Will ECPR Move the Needle on Cardiac Arrest Survival?

Extracorporeal cardiopulmonary resuscitation (ECPR) can be defined as the emergent use of extracorporeal membrane oxygenation (ECMO) on patients in cardiac arrest for whom conventional CPR has failed. 
According to some estimates, out-of-hospital cardiac arrest (OHCA) is responsible for as many as 313,000 deaths annually in the United States and 4-5 million globally, despite administration of chest compressions and cardiac defibrillation. There is growing interest in ECPR as a way to improve survival and return to full cardiac and neurologic function.
Bypass at the Bedside
“ECMO is a medical procedure that removes blood from the vein, puts it through an oxygenator, then pumps the oxygenated blood back into the artery to bypass the heart and lungs,” Demetris Yannopoulos, MD, professor of medicine at the Center for Resuscitation Medicine and director of resuscitation medicine at University of Minnesota Medical School in Minneapolis, told Medscape Medical News. “It’s basically a heart-lung machine that enables the organs to remain oxygenated, even though the patient is in cardiac arrest.” 
But ECPR is far more than ECMO. Jason Bartos, MD, PhD, associate professor of medicine in the cardiology division at University of Minnesota Medical School, told Medscape Medical News that ECPR is an “entire system of care that encompasses the whole process, beginning with the patient’s cardiac arrest [and] continuing with the measures taken to address that cardiac arrest — including bystander CPR — identification of the patient as a potential candidate for ECPR, arrival of the paramedics, activation of the ECPR team, the cannulation and nuts-and-bolts of getting the patient hooked up to the ECMO machine, the care the patient receives in the hospital, and postdischarge care leading to full recovery.”
Yannopoulos characterized survival rates following OHCA in the US as “very low” (< 10%), especially following extensive resuscitative efforts. He called functional and neurological outcomes “generally dismal.”
ECPR isn’t new, he noted, citing a report published in 1966 of successful ECPR in eight adult patients. “Even then, the author said readily available teams were necessary, and perfusionists were needed to establish assisted circulation within 30 minutes [of arrest]. Moreover, ECPR techniques should only supplement but not replace conventional CPR.” 
These principles hold, although contemporary ECPR is more sophisticated. “ECPR is an additional tool, a continuation of CPR, not an either-or intervention,” Yannopoulos said. “Unfortunately, CPR becomes insufficient after about 30 minutes, and that’s where ECPR comes in.”
The use of ECPR has dramatically risen in recent years. According to recent data from the Extracorporeal Life Support Organization, a total of 18,389 cases of ECPR have been performed globally in adult patients, with a survival rate of 31%.
How Does ECPR Work?
Venoarterial ECMO provides gas exchange and circulatory support by draining the blood from a central vein, pumping it through a membrane lung, and returning it through an artery, Yannopoulos explained. Venovenous ECMO is used for lung support only.
Yannopoulos noted that ECPR is performed via femoral cannulation, with the reinfused oxygenated blood reaching the coronary and cerebral vascular beds rapidly. This enables the patient to be stabilized more efficiently compared to conventional CPR, thus allowing time to address and (ideally) reverse the impact of the arrest.
However, the arterial return cannula has the risk of causing several adverse events, including distal limb ischemia. Use of ultrasound guidance, percutaneous vascular access, and fluoroscopic verification of wire positioning have reduced the risk for this outcome — especially in high-volume centers. 
ECMO machines are made by multiple manufacturers, and all devices have the same basic elements and utilize the same strategy, Bartos said. These include a pump, oxygenators, and cannulas, “even if various devices may have different types of ‘bells and whistles,’ so to say,” he said.
However, most centers typically use one device that all practitioners have been trained on and know how to troubleshoot, “which enables us to lower or eliminate the impact of device-related complications,” Bartos said.
The term “extracorporeal life support” (ECLS) is sometimes used interchangeably with ECMO, However, Bartos clarified that ECMO “is a form of ECLS, but not every ECLS is ECMO.” 
The Center for Resuscitation Medicine at the University of Minnesota, which established the Minnesota Mobile Resuscitation Consortium, developed an approach for ECMO-facilitated resuscitation treatment of refractory ventricular fibrillation (VF)/ventricular tachycardia OHCA, Bartos said. By 2015, the program included the entire metropolitan community. It comprised a single, centralized ECMO intensive care unit at the University of Minnesota, where postarrest care was delivered; three additional ECMO initiation hospitals, with emergency department ECMO cannulation site availability; a “core” 24/7 mobile ECMO cannulation team; four dedicated ECMO cannulation team rapid response vehicles; and various types of intensive training. 
The community-wide program was activated at the end of 2019, with encouraging findings regarding its viability and success rates, he said. The Leona M. and Harry B. Helmsley Charitable Trust provided a substantial monetary donation to expand delivery of ECMO beyond a single medical center.
What’s the Evidence on ECPR?
The success of ECPR transcends survival, said Bartos. Functional status and neurologic recovery are critical components, “which goes hand-in-hand with seeing ECPR not only as a procedure and technique but as an entire continuum.” In fact, the International Liaison Committee on Resuscitation recommends using not only short-term functional assessments but also longer-term health-related quality-of-life measures when assessing success in cardiac arrest trials.
In-hospital cardiac arrest treated with ECPR has shown encouraging survival rates (20%-45%). However, its success in the setting of OHCA has been mixed.
There are three major trials. The ARREST trial, spearheaded by Yannopoulos and Bartos, studied patients who presented to the University of Minnesota Medical Center with OHCA and refractory VF, no return of spontaneous circulation after three shocks, automated CPR, and estimated transfer time of less than 30 minutes. Patients were randomly assigned to receive either early ECMO-facilitated resuscitation or standard treatment on hospital arrival.
Survival to hospital discharge occurred in only 7% of patients in the standard treatment group vs 43% of patients in the early ECMO group. The study was terminated early by the National Heart, Lung, and Blood Institute because the superiority of ECMO led them to deem it unethical to continue the trial. Cumulative 6-month survival remained superior in the early ECMO group compared with the standard treatment group. The authors describe vascular and bleeding adverse events as “low.”
Bartos was the lead author on an observational cohort study of 58 patients who were treated as part of the Minnesota Mobile Resuscitation Consortium’s ECMO-facilitated resuscitation program. Of these, 100% were successfully cannulated, with no safety issues identified, and 54% were discharged from the hospital and alive at 3 months, with a Cerebral Performance Category Scale score of 1 or 2. As covered by Medscape Medical News, Bartos’ group found ECPR to be associated with favorable neurologic survival at all CPR durations under 60 minutes, even in patients with progressive metabolic derangement associated with prolonged resuscitation. 
 In contrast, the INCEPTION trial, conducted in the Netherlands, randomly assigned patients with OHCA to receive ECPR or conventional CPR and found no significant difference between the groups. At 30 days, only 14 of 70 patients in the ECPR group were alive, with favorable neurologic outcomes, compared with 10 of the 64 patients in the conventional CPR group. 
And a trial conducted in Prague, Czech Republic, compared 124 OHCA patients treated with an invasive strategy (mechanical compression, intra-arrest transfer to a cardiac center for ECPR, and immediate invasive assessment and treatment) with 132 patients who received standard treatment. 
The trial was stopped at the recommendation of the data and safety monitoring board for reasons of “futility,” with only 32% of the invasive strategy group and 22% of the standard strategy group surviving to 180 days with good neurologic outcome, which was the primary endpoint. Bleeding occurred more frequently in the invasive group (31% vs 15% with the standard strategy).
Bartos believes the ARREST trial was positive because “we have a standard system of ECPR already in place, developed and established throughout the community. But these systems weren’t similarly in place in the Netherlands, for example. And because these patients are so sick, every part of the system has to work seamlessly, which wasn’t the case in those two centers.” 
Time is arguably the most important factor for survival. “We know that if people get to us at the University of Minnesota within 30 minutes of the cardiac arrest, there’s an almost 100% chance of neurologically intact survival. For every 10 minutes beyond the initial 30, we lose 25% more people. So after 50 minutes, the patient still has a 50% chance of survival. But there’s a steep curve where patients lose the benefits of ECPR with longer CPR times,” Bartos said.
Moreover, the median length of ECMO time for each patient in the INCEPTION trial was only 1 day. “This isn’t long enough to determine with certainty how these patients will do,” Bartos said.
The Critical Role of Patient Selection
Patient selection is another key component. “Every program chooses some combination of leniency and strictness,” Bartos explained. For example, the ARREST trial was limited to patients with shockable rhythms, whereas the Prague study included all presenting rhythms. “If you removed patients with nonshockable rhythms, the findings were much more promising,” he said
The Extracorporeal Life Support Organization recommended inclusion criteria for ECPR are: 
Age < 70 years
Witnessed cardiac arrest
Time from arrest to CPR (“no-flow interval”) < 5 minutes
Initial cardiac rhythm of VF/pulseless electrical activity
Time from arrest to initiation of ECMO flow (“low-flow interval”) < 60 minutes
End-tidal carbon dioxide > 10 mm Hg during CPR prior to ECMO cannulation
Intermittent return of spontaneous circulation or recurrent VF
“Signs of life” during conventional CPR
No previously known limiting comorbidities
No known moderate or severe aortic valve incompetence
Additionally, the American Heart Association (AHA) expert consensus statement defines ECPR as a recommended pathway for patients with refractory cardiac arrest with similar criteria; and the AHA ECLS 2023 guideline update lists ECPR as a class IIa recommendation for well-organized systems of care similar to defibrillation.
No One-Size-Fits-All Solution
Sung-Min Cho, DO, MHS, associate professor in the Department of Anesthesiology and Critical Care Medicine, Division of Neuroscience Critical Care, Johns Hopkins Hospital, Baltimore, Maryland, told Medscape Medical News that the program in Minnesota “has done quite well, compared to other centers.”
However, he cautioned, “we’ve learned in subsequent trials that it’s not so easy. Cannulation time has been an issue, for example. In the INCEPTION and Prague trials, the time was longer than 60 minutes. The problem with ECPR is that it’s not yet standardized, and a lot of centers don’t want to set up such an expensive program.”
According to Yannopoulos, one major limitation is that the equipment is large and heavy. Additionally, the current technology “requires many wires, and those can only be placed by very skilled technicians. The process has to be democratized and simplified if it’s going to have a big impact.”
Cho believes that “devices will improve over time. And as the ECPR field evolves, the major outcome metric will be the neurologic outcomes, which are an issue for all ECMO patients but more pronounced in ECPR.”
Bartos says ECPR isn’t “one-size-fits-all” and must be adapted to the particular region, with its demographics, geography, and similar factors. “Success lies in these details.” 
For example, helicopters may be useful in rural areas, “but Minneapolis has traffic and high-rise buildings, which create a different set of challenges.”
Yannopoulos noted that very cold weather can make certain machines freeze, and very hot weather can likewise interfere. Certain streets don’t have space for large ambulances, with all the machinery required.
“The best way to make this work in the US is to collaborate with EMS and other hospitals to have one team on call for two or three hospitals,” Yannopoulos said. And consistency is essential. “Most places that have tried and failed are inconsistent in who cannulates, where, and when.”
Expertise can be taught, Bartos agreed. Cannulation teams can be built, mobilized, and brought to patients in a variety of settings. “We need people who are willing to put time into doing it and community buy-in and involvement. But this care can be replicated across the nation. I have ultimate faith that every community will do this.”
Zack Shinar, MD, chair of emergency medicine at Sharp Memorial Hospital, San Diego, California, and co-chair of the Emergency ECMO Program, told Medscape Medical News that the center that he is affiliated with has a different model than the one used in Minnesota.
“One of the benefits of the Minnesota program is that the doctors are already there, waiting for the patient. In other places, such as the Netherlands, they first called the doctor after the patient arrived,” said Shinar, who hosts an international podcast on ECPR and ECMO. 
“Here in San Diego, we have emergency physicians cannulating. We have a program where OHCA patients bypass closer hospitals to come to ECPR receiving centers. There, we have a doctor or two or three waiting to initiate ECMO immediately upon presentation to the hospital. We are training many more cannulators and seeing success,” said Shinar, whose group published a retrospective analysis and other reports supporting the success of emergency physician-initiated ECPR.
One of the advantages of this model is that there’s no need for charitable donations, Shinar said. “The ER physicians are paid as usual. The ECMO machine operates as usual, so from an economic standpoint, that’s arguably the best scenario.” Although his group has not yet published their latest outcomes, “if we can show that our outcomes are at least reasonable, compared to others, then this may be a way we can move forward with scaling ECPR in every city,” he said.
He added that throughout the world there are slightly different variations of what an “ideal” patient might be. He regards his group as more lenient. “We have a lot of patients who may not fit the traditional profile simply because an ER physician is always available, always ready to put the patient on ECMO.”
An ECPR protocol was implemented in the Los Angeles County Emergency Medical Services (EMS) Agency, which “included coordination across multiple EMS provider agencies and hospitals to route patients with refractory VF OHCA to ECPR-capable centers.” Of the 25 treated patients, 11 received ECPR, and three survived and had a full neurologic recovery. 
Long-Term Recovery and Psychosocial Support
A “very valuable aspect of the discussion” about ECPR is that even if the patient dies, ECMO allows the organs to remain perfused and usable for donation, Yannopoulos said. “This isn’t the reason we do it, of course, but it’s a very welcome byproduct.”
The International Liaison Committee on Resuscitation issued a scientific statement designed to “define pathways” for patients with OHCA to become organ donors and further expand the pool of potential organ donors. 
Yannopoulos noted that ECMO “can provide a bridge to solutions we didn’t have before.” He described a study participant who had a cardiomyopathy, followed by cardiac arrest, with an ejection fraction of 5%. “He couldn’t get off ECMO because his heart was too weak, but it sustained him until he was able to get a heart transplant. He went home and now he leads a normal life.”
As the ECPR field gets standardized, there needs to be a research effort on how to improve long-term outcomes, Cho said.
Bartos agreed. “We know from cardiac arrest populations in general that depression, anxiety, and PTSD are common — not only in patients but also in their family members. We see that if they survive, their neurological outcomes are good, but often their psychiatric outcomes aren’t as good.” 
As covered by Medscape Medical News, Cho and colleagues performed a systematic review and meta-analysis of 59 studies involving 3280 patients who underwent ECMO and found the overall prevalence of neuropsychiatric symptoms to be 41% at long-term follow-up. 
All patients who have undergone ECPR at the Minnesota program go to a survivor clinic where they are offered support and resources to help them work through common psychiatric issues.
Family members are also offered support and resources. “A patient may be in a coma for a week, but it’s often the family member who remembers every day and every minute, so the trauma may be even worse for the family member than for the patient.” Often, family members are afraid to allow patients who survived cardiac arrest to engage in daily activities, Bartos observed.
Bartos wants “to see patients get back to normal and live their best life, even better than before. They may have to make some serious life changes in diet or exercise, but often this is a defining moment where they turn their lives in a new direction that actually makes them happier. This is what I would love for all of our patients.” 
Yannopoulos receives funding from the National Institutes of Health (NIH) for resuscitation science and grants from the Helmsley Charitable Foundation for ECPR and resuscitation program implementation. Cho receives support from the NIH. Bartos and Shinar report no relevant financial relationships. 
Batya Swift Yasgur, MA, LSW, is a freelance writer with a counseling practice in Teaneck, New Jersey. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer-oriented health books as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom (the memoir of two brave Afghan sisters who told her their story).
 
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