1. Recruitment and PEEP in ALI/ARDS
Paolo Pelosi
Department of Ambient, Health and Safety, University of Insubria, Varese, Italy

3. Outcomes in ARDS – “In the real life”
Esteban, Ferguson, Meade, …. Pelosi et al AJRCCM 2008;15;177:170-7
(n 135) (n 198) P Value
Duration of intubation,
median (IQR), days (5, 15) (5,16)
Length of stay in the ICU,
median (IQR), days (7, 23) (7, 21)
ICU mortality, n (%) (61) (56)
Hospital mortality, n (%) 87/126 (69) 117/185(63)

4. The ARDS Lung
Gattinoni JAMA 1993, Pelosi AJRCCM 1994, Gattinoni AJRCCM 2002, Gattinoni ICM 2005
Rouby Intensive Care Med 2000
Superimposed
Pressure
Opening
Normal
Alveolar Collapse
(Reabsorption)
20-30 cmH2O
Small Airway
Collapse
10-20 cmH2O
Consolidation 

5. Ventilator induced lung injury
volutrauma
zone of
overdistension V
UIP
zone of derecruitment
and atelectasis
"safe"
window
LIP
atelectrauma P

6. Ventilator induced lung injury
volutrauma
zone of
overdistension V
UIP
zone of derecruitment
and atelectasis
"safe"
window
LIP
atelectrauma P

7. TIDAL VOLUME AND INSPIRATORY PLATEAU PRESSURE
HOW MUCH
TIDAL VOLUME AND INSPIRATORY PLATEAU PRESSURE
IN ALI/ARDS PATIENTS ?

8. Ventilation strategies and outcomes of the ALI/ARDS : a Meta-analysis
Putensen C, Theuerkauf N, Zinserling J, Wrigge H, Pelosi P
Ventilation strategies and outcomes of acute respiratory distress syndrome and acute lung injury: a meta-analysis
Ventilation strategies and outcomes of the ALI/ARDS :
a Meta-analysis
Ann Intern Med 2009; 151:
Ventilation strategies and outcomes of acute respiratory distress syndrome and acute lung injury: a meta-analysis
Hospital Mortality:
Lower vs Higher VT at the same PEEP
Patients,n
Low VT
Similar PEEP
High VT
Similar PEEP
Odds ratio
(95% CI)
Brower, 1998
Brower, 2000 52
120
13/26
134/432
171/429
12/26
1.17( )
0.68( )
0.75( )
Summary
861
Stewart, 1998
30/60
28/60
1.14( )
P<0.02; I2 =18.3

9. Ventilation strategies and outcomes of the ALI/ARDS :
Ventilation strategies and outcomes of acute respiratory distress syndrome and acute lung injury: a meta-analysis
Putensen C, Theuerkauf N, Zinserling J, Wrigge H, Pelosi P
Ventilation strategies and outcomes of the ALI/ARDS :
a Meta-analysis
Ann Intern Med 2009; 151:
Low VT ventilation did not improve outcome when higher VT ventilation resulted in Pei less or equal to 30 cm H2O.
Low VT ventilation was associated with greater use of NMBAs
Low VT ventilation may not be beneficial if:
- pH<7.20 (administering sodium bicarbonate, increasing VT , ECMO)
- side effects (hypercapnia/respiratory acidosis) are contraindicated

10. HOW MUCH
RECRUITABLE LUNG
IN ALI/ARDS PATIENTS ?

11. EDEMA – ATELECTASIS IN ALI/ARDS
ρ x g x h
P = 5 cmH2O
P = 10 cmH2O
LESS EDEMA-ATELECTASIS
LOWER PEEP
HIGHER EDEMA-ATELECTASIS
LOWER PEEP

12. Non recruiter Paw 45cmH2O Gattinoni et al NEJM 2006, 354(17):1775-862 4 6 8 10 12 14
overaerated
normally aerated
poorly aerated
non aerated
Weight (grams)
Peep 5 cmH2O
Paw 45cmH2O
Peep 5 cmH2O

13. Recruiter Paw 45cmH2O Gattinoni et al NEJM 2006, 354(17):1775-86
Weight (grams)
overaerated
normally aerated
poorly aerated
non aerated 10 20 30 40 50 60
Peep 5 cmH2O
Paw 45cmH2O
Peep 5 cmH2O

14. Potential for lung recruitment
Gattinoni et al NEJM 2006, 354(17):
potential for lung recruitment [% total lung weight]
-10 -5
-5 0
0-5
5-10
10-15
15-20
20-25
25-30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
Frequency [no. of patients] 2 4 6 8 10 12 14 16 18 20 22 24
ALI patients
ARDS patients
higher
21 ± 10%
(374 ± 236 grams)
lower
5 ± 4%
(59 ± 51 grams)

15. Mortality at ICU-discharge
Gattinoni et al NEJM 2006, 354(17):
mortality
[%]
quartiles of potential for lung recruitment
1st 10 20 30 40 50 60
lower-
potential
2nd
3rd
4th 17
n =
higher-
P=0.006

16. Inflammation spreading
Possible model
Core disease
24%
Inflammation spreading
Lower
24% 5%
71%
Higher
24%
21%
55%
Lower severity and mortality
Higher severity and mortality

17. WHICH IS THE “BEST” RECRUITMENT
MANEUVER ?

18. The concept of PEEP and Recruitment
Pelosi P et al. Crit Care Mar 9;14(2):
optimal-PEEP
recruited vol.

19. Old and new recruitment maneuvers in ALI/ARDS
Pelosi P et al. Crit Care Mar 9;14(2):
ICM 2003,29:218
45%
23%
CCM 2001, 1255: 1260
20%

20. Recruitment Maneuvers for Acute Lung Injury:
A Systematic Review
Fan E et al. Am J Respir Crit Care Med Vol 178. pp 1156–1163, 2008
Hypotension 10%
Desaturation 8%

21. Respiratory and hemodynamic changes during decremental open lung PEEP titration in ARDS
Gernoth W, et al Critical Care 2009, 13:R59; Epub 2009 Apr 17
Right ventricular Tei index [%]
Before
During RM
After
39±11
42±10
36±11

22. Riva M et al Respiratory Physiol & Neurobiol 2009; 169:62-68
Recruitment maneuver: RAMP versus CPAP pressure profile in a model of ALI
Riva M et al Respiratory Physiol & Neurobiol 2009; 169:62-68

23. HOW TO PREDICT
“RECRUITERS”
AT BEDSIDE ?

24. Oxygenation and collapsed tissue
Borges et al Am J Respir Crit Care Med 174; , 2006
PaO2 / FiO2 < 150
at PEEP 5 cmH2O

25. Assessment of Pulmonary Morphology in ALI
Absence of Lower Inflection Point in the P-V Curve
Vieira et al. Am J Resp Crit Care Med 1999; 159:
Overdistension
PEEP 10 cmH2O
PEEP 15 cmH2O
ZEEP

26. Assessment of Pulmonary Morphology in ALI
Significance of Lower Inflection Point in the P-V Curve
Vieira et al. Am J Resp Crit Care Med 1999; 159:
Overdistension
LIP + 2 cmH2O
LIP + 7 cmH2O
ZEEP

27. OXYGENATION OR MECHANICS TO SET “OPTIMAL” PEEP ?

28. Is ∆PaO2 is assocated with recruitment ?
Malbouisson et al Am J Respit Crit Care Med 2001; 163:32-40

29. Elastance to titrate PEEP in ALI/ARDS
Carvalho AR et al. Intensive Care Med Dec;34(12):2291-9

30. The stress index: is it useful to set TV ?
Grasso et al Crit Care Med Apr;32(4):
Ranieri et al. Am J Respir Crit Care Med Jan;149(1):19-27.
Carvalho, Pelosi, Abreu et al Intenisve Care Med 2008 ( on line)

31. THE IMPORTANCE OF ESOPHAGEAL PRESSURE TO SET “OPTIMAL” PEEP ?

33. Esophageal Pressure vs SP gradient
Pelosi P et al Am J Respir Crit Care Med Jul 1;164(1):
PEEP (Intraalveolar P)
>=
Pes,exp ( Extraalveolar P)

34. IAP and Respiratory Function in ALI/ARDS
Krebs J, Pelosi P, Luecke T. Crit Care 2009 Oct 5; 13(5):R160

36. Mechanical Ventilation Guided by Esophageal Pressure in Acute Lung Injury
Talmor D et al. N Engl J Med 2008;359:

37. Mechanical Ventilation Guided by Esophageal Pressure in Acute Lung Injury
Talmor D et al. N Engl J Med 2008;359:

38. Mechanical Ventilation Guided by Esophageal Pressure in Acute Lung Injury
Talmor D et al. N Engl J Med 2008;359:

39. CLINICAL EVIDENCE FROM RCTs:
High vs Low PEEP
(7-10 vs cmH2O)
Neuromuscular blockade (48 hrs)
Prone position
ECMO

40. systematic review and meta-analysis
Higher vs lower positive end-expiratory pressure in patients with ALI/ARDS :
systematic review and meta-analysis
Briel M et al. JAMA. 2010;303(9):

41. Ventilation strategies and outcomes of the ALI/ARDS : a Meta-analysis
Ventilation strategies and outcomes of acute respiratory distress syndrome and acute lung injury: a meta-analysis
Putensen C, Theuerkauf N, Zinserling J, Wrigge H, Pelosi P
Ventilation strategies and outcomes of the ALI/ARDS :
a Meta-analysis
Ann Intern Med 2009; 151:
Rescue Therapies and ICU Mortality:
Lower vs Higher PEEP at the same VT
Patients,n
Odds ratio
(95% CI)
Low PEEP
At Low VT
High PEEP
At Low VT
Meade, 2008
Mercat, 2008
983
767
45/508
62/382
37/385
20/475
0.45( )
0.55( )
0.51( )
Summary
P<0.01; I2 =0

42. Ventilation strategies and outcomes of the ALI/ARDS :
Ventilation strategies and outcomes of acute respiratory distress syndrome and acute lung injury: a meta-analysis
Putensen C, Theuerkauf N, Zinserling J, Wrigge H, Pelosi P
Ventilation strategies and outcomes of the ALI/ARDS :
a Meta-analysis
Ann Intern Med 2009; 151:
Based on available evidence from a limited number of RCTs routine use of low VT tends to be beneficial in all ALI/ARDS patients (if potential side effects of hypercapnia and respiratory acidosis are not contraindicated)
Higher PEEP strategies during lower VT ventilation did not improve hospital mortality and cannot be recommended in unselected ALI/ARDS patients.
Higher PEEP strategies during lower VT ventilation may be suggested in severe ARDS (PaO2/FiO2 <150 at PEEP 5) and to prevent life threatening hypoxemia

43. Effect of prone ventilation on mortality
(hospital discharge or longest follow-up)
Sud S et al. Intensive Care Med Apr;36(4):585-99

44. Other “effects” of Prone position RR(95%CI) P
Prone position reduces mortality in pts with ARF and severe hypoxemia: systematic review & meta-analysis
Sud S et al. Intensive Care Med Apr;36(4):585-99
Other “effects” of Prone position
RR(95%CI) P
Reduction in VAP
0.81 ( )
Increase in ET obstruction
1.58 ( )
Increase in pressure ulcers
1.29 ( )
Increase in thoracostomy
tube dislodgment
3.14 ( )

45. PP is an effective rescue maneuver for hypoxemia
Prone position reduces mortality in patients with ARF and severe hypoxemia: systematic review & meta-analysis.
Sud S et al. Intensive Care Med Apr;36(4):585-99
PP is an effective rescue maneuver for hypoxemia
In ALI and moderate ARDS (likely low recruiters) PP does not influence mortality
In severe ARDS (PaO2/FiO2 < 150 at PEEP 5 cmH2O), likely higher recruiters, the available data strongly suggest that PP may provide survival benefits
(about 10%)

46. Efficacy and economic assessment of conventional
ventilatory support versus extracorporeal membrane
oxygenation for severe adult respiratory failure (CESAR):
a multicentre randomised controlled trial
Peek JL et al. Lancet 2009; 374: 1351–63
Murray score > 3
FiO2>90% needed to
to maintain SaO2>90%
Respiratory metabolic
acidosis pHa<7.2
Haemodynamically unstable
Transfer to a centre with an ECMO-based
management protocol

47. CONCLUSIONS:
HOW TO VENTILATE
ALI/ARDS PATIENTS

48. YES! Low VT (6 ml/Kg) and Pplat < 27-30 cmH2O
FOR ALL ALI/ARDS PATIENTS !!
YES!

49. If: PaO2/FiO2 > 150 mmHg at PEEP 5
Patient targetted MV strategy in ALI/ARDS ?
Rocco PR, Abreu GM, Pelosi P Expert Review 2010 (Epub ahead of print)
If: PaO2/FiO2 > 150 mmHg at PEEP 5
Lobar Chest X ray densities
- Assisted MV (VT 6-8 ml/kg; Pplat cmH2O)
- PEEP 7-10 cmH2O, no RM
- Supine position
If: PaO2/FiO2 < 150 mmHg at PEEP 5
Patchy/Diffuse Chest X ray densities
- CMV (VT 6-8 ml/kg; Pplat cmH2O)
- SRM, PEEP cmH2O
- Prone position, NMBAs (48 hrs)

50. Rocco PR, Abreu GM, Pelosi P Expert Review 2010 (Epub ahead of print)
VCV or PCV
VT=6 ml/kg IBW and PEEP=5 cmH2O
PaO2/FiO2 > 150 mmHg
PaO2/FiO2 ≤ 150 mmHg
Chest X-ray
Lobar dependent densities
Chest X-ray
Patchy or Diffuse densities
CT scan whole lung at PEEP 5 cmH20
No Recruitment Maneuver
PEEP= 7-10 cmH2O
Patchy or diffuse densities
Lobar dependent densities
CT scan 2 slices (5 and 45 cmH20)
at apex, hilus and base
No evident decrease of nonaerated tissue
Evident decrease of nonaerated tissue
PEEP=7-10 cmH2O
Slow and Prolonged Recruitment Maneuver, decremental PEEP trial
Rocco PR, Abreu GM, Pelosi P
Expert Review 2010 (Epub ahead of print)

51. How to perform a PEEP trial in most severe ARDS patients ?
Pelosi P, Abreu GM, Rocco PR Crit Care 2010 (Epub ahead of print)
PEEP to achieve
the “best” Cst,rs
VT 6 ml/Kg IBW
Time 5 10 15 20 25 30 35 40
Pressure (cmH2O)
5 min
1-2 min
5-10 min per step

52. How to perform a PEEP trial in most severe ARDS patients ?
Pelosi P, Abreu GM, Rocco PR Crit Care 2010 (Epub ahead of print)
Time 5 10 15 20 25 30 35 40
Pressure (cmH2O)
5 min
1-2 min
5-10 min per step
Maximal PEEP to achieve
VT 6 ml/Kg IBW,
with Pplat,rs = cmH2O

53. Thanks “Sometimes, it’s the simple things that work best”
(Jeremy Laurance, The Independent, 15 January 2009)
Thanks