| Home | E-Submission | Sitemap | Contact Us |  
Search
Clin Exp Emerg Med Search

CLOSE

Clin Exp Emerg Med > Volume 10(3); 2023 > Article
Jeung, Jung, Gumucio, Salcido, and Menegazzi: Benefits, key protocol components, and considerations for successful implementation of extracorporeal cardiopulmonary resuscitation: a review of the recent literature

Abstract

The application of venoarterial extracorporeal membrane oxygenation (ECMO) in patients unresponsive to conventional cardiopulmonary resuscitation (CPR) has significantly increased in recent years. To date, three published randomized trials have investigated the use of extracorporeal CPR (ECPR) in adults with refractory out-of-hospital cardiac arrest. Although these trials reported inconsistent results, they suggest that ECPR may have a significant survival benefit over conventional CPR in selected patients only when performed with strict protocol adherence in experienced emergency medical services–hospital systems. Several studies suggest that identifying suitable ECPR candidates and reducing the time from cardiac arrest to ECMO initiation are key to successful outcomes. Prehospital ECPR or the rendezvous approach may allow more patients to receive ECPR within acceptable timeframes than ECPR initiation on arrival at a capable hospital. ECPR is only one part of the system of care for resuscitation of cardiac arrest victims. Optimizing the chain of survival is critical to improving outcomes of patients receiving ECPR. Further studies are needed to find the optimal strategy for the use of ECPR.

INTRODUCTION

Cardiac arrest is a major cause of mortality worldwide, affecting 500,000 people annually in the United States alone [15]. In Korea, approximately 30,000 patients with cardiac arrest are treated using emergency medical services (EMS) each year [6]. Chances of survival after cardiac arrest decrease rapidly as the duration of cardiopulmonary resuscitation (CPR) increases [79]. Outcomes of patients’ refractory to initial resuscitation efforts are highly unfavorable [10,11].
The application of venoarterial extracorporeal membrane oxygenation (ECMO) in patients unresponsive to conventional CPR (commonly referred to as extracorporeal CPR [ECPR]) has significantly increased in recent years [12]. Cardiac output generated during conventional CPR is insufficient to maintain vital organ perfusion [13,14], and hypoxic-ischemic injury risk increases until the return of spontaneous circulation (ROSC). ECMO effectively restores vital organ perfusion, facilitating ROSC and buying time to identify and treat the underlying cause of cardiac arrest. Despite its increased use, the clinical efficacy of and the patient population most suitable for ECPR remain unclear. Although current resuscitation guidelines recommend ECPR as a rescue method in refractory cardiac arrest [15], a standard protocol for ECPR is lacking.
Here, we provide insights regarding the optimal implementation of ECPR based on a review of recent evidence on the clinical efficacy of ECPR and a summary of recent research on the key components of ECPR protocols and considerations for incorporating ECPR within a system of care.

IS ECPR MORE EFFECTIVE THAN CONVENTIONAL CPR?

A number of studies have investigated the relationships between ECPR and outcomes in patients with refractory cardiac arrest [1619]. Although these studies report inconsistent results, several studies reported significant associations between ECPR use and positive outcomes [17,18]. To date, three published randomized trials have investigated ECPR use in adult patients with refractory cardiac arrest (Table 1) [2022]. The first is the ARREST (Advanced Reperfusion Strategies for Refractory Cardiac Arrest) trial [20], which included adult patients with refractory ventricular fibrillation out-of-hospital cardiac arrest (OHCA) who had estimated transfer times to the University of Minnesota medical center of less than 30 minutes. The patients were randomized to either ECMO-facilitated resuscitation or standard advanced cardiovascular life support (ACLS) on arrival at the catheterization lab. The ARREST trial showed a significantly higher rate of survival to hospital discharge in the ECMO group compared to the standard ACLS group (43% vs. 7%) in the interim preplanned analysis after enrolling 30 patients, leading to premature termination of the trial because of the apparent survival benefit of ECMO-facilitated resuscitation.
The Prague OHCA study [21] was a single-center trial conducted in Prague, Czech Republic, which included 256 adult patients with refractory OHCA of presumed cardiac origin randomized during on-scene CPR to either an invasive strategy including prompt intra-arrest transport to a cardiac center under mechanical CPR, in-hospital ECPR, and immediate invasive assessment and treatment (n=124) or to the standard strategy (continued on-scene ACLS, n=132). In the study, the primary outcome was survival with a good neurologic outcome at 180 days, which was comparable between groups (31.5% vs. 22.0% for the invasive and standard strategies, respectively; P=0.09) in the intention-to-treat analysis, and the study was terminated based on a prespecified stopping rule for futility. However, in the Prague OHCA study, 66% of the invasive strategy group underwent ECPR compared to 8% of the standard strategy group. The crossovers could have affected the results of the intention-to-treat analysis. A secondary analysis of the Prague OHCA study revealed that the use of ECPR was significantly associated with 180-day survival in patients without prehospital ROSC [23]. Although both trials were terminated before enrolling the originally planned number of patients, both favored ECPR over conventional CPR. A meta-analysis by Scquizzato et al. [24] that included the two randomized trials and four propensity score–matched studies showed significant benefit of ECPR over conventional CPR with regard to survival with good neurologic outcomes.
The INCEPTION (Early Initiation of Extracorporeal Life Support in Refractory Out-of-Hospital Cardiac Arrest) trial [22] is the most recent randomized trial and involved 10 cardiosurgical centers served by 12 EMS agencies in the Netherlands. In this trial, 134 adult patients with witnessed refractory OHCA with initial shockable rhythm randomly received ECPR (n=70) or conventional CPR (n=64) at one of the participating centers. The authors found no significant between-group difference in 30-day survival with good neurologic outcomes (20% vs. 16% in the ECPR and conventional CPR groups, respectively; P=0.52).
In view of the inconsistent findings from the three randomized trials, whether ECPR can yield better outcomes than conventional CPR in patients with refractory OHCA remains unclear. However, considering that all three trials showed numerically higher survival rates for the ECPR groups, these trials may have been underpowered to detect any survival benefit that was present.
These three trials also had considerable differences in patient selection, trial setting, and EMS treatment strategy. The ARREST trial included only patients with shockable rhythms, randomized patients to treatment on arrival to the catheterization lab, and was performed at an experienced, high-volume center with a specific protocol. In contrast, 39.1% of patients in the Prague OHCA study presented with nonshockable rhythms. The randomization was performed during on-scene CPR, and thus patients assigned to the standard strategy group received continued on-scene resuscitation. The INCEPTION trial was performed at multiple centers with relatively low case volumes without a standardized ECPR protocol. The characteristics of the Prague OHCA study and INCEPTION trial could have contributed to the lower survival rates of ECPR groups and higher survival rates of conventional treatment groups in these trials compared to those in the ARREST trial, ultimately leading to the lack of significant survival benefit of ECPR seen in these two trials. Results of these trials suggest that ECPR may have a significant survival benefit over conventional CPR in selected patients only when performed in an experienced system with strict protocol adherence.
Given the greater accessibility to ECMO in in-hospital settings than out-of-hospital settings, patients with in-hospital cardiac arrest (IHCA) are likely better candidates for ECPR than those with OHCA. Although several observational studies have suggested survival benefits of ECPR in IHCA [7,25], results of randomized trials evaluating the effectiveness of ECPR in IHCA are currently lacking. Further studies are required to resolve the existing uncertainty over the benefits of ECPR.

KEY COMPONENTS OF THE ECPR PROTOCOL

The complete ECPR process must be well-defined through a rapidly deployable protocol to enable timely initiation of ECMO. ECPR outcomes in the absence of a well-defined ECPR protocol can be highly unfavorable [2628]. Various protocols with differing candidate selection criteria, and cannulation and postcannulation managements are used for ECPR [29], none of which have been widely accepted.

Candidate selection

Clearly defined candidate selection criteria in an ECPR protocol would allow rapid recognition of potential candidates for ECPR. A variety of candidate selection criteria have been used in ECPR protocols [29,30]. Most are based on cardiac arrest-related factors known to be associated with outcomes of patients undergoing conventional CPR. Several factors, including witnessed arrest, presenting rhythm, and CPR duration, have been associated with outcomes after ECPR (Fig. 1) [23,3137].
Advanced age has been included as an exclusion criterion in many protocols [29], although the cutoffs vary widely. Some studies reported significant associations between advanced age and poor outcomes in patients undergoing ECPR [3841]; however, other studies reported no associations between advanced age and poor outcomes [32,33]. A recent study suggested that a significant number of elderly patients (>75 years) survive with good neurologic outcomes after ECPR [42]. ECPR should therefore not be excluded from treatment options based only on advanced age.
Initial electrocardiogram rhythm has frequently been used as an inclusion or exclusion criterion [29]. Several studies have shown significant associations between shockable rhythms and good outcomes in patients undergoing ECPR [3136,43,44]. The survival rate in the invasive strategy group in the Prague OHCA study (31.5%) was lower than that in the ARREST trial (43.0%) that included only patients with initial shockable rhythms [20,21]. In the Prague OHCA study, the survival rate of patients with initial shockable rhythms in the invasive strategy group (48.6%) was close to that in the ARREST trial. In a post hoc analysis of the Prague OHCA study [43], initial shockable rhythm was significantly associated with neurologically favorable survival. Considering the results of these studies [20,21,3136,43,44], only selecting patients with an initial shockable rhythm would improve outcomes after ECPR. Although patients with initial nonshockable rhythms have worse prognosis than those with initial shockable rhythms, patients with refractory cardiac arrest should not be excluded from ECPR only because of initial nonshockable rhythms. Several studies suggest that ECPR yields favorable outcomes in patients with initial nonshockable rhythms in the presence of other findings indicating likely good neurologic recovery (i.e., witnessed arrest, bystander CPR, and signs of life) [45,46]. In addition, a recent study reported that ECPR was associated with increased survival among patients whose electrocardiogram rhythm was initially nonshockable but later converted to a shockable rhythm [47].
The duration of CPR until ECPR initiation is a key determinant of outcomes after ECPR administration. Multiple studies suggest significant associations between prolonged CPR duration and poor outcomes after ECPR administration [36,4850]. Defining refractory cardiac arrest with a shorter CPR duration in a protocol would lead to improved ECPR outcomes. Lamhaut et al. [26] reported an increase in survival from 8% to 29% after reducing the CPR duration for patient selection from 30 to 20 minutes. However, a shorter CPR duration may increase the risk of unnecessary exposure of patients who would survive with conventional CPR alone to ECMO. Although the maximal CPR duration beyond which ECPR becomes futile remains uncertain, 60 minutes is the most frequently used maximum allowable CPR duration [29]. Several studies suggest that the time to ECMO initiation of ≤60 minutes is associated with better outcomes [51,52]. The current Extracorporeal Life Support Organization (ELSO) guidelines also recommend commencing ECMO support within 60 minutes after cardiac arrest [53]. The time required to initiate ECMO support after the decision to apply ECPR may vary between institutions depending on the infrastructure and capabilities of the cannulation team. The mean time from catheterization lab arrival to ECMO initiation in the ARREST trial was 7 minutes [20], whereas the median time required for cannulation in the INCEPTION trial was 20 minutes [22]. Therefore, it is reasonable to set a maximal CPR duration in ECPR protocols, taking the time required for cannulation in each setting into account, with the goal of initiating ECMO within 60 minutes after cardiac arrest.
Clinical characteristics such as gasping, body movements, and reactive pupils, commonly referred to as signs of life, can help identify ECPR candidates. Signs of life have been associated with good outcomes after ECPR [54]. Several studies suggested that initial laboratory markers, including pH and lactate levels, can also identify favorable candidates for ECPR [34,5557]. These laboratory markers are objective but not always available before ECPR implementation.
Several scoring systems have been proposed to assist in candidate selection for ECPR [58]. The TiPS65 score was developed using data from adult patients with shockable OHCA treated with ECPR in Japan. It is calculated by adding points from four variables: time from call to hospital arrival ≤25 minutes (Ti), pH ≥7.0 (P), shockable rhythm (S), and age <65 years (65). Validation studies of the TiPS65 score showed a C-statistic of 0.729 (95% confidence interval, 0.672–0.786) for prediction of 30-day survival with good neurologic outcomes [59]. The RESCUE-IHCA (Resuscitation Using ECPR During IHCA) score was developed using data from adult patients with IHCA treated with ECPR from Get With The Guidelines–Resuscitation (GWTG-R) [60]. This score considers six variables (age, preexisting renal insufficiency, time of day, illness category, presenting rhythm, and duration of cardiac arrest) and shows fair discriminatory (area under the curve, 0.676; 95% confidence interval, 0.606–0.746) and good calibration performances in a validation cohort from the ELSO registry. Clinical utility of these scoring systems remains to be determined.
Several studies have suggested that strict candidate selection criteria may improve ECPR outcomes [26,30,6163]. A systematic review that assessed the effects of predefined selection criteria on survival after ECPR showed that an increased number of inclusion criteria was associated with improved outcomes in prospective studies [30]. However, using stricter criteria results in identifying fewer eligible patients, thereby increasing the risk of excluding potential candidates from receiving ECPR. Further studies are needed to determine candidate selection criteria that can maximize the benefits of ECPR while minimizing futile ECMO initiation.

Implementing ECPR

ECPR involves a series of time-critical interventions. Detailed information on the procedures, materials, and equipment necessary for ECPR (Fig. 2), should be included in ECPR protocols. Using preprimed ECMO circuits can reduce the time to ECMO initiation. Several studies reported that sterility of preprimed ECMO circuits remained uncompromised for more than 1 month [64,65]. Ultrasonography plays an important role in ECMO cannulation by localizing the femoral vessels and providing real-time imaging during cannulation (Fig. 3), leading to faster ECMO cannulation [66].
The percutaneous Seldinger or surgical cutdown techniques are the most commonly used for inserting the ECMO cannula into the common femoral artery and vein. Although the percutaneous Seldinger technique is more frequently used [29], it often fails even with ultrasonographic guidance [67]. The surgical technique is mostly used as a salvage measure after failed percutaneous access attempts and is associated with higher risk of local infection [68]. Which technique is better between the two remains unestablished, and the first choice of technique may depend on the operator’s preference and the patient’s anatomic characteristics. Chen et al. [67] reported that arterial diameter was significantly associated with the success of percutaneous ECMO cannulation using the Seldinger technique, with an arterial diameter of >4.5 mm yielding a relatively high success rate.
Because inadvertent venous placement of the arterial cannula can impede timely ECMO initiation, procedures to differentiate between arterial and venous puncture must be included in ECPR protocols. The color of blood taken at the puncture site can help in differentiating between arterial and venous puncture before guidewire insertion [69]. A guidewire-induced hyperechoic shadow within the inferior vena cava on ultrasonography confirms venous puncture (Fig. 4). Even after successful guidewire insertion, complications such as guidewire kinking or vessel perforation can occur during sequential dilations or cannula advancement. Moving the guidewire back and forth during sequential dilations and cannula advancement may help reduce complications. Upon sensing resistance to guidewire movement, advancement of the dilator or cannula should be stopped. When an arterial catheter is placed at the time of ECMO initiation, observing the arterial pressure waveform may also help in detecting cannula misplacement. Cannula misplacement should be suspected if there is no gradual increase in arterial pressure immediately after ECMO initiation (Fig. 5).
ECMO should be initiated as soon as possible after the decision to apply ECPR is made. Placing angiocatheters in the femoral artery and vein during the initial assessment for ECPR candidacy and replacing the angiocatheters with ECMO cannulas after the decision to apply ECPR is made, rather than initiating ECMO cannulation after the decision, may help reduce the time taken to initiate ECMO [70]. High-quality CPR should be provided throughout the resuscitation until ECMO support is initiated. Multiple studies have reported no survival benefit of mechanical CPR over manual CPR [71,72]. However, the use of a mechanical CPR device may enable provisioning high-quality CPR until initiation of ECMO support and more space around the patient for ECMO cannulation, thus facilitating successful ECPR implementation.

Post-ECMO implementation care

Management after ECMO implementation should be part of ECPR protocols to ensure a highly protocolized sequence of care for patients, including diagnosis and treatment of arrest cause, hemodynamic and oxygenation support, monitoring and management of ECMO-related complications, and neuroprognostication. Several studies suggest a significant association between post-ECMO implementation care and good outcomes in patients undergoing ECPR [73,74].
Promptly diagnosing and treating the arrest cause after ECMO initiation can maximize chances of recovery. Patients with refractory cardiac arrest have a high prevalence of coronary artery disease (70%–80%) [75,76]. Therefore, emergent coronary angiography should be included in the ECPR protocol. Current ELSO guidelines recommend emergent coronary angiography for all patients undergoing ECPR without an obvious noncardiac etiology of arrest [53]. Multiple studies suggest a significant association between coronary angiography and/or percutaneous coronary intervention with improved outcomes in patients undergoing ECPR [36,73,77].
Current ELSO guidelines recommend routine computed tomography (CT) imaging of the brain, chest, and abdomen/pelvis as soon as possible in all ECPR cases [53]. Head CT helps in identifying intracranial hemorrhage, a common cause of cardiac arrest [78], and in predicting neurologic outcomes [78,79]. CT of the chest and abdomen/pelvis helps elucidate the cause of cardiac arrest, such as pulmonary embolism, and complications from prolonged CPR or ECMO cannulation. Several studies indicate the utility of whole-body CT after ECPR [8082]. Osofsky et al. [82] evaluated the utility of whole-body CT in detecting clinically significant findings in 38 patients who underwent ECPR and whole-body CT. They reported that whole-body CT detected clinically significant findings in 37 patients (97%) and led to subsequent interventions in 20 patients (54%). ECMO poses unique technical challenges to contrast-enhanced CT imaging. For example, a significant volume of contrast material administered intravenously can be aspirated into the venous cannula and returned to the aorta via the arterial cannula, bypassing the pulmonary artery. ECMO flow needs to be temporarily reduced or stopped after contrast material administration to obtain images of sufficient quality to diagnose pulmonary embolism.
Treatment-refractory shock is the most common cause of death after ECPR [83]. Hemodynamic monitoring in patients receiving ECMO is challenging. Hemodynamic measurements using thermodilution techniques and those based on pulse contour analysis algorithms are unreliable during ECMO. An arterial line should be placed immediately (preferably in the right radial artery). Several studies reported significant associations between mean arterial pressure (MAP) and outcomes in patients resuscitated with ECPR [35,49,84,85]. In an observational study including 253 adult patients resuscitated with ECPR [49], patients with MAP of approximately 75 mmHg had the lowest probability of poor neurologic outcomes. Setting the MAP target to 60–80 mmHg according to the ELSO guidelines would be reasonable [53]. The optimal ECMO flow target in the early post-ECMO implementation period is unknown. The ECMO flow rate can be adjusted by referring to the method used in the ARREST trial [86]. In the ARREST trial, ECMO flow was maximized until vasopressors were discontinued and then decreased as tolerated to promote native cardiac function [86]. Pulse pressure on arterial pressure waveform is dependent on cardiac contractility and afterload and can be used to monitor hemodynamic state in patients undergoing venoarterial ECMO. A low pulse pressure has been associated with unsuccessful weaning from ECMO support and in-hospital mortality in patients undergoing ECPR [87,88]. Loss of pulse pressure indicates a predominance of blood flow through the ECMO circuit, with negligible blood flow through the native heart, which can cause left ventricular dilation. Left ventricular dilation can in turn cause pulmonary edema and myocardial injury, impeding cardiac recovery. Echocardiographic assessment of left ventricular dimensions and function and aortic valve opening help in diagnosing this complication. Several studies suggest a significant association between the use of mechanical left ventricular unloading and improved survival in patients undergoing ECPR [73,89]. ECPR protocols should include diagnostic and therapeutic options that can be used when pulse pressure is lost (e.g., inotropic support, afterload reduction, and intra-aortic balloon pump).
Upon ECMO initiation, sweep gas containing 100% oxygen is typically delivered at a flow rate matching the ECMO flow, frequently leading to hyperoxemia and hypocarbia. Pulmonary complications including pulmonary edema and acute respiratory distress syndrome frequently occur in patients with cardiac arrest [90,91]. Patients with impaired pulmonary gas exchange can be exposed to hypoxemia despite ECMO support because of a phenomenon known as Harlequin syndrome (difference in cerebral and lower extremity oxygenation due to hypoxic blood from the native heart flowing to the brain and hyperoxic blood from the ECMO circuit flowing to the lower extremities). Multiple studies reported significant associations between arterial blood gas derangement and poor outcomes in patients undergoing ECPR [73, 9295]. In a retrospective study including 3,125 patients that received ECPR [92], severe hyperoxemia (≥300 mmHg) was associated with ischemic stroke, intracranial hemorrhage, and in-hospital mortality. Given the associations between arterial blood gas derangement and poor outcomes [9296], frequent evaluation of arterial blood gases and careful titration of the ECMO gas blender setting are required to avoid arterial blood gas derangement that can adversely affect outcomes.
Whether targeted temperature management (TTM) improves outcomes of patients receiving ECPR remains unknown. Observational studies have yielded inconsistent results [36,9799]. Randomized trials evaluating the effects of TTM on outcomes of patients treated with ECPR are lacking. However, given the high incidence of hypoxic-ischemic brain injury in patients undergoing ECPR [100], TTM can be reasonably considered for patients who remain comatose after ECPR. The ELSO guidelines recommend application of TTM targeting 33 to 36 °C for 24 hours to comatose patients after ECPR according to protocols that yielded excellent results [53,76,101].
ECMO is a highly invasive intervention with a high risk of complications [102,103]. Bleeding is a common complication and usually occurs at the cannulation site [104]. In the Prague OHCA study [21], bleeding was twice as common in the invasive strategy group (31%) than in the standard strategy group (15%). Cannulation site bleeding is usually controlled with manual pressure and rarely requires surgery [23,67]. Uncontrollable or serious bleeding within the central nervous system, thoracic cavity, or gastrointestinal tract, although uncommon, has been reported in patients undergoing ECPR [101,105]. In a study that investigated the effect of bleeding and red blood cell transfusion during ECMO on mortality [106], the volume of red blood cells transfused was significantly associated with in-hospital mortality. Screening measures for early detection of bleeding complications (e.g., complete blood count and ultrasonography) should be included in ECPR protocols.
Although anticoagulation strategies vary among ECMO protocols, anticoagulation is typically provided by an initial intravenous bolus of unfractionated heparin (5,000 units) followed by a continuous infusion titrated to maintain an activated clotting time (ACT) of 180 to 220 seconds or a partial thromboplastin time of 1.5 times the upper normal limit. Patients undergoing ECPR are prone to coagulation disorders, such as prolonged prothrombin time and partial thromboplastin time with thrombocytopenia [107,108], which may reduce anticoagulant requirements. Several studies suggest that avoiding the initial bolus dose or targeting low ACT levels may be helpful [109111]. In a meta-analysis that evaluated the effect of different anticoagulant methods on bleeding/thromboembolic complications in patients receiving ECPR [111], the incidence of bleeding events and of thromboembolic events were higher among those who received an initial heparin loading dose than those who did not. In comparisons among the three different ACT level groups, the incidences of both bleeding and thromboembolic events were the highest in the high ACT group. Further studies are needed to confirm the safety and efficacy of the reduced anticoagulation strategy.
Limb ischemia distal to the arterial cannula site is a common complication of peripheral venoarterial ECMO, with an incidence of 10% to 20% [67,82,112]. A larger cannula size, diabetes, and CPR duration have been suggested as risk factors for distal limb ischemia [67,113]. Placing a distal limb perfusion cannula is recommended to prevent distal limb ischemia [53]. Distal limb perfusion cannula placement may not only decrease the risk of distal limb ischemia, but also improve survival in patients undergoing ECPR [73,114]. In a study including 7,488 adult patients treated with ECPR [73], placement of a distal limb perfusion cannula was independently associated with improved survival. Distal limb ischemia can still occur despite distal limb perfusion through the cannula [114]. Regular monitoring of distal limb perfusion should be included in ECPR protocols. Current ELSO guidelines suggest near-infrared spectroscopy for monitoring distal limb perfusion [53]. Several studies have suggested that monitoring calf tissue oxygen saturation using near-infrared spectroscopy may be useful for detecting distal limb ischemia [115,116].
According to current resuscitation guidelines [15], multimodal neuroprognostication should be performed at least 72 hours after achieving normothermia. Although whether the same approach reliably predicts neurologic outcomes in patients resuscitated with ECPR remains to be established, several studies have suggested that prognostic measures used for patients experiencing cardiac arrest not treated with ECMO may also be applicable to patients resuscitated with ECPR [117119]. Ben-Hamouda et al. [117] compared the performance of prognostic measures, including pupillary reflex, electroencephalogram, somatosensory evoked potentials, and neuron specific enolase, between comatose cardiac arrest survivors treated with and without ECMO and reported comparable performances between both groups. Further studies are needed to identify the optimal neuroprognostication method in the ECPR population.

APPROACHES OF ECPR INITIATION FOR REFRACTORY OHCA

Three approaches are currently used for ECPR initiation in patients with refractory OHCA: initiation at an ECPR-capable hospital, prehospital initiation, and the rendezvous approach. The most commonly used approach is intra-arrest transport to an ECPR-capable hospital followed by initiation of ECPR at the hospital. The three published randomized trials on ECPR [2022] followed this approach. Initiation of ECPR with this approach is the least complicated, because ECPR is typically performed by experienced providers at a high-volume ECMO center. However, with this approach, only a limited number of patients can receive ECPR within acceptable timeframes, because on-scene resuscitation and transport to a hospital usually take a significant amount of time. ECPR is only performed at a small number of tertiary hospitals, limiting the geographic coverage of ECPR. To overcome this limitation, alternative approaches including the prehospital initiation and rendezvous approach have been developed. In the rendezvous approach, an ECPR candidate is transferred to a hospital closer to the scene of arrest while an ECMO cannulation team is deployed to that hospital. The patient undergoes ECPR in the rendezvous hospital and is transferred to an ECMO center for postresuscitation care. The investigators of the ARREST trial extended their ECMO-facilitated resuscitation program to the Minneapolis–St. Paul metropolitan area using this approach and reported achieving a neurologically favorable survival rate similar to that in the ARREST trial (43%) [120]. Several systems, including the Service d’Aide Médicale Urgente of Paris, have adopted prehospital ECPR, which brings ECMO to patients with OHCA instead of taking the patients to an ECMO-capable center [26,121,122]. Lamhaut et al. [26] compared the mean CPR duration and survival rate before and after a change in the ECPR strategy in 156 patients treated with ECPR and reported a shorter mean CPR duration and higher survival rate in the prehospital ECPR-based strategy than in the strategy that allowed liberal allocation between prehospital or inhospital ECPR.
Several studies have suggested that the prehospital ECPR or rendezvous approach could allow more patients to receive ECPR than initiation on arrival to an ECPR-capable hospital [123,124]. Song et al. [124] quantified patient catchment areas of the three approaches in Sydney, Australia, and reported that the rendezvous (n=2,175,096) and prehospital ECPR models (n=3,851,727) substantially increased the catchment of eligible patients with OHCA compared to the in-hospital ECPR model (n=811,091). However, implementation of ECPR using these approaches is challenging. Both the rendezvous and prehospital ECPR approaches require substantial planning, training, and logistics efforts and highly coordinated collaboration between prehospital EMS and ECMO centers. The optimal approach for ECPR remains elusive, but may vary depending on geographical characteristics, population density, and medical resources of the region. The ECPR-capable hospital-based approach may be effective if multiple ECPR-capable hospitals are sufficiently dispersed across the region to handle most patients requiring ECPR. However, this is not the case in most regions, wherein the rendezvous approach or prehospital ECPR may be desirable to maximize the coverage of ECPR service.

CONSIDERATIONS FOR INCORPORATING ECPR WITHIN A SYSTEM OF CARE

All elements of the system of care for resuscitation of patients with cardiac arrest should be optimized to achieve neurologically favorable survival with ECPR. Efforts to increase provision of bystander CPR may improve outcomes of patients undergoing ECPR and increase the number of patients receiving ECPR [31]. Most patients with refractory OHCA are not eligible for ECPR due to a prolonged CPR time [125]. Efforts to reduce the time from cardiac arrest to ECMO initiation may therefore be critically important for successful ECPR implementation. Read et al. [126] reported a significant reduction in the time from cardiac arrest to ECMO initiation after implementing a dedicated simulation program for ECPR. Early communication and effective coordination between EMS and ECMO centers are also critical in limiting the time from cardiac arrest to ECMO initiation.
ECPR is only one part of the system of care for resuscitation of patients with cardiac arrest. Only a minority of patients with OHCA are ultimately considered suitable for ECPR [26,127,128]. Changes in EMS for successful ECPR implementation should not hinder resuscitation of patients not receiving ECPR. Intra-arrest transport for in-hospital ECPR can compromise CPR quality during transport, thus adversely affecting outcomes of patients not receiving ECPR [129,130]. Therefore, in cases of hospital-based ECPR, efforts should be made to select ECPR candidates requiring intra-arrest transport and to maintain high-quality CPR during intra-arrest transport (e.g., mechanical CPR).
ECPR requires a high level of expertise and experience. A recent study reported a significant association between higher ECPR case volume and improved survival [73]. ECPR-specific simulation training may help clinicians to develop and maintain the skills and experience needed to expeditiously and safely perform ECPR. Several studies have reported significantly reduced the time to ECMO initiation after ECPR-specific simulation training [126,131].

CONCLUSION

The efficacy of ECPR over conventional treatment in patients with refractory OHCA remains unclear. ECPR may render significant survival benefits over conventional CPR in selected patients only when performed with strict protocol adherence in an experienced system and with a high level of collaboration between EMS and ECMO centers. ECPR is only one part of the system of care for resuscitation of cardiac arrest victims. Optimizing the chain of survival is critical to improving outcomes of patients receiving ECPR.

NOTES

ETHICS STATEMENTS
Not applicable.
CONFLICT OF INTEREST
No potential conflict of interest relevant to this article was reported.
FUNDING
None.
AUTHOR CONTRIBUTIONS
Conceptualization: all authors; Visualization: YHJ; Writing–original draft: KWJ, YHJ; Writing–review & editing: all authors. All authors read and approved the final manuscript.

REFERENCES

1. Berdowski J, Berg RA, Tijssen JG, Koster RW. Global incidences of out-of-hospital cardiac arrest and survival rates: systematic review of 67 prospective studies. Resuscitation 2010; 81:1479-87.
crossref pmid
2. Grasner JT, Herlitz J, Tjelmeland IB, et al. European Resuscitation Council Guidelines 2021: epidemiology of cardiac arrest in Europe. Resuscitation 2021; 161:61-79.
crossref pmid
3. Ong ME, Shin SD, De Souza NN, et al. Outcomes for out-ofhospital cardiac arrests across 7 countries in Asia: the Pan Asian Resuscitation Outcomes Study (PAROS). Resuscitation 2015; 96:100-8.
crossref pmid
4. Virani SS, Alonso A, Benjamin EJ, et al. Heart disease and stroke statistics: 2020 update. A report from the American Heart Association. Circulation 2020; 141:e139-596.
pmid
5. Tsao CW, Aday AW, Almarzooq ZI, et al. Heart disease and stroke statistics: 2022 update. A report from the American Heart Association. Circulation 2022; 145:e153-639.
pmid
6. Korea Disease Control and Prevention Agency (KDCA). Outof-hospital cardiac arrest surveillance [Internet]. KDCA; 2020 [cited 2023 Apr 30]. Available from: https://www.kdca.go.kr/contents.es?mid=a20601030501.

7. Chen YS, Lin JW, Yu HY, et al. Cardiopulmonary resuscitation with assisted extracorporeal life-support versus conventional cardiopulmonary resuscitation in adults with in-hospital cardiac arrest: an observational study and propensity analysis. Lancet 2008; 372:554-61.
crossref pmid
8. Reynolds JC, Frisch A, Rittenberger JC, Callaway CW. Duration of resuscitation efforts and functional outcome after out-of-hospital cardiac arrest: when should we change to novel therapies? Circulation 2013; 128:2488-94.
crossref pmid pmc
9. Goto Y, Funada A, Goto Y. Relationship between the duration of cardiopulmonary resuscitation and favorable neurological outcomes after out-of-hospital cardiac arrest: a prospective, nationwide, population-based cohort study. J Am Heart Assoc 2016; 5:e002819.
crossref pmid pmc
10. Wampler DA, Collett L, Manifold CA, Velasquez C, McMullan JT. Cardiac arrest survival is rare without prehospital return of spontaneous circulation. Prehosp Emerg Care 2012; 16:451-5.
crossref pmid
11. Drennan IR, Lin S, Sidalak DE, Morrison LJ. Survival rates in out-of-hospital cardiac arrest patients transported without prehospital return of spontaneous circulation: an observational cohort study. Resuscitation 2014; 85:1488-93.
crossref pmid
12. Richardson AS, Schmidt M, Bailey M, Pellegrino VA, Rycus PT, Pilcher DV. ECMO cardio-pulmonary resuscitation (ECPR), trends in survival from an international multicentre cohort study over 12-years. Resuscitation 2017; 112:34-40.
crossref pmid
13. Halperin HR, Tsitlik JE, Guerci AD, et al. Determinants of blood flow to vital organs during cardiopulmonary resuscitation in dogs. Circulation 1986; 73:539-50.
crossref pmid
14. Duggal C, Weil MH, Gazmuri RJ, et al. Regional blood flow during closed-chest cardiac resuscitation in rats. J Appl Physiol (1985) 1993; 74:147-52.
crossref pmid
15. Panchal AR, Bartos JA, Cabanas JG, et al. Part 3: adult basic and advanced life support. 2020 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 2020; 142(16_suppl_2):S366-468.
pmid
16. Holmberg MJ, Geri G, Wiberg S, et al. Extracorporeal cardiopulmonary resuscitation for cardiac arrest: a systematic review. Resuscitation 2018; 131:91-100.
crossref pmid pmc
17. Sakamoto T, Morimura N, Nagao K, et al. Extracorporeal cardiopulmonary resuscitation versus conventional cardiopulmonary resuscitation in adults with out-of-hospital cardiac arrest: a prospective observational study. Resuscitation 2014; 85:762-8.
crossref pmid
18. Miraglia D, Miguel LA, Alonso W. Long-term neurologically intact survival after extracorporeal cardiopulmonary resuscitation for in-hospital or out-of-hospital cardiac arrest: a systematic review and meta-analysis. Resusc Plus 2020; 4:100045.
crossref pmid pmc
19. Bougouin W, Dumas F, Lamhaut L, et al. Extracorporeal cardiopulmonary resuscitation in out-of-hospital cardiac arrest: a registry study. Eur Heart J 2020; 41:1961-71.
pmid
20. 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; 396:1807-16.
crossref pmid pmc
21. 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; 327:737-47.
pmid pmc
22. Suverein MM, Delnoij TS, Lorusso R, et al. Early extracorporeal CPR for refractory out-of-hospital cardiac arrest. N Engl J Med 2023; 388:299-309.
pmid
23. Rob D, Smalcova J, Smid O, et al. Extracorporeal versus conventional cardiopulmonary resuscitation for refractory outof-hospital cardiac arrest: a secondary analysis of the Prague OHCA trial. Crit Care 2022; 26:330.
crossref pmid pmc pdf
24. Scquizzato T, Bonaccorso A, Consonni M, et al. Extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest: a systematic review and meta-analysis of randomized and propensity score-matched studies. Artif Organs 2022; 46:755-62.
crossref pmid pmc pdf
25. Shin TG, Choi JH, Jo IJ, et al. Extracorporeal cardiopulmonary resuscitation in patients with inhospital cardiac arrest: a comparison with conventional cardiopulmonary resuscitation. Crit Care Med 2011; 39:1-7.
crossref
26. Lamhaut L, Hutin A, Puymirat E, et al. A pre-hospital extracorporeal cardio pulmonary resuscitation (ECPR) strategy for treatment of refractory out hospital cardiac arrest: an observational study and propensity analysis. Resuscitation 2017; 117:109-17.
crossref pmid
27. Chouihed T, Kimmoun A, Lauvray A, et al. Improving patient selection for refractory out of hospital cardiac arrest treated with extracorporeal life support. Shock 2018; 49:24-8.
crossref pmid
28. Pozzi M, Grinberg D, Armoiry X, et al. Impact of a modified institutional protocol on outcomes after extracorporeal cardiopulmonary resuscitation for refractory out-of-hospital cardiac arrest. J Cardiothorac Vasc Anesth 2022; 36:1670-7.
crossref pmid
29. Koen ‘J, Nathanael T, Philippe D. A systematic review of current ECPR protocols. A step towards standardisation. Resusc Plus 2020; 3:100018.
crossref pmid pmc
30. Karve S, Lahood D, Diehl A, et al. The impact of selection criteria and study design on reported survival outcomes in extracorporeal oxygenation cardiopulmonary resuscitation (ECPR): a systematic review and meta-analysis. Scand J Trauma Resusc Emerg Med 2021; 29:142.
crossref pmid pmc pdf
31. Wang J, Ma Q, Zhang H, Liu S, Zheng Y. Predictors of survival and neurologic outcome for adults with extracorporeal cardiopulmonary resuscitation: a systemic review and metaanalysis. Medicine (Baltimore) 2018; 97:e13257.
pmid pmc
32. Debaty G, Babaz V, Durand M, et al. Prognostic factors for extracorporeal cardiopulmonary resuscitation recipients following out-of-hospital refractory cardiac arrest. A systematic review and meta-analysis. Resuscitation 2017; 112:1-10.
crossref pmid
33. D’Arrigo S, Cacciola S, Dennis M, et al. Predictors of favourable outcome after in-hospital cardiac arrest treated with extracorporeal cardiopulmonary resuscitation: a systematic review and meta-analysis. Resuscitation 2017; 121:62-70.
crossref pmid
34. Bertic M, Worme M, Foroutan F, et al. Predictors of survival and favorable neurologic outcome in patients treated with eCPR: a systematic review and meta-analysis. J Cardiovasc Transl Res 2022; 15:279-90.
crossref pmid pdf
35. Podell JE, Krause EM, Rector R, et al. Neurologic outcomes after extracorporeal cardiopulmonary resuscitation: recent experience at a single high-volume center. ASAIO J 2022; 68:247-54.
crossref pmid
36. Kawakami S, Tahara Y, Koga H, Noguchi T, Inoue S, Yasuda S. The association between time to extracorporeal cardiopulmonary resuscitation and outcome in patients with out-ofhospital cardiac arrest. Eur Heart J Acute Cardiovasc Care 2022; 11:279-89.
crossref pmid pdf
37. Daubin C, Brunet J, Huet J, et al. Extracorporeal cardiopulmonary resuscitation and survival after refractory cardiac arrest: is ECPR beneficial? ASAIO J 2021; 67:1232-9.
crossref pmid
38. Kim YS, Cho YH, Yang JH, et al. Impact of age on the outcomes of extracorporeal cardiopulmonary resuscitation: analysis using inverse probability of treatment weighting. Eur J Cardiothorac Surg 2021; 60:1318-24.
crossref pmid pdf
39. Miyamoto Y, Matsuyama T, Goto T, et al. Association between age and neurological outcomes in out-of-hospital cardiac arrest patients resuscitated with extracorporeal cardiopulmonary resuscitation: a nationwide multicentre observational study. Eur Heart J Acute Cardiovasc Care 2022; 11:35-42.
crossref pmid pdf
40. Goto T, Morita S, Kitamura T, et al. Impact of extracorporeal cardiopulmonary resuscitation on outcomes of elderly patients who had out-of-hospital cardiac arrests: a single-centre retrospective analysis. BMJ Open 2018; 8:e019811.
crossref pmid pmc
41. Park SB, Yang JH, Park TK, et al. Developing a risk prediction model for survival to discharge in cardiac arrest patients who undergo extracorporeal membrane oxygenation. Int J Cardiol 2014; 177:1031-5.
crossref pmid
42. Kikuta S, Inoue A, Ishihara S, et al. Long-term outcomes and prognostic factors of extracorporeal cardiopulmonary resuscitation in patients older than 75 years: a single-centre retrospective study. Emerg Med J 2023; 40:264-70.
crossref pmid
43. Havranek S, Fingrova Z, Rob D, et al. Initial rhythm and survival in refractory out-of-hospital cardiac arrest. Post-hoc analysis of the Prague OHCA randomized trial. Resuscitation 2022; 181:289-96.
crossref pmid
44. Panagides V, Laine M, Fond G, et al. Survival and factors associated with survival with extracorporeal life support during cardiac arrest: a systematic review and meta-analysis. ASAIO J 2022; 68:987-95.
crossref pmid
45. Shirasaki K, Hifumi T, Goto M, et al. Clinical characteristics and outcomes after extracorporeal cardiopulmonary resuscitation in out-of-hospital cardiac arrest patients with an initial asystole rhythm. Resuscitation 2023; 183:109694.
crossref pmid
46. Tanimoto A, Sugiyama K, Tanabe M, Kitagawa K, Kawakami A, Hamabe Y. Out-of-hospital cardiac arrest patients with an initial non-shockable rhythm could be candidates for extracorporeal cardiopulmonary resuscitation: a retrospective study. Scand J Trauma Resusc Emerg Med 2020; 28:101.
crossref pmid pmc pdf
47. Fukushima K, Aoki M, Nakajima J, et al. Favorable prognosis by extracorporeal cardiopulmonary resuscitation for subsequent shockable rhythm patients. Am J Emerg Med 2022; 53:144-9.
crossref pmid
48. Wengenmayer T, Rombach S, Ramshorn F, et al. Influence of low-flow time on survival after extracorporeal cardiopulmonary resuscitation (eCPR). Crit Care 2017; 21:157.
crossref pmid pmc pdf
49. Lee YI, Ko RE, Yang JH, Cho YH, Ahn J, Ryu JA. Optimal mean arterial pressure for favorable neurological outcomes in survivors after extracorporeal cardiopulmonary resuscitation. J Clin Med 2022; 11:290.
crossref pmid pmc
50. Ohbe H, Tagami T, Ogura T, Matsui H, Yasunaga H. Low-flow duration and outcomes of extracorporeal cardiopulmonary resuscitation in adults with in-hospital cardiac arrest: a nationwide inpatient database study. Crit Care Med 2022; 50:1768-77.
crossref pmid
51. Nagao K, Kikushima K, Watanabe K, et al. Early induction of hypothermia during cardiac arrest improves neurological outcomes in patients with out-of-hospital cardiac arrest who undergo emergency cardiopulmonary bypass and percutaneous coronary intervention. Circ J 2010; 74:77-85.
crossref pmid
52. Otani T, Sawano H, Natsukawa T, et al. Low-flow time is associated with a favorable neurological outcome in out-ofhospital cardiac arrest patients resuscitated with extracorporeal cardiopulmonary resuscitation. J Crit Care 2018; 48:15-20.
crossref pmid
53. Richardson AS, Tonna JE, Nanjayya V, et al. Extracorporeal cardiopulmonary resuscitation in adults. interim guideline consensus statement from the extracorporeal life support organization. ASAIO J 2021; 67:221-8.
crossref pmid pmc
54. Debaty G, Lamhaut L, Aubert R, et al. Prognostic value of signs of life throughout cardiopulmonary resuscitation for refractory out-of-hospital cardiac arrest. Resuscitation 2021; 162:163-70.
crossref pmid
55. Daou O, Winiszewski H, Besch G, et al. Initial pH and shockable rhythm are associated with favorable neurological outcome in cardiac arrest patients resuscitated with extracorporeal cardiopulmonary resuscitation. J Thorac Dis 2020; 12:849-57.
crossref pmid pmc
56. Okada Y, Kiguchi T, Irisawa T, et al. Association between low pH and unfavorable neurological outcome among out-of-hospital cardiac arrest patients treated by extracorporeal CPR: a prospective observational cohort study in Japan. J Intensive Care 2020; 8:34.
pmid pmc
57. Bartos JA, Grunau B, Carlson C, et al. Improved survival with extracorporeal cardiopulmonary resuscitation despite progressive metabolic derangement associated with prolonged resuscitation. Circulation 2020; 141:877-86.
crossref pmid pmc
58. Okada Y, Kiguchi T, Irisawa T, et al. Development and validation of a clinical score to predict neurological outcomes in patients with out-of-hospital cardiac arrest treated with extracorporeal cardiopulmonary resuscitation. JAMA Netw Open 2020; 3:e2022920.
crossref pmid pmc
59. Makino Y, Okada Y, Irisawa T, et al. External validation of the TiPS65 score for predicting good neurological outcomes in patients with out-of-hospital cardiac arrest treated with extracorporeal cardiopulmonary resuscitation. Resuscitation 2023; 182:109652.
crossref pmid
60. Tonna JE, Selzman CH, Girotra S, et al. Resuscitation using ECPR during in-hospital cardiac arrest (RESCUE-IHCA) mortality prediction score and external validation. JACC Cardiovasc Interv 2022; 15:237-47.
crossref pmid pmc
61. Poppe M, Schriefl C, Steinacher A, et al. Extracorporeal cardiopulmonary resuscitation at the emergency department: a retrospective patient selection evaluation. Eur J Anaesthesiol 2020; 37:280-5.
pmid
62. Lunz D, Calabro L, Belliato M, et al. Extracorporeal membrane oxygenation for refractory cardiac arrest: a retrospective multicenter study. Intensive Care Med 2020; 46:973-82.
crossref pmid pdf
63. Okada Y, Irisawa T, Yamada T, et al. Clinical outcomes among out-of-hospital cardiac arrest patients treated by extracorporeal cardiopulmonary resuscitation: the CRITICAL study in Osaka. Resuscitation 2022; 178:116-23.
crossref pmid
64. Weinberg A, Miko B, Beck J, Bacchetta M, Mongero L. Is it safe to leave an ECMO circuit primed? Perfusion 2015; 30:47-9.
crossref pmid pdf
65. Tan VE, Evangelista AT, Carella DM, et al. Sterility duration of preprimed extracorporeal membrane oxygenation circuits. J Pediatr Pharmacol Ther 2018; 23:311-4.
crossref pmid pmc pdf
66. Voicu S, Henry P, Malissin I, et al. Improving cannulation time for extracorporeal life support in refractory cardiac arrest of presumed cardiac cause: comparison of two percutaneous cannulation techniques in the catheterization laboratory in a center without on-site cardiovascular surgery. Resuscitation 2018; 122:69-75.
crossref pmid
67. Chen Y, Chen J, Liu C, Xu Z, Chen Y. Impact factors of POCUS-guided annulation for peripheral venoarterial extracorporeal membrane oxygenation: one single-center retrospective clinical analysis. Medicine (Baltimore) 2022; 101:e29489.
pmid pmc
68. Danial P, Hajage D, Nguyen LS, et al. Percutaneous versus surgical femoro-femoral veno-arterial ECMO: a propensity score matched study. Intensive Care Med 2018; 44:2153-61.
crossref pmid pdf
69. Park JS, Lee BK, Jeung KW, et al. Reliability of blood color and blood gases in discriminating arterial from venous puncture during cardiopulmonary resuscitation. Am J Emerg Med 2015; 33:553-8.
crossref pmid
70. Bellezzo JM, Shinar Z, Davis DP, et al. Emergency physicianinitiated extracorporeal cardiopulmonary resuscitation. Resuscitation 2012; 83:966-70.
crossref pmid
71. Perkins GD, Lall R, Quinn T, et al. Mechanical versus manual chest compression for out-of-hospital cardiac arrest (PARAMEDIC): a pragmatic, cluster randomised controlled trial. Lancet 2015; 385:947-55.
crossref pmid
72. Gates S, Quinn T, Deakin CD, Blair L, Couper K, Perkins GD. Mechanical chest compression for out of hospital cardiac arrest: systematic review and meta-analysis. Resuscitation 2015; 94:91-7.
crossref pmid
73. Tonna JE, Selzman CH, Bartos JA, et al. The association of modifiable postresuscitation management and annual case volume with survival after extracorporeal cardiopulmonary resuscitation. Crit Care Explor 2022; 4:e0733.
crossref pmid pmc
74. Duan J, Ma Q, Zhu C, Shi Y, Duan B. eCPR combined with therapeutic hypothermia could improve survival and neurologic outcomes for patients with cardiac arrest: a meta-analysis. Front Cardiovasc Med 2021; 8:703567.
crossref pmid pmc
75. Lamhaut L, Tea V, Raphalen JH, et al. Coronary lesions in refractory out of hospital cardiac arrest (OHCA) treated by extra corporeal pulmonary resuscitation (ECPR). Resuscitation 2018; 126:154-9.
crossref pmid
76. Yannopoulos D, Bartos JA, Raveendran G, et al. Coronary artery disease in patients with out-of-hospital refractory ventricular fibrillation cardiac arrest. J Am Coll Cardiol 2017; 70:1109-17.
crossref pmid
77. Shin TG, Jo IJ, Sim MS, et al. Two-year survival and neurological outcome of in-hospital cardiac arrest patients rescued by extracorporeal cardiopulmonary resuscitation. Int J Cardiol 2013; 168:3424-30.
crossref pmid
78. Shin J, Kim K, Lim YS, et al. Incidence and clinical features of intracranial hemorrhage causing out-of-hospital cardiac arrest: a multicenter retrospective study. Am J Emerg Med 2016; 34:2326-30.
crossref pmid
79. Ryu JA, Chung CR, Cho YH, et al. The association of findings on brain computed tomography with neurologic outcomes following extracorporeal cardiopulmonary resuscitation. Crit Care 2017; 21:15.
crossref pmid pmc pdf
80. Yang KJ, Wang CH, Huang YC, Tseng LJ, Chen YS, Yu HY. Clinical experience of whole-body computed tomography as the initial evaluation tool after extracorporeal cardiopulmonary resuscitation in patients of out-of-hospital cardiac arrest. Scand J Trauma Resusc Emerg Med 2020; 28:54.
crossref pmid pmc pdf
81. Zotzmann V, Rilinger J, Lang CN, et al. Early full-body computed tomography in patients after extracorporeal cardiopulmonary resuscitation (eCPR). Resuscitation 2020; 146:149-54.
crossref pmid
82. Osofsky R, Owen B, Elks W, et al. Protocolized whole-body computed tomography imaging after extracorporeal membrane oxygenation (ECMO) cannulation for cardiac arrest. ASAIO J 2021; 67:1196-203.
crossref pmid
83. Zotzmann V, Lang CN, Bemtgen X, et al. Mode of death after extracorporeal cardiopulmonary resuscitation. Membranes (Basel) 2021; 11:270.
crossref pmid pmc
84. Saemann L, Maier S, Rosner L, et al. A systematic review with meta-analysis investigating the impact of targeted perfusion parameters during extracorporeal cardiopulmonary resuscitation in out-of-hospital and inhospital cardiac arrest. J Extra Corpor Technol 2022; 54:191-202.
crossref pmid pmc
85. Sun F, Mei Y, Lv J, et al. Average mean arterial pressure in the first 6hours of extracorporeal cardiopulmonary resuscitation in the prediction of the prognosis of neurological outcome: a single-center retrospective study. Perfusion 2022; 37:805-11.
crossref pmid pdf
86. Yannopoulos D, Kalra R, Kosmopoulos M, et al. Rationale and methods of the Advanced R2Eperfusion STrategies for Refractory Cardiac Arrest (ARREST) trial. Am Heart J 2020; 229:29-39.
crossref pmid
87. Rilinger J, Riefler AM, Bemtgen X, et al. Impact of pulse pressure on clinical outcome in extracorporeal cardiopulmonary resuscitation (eCPR) patients. Clin Res Cardiol 2021; 110:1473-83.
crossref pmid pmc pdf
88. Lee SI, Lim YS, Park CH, Choi WS, Choi CH. Importance of pulse pressure after extracorporeal cardiopulmonary resuscitation. J Card Surg 2021; 36:2743-50.
crossref pmid
89. Kashiura M, Kishihara Y, Ozawa H, Amagasa S, Yasuda H, Moriya T. Intra-aortic balloon pump use in out-of-hospital cardiac arrest patients who underwent extracorporeal cardiopulmonary resuscitation. Resuscitation 2023; 182:109660.
crossref pmid
90. Shih JA, Robertson HK, Issa MS, et al. Acute respiratory distress syndrome after in-hospital cardiac arrest. Resuscitation 2022; 177:78-84.
crossref pmid pmc
91. Kim JS, Kim YJ, Kim M, et al. The impact of severity of acute respiratory distress syndrome following cardiac arrest on neurologic outcomes. Ther Hypothermia Temp Manag 2021; 11:96-102.
crossref pmid
92. Shou BL, Ong CS, Premraj L, et al. Arterial oxygen and carbon dioxide tension and acute brain injury in extracorporeal cardiopulmonary resuscitation patients: analysis of the extracorporeal life support organization registry. J Heart Lung Transplant 2023; 42:503-11.
crossref pmid pmc
93. Bonnemain J, Rusca M, Ltaief Z, et al. Hyperoxia during extracorporeal cardiopulmonary resuscitation for refractory cardiac arrest is associated with severe circulatory failure and increase mortality. BMC Cardiovasc Disord 2021; 21:542.
pmid pmc
94. Chang WT, Wang CH, Lai CH, et al. Optimal arterial blood oxygen tension in the early postresuscitation phase of extracorporeal cardiopulmonary resuscitation: a 15-year retrospective observational study. Crit Care Med 2019; 47:1549-56.
crossref pmid
95. Halter M, Jouffroy R, Saade A, Philippe P, Carli P, Vivien B. Association between hyperoxemia and mortality in patients treated by eCPR after out-of-hospital cardiac arrest. Am J Emerg Med 2020; 38:900-5.
crossref pmid
96. Tonna JE, Selzman CH, Bartos JA, et al. The association of modifiable mechanical ventilation settings, blood gas changes and survival on extracorporeal membrane oxygenation for cardiac arrest. Resuscitation 2022; 174:53-61.
crossref pmid pmc
97. Sakurai T, Kaneko T, Yamada S, Takahashi T. Extracorporeal cardiopulmonary resuscitation with temperature management could improve the neurological outcomes of out-ofhospital cardiac arrest: a retrospective analysis of a nationwide multicenter observational study in Japan. J Intensive Care 2022; 10:30.
crossref pmid pmc pdf
98. Huang M, Shoskes A, Migdady I, et al. Does targeted temperature management improve neurological outcome in extracorporeal cardiopulmonary resuscitation (ECPR)? J Intensive Care Med 2022; 37:157-67.
crossref pmid pdf
99. Nakashima T, Ogata S, Noguchi T, et al. Association of intentional cooling, achieved temperature and hypothermia duration with in-hospital mortality in patients treated with extracorporeal cardiopulmonary resuscitation: an analysis of the ELSO registry. Resuscitation 2022; 177:43-51.
crossref pmid
100. Migdady I, Rice C, Deshpande A, et al. Brain injury and neurologic outcome in patients undergoing extracorporeal cardiopulmonary resuscitation: a systematic review and metaanalysis. Crit Care Med 2020; 48:e611-9.
crossref pmid
101. Stub D, Bernard S, Pellegrino V, et al. Refractory cardiac arrest treated with mechanical CPR, hypothermia, ECMO and early reperfusion (the CHEER trial). Resuscitation 2015; 86:88-94.
crossref pmid
102. Wong JK, Melvin AL, Joshi DJ, et al. Cannulation-related complications on veno-arterial extracorporeal membrane oxygenation: prevalence and effect on mortality. Artif Organs 2017; 41:827-34.
crossref pmid pdf
103. Kashiura M, Sugiyama K, Tanabe T, Akashi A, Hamabe Y. Effect of ultrasonography and fluoroscopic guidance on the incidence of complications of cannulation in extracorporeal cardiopulmonary resuscitation in out-of-hospital cardiac arrest: a retrospective observational study. BMC Anesthesiol 2017; 17:4.
crossref pmid pmc pdf
104. Thiagarajan RR, Barbaro RP, Rycus PT, et al. Extracorporeal Life Support Organization registry international report 2016. ASAIO J 2017; 63:60-7.
crossref pmid
105. Downing J, Al Falasi R, Cardona S, et al. How effective is extracorporeal cardiopulmonary resuscitation (ECPR) for outof-hospital cardiac arrest? A systematic review and metaanalysis. Am J Emerg Med 2022; 51:127-38.
crossref pmid
106. Mazzeffi M, Greenwood J, Tanaka K, et al. Bleeding, transfusion, and mortality on extracorporeal life support: ECLS Working Group on Thrombosis And Hemostasis. Ann Thorac Surg 2016; 101:682-9.
crossref pmid
107. Ruggeri L, Franco A, Alba AC, et al. Coagulation derangements in patients with refractory cardiac arrest treated with extracorporeal cardiopulmonary resuscitation. J Cardiothorac Vasc Anesth 2019; 33:1877-82.
crossref pmid
108. Tsuchida T, Wada T, Gando S. Coagulopathy induced by veno-arterial extracorporeal membrane oxygenation is associated with a poor outcome in patients with out-of-hospital cardiac arrest. Front Med (Lausanne) 2021; 8:651832.
crossref pmid pmc
109. Kim BK, Hong JI, Hwang J, Shin HJ. Satisfactory outcome with activated clotting time <160 seconds in extracorporeal cardiopulmonary resuscitation. Medicine (Baltimore) 2022; 101:e30568.
crossref pmid pmc
110. Zhang L, Liu W, Liu J, et al. Heparin loading dose in patients undergoing extracorporeal cardiopulmonary resuscitation. J Cardiothorac Vasc Anesth 2023; 37:1201-7.
crossref pmid
111. Zhang L, Lin C, Liu L, Wang X. A systematic review and meta-analysis of anticoagulation practices and mortality in extracorporeal cardiopulmonary resuscitation. Asian J Surg 2022; 45:3003-4.
crossref pmid
112. Cheng R, Hachamovitch R, Kittleson M, et al. Complications of extracorporeal membrane oxygenation for treatment of cardiogenic shock and cardiac arrest: a meta-analysis of 1,866 adult patients. Ann Thorac Surg 2014; 97:610-6.
crossref pmid
113. Kim J, Cho YH, Sung K, et al. Impact of cannula size on clinical outcomes in peripheral venoarterial extracorporeal membrane oxygenation. ASAIO J 2019; 65:573-9.
crossref pmid
114. Tanaka D, Hirose H, Cavarocchi N, Entwistle JW. The impact of vascular complications on survival of patients on venoarterial extracorporeal membrane oxygenation. Ann Thorac Surg 2016; 101:1729-34.
crossref pmid
115. Patton-Rivera K, Beck J, Fung K, et al. Using near-infrared reflectance spectroscopy (NIRS) to assess distal-limb perfusion on venoarterial (V-A) extracorporeal membrane oxygenation (ECMO) patients with femoral cannulation. Perfusion 2018; 33:618-23.
crossref pmid pdf
116. Vinogradsky A, Kurlansky P, Ning Y, et al. Continuous nearinfrared reflectance spectroscopy monitoring to guide distal perfusion can minimize limb ischemia surgery for patients requiring femoral venoarterial extracorporeal life support. J Vasc Surg 2023; 77:1495-503.
crossref pmid
117. Ben-Hamouda N, Ltaief Z, Kirsch M, et al. Neuroprognostication under ECMO after cardiac arrest: are classical tools still performant? Neurocrit Care 2022; 37:293-301.
crossref pmid pdf
118. Schrage B, Rubsamen N, Becher PM, et al. Neuron-specificenolase as a predictor of the neurologic outcome after cardiopulmonary resuscitation in patients on ECMO. Resuscitation 2019; 136:14-20.
crossref pmid
119. Floerchinger B, Philipp A, Camboni D, et al. NSE serum levels in extracorporeal life support patients: relevance for neurological outcome? Resuscitation 2017; 121:166-71.
crossref pmid
120. 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.
crossref pmid pmc
121. Petermichl W, Philipp A, Hiller KA, et al. Reliability of prognostic biomarkers after prehospital extracorporeal cardiopulmonary resuscitation with target temperature management. Scand J Trauma Resusc Emerg Med 2021; 29:147.
crossref pmid pmc pdf
122. Kruit N, Rattan N, Tian D, Dieleman S, Burrell A, Dennis M. Prehospital extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest: a systematic review and meta-analysis. J Cardiothorac Vasc Anesth 2023; 37:748-54.
crossref pmid
123. Spigner M, Braude D, Pruett K, Ortiz C, Glazer J, Marinaro J. The use of predictive modeling to compare prehospital eCPR strategies. Prehosp Emerg Care 2023; 27:184-91.
crossref pmid
124. Song C, Dennis M, Burns B, et al. Improving access to extracorporeal membrane oxygenation for out of hospital cardiac arrest: pre-hospital ECPR and alternate delivery strategies. Scand J Trauma Resusc Emerg Med 2022; 30:77.
crossref pmid pmc pdf
125. Hsu CH, Meurer WJ, Domeier R, et al. Extracorporeal cardiopulmonary resuscitation for refractory out-of-hospital cardiac arrest (EROCA): results of a randomized feasibility trial of expedited out-of-hospital transport. Ann Emerg Med 2021; 78:92-101.
crossref pmid pmc
126. Read AC, Morgan S, Reynolds C, et al. The effect of a structured ECPR protocol aided by specific simulation training in a quaternary ECMO centre: a retrospective pre-post study. Resusc Plus 2022; 10:100234.
crossref pmid pmc
127. Poppe M, Weiser C, Holzer M, et al. The incidence of “load&go” out-of-hospital cardiac arrest candidates for emergency department utilization of emergency extracorporeal life support: a one-year review. Resuscitation 2015; 91:131-6.
crossref pmid
128. Grunau B, Scheuermeyer FX, Stub D, et al. Potential candidates for a structured Canadian ECPR program for out-ofhospital cardiac arrest. CJEM 2016; 18:453-60.
crossref pmid
129. Eastin C, Karim S, Hawthorn C, et al. Mandated 30-minute scene time interval correlates with improved return of spontaneous circulation at emergency department arrival: a before and after study. J Emerg Med 2019; 57:527-34.
crossref pmid
130. Grunau B, Kime N, Leroux B, et al. Association of intra-arrest transport vs continued on-scene resuscitation with survival to hospital discharge among patients with out-of-hospital cardiac arrest. JAMA 2020; 324:1058-67.
crossref pmid pmc
131. Su L, Spaeder MC, Jones MB, et al. Implementation of an extracorporeal cardiopulmonary resuscitation simulation program reduces extracorporeal cardiopulmonary resuscitation times in real patients. Pediatr Crit Care Med 2014; 15:856-60.
crossref pmid

Fig. 1.
Favorable and unfavorable factors for extracorporeal cardiopulmonary resuscitation (ECPR).
ceem-23-063f1.jpg
Fig. 2.
An example of a list of materials and equipment needed to perform extracorporeal cardiopulmonary resuscitation (ECPR). IV, intravenous; ECMO, extracorporeal membrane oxygenation.
ceem-23-063f2.jpg
Fig. 3.
Transverse view of the common femoral artery and vein. Arrows point to shadow artifact of needle entering the femoral artery. (A) The needle tip is in the muscle layer above the common femoral artery (CFA). (B) The needle tip is about to enter the CFA. CFV, common femoral vein.
ceem-23-063f3.jpg
Fig. 4.
Ultrasonographic image showing guidewire-induced hyperechoic shadow (arrow) within the inferior vena cava.
ceem-23-063f4.jpg
Fig. 5.
Screenshots of patient monitor (A) before and (B) immediately after extracorporeal membrane oxygenation (ECMO) initiation. Green, red, and white lines indicate electrocardiographic, arterial pressure, and right atrial pressure data, respectively. Note the progressive increase in the arterial pressure immediately after ECMO initiation.
ceem-23-063f5.jpg
Table 1.
Overview of published randomized trials investigating ECPR in adult patients with refractory OHCA
Study Study design No. of patients Location Group assignment Witnessed arrest Bystander CPR Shockable rhythm Trial protocol Time to ECMO initiation (min) Primary outcome
ARREST trial [20] Single-center RCT 30 USA After hospital arrival 24 (80.0) 25 (83.3) 30 (100) Present 59 ± 28 Survival to hospital discharge: ECMO-facilitated resuscitation 6 of 14 (42.9%) vs. standard ACLS 1 of 15 (6.7%)
Prague OHCA study [21] Single-center RCT 256 Czech Republic During prehospital CPR 256 (100) 252 (98.4) 156 (60.9) Present 61 (55–70) 180-Day survival with good neurologic outcome: invasive strategy 39 of 124 (31.5%) vs. standard strategy 29 of 132 (22.0%)
INCEPTION trial [22] Multicenter RCT 134 Netherlands During intra-arrest transport 131 (97.8) 130 (97.0) 132 (98.5) Absent 74 (63–87) 30-Day survival with good neurologic outcome: ECPR 14 of 70 (20.0%) vs. conventional CPR 10 of 62 (16.1%)

Values are presented as number only, number (%), mean±standard deviation, or median (interquartile range).

ECPR, extracorporeal cardiopulmonary resuscitation; OHCA, out-of-hospital cardiac arrest; CPR, cardiopulmonary resuscitation; ECMO, extracorporeal membrane oxygenation; ARREST, Advanced Reperfusion Strategies for Refractory Cardiac Arrest; RCT, randomized clinical trial; ACLS, advanced cardiovascular life support; INCEPTION, Early Initiation of Extracorporeal Life Support in Refractory Out-of-Hospital Cardiac Arrest.

TOOLS
PDF Links  PDF Links
PubReader  PubReader
ePub Link  ePub Link
XML Download  XML Download
Full text via DOI  Full text via DOI
Download Citation  Download Citation
  Print
Share:      
METRICS
1
Web of Science
2
Crossref
0
Scopus
2,632
View
248
Download
Editorial Office
The Korean Society of Emergency Medicine
101-3104, Brownstone Seoul, 464 Cheongpa-ro, Jung-gu, Seoul 04510, Korea
TEL: +82-31-709-0918   E-mail: office@ceemjournal.org
About |  Browse Articles |  Current Issue |  For Authors and Reviewers
Copyright © by The Korean Society of Emergency Medicine.                 Developed in M2PI