Discussion:
In this single-center experience, we demonstrated that neither physician
adjudicated arrest rhythm (VT/VF versus PEA) nor underlying origin of
the cardiac arrest (cardiac versus non-cardiac) were significantly
associated with the primary outcome of survival to discharge following
ECPR, either alone or in combination. Of the multiple baseline,
peri-arrest, and on-circuit characteristics assessed, only younger age
and arresting in the emergency department were significantly associated
with survival following ECPR, and of the range of arrest etiologies
described, only pulmonary embolism approached significance. We found
that while ECPR therapy was associated with a high complication burden,
with the majority of patients experiencing major bleeding or requiring
de novo renal replacement therapy, of the patients who survived to
discharge, nearly all experienced myocardial recovery and left the
hospital with a good functional neurological status. Of the patients who
did not survive, the most common cause of death was the decision to
pursue comfort measures only in the setting of multiorgan failure.
The initiation of ECMO at the time of in-hospital cardiac arrest with
active CPR remains an evolving treatment strategy without a robust
evidence base to discern who benefits most from its deployment. Our
study had the advantage of detailed physician review of cardiac arrest
origin, etiology, and rhythm and highlights the heterogeneity in
adjudicated causes of cardiac arrest preceding ECPR initiation. In doing
so, it adds to the existing literature that underscores the salient
challenge in predicting survival following ECPR: the complex and
heterogeneous epidemiology of cardiac arrest as a whole.
The most parsimonious approach to predicting survival in ECPR may center
on a clinical assessment of the reversibility of either the proximal
cause of arrest or the clinical characteristics surrounding it.
Historically, factors associated with survival in CCPR have included
findings such as shockable arrest rhythm29 and
cardiac origin of cardiac
arrest1.
We found no such relationship with survival in ECPR. This study adds to
the growing body of literature that suggests these traditional risk
stratifiers may not be reliable indicators of survival in ECPR and thus
may not deserve a prominent role in the decision to provide
extracorporeal support during CPR.
As the utilization of ECPR as a salvage therapy for patients with
complete cardiopulmonary collapse expands, more work is needed to
identify the patients for whom this resource intensive therapy with high
morbidity and mortality would provide a durable benefit. Our results
suggest that younger age, pulmonary embolism, and arresting in the
emergency department may be associated with survival in ECPR. This does
not imply that these should be entertained as possible initiation
criteria, but rather that they should serve as hypothesis generating
metrics for prospective evaluation of the potential for survival that
this population represents.
Younger age may speak to the physiologic reserve required to tolerate
not just the arrest event itself and attendant ischemic risks, but also
the subsequent ECMO therapy and its high complication burden. Arrest
location in the emergency department may be related to the heightened
staff awareness regarding potential for decompensation, allowing for
swifter response, though the intensive care unit will have as much or
more monitoring potential. Therefore, it may also be that compared to
patients who present and arrest in the emergency department, those who
are already admitted and then arrest as an inpatient may have a poorer
prognosis due to their relative comorbid state secondary to their
initial, non-arrest presenting diagnosis. Nevertheless, the overall high
functional status of those who survive to discharge, despite the high
frequency of significant underlying conditions as described in Table 1,
can justify the use of this therapy even in patients with multiple
pre-existing medical problems.
This study has several important limitations. First, it was subject to
limitations inherent in a retrospective, observation design. Second, our
findings reflected a small set of ECPR patients at a single center,
limiting its generalizability. Third, we were lacking what may arguably
be the most important prognostic factors in ECPR: the time from arrest
onset to cannulation, and the duration and quality of CPR provided prior
to ECMO initiation. It may be that arrest origin, etiology, and rhythm
gain prognostic significance when considered alongside these
resuscitation metrics. For example, there is evidence that taking into
account initial rhythm along with low flow time could help predict
neurological outcomes1,31. Ultimately, the potential for ECMO as a rescue strategy may be limited
at its onset by the extent of ischemic damage suffered prior to it its
initiation. Future prospective studies of ECPR should focus on variables
which might capture the depth and severity of ischemic insults sustained
in the period after arrest but before ECMO deployment, especially those
variables which have the potential to be easily incorporated into future
advanced cardiovascular life support protocols. Finally, this study does
not account for potential improvements in ECPR initiation and post-ECPR
care over time, nor do we provide the total number of patients placed on
venoarterial ECMO over the duration of the study period. The current
registry also does not include cardiac arrest patients for whom ECMO
support was considered but ultimately not provided. While emblematic of
the challenges with ECPR studies, our findings should be viewed as
primarily hypothesis generating and complimentary to the existing
evidence base with similar limitations.