Dissecting VILI from ARDS

Luciano Gattinoni, MD, FRCP

Università di Milano

Fondazione IRCCS Ca’ Granda

Ospedale Maggiore Policlinico

Milan, Italy

2013, Toronto

Collagen and Elastin

1000

50

ST

RE

SS

(K

Pa)

STRAIN (%)

40 80

Elastin 10%

Collagen 2%

If empty zone (air)

to full zone ratio 100:1

Stress failure

100cmH2O

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

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

Hours of mechanical ventilation

0 12 24 36 48 60

L

un

g W

eig

ht

(g)

-200

-100

0

100

200

300

400

500

600

Str

ain

(V

t/F

RC

)

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.

VT/Kg (mL)

0 5 10 15 20 25 30 35 40 45 50

0

10

20

30

40

50

60

70

80

90

100

110

120

man

rat

rabbit mouse

Mercer RR. Et al. J Appl Physiol 1994 Sep;77(3):1060-66

Str

ain

in

dex

at

10m

L/K

g

1

2.13

3.08 3.18

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

un

g C

ap

acit

y

0.0

1.0

2.0

Resting Biotrauma Stress at rupture

Agostoni, Mead,

Weibel,

Gattinoni

Specific Lung Elastance

12 (cmH2O)

1.5

0.5

Strain

1 2 3

V V

V V

Lung expansion/gas-free state

STRESS RISER=(10/1)2/3 = 4.64

10

1

Mead J J Appl Physiol. 1970 May;28(5):596-608.

Voxel

Vgas

Weighted gas ratio = Vgas1/Vgas0 * fraction of tissue

Gas fraction = Vgas0/Vvoxel

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

Healthy subject

Moderate ARDS

Severe ARDS

Average ratio in normal subjects : 1.37±0.15

How do stress and

strain cause VILI?

Energy load into ventilatable

lung structures

Tidal Strain

P*ΔV = Energy Input

Dissipated Undissipated

Surface Tension

Sliding EM

Opening and Closing Elastic System

PEEP *ΔV = Energy Input = 0

Continuous Strain

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.

Vo

lum

e

Pressure

Volume-Pressure curve and energy (PΔV)

Recovered

Dissipated

Where is the

energy

dissipated?

Gas motion (resistance

etc.)

Extracellular sliding

(stress relaxation)

Surface tension

Opening/Closing

Degradation of 10% Vistanex 100 in cetane under laminar flow conditions. The

data show a linear decrease of molecular weight with increasing shear stress,

independent of the temperature. Reprinted with permission from ref 46.

Copyright 1959, American Chemical Society, Washington, DC.

Beyer MK, Clausen-Schaumann H. Chem Rev. 2005 Aug;105(8):2921-48.

Mechanical polymer fragmentation

O’Neill et al. Nature Medicine 11, 1161 - 1162 (2005)

Healthy Pig

Airway pressure (cmH2O)

0 5 10 15 20 25 30 35 40

Infl

ated

Volu

me

(mL

)

0

20

40

60

80

100

120

140

160

180

200

Dissipated Energy

1316 cmH2O*mL 1160 cmH2O*mL (-12%) 1478 cmH2O*mL (+12%) 1960 cmH2O*mL (+49%)

Constant VT, different PEEP

Airway pressure (cmH2O)

0 5 10 15 20 25 30 35 40

Infl

ated

Volu

me

(mL

)

0

100

200

300

400

500

600

700

800

900

1000

1100

1200

1300

0 cmH2O PEEP

5 cmH2O PEEP

10 cmH2O PEEP

13 cmH2O PEEP

ARDS

PEEP (cmH2O)

0 5 10 15D

issi

pat

ed E

ner

gy (

cmH

2O

*m

L)

1000

2000

3000

4000

5000

6000

7000

8000

Same plateau pressure, different PEEP

Strain

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1.1

1.2

1.3

1.4

1.5

1.6

1.7

1.8

1.9

2.0

2.1

2.2

2.3

2.4

2.5

2.6

2.7

2.8

2.9

3.0

3.1

3.2

3.3

Nu

mb

er o

f p

igs

0

1

2

3

4

5

6

7

8

ZEEP ALIVE

ZEEP DEAD

PEEP ALIVE

PEEP DEAD

95% ALIVE ALL DEAD ≈50%

Protective effect of PEEP?

Conclusions

For VILI what matters is a tidal volume in a

ventilatable lung

Tidal strain ≥ 1.5 and total stress around 20 in man

are possible thresholds.

The stress risers allow to reach the threshold locally

and a moltiplication of pressure is nearly 2

PEEP does not produce energy load and its

positive effects may be due to the decraesed tidal

volume