27/04/16 1 Lung Protection 2016, Antalya Luciano Gattinoni, MD, FRCP Georg-August-Universität Göttingen Germany Exessive power VILI comes from Small, inhomogeneous lung Power (Energy/Minute) Includes ∆Pressure, ∆Volume, Rate, Flow. Chest wall elastance Etot Etot cmH 2 O Stiff Stiff 25 25 L E EL “Soft” “Soft” Ew Ew 5 5 Stiff Stiff 15 15 Ew Ew “Soft” “Soft” 15 15 L E EL Etot tot E 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 ΔTranspulmonary plateau pressue (cmH 2 O) 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 Slope P L /P aw = E w /E tot [0.2 - 0.8] Slope P L /P aw = E w /E tot [0.2 - 0.8]
1. The anatomial tresholds 2. The associated power
Transpulmonary pressure (PL cmH2O)
0 4 8 12 16 20 24 28 32 36 40
40
50
60
70
80
90
100
%T
otal
Lun
g C
apac
ity
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
FRC ml
TLC ml
Sp E cm H2O
PL (TLC)
cm H2O
Strain at 6 ml/kg
TV
2.5 7.5 4 8 0.72
300 900 6 12 0.46
2000 6000 12 24 0.21
Pressure (cmH2O)
0 5 10 15 20 25 30 35 40 45
Vol
ume
(mL/
kg)
05
1015202530354045505560
43 PIGS
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3
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
ΔLu
ng W
eigh
t (g)
-200
-100
0
100
200
300
400
500
600
Stra
in (V
t/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
Stre
ss (P
L, c
mH
2O)
05
10152025303540455055
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.
TLC
FRC
Lung
Vol
ume
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. Amato MB et al. N Engl J Med 2015;372:747-755.
Relative Risk of Death in the Hospital across Relevant Subsamples after Multivariate Adjustment — Survival Effect of
Ventilation Pressures.
Tidal Strain
P*ΔV = Energy Input
Dissipated Undissipated Surface Tension Sliding EM Opening and Closing
Elastic System
PEEP *ΔV = Energy Input = 0
Continuous Strain
LOW INTERMEDIATE HIGH
Insp
irato
ry V
olum
e/kg
(mL/
kg)
0
10
20
30
40
50
60
70
80
90
100
SURVIVEDDEAD SURVIVED DEAD SURVIVEDDEAD
TOTAL VOLUME/kg SURVIVEDTOTAL VOLUME/kg DEADTV/kg SURVIVED TV/kg DEAD
28 pigs 1 18 20 3 6
TOTAL VOLUME/kg SURVIVEDTOTAL VOLUME/kg DEADTV/kg SURVIVED TV/kg DEAD
76 PIGS
27/04/16
4
FRC ml
TLC ml
Sp E cm H2O
PL (TLC) cm H2O
2.5 7.5 4 8
300 900 6 12
2000 6000 12 24
Global stress able to damage healthy (or “baby”?) lung in clinical practice is uncommon However, when the lung starts to deteriorate the rate of damage is impressively fast, why? If global stress is so rare, how can we explain the following slide?
ARR = absolute risk reduction
Hager et al. Am J Respir Crit Care Med. 2005 Nov 15;172(10):1241-5.
min max
Stress distribution: high stiffness zone
Mead J et al. J. Appl. Physiol. 28(5):596-608 1970
Voxel Vgas
Weighted gas ratio = Vgas1/Vgas0 * fraction of tissue
Lesions should first occur where physiological stress risers are located
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.
27/04/16
6
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.
Hours 0 5 10 15 20 25
Seve
rity
trend
CT scan only
+ Lung mechanics
+ Gas Exchange
T2
T3
T4-5
VILI cumulative time course
Courtesy of dr. Cressoni M.
VILI prerequisite
Anatomical limit: whole lung
Stress risers with severity
To decrease stress risers high PEEP and prone position
Anatomical limit: regions (Sress risers)
PET FDG UPTAKE
CT SCAN INFLATION INHOMOGENEITY
LUNG IMAGING Ki/lung inhomogeneity interaction and gas/tissue
composition
MILD
MODERATE
SEVERE
27/04/16
7
Conclusions For VILI what matters is a tidal volume in a ventilatable lung Tidal strain ≥ 1.5 and total stress around 20 cmH2O 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
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