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[email protected] www.paris-ecmo.org Cardiology Institute [email protected] www.paris-tcsecmo.org Cardiology Institute ECMO/ECCO 2 R in Acute Respiratory Failure Alain Combes, MD, PhD Cardiology Institute, 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 [email protected]

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[email protected] www.paris-ecmo.orgCardiology Institute [email protected] www.paris-tcsecmo.orgCardiology Institute

ECMO/ECCO2R in Acute Respiratory Failure

Alain Combes, MD, PhDCardiology Institute, Hôpital Pitié-Salpêtrière, AP-HP

Inserm UMRS 1166, iCAN, Institute of Cardiometabolism and Nutrition

Sorbonne Pierre et Marie Curie University, Paris, [email protected]

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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

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ECMO and ECCO2R…To decrease the intensity of MV?

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LUNG SAFEEpidemiology of ARDS

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Probability of hospital survival by driving

pressure

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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 <2 ml/kg IBW• To decrease Pplat <25 cm H2O• To decrease ∆P < 12-14 cm H2O• With sufficient PEEP to prevent lung derecruitment

• Extracorporeal gas exchange for• Blood Oxygenation/Decarboxylation• Decrease the intensity of MV

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What areECMO and ECCO2R?Same Technology

Different Objectives…

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Membrane lung O2/CO2 transfer

O2 transferCO2 transfer

ECMO for oxygenation

ECCO2R for Decarboxylation

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Influence of ECMO flow

Schmidt et al, Intensive Care Med, 2013

Adequate Oxygenation

Qecmo > 60% Qco

PaO2 mmHg

SaO2, %

PaCO2 mmHg

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Influence of Sweep Gas Flow

Schmidt et al, Intensive Care Med, 2013

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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

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ECMO and ECCO2R…What is the Evidence?

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Results of series of VV-ECMO in ARDS patients

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The CESAR trial

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• 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

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Time from randomization to death

Log rank p = 0.03

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17 (25%)

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Et al…

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Et al…

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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

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Why early ECMO?

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Results ECCO2R seriesin ARDS patients

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Morris AH, et al. Am J Respir Crit Care 1994;349:295−305.

Randomised clinical trial of pressure-controlled inverse ratio ventilation and ECCO2R for ARDS

Study design

• Randomised controlled clinical trial

• 40 patients with severe ARDS

• ECCO2R versus MV

– Low-flow veno-venous ECCOR2 device

Results

• No significant difference in survival at 30 days (p = 0.08):

– 42% in the MV group (n = 19)

– 33% in the ECCO2R patients (n = 21)

– All deaths occurred within 30 days of randomization

• Study stopped for futility

• >30% patients with severe haemorrhage

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Techniques of the 2000’s…

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Novalung, ILA, Pumpless AV shunt

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Novalung, ILA pumpless AV shunt

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Frequency of complications and adverse effects

Complication / side effect Patients (n)

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

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norepinephrineOverall frequency

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Hemodec DECAP

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Individual and average (horizontal bar) respiratory variables

before and after initiating CO2 removal

VT (mL/kg PBW) Pplat (cm H2O) PEEP (cm H2O) PaO2 / FiO2)

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Techniques of the 2010’s…

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NOVALUNG

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• 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

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Hemolung, Alung Technologies

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Feasibility and safety of low-flow extracorporeal carbon dioxide

removal to facilitate ultra-protective ventilation in patients with

moderate ARDS

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Time course of CRS Time course of driving pressure

Feasibility and safety of low-flow extracorporeal carbon dioxide

removal to facilitate ultra-protective ventilation in patients with

moderate ARDS

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PALP, MAQUET®

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PrismaLung (Baxter)

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Anesth Crit Care Pain Med 2014

Mean CO2 removal rates at FsO2 1

Preclinical study in 5 adult hypercapnic pigs to investigate the performance of thePrismaLung system with different flow rates (blood flow/ sweep gas flow)

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More to come…

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A new paradigm…

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Mild ARDS Severe ARDSModerate ARDS

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NIV

Neuromuscular Blockade

Inhaled NO

ECCO2R

ECMO

HFOV

The ARDS Definition Taskforce. JAMA 2012;307:2526-2533.

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“In God we (may) trust; all others

must bring data…”W. Edwards Deming

(1900-1993)

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We need EOLIA… A new trial of

ECMO for severe pneumonia/ARDS241 patients randomized so far…

YESWECAN

YESWECAN

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A Strategy of UltraProtective lung ventilation

With Extracorporeal CO2 Removal for

New-Onset moderate to seVere ARDS

The SUPERNOVA trial

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Conclusion

• ECMO/ECCO2R: Potential for use in moderate to severe ARDS patients

• To allow further reduction of Vt/Pplat/∆P, to limit VILI…

• ExtraCorporeal CO2 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…

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