VV-ECMO for

refractory ARDS…

Alain Combes

Service de Réanimation

iCAN, Institute of Cardiometabolism and Nutrition

Hôpital Pitié-Salpêtrière, AP-HP, Paris

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

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

Severe ARDS

Is still a severe disease…

Hospital mortality: 58%

PaO2/FiO2 < 100 Subgroup

Should we use

VV-ECMO for severe

ARDS? Analyzing evidence-based medicine data…

ECMO and

ARDS…

« Historical » studies

ECMO for acute respiratory

failure

1968: Kolobow and Zapol develop the first membrane oxygenator Permitting prolonged extracorporeal oxygenation

1971: First clinical report of the use of the Bramson machine Donald Hill, 1972; NEJM

NEJM, 1972

24 yrs old male

Blunt thoracic trauma

« Shock Lung »

VA ECMO for 75h

Fully recovered

NEJM, 1972

Bramson

ECMO

machine

NEJM, 1972

Did he survive despite ECMO????

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

Zapol, W

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“Outdated” devices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

Severe hemorrhage

Randomized clinical trial of pressure-controlled inverse ratio

ventilation and extracorporeal CO2 removal for adult

respiratory distress syndrome

Randomized controlled trial

40 patients, severe ARDS

CO2 epuration:

« Low-flow veno-venous device »

ECCO2R

D30 survival:

42% for the 19 patients in the control arm

33% for the 21 « ECCO2R » patients (p = 0.8)

Trial stopped for futility

>30% patients with severe hemorrhage

Morris, AH, AJRCCM, 94

More recent

studies…

ELSO registry from 1986–2006

1,473 patients with severe respiratory failure

50% survived to hospital discharge

Median age was 34 years

Most patients (78%) supported with venovenous ECMO

Influenza A

(H1N1)v09 …

17 (25%)

Et al…

Et al…

The French REVA H1N1 ECMO

cohort

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

Am J Resp Crit Care Med, in press

The French REVA H1N1 ECMO

cohort Am J Resp Crit Care Med, in press

BUT… data from retrospective

series…

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

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

We need a new trial to

convince the skeptics…

Hubmayr, Rolf D., M.D. rhubmayr@mayo.edu

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…

Cohort ANZ

Anzic group NEJM, 09

Canada, Kumar

JAMA, 2009

Utah, The USA Miller

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

Hubmayr, Rolf D., M.D. rhubmayr@mayo.edu

At this time, we do not

support the position that as

a nation we should invest in

the development of

additional ECMO centers

PaO2 = 25 mm Hg

SaO2 = 55%

Designing

a new trial…

EOLIA:

ECMO to rescue Lung Injury in severe ARDS

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

• CardioHelp, from Maquet

Inclusion of some non-ECMO centers with a mobile ECMO rescue team available from the referral center in less than 1 hour

• 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

EOLIA: ECMO to rescue Lung Injury

in severe ARDS

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

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

EOLIA: ECMO to rescue Lung

Injury in severe ARDS

EOLIA: ECMO to rescue Lung Injury

in severe ARDS

Conclusion

For the most severe forms of acute respiratory

failure, ECMO:

Replaces pulmonary function

Allows ultraprotective MV settings

Should allow facilitated lung healing

Only experienced centers should run these programs

With a mobile ECMO retrieval team available 24H/7D

Still a controversy on the use of ECMO

Need for a confirmation trial…

47 patients randomized in the EOLIA Trial…