Stress & Strain During Lung Protective Ventilation. Presentation of Dr Lluis Blanch at Pulmonary Critical Care Egypt 2014 , the leading educational event and exhibition for Critical Care Medicine in Egypt. www.pccmegypt.com

1. Stress & Strain during Lung Protective
Ventilation
Lluis Blanch MD, PhD
Senior Critical Care Department
Director Research and Innovation
Corporació Sanitaria Parc Tauli. Sabadell. Spain.
Universitat Autònoma de Barcelona. Spain.
22-23 January 2014 Cairo, Egypt

2. JAMA 2012; 307:2526-33
Consensus Process
•
•
•
•
May-Sept 2011: pre-meeting preparations
Sept 30-Oct 2, 2011: In-person discussions, ESICM, Berlin
Oct 2011-January 2012: Empirical evaluation of draft definition
Feb 2012 by multiple teleconferences: Discussions and analysis
•
•
•
•
ALI/ARDS as defined by AECC (PaO2/FiO2 ≤300).
7 datasets: 4.188 patients (4 multicenter), 269 patients (3 single-center)
518 patients excluded because PEEP<5 cmH2O or data missing
Empirical classification:
– Mild ARDS (P/F 201-300 on PEEP/CPAP ≥5)
– Moderate ARDS (P/F 101-200, PEEP≥5)
– Severe ARDS (P/F ≤100, PEEP≥5)
mortality 27%
mortality 32%
mortality 45%

3. 2013 in press
70
60
282 ARDS (AECC) patients on Day 1 in response to
PEEP≥10 with FiO2≥0.5
95%CI 47.7-68.5
p=0.00001
PEEP ≥10
FiO2 ≥0.5
Mortality, %
50
40
n=86
30
95%CI 33.6-48.2
n=149
95%CI 6.3-27.7
20
n=47
10
0
severe
PaO2/FiO2 ≤100
moderate
PaO2/FiO2 101-200
mild
PaO2/FiO2 >200

4. 2013 in press
n=47
Kaplan-Meier 28day probability of
survival for 3
ARDS phenotypes
n=149
n=86
p<0.0001

5. Targets during MV in Patients with ARDS
VT 6
PEEP
VT 6
VT 12
VT 12
PEEP
ARDS Network
N Eng J Med 2000; 342:1301-8
VT 6
Amato MBP et al.
N Eng J Med 1998; 338:347-54
ARDS Network
N Eng J Med 2004; 351:327-36

6. 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

7. Mechanical Ventilation & Lung Deformation
Stress: force per unit area
Strain: the change in lenght in relation to be initial lenght
Shear Stress: force per unit surface area in the direction
of flow exerted by the fluid
Mechanical Stimulus
large deformations
Biochemical Stimulus
local or systemic

8. VILI & Stress & Strain Results from a
Complex Interplay between
• Alveolar pressure
• Lung volume
• Surface tension
• Capillary pressure
• Wound healing
• Lung maturity
• Flow through pulmonary vessels
• Rate of lung expansion

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

10. Am J Respir Crit Care Med 2004;169:57-63
Control
Tween
VT 10 ml/kg
PEEP 3 cmH2O
Stable Little Change in Area
Unstable Changing Size Greatly

11. Lung hyperinflation to 82% TLC distented segments of alveolar
perimeter as little of 5% or as much as 25 % of initial, suggesting
preferred locations for injury during lung overinflation

12. Evidence for Structural Fatigue ?
Isolated, Perfused Rabbit Lung
Observations of: Hotchkiss J, Murias G, Blanch L

13. Crit Care Med 2003;31:1993-98
Time for Ers reach
150% of Baseline
(min)
Paw
cmH2O
43
44
46

14. Titrating VT to PBW, the lungs of
patients with a small FRC are exposed
to much larger deformations than those
of patients with relatively normal FRC.
The above definition of strain ignores
the independent effects of VT & PEEP
Chiumello D et al.
Lung Stress and Strain in ALI/ARDS
AJRCCM 2008;178:346–355

15. Crit Care Med 2013; 41:1046–1055
Strain=VT/VPEEP
Dynamic Strain
Static Strain

16. Crit Care Med 2013; 41:1046–1055
IL-6 BAL: no increase
Lung Water: no increase

17. Lung Strain and Biological Response in
Mechanically Ventilated Patients
22 MV patients (6 control, 16 ALI).
Strain = Tidal Volume / End Expiratory Lung Volume
No differences in gas exchange, respiratory mechanics, or markers of
matrix remodeling between ALI patients with normal and high strain.
Concentrations of IL-6 and IL-8 measured in BALF
Gonzalez A, Garcia E, Batalla E,Amado L, Avello N,
Blanch L, Albaiceta G. Intensive Care Med 2012.

18. Am J Respir Crit Care Med Vol 181. pp 578–586, 2010
Low
Recruitability
High
Recruitability
Potentially Recruitable Lung

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

20. 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.

21. Weight gain (g/g lung tissue)
PMID: 16484897. Crit Care Med 2006
Isolated heart/lung model:
PCV: Paw 30 cmH2O, PEEP 5 cmH2O
Pcap: 10 & 20 mmHg
160
140
120
100
*
80
†
High Flow
Groups
60
40
20
Low Flow
Groups
0
0
5
10
15
20
25
30
tim e (m inutes)
Perfusion at high vascular flow promotes lung damage, edema, and
hemorrhage independent of the level of pulmonary capillary pressure

22. Transpulmonary Pressure and Lung Volume
Ptp = Paw - Peso
20
-5
Ptp = 25
20
+5
Ptp = 15

23. Esophageal-Pressure Guided Group:
Better oxygenation & Crs
Less mortality (17% vs 39%, p=0.05)

24. Airway Pressure
Esophageal Pressure
Transpulmonary Pressure

25. Airway Pressure
Esophageal Pressure
Transpulmonary Pressure
PEEP titrated in order to obtain values of end-expiratory
transpulmonary pressure ranging between 0 and 10 cmH2O

26. VT 6-8 & Pplat< 30 cmH2O or
VT 4 ml/kg & Pplat 35 cmH2O
PEEP for best Crs
(Suter’s method)
FiO2/PEEP Table
(ARDS Net 2000)
RESPIRATORY CARE • SEPTEMBER 2013 VOL 58 NO 9

27. Effect of VT & PEEP on Compliance
Suter PM et al. Chest 1978; 73:158

28. Multipleorgan-dysfunction, respiratory and hemodynamic failure free
days at 28 d were significantly higher in Crs-guided setting of PEEP.
RESPIRATORY CARE • SEPTEMBER 2013 VOL 58 NO 9

29. JAMA, Feb.13, 2008;209:646-55
ALI pts. (n=767)
Minimal Distension (n=382):
- VT 6 ml/kg PBW
- PEEP 5 – 9 cmH2O
Increased Recruitment (n=385)
- VT 6 ml/kg PBW
- PEEP to reach Pplat 28-30 cmH2O
Mortality: MD 31.2%, IR 27.8 %, p=.31
Vent. Free Days: MD 3, IR 7, p=.04
Organ Failure Free Days: MD 2, IC 6, p=.04
IR assocaited with better PaO2, Crs, less
adjunctive therapies and larger fluid requir.

30. JAMA, Feb.13, 2008;209:637-45
ALI pts. & PaO2 < 250 mmHg (n=983)
Control Ventilation (n=508):
- VT 6 ml/kg PBW, Pplat < 30 cmH2O,
- PEEP mean 9.8 cmH2O -TableLung Open Ventilation (n=475)
- VT 6 ml/kg PBW, Pplat < 40 cmH2O
- PEEP mean 14.6 cmH2O -Table- & RMs.
Mortality: CV 40.4%, LOV 36.4%, p=.19
Refractory Hipoxemia: CV 10%, LOV 5% p=.01
Rescue Therapies: CV 13%, LOV 8%, p=.05
RM associated with a complication in 22.1% of p.

31. In-Hospital Time to Death

32. Crit Care Med 2012; 40
Settings: PCV at 20 cmH2O; VT 7-9 ml/kg
PEEP 8 cmH2O; FiO2 1 for 4 hours
SB weak (propofol)
Ptp 29.6 cmH2O
SB strong (doxapram)
Ptp 34.5 cmH2O

33. Crit Care Med 2013; 41:536–545
4 groups of 7 rabbits
VT 5-7 ml/kg. Pplat<30 cmH2O. PEEP 9-11 cmH2O
Mild ALI
+ NMBA
Mild ALI
+ SB
Severe ALI
+ NMBA
Severe ALI
+ SB

34. n engl j med 363;12 nejm.org september 16, 2010
cisatracurium
177
placebo
162
Once the assigned Ramsay
sedation score was 6 and the
ventilator settings were
adjusted, a 3-ml rapid
intravenous infusion of 15 mg
of cisatracurium besylate or
placebo was administered,
followed by a continuous
infusion of 37.5 mg per hour
for 48 hours.

35. n engl j med 363;12 nejm.org september 16, 2010
At 28 days in
cisatracurium
group more:
- ventilator-free days
- days without organ
failure
- less pneumothorax
At 28 days in
cisatracurium
group similar number of
pateints with ICU-acquired
paresis

36. n engl j med 363;12 nejm.org september 16, 2010
The mechanisms underlying the beneficial effect of neuromuscular
blocking agents remain speculative. A brief period of paralysis early
in the course of ARDS may facilitate lung-protective mechanical
ventilation by improving patient–ventilator synchrony and allowing for
the accurate adjustment of tidal volume and pressure levels,
thereby limiting the risk of both asynchrony related alveolar
collapse and regional alveolar pressure increases with
overdistention. Another possible mechanism of the benefit
involves a decrease in lung or systemic inflammation.

38. N Engl J Med 2013;368:806-13.

39. TIPS to ventilate ARDS patients
• Minimize alveolar overdistension during
inspiration:
• Pplat < 30 cmH2O, VT < 7 ml/kg
• Minimize alveolar de-recruitment during
expiration:
• moderate, high PEEP
• Decrease transpulmonary cycling pressure
(difference between Pplat and PEEP)
• Adjuncts to mechanical ventilation: NMB,
Prone YES, RM ?.
• Last options: ONLY in selected patients.

40. Thank you! lblanch@tauli.cat