Research in ECMO: A revolution is coming

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Research in ECMO: A revolution is coming Daniel Brodie Critical Care Canada Forum Toronto, Ontario October 27 th, 2015

Research in ECMO: A revolution is coming??? Daniel Brodie Critical Care Canada Forum Toronto, Ontario October 27 th, 2015

Faculty Disclosures Daniel Brodie Maquet Cardiovascular Research support Research consulting ALung Technologies Medical Advisory Board Kadence Medical Advisory Board International ECMO Network Chairman, Executive Committee ECMO is off label

Advances in technology Pumps Oxygenators Biocompatible circuits Catheters

Rapid growth of ECMO 2009 to present

2009 Influenza A (H1N1) pandemic

CESAR Trial Peek G, et al. Lancet 2009

Active ECLS Centers ELSO Registry January 2015

Adult Respiratory Cases ELSO Registry January 2015

Adult Cardiac Cases ELSO Registry January 2015

But wait...

Where s the evidence?

Del Sorbo et al. AJRCCM 2012

900 800 700 600 500 Pubmed search: Extracorporeal membrane oxygenation OR Extracorporeal carbon dioxide OR Extracorporeal CPR 9,192 references dating back to 1960 Spike 2010 to ~650 (from 300 in 09) 2015 annualized to 800 (same as 2014) 2010 400 1989 300 200 100 0 60 62 64 66 68 70 72 74 76 78 80 82 84 86 88 90 92 94 96 98 0 2 4 6 8 10 12 14 Publication Volume

What is the quality of the literature in ECMO?

* Abrams D, Combes A, Brodie D. JACC 2014

* *Cohort study with propensity analysis Abrams D, Combes A, Brodie D. JACC 2014

RCTs for ECMO in ARDS

Zapol 1979 Morris 1994

Advances in technology...

Modern RCT in ECMO

CESAR Trial Peek G, et al. Lancet 2009

Peek G, et al. Lancet 2009

Where should we go from here?

Collaboration

Why is collaboration so important to the future of ECMO research?

ECMO is... Complex High risk Expensive Wide variations in technique

We need to settle the most basic questions Does it work? Who might benefit? How to use it? How do our patients do long term?

Need to advance the science of ECMO Basic Translational Clinical questions

How are we doing?

ECMO Research Fragmented across centers, countries, continents

What should we do?

First...

Build top quality ECMO centers Perform quality ECMO Combes A, et al. AJRCCM 2014

Why build top quality clinical centers before we even know ECMO works?

To participate meaningfully in high quality research Zapol Morris Combes A, et al. AJRCCM 2014

AJRCCM 2014 Call for research centers

Do we need top quality centers Or just more centers?

Volume-outcome in ECMO?

Retrospective review of ELSO database 1989-2013 290 centers 56,222 patients (30k neonatal, 15k peds, 11k adult) AJRCCM 2015

Higher age group-specific ECMO volume associated with lower odds of mortality in neonatal & adult populations 2008-2013 only held in adults 30 adult ECMO cases/y OR mortality 0.61 (compared with < 6 cases/y) AJRCCM 2015

Not every center should be doing ECMO in 2015 Regionalization Highest quality, best practices Combes A, et al. AJRCCM 2014

Next...

Drive collaboration Across centers, countries & continents

We need a research network in ECMO

ECMONet INTERNATIONAL ECMO NETWORK www.internationalecmonetwork.org

ECMONet Vision To serve the ECMO research community

Foster & support High-quality, high-impact research ideas by investigators throughout the world

International ECMO Network Ongoing & Upcoming Studies

ECMO to rescue Lung Injury in severe ARDS EOLIA International RCT PI: Alain Combes Enrolling December 2011

ECCO 2 R for Lung-protection Moderate to severe ARDS SUPERNOVA Pilot Study International, multicenter, RCT PI: Alain Combes, Marco Ranieri

LIFEGARDS ventilation management of patients with Extracorporeal membrane oxygenation for Acute Respiratory Distress Syndrome An international observational study Steering committee Matthieu Schmidt (Paris, Melbourne) = PI Carol Hodgson (Melbourne) Vincent Pellegrino (Melbourne) Alain Combes (Paris) Eddy Fan (Toronto) Daniel Brodie (New York)

Low-dose heparin in critically ill patients undergoing ECMO Single center, unblinded, randomized, feasibility study The HELP-ECMO Study Investigators: C Aubron, V Pellegrino, D Pilcher, J Sheldrake, D Murphy, J Board, L Hockings, J Cooper

What percentage of ICU patients may be candidates for gas exchange extracorporeal techniques? The XXL study PI: Laurent Brochard & Eddy Fan

ASAP ECMO Antibiotic, Sedative and Analgesic Pharmacokinetics during ECMO PI: Kiran Shekar Multicentre study of population PK models in ECMO 250 subjects Develop evidence-based guidelines

International ECMO Network Proposed Studies

protective ventilation with venovenous lung assist in respiratory failure REST Study UK collaborative Multicentre, RCT PI: Danny McAuley & James McNamee ECCO 2 R for acute hypoxemic respiratory failure Not just ARDS P:F < 150 1,120 subjects 28 day mortality

ANCHOR Assessment of ECMO in acute myocardial infarction with Non-reversible, Cardiogenic shock to Halt Organ failure & Reduce mortality Prospective, open-label, multicenter, randomized, controlled trial PI: Alain Combes

ECMO PT ECMO early staged physical training Carol Hodgson ANZIC-RC ACTION CRE 240 subjects Multicentre, assessor-blinded, RCT Physical rehab within 48 hours of ECMO vs. no rehab Outcomes: functional status & muscle strength

ImmunoDeficiency and ECMO for Acute respiratory failure IDEA study Multicenter, retrospective cohort study Matthieu Schmidt, Vincent Pellegrino, Carol Hodgson, Alain Combes, Eddy Fan, Daniel Brodie

Multiple other high quality research efforts beyond ECMONet

ECCO 2 R for COPD? Need RCTs Multiple planned international, multicenter RCTs

Is a revolution coming?

Certainly an evolution

Active ECLS Centers ELSO Registry January 2015

Need for high quality research ECMONet INTERNATIONAL ECMO NETWORK www.internationalecmonetwork.org