ARDS et Assistances respiratoires extracorporelles

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 matthieu.schmidt@aphp.fr

2. ECMO and ECCO2R?Same TechnologyDifferent Objectives…

3. Membrane lung O2/CO2transfer ECMO for oxygenation ECCO2R for Decarboxylation O2 transfer CO2 transfer

4. ECMO and ECCO2R ECMO ECCO2R Double lumen catheter Low flow, respiratory dialysis 250-1000 ml/min Medium size oxygenator No blood oxygenation Partial blood decarboxylation Regular ICU • Large cannulas • High extracorporeal flow • >5000 ml/min • Large membrane oxygenator • Full blood oxygenation • Full blood decarboxylation • High technicity, ECMO center

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. hospitalmortality for severe ARDS 46%

9. Increasing Intensity of Intervention ECMO Inhaled NO Lower Tidal Volume/Pplat HFVO Prone Positioning Neuromuscular Blockade Higher PEEP NIV Low-Moderate PEEP The ARDS Definition Taskforce. JAMA 2012;307:2526-2533. Low Tidal Volume Ventilation Mild ARDS Moderate ARDS Severe ARDS 0 200 300 250 150 100 50 PaO2/FiO2

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. UK, 2001-2006 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. Lancet, 2009 • Time fromrandomization to death • Log rank p = 0.03 Exclusion criteria: Duration of MV > 7 days

25. no transfer on ECMO 6% diedwithout 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 • Refractoryhypoxemia • SaO2<80% for >6 hours • Despitemandatory trial of • PronepositioningAND • Recruitment maneuver AND • iNOor inhaled prostacyclin • AND If the treatingphysicianfeltthat • Patient had no irreversible multi-organfailureAND • ECMO might change the outcome

32. PrimaryEndpoint Relative Risk, 0.76, 95% Cl, 0.55-1.04; P=0.087 Hazard Ratio, 0.70; 95% CI, 0.47-1.04, P=0.074 by log-rank test

33. Key SecondaryEndpoint Hazard ratio, 0.48; 95% CI, 0.34-0.70, P <0.001 by log-rank test Relative Risk, 0.62; 95% CI, 0.47-0.82; P<0.001 Percent D60 TreatmentFailure • Death in ECMO group patients; Death or Crossover to ECMO in control patients

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 CrossoverOutcomes

37. Rank-preserving structural failure time analysis - Controlling for crossover in controls Treatment Failure Intention to Treat RFSFT Hazard ratio, 0.51; 95% CI, 0.24-1.02 P = 0.055 by log-rank test Hazard ratio, 0.48; 95% CI, 0.34-0.70 P <0.001 by log-rank test Hazard Ratio, 0.70; 95% CI, 0.47-1.04 P = 0.074 by log-rank test

38. Which patient for VV-ECMO ?

39. Increasing Intensity of Intervention ECMO Lower Tidal Volume/Pplat Inhaled NO Prone Positioning Neuromuscular Blockade Higher PEEP NIV Low-Moderate PEEP The ARDS Definition Taskforce. JAMA 2012;307:2526-2533. Low Tidal Volume Ventilation Mild ARDS Moderate ARDS Severe ARDS 0 200 300 250 150 100 50 PaO2/FiO2

40. ECMO : potential indications EOLIA trial

41. Exclusion criteria • Patients who are moribund and have anycontra-indication to continuation of active treatment • Irreversible ARDS • Duration of high pressure and/or high FIO2ventilation > 7d • Intra-cranialbleeding • Anyothercontra-indication to limitedheparinisation

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. Predictivesurvival 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

50. www.respscore.com