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© Annals of Translational Medicine. All rights reserved. Ann Transl Med 2017;5(5):119atm.amegroups.com
Editorial
Meta-analysis on extracorporeal life support during cardiac arrest:
do not compare apples and oranges
Sacha Rozencwajg, Matthieu Schmidt
Medical Intensive Care Unit, iCAN, Institute of Cardiometabolism and Nutrition, La Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de
Paris, Paris, France
Correspondence to: Matthieu Schmidt, MD, PhD. Service de Réanimation Médicale, iCAN, Institute of Cardiometabolism and Nutrition, Hôpital de
la Pitié–Salpêtrière, 47, bd de l’Hôpital, 75651 Paris Cedex 13, France. Email: matthieu.schmidt@aphp.fr.
Provenance: This is a Guest Editorial commissioned by Section Editor Zhi Mao, MD (Department of Critical Care Medicine, Chinese People’s
Liberation Army General Hospital, Beijing, China).
Comment on: Ouweneel DM, Schotborgh JV, Limpens J, et al. Extracorporeal life support during cardiac arrest and cardiogenic shock: a systematic
review and meta-analysis. Intensive Care Med 2016;42:1922-34.
Submitted Dec 15, 2016. Accepted for publication Dec 23, 2016.
doi: 10.21037/atm.2017.01.24
View this article at: http://dx.doi.org/10.21037/atm.2017.01.24
In a recent issue of Intensive Care Medicine, Ouweneel
et al. provided a meta-analysis on extracorporeal life
support (ECLS) during cardiac arrest (CA) and cardiogenic
shock (1). Cardiogenic shock analysis compared ECLS
vs. Impella, TandemHeart, or intra-aortic balloon pump
(IABP). As these devices have various support levels,
different specifications, and therefore different clinical
indications, results issued from this analysis are clinically
questionable. In addition, based on the recent IABP Shock
II trial (2), current European guidelines on cardiogenic
shock no longer support routine IABP therapy use, except
for mechanical complications (class IIaC). As reported by
the authors, caution is required in interpreting this part of
the meta-analysis and our interest was therefore focused
on the evaluation of ECLS during CA.
ECLS on cardiopulmonary resuscitation (E-CPR) is the
ultimate rescue therapy, which might be offered only when
conventional resuscitation measures have failed. Latest
guidelines from the American Heart Association (AHA) (3)
recommend that E-CPR should be considered “when ECPR
is readily available, (…) the time without blood ow is short
and the condition leading to CA is deemed reversible or
amenable to heart transplantation or revascularization” (class
IIb). As stated in this recommendation by a level of evidence
at C, studies supporting these guidelines are actually limited
(4-6). Most of them had small numbers of patients, and
unbalanced comparison groups with respect to age, witness
status, bystander CPR, and the quality of conventional
CPR. In this setting, Ouweneel et al. gathered these
heterogeneous studies and their meta-analysis brings new
insights although no prospective randomized controlled
trials exist yet. They selected nine retrospective studies
(4,7-14), comparing E-CPR vs. conventional CPR (C-CPR),
resulting in a total of 3.098 patients (708 ECLS vs. 2.390
control). Outcomes were 30-day survival rate and favorable
neurological outcomes [Glasgow-Pittsburgh cerebral-
performance categories (CPC) score of 1 or 2] at 30 days
evaluated by total cohort and propensity-matched cohort
analysis (when available). The usage of ECLS in this setting
was associated with increased survival at 30 days (absolute
risk difference 13%; 95% CI 6–20%; P>0.001) and higher
rate of favorable neurological outcome at both 30 days
(risk difference 14%; 95% CI 7–20%; P>0.001) and during
long-term follow-up. Same tendencies were observed with
propensity score matching (Table 1).
As mentioned by the authors, total-cohort analysis results
should be taken with precaution and warrant discussion.
First, all studies included CA patients with different
inclusion criteria such as in-hospital cardiac arrest (IHCA),
out-of-hospital cardiac arrest (OHCA), witnessed or non-
witnessed CA and differing duration of CPR. Overall, ECLS
patients were more likely to be younger, male, suffer from
myocardial infarction and to undergo primary percutaneous
coronary intervention (PCI). Second, the total-cohort
Rozencwajg and Schmidt. Meta-analysis on ECLS during CA
© Annals of Translational Medicine. All rights reserved. Ann Transl Med 2017;5(5):119atm.amegroups.com
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analysis of survival rate is driven by Lee et al.’s cohort (10)
(34% of total patients population included) whose E-CPR
and C-CPR patients’ characteristics were significantly
different in term of age, co-morbidities, CA’s location and
cause and initial shockable rhythm (P<0.0001). These
relevant factors were consistently reported as risk factors
in studies on C-CPR (15,16). Third, revascularization
procedures were more frequent in the E-CPR groups in
several studies (4,11), which is an important bias to consider.
Indeed, it is worth remembering that PCI is associated with
better survival, which is made possible by ECLS for the
most severe patients. Lastly, this meta-analysis constantly
mixes studies focused on IHCA (4,7,8,10) and OHCA
(9-12) with obviously very different survival rates (17).
In our opinion, IHCA and OHCA have such distinct
presentation, management delays, and outcome that
mixing these two populations preclude raising any solid
clinical message on E-CPR use. For the same reasons,
neurological outcome in the total-cohort analysis is biased.
Although it’s impact on neurological outcome remains
uncertain (especially in the absence of an initial shockable
rhythm) (18), hypothermia also differed between studies,
introducing another potential confounding bias.
In absence of randomized controlled trial on this topic,
propensity-matched support analysis where the propensity
score reflects the probability of receiving ECLS therapy,
could minimize these biases. Herein, 438 and 195 patients
were matched for 30-day survival and neurological outcome
evaluation, respectively (4,7,9,11,14). Despite a major
reduction in the number of included patients, results remain
in favor of E-CPR group for both 30-day survival rates
(risk difference 14%; 95% CI 2–25%; P=0.02; number
needed to treat 7.1) and favorable neurological outcome
(risk difference 13%; 95% CI 7–20%; P=0.0001; NNT
7.7) (Table 1). These results were consistent with long-term
outcomes. However, substantial heterogeneity (I
2
=54%)
was reported in this analysis. That was mainly explained
by the study of Shin et al. (14) where PCI and return of
spontaneous circulation (ROSC) were significantly more
frequent in the E-CPR group (P<0.001 and P=0.004,
respectively) and consequently weighted in the analysis with
a higher risk difference (0.25; 95% IC 0.10–0.43). Lastly,
although the number of patients included in the propensity-
matched support analysis was limited, the most interesting
result were obtained for 30-day and long-term neurological
outcome evaluation, which remain in favor of the E-CPR
group. However, it is worth pointing out that favorable
neurological was observed only in 23% and 14% patients
at 30 days and after long-term follow-up, respectively. In
regard of this outcome, performing a secondary analysis
aimed at differentiating between IHCA and OHCA
would have been of interest to enable a more thorough
interpretation of results. However, the small number of
patients in each group would have unfortunately, limited
this analysis.
In the context of E-CPR, the Pygmalion effect (or
Rosenthal effect or self-fulfilling prophecy), phenomena
whereby higher expectations lead to an increase in
performance (19), has had a particular impact. Patients
receiving E-CLS for CA are systematically younger with
less co-morbidity. In this context, a full-code therapy which
involves all stakeholders (pre-hospital team, mobile ECMO
Table 1 Pooled risk difference of 30-day survival and favorable neurologic outcome (CPC 1 or 2) in the total cohort and after propensity-matched
analysis in patients with cardiac arrest
Outcomes
Total cohort Propensity-matched cohort
N
Risk difference which
favors E-CPR
P N
Risk difference which
favors E-CPR
P
30-day follow-up
Survival 2,774 0.13 (0.06–0.20) 0.0002 438 0.14 (0.02–0.25) 0.02
Favorable neurological outcome 1,590 0.14 (0.07–0.20) <0.0001 390 0.13 (0.07–0.20) 0.0001
Long-term follow-up
Survival 2,040 0.15 (0.11–0.20) <0.0001 438 0.13 (0.06–0.20) 0.0002
Favorable neurological outcome 1,750 0.11 (0.06–0.16) <0.0001 438 0.14 (0.08–0.20) <0.0001
E-CPR, extracorporeal life support on cardiopulmonary resuscitation.
Annals of Translational Medicine, Vol 5, No 5 March 2017
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© Annals of Translational Medicine. All rights reserved. Ann Transl Med 2017;5(5):119atm.amegroups.com
team, intensivists, nurses…) is more likely to be done.
Indeed, patients who received E-CPR underwent more
frequently PCI and hypothermia, which both may have
an impact on the outcome. In the absence of randomized
controlled trial, such propensity-matched analysis is still
insufficient to evaluate the benefit of E-CPR vs. C-CPR.
In the interim, E-CPR should be limited to refractory CA
in young adults without comorbidities who received CPR
from a bystander with a shockable rhythm. Ouweneel et al.’s
meta-analysis pointed out the urgent need for a randomized
controlled trial on this topic to determine which patients
are likely to be the best candidates and how this costly
rescue therapy should be performed.
Acknowledgements
None.
Footnote
Conicts of Interest: The authors have no conicts of interest
to declare.
References
1. Ouweneel DM, Schotborgh JV, Limpens J, et al.
Extracorporeal life support during cardiac arrest and
cardiogenic shock: a systematic review and meta-analysis.
Intensive Care Med 2016;42:1922-34.
2. Thiele H, Zeymer U, Neumann FJ, et al. Intraaortic
balloon support for myocardial infarction with cardiogenic
shock. N Engl J Med 2012;367:1287-96.
3. Cave DM, Gazmuri RJ, Otto CW, et al. Part 7: CPR
techniques and devices: 2010 American Heart Association
Guidelines for Cardiopulmonary Resuscitation
and Emergency Cardiovascular Care. Circulation
2010;122:S720-8.
4. Chen YS, Lin JW, Yu HY, et al. Cardiopulmonary
resuscitation with assisted extracorporeal life-support
versus conventional cardiopulmonary resuscitation in
adults with in-hospital cardiac arrest: an observational
study and propensity analysis. Lancet 2008;372:554-61.
5. Chen YS, Yu HY, Huang SC, et al. Extracorporeal
membrane oxygenation support can extend the duration
of cardiopulmonary resuscitation. Crit Care Med
2008;36:2529-35.
6. Nagao K, Kikushima K, Watanabe K, et al. Early
induction of hypothermia during cardiac arrest improves
neurological outcomes in patients with out-of-hospital
cardiac arrest who undergo emergency cardiopulmonary
bypass and percutaneous coronary intervention. Circ J
2010;74:77-85.
7. Blumenstein J, Leick J, Liebetrau C, et al. Extracorporeal
life support in cardiovascular patients with observed
refractory in-hospital cardiac arrest is associated with
favourable short and long-term outcomes: A propensity-
matched analysis. Eur Heart J Acute Cardiovasc Care
2016;5:13-22.
8. Chou TH, Fang CC, Yen ZS, et al. An observational
study of extracorporeal CPR for in-hospital cardiac
arrest secondary to myocardial infarction. Emerg Med J
2014;31:441-7.
9. Kim SJ, Jung JS, Park JH, et al. An optimal transition
time to extracorporeal cardiopulmonary resuscitation for
predicting good neurological outcome in patients with
out-of-hospital cardiac arrest: a propensity-matched study.
Crit Care 2014;18:535.
10. Lee SH, Jung JS, Lee KH, et al. Comparison of
Extracorporeal Cardiopulmonary Resuscitation with
Conventional Cardiopulmonary Resuscitation: Is
Extracorporeal Cardiopulmonary Resuscitation Benecial?
Korean J Thorac Cardiovasc Surg 2015;48:318-27.
11. Maekawa K, Tanno K, Hase M, et al. Extracorporeal
cardiopulmonary resuscitation for patients with out-of-
hospital cardiac arrest of cardiac origin: a propensity-
matched study and predictor analysis. Crit Care Med
2013;41:1186-96.
12. Sakamoto T, Morimura N, Nagao K, et al. Extracorporeal
cardiopulmonary resuscitation versus conventional
cardiopulmonary resuscitation in adults with out-of-
hospital cardiac arrest: a prospective observational study.
Resuscitation 2014;85:762-8.
13. Siao FY, Chiu CC, Chiu CW, et al. Managing cardiac
arrest with refractory ventricular brillation in the
emergency department: Conventional cardiopulmonary
resuscitation versus extracorporeal cardiopulmonary
resuscitation. Resuscitation 2015;92:70-6.
14. Shin TG, Jo IJ, Sim MS, et al. Two-year survival and
neurological outcome of in-hospital cardiac arrest patients
rescued by extracorporeal cardiopulmonary resuscitation.
Int J Cardiol 2013;168:3424-30.
15. Hajbaghery MA, Mousavi G, Akbari H. Factors
inuencing survival after in-hospital cardiopulmonary
resuscitation. Resuscitation 2005;66:317-21.
16. Hazinski MF, Nolan JP, Billi JE, et al. Part 1:
Executive summary: 2010 International Consensus
Rozencwajg and Schmidt. Meta-analysis on ECLS during CA
© Annals of Translational Medicine. All rights reserved. Ann Transl Med 2017;5(5):119atm.amegroups.com
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Cite this article as: Rozencwajg S, Schmidt M. Meta-analysis
on extracorporeal life support during cardiac arrest: do not
compare apples and oranges. Ann Transl Med 2017;5(5):119. doi:
10.21037/atm.2017.01.24
on Cardiopulmonary Resuscitation and Emergency
Cardiovascular Care Science With Treatment
Recommendations. Circulation 2010;122:S250-75.
17. Mozaffarian D, Benjamin EJ, Go AS, et al. Heart
Disease and Stroke Statistics—2016 Update—A Report
From the American Heart Association. Circulation
2015;CIR.0000000000000350.
18. Highlights of the 2015 AHA Guidelines Update for CPR
& ECC. Available online: http://eccguidelines.heart.org/
wp-content/uploads/2015/10/2015-AHA-Guidelines-
Highlights-English.pdf
19. Rosenthal R, Jacobson L. Pygmalion in the classroom.
Urban Rev 1968;3:16-20.