eolia, defining the role of ecmo for ards: an update combes.pdf · eolia, defining the role of ecmo...

EOLIA, Defining The Role Of ECMO For ARDS: An Update …

Alain Combes

Service de Réanimation

iCAN, Institute of Cardiometabolism and Nutrition

Hôpital Pitié-Salpêtrière, AP-HP, Paris

Université Pierre et Marie Curie, Paris 6www.reamedpitie.com

26° Congresso Nazionale della Società Italiana di Terapia Intensiva

Name…COMBES………………Surname…Alain…………..

I declare that in the last two years I had funding relationship with the followingsubjects with commercial interest:

Names of the Companies

___MAQUET, co-sponsor of the EOLIA trial, NCT01470703_______

___ GAMBRO, co-sponsor of the HEROICS trial, NCT01077349

_____

I also declare that these relationships are not such as to influence the teachingactivities of the present congress.

So I’m not in a situation of conflict of interest.

Conflict of interest

Principal Investigator: HEROICS trial HVHF after complicated heart surgery NCT01077349 Sponsored by GAMBRO

Principal Investigator: EOLIA trial VV ECMO in ARDS NCT01470703 Sponsored by MAQUET, Getinge Group

Received honoraria from MAQUET, Getinge Group

Do we really need more trials of ECMO for ARDS????

Analyzing evidence-based medicine data…

YES, because ARDS is still a severe disease

Hospital mortality: 58%

PaO2/FiO2 < 100 Subgroup

YES, because VV-ECMO can result in good prognosis for severe ARDS

Study population

YES, because data fromretrospective series…

Will never eliminate the bias of patients’ selection to receive ECMO

Et al…

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

YES, because only 3 randomized trials…

And only one with 21st

century standard of care

Zapol, W

Nine medical centers, Mid 70’s

Prospective randomized trial to evaluate ECMO for ARDS

90 adult patients selected

Mechanical ventilation + venoarterial ECMO (42 patients)

Conventional mechanical ventilation (48 patients)

Four patients in each group survived

Patients died of:

Progressive reduction of transpulmonary gas exchange

Decreased compliance due to diffuse pulmonary inflammation, necrosis, and fibrosis

“ECMO can support respiratory gas exchange but did not increase the probability of survival for severe ARDS”

Zapol, W

Caveats of this first study

“Outdated” devices

Veino-arterial bypass only

ECMO weaned systematically at D5

Prolonged MV before randomization

“Old-fashioned” MV

Profound anticoagulation

NEJM, 1972

BramsonECMO

machine

NEJM, 1972

Did he survive despiteECMO????

The “CESAR” trial…

Time from randomization to death

Log rank p = 0.03

“Dissecting” CESAR…

14/17 (82%) survived with conventional ICU management alone after transfer to Leicester

Benefit reported not for ECMO alone But for a strategy of referral to a

single ECMO-capable hospital

For ECMO assessment and management if criteria are met

Did improved care at the single ECMO hospital lead to the relative risk observed???

About †, ‡ and …

† Based on 177 patients with known primary outcome‡ % calculated with denominator of 87 patients

§ 3 patients discharged alive, alive at 6 months, but no information on disability

If the 3 patients in the control group had all been severely disabled, RR of the 1st outcome would be 0.72 (0.51–1.01, p=0.051)

Should we transport severe ARDS patients without ECMO?

6% died without ECMO

YES, we need a new trial to convince the skeptics…

Hubmayr, Rolf D., [email protected]

Who really knows how the absolute risk of a plateau

pressure >30 “stacks up” against the risk associated with an ECMO run?

Who is to say that an Fio2 of 1.0 cannot be tolerated for some duration

without long-term consequence? There are those who believe

hypercapnic acidosis is lung protective…

CohortANZ

Anzic groupNEJM, 09

Canada, Kumar

JAMA, 2009

Utah, The USAMiller

Chest 2010

Confirmed H1N1, n 722 162 47

Received MV, % 63% 84% 79%

Received ECMO, % 12% 4% 0

Mortality, % 15% 17% 17%

Critically ill patients during the 2009 H1N1 Influenza pandemic


At this time, we do not support the position that as a nation we should invest in

the development of additional ECMO centers


At this time, we do not support the position that as a nation we should invest in

the development of additional ECMO centers

Situation of EQUIPOISE

PaO2 = 25 mm Hg

SaO2 = 55%

Designing a new trial…

EOLIA: ECMO to rescue Lung Injury in severe ARDS


Multicenter international randomized controlled trial

Best care possible in the ECMO arm

ECMO initiated asap for every patient randomized

• Using the most recent ECMO technology

Transport of randomized patients to the referral center UNDER ECMO

ECMO managed only in highly experienced centers

“Highly protective” MV

• Plateau pressure limited to ≤ 24 cm H2O


Best care possible in the control arm

MV protocolized using the “high PEEP – high recruitment” strategy of the EXPRESS trial

To limit plateau pressure <28-30 cm H2O• Vt limited to 6 ml/kg IBW

Including Prone positioning

“Ethical” cross-over option to ECMO if the patient develops refractory hypoxemia

We need EOLIA… A new trial of ECMO for severe pneumonia/ARDS

105 patients randomized so far…

YESWECAN

YESWECAN

Conclusion

VV-ECMO can rescue 50-80% of the patients

with severe respiratory failure

50-70% of whom have severe pneumonia

Controversy still highly active regarding its

Real impact on the outcomes of patients with the

most severe forms of ARDS

EQUIPOISE for a new trial… the EOLIA trial!...

May 21-24 2014

eolia, defining the role of ecmo for ards: an update combes.pdf · eolia, defining the role of ecmo...

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