ECMO outperforms traditional CPR for certain cardiac arrest patients, a new meta-analysis revealed. But ECMO’s large-scale implementation would require substantial considerations.
By Alyx Arnett
Extracorporeal membrane oxygenation (ECMO) has garnered renewed attention in recent years as a potential alternative to traditional cardiopulmonary resuscitation (CPR) for improving cardiac arrest outcomes, which remain low despite advances in resuscitation and critical care.
Survival rates for out-of-hospital cardiac arrest are estimated at roughly 2-11%, and in-hospital cardiac arrest survival rates range from 15-25%.1 Still, CPR remains the primary resuscitation method with a proven positive impact on prognosis.
Venoarterial ECMO, which supports both heart and lung function and can provide hemodynamic support and respiratory stabilization for those undergoing extracorporeal CPR (ECPR), may offer another option.2 While its first successful use was documented in 1971, the method largely fell out of favor in adult patients due to few successes in subsequent years.3
However, advances in technology have improved ECMO outcomes over the years. ECMO is increasingly being adopted due to the advent of small, portable ECMO devices and circuit improvements.4 Other advances include the development and increased use of centrifugal pumps instead of roller pumps and low-resistance hollow fiber oxygenators that may reduce hemolysis and make centrifugal pumps even more efficient.5
“With changes like coded circuits, centrifugal pumps, and different types of oxygenators, it’s made the technology more tolerable with fewer complications,” said Dustin Money, ECMO specialist at the University of Virginia Health System and research assistant at the University of Virginia School of Medicine. “There’s been more adults put on ECMO in the last 10 years than there were the preceding 20 years.”
Recent research also has put ECMO back in the spotlight. Since 2020, three landmark randomnized controlled trials—ARREST,6 Prague OHCA,7 and INCEPTION8—have been published on the use of ECMO versus conventional CPR for cardiac arrest resuscitation. However, these studies yielded varied outcomes, with one (ARREST) showing improved survival rates with ECMO and the other two not demonstrating significant differences.
Fluctuating study results have transitioned ECMO perceptions from definitive efficacy, to a more tentative belief in its advantages, to outright uncertainty, raising questions about its true potential.
Due to the lack of definitive evidence of the benefit of ECMO over CPR, a new meta-analysis collates insights from all current literature to evaluate ECMO’s efficacy and assess possible reasons for differences between studies.1
Investigators included 11 studies involving 4,595 patients receiving ECPR and 4,597 receiving conventional CPR from January 2000 to April 2023. They found that, compared to CPR, ECPR significantly reduced mortality for patients with in-hospital cardiac arrests and improved long-term neurological outcomes and post-arrest survival.
However, no meaningful benefit was found for out-of-hospital cardiac arrest patients, which investigators posited could be due to the time required to transport patients to a hospital, increasing the time to cannulation. Patients with in-hospital arrests were likely to have not only shorter low-flow times (duration of conventional CPR) but also higher rates of witnessed arrest and bystander CRP, reducing no-flow time (time from cardiac arrest to CPR) as well—factors investigators determined can influence outcomes.
Other influential factors were adequate training and experience. Investigators found that centers with increasing volumes—the number of ECPR runs done per year—were associated with reductions in odds of mortality.
The most common complication with ECPR was bleeding, affecting 32–70% of patients, while other complications included infection and leg ischemia.
With findings suggesting that ECMO could significantly improve outcomes for certain patients, study authors Kollengode Ramanathan, MD, an adult cardiac intensivist at the Cardiothoracic Intensive Care Unit at the National University Heart Centre in Singapore and adjunct associate professor at the National University of Singapore, and Christopher Jer Wei Low, a medical education undergraduate at the National Univeristy of Singapore, believe the meta-analysis will lead to increased credibility for the consideration of ECMO for cardiac arrest patients.
“We believe that ECMO can be looked at as a way to not only improve survival but also neurological outcomes. Therefore, the treatment paradigm is likely to shift from not only preserving life but also quality of life. By reducing low-flow time, ECMO achieves adequate end-organ perfusion faster and better than conventional CPR, thus ensuring good perfusion of the brain and thus likely improving neurological outcomes,” said Ramanathan and Low in a joint response to RT.
However, broader implementation of ECMO for cardiac arrest patients would require significant considerations and greater resources.
According to Ramanathan and Low, comprehensive clinician training in ECMO cannulation and post-resuscitation care is essential and should be paired with an integrated team approach—bringing together professionals like respiratory therapists, nurses, perfusionists, surgeons, intensivists, physiotherapists, and social workers to care for each patient.
The researchers added that implementing ECPR services also would require more detailed logistical preparation compared to introducing standard ECMO services. For example, efficient hospital protocols and pathways must be in place to ensure rapid transport of patients to the hospital and to address the needs of ECMO-suitable patients. An ECMO team should always have a physician available for immediate cannulation, supported by specialists in post-resuscitation care, the authors said.
“Thus, when considering the adoption of ECMO by hospitals, hospitals need to evaluate if they are adequately prepared to train physicians and other members of the care team, if they have adequate finances to fund such an ECMO team, and whether they have sufficient infrastructural and manpower capacities,” said Ramanathan and Low. “It is fundamentally unrealistic to expect every hospital to be able to achieve such capacities.”
Smaller or more rural hospitals may not have the means to implement such programs, they said. ECMO specialist Money, whose hospital is in Charlottesville, Va—a smaller city surrounded by a small suburban area, surrounded by a very rural area—agreed.
“There’s a very different thing about employing ECPR for out-of-hospital cardiac arrest in a metropolitan area versus a suburban area versus a rural environment,” Money said. “For me, if I were to compare myself to a place like Minneapolis, out-of-hospital cardiac arrest time is going to be pretty long. It’s going to be longer downtimes, longer transport times to my facility from a logistical standpoint. It’s a harder thing for me to provide versus a place like Baltimore, San Diego, San Francisco, LA—large, urban environments with short transport times and short downtimes.”
Ramanathan and Low said a hub-and-spoke model would be the most practical approach. Such a model would entail having dedicated, specialized cardiac arrest centers from which ECMO teams could be deployed to nearby hospitals to stabilize patients before transferring them for centralized, specialized care.
“This would ensure ECMO can be a standard of care in cardiac arrest while realistically balancing limitations in smaller centers that may not have the capacity to manage their own ECMO cases,” Ramanathan and Low said.
Another crucial factor for successful outcomes is implementing strict, standardized inclusion criteria to ensure only the most suitable candidates receive ECMO.
Protocols and guidelines aim to identify cases most likely to survive with favorable neurological outcomes, such as those with witnessed arrests where high-quality CPR was initiated quickly and cases that have a presumed reversible pathology, like acute coronary occlusions, according to an interim consensus statement from the Extracorporeal Life Support Organization (ELSO).9
The guidelines recommend formulating locally agreed inclusion criteria “to guide clinicians on balancing the wise use of resources amongst patients who are thought to have an improved chance of survival following cardiac arrest.”
Ramanathan and Low agreed. “Our study and the three trials highlighted that a strict inclusion criteria for well-selected patients is most likely to benefit, as opposed to implementing it for all cardiac arrest cases. This was shown in the highly selected ARREST trial and may also suggest why a pragmatic trial like INCEPTION failed to highlight any benefit,” they said.
Such criteria should be complemented by well-structured protocols and the necessary supporting infrastructure—elements that were evident in the Minnesota Mobile Resuscitation Consortium’s ECMO-facilitated resuscitation program, the first community-wide initiative of this nature in the US.10
From December 2019 to April 2020, the mobile program transported 63 consecutive patients. Of these, 58 met inclusion criteria that were identical to the ARREST trial: patients aged 18-75, ventricular tachycardia/ventricular fibrillation out-of-hospital cardiac arrest, no return spontaneous circulation after three shocks, automated CPR with a Lund University Cardiac Arrest System, and an estimated transfer time of less than 30 minutes.
Patients meeting these criteria were treated by the mobile ECMO service. The program demonstrated a 100% success rate in cannulation and 43% favorable functional survival rates at hospital discharge and at three months.
According to that study, the program’s success hinged on other key components, including emergency medical services, three community ECMO initiation hospitals with emergency department ECMO cannulation sites and 24/7 cardiac catheterization laboratories, a 24/7 mobile ECMO cannulation team, and a single, centralized ECMO intensive care unit.
“This study demonstrates that ECMO can be delivered across a metropolitan area safely with a specialized team, meeting patients at predetermined ECMO cannulation sites closer to the location of the patient’s arrest,” the study authors wrote. “The rate of neurologically favorable survival (43%) was similar to prior ECMO studies with geographically constrained cohorts as well as the…single-center ARREST trial.”
According to Money, “It’s very promising to see that, with appropriate inclusion-exclusion criteria and appropriate logistics, you’re able to afford these really good outcomes. And so it shows that it’s very possible, but it requires a lot of planning and logistics.”
Continued research and technological advancements may further improve outcomes. A recent study suggests that developments in blood-wetted biomaterials and hemodynamically favorable geometric designs can help with challenges like thrombosis, hemolysis, and site infection.11
The study also highlights the potential of MRI technology in augmenting ECMO by enabling real-time evaluation of brain blood flow and oxygen usage and suggests that integrating ECMO with therapeutic hypothermia—one of the few treatments beyond ECMO that enhances cardiac and neurological function and survival outcomes—could elevate survival rates.11
According to Ramanathan and Low, other promising research explores the potential of a pulsatile ECMO that works in conjunction with the cardiac cycle, which would be useful for post-cardiac arrest shock scenarios, where easing the left ventricular workload is crucial for myocardial recovery. Additionally, they highlighted ongoing studies into mean arterial pressure targets in post-cardiac arrest care, involving the possibility of titratable pressure targets based on individual patient needs.
“As technology improves and as research improves—and we figure out what subpopulations in cardiac arrest may truly benefit from ECPR—this is going to get better, and you’re going to see it used more widely,” said Money.
Recent US Food and Drug Administration clearances already are giving clinicians newer and potentially more effective tools. In February 2020, Fresenius Medical Care North America’s Novalung ECMO system received clearance. According to the manufacturer, the system includes features that may optimize cardiac arrest survival, such as pressure-limiting flow control, low-flow precision, auto-set alarm limits, and visual parameter trending.
In November 2022, LivaNova secured clearance for LifeSPARC, its next-generation advanced circulatory support pump and controller system. Designed to simplify the often complex nature of ECMO devices, the LifeSPARC system features a streamlined process that minimizes priming time and offers enhanced portability for in-hospital transport, according to LivaNova.
Additionally, in April 2023, the FDA cleared Abbott’s CentriMag pre-connected pack for urgent cardiopulmonary support. The pre-connected pack combines several components, including the blood pump and oxygenator, enabling clinicians to offer full support in fewer steps. Before this clearance, the system had to be assembled from separate components, potentially causing delays in urgent care.
Alyx Arnett is associate editor of RT. For more information, contact [email protected].
- Low CJW, Ramanathan K, Ling RR, et al. Extracorporeal cardiopulmonary resuscitation versus conventional cardiopulmonary resuscitation in adults with cardiac arrest: a comparative meta-analysis and trial sequential analysis. Lancet Respir Med. 2023 May 22;S2213-2600(23)00137-6.
- De Charrière A, Assouline B, Scheen M, et al. ECMO in cardiac arrest: a narrative review of the literature. J Clin Med. 2021 Feb 2;10(3):534.
- Featherstone PJ, Ball CM. The early history of extracorporeal membrane oxygenation. Anaesth Intensive Care. 2018;46(6):555-7.
- Dennis M, Lal S, Forrest P, et al. In-depth extracorporeal cardiopulmonary resuscitation in adult out-of-hospital cardiac arrest. J Am Heart Assoc. 2020;9(10):e016521.
- Dalton HJ, Menon S. Chapter 53 – Extracorporeal Life Support. Pediatric Critical Care. 4th ed; 2011:717-37
- 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;396(10265):1807-16.
- Belohlavek J, Smalcova J, Rob D, et al. Effect of intra-arrest transport, extracorporeal cardiopulmonary resuscitation, and immediate invasive assessment and treatment on functional neurologic outcome in refractory out-of-hospital cardiac arrest: a randomized clinical trial. JAMA. 2022;327(8):737-47.
- Suverein MM, Delnoij TSR, Lorusso R, et al. Early extracorporeal CPR for refractory out-of-hospital cardiac arrest. N Engl J Med. 2023;388(4):299-309.
- Richardson ASC, Tonna JE, Nanjayya V, et al. Extracorporeal cardiopulmonary resuscitation in adults. Interim guideline consensus statement from the extracorporeal life support organization. ASAIO J. 2021;67(3):221-8.
- 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;29-30:100632. 2020 Nov 13.
- Ambinder DI, Oberdier MT, Miklin DJ, et al. CPR and ECMO: the next frontier. Rambam Maimonides Med J. 2020 Apr 29;11(2):e0013.