March 4, 2021

The ARREST Trial: ECMO or EC-No for Refractory Cardiac Arrest?

Background:  Despite medical advances, survival after out of hospital cardiac arrest (OHCA) is still largely dependent on high-quality CPR. Many of these events are due to a primary cardiac event, likely coronary artery occlusion. Current guidelines recommend reperfusion therapy following cardiac arrest with signs of acute coronary occlusion on EKG. But this only applies when return of spontaneous circulation (ROSC) is achieved. What about those in refractory arrest? Is there a way to increase survival in those patients? Keeping in mind that achieving ROSC may be impossible without reperfusion and reperfusion will likely not occur without ROSC.

Paper:  Yannopoulos 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 Control Trial. Lancet. PMID: 33197396

Clinical question:  Does extracorporeal membrane oxygenation (ECMO) resuscitation coupled with immediate coronary angiography/catheterization improve survival compared to standard ACLS in the emergency department?

What They Did:   

  • Phase 2, single center, open-label, safety and efficacy, pragmatic randomized controlled trial
  • Emergency Department (ED) at University of Minnesota Medical Center
  • Randomized all consecutive adult patients to standard ACLS or early ECMO treatment
  • Inclusion Criteria
    • Initial OHCA rhythm of ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT)
    • No ROSC after 3 defibrillation attempts
    • Body morphology able to accommodate the Lund University Cardiac Arrest System (LUCAS) device
    • Estimated transfer time to ED of less than 30 minutes
  • Exclusion Criteria:
    • Valid do not resuscitate order
    • Traumatic arrest
    • Drowning
    • Known overdose
    • Known pregnancy
    • Incarcerated patients
    • Nursing home residents
    • Presence of an opt-out study bracelet
    • Unavailability of the catheterization lab
    • Terminal cancer
    • Absolute contraindications to emergent angiography
    • Contrast allergies
    • Active bleeding
  • Early ECMO group
    • Gained immediate access to catheterization lab regardless of presence or absence of pulse on hospital arrival with continual mechanical CPR
    • Resuscitation discontinuation criteria assessed on arterial blood gas (2 or more of the following met criteria for discontinuation)
      • End-tidal CO2 < 10
      • PaO2 < 50 or O2 saturation < 85%
      • Lactic acid > 18 mmol/L
    • ECMO cannulas placed by cardiologist and perfusion started
    • Coronary angiography was then completed
  • Standard ALCS group
    • Stayed in ED under the care of the emergency physician
    • Treatment was continued for at least 15 minutes after arrival or at least 60 minutes after 911 call
    • If ROSC obtained, patient then transferred for angiography, angioplasty or circulatory support as needed per clinical protocol
  • Intention to treat principle used for primary and safety analysis
  • Safety Monitoring Board obliged to provide forma recommendation on whether to stop trial if strong evidence was found of a difference in survival to discharge rates between groups during interim analysis

Outcomes:  

  • Primary Outcome
    • Survival to hospital discharge
  • Secondary Outcomes:
    • Survival and functionally favorable status at discharge and at 3 and 6 months after discharge defined as a modified Rankin score ≤ 3

Results:  

  • Enrollment terminated 10 months after starting following safety board recommendation
    • 36 patients assessed, 6 excluded
    • Mean age: 59 years old
    • 83% male
  • Primary Outcome achieved in 29 patients (1 withdrew participation before hospital discharge
    • Survival
      • ECMO group: 43% (6/14)
      • ACLS group: 7% (1/15)
    • Secondary Outcome: Cumulative survival better in ECMO group (hazard ratio of 0.16 [p<0.0001])
    • All survivors had good functional assessment scores at 6 months (modified Rankin score ≤ 3)

Strengths:  

  • Randomized control trial
  • Consecutive enrollment
  • Simple inclusion/exclusion criteria making results more generalizable
  • Objective and dichotomous primary outcome
  • Facility with highly orchestrated collaboration between service lines and coordinated implementation of chain of survival

Limitations: 

  • Single center
  • Care provided by local emergency system and highly experienced interventional critical care cardiology team
  • Need for substantial systematic reorganization of emergency response infrastructure and centralization of care
  • Need for highly trained and expert teams that can respond in minutes
  • Resuscitation with ECMO vs no ECMO was not really compared. Instead, it was standard ACLS vs ECMO plus angiography
  • Multiple baseline differences between patients, which may have favored the ECMO group. Difficult to interpret due to small sample size
  • Secondary outcome more clinically relevant than primary outcome

Discussion:  This is the first randomized-controlled study to show resuscitation with ECMO plus coronary angiography can improve survival compared to standard ACLS in OHCA with refractory VF or VT. ECMO achieves three goals pertinent to survival of OHCA: reliable normalization of perfusion, provides cardiopulmonary support to facilitate identification and treatment of the most common cause of refractory arrest (severe coronary artery disease with chronic or acute occlusion), become bridge to recovery in ICU when multiorgan injury is sustained during long resuscitation. The question still remains, however, if resuscitation with ECMO plus angiography is superior to angiography with continual mechanical CPR without ECMO.

Author Conclusion: “Early ECMO-facilitated resuscitation for patients with OHCA and refractory ventricular fibrillation significantly improved survival to hospital discharge and functional status compared with patients receiving standard ACLS resuscitation.”

Clinical Take Home Point:  ECMO provides a promising opportunity to increase meaningful survival for OHCA patients with refractory VF or VT. However, this is a time- and resource-intensive modality that is not available in all settings. Continue to provide high-quality CPR, defibrillate early, and search for reversible causes. If ROSC is achieved, evaluate for evidence of acute coronary occlusion and the need for emergent coronary revascularization.

For More Thoughts on This Topic Checkout:

Post Peer Reviewed By: Anand Swaminathan, MD (Twitter: @EMSwami)

Cite this article as: Matt Astin, "The ARREST Trial: ECMO or EC-No for Refractory Cardiac Arrest?", REBEL EM blog, March 4, 2021. Available at: https://rebelem.com/the-arrest-trial-ecmo-or-ec-no-for-refractory-cardiac-arrest/.
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Matt Astin

Clinical Assistant Professor of Emergency Medicine/Internal Medicine at Medical Center of Central Georgia
REBEL EM Associate Editor and Author
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