Bridge-to-transplant temporary mechanical circulatory support and risk of allosensitization.

INTRODUCTION: Since the 2018 change in the US adult heart allocation policy, more patients are bridged-to-transplant on temporary mechanical circulatory support (tMCS). Previous studies indicate that durable left ventricular assist devices (LVAD) may lead to allosensitization. The goal of this study was to assess whether tMCS implantation is associated with changes in sensitization. METHODS: We included patients evaluated for heart transplants between 2015 and 2022 who had alloantibody measured before and after MCS implantation. Allosensitization was defined as development of new alloantibodies after tMCS implant. RESULTS: A total of 41 patients received tMCS before transplant. Nine (22.0%) patients developed alloantibodies following tMCS implantation: 3 (12.0%) in the intra-aortic balloon pump group (n = 25), 2 (28.6%) in the microaxial percutaneous LVAD group (n = 7), and 4 (44.4%) in the veno-arterial extra-corporeal membrane oxygenation group (n = 9)-p = .039. Sensitized patients were younger (44.7 ± 11.6 years vs. 54.3 ± 12.5 years, p = .044), were more likely to be sensitized at baseline - 3 of 9 (33.3%) compared to 2 out of 32 (6.3%) (p = .028) and received more transfusions with red blood cells (6 (66.6%) vs. 8 (25%), p = .02) and platelets (6 (66.6%) vs. 5 (15.6%), p = .002). There was no significant difference in tMCS median duration of support (4 [3,15] days vs. 8.5 [5,14.5] days, p = .57). Importantly, out of the 11 patients who received a durable LVAD after tMCS, 5 (45.5%) became sensitized, compared to 4 out of 30 patients (13.3%) who only had tMCS-p = .028. CONCLUSIONS: Our findings suggest that patients bridged-to-transplant with tMCS, without significant blood product transfusions and a subsequent durable LVAD implant, have a low risk of allosensitization. Further studies are needed to confirm our findings and determine whether risk of sensitization varies by type of tMCS and duration of support.

Prehospital Ground and Helicopter-Based Extracorporeal Cardiopulmonary Resuscitation (ECPR) Reduce Barriers to ECPR: A GIS Model.

INTRODUCTION: Evidence suggests that Extracorporeal Cardiopulmonary Resuscitation (ECPR) can improve survival rates for nontraumatic out-of-hospital cardiac arrest (OHCA). However, when ECPR is indicated over 50% of potential candidates are unable to qualify in the current hospital-based system due to geographic limitations. This study employs a Geographic Information System (GIS) model to estimate the number of ECPR eligible patients within the United States in the current hospital-based system, a prehospital ECPR ground-based system, and a prehospital ECPR Helicopter Emergency Medical Services (HEMS)-based system. METHODS: We constructed a GIS model to estimate ground and helicopter transport times. Time-dependent rates of ECPR eligibility were derived from the Resuscitation Outcome Consortium (ROC) database, while the Cardiac Arrest Registry to Enhance Survival (CARES) registry determined the number of OHCA patients meeting ECPR criteria within designated transportation times. Emergency Medical Services (EMS) response time, ECPR candidacy determination time, and on-scene time were modeled based on data from the EROCA trial. The combined model was used to estimate the total ECPR eligibility in each system. RESULTS: The CARES registry recorded 736,066 OHCA patients from 2013 to 2021. After applying clinical criteria, 24,661 (3.4%) ECPR-indicated OHCA were identified. When considering overall ECPR eligibility within 45 minutes from OHCA to initiation, only 11.76% of OHCA where ECPR was indicated were eligible in the current hospital-based system. The prehospital ECPR HEMS-based system exhibited a four-fold increase in ECPR eligibility (49.3%), while the prehospital ground-based system showed a more than two-fold increase (28.4%). CONCLUSIONS: The study demonstrates a two-fold increase in ECPR eligibility for a field-deployable ground-based system and a four-fold increase for a prehospital ECPR HEMS-based system compared to the current hospital-based OHCA system. This novel GIS model can inform future ECPR implementation strategies, optimizing systems of care.

Sex-Related Differences in Utilization and Outcomes of Extracorporeal Cardio-Pulmonary Resuscitation for Refractory Cardiac Arrest.

Sparse data exist on sex-related differences in extracorporeal cardiopulmonary resuscitation (ECPR) for refractory cardiac arrest (rCA). We explored the role of sex on the utilization and outcomes of ECPR for rCA by retrospective analysis of the Extracorporeal Life Support Organization (ELSO) International Registry. The primary outcome was in-hospital mortality. Exploratory outcomes were discharge disposition and occurrence of any specific extracorporeal membrane oxygenation (ECMO) complications. From 1992 to 2020, a total of 7,460 adults with ECPR were identified: 30.5% women; 69.5% men; 55.9% Whites, 23.7% Asians, 8.9% Blacks, and 3.8% Hispanics. Women's age was 50.4 ± 16.9 years (mean ± standard deviation) and men's 54.7 ± 14.1 (p < 0.001). Ischemic heart disease occurred in 14.6% women vs. 18.5% men (p < 0.001). Overall, 28.5% survived at discharge, 30% women vs. 27.8% men (p = 0.138). In the adjusted analysis, sex was not associated with in-hospital mortality (odds ratio [OR] = 0.93 [confidence interval {CI} = 0.80-1.08]; p = 0.374). Female sex was associated with decreased odds of neurologic, cardiovascular, and renal complications. Despite being younger and having fewer complications during ECMO, women had in-hospital mortality similar to men. Whether these findings are driven by biologic factors or disparities in health care warrants further investigation.

Pao2 and Mortality in Neonatal Extracorporeal Membrane Oxygenation: Retrospective Analysis of the Extracorporeal Life Support Organization Registry, 2015-2020.

OBJECTIVES: Extracorporeal life support can lead to rapid reversal of hypoxemia but the benefits and harms of different oxygenation targets in severely ill patients are unclear. Our primary objective was to investigate the association between the Pao2 after extracorporeal membrane oxygenation (ECMO) initiation and mortality in neonates treated for respiratory failure. DESIGN: Retrospective analysis of the Extracorporeal Life Support Organization (ELSO) Registry data, 2015-2020. PATIENTS: Newborns supported by ECMO for respiratory indication were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Pao2 24 hours after ECMO initiation (H24 Pao2) was reported. The primary outcome was 28-day mortality. We identified 3533 newborns (median age 1 d [interquartile range (IQR), 1-3]; median weight 3.2 kg [IQR, 2.8-3.6]) from 198 ELSO centers, who were placed on ECMO. By 28 days of life, 731 (20.7%) had died. The median H24 Pao2 was 85 mm Hg (IQR, 60-142). We found that both hypoxia (Pao2 < 60 mm Hg) and moderate hyperoxia (Pao2 201-300 mm Hg) were associated with greater adjusted odds ratio (aOR [95% CI]) of 28-day mortality, respectively: aOR 1.44 (95% CI, 1.08-1.93), p = 0.016, and aOR 1.49 (95% CI, 1.01-2.19), p value equals to 0.045. CONCLUSIONS: Early hypoxia or moderate hyperoxia after ECMO initiation are each associated with greater odds of 28-day mortality among neonates requiring ECMO for respiratory failure.

Extracorporeal Life Support Organization Registry International Report 2022: 100,000 Survivors.

The Extracorporeal Life Support Organization (ELSO) maintains the world's largest extracorporeal membrane oxygenation (ECMO) registry by volume, center participation, and international scope. This 2022 ELSO Registry Report describes the program characteristics of ECMO centers, processes of ECMO care, and reported outcomes. Neonates (0-28 days), children (29 days-17 years), and adults (≥18 years) supported with ECMO from 2009 through 2022 and reported to the ELSO Registry were included. This report describes adjunctive therapies, support modes, treatments, complications, and survival outcomes. Data are presented descriptively as counts and percent or median and interquartile range (IQR) by year, group, or level. Missing values were excluded before calculating descriptive statistics. Complications are reported per 1,000 ECMO hours. From 2009 to 2022, 154,568 ECMO runs were entered into the ELSO Registry. Seven hundred and eighty centers submitted data during this time (557 in 2022). Since 2009, the median annual number of adult ECMO runs per center per year increased from 4 to 15, whereas for pediatric and neonatal runs, the rate decreased from 12 to 7. Over 50% of patients were transferred to the reporting ECMO center; 20% of these patients were transported with ECMO. The use of prone positioning before respiratory ECMO increased from 15% (2019) to 44% (2021) for adults during the coronavirus disease-2019 (COVID-19) pandemic. Survival to hospital discharge was greatest at 68.5% for neonatal respiratory support and lowest at 29.5% for ECPR delivered to adults. By 2022, the Registry had enrolled its 200,000th ECMO patient and 100,000th patient discharged alive. Since its inception, the ELSO Registry has helped centers measure and compare outcomes across its member centers and strategies of care. Continued growth and development of the Registry will aim to bolster its utility to patients and centers.

Timing of Initiation of Extracorporeal Membrane Oxygenation Support and Outcomes Among Patients With Cardiogenic Shock.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (ECMO) provides full hemodynamic support for patients with cardiogenic shock, but optimal timing of ECMO initiation remains uncertain. We sought to determine whether earlier initiation of ECMO is associated with improved survival in cardiogenic shock. METHODS AND RESULTS: We analyzed adult patients with cardiogenic shock who received venoarterial ECMO from the international Extracorporeal Life Support Organization (ELSO) registry from 2009 to 2019, excluding those cannulated following an operation. Multivariable logistic regression evaluated the association between time from admission to ECMO initiation and in-hospital death. Among 8619 patients (median, 56.7 [range, 44.8-65.6] years; 33.5% women), the median duration from admission to ECMO initiation was 14 (5-32) hours. Patients who had ECMO initiated within 24 hours (n=5882 [68.2%]) differed from those who had ECMO initiated after 24 hours, with younger age, more preceding cardiac arrest, and worse acidosis. After multivariable adjustment, patients with ECMO initiated >24 hours after admission had higher risk of in-hospital death (adjusted odds ratio, 1.20 [95% CI, 1.06-1.36]; P=0.004). Each 12-hour increase in the time from admission to ECMO initiation was incrementally associated with higher adjusted in-hospital mortality rate (adjusted odds ratio, 1.06 [95% CI, 1.03-1.10]; P<0.001). The association between longer time to ECMO and worse outcomes appeared stronger in patients with lower shock severity. CONCLUSIONS: Longer delays from admission to ECMO initiation were associated with higher a mortality rate in a large-scale, international registry. Our analysis supports optimization of door-to-support time and the avoidance of inappropriately delayed ECMO initiation.

The state of emergency department extracorporeal cardiopulmonary resuscitation: Where are we now, and where are we going?

Extracorporeal cardiopulmonary resuscitation (ECPR) has emerged in the context of the emergency department as a life-saving therapy for patients with refractory cardiac arrest. This review examines the utility of ECPR based on current evidence gleaned from three pivotal trials: the ARREST trial, the Prague study, and the INCEPTION trial. We also discuss several considerations in the care of these complex patients, including prehospital strategy, patient selection, and postcardiac arrest management. Collectively, the evidence from these trials emphasizes the growing significance of ECPR as a viable intervention, highlighting its potential for improved outcomes and survival rates in patients with refractory cardiac arrest when employed judiciously. As such, these findings advocate the need for further research and protocol development to optimize its use in diverse clinical scenarios.

Pediatric Highlights From the Extracorporeal Life Support Organization Registry: 2017-2022.

The Extracorporeal Life Support Organization (ELSO) registry which collects data from hundreds of participating centers supports research in ECMO to help improve patient outcomes. The ELSO Scientific Oversight Committee, an international and diverse group of ECMOlogists ( https://www.elso.org/registry/socmembers.aspx ), selected the most impactful and innovative research articles on pediatric ECMO emerging from ELSO data. Here they present brief highlights of these publications.

Adult Highlights From the Extracorporeal Life Support Organization Registry: 2017-2022.

The Extracorporeal Life Support Organization (ELSO) registry captures clinical data and outcomes on patients receiving extracorporeal membrane oxygenation (ECMO) support across the globe at participating centers. It provides a very unique opportunity to benchmark outcomes and analyze the clinical course to help identify ways of improving patient outcomes. In this review, we summarize select adult ECMO articles published using the ELSO registry over the past 5 years. These articles highlight innovative utilization of the registry data in generating hypotheses for future clinical trials. Members of the ELSO Scientific Oversight Committee can be found here: https://www.elso.org/registry/socmembers.aspx .

Death by Neurologic Criteria in Children Undergoing Extracorporeal Cardiopulmonary Resuscitation: Retrospective Extracorporeal Life Support Organization Registry Study, 2017-2021.

OBJECTIVES: To determine factors associated with brain death in children treated with extracorporeal cardiopulmonary resuscitation (E-cardiopulmonary resuscitation). DESIGN: Retrospective database study. SETTINGS: Data reported to the Extracorporeal Life Support Organization (ELSO), 2017-2021. PATIENTS: Children supported with venoarterial extracorporeal membrane oxygenation (ECMO) for E-cardiopulmonary resuscitation. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Data from the ELSO Registry included patient characteristics, blood gas values, support therapies, and complications. The primary outcome was brain death (i.e., death by neurologic criteria [DNC]). There were 2,209 children (≥ 29 d to < 18 yr of age) included. The reason for ECMO discontinuation was DNC in 138 patients (6%), and other criteria for death occurred in 886 patients (40%). Recovery occurred in 1,109 patients (50%), and the remaining 76 patients (4%) underwent transplantation. Fine and Gray proportional subdistribution hazards' regression analyses were used to examine the association between variables of interest and DNC. Age greater than 1 year ( p < 0.001), arterial blood carbon dioxide tension (Pa co2 ) greater than 82 mm Hg ( p = 0.022), baseline lactate greater than 15 mmol/L ( p = 0.034), and lactate 24 hours after cannulation greater than 3.8 mmol/L ( p < 0.001) were independently associated with greater hazard of subsequent DNC. In contrast, the presence of cardiac disease was associated with a lower hazard of subsequent DNC (subdistribution hazard ratio 0.57 [95% CI, 0.39-0.83] p = 0.004). CONCLUSIONS: In children undergoing E-cardiopulmonary resuscitation, older age, pre-event hypercarbia, higher before and during ECMO lactate levels are associated with DNC. Given the association of DNC with hypercarbia following cardiac arrest, the role of Pa co2 management in E-cardiopulmonary resuscitation warrants further studies.

Bilateral Femoral Cannulation Is Associated With Reduced Severe Limb Ischemia-Related Complications Compared With Unilateral Femoral Cannulation in Adult Peripheral Venoarterial Extracorporeal Membrane Oxygenation: Results From the Extracorporeal Life Support Registry.

OBJECTIVES: Peripheral venoarterial extracorporeal membrane oxygenation (ECMO) with femoral access is obtained through unilateral or bilateral groin cannulation. Whether one cannulation strategy is associated with a lower risk for limb ischemia remains unknown. We aim to assess if one strategy is preferable. DESIGN: A retrospective cohort study based on the Extracorporeal Life Support Organization registry. SETTING: ECMO centers worldwide included in the Extracorporeal Life Support Organization registry. PATIENTS: All adult patients (≥ 18 yr) who received peripheral venoarterial ECMO with femoral access and were included from 2014 to 2020. INTERVENTIONS: Unilateral or bilateral femoral cannulation. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the occurrence of limb ischemia defined as a composite endpoint including the need for a distal perfusion cannula (DPC) after 6 hours from implantation, compartment syndrome/fasciotomy, amputation, revascularization, and thrombectomy. Secondary endpoints included bleeding at the peripheral cannulation site, need for vessel repair, vessel repair after decannulation, and in-hospital death. Propensity score matching was performed to account for confounders. Overall, 19,093 patients underwent peripheral venoarterial ECMO through unilateral ( n = 11,965) or bilateral ( n = 7,128) femoral cannulation. Limb ischemia requiring any intervention was not different between both groups (bilateral vs unilateral: odds ratio [OR], 0.92; 95% CI, 0.82-1.02). However, there was a lower rate of compartment syndrome/fasciotomy in the bilateral group (bilateral vs unilateral: OR, 0.80; 95% CI, 0.66-0.97). Bilateral cannulation was also associated with lower odds of cannulation site bleeding (bilateral vs unilateral: OR, 0.87; 95% CI, 0.76-0.99), vessel repair (bilateral vs unilateral: OR, 0.55; 95% CI, 0.38-0.79), and in-hospital mortality (bilateral vs unilateral: OR, 0.85; 95% CI, 0.81-0.91) compared with unilateral cannulation. These findings were unchanged after propensity matching. CONCLUSIONS: This study showed no risk reduction for overall limb ischemia-related events requiring DPC after 6 hours when comparing bilateral to unilateral femoral cannulation in peripheral venoarterial ECMO. However, bilateral cannulation was associated with a reduced risk for compartment syndrome/fasciotomy, lower rates of bleeding and vessel repair during ECMO, and lower in-hospital mortality.

A randomized, double-blinded, placebo-controlled clinical trial of sterile filtered human amniotic fluid for treatment of COVID-19.

IMPORTANCE: Acellular human amniotic fluid (hAF) is an antimicrobial and anti-inflammatory fluid that has been used to treat various pro-inflammatory conditions. In a feasibility study, we have previously demonstrated that hAF could be safely administered to severely ill patients with coronavirus disease-19 (COVID-19). The impact of acellular hAF on markers of systemic inflammation and clinical outcomes during COVID-19 infection remain unknown. OBJECTIVE: To determine the safety and efficacy of acellular, sterile processed intravenously administered hAF on markers of systemic inflammation during COVID-19. DESIGN, SETTINGS AND PARTICIPANTS: This single-center Phase I/II randomized, placebo controlled clinical trial enrolled adult (age ≥ 18 years) patients hospitalized for respiratory symptoms of COVID-19, including hypoxemia, tachypnea or dyspnea. The study was powered for outcomes with an anticipated enrollment of 60 patients. From 09/28/2020 to 02/04/2022 we enrolled and randomized 47 (of an anticipated 60) patients hospitalized due to COVID-19. One patient withdrew consent after randomization but prior to treatment. Safety outcomes to 30 days were collected through hospital discharge and were complete by the end of screening on 6/30/2022. INTERVENTIONS: Intravenous administration of 10 cc sterile processed acellular hAF once daily for up to 5 days vs placebo. MAIN OUTCOME AND MEASURES: Blood biomarkers of inflammation, including C-Reactive protein (CRP), lactate dehydrogenase, D-dimer, and interleukin-6 (IL-6), as well as safety outcomes. RESULTS: Patients who were randomized to hAF (n = 23) were no more likely to have improvements in CRP from baseline to Day 6 than patients who were randomized to placebo (n = 24) hAF: -5.9 [IQR -8.2, -0.6] vs placebo: -5.9 [-9.4, -2.05]; p = 0.6077). There were no significant differences in safety outcomes or adverse events. Secondary measures of inflammation including lactate dehydrogenase, D-dimer and IL-6 were not statistically different from baseline to day 6. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial involving hospitalized patients with COVID-19, the intravenous administration of 10 cc of hAF daily for 5 days did not result in statistically significant differences in either safety or markers of systemic inflammation compared to placebo, though we did not achieve our enrollment target of 60 patients. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov as #NCT04497389 on 04/08/2020.

Characterizing the Racial Discrepancy in Hypoxemia Detection in VV-ECMO: An ELSO Registry Analysis.

Importance: Skin pigmentation influences peripheral oxygen saturation (SpO2) measured by pulse oximetry compared to the arterial saturation of oxygen (SaO2) measured via arterial blood gas analysis. However, data on SpO2-SaO2 discrepancy are limited in venovenous-extracorporeal membrane oxygenation (VV-ECMO) patients. Objective: To determine whether there is racial/ethnical discrepancy between SpO2 and SaO2 in patients receiving VV-ECMO. We hypothesized VV-ECMO cannulation, in addition to race/ethnicity, accentuates the SpO2-SaO2 discrepancy due to significant hemolysis. Design: Retrospective cohort study of the Extracorporeal Life Support Organization Registry from 1/2018-5/2023. Setting: International, multicenter registry study including over 500 ECMO centers. Participants: Adults (≥ 18 years) supported with VV-ECMO with concurrently measured SpO2 and SaO2 measurements. Exposure: Race/ethnicity and ECMO cannulation. Main outcomes and measures: Occult hypoxemia (SaO2 ≤ 88% with SpO2 ≥ 92%) was our primary outcome. Multivariable logistic regressions were performed to examine whether race/ethnicity was associated with occult hypoxemia in pre-ECMO and on-ECMO SpO2-SaO2 calculations. Covariates included age, sex, temporary mechanical circulatory support, pre-vasopressors, and pre-inotropes for pre-ECMO analysis, plus single-lumen versus double-lumen cannulation, hemolysis, hyperbilirubinemia, ECMO pump flow rate, and on-ECMO 24h lactate for on-ECMO analysis. Results: Of 13,171 VV-ECMO patients (median age = 48.6 years, 66% male), there were 7,772 (59%) White, 2,114 (16%) Hispanic, 1,777 (14%) Black, and 1,508 (11%) Asian patients. The frequency of on-ECMO occult hypoxemia was 2.0% (N = 233). Occult hypoxemia was more common in Black and Hispanic versus White patients (3.1% versus 1.7%, P < 0.001 and 2.5% versus 1.7%, P = 0.025, respectively).In multivariable logistic regression, Black patients were at higher risk of pre-ECMO occult hypoxemia versus White patients (adjusted odds ratio [aOR] = 1.55, 95% confidence interval [CI] = 1.18-2.02, P = 0.001). For on-ECMO occult hypoxemia, Black patients (aOR = 1.79, 95%CI = 1.16-2.75, P = 0.008) and Hispanic patients (aOR = 1.71, 95%CI = 1.15-2.55, P = 0.008) had higher risk versus White patients. Furthermore, higher pump flow rate (aOR = 1.29, 95%CI = 1.08-1.55, P = 0.005) and higher on-ECMO 24h lactate (aOR = 1.06, 95%CI = 1.03-1.10, P < 0.001) significantly increased the risk of on-ECMO occult hypoxemia. Conclusions and Relevance: Hispanic and Black VV-ECMO patients experienced occult hypoxemia more than White patients. SaO2 should be carefully monitored during ECMO support for Black and Hispanic patients especially for those with high pump flow and lactate values at risk for occult hypoxemia.

Extracorporeal membrane oxygenation for cardiac arrest: what, when, why, and how.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) facilitated resuscitation was first described in the 1960s, but only recently garnered increased attention with large observational studies and randomized trials evaluating its use. AREAS COVERED: In this comprehensive review of extracorporeal cardiopulmonary resuscitation (ECPR), we report the history of resuscitative ECMO, terminology, circuit configuration and cannulation considerations, complications, selection criteria, implementation and management, and important considerations for the provider. We review the relevant guidelines, different approaches to cannulation, postresuscitation management, and expected outcomes, including neurologic, cardiac, and hospital survival. Finally, we advocate for the participation in national/international Registries in order to facilitate continuous quality improvement and support scientific discovery in this evolving area. EXPERT OPINION: ECPR is the most disruptive technology in cardiac arrest resuscitation since high-quality CPR itself. ECPR has demonstrated that it can provide up to 30% increased odds of survival for refractory cardiac arrest, in tightly restricted systems and for select patients. It is also clear, though, from recent trials that ECPR will not confer this high survival when implemented in less tightly protocoled settings and within lower volume environments. Over the next 10 years, ECPR research will explore the optimal initiation thresholds, best practices for implementation, and postresuscitation care.

Prognostic factors associated with favourable functional outcome among adult patients requiring extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest: A systematic review and meta-analysis.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR), has demonstrated promise in the management of refractory out-of-hospital cardiac arrest (OHCA). However, evidence from observational studies and clinical trials are conflicting and the factors influencing outcome have not been well established. METHODS: We conducted a systematic review and meta-analysis summarizing the association between pre-ECPR prognostic factors and likelihood of good functional outcome among adult patients requiring ECPR for OHCA. We searched Medline and Embase databases from inception to February 28, 2023 and screened studies with two independent reviewers. We performed meta-analyses of unadjusted and adjusted odds ratios, adjusted hazard ratios and mean differences separately. We assessed risk of bias using the QUIPS tool and certainty of evidence using the GRADE approach. FINDINGS: We included 29 observational and randomized studies involving 7,397 patients. Factors with moderate or high certainty of association with increased survival with favourable functional outcome include pre-arrest patient factors, such as younger age (odds ratio (OR) 2.13, 95% CI 1.52 to 2.99) and female sex (OR 1.37, 95% CI 1.11 to 1.70), as well as intra-arrest factors, such as shockable rhythm (OR 2.79, 95% CI 2.04 to 3.80), witnessed arrest (OR 1.68 (95% CI 1.16 to 2.42), bystander CPR (OR 1.55, 95% CI 1.19 to 2.01), return of spontaneous circulation (OR 2.81, 95% CI 2.19 to 3.61) and shorter time to cannulation (OR 1.14, 95% CI 1.17 to 1.69 per 10 minutes). INTERPRETATION: The findings of this review confirm several clinical concepts wellestablished in the cardiac arrest literature and their applicability to the patient for whom ECPR is considered - that is, the impact of pre-existing patient factors, the benefit of timely and effective CPR, as well as the prognostic importance of minimizing low-flow time. We advocate for the thoughtful consideration of these prognostic factors as part of a risk stratification framework when evaluating a patient's potential candidacy for ECPR.