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Concise Critical Appraisal: ARREST Trial: ECMO Versus Advanced Cardiac Life Support

Despite having the best outcomes in out-of-hospital cardiac arrest (OHCA), ventricular fibrillation (VF) and ventricular tachycardia (VT) have high mortality and neurologic morbidity. As many as one-half of these patients’ conditions are refractory to standard advanced cardiac life support (ACLS) treatment, and a significant proportion of those have coronary lesions as the etiology of their arrest.1 Observational trials show that extracorporeal membrane oxygenation (ECMO) improves outcomes as it allows other interventions such as angioplasty to occur while maintaining coronary and cerebral perfusion.2,3 However, prospective randomized trials had not previously been performed. The Advanced Reperfusion Strategies for Patients with Out-of-Hospital Cardiac Arrest and Refractory Ventricular Fibrillation (ARREST) trial was conducted to compare early ECMO-facilitated resuscitation with standard ACLS in refractory OHCA.4
 
The ARREST trial was a randomized single-center trial. The study population included patients aged 18-75 years with an initial OHCA rhythm of VF or pulseless VT with no return of spontaneous circulation (ROSC) after 3 defibrillations. Inclusion criteria were body habitus accommodating mechanical CPR device and emergency medical services (EMS) transfer time under 30 minutes. Exclusion criteria included trauma, overdose, pregnancy, terminal cancer, significant bleeding, and contraindications to angiography, among others. Thirty patients were enrolled, with 15 patients randomly assigned to early ECMO-facilitated resuscitation and 15 patients randomly assigned to receive standard ACLS treatment. Those randomized to early ECMO-facilitated resuscitation had immediate venoarterial ECMO initiated and angiography performed, with revascularization if indicated. Those randomized to standard emergency department (ED) resuscitation had ACLS performed for at least 15 minutes after arrival in the ED and 60 minutes after the call to EMS.
 
The trial was terminated early based on termination criteria. The primary outcome of survival to hospital discharge occurred in 6 of 14 patients (43%) in the ECMO group, compared with 1 of 15 patients (7%) in the ACLS group. Secondary outcomes of survival and favorable functional status at discharge and at 3 months and 6 months after discharge showed that cumulative survival was higher in the early ECMO group, with hazard ratio 0.16 (95% CI, 0.06-0.41; p < 0.0001). The 1 survivor to discharge in the ACLS group had modified Rankin score (MRS) of 5 and Cerebral Performance Category (CPC) score of 4 and died prior to 3 months. In the early ECMO group, all survivors survived to 6 months. MRS of the survivors were 0 through 3, and CPC scores were mostly 1, with 1 patient scoring 2.
 
This is the first randomized trial of ECMO in refractory OHCA in the United States. The authors should be applauded for their efforts in this difficult patient population. The results are encouraging but not without limitations. This was a single-center study at a site with an experienced ECMO team. Yannopoulos et al were able to initiate venoarterial ECMO a mean 7 minutes from patient arrival to the cardiac catheterization laboratory.4 These results may not be reproducible in less-experienced, low-volume centers. However, the authors show what is possible with a commitment to teamwork, coordination, and clinician experience. Another limitation is the size of the trial. Results from a population of 30 patients should not change patient management for a disease as prevalent as cardiac arrest and a treatment as resource intensive as ECMO. It is intriguing, however, that it was deemed unethical to continue standard ACLS at this ECMO center, and the results of ACLS were almost universally dismal in this patient population.
 
If the results of the ARREST trial are validated, this may have dramatic implications for cardiac arrest care. The need for centralization of resources and ECMO expertise to care for cardiac arrest patients in a timely fashion will likely require restructuring of systems similar to the way stroke and trauma care are approached in the United States and other countries. Other important considerations include selection of patient population, regionalization of healthcare, and transport of OHCA patients to specialized centers.
 
Finally, who cannulates and where? Is it performed in the ED, catheterization lab, or operating room? This group also published data on initiation of ECMO in the out-of-hospital environment by deploying a mobile response team in a vehicle equipped for performing ECMO, which could be adopted in locales with a long EMS transport system.5 Further work is required to define optimal strategies for ECMO delivery in different healthcare systems. This study is an important step toward further understanding that role. The results of the ARREST trial support the use of ECMO in refractory OHCA as it significantly improved survival to hospital discharge and functional status.

Coauthors of this installment of Concise Critical Appraisal:
 
Tatyana Shvilkina, DO, is an assistant professor and clinical resuscitation fellow in the Department of Emergency Medicine at Stony Brook Medicine.
 
Brian J. Wright, MD, MPH, is a clinical associate professor and the program director for the Advanced Resuscitation Training Program in the Department of Emergency Medicine at Stony Brook Medicine. Dr. Wright is an editor of Concise Critical Appraisal.

References

  1. Yannopoulos D, Bartos JA, Aufderheide TP, et al; American Heart Association Emergency Cardiovascular Care Committee. The evolving role of the cardiac catheterization laboratory in the management of patients with out-of-hospital cardiac arrest: a scientific statement from the American Heart Association. Circulation. 2019 Mar 19;139(12):e530-e552. https://pubmed.ncbi.nlm.nih.gov/30760026/
  2. Kim SJ, Kim HJ, Lee HY, Ahn HS, Lee SW. Comparing extracorporeal cardiopulmonary resuscitation with conventional cardiopulmonary resuscitation: a meta-analysis. Resuscitation. 2016 Jun;103:106-116. https://pubmed.ncbi.nlm.nih.gov/26851058/
  3. Bartos JA, Carlson K, Carlson C, et al. Surviving refractory out-of-hospital ventricular fibrillation cardiac arrest: critical care and extracorporeal membrane oxygenation management. Resuscitation. 2018 Nov;132:47-55. https://pubmed.ncbi.nlm.nih.gov/30171974/
  4. Yannopoulos D, Bartos J, Raveendran G, et al. Advanced reperfusion strategies for patients with out-of-hospital cardiac arrest and refractory ventricular fibrillation (ARREST): a phase 2, single centre, open-label, randomised controlled trial. Lancet. 2020 Dec 5;396(10265):1807-1816. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32338-2/fulltext
  5. Bartos JA, Frascone RJ, Conterato M, et al. The Minnesota mobile extracorporeal cardiopulmonary resuscitation consortium for treatment of out-of-hospital refractory ventricular fibrillation: program description, performance, and outcomes. EClinicalMedicine. 2020 Nov 13. Online ahead of print. https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(20)30376-X/fulltext




Posted: 12/10/2020 | 1 comments

Comments
Alan H Morris, MD (University of Utah)
Congratulations to the investigators for conducting an RCT, an undertaking most extracorporeal enthusiasts would not engage. They did a scholarly job of organizing a complicated RCT, within their local environmental restraints. In addition to the comments/shortcomings of the study articulated in this Concise Critical Appraisal, I add requirements that will make the next study, and would have made the reported ARREST RCT, more scientifically robust. A well-designed RCT will make the tested intervention (ECMO in this case) the ONLY difference between decision-making and action in the 2 treatment groups. The protocols in the ARREST RCT (see their Appendix) are replete with guiding statements that require bedside clinician judgment. These statements include "Is patient clinically stable," "Consider circulatory support," and several similarly vague recommendations and questions that are common in many RCTs. A large literature confirms that clinicians' responses to such vague guideline statement are variable and frequently unlinked to best evidence. this precludes the ability of other interested investigators to replicate this work for two reasons: 1- the detailed method is not specified, and 2- we have no information about how clinicians made their decisions and whether they complied with the vague guideline statements and questions. We therefore do not know the detailed method nor do we know if clinicians followed the vague method guidelines, or why they deviated when they did not. To achieve these fundamental scientific experimental goals would require detailed protocols (undoubtedly computerized) for managing blood pressure, arterial oxygenation, alveolar ventilation, fluid infusion, body temperature, and other facets of care that could act as co-interventions that influence pertinent clinical outcomes and could obscure the true effect of the intervention under study. This has been done in the past and should be part of rigorous trials, particularly those, like ECMO trials, that cannot be blinded. The scholarship evident in the statistical design should, in clinical trials, be matched by scientifically rigorous articulation and execution of the experimental intervention and important co-interventions. Nevertheless, I take my hat off to the investigators who conducted and reported the ARREST RCT. I believe this is a significant step forward.
12/11/2020 7:48:26 PM


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