ARDS and VILI CEEA 2015, Kosice Luciano Gattinoni, MD, FRCP Università di Milano Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico Milan, Italy
VILI 3
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
Chest wall elastance Stiff Soft Soft Stiff ELL Ew ELL Ew 25 5 cmh 2 O 15 15 E tot E tot
Driving pressure Drive the lungs Drive the chest wall On the ventilator Transpulmonary pressure Pleural pressure Paw = P L + Ppl
How to measure the pleural pressure
Esophageal and gastric baloon
Anatomical section of a frozen cadaver between the thoracic vertebra 8 and 9 Bo WJ, Wolfman NT, Krueger WA, Meschan I. 1990. Basic Atlas of Sectional Anatomy with Correlated Imaging. 2nd edition; WB Saunders Co. page 99
PES and Ppl 20 15 Ppl 1 Ppl 2 Ppl 3 Non dependent middle dependent Ppl (cmh 2 O) 10 5-5 -5 0 5 10 15 20 PES (cmh 2 O) Inspiratory Expiratory 6 dogs, oleic acid Pelosi et al. Am J Respir Crit Care Med pp 122-130, 2001
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
Clinical equivalents Stress PL transpulmonary pressure Strain V T / FRC The linkage is the specific elastance PL E = lspec * V T FRC Barotrauma Volotrauma
DTranspulmonary Pressure (cm H 2 O) Specific lung elastance in ARDS is normal Control subjects (30) 26 ALI/ARDS patients (50) 24 22 20 18 16 14 12 10 8 0 0.0 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 2.2 2.4 Lung Strain
DTranspulmonary plateau pressue (cmh 2 O) A Surgical control group Medical control group B ALI patients ARDS patients 60 60 50 50 40 40 30 30 20 20 10 10 0 0 10 20 30 40 50 60 0 0 10 20 30 40 50 60 Airway plateau pressure (cmh 2 O) Airway plateau pressure (cmh 2 O) Chiumello et al, Am J Respir Crit Care Med. 2008
%Total Lung Capacity Percentage Resting Biotrauma Stress at rupture 3V 0 100 90 80 40 ALI/ARDS 30 Healthy sbj 20 2V 0 70 60 50 10 0 Specific Lung Elastance 12 (cmh 2 O) V 0 40 0 4 8 12 16 20 24 28 32 36 40 Transpulmonary pressure (PL cmh 2 O)
Peripheral FRC 80% TLC
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)
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)
Time course of ventilator induced lung injury 600 3.0 DLung Weight (g) 500 400 300 200 100 0-100 2.5 2.0 1.5 1.0 Strain (Vt/FRC) -200 0 12 24 36 48 60 Hours of mechanical ventilation 0.5 Protti A. et al. Am J Respir Crit Care Med. 2011 Feb 4.
Stress-strain curve of healthy pigs Stress (PL, cmh2o) 55 50 45 40 35 30 25 20 15 10 5 0 Specific Lung Elastance 5.8 cmh 2 O 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 Strain (dvgas/vgas0) Protti A. et al. Am J Respir Crit Care Med. 2011 Feb 4.
Volumes and Pressures FRC [ml] TLC [ml] TLC/FRC Espec [cmh 2 O] PL to TLC [cmh 2 O] MICE 0.3-0.5 1-1.5 2-2.3?? RATS 2.5-3 10 2-3 4 8-12 PIGS 300 780 2.6 6 15.6 MEN 2200 7000 2.2 12 26.4
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. 2013 Feb 4.
Tidal Strain P*ΔV = Energy Input Dissipated Surface Tension Sliding EM Opening and Closing Undissipated Elastic System Continuous Strain PEEP *ΔV = Energy Input = 0
ZEEP 600 Total Inspiratory Volume Volume 400 200 EXAPLES OF ENERGY COMPUTATIONS AT DIFFERENT PRESSURES 0 ZEEP Peak Pressure 0 10 20 30 Pressure 1200 1000 Total Inspiratory Volume LOW PEEP 1200 1000 Total Inspiratory Volume HIGH PEEP 800 800 PEEP Volume Volume 600 PEEP Volume Volume 600 400 400 200 200 0 PEEP Peak Pressure 0 PEEP Peak Pressure 0 10 20 30 40 50 60 Pressure 0 10 20 30 40 Pressure
76 PIGS 10 Total Peak Power SURVIVED Total Peak Power DEAD Dynamic Peak Power SURVIVED Dynamic Peak Power DEAD 8 Power (Watt) 6 4 2 0 SURVIVED DEAD SURVIVED DEAD SURVIVED DEAD 28 1 18 20 3 6 LOW INTERMEDIATE HIGH
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
Baseline
After 12 hours
After 45 hours
After 50 hours!
Whole lung edema One-field edema Isolated densities Baseline 0 5 10 15 20 25 Delivered dynamic transpulmonary energy load (J/min)
Volume (ml) Volume (ml) 800 600 400 200 0 800 RR3 RR6 RR9 RR12 RR15 Paw (cmh 2 O) 0 10 20 30 40 50 60 70 Start 600 400 End 200 0 Paw (cmh 2 O) 0 10 20 30 40 50 60 70
Therefore VILI arises from mechanical power: PL TV RR
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
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
Stress distribution: homogeneous system VILI 29 F T min max Mead J et al. J. Appl. Physiol. 28(5):596-608 1970
Stress distribution: VILI 30 high stiffness zone min max Mead J et al. J. Appl. Physiol. 28(5):596-608 1970
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. 2014 Jan 15;189(2):149-58
Average ratio in normal subjects : 1.37±0.15 Healthy subject Moderate ARDS Severe ARDS
Lung expansion from F a gas-free state F F V V V Homogeneous lung F F F V V STRESS RISER
Stress risers and shape
Lung dishomogeneity and ARDS Mild (N=82) Moderate (N=71) Severe (N=12) P Dishomogeneity 1.49 ± 0.17 1.58 ± 0.29 1.75 ± 0.41 0.03 Dishomogeneity 2/3 1.30 ± 0.31 1.36 ± 0.44 1.45 ± 0.55 Extent 0.3 ± 0.1 0.36 ± 0.16 0.46 ± 0.18 0.01 Intensity 2.69 ± 0.27 2.76 ± 0.27 2.84 ± 0.41 0.31 Intensity 2/3 1.93 ± 0.42 1.97 ± 0.42 2.01 ± 0.55 Courtesy of Dr. Cressoni
Hypothesis Lesions should first occur where physiological stress risers are located
KIND OF DENSITIES Subpleural 61 [57-76]% Peribronchial 19 [11-23]% Courtesy of dr. Cressoni M. Parenchymal 19 [6-25]%
Before appearance first new densities END EXPIRATION END INSPIRATION TIME 1: 5.7±6.5 hours Courtesy of dr. Cressoni M.
First CT scan with new densities END EXPIRATION END INSPIRATION TIME 2: 8.4±6.3 hours Courtesy of dr. Cressoni M.
Last CT scan with distinguishable densities END EXPIRATION END INSPIRATION TIME 3: 15±12 hours Courtesy of dr. Cressoni M.
First CT scan with one-field edema END EXPIRATION END INSPIRATION TIME 4: 18±11 hours Courtesy of dr. Cressoni M.
First CT scan with all-field edema END EXPIRATION END INSPIRATION TIME 5: 20±11 hours Courtesy of dr. Cressoni M.
Severity trend VILI cumulative time course T4-5 + Gas Exchange T3 + Lung mechanics T2 CT scan only 0 5 10 15 20 25 Hours Courtesy of dr. Cressoni M.
CT SCAN INFLATION LUNG IMAGING INHOMOGENEITY PET FDG UPTAKE
Ki/lung inhomogeneity interaction and gas/tissue composition MILD MODERATE SEVERE
Prevention of VILI Decrease mechanical power Tidal Volume Pressure variation Respiratory rate Flow Increasing Homogeneity PEEP Prone Position
Lung protective strategy Less energy + More homogeneous lung
Lung protective strategy recipe: the ingredients Assess severity Select Tidal Volume Select PEEP Select RR-IE Watch hemodynamics
Lung and gasless tissue weight in acute respiratory failure n=39 n=34 n=34 n=34 lung tissue weight [gr] 3500 3000 2500 total lung tissue non-aerated lung tissue 2000 1500 1000 500 0 * * * * * * 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.
Severity Edema Baby Lung Gas Exchange Lung Mechanics
Severity trend VILI cumulative time course T4-5 + Gas Exchange T3 + Lung mechanics T2 CT scan only 0 5 10 15 20 25 Hours Courtesy of dr. Cressoni M.
PaO2/FiO2 at 5 cmh 2 O PEEP 350 300 250 200 150 100 50 139 ARDS patients b[0] 235 b[1] -0.055 r 0.226 P <0.0001 0 500 1000 1500 2000 2500 3000 3500 Lung weight at 5 cmh 2 O PEEP (grams)
Assess severity The simplest P/F at 5 cmh 2 O PEEP (300, 200, 100) Berlin definition
Lung protective strategy recipe: the ingredients Assess severity Select Tidal Volume Select PEEP Select RR-IE Watch hemodynamics
Lung gas volume and body weight Total gas volume at 5 cmh 2 O PEEP 5000 Mild Moderate 4000 Severe 3000 2000 1000 0 P=0.025 R 2 = 0.0284 40 50 60 70 80 90 Ideal body weight (kg)
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
Select tidal volume The simplest Tidal volume 6 ml/kg IBW (check plateau pressure)
Lung protective strategy recipe: the ingredients Assess severity Select Tidal Volume Select PEEP Select RR-IE Watch hemodynamics
Frequency [no. of patients] Figure 1 Potential for lung recruitment 24 22 20 18 16 14 12 10 8 6 4 2 0 5 ± 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):1775-86
PEEP selection methods comparison CT scan derived PEEP Esophageal Pressure The Stress Index method The ExPress study The LOVs study
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. 2014 Feb;42(2):252-64
Superimposed pressure Superimposed pressure The same transpulmonary pressure is required to keep the lung open!!!
Select PEEP The simplest Mild ARDS: below 10 cmh O 2 Moderate: 10-15 cmh O 2 Severe: >15 cmh O 2
ARDS Mild Moderate Severe 300 200 100 Paw plat/pl plat 30 cmh 2 O/ 20 cmh 2 O Tidal Volume/strain 6 ml/kg IBW/ 1.5-2 PEEP 10 cmh 2 O > 15 cmh 2 O ECMO ALTERNATIVE TREATMENTS ECCO 2 -R Neuromusc.Blockade Prone Position HFO
Thank you for your attention Grazie