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.