As the data for ECPR in refractory OHCA has evolved, the use of ECPR in both OHCA and in-hospital cardiac arrest has increased dramatically. The extracorporeal life support organization (ELSO) 2023 registry report published 17,762 cases of adult ECPR within the ELSO registry through 2023 with a 31% survival rate. That number is nearly 3 times the 6,994 cases reported in 2019, prior to the publication of the ARREST, Prague OHCA, and INCEPTION trials. The number of adult ECPR cases continues to increase with the ELSO Live Registry Dashboard reporting 20,838 cases (31% survival) as of February 2025.

Several studies, including 3 randomized controlled trials (RCTs), have evaluated the effects of ECPR in refractory OHCA. The 3 RCTs, which evaluated ECPR for OHCA, have significant variation along the pragmatic-to-explanatory continuum, as has been previously assessed using the PRagmatic Explanatory Continuum Indicator Summary-2 (PRECIS-2) tool. RCTs that are designed to be explanatory, such as the ARREST Trial, assess the effect of an intervention in fully optimized conditions, singularly focusing on the efficacy of the intervention. RCTs designed to be pragmatic, like the INCEPTION Trial, assess the intervention in the context of real-world conditions, allowing factors external to the intervention to influence the outcome of the study. Interpreting these studies within the context of their position along the pragmatic-to-explanatory continuum allows us to both evaluate the efficacy of ECPR in refractory OHCA and gain insights into external factors that affect the implementation of ECPR in real-world conditions. The 3 RCTs highlight different, but important, aspects of ECPR and provide insights into how we should design future ECPR systems of care.

The minimization of time from OHCA to ECPR flow initiation is critical to the success of ECPR. The time from OHCA to initiation of CCPR is termed the no-flow period and the time from CCPR to ECPR flow initiation is termed the low-flow period. Increased duration of both the no-flow and low-flow periods is associated with significant decreases in neurologically intact survival. Prior studies have demonstrated that no-flow time has a more severe impact on neurologic injury in OHCA patients who receive ECPR, resulting in a 13% decrease in favorable neurologic outcome for every additional minute without CCPR. ^, However, increased low-flow time also worsens outcomes with a 2.5% decrease in favorable neurologic outcome for every minute of ongoing ACLS. ^,,, ECPR systems of care should place the highest priority on minimizing both low no-flow and low-flow times with all aspects of the system designed to minimize these time intervals.

Bystander CPR is the most effective mechanism to decrease no-flow time and is associated with an increased 30-d neurologically intact survival in OHCA patients who undergo ECPR. ECPR systems of care should lead efforts to increase bystander CPR rates and explore innovative methods to facilitate bystander CPR. Traditional methods include community wide-education campaigns and dispatcher-aided CPR to increase rates of bystander CPR. New smartphone-based dispatch of community first responders has been developed to increase bystander CPR rates in some communities using mobile alerts sent to train volunteers in the vicinity of an ongoing cardiac arrest. Medical drones have also recently been investigated as a means to provide automated external defibrillator (AEDs) and dispatcher-aided CPR to the scene of patients suffering OHCA. Loss of pulse detection technology developed for smart watches may additionally assist in quickly identifying OHCA patients, providing the opportunity for bystander CPR with the potential to minimize no-flow times.

Minimizing low-flow time is a challenge as it requires a coordinated system-wide effort to streamline complex logistics in a parallel and expedited manner. Pre-hospital scene times exceeding greater than 20 min, as observed in the ARREST Trial, provide a major limitation to shortening low-flow times. Minimizing on-scene time is a critical challenge as EMS needs to initiate and provide ACLS therapies, quickly identify potential ECPR candidates, package the patient for transport while performing ongoing ACLS, and communicate the plan to family or friends at the scene. Use of mechanical CPR devices is critical during transport to provide consistent CPR while maintaining the safety of the EMS crew. Transportation is also logistically challenging with a limited number of ECPR centers and traffic and road conditions limiting rapid delivery of patients. Some systems of care have developed rendezvous points for ECPR initiation, outside of the central specialized centers, to minimize transport time and ultimately decrease low-flow time as described by Bartos and colleagues

Pre-hospital ECPR has been used by some programs to eliminate the need for EMS to package and transport the patient. While pre-hospital ECPR can considerably reduce low-flow time, the logistical challenges of delivering the ECPR team and their equipment to the scene, establishing and maintaining an operative field throughout the cannulation procedure, and providing effective ECPR with limited environmental control and resources makes prehospital ECPR very challenging. Despite these challenges, multiple systems of care have developed prehospital ECPR, and this is currently being investigated by the ON-SCENE Trial. ^,,,,

A dedicated and experienced ECPR team—for both the cannulation and subsequent management—is integral to the outcome of OHCA patients who receive ECPR. This team develops and maintains the expertise required for final patient selection, rapid and effective cannulation while minimizing complications, and the specialized post-cannulation resuscitation of a patient receiving prolonged CPR and ECPR. Staffing a dedicated team available 24 h/d and 7 d/w allows for immediate availability for all OHCA patients who are geographically eligible ECPR candidates, eliminating preventable delays related to team availability. Furthermore, a dedicated team allows for rigorous ECPR specific training for all members of the team to optimize pre-hospital and in-hospital logistics and clinical care. As the delivery of ECPR is complex, ECPR specific training programs are necessary and have been previously described. However, the optimal methods for establishing the necessary ECPR knowledge and procedural skills, in addition to maintaining those skills, are unclear.

The composition of a dedicated ECPR team varies based on regional practices. All teams have a cannulating provider responsible for inserting ECMO cannulas and establishing flow. There is evidence to suggest that providers of multiple medical backgrounds are capable of initiating ECPR, with intensivists, interventional cardiologists, and emergency physicians all shown to be suitable in different systems. ^,, The speed of cannulation (time between the start of cannulation and the start of ECMO-flow) is associated with provider skills and provider experience, an important mechanism to decrease low-flow time. Prolonged cannulation times, likely driven by highly variable ECPR providers, were a major limitation to the success of the INCEPTION Trial. Dedicated ECPR cannulators facilitate increased procedural volume for each provider improving their technical skills and speed with which they are able to initiate ECPR. A small but highly-trained group of providers facilitates a highly protocolized and continually optimized process, which also serves to maximize the speed of cannulation. Many ECPR systems include an ECMO specialist with specific training related to the mechanics and troubleshooting of the ECMO machine, cannulas, and procedures. In some systems, these ECMO specialists are cross-trained regarding the cannulation procedure, so they can assist with equipment during the cannulation procedure itself. Depending on the center, this ECMO specialist may have a medical background as a nurse, respiratory therapist, or paramedic. In many systems, the cannulating physicians are also cross-trained in ECMO specialist skills to ensure that all issues can be managed. In addition to the ECMO specialist and cannulating physician, EMS and emergency department staff play vital roles within the chain of resuscitation as they provide ACLS before and during ECPR while also potentially playing ECPR-specific roles in some systems related to patient selection and portions of the ECPR procedure itself, although often with less ECPR specific training. Given the number of providers involved and the time-sensitivity of ECPR, it is important to have predefined protocols to guide team dynamics and allow prompt decision making, resulting in decisive action on behalf of the patient. Irrespective of the initial training and background, a dedicated team of high-trained providers is critical to ensure successful cannulation and minimize low-flow times.

While cannulator and provider-level patient volume is often considered to be related to procedural outcomes, the requirement for a highly effective and organized system-level approach to ECPR patients suggest that system-level patient volume requirements may also exist. System patient volume was highly variable across the 3 RCTs evaluating ECPR in refractory OHCA, providing valuable insights to guide both current and future ECPR systems of care. The INCEPTION Trial had significantly less volume (0.29 patients/center/month attempted ECPR) compared to both the ARREST (1.5 patients/center/mo receiving ECPR) and Prague OHCA trials (1 patient/center/mo receiving ECPR) raising questions regarding the effect of volume on outcomes and any potential threshold effect below which systemic efficacy cannot be maintained. ^,, The challenges associated with low volume centers was also observed in the EROCA trial, which demonstrated that expedited transport and emergency department initiation of ECPR were not feasible in a system with 0.375 patients/center/mo.

A retrospective analysis of the ELSO registry evaluating 351 centers (307 centers <6 ECPR/y; 34 centers 6–12 ECPR/y; 10 centers >12 ECPR/y) demonstrated that neurologically intact survival to hospital discharge was 26% greater at centers treating greater than 12 ECPR patients/y when compared to centers treating less than 6 ECPR patients/y (adjusted odds ratio [aOR], 1.26; 95% CI, 1.06–1.49; P =.07). In this study by Tonna and colleagues, each additional 10 ECPR patients/center/y increased the odds of survival by 11% (aOR, 1.11; 95% CI, 1.07–1.16; P <.001). A secondary analysis of 1740 patients at 34 centers (5 high-volume center with ≥21 ECPR patients annually; 7 medium-volume centers with 11–20 ECPR patients annually; 24 low–volume centers with < 11 ECPR patients annually) receiving ECPR from the SAVE-J II study further supported these findings. The analysis of the SAVE-J II study demonstrated that centers with the highest annual volume had significantly higher survival rates at discharge (high-volume centers: 33.4% vs medium-volume centers: 24.1% vs low-volume centers: 26.8%, respectively; P =.001) and lower complication rates throughout their admission. Conversely, a retrospective evaluation of 2315 OHCA patients receiving ECPR at 87 centers from the Japanese Association for Acute Medicine– Out-of-Hospital Cardiac Arrest (JAAM–OHCA) registry, a nationwide multicenter database containing information on OHCA patients in Japan, between June 2014 and December 2020 did not show a survival benefit with increased center volume. However, this study did demonstrate that the speed of cannulation increased significantly at high-volume centers. It should be noted that high-volume centers in the JAAM-OHCA study were defined as greater than 53 patients/7 study period (7.7 ECPR patients/y), which is significantly lower than the definition of high-volume centers in the studies evaluating the ELSO registry and the SAVE-J II study.

Consistent with previous studies demonstrating improved survival for OHCA patients at high-volume centers, these studies demonstrate that centers likely need at least 12 ECPR patients/y to be a high-performing ECPR system of care. The retrospective evaluation of the JAAM-OHCA registry demonstrates that while 7.7 ECPR patients/year may not be enough to be a high-performing ECPR system of care, it may be sufficient to be a high-performing ECPR cannulation center as they demonstrated increased speed of cannulation. This demonstrates that the volume needed to be a high-performing ECPR system of care may be different from the volume needed to be a high-performing ECPR cannulation center. The improved cannulation times and patient survival associated with increased ECPR volume is likely secondary to the challenges associated with optimizing ECPR logistics and maintaining skills in centers with little exposure as demonstrated in the EROCA Trial. It is implied that case load leads to expertise in both cannulating for ECPR and treating OHCA patients who receive ECPR throughout their complex hospital course. As such, multi-system and multi-agency coordination is necessary across regions to support high-volume centers to concentrate expertise and best serve patients. Regionalized “hub-and-spoke” models have previously demonstrated improved outcomes in other complex or specialized procedures, such as trauma surgery, cardiovascular surgery or organ transplantation, where patient outcomes have been reported to be largely dependent on center volume. ^,,

The successful implementation of ECPR for refractory OHCA necessitates a protocolized regional system of care to ensure rapid and coordinated decision-making across multiple agencies. ECPR is a resource-intensive intervention that requires seamless integration between EMS, receiving hospitals, and specialized ECPR teams (in both pre-hospital and in-hospital systems of care). Standardized protocols are imperative for the early identification of ECPR-eligible patients, efficient activation of the ECPR team, and streamlined transport to designated cannulation centers or the deployment of a prehospital ECPR team. A well-defined, parallel processing approach—where transport and ECPR logistics proceed simultaneously—minimizes low-flow time, a key determinant of survival and neurologic outcomes. Without such a highly protocolized structured system, delays in initiation and inconsistencies in patient selection may compromise outcomes, reducing the overall efficacy of ECPR. This was apparent in the INCEPTION trial, where there was no specific protocol adopted by EMS and hospital personnel. The ARREST trial demonstrated the feasibility of an organized ECPR system; however, it did not highlighted the logistical challenge of superfluous team activations when a rigorous protocol is meticulously followed, where patients either achieved ROSC or were later deemed ineligible for ECPR due to emerging contraindications. While activations that do not ultimately require patient cannulation either due to ROSC prior to or at arrival or patient ineligibility, they are an inherent part of time-sensitive decision-making, they underscore the opportunity for protocol refinement to optimize resource allocation.

Beyond the initial resuscitation phase, a protocolized approach to establish a minimum standard of care that is then personalized by highly trained experts remains essential for postresuscitation care and neuroprognostication following ECPR initiation. Standardized post-resuscitation pathways ensure that patients receive consistent, high-quality care, including temperature control strategy, hemodynamic stabilization, and structured neurologic assessment to guide long-term prognostication. Furthermore, integrating rehabilitation strategies into structured ECPR protocols ensures a continuum of care beyond the acute phase, improving functional recovery and long-term survival. Thus, a regionalized, protocol-driven ECPR system is essential for maximizing the benefits of this advanced resuscitation strategy while ensuring judicious use of health care resources.

There is no globally agreed upon consensus on patient selection criteria for ECPR in refractory OHCA. However, key patient and arrest characteristics serve as primary determinants of candidacy due to their association with survival and neurologic outcomes. Refractory cardiac arrest, typically defined as persistent arrest despite standard ACLS interventions, is the most common inclusion criterion in ECPR protocols, appearing in 84% of protocols, though definitions vary widely. Common selection criteria include patient age, witnessed arrest, no-flow duration, and low-flow duration, as these factors significantly impact survival. ^,, Older age correlates with worse outcomes; initial studies demonstrated that fewer than 2% of ECPR patients over 75 y achieve favorable neurologic recovery, and existing protocols set upper age limits between 65 and 80 y. ^,, However, later studies demonstrated that patients of 70 to 79 y old still had a 23% survival as such caution should be used when choosing age criteria for patient selection. Initial shockable rhythm (VT/VF) is another key predictor, included in 24% of protocols, given its strong association with improved neurologic outcomes. Furthermore, sustained VT/VF at ECPR initiation is linked to better prognosis, whereas conversion to asystole before cannulation may be associated with increased mortality when additionally criteria is not applied. ^, Nearly half of ECPR protocols also incorporate etiology-specific inclusion criteria, prioritizing highly reversible etiologies, such as acute coronary syndrome, hypothermia, pulmonary embolism, peripartum cardiomyopathy, amniotic fluid embolism, and drug overdose. ^,,,, Primary diagnoses, such as acute myocardial infarction, cardiogenic shock, and myocarditis, have demonstrated a survival advantage in a retrospective analysis of the ELSO registry.

Beyond arrest characteristics, clinical signs and physiologic markers can be used to further refine ECPR candidacy. The presence of gasping, pupillary light reflex, and spontaneous movements (e.g. gagging and eye opening), often termed “signs of life”, has been associated with increased odds of favorable neurologic outcomes. ^,, A French cohort study demonstrated that any “sign of life” was a strong predictor of 30-d neurologic recovery (aOR 7.35; 95% CI, 2.71–19.97), with increasing prognostic value for multiple concurrent signs. However, it should be noted that the reverse is not true, no signs of life does not mean that you will have a poor neurologic outcome as demonstrated by the little utility of an absent pupillary response during CPR. Physiologic and point-of-care laboratory parameters on presentation, such as regional cerebral oxygen saturation (rSO ₂ ), pH, partial pressure of oxygen in arterial blood (paO ₂ ), and lactate, may also guide patient selection. ^,,,,, Higher rSO ₂ during CPR (>16%; measured by a disposable near-infrared spectrometer, INVOSTM 5100C; Covidien, Boulder, CO, USA) has been linked to improved neurologic outcomes, whereas levels below this threshold predict poor prognosis. ^, Although end-tidal carbon dioxide has been used in some selection criteria as a surrogate for quality of CPR due to its correlation with cardiac output, its predictive value for neurologic outcomes remains uncertain due to confounding factors, such as ventilation status and pulmonary perfusion. ^, Retrospective analyses indicate that a pH greater than 7.0 and lactate less than 13 mmol/L at ECPR initiation are associated with better survival. ^, Each ECPR system of care should work to develop a standardized, data-driven approach incorporating these clinical, physiologic, and biochemical criteria to allow for swift decision-making to optimize ECPR outcomes. When developing patient selection criteria system, leaders should acknowledge that more restrictive criteria will exclude some patients who may have a favorable neurologic outcome while making it challenging to maintain skills with the ECPR system of care.

Vascular access site complications are the most common adverse event associated with ECMO cannulation. While rapid and safe ECMO cannulation is required for successful patient outcomes. Imaging modalities play a crucial role in optimizing cannulation speed and reducing complications. Ultrasound guidance is widely used in both the prehospital setting (as described in the Sub30 Trial ) and in OHCA cannulated within the in-hospital settings to facilitate vascular access, improving first-pass success and reducing complications, such as arterial injury and catheter misplacement. ^,,, In the pre-hospital environment, portable ultrasound allows for real-time vessel identification and differentiation between arterial and venous structures, crucial in time-sensitive scenarios. In contrast, fluoroscopy, available primarily for cannulation in the hospital, provides real-time guidance for wire positioning and catheter advancement, significantly reducing the risk of vascular complications, such as dissection or malposition. Some advanced prehospital environments, such as the Minnesota Resuscitation Consortium (MRC) ECPR program, have developed prehospital fluoroscopy capabilities. Transesophageal echocardiography (TEE) serves as an adjunct for in-hospital cannulation, confirming correct guidewire placement, assessing cardiac function, and identifying complications, such as pericardial effusion. While ultrasound is the most accessible modality across all settings, fluoroscopy and TEE offer enhanced visualization but are largely confined to programs that cannulate OHCA patients within the hospital. Given the association between faster cannulation and improved outcomes, integrating multimodal imaging strategies tailored to the clinical environment is critical in refining ECPR workflows and minimizing procedural risks.

Routine coronary angiography and percutaneous coronary intervention (PCI) after cannulation is a mainstay of therapy of many ECPR programs; however, comparative data to programs who do not routinely undergo angiography are limited. ^,,,, In conventional OHCA patients’ data for PCI following OHCA is unclear. Initial studies demonstrated an improved mortality with immediate PCI following OHCA with ROSC from all causes, while further studies of patients who obtained stable ROSC demonstrated no increase in neurologically intact survival in patients without an ST-segment elevation myocardial infarction (STEMI). ^,,, However, Song and colleagues later demonstrated that high-risk patients (identified as patients with a Global Registry of Acute Coronary Events (GRACE) score >140, with prolonged ROSC times, or significant acidosis) who did not have an STEMI had increased neurologically intact survival from early PCI. What remains clear is that PCI is beneficial for patients with evidence of coronary ischemia following OHCA, such as that reflected in patients suffering from an STEMI, with a shockable ventricular rhythm, or those otherwise identified as high risk. As such, PCI is advocated for all cardiac arrest patients with suspected cardiac cause of arrest and ST-segment elevation on electrocardiogram by the American Heart Association (AHA). They also recommend that emergent PCI is reasonable for patients with elevated risks for coronary artery disease and shock, electrical instability, or signs of coronary ischemia. ^,

Frequently, inclusion criteria for ECPR currently target a population with ischemic coronary artery disease. In an observational cohort study evaluating variation in resuscitation management practices in ECPR patients, survival was associated with PCI among ECPR patients. This is consistent with previous data demonstrating a benefit in PCI for OHCA patients with evidence of coronary ischemia. While there are limited data on PCI after ECPR, a study by Kagawa and colleagues demonstrates a higher rate of PCI in ECPR patients with neurologically intact survival. As such, coronary angiography and PCI are a common aspect of ECPR programs in an effort to reverse the underlying etiology of the OHCA. While coronary revascularization may not be necessary for reversal of refractory VF in ECPR patients, the impact of coronary revascularization on cardiac recovery is unclear.

The adjusted survival across centers providing ECPR to patients in refractory OHCA varies by as much as 44% across centers (median OR 1.44, 95% CI, 1.40–1.48) with highly inconsistent patient volumes, eligibility, and cannulation protocols. Centralizing ECPR services, through ECPR Centers of Excellence (ECE), allows for the implementation of refined care pathways, increased procedural volumes, and enhanced provider expertise. The establishment of an ECE allows for the support needed to have a dedicated ECPR team 24-h a day and 7-d a week adept in streamlined cannulation processes, significantly reducing low-flow times, and nuanced resuscitation protocols thereby improving patient outcomes. Additionally, ECE allows for highly protocolized care along the whole continuum of care through the integration of structured post-resuscitation care and post-arrest clinics. While data for ECE are limited, Cardiac Arrest Centers have demonstrated promise with some studies describing an association with improved survival and neurologic outcomes at 30 d among OHCA patients. ^, This comprehensive approach requires further investigation but has the potential to ensure that patients receive optimal care throughout the continuum of resuscitation and recovery.

Expanding the reach of extracorporeal cardiopulmonary resuscitation

The ARREST Trial demonstrated that ECPR can be highly efficacious with subsequent trials providing insight into factors, which are important for future ECPR systems of care. Many aspects of high-functioning ECPR systems of care, such as minimizing low-flow time and maximizing system volume, can be challenging to implement given the time-sensitive nature of ECPR. A study by Gottula and colleagues used geographic location as an inclusion criterion for ECPR, demonstrating that nearly 50% of eligible ECPR patients are not located within a 45-min drive time of ECPR capable centers. Later studies evaluating the current systems of care, where patients are cannulated in the hospital at an ECPR capable center, demonstrated that nearly 90% of clinically eligible ECPR patients were not eligible based on the geographic location of the OHCA. As such, prehospital ECPR systems ( Fig. 1 B and C ) of care have been explored as a method to increase patient eligibility and system volume while decreasing low-flow time in the already eligible ECPR patient. Gottula and colleagues further demonstrated that a prehospital ground-based system would increase eligible patients’ access for 2-fold while a prehospital HEMS-based system of care would increase eligible patients’ access to ECPR facilities by 4-fold.

Sixty-Minute Timeline for Hospital-Based and Prehospital ECPR Systems of Care. Sixty-Minute Timeline from OHCA to ECPR Initiation for ( A ) In-Hospital Ground-Based ECPR System, ( B ) Prehospital Ground-Based ECPR System, ( C ) Prehospital HEMS-Based ECPR System. Created using Microsoft Powerpoint. ECMO, extracorporeal membrane oxygenation, ECPR, extracorporeal cardiopulmonary resuscitation, EMS, emergency medical services, HEMS, helicopter emergency medical services, OHCA, out of hospital cardiac arrest.

A deployable prehospital team would truncate the timeline to ECPR (see Fig. 1 ) by offering the opportunity to initiate ECPR immediately after the indication has been established and not requiring EMS to package the patient for transport. Prehospital teams with the ability to initiate ECPR in the prehospital setting have the potential to significantly shorten low-flow times (15 min vs 30 min; see Fig. 1 A vs B) while allowing ECPR capable centers to cover significantly larger geographic regions ( Fig. 2 ) and increase system patient volumes. Additionally, a HEMS-based team would facilitate faster, more direct transport, allowing a specialized team to cover an even larger geographic region, as has been demonstrated in trauma systems of care. Given the time-sensitive nature of OHCA resuscitation, this would be expected to improve patient eligibility and outcomes more than systems that do not initiate ECPR in the prehospital setting. Efforts are ongoing to develop ground and HEMS-based prehospital ECPR teams internationally.

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