Stress & Strain during Lung Protective
Ventilation
Lluis Blanch MD, PhD
Senior Critical Care Department
Director Research ...
JAMA 2012; 307:2526-33

Consensus Process
•
•
•
•

May-Sept 2011: pre-meeting preparations
Sept 30-Oct 2, 2011: In-person ...
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

P...
2013 in press

n=47

Kaplan-Meier 28day probability of
survival for 3
ARDS phenotypes

n=149
n=86

p<0.0001
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
...
The concept of “Barotrauma”
Increased Microvascular Permeability in Dog Lungs
due to High Peak Airway Pressures

Parker JC...
Mechanical Ventilation & Lung Deformation
Stress: force per unit area
Strain: the change in lenght in relation to be initi...
VILI & Stress & Strain Results from a
Complex Interplay between
• Alveolar pressure
• Lung volume
• Surface tension
• Capi...
Alveolar Interdependence
Stress
(tensión)

Strain
(deformación)

Strech
(estiramiento)

Shear
(cizallamiento)

Mead J et a...
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...
Lung hyperinflation to 82% TLC distented segments of alveolar
perimeter as little of 5% or as much as 25 % of initial, sug...
Evidence for Structural Fatigue ?
Isolated, Perfused Rabbit Lung

Observations of: Hotchkiss J, Murias G, Blanch L
Crit Care Med 2003;31:1993-98

Time for Ers reach
150% of Baseline
(min)

Paw
cmH2O

43

44

46
Titrating VT to PBW, the lungs of
patients with a small FRC are exposed
to much larger deformations than those
of patients...
Crit Care Med 2013; 41:1046–1055

Strain=VT/VPEEP

Dynamic Strain
Static Strain
Crit Care Med 2013; 41:1046–1055

IL-6 BAL: no increase
Lung Water: no increase
Lung Strain and Biological Response in
Mechanically Ventilated Patients
22 MV patients (6 control, 16 ALI).
Strain = Tidal...
Am J Respir Crit Care Med Vol 181. pp 578–586, 2010

Low
Recruitability

High
Recruitability

Potentially Recruitable Lung
High Capillary Pressure is More Injurious
at High Lung Volume
Scanning
Transmission Electron Microscopy

Fu Z et al. J App...
Pulmonary Capillary in an Alveolar Wall Showing The
Three Principal Forces to which The Vessel Is Exposed
Increase in
Lung...
Weight gain (g/g lung tissue)

PMID: 16484897. Crit Care Med 2006

Isolated heart/lung model:
PCV: Paw 30 cmH2O, PEEP 5 cm...
Transpulmonary Pressure and Lung Volume
Ptp = Paw - Peso
20

-5

Ptp = 25

20

+5

Ptp = 15
Esophageal-Pressure Guided Group:
Better oxygenation & Crs
Less mortality (17% vs 39%, p=0.05)
Airway Pressure

Esophageal Pressure

Transpulmonary Pressure
Airway Pressure

Esophageal Pressure

Transpulmonary Pressure

PEEP titrated in order to obtain values of end-expiratory
t...
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 200...
Effect of VT & PEEP on Compliance

Suter PM et al. Chest 1978; 73:158
Multipleorgan-dysfunction, respiratory and hemodynamic failure free
days at 28 d were significantly higher in Crs-guided s...
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 R...
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...
In-Hospital Time to Death
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 2...
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...
n engl j med 363;12 nejm.org september 16, 2010

cisatracurium

177

placebo

162

Once the assigned Ramsay
sedation score...
n engl j med 363;12 nejm.org september 16, 2010

At 28 days in
cisatracurium
group more:
- ventilator-free days
- days wit...
n engl j med 363;12 nejm.org september 16, 2010

The mechanisms underlying the beneficial effect of neuromuscular
blocking...
N Engl J Med 2013;368:806-13.
TIPS to ventilate ARDS patients
• Minimize alveolar overdistension during
inspiration:
• Pplat < 30 cmH2O, VT < 7 ml/kg
• ...
Thank you! lblanch@tauli.cat
Stress & Strain during  Lung Protective Ventilation  Egypt Pulmonary Critical Care
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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

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Stress & Strain during Lung Protective Ventilation Egypt Pulmonary Critical Care

  1. 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. 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. 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. 4. 2013 in press n=47 Kaplan-Meier 28day probability of survival for 3 ARDS phenotypes n=149 n=86 p<0.0001
  5. 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. 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. 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. 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. 9. Alveolar Interdependence Stress (tensión) Strain (deformación) Strech (estiramiento) Shear (cizallamiento) Mead J et al. J Appl Physiol 1970; 28:596-608
  10. 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. 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. 12. Evidence for Structural Fatigue ? Isolated, Perfused Rabbit Lung Observations of: Hotchkiss J, Murias G, Blanch L
  13. 13. Crit Care Med 2003;31:1993-98 Time for Ers reach 150% of Baseline (min) Paw cmH2O 43 44 46
  14. 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. 15. Crit Care Med 2013; 41:1046–1055 Strain=VT/VPEEP Dynamic Strain Static Strain
  16. 16. Crit Care Med 2013; 41:1046–1055 IL-6 BAL: no increase Lung Water: no increase
  17. 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. 18. Am J Respir Crit Care Med Vol 181. pp 578–586, 2010 Low Recruitability High Recruitability Potentially Recruitable Lung
  19. 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. 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. 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. 22. Transpulmonary Pressure and Lung Volume Ptp = Paw - Peso 20 -5 Ptp = 25 20 +5 Ptp = 15
  23. 23. Esophageal-Pressure Guided Group: Better oxygenation & Crs Less mortality (17% vs 39%, p=0.05)
  24. 24. Airway Pressure Esophageal Pressure Transpulmonary Pressure
  25. 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. 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. 27. Effect of VT & PEEP on Compliance Suter PM et al. Chest 1978; 73:158
  28. 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. 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. 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. 31. In-Hospital Time to Death
  32. 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. 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. 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. 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. 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.
  37. 37. N Engl J Med 2013;368:806-13.
  38. 38. 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.
  39. 39. Thank you! lblanch@tauli.cat

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