3 VILI 28 HOMOGENEOUS SYSTEM F f=f/3 f=f/3 L 0 +DL HOMOGENEOUS f<f/3 F f>>f/3 f<f/3 L 0 +DL INCLUSION RUPTURE F f=f/2 f=0 f=f/2 L. Gattinoni, 2003 L 0 +DL RUPTURE

36 Stress distribution: homogeneous system VILI 29 F T min max Mead J et al. J. Appl. Physiol. 28(5):

37 Stress distribution: VILI 30 high stiffness zone min max Mead J et al. J. Appl. Physiol. 28(5):

38 Voxel Vgas Gas fraction = V gas0 /V voxel Weighted gas ratio = V gas1 /V gas0 * fraction of tissue Cressoni et al. Am J Respir Crit Care Med Jan 15;189(2):149-58

39 Average ratio in normal subjects : 1.37±0.15 Healthy subject Moderate ARDS Severe ARDS

40 Lung expansion from F a gas-free state F F V V V Homogeneous lung F F F V V STRESS RISER

41 Stress risers and shape

42 Lung dishomogeneity and ARDS Mild (N=82) Moderate (N=71) Severe (N=12) P Dishomogeneity 1.49 ± ± ± Dishomogeneity 2/ ± ± ± 0.55 Extent 0.3 ± ± ± Intensity 2.69 ± ± ± Intensity 2/ ± ± ± 0.55 Courtesy of Dr. Cressoni

43

44 Hypothesis Lesions should first occur where physiological stress risers are located

45 KIND OF DENSITIES Subpleural 61 [57-76]% Peribronchial 19 [11-23]% Courtesy of dr. Cressoni M. Parenchymal 19 [6-25]%

46 Before appearance first new densities END EXPIRATION END INSPIRATION TIME 1: 5.7±6.5 hours Courtesy of dr. Cressoni M.

47 First CT scan with new densities END EXPIRATION END INSPIRATION TIME 2: 8.4±6.3 hours Courtesy of dr. Cressoni M.

48 Last CT scan with distinguishable densities END EXPIRATION END INSPIRATION TIME 3: 15±12 hours Courtesy of dr. Cressoni M.

49 First CT scan with one-field edema END EXPIRATION END INSPIRATION TIME 4: 18±11 hours Courtesy of dr. Cressoni M.

50 First CT scan with all-field edema END EXPIRATION END INSPIRATION TIME 5: 20±11 hours Courtesy of dr. Cressoni M.

51 Severity trend VILI cumulative time course T4-5 + Gas Exchange T3 + Lung mechanics T2 CT scan only Hours Courtesy of dr. Cressoni M.

52 CT SCAN INFLATION LUNG IMAGING INHOMOGENEITY PET FDG UPTAKE

53 Ki/lung inhomogeneity interaction and gas/tissue composition MILD MODERATE SEVERE

54 Prevention of VILI Decrease mechanical power Tidal Volume Pressure variation Respiratory rate Flow Increasing Homogeneity PEEP Prone Position

55 Lung protective strategy Less energy + More homogeneous lung

56 Lung protective strategy recipe: the ingredients Assess severity Select Tidal Volume Select PEEP Select RR-IE Watch hemodynamics

57 Lung and gasless tissue weight in acute respiratory failure n=39 n=34 n=34 n=34 lung tissue weight [gr] total lung tissue non-aerated lung tissue * * * * * * Healthy lungs Unilateral pneumonia ALI/ARDS: lower-potential for lung recruitment ALI/ARDS: higher-potential for lung recruitment Submitted for publication * P<0.01 vs. patients with healthy lungs, P<0.01 vs. other groups.

58 Severity Edema Baby Lung Gas Exchange Lung Mechanics

59 Severity trend VILI cumulative time course T4-5 + Gas Exchange T3 + Lung mechanics T2 CT scan only Hours Courtesy of dr. Cressoni M.

60 PaO2/FiO2 at 5 cmh 2 O PEEP ARDS patients b[0] 235 b[1] r P < Lung weight at 5 cmh 2 O PEEP (grams)

61 Assess severity The simplest P/F at 5 cmh 2 O PEEP (300, 200, 100) Berlin definition

62 Lung protective strategy recipe: the ingredients Assess severity Select Tidal Volume Select PEEP Select RR-IE Watch hemodynamics

63 Lung gas volume and body weight Total gas volume at 5 cmh 2 O PEEP 5000 Mild Moderate 4000 Severe P=0.025 R 2 = Ideal body weight (kg)

64 The ARDS lung is small and not stiff Normal V T FRC = 500 ml 2500 ml = 0.2 ARDS V T FRC = 500 ml 500 ml = 1

65 Select tidal volume The simplest Tidal volume 6 ml/kg IBW (check plateau pressure)

66 Lung protective strategy recipe: the ingredients Assess severity Select Tidal Volume Select PEEP Select RR-IE Watch hemodynamics

67 Frequency [no. of patients] Figure 1 Potential for lung recruitment ± 4% (59 ± 51 grams) lower 21 ± 10% (374 ± 236 grams) higher ALI patients ARDS patients potential for lung recruitment [% total lung weight] Gattinoni L, Caironi P, Cressoni M, Chiumello D, Ranieri VM, Quintel M, Russo S, Cornejo R, Bugedo G, NEJM 2006, 354(17):

68 PEEP selection methods comparison CT scan derived PEEP Esophageal Pressure The Stress Index method The ExPress study The LOVs study

69 PEEP (cmh 2 O) Mild (n=7) ARDS Moderate (n=33) Severe (n=11) LOV ExPress 8±2 $ 11±3 $ 15±3 14±2 * 14±3 * 16±3 Stress Index Esophageal pressure 11±2 14±3 * 14±3 13±3 * 12±4 13±4 $ p<0.05 vs severe ARDS * p<0.05 vs LOV selection method p (method) <0.001 p (classification according to Berlin definition) 0.02 p (interaction) 0.01 Crit Care Med Feb;42(2):252-64

70 Superimposed pressure Superimposed pressure The same transpulmonary pressure is required to keep the lung open!!!

71 Select PEEP The simplest Mild ARDS: below 10 cmh O 2 Moderate: cmh O 2 Severe: >15 cmh O 2

72 ARDS Mild Moderate Severe Paw plat/pl plat 30 cmh 2 O/ 20 cmh 2 O Tidal Volume/strain 6 ml/kg IBW/ PEEP 10 cmh 2 O > 15 cmh 2 O ECMO ALTERNATIVE TREATMENTS ECCO 2 -R Neuromusc.Blockade Prone Position HFO

73 Thank you for your attention Grazie