This document discusses ventilator induced lung injury (VILI) from barotrauma to biotrauma. It explores how injurious ventilator strategies can increase cytokines and lead to inflammation in isolated rat lung models. High pulmonary vascular flow and pulmonary capillary pressure were shown to promote lung damage, edema, and hemorrhage independent of ventilator settings. A study on isolated perfused rabbit lungs found that high pulmonary vascular flow and low positive end-expiratory pressure (PEEP) led to increased lung weight gain and hemorrhage scores compared to low flow and high PEEP settings, particularly in a two-hit lung injury model using oleic acid pre-injury.

1. 8th Pulmonary Medicine Update Course
The Egyptian Society of ICM & Trauma
Ventilator Induced Lung Injury:
from Barotrauma to Biotrauma
Lluis Blanch M.D.
Consultant, Critical Care Center, Hospital of Sabadell
Scientific Director, Corporacio Parc Tauli
University Institut Fundació Parc Taulí
Universitat Autónoma de Barcelona
Sabadell, Spain
lblanch@tauli.cat
Cairo, February 6 - 7, 2008

2. Webb & Tierney 1970. Dreyfuss & Saumon 1998.

3. Alveolar Interdependence
Stress
(tensión)
Strain
(deformación)
Strech
(estiramiento)
Shear
(cizallamiento)
Mead J et al. J Appl Physiol 1970; 28:596-608

4. The concept of “Barotrauma”
Increased Microvascular Permeability in Dog Lungs
due to High Peak Airway Pressures
Parker JC et al. J Appl Physiol 1984;57:1809

5. The concept of “Biotrauma”
Mechanical Injury Leads to Inflammation
ARDS Baro-Volu-Atelectrauma
Surfactant Biotrauma
Depletion
Stress Failure
Shear Forces
TNFα
Overdistension
IL-1
IL-8
Cell Trigger Mechanism

7. Injurious Ventilatory Strategies Increase Cytokines in
an isolated Rat Lung Model (Saline Injected Group)
Tremblay L et al. J Clin Invest 1997;99:944-952

8. JAMA 2003;289:2104

9. Effect of Mechanical Ventilation Strategy on
Dissemination of Intratracheally Instilled
Escherichia coli in Dogs “second hit”
+ Blood Cultures
Group Overall 30 min.6 hours
Ptp 15, PEEP 3 0/6 0/6 0/6
Ptp 35, PEEP 3 5/6 5/6 2/4
Ptp 35, PEEP 10 1/6 1/6 1/6
Nahum A, et al Crit Care Med 1997; 25:1733-43.

10. VILI & Stress Distribution along the
Blood-Gas Barrier Results from a
Complex Interplay between
• Alveolar pressure
• Lung volume
• Surface tension
• Capillary pressure
• Flow through pulmonary vessels
• Rate of lung expansion

12. High Capillary Pressure is More Injurious
at High Lung Volume Scanning
Transmission Electron Microscopy Electron Microscopy
Fu Z et al. J Appl Physiol 1992;73:123-133

13. Pulmonary Capillary in an Alveolar Wall Showing The
Three Principal Forces to which The Vessel Is Exposed
Increase in
Lung Inflation
Increase
in Pcap Stretch & Stress
The Capillary Wall
West JB & Mathieu-Costello O. Lancet 1992;340:762-767.

14. Perfusion (ml/min) Ptp (cmH2O)
Control 500 10
Low Flow 300 30
High Flow 900 30
Am J Respir Crit Care Med 1998; 157:1935-42

15. Prospective study designed to Systolic PAP
identify factors influencing
pathogenesis, severity and
prognosis of ARDS.
Patients: 586 (38 European ICUs)
Results:
- PaO2/FiO2 & Qs/Qt predicted
survival.
- High PAP and low SAP were
strong indicators of survival
(adverse prognostic significance).

16. 3
Weight Gain
(gm/gm lung)
1
* f: resp. rate
* P: PA pressure
0
High f Low f High f
Low P High P High P
Am J Respir Crit Care Med 2000; 161:463.

18. Contributions of Vascular Flow & Pulmonary
Capillary Pressure to VILI
Study Design
Stabilization 15’ Pressure Controlled Ventilation 30’
Heart-Lung Block Measurements Measuremetns
Ischemic Time < 25 min
Pump Flow PAP LAP Pcap Paw PEEP
(ml/min) (mmHg) (mmHg) (mmHg) (cmH2O) (cmH2O)
↓Flow ↓Pcap 40 20 10 10 30 5
↑Flow ↑Pcap 500 35 10 20 30 5
↓Flow ↑Pcap 40 20 20 20 30 5
↑Flow ↓Pcap 500 35 5 10 30 5

19. Contributions of Vascular Flow & Pulmonary
Capillary Pressure to VILI
*† *†
% change in Cst
Vascular
*
*
failure was
observed
* †
ONLY in high
* †
flow groups
*† *†

20. Crit Care Med 2006;34:1106-1112
quot;%
quot;$
quot;
quot;
High Flow
& * †
Groups
%
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Low Flow
Groups
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Perfusion at high vascular flow promotes lung damage, edema, and
hemorrhage independent of the level of pulmonary capillary pressure

21. Effects of vascular flow and PEEP in a
multiple hit model of lung injury in isolated
perfused rabbit lung
To evaluate the protective role of PEEP in
lung injury development in two isolated and
perfused lung model of VILI:
High vascular flow model (one hit)
Oleic acid pre-injury and high vascular flow
model (two hit)

22. Effects of vascular flow and PEEP in a
multiple hit model of lung injury in isolated
perfused rabbit lung
• Experimental, prospective and acute study
• 30 Isolated perfused and ventilated lungs from New
Zealand rabbits ( 3.3 ± 0.5 kg)
• 6 Experimental groups (3 with and 3 without OA):
Group Flow PAP LAP Pcap
ml/min mmHg mmHg mmHg
Low Flow/Peep 5 40 20 10 12
High Flow/Peep 5 600 35 10 20
HighFlow/Peep15 600 35 10 20

23. Effects of vascular flow and PEEP in a
multiple hit model of lung injury in isolated
perfused rabbit lung
6 10
weight gain (g/g lung tissue)
†
*
weight gain (g/g lung tissue)
a
5
* + b
+
8
4
3
6
*
4 *
2
1 2
0 0
0 5 10 15 20 25 30 0 5 10 15 20 25 30
Time (minutes) Time (minutes)
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24. Effects of vascular flow and PEEP in a multiple hit model
of lung injury in isolated perfused rabbit lung
a
3
6
* +
Perivascular hemorrhage score
* + *†
Alveolar hemorrhage score
†
5 *
4 2
3
2 1
1
0 0
LFLP HFLP HFHP LFLP HFLP HFHP
8 b 4
+ +
Perivascular hemorrhage score
* * *
Alveolar hemorrhage score
*
7
6 3
5
4 2
3
2 1
1
0 0
LFLPOA HFLPOA HFHPOA LFLPOA HFLPOA HFHPOA

25. Factors Influencing Liquid Movement in
the Pulmonary Capillaries:
The Starling Equation
Qf = Kf {(Pc - Pis) - σ (πpl - πis)}
(π
Qf: net flow of fluid
Kf: capillary filtration coefficient
Pc: capillary hydrostatic pressure
Pis: hydrostatic pressure of the interstitial fluid
σ: reflection coefficient
πpl: oncotic pressure of the plasma
πis: oncotic pressure of the interstitial fluid

26. Assessing practice changes
),, )- - . )/0(

27. Potential effects of usual practice control group in the
ARDSNet low tidal volume (ARMA) trial