ECMO/ECCO 2 R in Acute Respiratory Failure Alain Combes, MD, PhD, Hôpital Pitié-Salpêtrière, AP-HP Inserm UMRS 1166, ican, Institute of Cardiometabolism and Nutrition Sorbonne Pierre et Marie Curie University, Paris, France www.paris-tcsecmo.org alain.combes@aphp.fr
Conflict of interest Principal Investigator: EOLIA trial VV ECMO in ARDS NCT01470703 Sponsored by MAQUET, Getinge Group Received honoraria for lectures from MAQUET, XENIOS, BAXTER
ECMO and ECCO 2 R To decrease the intensity of MV?
LUNG SAFE Epidemiology of ARDS
Probability of hospital survival by driving pressure
The evolving paradigm ARDSnet strategy might not protect against tidal hyperinflation When Pplat remains >28-30 cm H 2 O Further decrease of Vt to reduce VILI From 6 to <2 ml/kg IBW To decrease Pplat <25 cm H 2 O To decrease P < 12-14 cm H 2 O With sufficient PEEP to prevent lung derecruitment Extracorporeal gas exchange for Blood Oxygenation/Decarboxylation Decrease the intensity of MV
What are ECMO and ECCO R? 2 Same Technology Different Objectives
Membrane lung O2/CO2 transfer ECMO for oxygenation ECCO2R for Decarboxylation CO 2 transfer O 2 transfer
Influence of ECMO flow PaO2 mmhg SaO2, % Adequate Oxygenation Qecmo > 60% Qco PaCO2 mmhg Schmidt et al, Intensive Care Med, 2013
PaO2 (mmhg) PaCO2 (mmhg) PASP (mmhg) PASP PaO2 (mmhg) PaO2 PaCO2 (mmhg) 70 140 65 130 60 120 55 110 50 100 45 90 40 80 35 70 30 60 25 150 65 140 60 130 55 120 50 110 45 100 40 90 35 80 30 70 25 60 20 50 65 60 55 50 45 40 35 30 P < 0.001 P < 0.001 140 Influence of Sweep Gas Flow 110 PaO2 mmhg 10 8 6 4 2 P Sweep < 0.001 gas flow (L.min -1 ) PASP (mmhg) PaO2 (mmhg) 130 120 100 90 80 70 60 50 65 60 55 50 45 40 35 30 25 20 P < 0.001 PAPS mmhg 10 8 6 4 2 Sweep gas flow (L.min -1 ) 110 Schmidt et al, Intensive Care Med, 2013 PASP (mmhg) PaO2 (mmhg) 150 140 130 120 110 100 90 80 70 60 75 50 65 70 60 65 55 60 50 55 45 50 45 40 4035 3530 3025 2520 150 140 130 120 100 90 80 70 P < 0.001 PaCO2 mmhg 10 8 6 4 2 Sweep gas flow (L.min -1 )
ECMO and ECCO2R ECMO Large cannulas High extracorporeal flow >5000 ml/min Large membrane oxygenator Full blood oxygenation Full blood decarboxylation High technicity, ECMO center ECCO2R Double lumen catheter Low flow, respiratory dialysis 250-1000 ml/min Medium size oxygenator No blood oxygenation Partial blood decarboxylation Regular ICU
ECMO and ECCO 2 R What is the Evidence?
Results of series of VV-ECMO in ARDS patients
The CESAR trial
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
Time from randomization to death Log rank p = 0.03
17 (25%)
Et al
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The French REVA Registry collected data of patients hospitalized in ICUs For H1N1-associated ARDS Analysis of factors associated With death among 123 patients who received ECMO Case-control study with Matching on a propensity score to receive ECMO
Why early ECMO?
1 P <0.005, log-rank 0.8 0.6 0.4 0.2 MV <7 days before ECMO MV >7 days before ECMO 0 0 20 40 60 80 100 120 140 160 180
30 Before ECMO After ECMO 500 40 25 400 35 20 300 30 15 200 25 10 100 20 0 0 0 Driving Pressure Tidal Volume Plateau Pressure
Results ECCO R series 2 in ARDS patients
Randomised clinical trial of pressurecontrolled inverse ratio ventilation and ECCO 2 R for ARDS Study design Randomised controlled clinical trial 40 patients with severe ARDS ECCO 2 R versus MV Low-flow veno-venous ECCO R 2 device Results No significant difference in survival at 30 days (p = 0.08): 42% in the MV group (n = 19) 33% in the ECCO 2 R patients (n = 21) All deaths occurred within 30 days of randomization Study stopped for futility >30% patients with severe haemorrhage Morris AH, et al. Am J Respir Crit Care 1994;349:295 305.
Techniques of the 2000 s
Novalung, ILA, Pumpless AV shunt
Novalung, ILA pumpless AV shunt
Frequency of complications and adverse effects Complication / side effect Patients (n) Limb ischemia due to arterial cannulation + need for IV norepinephrine Ischemia of lower limb after cannulation 9 Cannula thrombosis 4 Compartmental syndrome in a lower limb 4 Haematoma / aneurysm at cannulation site 2 Haemolysis 1 Intracerebral haemorrhage 1 Diffuse bleeding / shock syndrome during cannulation 1 All 22 (24.4%) Overall frequency of complications and side effects was 24%
Hemodec DECAP
Individual and average (horizontal bar) respiratory variables before and after initiating CO 2 removal V T (ml/kg PBW) P plat (cm H 2 O) PEEP (cm H 2 O) PaO 2 / FiO 2 )
Techniques of the 2010 s
NOVALUNG
ila activve, Novalung, ILA membrane 22 French double lumen cannula Ten patients hypercapnic respiratory failure Step 1: Sweep gas flow increased from 1 to 14 L/min At constant blood flow Step 2: Blood flow gradually increased at constant sweep gas flow At each step measurement of Arterial blood gas AND Membrane gas transfer
Hemolung, Alung Technologies
Feasibility and safety of low-flow extracorporeal carbon dioxide removal to facilitate ultra-protective ventilation in patients with moderate ARDS
Feasibility and safety of low-flow extracorporeal carbon dioxide removal to facilitate ultra-protective ventilation in patients with moderate ARDS Time course of C RS Time course of driving pressure
PALP, MAQUET
PrismaLung (Baxter)
Anesth Crit Care Pain Med 2014 Mean CO 2 removal rates at F s O 2 1 Preclinical study in 5 adult hypercapnic pigs to investigate the performance of the PrismaLung system with different flow rates (blood flow/ sweep gas flow)
More to come
A new paradigm
Increasing Intensity of Intervention ECMO Inhaled NO Neuromuscular Blockade Prone Positioning ECCO 2 R HFOV NIV Higher PEEP Low-Moderate PEEP Low Tidal Volume Ventilation Mild ARDS Moderate ARDS Severe ARDS 300 250 200 150 100 50 0 The ARDS Definition Taskforce. JAMA 2012;307:2526-2533. PaO 2 /FiO 2
In God we (may) trust; all others must bring data W. Edwards Deming (1900-1993)
We need EOLIA A new trial of ECMO for severe pneumonia/ards 241 patients randomized so far YES WE CAN
A Strategy of UltraProtective lung ventilation With Extracorporeal CO 2 Removal for New-Onset moderate to severe ARDS The SUPERNOVA trial
Conclusion ECMO/ECCO2R: Potential for use in moderate to severe ARDS patients To allow further reduction of Vt/Pplat/ P, to limit VILI ExtraCorporeal CO 2 Removal Respiratory dialysis for moderate ARDS VV-ECMO For refractory hypoxemia For severe ARDS? Before large diffusion, (re)test the concept in large randomized clinical trials