Discussion:
In this single-center study, we demonstrate that physician adjudicated
arrest rhythm (VT/VF versus PEA) or underlying origin of the cardiac
arrest (cardiac versus non-cardiac) were not significantly associated
with survival to hospital discharge following ECPR, either alone or in
combination. Of the multiple baseline, peri-arrest, and on-circuit
characteristics assessed, only younger age was significantly associated
with survival following ECPR. Of those cardiac arrest etiologies
evaluated, only pulmonary embolism approached statistical significance
for the primary outcome of survival to hospital discharge. We found that
ECPR therapy was associated with a high complication burden, with the
majority of patients experiencing major bleeding or requiring de novo
renal replacement therapy. Nearly all ECPR survivors to discharge
experienced myocardial recovery, in addition to a CPC score consistent
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 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 guide appropriate patient selection. Our study had the
advantage of a detailed physician review of cardiac arrest origin,
etiology, and rhythm and highlights the heterogeneity in adjudicated
causes of cardiac arrest preceding ECPR initiation. This study
corroborates the existing literature that underscores the salient
challenge in predicting survival following ECPR attributed to the
complexity and heterogeneity of the cardiac arrest event.
As rescue ECPR utilization expands, patient selection remains a critical
determinant in ensuring the appropriate implementation of a
resource-intense therapy to ensure clinical benefit. Our results suggest
that younger age and a cardiac arrest etiology attributed to pulmonary
embolism may be associated with survival in ECPR. In pulmonary embolism
cases, ECMO affords both critical cardiopulmonary support in addition to
obligate anticoagulation that may relieve a potentially reversible
pulmonary vascular obstruction leading to an arrest. Younger age may
speak to the physiologic reserve required to tolerate not just the
arrest event itself and attendant ischemic risk, but also the subsequent
ECMO therapy and its potential high complication burden. 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, may justify the use of this therapy even in
patients with multiple pre-existing medical problems.
There are inherent limitations to this study attributed to a
retrospective analysis, sample size, and a dependence on the quality of
clinical record keeping at the time of each ECPR event. Conventional
ACLS resuscitation algorithms are delineated by a cardiac arrest’s
rhythm and etiology. However, our analysis suggests that as an initial
trigger point, ECPR outcomes are not dependent on the arrest rhythm or
etiology. It may be that at the time of ECMO initiation, the consequent
severity of the arrest’s cardiopulmonary failure may render a survivable
ECPR outcome futile. To this end, metrics that could provide additional
insight into the relationship between the quality of the initial arrest
resuscitation efforts and ECPR survival, including end-tidal
CO2 prior to ECMO initiation and the frequency and
duration of ROSC could not be reliably obtained. However, our study did
find that in the 40 patients for whom low-flow time was recorded, the
duration of mechanical CPR was not associated with ECPR survival
outcomes.
Moreover, the current findings do not account for potential improvements
in ECPR initiation and post-ECPR care over the study period. The current
registry 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.
It may be that arrest origin, etiology, and rhythm gain prognostic
significance when considered alongside 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; if adequately characterized, this could define the upper
limit to therapeutic benefit of ECPR and thereby inform point of care
decision making. Future prospective studies of ECPR should focus on
combinations of variables which might capture the depth and severity of
ischemic insults sustained in the period after arrest but before ECMO
deployment, especially those which are readily attainable and have the
potential to be easily incorporated into future advanced cardiovascular
life support protocols.