ARTICLE IN PRESS

Journal of Cardiothoracic and Vascular Anesthesia 000 (2019) 16

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Journal of Cardiothoracic and Vascular Anesthesia

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Original Article
A 266 Patient Experience of a Quaternary Care
Referral Center for Extracorporeal Membrane
Oxygenation with Assessment of Outcomes for
Transferred Versus In-House Patients
Adam A. Dalia, MD, MBA*, , Andrea Axtel, MDy,
1

Mauricio Villavicencio, MDy, David D’Allesandro, MDy,

Ken Shelton, MD*, Gaston Cudemus, MD*, Jamel Ortoleva, MDz
*
Department of Anesthesiology, Critical Care, and Pain Medicine Massachusetts General Hospital,
Boston, MA
y
Department of Cardiothoracic Surgery, Massachusetts General Hospital, Boston, MA
z
Department of Anesthesiology and Perioperative Medicine, Tufts Medical Center, Boston, MA

Objective: Patients undergoing venoarterial extracorporeal membrane oxygenation (VA-ECMO) require highly trained specialists and resources
to be cared for safely. Interestingly, comparisons of outcomes for patients cannulated for VA-ECMO by outside institutions and transferred to
referral centers for further care versus those cannulated and taken care of in house at the referral center have not been reported on a large scale.
This study aimed to perform the first comparison of these 2 populations based on the experience of a single quaternary referral center.
Design: A retrospective chart reviewbased study in a single quaternary care center of patients cannulated by referring institutions for
VA-ECMO then transferred versus patients who were cannulated in house was performed to assess for a difference in survival (both of ECMO
therapy and survival to discharge).
Setting: Single quaternary academic referral center for ECMO.
Participants: All patients undergoing VA-ECMO who were at least 18 years old from 20112018 (266 patients).
Intervention: None.
Measurements and Main Results: The study comprised 215 patients cannulated for VA-ECMO in house and 51 patients cannulated by 17 differ-
ent outside institutions then transferred. Survival of the ECMO run for in-house patients (122/215) was 56.7% (95% confidence interval [CI]
50.1-63.3), and survival of transferred patients (31/51) for the ECMO run was 60.8% (95% CI 47.4-74.2; p = 0.58). Survival to discharge in
patients cannulated in house (82/215) was 38.1% (95% CI 31.6-44.6) and for outside hospital transfers (24/51 patients) was 47.1% (95% CI
33.4-60.8; p = 0.23).
Conclusions: This retrospective chart review of 266 patients found no difference in survival of the ECMO therapy or survival to discharge in
patients cannulated by other institutions and transferred versus those who were cannulated in house. Even though analysis on the feasibility of
transfer centers has been performed extensively in patients with respiratory failure requiring venovenous ECMO, minimal investigation has been
performed in patients requiring VA-ECMO. These results should be considered hypothesis-generating because larger sample sizes are necessary
to guide care of these patients more definitively.
Ó 2019 Elsevier Inc. All rights reserved.

Key Words: extracorporeal membrane oxygenation; extracorporeal life support; transferred patients; outside hospital extracorporeal membrane oxygenation

1 EXTRACORPOREAL MEMBRANE oxygenation (ECMO)

Address reprint requests to Adam A. Dalia, MD, MBA, Division of Cardiac
Anesthesiology, Department of Anesthesia, Critical Care and Pain Medicine,
Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114.
E-mail address: aadalia@mgh.harvard.edu (A.A. Dalia).
is used to support patients with cardiac, respiratory, or combined
cardiorespiratory failure that is refractory to medical; pharmaco-
logic; and more commonly used modes of organ support, such

https://doi.org/10.1053/j.jvca.2019.05.017
1053-0770/Ó 2019 Elsevier Inc. All rights reserved.
 ARTICLE IN PRESS
2 A.A. Dalia et al. / Journal of Cardiothoracic and Vascular Anesthesia 00 (2019) 16
as vasoactive medications and intubation with mechanical ven-
tilation.15 ECMO has been used in a variety of pathologies
including acute respiratory distress syndrome owing to H1N1,
pulmonary embolism, myocarditis; as a bridge to transplantation
or another bridge; as a treatment with cardiopulmonary resusci-
tation (CPR) (venoarterial [VA]-ECMO cannulation during car-
diopulmonary resuscitation [eCPR]); and for postcardiotomy
shock among other indications.1,3,6,7 ECMO strategies include
venovenous (VV) for lung support; right atrial to pulmonary
artery with an oxygenator for right ventricular and lung support,
and VA for heart and lung support.1,2 ECMO may be deployed
centrally (with sternotomy) or peripherally, with different con-
siderations and personnel required for each access site. ECMO
is a very complex and resource-intensive technology with multi-
ple complications, including but not limited to limb ischemia,
retroperitoneal hematoma, arterial access complications, intra-
cranial hemorrhage, stroke, and North-South syndrome (differ-
ential hypoxia).2,810 Given the complexity of caring for
patients on ECMO, admission to an institution with facile access
to multiple specialty services is important.
VA-ECMO referral centers exist throughout the world, but
investigations into the feasibility of transferring patients
undergoing this type of support have been extremely limited.
It is notable that VA-ECMO performed in patients not requir-
ing CPR carries a 42% survival to discharge, whereas VA-
ECMO with CPR has demonstrated a 29% survival, a
markedly worse prognosis than that with VV-ECMO, which
carries a 59% survival to discharge, according to the Extracor-
poreal Life Support Organization (ELSO) database.8 Thus, it
is reasonable to investigate the experience of a referral model
specifically for VA-ECMO patients.
Adult ECMO was started at the authors’ institution in 2009,
and the authors previously have reported on various aspects of
their experience.1113 The patients are heterogenous and diag-
noses include postcardiotomy shock, myocardial infarction,
myocarditis, and cardiopulmonary arrest. The present study
focuses on the authors’ 20112018 ECMO referral experience
at their institution.
Methods
After obtaining Institutional Review Board (IRB) approval
(Massachusetts General Hospital IRB), a database of adult
(age 18 years or older) ECMO patients at the authors’ quater-
nary referral center was searched, resulting in 433 ECMO
placements. Requirement for written informed consent was
waived by the IRB. The database starts in 2009 and extends to
the present, but the year 2011 was deemed as the first year for
analysis because that was the year of the first accepted VA-
ECMO transfer. In addition, this time frame was selected to
account for any improvement in ECMO care that may have
occurred during the 2009 to 2010 period before transfers were
accepted. The database query resulted in 399 ECMO place-
ments since 2011. Patients who required more than 1 place-
ment of ECMO of any kind were removed (34 cases). For
further specificity, VV or right atrial-to-pulmonary artery
ECMO patients were removed (99 patients). This resulted in
266 patients who underwent VA-ECMO at the authors’ center
or by an outside hospital before transfer to the authors’ institu-
tion. Patients were stratified into the following 2 groups:
patients cannulated for VA-ECMO at the authors’ center (215
patients) and those cannulated by an outside hospital (51
patients) (Fig 1). The following 2 survival parameters were
investigated: survival of ECMO therapy and survival to dis-
charge. Survival of ECMO therapy was defined per ELSO as
surviving >12 hours after decannulation without a withdrawal
of care. The authors defined survival to discharge as being
alive at the time of discharge, which generally was to a reha-
bilitation facility or long-term acute care hospital, or rarely as
return to the outside hospital that initially transferred the
patient after ECMO cannulation. In addition, the number of
days on ECMO before being transferred to the authors’ institu-
tion, age, and total length of ECMO placement for all patients
were reviewed.
The decision to pursue ECMO cannulation is generally at
the discretion of the outside hospital, although occasionally
the authors’ institution is contacted to assist in the decision-
making process. It is very rare for an ECMO team from the
authors’ institution to travel to an outside institution and can-
nulate; the authors’ institution does not offer a “cannulate and
retrieve” service. VA-ECMO patients at the outside institution
are cannulated by a team from that institution and then gener-
ally transported by ground ambulance to the authors’ cardio-
thoracic intensive care unit. In-house patients are cared for by
a dedicated ECMO team that includes intensivists, cardiotho-
racic surgeons, cardiac anesthesiologists, respiratory thera-
pists, ECMO specialists, physical therapists, and bedside
nurses; this team-based approach is further delineated in prior
work.11 The indications for ECMO are diverse and include
postcardiotomy shock, myocardial infarction, myocarditis, and
cardiopulmonary arrest. Patients cannulated at outside institu-
tions who are stable for transfer are generally accepted, unless
ECMO circuit capacity or physical bed space is an issue.
Patients accepted from outside institutions who were not yet
cannulated for ECMO were counted as in-house cannulations
if they were placed on ECMO after admission to the authors’
institution.
The authors hypothesized that in this series of patients, sur-
vival of ECMO therapy and survival of the hospitalization in
patients cannulated by outside institutions and transferred for
further care would be the same as in-house cannulated and
cared for patients. In addition, this study attempted to explore
the differences in indications for ECMO between in-house and
transferred patients. The goal of the present study was to serve
as a hypothesis-generating avenue for future work on this
understudied subject.
Patients cannulated for ECMO by outside hospitals and
transferred for further care were compared with patients who
received all their ECMO care (from cannulation to discharge)
at the authors’ institution. Chi-square tests were used to com-
pare survival of ECMO therapy and survival until hospital dis-
charge. In addition, 95% confidence intervals (CI) for these 2
survival parameters were computed using the standard error
and the corresponding z score of 1.96, or with patient numbers
 ARTICLE IN PRESS
A.A. Dalia et al. / Journal of Cardiothoracic and Vascular Anesthesia 00 (2019) 16
Fig 1. Process of elimination and exclusion to study the 266 venoarterial extracorporeal membrane oxygenation patients. ECMO, extracorporeal membrane
oxygenation; RA-PA, right atrial to pulmonary artery; VA, venoarterial; VV, venovenous.
<30, the t score distribution was used. Two-tailed heterosce-
dastic t test (used to compare 2 sets of results with statistically
unequal variance) and homoscedastic t test (used to compare
2 sets of results with statistically similar variances) were used to
compare ECMO duration and age, depending on the difference
in variance (calculated using the F test). As a post-hoc analysis,
patients from each group undergoing eCPR and patients under-
going VA-ECMO in the absence of CPR were analyzed for dif-
ferences in survival of ECMO therapy and survival of the
hospitalization. Statistical analysis was performed with Micro-
soft Excel (Microsoft Corporation, Redmond, WA). A p value
< 0.05 was deemed to be statistically significant.
Results
Basic demographics and statistics for all patients included in
this review are listed in Table 1. Indications for VA-ECMO
cannulation for in-house patients are listed in Table 2, and
indications for patients cannulated by outside institutions and
transferred are listed in Table 3. A comparison of diagnoses in
the cohorts was performed. The incidence of postcardiotomy
shock was not significantly different between groups (21.9%
in-house v 19.6% outside transfer; p = 0.72), and there was a
higher percentage of myocardial infarctions in the transfer
group (30 of 215 in the in-house group [14%] v 13 of 51 in the
outside transfer group [25.5%]), and this difference was
3
statistically significant (p = 0.044). Finally, for the unknown
diagnosis group, there was a similar percentage of patients in
each group (67 of 215 [31.2%] for the in-house group and 13
of 51 [25.5%] in the transfer group [p = 0.43]).
There was no difference in age between the patients trans-
ferred on ECMO and those cannulated in house (in house 53.8
§ 13.5 years v outside transfer 53 § 17.4 years; p = 0.731).
The majority of patients were transferred to the authors’ insti-
tution the same day or within 1 day of cannulation (average
0.5 days). Only 2 patients were transferred after 3 days and
1 patient was transferred after 2 days of ECMO care at an out-
side hospital. There were 17 different outside hospitals that
transferred patients to the authors’ quaternary referral center.
The average length of VA-ECMO therapy for in-house
patients was 5.6 § 5.5 days v 6 §7.1 days for outside hospital
transfers (p = 0.747). Of note, the duration for outside ECMO
patients included the time on ECMO at the outside institution.
Survival of ECMO therapy for in-house patients (122 of 215)
was 56.7% (95% CI 50.1-63.3), and survival of transferred
patients for ECMO therapy (31 of 51) was 60.8% (95% CI
47.4-74.2) (p = 0.58). Survival to discharge for patients
cannulated in house (82 of 215) was 38.1% (95% CI 31.6-
44.6), and for outside hospital transfers (24 of 51) survival
to discharge was 47.1% (95% CI 33.4-60.8) (p = 0.23).
These survival rates are similar to the ELSO database dis-
charge survival of 42%.8
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4 A.A. Dalia et al. / Journal of Cardiothoracic and Vascular Anesthesia 00 (2019) 16

Table 1
VA-ECMO Demographics and Survival

Total VA-ECMO patients In House Transfers p Value

Age (y) 53 53.8 0.73

Length of ECMO (d) 5.6 6 0.75
Survival of ECMO (%) 56.7 (122 of 215) 60.8 (31 of 51) 0.58
Survival to discharge (%) 38.1 (82 of 215) 47.1 (24 of 51) 0.23
Non-eCPR VA-ECMO patients
Age (y) 53.4 52.9 0.88
Length of ECMO (d) 6.1 6.5 0.77
Survival of ECMO (%) 61.2 (93 of 152) 58.8 (20 of 34) 0.83
Survival to discharge (%) 42.1 (64 of 152) 50 (17 of 34) 0.38
eCPR VA-ECMO patients
Age (y) 52 55.5 0.39
Length of ECMO (d) 4.6 5.1 0.72
Survival of ECMO (%) 46 (29 of 63) 64.7 (11 of 17) 0.17
Survival to discharge (%) 28.6 (18 of 63) 41.2 (7 of 17) 0.40

Abbreviations: ECMO, extracorporeal membrane oxygenation; eCPR, extracorporeal membrane oxygenation cannulation during cardiopulmonary resuscitation;
VA-EMCO, venoarterial extracorporeal membrane oxygenation.

As a post-hoc analysis, results were further subdivided to For further post-hoc analysis, patients placed on VA-ECMO
compare patients who received VA-ECMO for eCPR; patients but not for the indication of eCPR also were analyzed. In-
who received in-house eCPR was compared with patients house non-eCPR was compared to with hospital transferred
transferred to the authors’ institution after being cannulated non-eCPR patients. There was no statistically significant dif-
for eCPR by outside hospitals (see Table 1). There was no sta- ference between age (53.4 § 18.3 y v 52.9 § 13.6 y;
tistically significant difference between age (in-house 52 § p = 0.881) or length of ECMO therapy (6.1 § 5.8 d v 6.5 § 8.3
15 years v transferred 55.5 § 13.5 years; p = 0.39) or length of d; p = 0.77) for in-house versus outside hospital patients. The
ECMO therapy (4.6 § 4.5 days v 5.1 § 3.5 days; p = 0.72) for rate of survival of non-eCPR VA-ECMO therapy for in-house
in-house versus outside hospital patients. Survival of eCPR patients (20/34) was 61.2% (95% CI 53.5-68.9) (93/152
VA-ECMO therapy for in-house patients (29 of 63) was 46% patients) compared with 58.8% (95% CI 42.3-75.3) for outside
(95% CI 33.7-58.3) compared with 64.7% (95% CI 40.1-89.3) hospital transfers (p = 0.83). In addition, in-house patients
in transferred patients (11 of 17) (p = 0.17). In addition, in- (64 of 152) had a rate of survival to discharge of 42.1% (95%
house patients (18 of 63) had a rate of survival to discharge of CI 34.3-49.9) compared with 50% (95% CI 33.2-66.8) survival
28.6% (95% CI 17.4-39.8) compared with 41.2% (95% CI to discharge for outside hospital transfers (17 of 34); this dif-
15.9-66.5) survival to discharge for outside hospital transfers ference was not found to be statistically significant (p = 0.38).
(7 of 17) (p = 0.4).
Discussion
Table 2
Indications for ECMO Cannulations in Patients Cannulated and Treated In In this retrospective review of VA-ECMO patients cannu-
House lated by teams at 1 of 17 outside hospitals before being
In-House ECMO Indications n % Table 3
Indications for ECMO Cannulations in Patients Cannulated at Outside Hospi-
Postcardiotomy 47 21.9
tals and Transferred to the Authors’ Institution for Additional Care
Myocardial infarction 30 14.0
Pulmonary embolus 20 9.3 ECMO Indications N %
Cardiomyopathy 18 8.4
Myocarditis 9 4.2 Myocardial infarction 13 25.5
VT/VF 8 3.7 Postcardiotomy 10 19.6
Perioperative/postoperative 5 2.3 Myocarditis 5 9.8
Sepsis 4 1.9 Pulmonary embolus 4 7.8
Drug overdose 3 1.4 Cardiomyopathy 3 5.9
Postpartum 2 0.9 Postpartum 1 2.0
TRALI 2 0.9 VT/VF 1 2.0
Other cardiogenic shock* 67 31.2 Aspiration 1 2.0
Other cardiogenic shock* 13 25.5
NOTE. Total number of patients = 215.
Abbreviations: ECMO, extracorporeal membrane oxygenation; TRALI, NOTE. Total number of patients = 51.
transfusion-related acute lung injury; VT/VF, ventricular tachycardia/ Abbreviations: ECMO, extracorporeal membrane oxygenation; VT/VF,
ventricular fibrillation. ventricular tachycardia/ventricular fibrillation.
* Other cardiogenic shock refers to patients with indications for cannulation * Other cardiogenic shock refers to patients with indications for cannulation
that were unclear from chart review. that were unclear from chart review.
 ARTICLE IN PRESS
A.A. Dalia et al. / Journal of Cardiothoracic and Vascular Anesthesia 00 (2019) 16
transferred to the authors’ institution, overall survival (of
ECMO and to discharge) was found to be the similar to that of
patients cannulated and cared for within the authors’ institu-
tion. There also was no statistically significant difference
between the overall length of VA-ECMO therapy in the
cohorts, although the variance was different, suggesting some
heterogeneity. The majority of patients cannulated at outside
hospitals were transferred to the authors’ institution within 0
to 1 days, a logical approach given the complexity and
required resource utilization of patients undergoing ECMO
therapy. This is the largest review to date that has examined
the experience of cannulation for VA-ECMO by outside hospi-
tals followed by transfer to a referral center.
Referring patients who may require VV-ECMO to a center
capable of their management or referral for possible ECMO
therapy has been investigated.14 In a trial of 180 patients
(CESAR trial) released in 2009, patients with severe acute
respiratory failure were randomly assigned to either conven-
tional management or referral for possible ECMO therapy.
VV-ECMO was the predominant modality used for these
patients given the nature of the cohort (respiratory failure).14
Questions regarding this trial arise because not all patients
received ECMO (68 of 90 patients in the referral group
received it). Multiple retrospective reviews, including an anal-
ysis of 8 years of VV-ECMO referrals at a large referral center
in Italy and the H1N1 experience by both the Australia and
New Zealand ECMO group and by Noah et al. from the Heart-
link ECMO Centre in England also reported outcomes in
patients with respiratory failure.6,15,16 A subsequent trial in
2018 further investigated VV-ECMO in respiratory failure
patients and included centers without ECMO capability but
with experience treating acute respiratory distress syndrome.
The aforementioned literature sheds light on the experience of
referral centers for VV-ECMO but gives no guidance on out-
comes with a VA-ECMO referral model. The present retro-
spective study, which focused on VA-ECMO patients being
transferred to a quaternary center, intends to serve as a prelimi-
nary look into this understudied patient population.
This study has multiple limitations. The retrospective nature
of this study carries inherent limitations, including the advance-
ment of medical care over the 8-year study period and selection
bias. It is unclear whether patients within the authors’ institution
had more complex comorbidities than those cannulated and
transferred to the authors’ institution. The indications for
ECMO cannulation in the in-house population differed from
those of the outside transfer population, with multiple patients
being cannulated for uncommon causes of decompensation,
such as scleroderma. Furthermore, having transfers from 17 dif-
ferent centers offers a level of uncertainty in terms of the unifor-
mity of cannulator experience and the specific inclusion and
exclusion criteria of those institutions. Future studies with a
larger number of patients and propensity matching would pro-
vide a more adjusted and accurate comparison. Even though
survival is an important metric, it does not capture all complica-
tions of ECMO, which include limb loss and stroke. Because of
the span of the retrospective review and the multiple iterations
of electronic medical records, identifying exact data for
5
complications and cannulation strategies (eg, central v periph-
eral) was not performed. In addition, vascular access complica-
tions, which were not assessed, have become an important
source of morbidity, increased cost, and mortality and may be
more likely at lower-volume centers.17 Perhaps an analysis of
vascular access site complications and the necessity of redo sur-
geries at the cannulation sites would show a difference between
the groups. It also is important to note that this work does not
capture patients who may have died during ECMO cannulation
at the outside facility or during or before the transport period.
This study also does not compare institution-specific criteria for
ECMO deployment at the outside institutions compared with
the in-house threshold for ECMO deployment. Finally, given
the relatively small number of patients in the study, there is
likely inadequate statistical power to detect a true difference, if
one exists. For example, in ideal circumstances, a prospective
study with 215 patients in one arm and 51 patients in the other,
with a power of 0.8 and alpha of 0.05, would be able to detect
an approximately 20% difference in survival. Thus, it is clear
that more data from more centers and perhaps an analysis of a
larger database such as the ELSO registry are paramount to
obtaining a more satisfactory answer.
It also is interesting to note that 46% of in-house eCPR
patients (29 of 63) versus 64.7% of transferred eCPR patients
(11 of 17) survived to discharge. Conclusions cannot be drawn
from this comparison because this difference most likely
reflects the small number of patients in the eCPR population,
but it would be enlightening to examine this on a larger scale
to assess whether a true difference exists. The eCPR popula-
tion is a very different set of patients compared with patients
placed on VA-ECMO not during CPR. This finding may be
spurious, but the outcomes in eCPR are likely heavily affected
by the circumstance of ECMO deployment. For example, if a
patient experiences a cardiac arrest while receiving a trans-
catheter aortic valve replacement and is placed on ECMO, the
time to ECMO initiation is likely to be far less than if a patient
experiences a cardiac arrest on a medical or surgical ward and
is cannulated for that indication.
Despite its limitations, this review of the authors’ experi-
ence suggests that having a large quaternary care center that
functions as a site of referral for smaller institutions capable of
VA-ECMO cannulation and initial stabilization may be a func-
tional model for VA-ECMO care. Work on analyzing this type
of model for VV-ECMO already has been performed, but
work on VA-ECMO referral centers is far more limit-
ed.4,6,1113 In the future, as patient outcomes and health care
costs become ever more scrutinized, the further development
of regionalized ECMO centers with satellite institutions that
transfer cannulated patients to them is likely to become the
norm. As a result, quaternary care centers must build detailed
databases to analyze outcomes and search for areas of
improvement to maximize patient benefit.
Conclusions
These results suggest that the practice of initiating VA-
ECMO at an outlying hospital and transferring patients to the
 ARTICLE IN PRESS
6 A.A. Dalia et al. / Journal of Cardiothoracic and Vascular Anesthesia 00 (2019) 16
authors’ larger referral center for continued care may result in
similar survival outcomes to cannulation and care at the
authors’ institution, allowing for expansion of the coverage of
patient care with ECMO therapy. This approach should be
explored further for feasibility in a larger, preferably prospec-
tive manner if these results are to be extrapolated to other qua-
ternary referral centers. Because this was an experience with
215 patients cannulated in house and 51 patients cannulated by
outside providers who were subsequently transferred, a defini-
tive determination cannot be made based on these data alone.
Conflict of interest
The authors do not have any conflicts of interest to report.
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