Review
Extracorporeal Cardiopulmonary Resuscitation for Refractory Out-of-Hospital Cardiac Arrest: The State of the Evidence and Framework for Application

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Abstract

Out-of-hospital cardiac arrest (OHCA) affects 134 per 100,000 citizens annually. Extracorporeal cardiopulmonary resuscitation (ECPR), providing mechanical circulatory support, may improve the likelihood of survival among those with refractory OHCA. Compared with in-hospital ECPR candidates, those in the out-of-hospital setting tend to be sudden unexpected arrests in younger and healthier patients. The aims of this review were to summarize, and identify the limitations of, the evidence evaluating ECPR for OHCA, and to provide an approach for ECPR program application. Although there are many descriptions of ECPR-treated cohorts, we identified a paucity of robust data showing ECPR effectiveness compared with conventional resuscitation. However, it is highly likely that ECPR, provided after a prolonged attempt with conventional resuscitation, does benefit select patient populations compared with conventional resuscitation alone. Although reliable data showing the optimal patient selection criteria for ECPR are lacking, most implementations sought young previously healthy patients with rapid high-quality cardiopulmonary resuscitation. Carefully planned development of ECPR programs, in high-performing emergency medical systems at experienced extracorporeal membrane oxygenation centres, may be reasonable as part of systematic efforts to determine ECPR effectiveness and globally improve care. Protocol evaluation requires regional-level assessment, examining the incremental benefit of survival compared with standard care, while accounting for resource utilization.

Résumé

L’arrêt cardiaque hors de l’hôpital (ACHH) touche 134 citoyens sur 100 00 par année. La réanimation cardiorespiratoire extracorporelle (RCR-E), qui offre une assistance circulatoire mécanique, pourrait permettre d’améliorer la survie chez ceux qui ont un ACHH réfractaire. Comparativement à la RCR-E à l’hôpital, la RCR-E hors de l’hôpital entraîne généralement des morts subites inopinées chez des patients plus jeunes et en meilleure santé. Les objectifs de la présente revue étaient de résumer et de déterminer les limites des données probantes qui évaluent la RCR-E lors d'ACHH, et de proposer une approche pour l’application du programme de RCR-E. Bien qu’il existe de nombreuses descriptions de cohortes traitées par RCR-E, nous trouvons peu de données fiables qui montrent l’efficacité de la RCR-E par rapport à celle de la réanimation classique. Toutefois, il est fort probable que la RCR-E offerte après une tentative prolongée de réanimation classique constitue un avantage pour certaines populations de patients par rapport à la réanimation classique seule. Bien qu’il manque de données fiables montrant les critères optimaux de sélection des patients admis à la RCR-E, la plupart de ces réanimations étaient pratiquées sur de jeunes patients auparavant en bonne santé qui avaient subi une réanimation cardiorespiratoire immédiate de haute qualité. L’élaboration de programmes de RCR-E minutieusement planifiée, dans des systèmes de soins d’urgence de haute performance de centres expérimentés dans l’oxygénation par membrane extracorporelle (ECMO, de l’anglais extracorporeal membrane oxygenation), serait raisonnable dans le cadre des efforts systématiques pour déterminer l’efficacité de la RCR-E et améliorer les soins à l’échelle mondiale. L’évaluation du protocole exige une évaluation à l’échelle régionale, qui examine les avantages supplémentaires de la survie par rapport aux soins courants en tenant compte de l’utilisation des ressources.

Section snippets

Search strategy, data extraction, and quality assessment

To provide an overview of the evidence of ECPR efficacy for OHCA, we (E.G.) designed a search strategy (Supplemental Appendix S1) to identify systematic reviews (SRs) and meta-analyses. From 2005 to May 29, 2017, we searched: MedLine (Ovid), Embase (Ovid), Cochrane (Wiley), PubMed (National Library of Medicine), and Web of Science (Thomson Reuters), with no language restrictions. We used text words in the title, abstract, or key word fields, and relevant subject indexing to retrieve SRs or

Results

Our systematic search produced 327 citations (Supplemental Appendix S1 and Fig. 1). After screening, we identified 12 SRs, 7 of which were excluded after full text retrieval,4, 12, 13, 14, 15, 16, 17 leaving 5 included studies.5, 18, 19, 20, 21

Four of the SRs limited study eligibility to those that compared ECPR with conventional resuscitation,18, 19, 20, 21 all including different combinations of 5 studies (Tables 1 and 2; Supplemental Appendixes S2 and S3). The review by Kim et al.19 included

Limitations in current research

Risk of bias resulted in a low or very low quality of evidence for ECPR in refractory OHCA.27 Selection bias by clinicians for ECPR therapy is a major limitation, in addition to significant heterogeneity in the intervention provided and study populations.

Most SRs included studies that compared those treated with ECPR, to those treated exclusively with conventional resuscitation, on the basis of clinical decision. The results of these comparisons are highly dependent on the group chosen to be

ECPR Effectiveness for Refractory OHCA: Completely Obvious or Entirely Unknown?

Previous studies define the limits of survivable CPR duration for patients who meet ECPR criteria, but who are treated exclusively with conventional resuscitation.28, 35 One North American study included 150 EMS agencies over a 3-year period and identified all patients who met an ECPR criteria but were treated with conventional resuscitation.28 The probability of survival showed a continual decline with increasing durations of elapsed resuscitative efforts. The longest duration until ROSC in a

EMS Differences and the Need for a True Denominator

With the exception of reports of ECPR initiated in the prehospital setting,42 the current literature is limited to outcomes of patients who have been transported to the hospital with ongoing CPR. Inclusion in studies has ranged from only those treated with ECPR during active CPR,7 those treated with ECPR after OHCA (some with ROSC),43 to those selected for ECPR (some without initiation because of ROSC or unsuccessful vascular access).6 The most appropriate denominator, however, is the number of

Who Are Ideal Candidates for ECPR?

ECPR deployment is typically highly selective,5, 17 with clinicians treating only patients believed to have the possibility of good outcomes, usually focusing on relatively young healthy patients with short no-flow durations, to minimize the risk of treating those with preceding irreversible cerebral injury. Therefore, our ability to ascertain the best ECPR candidates beyond these highly selected groups is limited. The alternative strategy, a wide application of ECPR resulting in data to

Potential Absolute Benefits

The overall incremental benefit of ECPR to the survivorship in a health region might be modest. One study in Vancouver (population approximately 1 million) reported that 10% of patients with OHCA met the local ECPR criteria, of whom one-third were refractory to conventional resuscitation and thus might have benefited from ECPR (approximately 12 per year).2 This estimate would be lower if restricted to shockable rhythms. A study from Vienna reported that 6% of OHCAs fulfilled their criteria for

Resource Implications and Readiness

OHCA patients treated with ECPR require resource-intensive management, which might not be feasible in all locales. In contrast, OHCA patients who do not have ROSC are pronounced dead in the prehospital setting or in the emergency department, with a relatively low cost. In the prehospital setting, ECPR implementation requires modification of protocols and training, which should seek to achieve the greatest chance of ROSC before transport, while at the same time minimizing delays for ECMO

Donation-Related Considerations

When using advanced resuscitation treatments, the first and foremost priority is saving the patient's life with the goal of neurologically favourable survival. However, although treatment advances have led to improvements in survival, the most common outcome remains death,1 with many patients suffering irreversible anoxic brain injury. Although organ donation has not traditionally been reported in OHCA studies, the 2015 International Liaison Committee on Resuscitation (ILCOR) recommendations

A Framework for ECPR Application

Canadian experience with ECPR for OHCA is limited. Although there have been reports on the use of ECPR for IHCA,51, 52 only 1 study has described the experience with a formal OHCA ECPR protocol.47

Although there are significant limitations in the literature regarding estimates of efficacy, it is highly likely that ECPR after prolonged conventional resuscitation for select patients is superior to conventional resuscitation alone. Nonetheless, acknowledging the state of the evidence, widespread

Conclusion

The incremental benefit and cost-effectiveness of incorporating ECPR into regional OHCA resuscitation systems of care remains unclear. However, it is highly likely that ECPR treatment, in select patients with OHCA refractory to prolonged attempts of conventional resuscitation, is superior to conventional efforts alone. Carefully planned development of ECPR programs in high-performing EMS systems at experienced ECMO centres with the requisite skills, training, and resources might be reasonable

Disclosures

L.H. and S.D.S. are paid consultants for Canadian Blood Services; J.B. has received consulting honoraria and an investigator-initiated research grant from Boston Scientific and Spectranetics; S.C.B. has received a CIHR grant for a national ECPR meeting in Canada. The other authors have no conflicts of interest to disclose.

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