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Background: Multidisciplinary Shock Teams have improved clinical outcomes for cardiogenic shock, but their implementation costs have not been studied. This study's objective was to compare costs between patients treated with and without a Shock Team and determine if the team's implementation is cost-effective compared with standard of care., Methods: We examined patients with refractory cardiogenic shock treated with or without a Shock Team at a tertiary academic hospital from 2009 to 2018. Real-world hospital data were used to compare costs and outcomes, including survival at discharge, 1-year survival, and quality-adjusted life years gained at 1 year. Incremental cost-effectiveness ratios were calculated over a 1-year time horizon, with parameter uncertainty evaluated through probabilistic sensitivity analysis using 1000 second-order Monte Carlo simulations., Results: The study involved 244 patients, with 123 treated by the Shock Team and 121 receiving standard of care. Patients were predominantly male (77.5%), with a mean age of 58 (18-92) years. The Shock Team approach improved survival rates at hospital discharge and 1-year follow-up (61.0% versus 47.9%; P =0.04 and 55.0% versus 40.5%; P =0.03, respectively). The incremental cost-effectiveness ratio for increases in survival probability at discharge for the multidisciplinary Shock Team compared with standard of care was $102 088. The incremental cost-effectiveness ratio for increases in survival probability at 1-year was estimated at $96 152 and at $127 862 per 1 quality-adjusted life year gained. Probabilistic sensitivity analysis estimates showed that the Shock Team was cost-effective in the majority of simulations using a willingness-to-pay threshold of $150 000, while it was also dominant in almost one-third of the simulations., Conclusions: The Shock Team approach for treating refractory cardiogenic shock may be a cost-effective alternative to traditional standard of care. These findings can help prioritize the implementation of Shock Team initiatives to further improve cardiogenic shock outcomes., Competing Interests: Dr Drakos serves as a consultant for Abbott Laboratories and Pfizer and has received research support from Novartis and Merck. Dr Ohsfeldt reports grant support from Bayer. Dr. Tonna is the Chair of the Extracorporeal Life Support Organization Registry. E.S. Davis serves as a consultant for Abbott Laboratories and Medtronic Inc. The other authors report no conflicts.

Background: Cardiogenic shock (CS) can stem from multiple causes and portends poor prognosis. Prior studies have focused on acute myocardial infarction-CS; however, acute decompensated heart failure (ADHF)-CS accounts for most cases. We studied patients suffering ADHF-CS to identify clinical factors, early in their trajectory, associated with a higher probability of successful outcomes., Methods: Consecutive patients with CS were evaluated (N=1162). We studied patients who developed ADHF-CS at our hospital (N=562). Primary end point was native heart survival (NHS), defined as survival to discharge without receiving advanced HF therapies. Secondary end points were adverse events, survival, major cardiac interventions, and hospital readmissions within 1 year following index hospitalization discharge. Association of clinical data with NHS was analyzed using logistic regression., Results: Overall, 357 (63.5%) patients achieved NHS, 165 (29.2%) died, and 41 (7.3%) were discharged post advanced HF therapies. Of 398 discharged patients (70.8%), 303 (53.9%) were alive at 1 year. Patients with NHS less commonly suffered cardiac arrest, underwent intubation or pulmonary artery catheter placement, or received temporary mechanical circulatory support, had better hemodynamic and echocardiographic profiles, and had a lower vasoactive-inotropic score at shock onset. Bleeding, hemorrhagic stroke, hemolysis in patients with mechanical circulatory support, and acute kidney injury requiring renal replacement therapy were less common compared with patients who died or received advanced HF therapies. After multivariable adjustments, clinical variables associated with NHS likelihood included younger age, history of systemic hypertension, absence of cardiac arrest or acute kidney injury requiring renal replacement therapy, lower pulmonary capillary wedge pressure and vasoactive-inotropic score, and higher tricuspid annular plane systolic excursion at shock onset (all P <0.05)., Conclusions: By studying contemporary patients with ADHF-CS, we identified clinical factors that can inform clinical management and provide future research targets. Right ventricular function, renal function, pulmonary artery catheter placement, and type and timing of temporary mechanical circulatory support warrant further investigation to improve outcomes of this devastating condition., Competing Interests: Dr Drakos serves as a consultant for Abbott Laboratories and Pfizer and has received research support from Novartis and Merck. Dr Tonna is the Chair of the Registry Committee of the Extracorporeal Life Support Organization. The other authors report no conflicts.

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., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Background: Cardiogenic shock (CS) mortality remains near 40%. In addition to inadequate cardiac output, patients with severe CS may exhibit vasodilation. We aimed to examine the prevalence and consequences of vasodilation in CS., Methods: We analyzed all patients hospitalized at a CS referral center who were diagnosed with CS stages B to E and did not have concurrent sepsis or recent cardiac surgery. Vasodilation was defined by lower systemic vascular resistance (SVR), higher norepinephrine equivalent dose, or a blunted SVR response to pressors. Threshold SVR values were determined by their relation to 14-day mortality in spline models. The primary outcome was death within 14 days of CS onset in multivariable-adjusted Cox models., Results: This study included 713 patients with a mean age of 60 years and 27% females; 14-day mortality was 28%, and 38% were vasodilated. The median SVR was 1308 dynes•s•cm -5 (interquartile range, 870-1652), median norepinephrine equivalent was 0.11 µg/kg per minute (interquartile range, 0-0.2), and 28% had a blunted pressor response. Each 100-dynes•s•cm -5 decrease in SVR below 800 was associated with 20% higher mortality (adjusted hazard ratio, 1.23; P =0.004). Each 0.1-µg/kg per minute increase in norepinephrine equivalent dose was associated with 15% higher mortality (adjusted hazard ratio, 1.12; P <0.001). A blunted pressor response was associated with a nearly 2-fold mortality increase (adjusted hazard ratio, 1.74; P =0.003)., Conclusions: Pathophysiologic vasodilation is prevalent in CS and independently associated with an increased risk of death. CS vasodilation can be identified by SVR <800 dynes•s•cm -5 , high doses of pressors, or a blunted SVR response to pressors. Additional studies exploring mechanisms and treatments for CS vasodilation are needed., Competing Interests: Dr Drakos served as a consultant to Abbott. The other authors report no conflicts.

Purpose: Skin pigmentation influences peripheral oxygen saturation (SpO 2 ) compared to arterial saturation of oxygen (SaO 2 ). Occult hypoxemia (SaO 2  ≤ 88% with SpO 2  ≥ 92%) is associated with increased in-hospital mortality in venovenous-extracorporeal membrane oxygenation (VV-ECMO) patients. We hypothesized VV-ECMO cannulation, in addition to race/ethnicity, accentuates the SpO 2 -SaO 2 discrepancy due to significant hemolysis., Methods: Adults (≥ 18 years) supported with VV-ECMO with concurrently measured SpO 2 and SaO 2 measurements from over 500 centers in the Extracorporeal Life Support Organization Registry (1/2018-5/2023) were included. Multivariable logistic regressions were performed to examine whether race/ethnicity was associated with occult hypoxemia in pre-ECMO and on-ECMO SpO 2 -SaO 2 calculations., Results: Of 13,171 VV-ECMO patients, there were 7772 (59%) White, 2114 (16%) Hispanic, 1777 (14%) Black, and 1508 (11%) Asian patients. The frequency of on-ECMO occult hypoxemia was 2.0% (N = 233). Occult hypoxemia was more common in Black and Hispanic patients 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. Higher pump flow rates (aOR = 1.29, 95% CI = 1.08-1.55, P = 0.005) and on-ECMO 24-h lactate (aOR = 1.06, 95% CI = 1.03-1.10, P < 0.001) significantly increased the risk of on-ECMO occult hypoxemia., Conclusion: SaO 2 should be carefully monitored if using SpO 2 during ECMO support for Black and Hispanic patients especially for those with high pump flow and lactate values at risk for occult hypoxemia., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: Dr. Tonna’s institution received funding from the National Heart, Lung, and Blood Institute; he disclosed he is the Chair of the Registry of the Extracorporeal Life Support Organization; he disclosed off label us of extracorporeal membrane oxygenation for greater than 6 hours. Dr. Levy has disclosed that she does not have any potential conflicts of interest.

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 Pa o2 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: Pa o2 24 hours after ECMO initiation (H24 Pa o2 ) 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 Pa o2 was 85 mm Hg (IQR, 60-142). We found that both hypoxia (Pa o2 < 60 mm Hg) and moderate hyperoxia (Pa o2 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., Competing Interests: Dr. Tonna is supported by a Career Development Award from the National Institutes of Health/National Heart, Lung, and Blood Institute (K23 HL141596). Dr. Tonna is the Chair of the Registry Committee of the Extracorporeal Life Support Organization. Dr. Moscatelli is a consultant for Air Liquide Santé International as a member of the advisory board on the use of inhaled nitric oxide for cardiothoracic indications. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background: Systemic hemodynamics and specific ventilator settings have been shown to predict survival during venoarterial extracorporeal membrane oxygenation (ECMO). How the right heart (the right ventricle and pulmonary artery) affect survival during venoarterial ECMO is unknown. We aimed to identify the relationship between right heart function with mortality and the duration of ECMO support., Methods: Cardiac ECMO runs in adults from the Extracorporeal Life Support Organization Registry between 2010 and 2022 were queried. Right heart function was quantified via pulmonary artery pulse pressure (PAPP) for pre-ECMO and on-ECMO periods. A multivariable model was adjusted for modified Society for Cardiovascular Angiography and Interventions stage, age, sex, and concurrent clinical data (ie, pulmonary vasodilators and systemic pulse pressure). The primary outcome was in-hospital mortality., Results: A total of 4442 ECMO runs met inclusion criteria and had documentation of hemodynamic and illness severity variables. The mortality rate was 55%; nonsurvivors were more likely to be older, have a worse Society for Cardiovascular Angiography and Interventions stage, and have longer pre-ECMO endotracheal intubation times ( P <0.05 for all) than survivors. Increasing PAPP from pre-ECMO to on-ECMO time (ΔPAPP) was associated with reduced mortality per 2 mm Hg increase (odds ratio, 0.98 [95% CI, 0.97-0.99]; P =0.002). Higher on-ECMO PAPP was associated with mortality reduction across quartiles with the greatest reduction in the third PAPP quartile (odds ratio, 0.75 [95% CI, 0.63-0.90]; P =0.002) and longer time on ECMO per 10 mm Hg (beta, 15 [95% CI, 7.7-21]; P <0.001)., Conclusions: Early on-ECMO right heart function and interval improvement from pre-ECMO values were associated with mortality reduction during cardiac ECMO. Incorporation of right heart metrics into risk prediction models should be considered., Competing Interests: Dr Tonna is the Chair-elect of the Registry Committee of the Extracorporeal Life Support Organization (ELSO). Dr Brodie has been on the medical advisory boards for Abiomed, Xenios, Medtronic, Inspira, and Cellenkos. He is the President-elect of ELSO and the Chair of the Executive Committee of the International ECMO Network (ECMONet), and he writes for UpToDate.

Competing Interests: Dr. Tonna is supported by a Career Development Award from the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (K23 HL141596); he disclosed that he is the Chair of the Registry of the Extracorporeal Life Support Organization; and he disclosed the off-label product use of extracorporeal membrane oxygenation for greater than 6 hours of use. Dr. Cho is supported by NIH (1K23HL157610) and Hyperfine. The remaining authors have disclosed that they do not have any potential conflicts of interest.

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 min 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 prehospital ECPR ground-based system and a four-fold increase for a prehospital ECPR HEMS-based system compared to the current hospital-based ECPR system. This novel GIS model can inform future ECPR implementation strategies, optimizing systems of care.

Objectives: We planned to synthesize evidence examining the potential efficacy and safety of performing physical rehabilitation and/or mobilization (PR&M) in adult patients receiving extracorporeal life support (ECLS)., Data Sources: We included any study that compared PR&M to no PR&M or among different PR&M strategies in adult patients receiving any ECLS for any indication and any cannulation. We searched seven electronic databases with no language limitations., Study Selection and Data Extraction: Two reviewers, independently and in duplicate, screened all citations for eligibility. We used the Cochrane Risk of Bias 2 and Cochrane Risk Of Bias In Non-randomized Studies of Interventions tools to assess individual study risk of bias. Although we had planned for meta-analysis, this was not possible due to insufficient data, so we used narrative and tabular data summaries for presenting results. We assessed the overall certainty of the evidence for each outcome using the Grading of Recommendations Assessment, Development, and Evaluation framework., Data Synthesis: We included 17 studies that enrolled 996 patients. Most studies examined venovenous extracorporeal membrane oxygenation (ECMO) and/or venoarterial ECMO as a bridge to recovery in the ICU. We found an uncertain effect of high-intensity/active PR&M on mortality, duration of mechanical ventilation, ICU length of stay, hospital length of stay, or quality of life compared with low-intensity/passive PR&M in patients receiving ECLS (very low certainty due to very serious imprecision). There was similarly an uncertain effect on safety events including clinically important bleeding, spontaneous intracerebral hemorrhage, limb ischemia, accidental decannulation, or ECLS circuit dysfunction (very low certainty due to very serious risk of bias and imprecision)., Conclusions: Based on the currently available summary of evidence, there is an uncertain effect of high-intensity/active PR&M on patient important outcomes or safety in patients receiving ECLS. Despite indirect data from other populations suggesting potential benefit of high-intensity PR&M in the ICU; further high-quality randomized trials evaluating the benefits and risks of physical therapy and/or mobilization in this population are needed., Competing Interests: Dr. Brodie receives research support from and consults for LivaNova. He has been on the medical advisory boards for Xenios, Medtronic, Inspira, and Cellenkos. He is the President-elect of the Extracorporeal Life Support Organization (ELSO) and the Chair of the Executive Committee of the International Extracorporeal Membrane Oxygenation (ECMO) Network, and he writes for UpToDate. Dr. Tonna is supported by a Career Development Award from the National Institutes of Health/National Heart, Lung, and Blood Institute (K23 HL141596) and is the Chair of the Registry Committee of ELSO. Dr. Hodgson sits on the Executive Committee of the International ECMO Network and leads the national ECMO Registry (EXCEL) in Australia and New Zealand. She also led one of the included randomized controlled trials. Dr. Fan reports personal fees from ALung Technologies, Baxter, Getinge, Inspira, Vasomune, and ZOLL Medical outside the submitted work. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

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., (© 2024 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

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., Competing Interests: Dr. Thiagarajan reports a relationship with the United States Department of Defense Clinical Trial Award (award number W81XWH2210301) for clinical trial, with the Society of Critical Care Medicine speaking and lecture fees, and with Extracorporeal Life Support Organization (ELSO) that speaking and lecture fees. Dr. Tonna reports a relationship with LivaNova USA, Inc. that includes speaking and lecture fees and travel reimbursement, he is the Chair of the ELSO Registry, and received support for article research from the National Institutes of Health. Dr. Rycus is the Executive Director of ELSO. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

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 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., Competing Interests: Disclosure: J.E.T. is the Chair of the Registry Committee of the Extracorporeal Life Support Organization (ELSO). P.S.B. receives salary support from ELSO. G.M. is the President of ELSO. M.P. is the Immediate past President of ELSO. D.B. receives research support from and consults for LivaNova. He has been on the medical advisory boards for Abiomed, Xenios, Medtronic, Inspira, and Cellenkos. He is the President-elect of ELSO and the Chair of the Executive Committee of the International ECMO Network (ECMONet), and he writes for UpToDate. M.A., A.H., and K.R. are the Immediate Past Co-Chairs of the Scientific Oversight Committee of ELSO. P.R. is the Executive Director of ELSO. C.S. is the Chief Executive Officer (CEO) of ELSO. N.A.B. is the President of European Chapter of ELSO. N.A.B. has been on the medical advisory boards for Xenios and Baxter. T.M. is on the Board of Directors of ELSO. R.D.G. is the President of the Latin-American Chapter of ELSO. P.M.K. is the President of the South West Asia and Africa Chapter of ELSO. J.F.F. is the President of Asia-Pacific Chapter of ELSO. P.M.A.A. is Treasurer of ELSO Board of Directors. P.M.A.A. is funded by U.S. DoD PRMRP Clinical Trial Award #W81XWH2210301, NIH (R13HD104432) and FDA UCSF-Stanford Center of Excellence in Regulatory Sciences and Innovation (U01FD004979/U01FD005978). None of the funding sources were involved in the design or conduct of the study, collection, management, analysis, or interpretation of the data, or preparation, review, or approval of the manuscript. No other conflicts of interest reported. R.P.B. is a member of the Board of Directors for ELSO and receives funding from the National Heart, Lung, And Blood Institute (R01 HL153519)., (Copyright © ASAIO 2024.)

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., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. JACEP Open published by Wiley Periodicals LLC on behalf of American College of Emergency Physicians.)

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 ., Competing Interests: Disclosure: P.S. received personal fees from Fresenius and Getinge and a scientific grant from the European Society of Intensive Care Medicine and the European Commission (Horizon 2020 Fast Track to Innovation: NCT04115709). K.S. acknowledges research support from Metro North Hospital and Health Service. A.A. receives research support from Francis Family Foundation and NIGMS P20 GM 103652 grant. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2023.)

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., (Copyright © 2023 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

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., Competing Interests: Drs. Brodie’s and Lorusso’s institutions received funding from LivaNova. Drs. Brodie, Broman, and Wiedemann received funding from Xenios AG (Heilbronn, Germany). Dr. Brodie received funding from Abided, Medtronic, Abiomed, Inspira, Xenios, and Cellenkos; he received research support from ALung Technologies; and he disclosed that he is President-elect of the Extracorporeal Life Support Organization (ELSO) and Chair of the Executive Committee of the International Extracorporeal Membrane Oxygenation Network. Dr. Taccone is a scientific advisor for Eurosets and Xenios. Drs. Belliato and Broman received funding from Eurosets srl (Medolla, Italy). Dr. Belliato received funding from Eswtor Spa and Hamilton Medical. Dr. Wiedemann received funding from Abbott; he is a scientific advisor for Xenios/Fresenius. Dr. Tonna’s institution received funding from the National Heart, Lung, and Blood Institute; he disclosed that he is Chair-Elect of the ELSO Registry Committee. Drs. Tonna and Barbaro received support for article research from the U.S. National Institutes of Health. Dr. Barbaro’s institution received funding from the NHBLI (R01 HL153519, R01 HD015434, and K12 HL138039); he disclosed that he is the ELSO Registry Chair. Dr. MacLaren disclosed that he serves on the Board of Directors of ELSO. Dr. Lorusso’s institution received funding from Medtronic, LivaNova, Abiomed, Getinge, and Eurosets; he disclosed that he is a member of the Medical Advisory Board for Eurosets, HemoCue, and Xenios. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

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., (© 2023. The Author(s).)

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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Alexandre Tran has no conflicts to report. Dr. Bram Rochwerg has no conflicts to report. Dr. Eddy Fan reports receiving personal fees from ALung Technologies, Baxter, Inspira, Vasomune, and Zoll Medical outside of the submitted work. He serves on the Executive Committee and is Chair of the Data Committee for the International ECMO Network (ECMONet). Dr. Jan Belohlavek reports receiving lecture and consultancy honoraria outside of the submitted work from Getinge, Abiomed, Xenios, Resuscitec, Novartis, Bayer, Boehringer-Ingelheim and AstraZeneca Companies. Dr. Martje M. Suverein has no conflicts to report. Dr. Marcel C. G. van de Poll has no conflicts to report. Dr. Roberto Lorusso reports consulting activities for Medtronic, Livanova, Getinge and receiving lecture fees from Abiomed. He serves on the Medical Advisory Board of Xenios and Eurosets. Dr. Susanna Price has no conflicts to report. Dr. Demetris Yannopoulos has no conflicts to report. Dr. Graeme MacLaren serves on the Executive Committee of the Extracorporeal Life Support Organization (ELSO). Dr. Kollengode Ramanathan is the co-Chair of the Scientific Oversight Committee at ELSO and has received honoraria for educational talks outside the submitted work from Fresenius and Baxter. Ryan Ruiyang Ling receives research support from the Clinician Scientist Development Unit, National University of Singapore. Dr. Sonny Thiara has no conflicts to report. Dr. Joseph E. Tonna is the Chair of the Registry of the Extracorporeal Life Support Organization (ELSO). Dr. Kiran Shekar serves on the Scientific Committee and Network Committee of ECMONet.He reports receiving lecture honoraria outside of the submitted work from Getinge and Abiomed. Dr. Carol L. Hodgson serves on the Executive Committee, Scientific Committee, and Data Committee of ECMONet. Dr. Damon C. Scales has no conflicts to report. Dr. Claudio Sandroni has no conflicts to report. Dr. Jerry P. Nolan receives support from Elsevier for his role as Editor-in-Chief for Resuscitation. Dr. Arthur S. Slutsky reports consulting for Baxter International Inc. and Xenios. He serves on the Executive Committee and is Chair of the Scientific Committee of ECMONet. Dr. Alain Combes reports receiving personal fees from Getinge, Xenios, and Baxter International Inc. He serves on the Executive Committee and Scientific Committee of ECMONet, and is Past-President of the European Extracorporeal Life Support Organization (EuroELSO). Dr. Daniel Brodie receives research support from and consults for LivaNova. He has been on the medical advisory boards for Abiomed, Xenios, Medtronic, Inspira and Cellenkos. He is the President-elect of the Extracorporeal Life Support Organization (ELSO) and the Chair of the Executive Committee of the International ECMO Network (ECMONet), and he writes for UpToDate. Dr. Shannon M. Fernando has no conflicts to report., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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.

There are minimal data on the use of venoarterial extracorporeal membrane life support (VA-ECLS) in adult congenital heart disease (ACHD) patients presenting with cardiogenic shock (CS). This study sought to describe the population of ACHD patients with CS who received VA-ECLS in the Extracorporeal Life Support Organization (ELSO) Registry. This was a retrospective analysis of adult patients with diagnoses of ACHD and CS in ELSO from 2009-2021. Anatomic complexity was categorized using the American College of Cardiology/American Heart Association 2018 guidelines. We described patient characteristics, complications, and outcomes, as well as trends in mortality and VA-ECLS utilization. Of 528 patients who met inclusion criteria, there were 32 patients with high-complexity anatomy, 196 with moderate-complexity anatomy, and 300 with low-complexity anatomy. The median age was 59.6 years (interquartile range, 45.8-68.2). The number of VA-ECLS implants increased from five implants in 2010 to 81 implants in 2021. Overall mortality was 58.3% and decreased year-by-year (β= -2.03 [95% confidence interval, -3.36 to -0.70], p = 0.007). Six patients (1.1%) were bridged to heart transplantation and 21 (4.0%) to durable ventricular assist device. Complications included cardiac arrhythmia/tamponade (21.6%), surgical site bleeding (17.6%), cannula site bleeding (11.4%), limb ischemia (7.4%), and stroke (8.7%). Utilization of VA-ECLS for CS in ACHD patients has increased over time with a trend toward improvement in survival to discharge., (Copyright © ASAIO 2023.)

Background: Despite the demonstrated benefits of rehabilitation, active physical therapy and early mobilization are not universally performed during critical illness, especially among patients receiving extracorporeal membrane oxygenation (ECMO), with variation among sites., Objective: What factors are predictive of physical mobility during venovenous (VV) ECMO support?, Methods: We performed an observational analysis of an international cohort using data from the Extracorporeal Life Support Organization (ELSO) Registry. We analyzed adults (≥18 years) supported with VV ECMO who survived for at least 7 days. Our primary outcome was early mobilization (ICU Mobility Scale score >0) at day 7 of ECMO support. Hierarchical multivariable logistic regression models were utilized to identify factors independently associated with early mobilization at day 7 of ECMO. Results are reported as adjusted odds ratios (aOR) with 95% confidence intervals (95%CI)., Results: Among 8,160 unique VV ECMO patients, factors independently associated with early mobilization included cannulation for transplantation (aOR 2.86 [95% CI 2.08-3.92]; p<0.001), avoidance of mechanical ventilation (aOR 0.51 [95% CI 0.41-0.64]; p<0.0001), higher center level patient volume (6-20 patients annually: aOR 1.49 [95% CI 1 to 2.23] and >20 patients annually: aOR 2 [95% CI: 1.37 to 2.93]; p<0.0001 for group), and cannulation with a dual-lumen cannula (aOR 1.25 [95% CI 1.08-1.42]; p = 0.0018). Early mobilization was associated with a lower probability of death (29 vs 48%; p<0.0001)., Conclusions: Higher levels of early mobilization on ECMO were associated modifiable and non-modifiable patient characteristics, including cannulation with a dual-lumen cannula, and with high center level patient volume., Competing Interests: Declaration of Competing Interest Dr. Tonna is the Chair of the Extracorporeal Life Support Organization (ELSO) Registry Committee. Dr. Abrams writes for UpToDate. Dr. Brodie receives research support from and consults for LivaNova. He has been on the medical advisory boards for Abiomed, Xenios, Medtronic, Inspira and Cellenkos. He is the President-elect of the Extracorporeal Life Support Organization (ELSO) and the Chair of the Executive Committee of the International ECMO Network (ECMONet), and he writes for UpToDate. Dr Hodgson serves on the Executive and Scientific Committee of the International ECMO Network and leads two randomized trials of early mobilization in ICU (TEAM RCT GNT1120319, ECMO-Rehab MRF2007591)., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Percutaneous cannulation is now accepted as the first-line strategy for extracorporeal cardiopulmonary resuscitation (ECPR) in adults. However, previous studies comparing percutaneous cannulation to surgical cannulation have been limited by small sample size and single-center settings. This study aimed to compare in-hospital outcomes in cardiac arrest (CA) patients who received femoro-femoral ECPR with percutaneous vs surgical cannulation., Methods: Adults with refractory CA treated with percutaneous (percutaneous group) or surgical (surgical group) femoro-femoral ECPR between January 2008 and December 2019 were extracted from the international Extracorporeal Life Support Organization registry. The primary outcome was severe neurological complication. Multivariable logistic regression analyses were performed to assess the association between percutaneous cannulation and in-hospital outcomes., Results: Among 3575 patients meeting study inclusion, 2749 (77%) underwent percutaneous cannulation. The proportion of patients undergoing percutaneous cannulation increased from 18% to 89% over the study period (p < 0.001 for trend). Severe neurological complication (13% vs 19%; p < 0.001) occurred less frequently in the percutaneous group compared to the surgical group. In adjusted analyses, percutaneous cannulation was independently associated with lower rate of severe neurological complication (odds ratio [OR] 0.62; 95% CI 0.46-0.83; p = 0.002), similar rates of in-hospital mortality (OR 0.93; 95% CI 0.73-1.17; p = 0.522), limb ischemia (OR 0.84; 95% CI 0.58-1.20; p = 0.341) and cannulation site bleeding (OR 0.90; 95% CI 0.66-1.22; p = 0.471). The comparison of outcomes provided similar results across different levels of center percutaneous experience or center ECPR volume., Conclusions: Among adults receiving ECPR, percutaneous cannulation was associated with probable lower rate of severe neurological complication, and similar rates of in-hospital mortality, limb ischemia and cannulation site bleeding., (© 2023. La Société de Réanimation de Langue Francaise = The French Society of Intensive Care (SRLF).)

Background: Thoracic aortic disease and bicuspid aortic valve (BAV) likely have a heritable component, but large population-based studies are lacking. This study characterizes familial associations of thoracic aortic disease and BAV, as well as cardiovascular and aortic-specific mortality, among relatives of these individuals in a large-population database., Methods: In this observational case-control study of the Utah Population Database, we identified probands with a diagnosis of BAV, thoracic aortic aneurysm, or thoracic aortic dissection. Age- and sex-matched controls (10:1 ratio) were identified for each proband. First-degree relatives, second-degree relatives, and first cousins of probands and controls were identified through linked genealogical information. Cox proportional hazard models were used to quantify the familial associations for each diagnosis. We used a competing-risk model to determine the risk of cardiovascular-specific and aortic-specific mortality for relatives of probands., Results: The study population included 3 812 588 unique individuals. Familial hazard risk of a concordant diagnosis was elevated in the following populations compared with controls: first-degree relatives of patients with BAV (hazard ratio [HR], 6.88 [95% CI, 5.62-8.43]); first-degree relatives of patients with thoracic aortic aneurysm (HR, 5.09 [95% CI, 3.80-6.82]); and first-degree relatives of patients with thoracic aortic dissection (HR, 4.15 [95% CI, 3.25-5.31]). In addition, the risk of aortic dissection was higher in first-degree relatives of patients with BAV (HR, 3.63 [95% CI, 2.68-4.91]) and in first-degree relatives of patients with thoracic aneurysm (HR, 3.89 [95% CI, 2.93-5.18]) compared with controls. Dissection risk was highest in first-degree relatives of patients who carried a diagnosis of both BAV and aneurysm (HR, 6.13 [95% CI, 2.82-13.33]). First-degree relatives of patients with BAV, thoracic aneurysm, or aortic dissection had a higher risk of aortic-specific mortality (HR, 2.83 [95% CI, 2.44-3.29]) compared with controls., Conclusions: Our results indicate that BAV and thoracic aortic disease carry a significant familial association for concordant disease and aortic dissection. The pattern of familiality is consistent with a genetic cause of disease. Furthermore, we observed higher risk of aortic-specific mortality in relatives of individuals with these diagnoses. This study provides supportive evidence for screening in relatives of patients with BAV, thoracic aneurysm, or dissection., Competing Interests: Disclosures None.

Background: Acute myocarditis can result in severe hemodynamic compromise requiring venoarterial extracorporeal membrane oxygenation (VA-ECMO). Outcomes and factors associated with mortality among myocarditis patients are not well described in the modern ECMO era., Methods: We queried the Extracorporeal Life Support Organization registry from 2011 to 2020 for adults with suspected acute myocarditis undergoing peripheral VA-ECMO support. The primary outcome was in-hospital mortality and was compared to all-comers receiving VA-ECMO in the registry over the same period. Secondary outcomes were rates of bridging to advanced therapies and ECMO complications. We used multivariable logistic regression to examine factors associated with in-hospital mortality., Results: Among 850 patients with suspected acute myocarditis receiving peripheral VA-ECMO, the mean age was 41 years, 52% were men, 39% Asian race, and 14.8% underwent extracorporeal cardiopulmonary resuscitation. During the study period, in-hospital mortality steadily declined and was 58.3% for all all-comers receiving VA-ECMO compared with 34.9% for patients with myocarditis ( P <0.001). After multivariable modeling, risk factors for mortality were earlier year of support, older age, higher weight, Asian race, need for extracorporeal cardiopulmonary resuscitation, sepsis, and lower mean arterial pressure and pH prior to ECMO initiation. ECMO complications including bleeding, limb ischemia, infections and ischemic stroke were more common among nonsurvivors and significantly declined during the study period., Conclusions: Compared with all-comers supported with VA-ECMO, in-hospital mortality for patients with acute myocarditis is significantly lower, with nearly two-thirds of patients surviving to discharge. Major modifiable risk factors for mortality were ongoing cardiopulmonary resuscitation requiring ECMO and markers of illness severity prior to ECMO., Competing Interests: Disclosures Dr Garan has received research support from Abbott Vascular and Verantos and is a consultant for Abiomed and NupulseCV. Dr Ho has received research support from Bayer AG. The other authors report no conflicts.

The primary objective was to investigate the association between partial pressure of carbon dioxide (PaCO 2 ) change after extracorporeal membrane oxygenation (ECMO) initiation and neurologic outcome in neonates treated for respiratory failure. A retrospective analysis of the Extracorporeal Life Support Organization (ELSO) database including newborns supported by ECMO for respiratory indication during 2015-2020. The closest Pre-ECMO (Pre-ECMO PaCO 2 ) and at 24 hours after ECMO initiation (H24 PaCO 2 ) PaCO 2 values allowed to calculate the relative change in PaCO 2 (Rel Δ PaCO 2 = [H24 PaCO 2 - Pre-ECMO PaCO 2 ]/Pre-ECMO PaCO 2 ). The primary outcome was the onset of any acute neurologic event (ANE), defined as cerebral bleeding, ischemic stroke, clinical or electrical seizure, or brain death during ECMO. We included 3,583 newborns (median age 1 day [interquartile range {IQR}, 1-3], median weight 3.2 kg [IQR, 2.8-3.6]) from 198 ELSO centers. The median Rel Δ PaCO 2 value was -29.9% [IQR, -46.2 to -8.5]. Six hundred nine (17%) of them had ANE (405 cerebral bleedings, 111 ischemic strokes, 225 seizures, and 6 brain deaths). Patients with a decrease of PaCO 2 > 50% were more likely to develop ANE than others (odds ratio [OR] 1.78, 95% confidence interval [CI], 1.31-2.42, p < 0.001). This was still observed after adjustment for all clinically relevant confounding factors (adjusted OR 1.94, 95% CI, 1.29-2.92, p = 0.001). A significant decrease in PaCO 2 after ECMO start is associated with ANE among neonates requiring ECMO for respiratory failure. Cautious PaCO 2 decrease should be considered after start of ECMO therapy., Competing Interests: J.E.T. is supported by a Career Development Award from the National Institutes of Health/National Heart, Lung, And Blood Institute (K23 HL141596). J.E.T. received speaker fees and travel compensation from LivaNova and Philips Healthcare, unrelated to this work. All other authors declare no conflict of interest., (Copyright © ASAIO 2022.)

Background: Exposure to hyperoxia, a high arterial partial pressure of oxygen (PaO2), may be associated with worse outcomes in patients receiving extracorporeal membrane oxygenator (ECMO) support. We examined hyperoxia in the Extracorporeal Life Support Organization Registry among patients receiving venoarterial ECMO for cardiogenic shock., Methods: We included Extracorporeal Life Support Organization Registry patients from 2010 to 2020 who received venoarterial ECMO for cardiogenic shock, excluding extracorporeal CPR. Patients were grouped based on PaO2 after 24 hours of ECMO: normoxia (PaO2 60-150 mmHg), mild hyperoxia (PaO2 151-300 mmHg), and severe hyperoxia (PaO2 >300 mmHg). In-hospital mortality was evaluated using multivariable logistic regression., Results: Among 9959 patients, 3005 (30.2%) patients had mild hyperoxia and 1972 (19.8%) had severe hyperoxia. In-hospital mortality increased across groups: normoxia, 47.8%; mild hyperoxia, 55.6% (adjusted odds ratio, 1.37 [95% CI, 1.23-1.53]; P <0.001); severe hyperoxia, 65.4% (adjusted odds ratio, 2.20 [95% CI, 1.92-2.52]; P <0.001). A higher PaO2 was incrementally associated with increased in-hospital mortality (adjusted odds ratio, 1.14 per 50 mmHg higher [95% CI, 1.12-1.16]; P <0.001). Patients with a higher PaO2 had increased in-hospital mortality in each subgroup and when stratified by ventilator settings, airway pressures, acid-base status, and other clinical variables. In the random forest model, PaO2 was the second strongest predictor of in-hospital mortality, after older age., Conclusions: Exposure to hyperoxia during venoarterial ECMO support for cardiogenic shock is strongly associated with increased in-hospital mortality, independent from hemodynamic and ventilatory status. Until clinical trial data are available, we suggest targeting a normal PaO2 and avoiding hyperoxia in CS patients receiving venoarterial ECMO.

Background: Acute brain injury (ABI) remains common after extracorporeal cardiopulmonary resuscitation (ECPR). Using a large international multicenter cohort, we investigated the impact of peri-cannulation arterial oxygen (PaO 2 ) and carbon dioxide (PaCO 2 ) on ABI occurrence., Methods: We retrospectively analyzed adult (≥18 years old) ECPR patients in the Extracorporeal Life Support Organization registry from 1/2009 through 12/2020. Composite ABI included ischemic stroke, intracranial hemorrhage (ICH), seizures, and brain death. The registry collects 2 blood gas data pre- (6 hours) and post- (24 hours) cannulation. Blood gas parameters were classified as: hypoxia (<60mm Hg), normoxia (60-119mm Hg), and mild (120-199mm Hg), moderate (200-299mm Hg), and severe hyperoxia (≥300mm Hg); hypocarbia (<35mm Hg), normocarbia (35-44mm Hg), mild (45-54mm Hg) and severe hypercarbia (≥55mm Hg). Missing values were handled using multiple imputation. Multivariable logistic regression analysis was used to assess the relationship of PaO 2 and PaCO 2 with ABI., Results: Of 3,125 patients with ECPR intervention (median age=58, 69% male), 488 (16%) experienced ABI (7% ischemic stroke; 3% ICH). In multivariable analysis, on-ECMO moderate (aOR=1.42, 95%CI: 1.02-1.97) and severe hyperoxia (aOR=1.59, 95%CI: 1.20-2.10) were associated with composite ABI. Additionally, severe hyperoxia was associated with ischemic stroke (aOR=1.63, 95%CI: 1.11-2.40), ICH (aOR=1.92, 95%CI: 1.08-3.40), and in-hospital mortality (aOR=1.58, 95%CI: 1.21-2.06). Mild hypercarbia pre-ECMO was protective of composite ABI (aOR=0.61, 95%CI: 0.44-0.84) and ischemic stroke (aOR=0.56, 95%CI: 0.35-0.89)., Conclusions: Early severe hyperoxia (≥300mm Hg) on ECMO was a significant risk factor for ABI and mortality. Careful consideration should be given in early oxygen delivery in ECPR patients who are at risk of reperfusion injury., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Neurologic complications can occur during neonatal Veno-Venous (VV) ECMO. The addition of a cephalad drainage cannula (i.e., VVDL+V) to dual lumen cannulation (i.e., VVDL) has been advocated to reduce such complications, but previous studies have presented mixed results., Methods: Data from the ECMO Registry of the Extracorporeal Life Support Organization was used to extract all neonates (≤28 days old) who underwent VV ECMO for respiratory support between 2000 and 2019. Primary outcomes were mortality, conversion to Veno-Arterial (VA) ECMO, pump flows, and complications. A mixed-effects, propensity score adjusted analysis was performed., Results: 4,275 neonates underwent VV ECMO, 581 (13.6%) via VVDL+V cannulation, and 3,694 (86.4%) via VVDL. On unadjusted analyses, VVDL+V patients had higher rates of mortality (25.5% vs 19.0%, p<0.001), conversion to VA ECMO (14.5% vs 4.1%, p<0.001), and higher pump flows at 4 h from ECMO initiation (112.7 vs 105.5 mL/Kg/min, p<0.001), but lower at 24 h (100.3 vs 104.0 mL/Kg/min, p = 0.004), and a higher proportion of them experienced hemorrhagic (29.3% vs 18.3%, p<0.001), cardiovascular (60.8% vs 45.8%, p<0.001), and mechanical (42.5% vs 32.6%, p<0.001) complications compared to VVDL patients. After adjusting for propensity scores and the multi-level nature of ELSO data, there were no differences in neurologic outcomes, pump flows, or mortality. Rather, VVDL+V cannulation was associated with higher rates of conversion to VA ECMO (adjusted odds ratio [AOR] 43.3, 95% CI 24.3 - 77.4, p<0.001), and increased mechanical (AOR 2.2, 95% CI 1.6 - 3.0, p<0.001) and hemorrhagic (AOR 2.0, 95% CI 1.4 - 3.0, p<0.001) complications., Conclusions: In this analysis, VVDL+V cannulation was not associated with any improvement in neurologic outcomes, pump flows, or mortality, but was rather associated with higher rates of conversion to Veno-Arterial ECMO, mechanical, and hemorrhagic complications., Competing Interests: Declarations of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Competing Interests: I am the Chair-elect of the Registry Committee of the Extracorporeal Life Support Organization. I am supported by a Career Development Award from the National Institutes of Health/National Heart, Lung, And Blood Institute (K23 HL141596). None of the funding sources were involved in the preparation of this Comment.

For patients on extracorporeal membrane oxygenation (ECMO) who require renal replacement therapy (RRT), dialysis can be achieved through a dedicated hemodialysis (HD) catheter or direct connection to the ECMO circuit. The relative effect of each on filtration efficacy is not known. We conducted a retrospective single-center analysis of patients on ECMO who required CRRT. We examined the outcomes of blood biomarkers and transmembrane filter pressures, comparing sessions by attachment approach. All analyses were clustered by patient. Of the 33 patients (7 ECMO access and 23 HD catheter access) that met the inclusion criteria, there were a total of 493 CRRT sessions (93 ECMO access and 400 HD catheter access). At the end of the first 12 h of CRRT therapy, the ECMO group had a greater rate of decline in serum BUN than the HD catheter access group (2.5 mg/dl (SD 11) vs. 2 mg/dl (SD 6), p = 0.035). Additionally, the platelet level was significantly higher in the ECMO group compared to the HD catheter access group after 72 h (94.5 k/uL (SD 41) vs. 71 k/uL (SD 29), p = 0.008). Utilizing the ECMO circuit as direct venous access for CRRT was associated with some improved filtration proximal outcomes.

Aims: Shock severity predicts mortality in patients with cardiogenic shock (CS). We evaluated the association between pre-cannulation Society for Cardiovascular Angiography and Intervention (SCAI) shock classification and mortality among patients receiving venoarterial (VA) extracorporeal membrane oxygenation (ECMO) support for CS., Methods and Results: We included Extracorporeal Life Support Organization (ELSO) Registry patients from 2010 to 2020 who received VA ECMO for CS. SCAI shock stage was assigned based on hemodynamic support requirements prior to ECMO initiation. In-hospital mortality was analyzed using multivariable logistic regression. We included 12 106 unique VA ECMO patient runs with a median age of 57.9 (interquartile range: 46.8, 66.1) years and 31.8% were females; 3472 (28.7%) were post-cardiotomy. The distribution of SCAI shock stages at ECMO initiation was: B, 821 (6.8%); C, 7518 (62.1%); D, 2973 (24.6%); and E, 794 (6.6%). During the index hospitalization, 6681 (55.2%) patients died. In-hospital mortality increased incrementally with SCAI shock stage (adjusted OR: 1.24 per SCAI shock stage, 95% CI: 1.17-1.32, P < 0.001): B, 47.5%; C, 52.8%; D, 60.8%; E, 65.1%. A higher SCAI shock stage was associated with increased in-hospital mortality in key subgroups, although the SCAI shock classification was only predictive of mortality in non-surgical (medical) CS and not in post-cardiotomy CS., Conclusion: The severity of shock prior to cannulation is a strong predictor of in-hospital mortality in patients receiving VA ECMO for CS. Using the pre-cannulation SCAI shock classification as a risk stratification tool can help clinicians refine prognostication for ECMO recipients and guide future investigations to improve outcomes., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The time between onset of cardiogenic shock and initiation of mechanical circulatory support is inversely related to patient survival as delays in transporting patients to the operating room (OR) for venoarterial extracorporeal membrane oxygenation (VA ECMO) could prove fatal. A primed and portable VA ECMO system may allow faster initiation of ECMO in various hospital locations and subsequently improve outcomes for patients in cardiogenic shock. We reviewed our institutional experience with VA ECMO based on two time periods: beginning of our VA ECMO program and from initiation of our primed and portable in-hospital ECMO system. The primary endpoint was patient survival to discharge. A total of 137 patients were placed on VA ECMO during the study period; n = 66 (48%) before and n = 71 (52%) after program initiation. In the second era, the proportion of OR ECMO initiation decreased significantly (from 92% to 49%, p < 0.01) as more patients received ECMO in other hospital units, including the emergency department (p < 0.01) and during cardiac arrest (12% vs. 38%, p < 0.01). Survival to hospital discharge was equivalent between the two groups (30% vs. 42%, p = 0.1) despite more patients being placed on ECMO during ongoing cardiac arrest. Finally, we observed increased clinical volume since initiation of the in-hospital, portable ECMO system. Developing an in-hospital, primed and portable VA ECMO program resulted in increased clinical volume with equivalent patient survival despite a sicker cohort of patients. We conclude that more rapid deployment of VA ECMO may extend the treatment eligibility to more patients and improve patient outcomes.

Background: Risk factors for bleeding complications during extracorporeal life support (ECLS) indicated for cardiac support remain poorly investigated. The aim is to develop and internally validate a prediction model to calculate the risk for bleeding complications in adult patients receiving veno-arterial (V-A) ECLS., Methods: Data of the Extracorporeal Life Support Organization registry of adult patients undergoing V-A ECLS between 2010 and 2020 were analyzed. The primary outcome was bleeding complications recorded during V-A ECLS. Multivariable logistic regression with backward stepwise elimination was used to develop the prediction model. Performance of the model was tested by discriminative ability and calibration with receiver operator characteristic, area under the curve, and visual inspection of the calibration plot. Internal validation was performed to detect overfitting of the model., Results: In total 28 767 adult patients were included, of which 29.0% developed bleeding complications. Sex, body mass index, surgical cannulation, pre-ECLS respiratory and hemodynamic variables, pre-ECLS support and interventions, and different type of diagnosis were included in the prediction model. This prediction model showed a predictive capability with an AUC of 0.66., Conclusion: The model is based on the largest cohort of V-A ECLS patients and is the best available predictive model for bleeding events given the predictors that are available in V-A ECLS compared to current literature. The model can help in identifying patients at high risk for bleeding complications and will help in developing further research and decision-making in terms of anticoagulation management. External validation is warranted to extrapolate this model in the clinical setting., (© 2022 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Background: There are limited studies regarding the effects of COVID-19 in patients with a concurrent diagnosis of opioid use disorder (OUD). Due to the rapidly developing nature and consequences of this disease, it is important to identify patients at an increased risk for serious illness. The aim of this study was to identify whether COVID-19 patients with OUD are at an increased risk of hospitalization and other adverse outcomes., Methods: This retrospective chart review compared clinical parameters from patients with positive COVID-19 status as identified by a positive SARS-CoV-2 PCR test and diagnosed OUD at the University of Utah Health. The primary outcome variables were hospitalization for COVID-19, length of hospital stay, and the presence of comorbidities in the OUD patient population. Descriptive statistics and prevalence ratios (PRs) were generated. Log binomial models generated PRs adjusted by age, sex, and race, and comorbidities of asthma, pneumonia, hypertension, cardiovascular disease, and diabetes., Results: COVID-19 patients with OUD were significantly more likely than patients without OUD to have asthma (p < 0.01), diabetes (p < 0.01), hypertension (p < 0.01), cardiovascular disease (p < 0.01), and chronic pneumonia (p < 0.01), and to be hospitalized (27.9 percent vs 3.6 percent; p < 0.01), admitted to the intensive care unit (11.5 percent vs 1.5 percent; p < 0.01), and receive mechanical ventilation (30.5 percent vs 0.1 percent; p < 0.01). After adjusting for age, sex, race, asthma, pneumonia, cardiovascular disease, hypertension, and diabetes, patients with OUD continued to be at increased risk for inpatient hospitalization (aPR = 4.27, 95 percent confidence interval [CI] = 1.66-10.94). Patients with OUD also averaged longer stays in the hospital than those without OUD (9.53 days vs 0.70 days, p < 0.001)., Conclusion: Patients with a diagnosis of OUD in the presence of COVID-19 are more likely to be hospitalized, have underlying health issues, and have longer hospital inpatient stays compared to patients without OUD.