Intensive Care Med (2023) 49:1456–1466

https://doi.org/10.1007/s00134-023-07199-1

ORIGINAL

Age and associated outcomes

among patients receiving venoarterial
extracorporeal membrane oxygenation–analysis
of the Extracorporeal Life Support Organization
registry
Shannon M. Fernando1,2* , Graeme MacLaren3,4, Ryan P. Barbaro5,6, Rebecca Mathew7, Laveena Munshi8,9,
Purnema Madahar10,11, Justin A. Fried12, Kollengode Ramanathan3,4, Roberto Lorusso13,14, Daniel Brodie15
and Daniel I. McIsaac1,16,17

© 2023 Springer-Verlag GmbH Germany, part of Springer Nature

Abstract
Purpose: Venoarterial extracorporeal membrane oxygenation (V-A ECMO) can be used to support severely ill patients with
cardiogenic shock. While age is commonly used in patient selection, little is known regarding its association with outcomes
in this population. We sought to evaluate the association between increasing age and outcomes following V-A ECMO.
Methods: We used individual-level patient data from 440 centers in the international Extracorporeal Life Support
Organization registry. We included all adult patients receiving V-A ECMO from 2017 to 2019. The primary outcome was
hospital mortality. Secondary outcomes included a composite of complications following initiation of V-A ECMO. We
conducted Bayesian analyses of the relationship between increasing age and outcomes of interest.
Results: We included 15,172 patients receiving V-A ECMO. Of these, 8172 (53.9%) died in hospital. For the analysis
conducted using weakly informed priors, and as compared to the reference category of age 18–29, the age bracket of
30–39 (odds ratio [OR] 0.94, 95% credible interval [CrI] 0.79–1.10) was not associated with hospital mortality, but age
brackets 40–49 (odds ratio [OR] 1.26, 95% CrI: 1.08–1.47), 50–59 (OR 1.78, 95% CrI: 1.55–2.06), 60–69 (OR 2.24, 95% CrI:
1.94–2.59), 70–79 (OR 2.90, 95% CrI: 2.49–3.39) and ≥ 80 (OR 4.02, 95% CrI: 3.13–5.20) were independently associated
with increasing hospital mortality. Similar results were found in the analysis conducted with an informative prior, as
well as between increasing age and post-ECMO complications.
Conclusions: Among patients receiving V-A ECMO for cardiogenic shock, increasing age is strongly associated with
increasing odds of death and complications, and this association emerges as early as 40 years of age.
Keywords: Cardiogenic shock, Extracorporeal membrane oxygenation, Extracorporeal life support

*Correspondence: sfernando@qmed.ca
1
Clinical Epidemiology Program, Ottawa Hospital Research Institute,
Ottawa, ON, Canada
Full author information is available at the end of the article
Shannon M. Fernando and Graeme MacLaren contributed equally as
co-first authors. Daniel Brodie and Daniel I. McIsaac contributed equally
as co-senior authors.

Introduction
Cardiogenic shock is defined as a state of low cardiac
output resulting in clinical and biochemical manifesta-
tions of end-organ hypoperfusion [1]. Cardiogenic shock
most commonly occurs secondary to myocardial infarc-
tion (complicating 15–20% of all cases), but can also occur
secondary to dilated cardiomyopathy, myocarditis, severe
septic shock, or other causes [2]. While the incidence of
cardiogenic shock appears to be decreasing over time, mor-
tality remains between 40% and 50% [3], likely secondary to
a lack of effective treatments and supportive measures [4].
Patients who deteriorate to higher severity shock
states may ultimately require temporary mechanical cir-
culatory support (MCS) devices, which may then serve
as a bridge to recovery, durable support, or cardiac
transplantation [5]. Venoarterial extracorporeal mem-
brane oxygenation (V-A ECMO) is a form of MCS that
provides both cardiac and respiratory support [6, 7], and
its use is increasing globally [8]. While many patients
receiving V-A ECMO for cardiogenic shock do survive
to hospital discharge [7], the use of V-A ECMO requires
substantial resources and incurs significant costs [9].
This is particularly true during surges in the demand
for critical care, such as the coronavirus disease 2019
(COVID-19) pandemic [10]. Clinical practice guidelines
support the use of temporary MCS (such as V-A ECMO)
in patients with cardiogenic shock, but make no specific
recommendations on candidacy [11, 12]. As such, there
is a strong need to identify patients most likely to ben-
efit from V-A ECMO. One of the most salient predic-
tors of outcomes among hospitalized patients appears to
be increasing age, and older patients represent a grow-
ing demographic of the critically ill [13]. Age also rep-
resents an important risk factor in both incidence and
outcome from cardiogenic shock [14]. However, few
data are available to provide insights into the associa-
tion between advancing age and outcomes for patients
receiving V-A ECMO for cardiogenic shock. Greater
understanding of the possible prognostic impact of age
on outcomes is needed to inform evidence-based selec-
tion of patients for V-A ECMO. Previous cohort studies
evaluating the association between age and outcomes
of patients receiving V-A ECMO for cardiogenic shock
have shown mixed results [15–20], but these studies
have been limited to small, predominantly single center
cohorts. Therefore, we sought to investigate this ques-
tion using the international Extracorporeal Life Sup-
port Organization (ELSO) registry, the largest registry of
ECMO cases in the world. We hypothesized that older
age, especially above 60 years, would be associated with
poorer outcomes following V-A ECMO.
1457
Take‑home message
In this multinational cohort study of 15,172 patients receiving veno-
arterial extracorporeal membrane oxygenation (V-A ECMO) at 440
centers, increasing age was associated with increasing odds of
death or complications following initiation of ECMO, with statisti-
cally higher risk emerging as early as 40 years of age.
Methods
Design and data source
This was a cohort study using prospectively collected
data from ELSO [21, 22]. The ELSO Registry is a volun-
tary registry with more than 440 centers worldwide con-
tributing data. Key data elements in the ELSO Registry
include pre-ECMO patient characteristics, ECMO dura-
tion and configuration, related complications, and in-
hospital outcomes. Pre-existing comorbidities and most
responsible diagnoses for the index hospital admission
are reported within the ELSO Registry using the Inter-
national Classification of Diseases, ­10th Edition (ICD-
10). A protocol was prespecified and registered at the
Center for Open Science (https://​osf.​io/​pmgx4). We fol-
lowed recommendations regarding conduct and report-
ing of both prognosis and causal inference in critical
care medicine and cardiology [23, 24], and our protocol
was generated considering best practice in prognos-
tic and Bayesian analyses [25, 26]. Results are reported
using the Transparent Reporting for Individual Prog-
nosis or Diagnosis (TRIPOD) Guidelines [27], as well
as the STrengthening the Reporting of OBservational
studies in Epidemiology (STROBE) statement, and the
Reporting of Bayes Used in clinical STudies (ROBUST)
criteria [28, 29]. Studies using the ELSO database are
exempt from Institutional Review Board approval due to
the retrospective analysis of de-identified data.
Cohorts
We included patients meeting the following eligibil-
ity criteria: (1) Age ≥ 18 years; (2) Admitted to hospital
from January 1, 2017, through December 31, 2019; and 3)
Receiving V-A ECMO, as indicated in the ELSO Registry.
The study dates were chosen to ensure minimal missing
data and concluded prior to the onset of the COVID-19
pandemic, which may have impacted availability of V-A
ECMO at some centers. We excluded patients receiving
extracorporeal cardiopulmonary resuscitation (ECPR) for
cardiac arrest, due to large differences in prognosis from
cardiogenic shock without sustained cardiac arrest [30].
Exposure
Chronological age at the time of hospital admission was
the primary exposure. This variable was categorically
1458
parameterized in approximately 10-year intervals: 18–29,
30–39, 40–49, 50–59, 60–69, 70–79, and ≥ 80 years.
The ELSO Registry does not collect the specific age of
enrolled patients 80 years and older.
Outcome
The primary outcome was all-cause in-hospital mortality.
We secondarily evaluated a composite outcome of com-
plications following initiation of V-A ECMO (defined as
any of the following: renal failure requiring initiation of
renal replacement therapy, ischemic stroke, intracerebral
hemorrhage, disseminated intravascular coagulopathy,
any limb complication [amputation, compartment syn-
drome, fasciotomy, ischemia], or any mechanical compli-
cation [air in circuit, cannula problems, circuit change,
clots and air emboli, oxygenator failure, pump failure]).
We further defined an ordinal outcome to clinically
reflect the differing severity across adverse outcomes,
which was coded as (from most to least severe): death = 5;
stroke (including intracerebral hemorrhage) = 4; new
renal replacement therapy = 3; limb complications,
mechanical complications (e.g., ECMO pump failure) or
coagulopathy = 2; alive without complications = 1.
Covariates
To support control for postulated confounders and factors
prognostic of outcome [1], we collected pre-ECMO patient
characteristics, similar to those used in other studies involv-
ing the ELSO Registry [31]. The primary diagnosis responsi-
ble for ECMO initiation was categorized into 33 categories,
on the basis of known data related to prognosis, particularly
among the elderly [32], based on ICD-10 coding. Pre-exist-
ing comorbidities were also identified using ICD-10 cod-
ing, which was used to derive the Charlson Comorbidity
Index using validated methods [33]. Sex, weight, index year,
and biochemical parameters from the initial arterial blood
gas values at the time of cannulation (pH, partial pressure
of arterial carbon dioxide ­[PaCO2], partial pressure of arte-
rial oxygen ­[PaO2], bicarbonate [­ HCO3], fraction of inspired
oxygen ­[FiO2]) were also collected.
Missing data
Multiple imputation using chained equations was pre-
specified as our approach to covariate data missing
for > 1% of values because we postulated that missing data
may be associated with exposure, covariate and outcome
values. For Bayesian analyses, which are computationally
expensive, we imputed 5 data sets, which supports accu-
rate estimation of point values [34].
Statistical analyses
All data manipulation and descriptive statistics were per-
formed using SAS v9.4 for Windows (SAS Institute, Cary,
NC). All Bayesian analyses were conducted using the R
package ‘brms’ (R Foundation for Statistical Computing,
Vienna, Austria) [35].
Descriptive statistics were used to compare charac-
teristics between patients who survived to hospital dis-
charge and those who died (with values in excess of 0.10
indicating a substantial difference [36]). For modelling, all
continuous variables were standardized to have a mean
of 0 and standard deviation of 1.
We sought to evaluate the association between age and
outcomes following V-A ECMO using methods of causal
inference. We identified confounding variables a priori,
on the basis of known or suspected associations between
both the exposure of interest (age) and outcomes follow-
ing V-A ECMO [7]. In keeping with guidelines [23], we
did not include variables that lie on the presumed causal
pathway between the exposure and the outcomes of
interest. Prespecified confounders included patient sex,
weight, index year, pre-existing comorbidities, and pri-
mary diagnosis.
Bayesian methods were used to estimate the associa-
tion of age with outcomes, using logistic regression for all
analyses. We employed Markov chain Monte Carlo simu-
lations to estimate odds ratios (OR, based on the median
value of the highest posterior density interval) and 95%
credible intervals (CrI), which can be interpreted as the
range of values, based on prior knowledge and the data,
that have 95% probability of containing the true associa-
tion. The probability of non-null association was also cal-
culated using the proportion of samples in the posterior
distribution that estimated an OR > 1 (the null value).
Each estimation used 2000 iterations after 1000 warmup
simulations, for a total of 8000 sampling iterations. This
process was carried out simultaneously across imputed
data sets, and results were automatically integrated
across posterior samples. As recommended, our primary
and sensitivity analyses used a prior distribution that was
weakly informative (Student’s t-distribution with a scale
of 3, mean of 0, and standard deviation of 2.5) unless oth-
erwise stated, which decrease the likelihood of estimat-
ing unrealistically large or small effects, without having
a substantive effect on regression parameters in moder-
ate to large datasets [37]. We also estimated the age-out-
come association using an informative prior, which was
equivalent to a 10% increase in the odds of death for each
increasing age category. Using ages 18–29 as a reference,
this corresponded in Student’s t-distributions with means
of 0.095 (age 30–39), 0.18 (age 40–49), 0.26 (age 50–59),
0.34 (age 60–69), 0.41 (age 70–79), and 0.47 (age ≥ 80).
This set of informative priors was based on a conservative

estimate that patients ≥ 65 years of age would have a 1.5-
fold increase in odds of mortality, compared to younger
patients, which is often seen in acute care settings. Ade-
quate mixing of chains and autocorrelation were evalu-
ated using the ‘ShinyStan’ package.
We estimated both the unadjusted and adjusted asso-
ciations of increasing age with hospital mortality. Our
unadjusted analysis contained only the categorical age
variable. The adjusted model included our pre-specified
covariates, and random intercepts for each participating
ELSO center. We then re-ran the primary models, but
with the composite outcome of ECMO-related complica-
tions as the dependent variable, and then with the ordi-
nal adverse event outcome as the dependent variable in a
proportional odds logistic regression model.
Sensitivity analyses
We performed several pre-specified sensitivity analyses,
as detailed in our protocol. We performed a sensitiv-
ity analysis testing the association using a linear param-
eterization (i.e., evaluating age as a continuous variable).
For patients in the “age ≥ 80 years” category, we assigned
an age of 84, based on the expected longevity for those
patients who reach 65 years of age in the United States,
and which is also the average age of Americans who
initiate renal replacement therapy as octogenarians, a
relatively invasive organ replacement therapy that is
well-studied [38]. We further tested age as a continuous,
non-linear exposure using a tensor product spline, which
required increasing the iterations per chain to 4000 and
thinning every tenth simulation. Due to possible con-
cerns that the ELSO Registry may not contain all data
on relevant comorbidities, we sought to assess whether
our primary results were consistent among those in the
cohort with baseline comorbidities documented. There-
fore, we repeated our analysis following the exclusion
of patients without any Charlson Comorbidity Index
comorbidities. Finally, given that the ELSO Registry con-
tains only the “most responsible diagnosis” attributable
to the decision to initiate ECMO, we performed a sensi-
tivity analysis that excludes patients with an ICD-10 code
of R57 (“Shock, not elsewhere classified”), or any ICD-10
code with a prevalence of < 1.0% in the cohort.
Protocol deviations
Our protocol specified both causal inference and pre-
dictive modelling objectives. The latter will be reported
in future reports. Post hoc analyses presented herein
included the use of a non-linear spline for the age expo-
sure, and use of an ordinal complications outcome.
1459
Results
We identified 15,172 patients from 440 centers within
the ELSO Registry receiving V-A ECMO for cardiogenic
shock. Of these, 8172 (53.9%) died in hospital, and 10,071
(66.4%) experienced at least one post-ECMO complica-
tion. Baseline characteristics among patients who sur-
vived to hospital discharge and those who died prior
are shown in Table 1. The cohort was relatively younger
in age, with a total of 12,361 patients (81.5%) under the
age of 70. Patients were also mostly without comor-
bidities prior to hospital admission, with 11,677 (77%)
having a Charlson Comorbidity Index of 0. The most
common primary diagnosis category was ‘non-specific
cardiogenic shock’ (n = 4491; 29.6%), followed by acute
myocardial infarction (n = 1188; 7.8%), congestive heart
failure (n = 843; 5.6%) and post-arrest myocardial stun-
ning (n = 660; 4.4%). Data on destination therapies, strati-
fied by age, are shown in Supplemental Table 1.
Association between age and outcomes following V‑A
ECMO
Table 2 depicts the association (with weak and strong
informative priors) between age and hospital mortal-
ity among all patients receiving V-A ECMO for cardio-
genic shock. Visual diagnostics and full model results
are shown in Supplemental Tables 2–4, and posterior
distributions and 95% and 50% CrI are depicted in Fig. 1.
Using a weakly informative prior, and compared to the
reference category of age 18–29, there was no difference
in odds of mortality at age 30–39 (OR 0.94 [95% CrI:
0.79–1.10]). However, there were stepwise increases in
mortality as age brackets increased to 40–49 (OR 1.26
[95% CrI: 1.08–1.47]), 50–59 (OR 1.78 [95% CrI: 1.55–
2.06]), 60–69 (OR 2.24 [95% CrI: 1.94–2.59]), 70–79
(OR 2.9 [95% CrI: 2.49–3.39]), and ≥ 80 (OR 4.02 [95%
CrI: 3.13–5.20]). Similar results were seen when using a
strong informative prior. Our sensitivity analysis evalu-
ating age as a continuous variable similarly showed a
significant association between age and hospital mortal-
ity (OR 1.48 [95% CrI: 1.43–1.54] per 10-year increase;
Supplemental Table 5). When age was parameterized
as a spline (Fig. 2), we estimated a flat association from
18 to 39, and then a nearly linear relationship above age
40 between increasing age and odds of hospital mortal-
ity among patients receiving V-A ECMO for cardiogenic
shock. Our findings were consistent across our sensitivity
analyses excluding patients without Charlson Comorbid-
ity Index comorbidities (Supplemental Table 6) and those
with a non-specific diagnosis for initiation of V-A ECMO
(Supplemental Table 7).
The association between age and complications follow-
ing initiation of V-A ECMO are also shown in Table 2,
with the outcome modeled as both a binary composite
1460

Table 1 Characteristics of patients receiving veno-arterial extracorporeal membrane oxygenation (n = 15,172)

Characteristic Survived to discharge Died in-hospital
(n = 7000) (n = 8172)

Age bracket, n (%)

18–29 646 (9.2) 412 (5)
30–39 869 (12.4) 530 (6.5)
40–49 1077 (15.4) 924 (11.3)
50–59 1576 (22.5) 1837 (22.5)
60–69 1761 (25.2) 2571 (31.5)
70–79 844 (12.1) 1542 (18.9)
  ≥ 80 120 (1.7) 305 (3.7)
Female Sex, n (%) 2304 (32.9) 2663 (32.6)
Primary diagnosis, n (%)
Cardiogenic shock 2033 (29) 2458 (30)
Acute myocardial infarction 501 (7.2) 687 (8.4)
Congestive heart failure 371 (5.3) 472 (5.8)
Post-cardiac arrest 269 (3.8) 391 (4.8)
Post-procedural hemorrhage 231 (3.3) 404 (4.9)
Atherosclerotic heart disease 220 (3.1) 276 (3.4)
Pulmonary embolism 315 (4.5) 173 (2.1)
Dilated cardiomyopathy 236 (3.4) 187 (2.3)
Post-cardiotomy syndrome 139 (2) 218 (2.7)
Aortic dissection 85 (1.2) 248 (3)
Acute respiratory failure 159 (2.3) 159 (2)
Hematopoietic stem cell transplantation 151 (2.2) 123 (1.5)
Aortic stenosis 90 (1.3) 129 (1.6)
Myocarditis 160 (2.3) 55 (0.7)
Renal transplantation 115 (1.6) 59 (0.7)
Mitral regurgitation 76 (1.1) 91 (1.1)
Primary pulmonary hypertension 81 (1.2) 80 (1)
Ventricular arrhythmia 82 (1.2) 49 (0.6)
Sepsis 47 (0.7) 82 (1)
Other 1639 (23.4) 1831 (22.4)
Charlson comorbidity index, n (%)
0 5600 (80) 6377 (78)
1 1025 (14.6) 1304 (16)
2 404 (4.3) 375 (4.6)
  ≥ 3 72 (1) 116 (1.4)

and an ordinal variable. Similar to mortality, we saw no
strong increase in odds of complications among patients
aged 30–39 (OR 0.86 [95% CrI 0.73–1.01]), as compared
to the reference category of 18–29. However, thereafter
we saw a stepwise increase in the odds of complications
at age brackets of 40–49 (OR 1.04 [95% CrI: 0.89–1.22]),
50–59 (OR 1.3 [95% CrI: 1.12–1.5]), 60–69 (OR 1.57 [95%
CrI: 1.36–1.81]), 70–79 (OR 1.74 [95% CrI: 1.48–2.04]),
and ≥ 80 (OR 2.07 [95% CrI: 1.59–2.69]). Evaluating the
outcome in an ordinal fashion yielded similar results
(Table 2). Individual complications, stratified by age
bracket, are included in Supplemental Table 8.
Discussion
In this multinational cohort study from the ELSO Reg-
istry of 15,172 patients receiving V-A ECMO, we found
that increasing patient age was associated with higher
odds of death or complications following initiation of
ECMO. Statistically increased risk of these outcomes
emerged as early as 40 years of age.
 1461

Table 2 Model results showing association of age with outcomes among cardiogenic shock patients receiving venoarte‑
rial ECMO (n = 15,172)
Age (Years) Hospital mortality with Hospital mortality with Hospital mortality or Ordinal hospital mortality
weakly informative prior strongly informative prior complications and complications
OR 95% CrI Pr > 0 % OR 95% CrI Pr > 0 % OR 95% CrI Pr > 0 OR 95% CrI Pr > 0

30–39 0.94 0.79–1.10 22 0.94 0.80–1.11 22 0.86 0.73–1.01 3 0.90 0.78–1.05 9

40–49 1.26 1.08–1.47 > 99 1.26 1.08–1.47 > 99 1.04 0.89–1.22 68 1.14 0.99–1.31 97
50–59 1.78 1.55–2.06 > 99 1.78 1.55–2.06 > 99 1.30 1.12–1.50 > 99 1.51 1.32–1.72 > 99
60–69 2.24 1.94–2.59 > 99 2.24 1.95–2.59 > 99 1.57 1.36–1.81 > 99 1.88 1.65–2.14 > 99
70–79 2.90 2.49–3.39 > 99 2.90 2.48–3.38 > 99 1.74 1.48–2.04 > 99 2.33 2.02–2.69 > 99
≥ 80 4.02 3.13–5.20 > 99 4.00 3.10–5.19 > 99 2.07 1.59–2.69 > 99 3.14 2.45–4.03 > 99
Reference age bracket is 18–29 years, OR odds ratio, CrI credible interval, Pr > 0 probability of outcome > 0 (%)

Fig. 1 Forest plot demonstrating adjusted odds of hospital mortality with increasing age decile among patients receiving venoarterial extracor-
poreal membrane oxygenation for cardiogenic shock. Included are posterior distributions for each parameter, along with a dot (representing the
median value), a thick bar (50% credible interval), and thin bar (95% credible interval). Credible intervals were based on the highest density interval
of the posterior distribution
1462
Fig. 2 Tensor product spline demonstrating relationship between age and probability of hospital mortality. SD Standard deviation
V-A ECMO represents the fastest growing modality
of temporary MCS for cardiogenic shock, increasing
in use nearly 1500% over the past two decades [39, 40].
Despite this, there has been a growing need to iden-
tify optimal candidates for treatment with V-A ECMO
because this treatment is costly and consumes a large
amount of resources [9]. Recent attempts at deriving
risk-stratification tools to assist in decision making for
evidence-based provision of V-A ECMO for cardio-
genic shock have not resulted in clear consensus [41].
The two most widely used decision instruments are the
Survival After V-A ECMO (SAVE) Score [18], and the
prEdictioN of Cardiogenic shock Outcome foR AMI
patients salvaGed by V-A ECMO (ENCOURAGE) Score
[19]. However, these tools have not performed well in
external validation, and it is questionable whether they
have sufficient discrimination to be used for clinical
decision making in individual patients [41]. As such,
optimization of selection for V-A ECMO remains an
important priority in cardiogenic shock [42]. Increasing
age has been demonstrated to be a prognostic factor for
mortality in critically ill populations [43], and age was
found to be predictive of mortality in the cohorts that
derived both SAVE and ENCOURAGE [18, 19]. How-
ever, in these smaller cohorts, age was given similar
prognostic weight as laboratory values such as serum
bicarbonate and prothrombin activity.
Consistent with rapid population ageing, the use of V-A
ECMO and other forms of MCS among older patients
with cardiogenic shock has grown nearly 20% over the
past two decades [32, 40]. Interestingly, despite consist-
ent associations between age and adverse outcomes in
most critical care literature, available small cohort stud-
ies evaluating the association between age and outcomes
of patients receiving V-A ECMO for cardiogenic shock
have shown mixed results, with most not demonstrat-
ing a strong association of age with patient outcomes
[15–19]. By contrast, our large multinational study found

strong and consistent evidence of an association between
advancing age and hospital mortality after V-A ECMO,
starting from the age of 40. While we hypothesized
that increasing age would be associated with outcomes
including mortality, seeing these differences emerge at
relatively younger ages was somewhat unexpected, par-
ticularly in a cohort that is known to be highly selected
for lack of major comorbidities at baseline. This was
clear in our cohort, where there was relatively minimal
multimorbidity, consistent with previous studies from
the ELSO Registry [21]. Furthermore, this early onset of
increased risk was consistent in both our primary anal-
ysis that categorized age by decile, as well as when age
was modeled as a non-linear spline term. This under-
scores the importance of incorporating age into clinical
decision making related to the provision of V-A ECMO,
and not only among the oldest patients. While our data
do not capture validated measures of frailty, the asso-
ciation between age and outcomes (even in younger age
groups) may represent the impact of the biologic ageing
process, for which frailty is a representative clinical con-
struct [44, 45]. Younger patients requiring V-A ECMO
may represent complex populations (such as congenital
heart disease) who might live with a meaningful degree
of frailty despite their chronological age. Such patients
may also be limited in their candidacy for destination
therapies. Therefore, it is clear that chronological age
should not be the only variable considered in prognosti-
cation among patients potentially receiving V-A ECMO
[46]. Future efforts at deriving externally valid and accu-
rate risk prediction models to assist patient selection for
V-A ECMO should include detailed parameterization of
patient age, and evaluate the interaction between age and
other important prognostic variables, particularly patient
frailty.
We also found that age was significantly associated
with complications arising after initiation of V-A ECMO.
Complication rates among patients receiving V-A ECMO
are high [47], which was consistent with our data. Two-
thirds of patients experienced at least one complication.
We found that increasing age was associated with com-
plications following V-A ECMO, showing a similar trend
and effect size as for mortality. An increasing burden of
complications during V-A ECMO has important patient-
centred implications because it may impede circulatory
support or prompt clinicians to interrupt V-A ECMO
support. It is possible that age affects the incidence of
these complications, and either directly or indirectly
influences mortality through such mechanisms [5, 47].
Providers may consider counseling patients and fami-
lies on this relationship, in order to guide expectations
related to outcomes after V-A ECMO.
1463
Study limitations
Our study has numerous strengths, including use of a
prospectively-collected, multinational cohort of patients
supported by V-A ECMO from 440 centers, with mini-
mal missing data over our study period. We pre-specified
our study protocol and used Bayesian statistical analy-
ses to provide estimates of credibility and probability of
harm, supporting causal inference. Our study also has
notable limitations. Most importantly, we are limited by
the granularity of the available data in the ELSO Registry.
There are likely a number of residual confounding fac-
tors that we were not able to include in our analyses. In
particular, decisions related to cessation of V-A ECMO
and withdrawal of life-sustaining therapy may be made
more commonly among older patients because they
are less likely to be bridged to durable mechanical sup-
port or cardiac transplantation. Furthermore, we were
limited in the availability of data related to numerous
patient comorbidities (e.g., dyslipidemia), nor we did not
have data on patient function or degree of frailty [44, 45],
which can represent the biologic, as opposed to chrono-
logic, ageing process. In addition, while the large major-
ity of patients likely had severe cardiogenic shock, data
specific to the Society for Coronary Angiography and
Intervention (SCAI) classification were not available,
and this severity classification has been closely associ-
ated with odds of mortality [48]. Other severity measures
such as acute physiology and chronic health evalua-
tion (APACHE) score, Sequential Organ Failure Assess-
ment (SOFA) score, or lactate were also unavailable, but
the prognostic accuracy of these measures among V-A
ECMO patients is mixed. We relied upon ICD-10 coding
for the primary diagnosis, for which there was substan-
tial heterogeneity. Multiple patients had an ICD-10 code
that only specified “Shock”. However, it is worth noting
that our sensitivity analysis excluding patients with non-
specific diagnoses yielded the same results as our pri-
mary analysis. The severity and etiology of cardiogenic
shock likely influences outcomes after V-A ECMO, and
we could not account for this fully. Furthermore, patients
receiving V-A ECMO are a highly selected patient popu-
lation, consistent with the relatively younger age distri-
bution and low comorbidity burden seen in our cohort.
Clinically, this type of selection bias might be expected
to move the effect of age toward the null, but as an obser-
vational study, caution must be exercised in generalizing
our results. Our data were also collected from 440 cen-
tres reporting data to the ELSO Registry, and therefore
our findings may not extend to other centres performing
V-A ECMO. Finally, the ELSO database only contains
outcomes occurring up to hospital discharge. As such,
we could not investigate the association of age and out-
comes of V-A ECMO survivors following discharge from
1464
hospital, especially with regard to physical and mental
health morbidity and dependence [49, 50], and these
remain important areas for future research.
Conclusion
In a multinational study using the ELSO Registry, we
found that increasing age was strongly associated with
higher risk of hospital mortality and complications
among patients receiving V-A ECMO for cardiogenic
shock, with differences emerging as early as 40 years of
age. Even among relatively younger patients, clinicians
should consider the prognostic importance of patient age
in decisions surrounding initiation and cessation of V-A
ECMO.
Supplementary Information
The online version contains supplementary material available at https://​doi.​
org/​10.​1007/​s00134-​023-​07199-1.
Author details
1
Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa,
ON, Canada. 2 Department of Critical Care, Lakeridge Health Corporation,
Oshawa, ON, Canada. 3 Yong Loo Lin School of Medicine, National University
of Singapore, Singapore, Singapore. 4 Cardiothoracic Intensive Care Unit,
National University Heart Centre, National University Hospital, Singapore,
Singapore. 5 Division of Pediatric Critical Care Medicine, University of Michigan,
Ann Arbor, MI, USA. 6 Child Health Evaluation and Research Center, University
of Michigan, Ann Arbor, MI, USA. 7 Division of Cardiology, University of Ottawa
Heart Institute, Ottawa, ON, Canada. 8 Interdepartmental Division of Critical
Care Medicine, University of Toronto, Toronto, ON, Canada. 9 Institute of Health
Policy, Management and Evaluation, Dalla Lana School of Public Health,
University of Toronto, Toronto, ON, Canada. 10 Division of Pulmonary, Allergy,
and Critical Care Medicine, Department of Medicine, Columbia University
College of Physicians and Surgeons, New York, NY, USA. 11 Center for Acute
Respiratory Failure, New York-Presbyterian Hospital, New York, NY, USA. 12 Divi-
sion of Cardiology, Department of Medicine, Columbia University College
of Physicians and Surgeons, New York, NY, USA. 13 Department of Cardio
Thoracic Surgery, Maastricht University Medical Centre, Maastricht University,
Maastricht, The Netherlands. 14 Cardiovascular Research Institute Maastricht,
Maastricht, The Netherlands. 15 Department of Medicine, Division of Pulmo-
nary and Critical Care Medicine, Johns Hopkins University School of Medicine,
Baltimore, MD, USA. 16 Department of Anesthesiology and Pain Medicine, Uni-
versity of Ottawa, Ottawa, ON, Canada. 17 School of Epidemiology and Public
Health, University of Ottawa, Ottawa, ON, Canada.
Author contributors
SMF, GM, DB, and DIM conceived the study idea. All authors participated in
study design. DIM performed data analyses. All authors interpreted the data
analyses. All authors co-wrote and revised the manuscript for intellectual
content. All authors provided their final approval for manuscript submission.
All authors agree to be accountable for all aspects of the work. SMF and GM
are co-first authors. DB and DIM are co-senior authors.
Funding
Authors did not received any funding for this work.
Declarations
Conflicts of interest
SMF has no conflicts to declare. GML is President of the Extracorporeal Life
Support Organization (ELSO). RPB is the ELSO Registry Chair. RM has no con-
flicts to declare. LM has no conflicts to declare. PM has no conflicts to declare.
JAF has no conflicts to declare. KR is Co-Chair of the ELSO Scientific Oversight
Committee. RL is a consultant and conducts clinical trials for LivaNova. He
receives research support from Medtronic, and serves as a consultant for
Medtronic, Getinge, and Abiomed. He serves on the medical advisory boards
of Fresenius, Hemocue, and Eurosets. DB receives research support from
and consults for LivaNova. He has been on the medical advisory boards for
Abiomed, Xenios, Medtronic, Inspira and Cellenkos. He is the President-elect
of the Extracorporeal Life Support Organization (ELSO) and the Chair of the
Executive Committee of the International ECMO Network (ECMONet), and he
writes for UpToDate. DIMcI receives salary support from The Ottawa Hospital
Anesthesia Alternate Funds Association and holds a Research Chair from the
University of Ottawa Faculty of Medicine.
Ethical approval
Not required.
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in pub-
lished maps and institutional affiliations.
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive
rights to this article under a publishing agreement with the author(s) or other
rightsholder(s); author self-archiving of the accepted manuscript version of
this article is solely governed by the terms of such publishing agreement and
applicable law.
Received: 4 May 2023 Accepted: 8 August 2023
Published: 4 October 2023
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