1. ARDS et Assistances respiratoires extracorporelles
Matthieu Schmidt, MD, PhD
Medical ICU
iCAN, Institute of Cardiometabolism and Nutrition
Hôpital Pitié-Salpêtrière, AP-HP, Paris
Université Pierre et Marie Curie, Paris 6

2. ECMO and ECCO2R? Same Technology Different Objectives…

3. Membrane lung O2/CO2 transfer
ECMO for oxygenation
ECCO2R for Decarboxylation
CO2 transfer
O2 transfer

4. ECMO and ECCO2R ECMO ECCO2R Large cannulas High extracorporeal flow
>5000 ml/min
Large membrane oxygenator
Full blood oxygenation
Full blood decarboxylation
High technicity, ECMO center
Double lumen catheter
Low flow, respiratory dialysis
ml/min
Medium size oxygenator
No blood oxygenation
Partial blood decarboxylation
Regular ICU

5. Full Flow ECMO
Mid-Flow ECMO
Low Flow ECCO2R

6. The evolving paradigm…
ARDSnet strategy might not protect against tidal hyperinflation
When Pplat remains >28-30 cm H2O
Further decrease of Vt to reduce VILI
From 6 to 5, 4 or 3 ml/kg IBW
To decrease Pplat <25 cm H2O
With sufficient PEEP to prevent lung derecruitment
Resulting in a significant decrease in ∆P
To decrease RR to <20… <15… <10?????
Induced Hypercapnia controlled by ECCO2 removal
“CO2 dialysis”
Low-flow devices

7. VV-ECMO and ARDS

8. hospital mortality for severe ARDS 46%

9. Increasing Intensity of Intervention
Mild ARDS
Severe ARDS
Moderate ARDS
Increasing Intensity of Intervention
300
200
250
100
150 50
PaO2/FiO2
Low Tidal Volume Ventilation
Higher PEEP
Low-Moderate PEEP
Prone Positioning
NIV
HFVO
Inhaled NO
ECMO
Neuromuscular Blockade
Lower Tidal Volume/Pplat
The ARDS Definition Taskforce. JAMA 2012;307:

10. VV-ECMO To replace pulmonary function To allow the lungs to rest…
To allow healing of the lungs…

12. 2009… ECMO strikes back!
Influenza A (H1N1)v09

15. 17 25%)

16. 17 25%)
14 (21)

17. 17 25%)
6 (43)

18. Et al…

19. 2013

20. ARDS…ECMO RCTs

21. ECMO provided only at the Glenfield Hospital, Leicester
UK,
ECMO provided only at the Glenfield Hospital, Leicester
Entry criteria:
Adult patients (18-65 years)
Severe, but potentially reversible ARDS
Murray score ≥3.0, or
Uncompensated hypercapnia: pH <7.20
Primary outcome measure
Death or severe disability 6 months
Analysis by intention to treat

22. Duration of MV > 7 days
Lancet, 2009
Time from randomization to death
Log rank p = 0.03
Exclusion criteria:
Duration of MV > 7 days

25. no transfer on ECMO
6% died without ECMO

27. EOLIA objectives EOLIA trial designed to determine the effect of
Early initiation of ECMO
In patients with the most severe forms of ARDS

28. Inclusion Criteria
American–European Consensus Conference definition for ARDS criteria
Intubated and on MV for <7 days
MV optimization before inclusion
FiO2 ≥80%
Vt = 6 ml/kg PBW
Trial of PEEP ≥10 cm H2O

29. Inclusion Criteria One of the 3 following disease severity criteria
PaO2:FiO2 <50 mmHg for >3 hours
Despite potential use of inhaled NO, recruitment maneuvers
Prone position, HFO ventilation, almitrine infusion
PaO2:FiO2 <80 mmHg for >6 hours
Despite similar criteria as above
pH <7.25 with PaCO2 >60 mmHg for >6 hours
Resulting from MV settings to keep Pplat ≤32 cm H2O
Despite respiratory rate increased to 35/minute

30. Rescue ECMO for Controls
Refractory hypoxemia
SaO2 <80% for >6 hours
Despite mandatory trial of
Prone positioning AND
Recruitment maneuver AND
iNO or inhaled prostacyclin
AND If the treating physician felt that
Patient had no irreversible multi-organ failure AND
ECMO might change the outcome

32. Primary Endpoint Relative Risk, 0.76, 95% Cl, 0.55-1.04; P=0.087
Hazard Ratio, 0.70; 95% CI, , P=0.074 by log-rank test

33. Key Secondary Endpoint
Relative Risk, 0.62; 95% CI, ; P<0.001
Hazard ratio, 0.48; 95% CI, , P <0.001 by log-rank test
Percent D60 Treatment Failure
Death in ECMO group patients; Death or Crossover to ECMO in control patients

34. Endpoint at D60 ECMO Group (N = 124) Control Group (N = 125)
Endpoint at D60
ECMO Group (N = 124)
Control Group (N = 125)
Median Difference
(95% CI)
Days alive and free of vasopressor use
49 [0–56]
40 [0–53]
9 (0 to 51)
Days alive and free of cardiac failure (SOFA)
48 [0–56]
41 [0–53]
7 (0 to 51)
Days alive and free of dialysis
50 [0–60]
32 [0–57]
18 (0 to 51)
Days alive and free of renal failure (SOFA)
46 [0–60]
21 [0–56]
25 (6 to 53)
Days alive and free of prone position
59 [0–59]
46 [0–57]
13 (5 to 59)
Days alive and free of NO/prostacyclin
59 [0–60]
39 [0–58]
20 (4 to 59)

35. Crossover to ECMO in Controls
Before crossover, of the 35 controls who had ECMO
9 had cardiac arrest
7 had severe right heart failure
11 developed renal failure requiring dialysis
Venoarterial ECMO applied to 7 patients
6 under cardiopulmonary resuscitation

36. Control Crossover Outcomes

37. Rank-preserving structural failure time analysis - Controlling for crossover in controls
Intention to Treat
RFSFT
Treatment Failure
Hazard Ratio, 0.70; 95% CI, P = by log-rank test
Hazard ratio, 0.51; 95% CI,
P = by log-rank test
Hazard ratio, 0.48; 95% CI, P <0.001 by log-rank test

38. Which patient for VV-ECMO ?

39. Neuromuscular Blockade
Mild ARDS
Severe ARDS
Moderate ARDS
Increasing Intensity of Intervention
300
200
250
100
150 50
PaO2/FiO2
Low Tidal Volume Ventilation
Higher PEEP
Low-Moderate PEEP
Prone Positioning
NIV
Inhaled NO
ECMO
Neuromuscular Blockade
Lower Tidal Volume/Pplat
The ARDS Definition Taskforce. JAMA 2012;307:

40. ECMO : potential indications
EOLIA trial

41. Exclusion criteria
Patients who are moribund and have any contra-indication to continuation of active treatment
Irreversible ARDS
Duration of high pressure and/or high FIO2 ventilation > 7d
Intra-cranial bleeding
Any other contra-indication to limited heparinisation

42. When to decide on the initiation of VV-ECMO for severe ARDS ?

43. not too late…. within the first 7 days on mechanical ventilation?

46. The Lancet Respiratory Medicine - July 2013

47. The Lancet Respiratory Medicine - July 2013

49. Predictive survival model (VV ECMO)
Pappalardo et al, ICM 2013
Schmidt et al, ICM 2013
Roch et al, ICM 2013
Schmidt et al, AJRCCM 2014
Enger et al, Crit Care 2014

51. Potential role of such scores
to help clinicians identifying “good” and “bad” candidates for ECMO: a simple bedside tool…

52. Potential role of such scores
to help clinicians identifying “good” and “bad” candidates for ECMO NO

53. Potential role of such scores
to help clinicians identifying “good” and “bad” candidates for ECMO NO
YES

54. Potential role of such scores
to help clinicians identifying “good” and “bad” candidates for ECMO NO
????
YES

55. We need high-volume centers for complex procedures…

56. Because high-volume ECMO centers have better outcomes…

58. with lower mortality was 22 (95% CI, 22–28)
0-19
20-49
>49
The minimum annual case load most significantly associated
with lower mortality was 22 (95% CI, 22–28)

59. Where to perform VV-ECMO?
Experienced centers in both ARDS and ECMO
Better if cardiac and respiratory ECMO combined on the same site
With experienced intensivists, cardiothoracic surgeons, perfusionists, nurses….
Minimum of 20 total ECMO runs per year
ECMO programs should include a mobile ECMO referral team
Available 24H/7D
Nationwide or regional EMCO networks necessary

61. Conclusion VV-ECMO can rescue 50-80% of the patients with severe ARDS
need to select patients who are more likely to survive
ECMO should not be a futile prolongation of the ICU stay
Important pathophysiological rational to use VV-ECMO early in severe ARDS
in case of prone positioning failure
< 7 days of MV
potential role of predictive survival models