ARDS and VILI

Luciano Gattinoni, MD, FRCP

Università di Milano

Fondazione IRCCS Ca’ Granda

Ospedale Maggiore Policlinico

Milan, Italy

CEEA 2015, Kosice

VILI 3

VILIWhat is due to the ventilator/ventilation:

Tidal Volume

Pressure change

Flow rate

Respiratory rate

EnergyPower

What is due to the lung:

Lung inhomogeneity

Stress risers

Chest wall elastance

EtotEtot

cmH2O

StiffStiff

2525

LEEL

“Soft”“Soft”

EwEw

55

StiffStiff

1515

EwEw

“Soft”“Soft”

1515

LEEL

EtottotE

Driving pressure

On the ventilator Paw

Drive the lungs

Drive the chest

wall

Transpulmonary

pressure

Pleural pressure

PL

Ppl

=

+

How to

measure the

pleural

pressure

Esophageal and gastric baloon

Bo WJ, Wolfman NT, Krueger WA, Meschan I. 1990.

Basic Atlas of Sectional Anatomy with Correlated Imaging. 2nd edition; WB Saunders Co. page 99

Anatomical section of a frozen cadaver between the thoracic vertebra 8 and 9

PES (cmH2O)

Pp

l (c

mH

2O)

PES and Ppl

6 dogs,oleic acid Pelosi et al. Am J Respir Crit Care Med pp 122-130, 2001

5 10 15 20-50

-5

5

10

15

20

Inspiratory

Expiratory

Ppl1 Non dependent

Ppl3dependent

middlePpl2

Stress and Strain

F

DLa

b

L0

S=a*b

Stress

Strain

s=F/S

e=DL/L0

Transpulmonary pressure

VT/EELV

Clinical equivalents

Stress PL transpulmonary pressure

Strain VT / FRC

The linkage is the specific elastance

PL VT

FRC= *

Elspec

Barotrauma Volotrauma

Specific lung elastance in ARDS is

normal

Lung Strain

0.0 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 2.2 2.4DT

ran

spulm

on

ary

Pre

ssure

(cm

H2O

)

0

8

10

12

14

16

18

20

22

24

26 ALI/ARDS patients (50)Control subjects (30)

Airway plateau pressure (cmH2O)

0 10 20 30 40 50 60

0

10

20

30

40

50

60

Airway plateau pressure (cmH2O)

0 10 20 30 40 50 60

DT

ran

spulm

on

ary

pla

teau

pre

ssue

(cm

H2O

)

0

10

20

30

40

50

60

A

Surgical control group

Medical control group ARDS patients

ALI patients

B

Chiumello et al, Am J Respir Crit Care Med. 2008

Transpulmonary pressure (PL cmH2O)

0 4 8 12 16 20 24 28 32 36 40

40

50

60

70

80

90

100

%T

ota

l L

ung C

apac

ity

V0

2V0

3V0

Resting Biotrauma Stress at rupture

Specific Lung Elastance

12 (cmH2O)

Per

cen

tage

0

10

20

30

40 ALI/ARDS

Healthy sbj

FRC 80% TLC

Peripheral

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)

AS =alveolar sac

P=pleura

V=blood vessel

Toshima et al. Arch Histol Cytol. 67(1):31-40 (2004)

Collagen fiber network in rat lung

Collapsed InflatedAE =alveolar entrances

(scale bar 100 μm) Toshima et al. Arch Histol Cytol. 67(1):31-40 (2004)

Time course of ventilator induced lung injury

Protti A. et al. Am J Respir Crit Care Med. 2011 Feb 4.

Hours of mechanical ventilation

0 12 24 36 48 60

DL

un

g W

eigh

t (g

)

-200

-100

0

100

200

300

400

500

600

Str

ain (

Vt/

FR

C)

0.5

1.0

1.5

2.0

2.5

3.0

Strain (dVgas/Vgas0)

0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0

Str

ess

(PL

, cm

H2

O)

0

5

10

15

20

25

30

35

40

45

50

55

Stress-strain curve of healthy pigs

Specific Lung

Elastance

5.8 cmH2O

Protti A. et al. Am J Respir Crit Care Med. 2011 Feb 4.

Volumes and Pressures

RATS

PIGS

MEN

4

6

12

MICE ?

Espec

[cmH2O]

FRC

[mL]

TLC

[mL]TLC/FRC

PL to TLC

[cmH2O]

2.5-3

300

2200

0.3-0.5

10

780

7000

1-1.5

2-3

2.6

2.2

2-2.3

8-12

15.6

26.4

?

TLC

FRC

Lun

g V

olu

me

VT 100%

VPEEP 0%

VT 75%

VPEEP 25%

VT 50%

VPEEP 50%

VT 25%

VPEEP 75%

Protti et al. Crit Care Med. 2013 Feb 4.

Tidal Strain

P*ΔV = Energy Input

Dissipated Undissipated

Surface Tension

Sliding EM

Opening and ClosingElastic System

PEEP *ΔV = Energy Input = 0

Continuous Strain

Pressure

0 10 20 30 40 50 60

Vo

lum

e

0

200

400

600

800

1000

1200

PE

EP

Pea

k

Pre

ssu

re

PEEP Volume

Total Inspiratory Volume

Pressure

0 10 20 30

Vo

lum

e

0

200

400

600Z

EE

P

Pea

k

Pre

ssu

re

Total Inspiratory Volume

Pressure

0 10 20 30 40

Vo

lum

e

0

200

400

600

800

1000

1200

PE

EP

Pea

k

Pre

ssu

re

PEEP Volume

Total Inspiratory Volume

EXAPLES OF ENERGY

COMPUTATIONS AT

DIFFERENT PRESSURES

ZEEP

LOW PEEP HIGH PEEP

76 PIGS

Total Peak Power SURVIVEDTotal Peak Power DEAD

Dynamic Peak Power SURVIVED Dynamic Peak Power DEAD

SURVIVEDDEAD SURVIVED DEAD SURVIVEDDEAD

Pow

er (

Wat

t)

0

2

4

6

8

10

LOW INTERMEDIATE HIGH

28 1 18 20 3 6

Tidal volume 38 ml/KgPlateau pressure 27 cmH2OLethal 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!

Delivered dynamic transpulmonary energy load (J/min)

0 5 10 15 20 25

Baseline

Isolated

densities

One-field

edema

Whole lung

edema

Volu

me

(ml)

0 10 20 30 40 50 60 70

0

200

400

600

800

Paw (cmH2O)

Volu

me

(ml)

0 10 20 30 40 50 60 70

0

200

400

600

800

Paw (cmH2O)

Start

End

RR3

RR6

RR9

RR12

RR15

Therefore VILI arises from

mechanical power:

PL × TV × RR

VILIWhat is due to the ventilator/ventilation:

Tidal Volume

Pressure change

Flow rate

Respiratory rate

EnergyPower

What is due to the lung:

Lung inhomogeneity

Stress risers

RUPTURE

HOMOGENEOUS

SYSTEM

L0+DLRUPTURE

F

L0+DLHOMOGENEOUS

F

L0+DLINCLUSION

F

f=F/3

f=F/3

f=F/3

f=F/2

f=F/2

f=0

f<F/3

f<F/3

f>>F/3

L. Gattinoni, 2003

VILI 28

FT

Stress distribution:

homogeneous system

min max

Mead J et al. J. Appl. Physiol. 28(5):596-608 1970

VILI 29

min max

Stress distribution:

high stiffness zone

Mead J et al. J. Appl. Physiol. 28(5):596-608 1970

VILI 30

Voxel

Vgas

Weighted gas ratio = Vgas1/Vgas0 * fraction of tissue

Gas fraction = Vgas0/Vvoxel

Cressoni et al. Am J Respir Crit Care Med. 2014 Jan 15;189(2):149-58

Healthy subject

Moderate ARDS

Severe ARDS

Average ratio in normal subjects : 1.37±0.15

F

V

VV

F F

V

F

F

F

V STRESS RISER

Homogeneous lung

Lung expansion from

a gas-free state

Stress risers and shape

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

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

Courtesy of Dr. Cressoni

Lung dishomogeneity and ARDS

Dishomogeneity2/3 1.30 ± 0.31 1.36 ± 0.44 1.45 ± 0.55

Intensity2/3 1.93 ± 0.42 1.97 ± 0.42 2.01 ± 0.55

Hypothesis

Lesions should first occur where

physiological stress risers are located

Subpleural

61 [57-76]%

Peribronchial

19 [11-23]%

Parenchymal

19 [6-25]%

KIND OF DENSITIES

Courtesy of dr. Cressoni M.

Before appearance first new densities

TIME 1: 5.7±6.5 hours

END EXPIRATION END INSPIRATION

Courtesy of dr. Cressoni M.

First CT scan with new densities

TIME 2: 8.4±6.3 hours

END EXPIRATION END INSPIRATION

Courtesy of dr. Cressoni M.

Last CT scan with distinguishable densities

TIME 3: 15±12 hours

END EXPIRATION END INSPIRATION

Courtesy of dr. Cressoni M.

First CT scan with one-field edema

TIME 4: 18±11 hours

END EXPIRATION END INSPIRATION

Courtesy of dr. Cressoni M.

First CT scan with all-field edema

TIME 5: 20±11 hours

END EXPIRATION END INSPIRATION

Courtesy of dr. Cressoni M.

Hours0 5 10 15 20 25

Sev

erit

y t

rend

CT scan only

+ Lung mechanics

+ Gas Exchange

T2

T3

T4-5

VILI cumulative time course

Courtesy of dr. Cressoni M.

PET

FDG UPTAKE

CT SCAN

INFLATION INHOMOGENEITY

LUNG IMAGING

Ki/lung inhomogeneity interaction and gas/tissue

composition

MILD

MODERATE

SEVERE

Prevention of VILI

Decrease

mechanical power

Increasing

Homogeneity

Tidal Volume

Pressure variation

Respiratory rate

Flow

PEEP

Prone Position

Lung protective strategy

Less energy

+

More homogeneous lung

Assess severity

Select Tidal Volume

Select PEEP

Select RR-IE

Watch hemodynamics

Lung protective strategy recipe:

the ingredients

lung tissue

weight [gr]

0

500

1000

1500

2000

2500

3000

3500

Healthy

lungs

Unilateral

pneumonia

ALI/ARDS:

lower-potential

for lung

recruitment

*°

*°

total lung tissuenon-aerated lung tissue

*

**

*

ALI/ARDS:

higher-potential

for lung

recruitment

* P<0.01 vs. patients with healthy lungs, ° P<0.01 vs. other groups.

n=39 n=34 n=34 n=34

Lung and gasless tissue weight in acute respiratory failure

Submitted for publication

Edema↑ Baby Lung↓

Gas Exchange↓ Lung Mechanics↓

Severity

Hours0 5 10 15 20 25

Sev

erit

y t

rend

CT scan only

+ Lung mechanics

+ Gas Exchange

T2

T3

T4-5

VILI cumulative time course

Courtesy of dr. Cressoni M.

139 ARDS patients

Lung weight at 5 cmH2O PEEP (grams)

500 1000 1500 2000 2500 3000 3500

PaO

2/F

iO2

at

5 c

mH

2O

PE

EP

0

50

100

150

200

250

300

350b[0]235

b[1]-0.055

r ˛0.226

P <0.0001

Assess severity

The simplest

P/F at 5 cmH2O PEEP

(300, 200, 100)

Berlin definition

Assess severity

Select Tidal Volume

Select PEEP

Select RR-IE

Watch hemodynamics

Lung protective strategy recipe:

the ingredients

Ideal body weight (kg)

40 50 60 70 80 90

To

tal

gas

vo

lum

e at

5 c

mH

2O

PE

EP

0

1000

2000

3000

4000

5000 Mild

ModerateSevere

Lung gas volume and body weight

P=0.025

R2 = 0.0284

The ARDS lung is small and not stiff

Normal VT

FRC=

500 ml

2500 ml= 0.2

ARDS VT

FRC=

500 ml

500 ml= 1

Select tidal volume

The simplest

Tidal volume

6 mL/kg IBW

(check plateau pressure)

Assess severity

Select Tidal Volume

Select PEEP

Select RR-IE

Watch hemodynamics

Lung protective strategy recipe:

the ingredients

potential for lung recruitment [% total lung weight]

Fre

quen

cy [

no. of

pat

ients

]

0

2

4

6

8

10

12

14

16

18

20

22

24

Figure 1

ALI patients

ARDS patients

higher

21 ± 10%

(374 ± 236 grams)

lower

5 ± 4%

(59 ± 51 grams)

Potential for lung recruitment

Gattinoni L, Caironi P, Cressoni M, Chiumello D, Ranieri VM, Quintel M,

Russo S, Cornejo R, Bugedo G, NEJM 2006, 354(17):1775-86

Esophageal Pressure

The Stress Index method

The ExPress study

The LOVs study

CT scan derived PEEP

PEEP selection methods comparison

8±2 $ 11±3 $ 15±3

14±2 * 14±3 * 16±3

11±2 14±3 * 14±3

13±3 * 12±4 13±4

Mild

(n=7)

Moderate

(n=33)

Severe

(n=11)

p (method) <0.001

p (classification according to Berlin definition) 0.02

p (interaction) 0.01

PEEP (cmH2O)

LOV

ExPress

Stress Index

Esophageal

pressure

$ p<0.05 vs severe ARDS

* p<0.05 vs LOV selection method

ARDS

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

cmH2O

Moderate: 10-15 cmH2O

Severe: >15 cmH2O

Mild Moderate Severe

300 200 100

ALTERNATIVE

TREATMENTS

ECMO

ECCO2-R

Neuromusc.Blockade

Prone Position

Paw plat/PL plat ≤ 30 cmH2O/≤ 20 cmH2O

Tidal Volume/strain 6 ml/kg IBW/≤ 1.5-2

PEEP ≈ 10 cmH2O > 15 cmH2O

ARDS

HFO

Thank you for your attention

Grazie