An ARREST-ing Development: A Community Approach to ECPR for OHCA (Part 2)

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Picture of Zaf Qasim
Zaf Qasim
Dr Zaf Qasim is an attending physician in Emergency Medicine and Critical Care based at the University of Pennsylvania in the United States. He has particular interests in trauma, prehospital care and advanced resuscitation including endovascular techniques. You can find him on Twitter as @ResusOne

The Pre-brief

Last week we discussed how a community came together to evolve the management of out-of-hospital cardiac arrest by developing a community-wide ECMO-facilitated resuscitation (ECPR) program. This was spurred by work out of a single center in that community. 

Of note, this was the first randomized interventional trial assessing the effectiveness of ECPR versus standard ACLS for these patients – previous attempts to look at this have been primarily observational. 

Given the current relatively poor neurologically intact survival from traditional methods, will ECPR be the way forward?

What did the authors do?

This was conducted as a phase-2 trial, primarily assessing safety and efficacy. It was a pragmatic, open-label, randomized controlled trial supported by the National Heart, Lung, and Blood Institute (NHLBI). It was completed at a single center – the University of Minnesota and built on earlier data that early transport and direct access to the cardiac cath lab for ECPR could yield better outcomes.

The study received an exemption from informed consent (EFIC) but consent was obtained within 24 hours of enrollment from authorized representatives when possible.

A mixed Bayesian and Frequentist method was used for analysis. Every 30 participants had an analysis of the primary outcome initially in a 1:1 ratio and then in a ratio defined by the outcomes. A Data Safety Monitoring Board was alerted if there was a clear benefit of one modality over the other.

Patients were randomly assigned on arrival to the hospital using permuted blocks with randomly varying block sizes to either standard ACLS or ECPR. There was pre-randomization blinding of emergency teams, although they could no longer be blinded once randomized. However, as both teams could present with or without an ECMO circuit to the ICU, the critical care teams were masked to group allocation. 

Eligible patients who were pulseless in the ECPR group received immediate ECMO access in the cath lab and coronary angiography with revascularization and circulatory support as indicated. If they had a pulse, they would just undergo angiography with or without angioplasty and circulatory support.

Eligible patients in the standard ACLS group stayed in the ED and were cared for as usual by the emergency physician. This had to be continued for at least 15 minutes from ED arrival or at least 60 minutes from the initial 911 call. If ROSC was achieved, they proceeded to the cath lab for further care as indicated.

All patients received critical care in a single cardiac ICU. This care was not protocolized but adhered to best evidence-based practice and included targeted temperature management, mechanical circulatory support if needed, head CT on admission and day 3, no neuroprognostication until 72 hours post-arrest, and continuous EEG until awake.

What were the inclusion and exclusion criteria?

Consecutive patients were enrolled if they met the following criteria:

  1. Adults 18-75 years
  3. No ROSC after 3 shocks
  4. Use of a LUCAS device
  5. Transfer time to the ED <30 minutes

Exclusions included:

  1. Advanced directive (e.g. DNR)
  2. Prisoner status
  3. Pregnancy
  4. Advanced/terminal malignancy
  5. Traumatic or toxicologic mechanism of arrest
  6. Absolute contraindication to angiography e.g. contrast allergy

The patient would be assessed on arrival and not be enrolled for ECPR if two or more of these criteria were met:

  1. End-tidal CO2 ≤10mmHg
  2. Arterial PaO2≤50mmHg or O2 saturations ≤85%
  3. Lactate≥18mmol/L

What outcomes measures were used?

The primary endpoint was survival to hospital discharge. 

Secondary outcomes included:

  1. functionally favorable survival (modified Rankin score [mRS] of 3 or lower and a cerebral performance category scale [CPC] of 2 or lower) at discharge. 
  2. functionally favorable survival (modified Rankin score of 3 or lower and a cerebral performance category scale [CPC] of 2 or lower) at 3- and 6-months from discharge 
  3. Incidence of adverse events

What were the results?

A sample size calculation was performed to include 174 patients (based on ECMO survival of 37% and ACLS 12%) with 90% power, and accounting for a 15% withdrawal or false positive activation rate.

From August 2019 to June 2020, 36 patients were assessed and 6 excluded. The 30 patients enrolled were randomized equally to ECPR or ACLS (though one later withdrew consent in the ECPR group) and were similarly matched in terms of demographics – mean age 59 years; primarily male; similar rates of chronic health problems including diabetes and respiratory disease (though a higher rate of coronary artery disease in the ACLS group of 27% vs 13%). 23% of patients enrolled were White. Bystander CPR occurred in >80% of patients in both groups, and most were witnessed arrests (ECPR 73.3% vs ACLS 86.7%). Average EMS scene time was about 23 minutes in both groups, with transport times of 20 minutes or less. No patient arrived with ROSC to the ED in either group. The mean time from the 911 call to ECPR initiation was 59 minutes. An intra-aortic balloon pump was placed 40% of the time in the ECPR group.

The primary outcome (survival to hospital discharge) was 43% in the ECPR group versus only 7% in the ACLS group. As a result of this marked benefit of the ECPR group, the trial was stopped early by the NHLBI on the recommendation of the DSMB.

In terms of secondary outcomes:

  • No ACLS group patient was alive at 3- or 6-months
  • 6 month survival was 43% in the ECPR group versus 0% in the ACLS group
  • Functional status at 6 months in the ECPR group was good with mean mRS of 1.3 and CPC of 1.16
  • ICU length of stays in the ECPR group averaged 21.5 days
  • Hospital length of stays in the ECPR group averaged 25.5 days
  • There were no device-related failures reported
  • There were four procedure-related adverse events including cracks in the tubing, access site bleeding requiring 3 or more units of blood, and injuries related to vascular trauma leading to retroperitoneal bleeding

Of note, some patients in the ECPR group could not walk unassisted at the time of discharge due to deconditioning which could have affected scores.

What were the limitations?

This was a single center study with a low number of patients. However, given that there were predetermined safety and data monitoring stops built into the protocol, this could have been predicted and did conform to data from prior studies. Additional limitations include the short transport times (<20 minutes) and so this may not be applicable to communities with longer prehospital transport times. The use of functional outcomes is important but does leave some room for variance, both in assessment as well as perception by the patient – some would want complete return to normal function and so even some disability may be intolerable. This is difficult to capture in this type of study. Finally it is important to remember that financial implications of these interventions need to be accounted for, and this was not discussed.

The Debrief

  • Again, the headline figure in this paper is astounding – 43% functional survival from OHCA versus only 7% in the ACLS group
  • Given the incredibly poor outcomes from standard ACLS despite years of attempting to tweak various variables, this is to be applauded. The fact that this benefit was seen early in the trial leading it to be stopped shows that is really a paradigm shift in management.
  • ECMO provides numerous benefits including reliable perfusion, mechanical cardiac support, and the ability to facilitate treatment of causes of refractory arrest. 
  • However it is dependent on a skilled clinician group, both for the procedure itself and for the post-procedure critical care which would likely only be based at major academic centers. 
  • Furthermore, it is dependent on a system of care that can reliably identify and deliver patients to these clinicians, as discussed in part 1 of this post. 
  • Focusing on these systems issues can go some way to shortening the time from the 911 call to ECPR initiation. 
  • Given the building body of evidence in support of this therapy for out-of-hospital arrests, it is time to really address the possibilities of providing this level of care in the wider United States – and worldwide.


  1. 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. The Lancet November 2020 DOI:
  2. 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 center, open-label, randomized controlled trial. The Lancet November 2020 DOI:
  3. Youngquist ST, Tonna JL, Bartos JA, et al. Current Work in Extracorporeal Cardiopulmonary Resuscitation. Crit Care Clin 2020 Oct;36(4):723-735 PMID: 32892825


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