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Bleeding is a well-known and severe complication of cardiac surgery. Cardiopulmonary bypass, along with heparinization and hemodilution, is thought to affect all pathways of the hemostatic process, leading to excessive bleeding and worsened morbidity and mortality. The traditionally used standard laboratory tests (SLTs) were not designed for the surgical setting, have long turnaround times, and are poor predictors of bleeding. This review aims to give an overview of viscoelastic assays (VEAs), compare VEAs to conventional testing methods, and summarize the evidence for VEAs in cardiac surgery. A search of Medline via Pubmed, Scopus, and Embase yielded 2,868 papers, which we reviewed and summarized the key findings. VEAs such as rotational thromboelastometry and thromboelastography provide a quick turnaround, graphical, global impression of hemostasis in whole blood. VEAs allow for the analysis of specific contributors to the coagulation process and may facilitate cause-oriented hemostatic treatment and the development of treatment algorithms. VEAs have been found to have a high specificity and high negative predictive value for coagulopathic bleeding. Patients treated with VEA-based algorithms have been shown to have lower rates of bleeding, transfusion requirements, and exposure to allogeneic blood products. However, VEA-based algorithms have not demonstrated a mortality benefit and evidence for outcomes such as surgical re-exploration and hospital length of stay remains equivocal. In conclusion, VEAs have been shown to be comparable if not superior to SLTs in cardiac surgery. Further large-scale studies are needed to better evaluate the impact of VEAs on clinical outcomes., Competing Interests: R.R.L. receives research support from the Clinician Scientist Development Unit, Yong Loo Lin School of Medicine, National University of Singapore. All other authors declare no competing interests., (Thieme. All rights reserved.)

Purpose: This study aimed to analyze data from the Extracorporeal Life Support Organization (ELSO) registry to elucidate the epidemiology and outcomes of patients with tuberculosis necessitating extracorporeal membrane oxygenation (ECMO), an intervention typically employed in treating severe acute respiratory distress syndrome (ARDS), but infrequently reported in tuberculosis contexts., Methods: A retrospective analysis was conducted utilizing the ELSO registry data spanning from 2003 to 2022, specifically targeting patients with tuberculosis who underwent ECMO. Primary outcomes included survival to hospital discharge, while secondary outcomes encompassed pre-ECMO support, ECMO duration, complications, and discharge destinations. Univariate and multivariate Cox proportional hazard regression analyses were employed to identify factors influencing survival rates., Results: The analysis included 169 patients with tuberculosis, with a median ECMO support duration of 233 h. The weaning success rate was recorded at 62.7 %, and 55 % of patients achieved survival to hospital discharge. Complications arose in 69.8 % of cases, predominantly mechanical complications (46.6 %). Multivariate Cox regression analysis identified complications (HR: 0.448, 95 % CI: 0.222-0.748, P=0.001), infections (HR: 0.483, 95 % CI: 0.241-0.808, P=0.001), and prolonged intervals from admission to ECMO initiation (HR: 0.698, 95 % CI: 0.396-0.901, P=0.018) as significant factors correlated with decreased survival likelihood., Conclusion: ECMO presents as a viable treatment option for patients with tuberculosis; however, timely initiation and meticulous management are critical to mitigate complications and enhance patient outcomes., Implication for Clinical Practice: Accurate identification of optimal ECMO initiation timing for eligible patients with tuberculosis can significantly enhance clinical outcomes in critical care settings, such as intensive care units., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Disclaimer: This Extracorporeal Life Support Organization guideline describes early rehabilitation or mobilization of patients on extracorporeal membrane oxygenation (ECMO). The guideline describes useful and safe practices put together by an international interprofessional team with extensive experience in the field of ECMO and ECMO rehabilitation or mobilization. The guideline is not intended to define the delivery of care or substitute sound clinical judgment. The guideline is subject to regular revision as new scientific evidence becomes available., Competing Interests: Disclosure: C.H. received research support from the NHMRC in Australia. She sits on the Executive and Scientific Committee of the International ECMO Network (ECMONet). She is leading an NHMRC-funded trial of early rehabilitation of patients during ECMO (NCT05003609). K.R. is the Extracorporeal Life Support Organization (ELSO) Chair of the Publications Committee. D.B. 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 ELSO and the Chair of the Executive Committee of the International ECMO Network (ECMONet) and he writes for UpToDate. K.S. received research support from the Metro North Hospital and Health Service. He is a member of the Scientific Committee of the International ECMO Network and Chair of the ELSO Guidelines & Protocol Committee. B.Z. is the ELSO Chair of Education. The other authors have no conflicts of interest to report., (Copyright © Extracorporeal Life Support Organization 2025.)

This retrospective analysis of the Extracorporeal Life Support Organization (ELSO) registry evaluates the outcomes and identifies risk factors associated with conversion from initial venovenous extracorporeal membrane oxygenation (ECMO) support to venoarterial or hybrid ECMO in patients with coronavirus disease 2019 (COVID-19). We collected deidentified data on all adult patients (≥18 years old) diagnosed with COVID who received venovenous extracorporeal membrane oxygenation between March 2020 and November 2022. Patients initially placed on an ECMO configuration other than venovenous (VV) ECMO were excluded from the analysis. Our analysis included data from 12,850 patients, of which 393 (3.1%) transitioned from VV ECMO to an alternative mode. The primary outcome measure was in-hospital mortality, and the conversion group exhibited a higher in-hospital mortality rate. We also examined baseline variables, including demographic information, biochemical labs, and inotrope requirements. Univariate analysis revealed that pre-ECMO arrest, the need for renal replacement therapy, and the use of inotropic agents, particularly milrinone, were strongly associated with the risk of conversion. Notably, even after implementing a 3:1 propensity score matching, the impact of conversion on both mortality and complications remained substantial. Our study underscores an elevated risk of mortality for COVID-19 patients initially treated with VV ECMO who subsequently require conversion to VA-ECMO or hybrid ECMO., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Background: Critical care of patients on extracorporeal membrane oxygenation (ECMO) with acute brain injury (ABI) is notable for a lack of high-quality clinical evidence. Here, we offer guidelines for neurological care (neurological monitoring and management) of adults during and after ECMO support., Methods: These guidelines are based on clinical practice consensus recommendations and scientific statements. We convened an international multidisciplinary consensus panel including 30 clinician-scientists with expertise in ECMO from all chapters of the Extracorporeal Life Support Organization (ELSO). We used a modified Delphi process with three rounds of voting and asked panelists to assess the recommendation levels., Results: We identified five key clinical areas needing guidance: (1) neurological monitoring, (2) post-cannulation early physiological targets and ABI, (3) neurological therapy including medical and surgical intervention, (4) neurological prognostication, and (5) neurological follow-up and outcomes. The consensus produced 30 statements and recommendations regarding key clinical areas. We identified several knowledge gaps to shape future research efforts., Conclusions: The impact of ABI on morbidity and mortality in ECMO patients is significant. Particularly, early detection and timely intervention are crucial for improving outcomes. These consensus recommendations and scientific statements serve to guide the neurological monitoring and prevention of ABI, and management strategy of ECMO-associated ABI., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the ASAIO.)

Purpose: Acute hypoxaemic respiratory failure (AHRF) is a common reason for intensive care unit (ICU) admission. However, patient characteristics, outcomes, and trends over time are unclear. We describe the epidemiology and outcomes of patients with AHRF over time., Methods: In this binational, registry-based study from 2005 to 2022, we included all adults admitted to an Australian or New Zealand ICU with an arterial blood gas within the first 24 h of ICU stay. AHRF was defined as a partial pressure of oxygen/inspired oxygen ratio (PaO 2 /FiO 2 ) ≤ 300. The primary outcome was adjusted in-hospital mortality, categorised based on PaO 2 /FiO 2 (mild: 200-300, moderate: 100-200, and severe < 100, and non-linearly). We investigated how adjusted mortality evolved based on temporal trends (by year of admission), sex, age, admission diagnosis and the receipt of mechanical ventilation., Results: Of 1,560,221 patients, 826,106 (52.9%) were admitted with or developed AHRF within the first 24 h of ICU stay. Of these 826,106 patients, 51.4% had mild, 39.3% had moderate, and 9.3% had severe AHRF. Compared to patients without AHRF (5.3%), patients with mild (8%), moderate (14.2%) and severe (29.9%) AHRF had higher in-hospital mortality rates. As PaO 2 /FiO 2 ratio decreased, adjusted in-hospital mortality progressively increased, particularly below an inflection point at a PaO 2 /FiO 2 ratio of 200. The adjusted in-hospital mortality for all patients decreased over time (13.3% in 2005 to 8.2% in 2022), and this trend was similar in patients with and without AHRF., Conclusion: The healthcare burden due to AHRF may be larger than expected, and mortality rates remain high in severe AHRF. Although mortality has decreased over time, this may reflect improvements in ICU care in general, rather than specifically in AHRF. More research is required to earlier identify AHRF and stratify these patients at risk of deterioration early, and to validate our findings., (© 2024. The Author(s).)

The management of cardiogenic shock is an ongoing challenge. Despite all efforts and tremendous use of resources, mortality remains high. Whilst reversing the underlying cause, restoring/maintaining organ perfusion and function are cornerstones of management. The presence of comorbidities and preexisting organ dysfunction increases management complexity, aiming to integrate the needs of vital organs in each individual patient. This review provides a comprehensive overview of contemporary literature regarding the definition and classification of cardiogenic shock, its pathophysiology, diagnosis, laboratory evaluation, and monitoring. Further, we distill the latest evidence in pharmacologic therapy and the use of mechanical circulatory support including recently published randomized-controlled trials as well as future directions of research, integrating this within an international group of authors to provide a global perspective. Finally, we explore the need for individualization, especially in the face of neutral randomized trials which may be related to a dilution of a potential benefit of an intervention (i.e., average effect) in this heterogeneous clinical syndrome, including the use of novel biomarkers, artificial intelligence, and machine learning approaches to identify specific endotypes of cardiogenic shock (i.e., subclasses with distinct underlying biological/molecular mechanisms) to support a more personalized medicine beyond the syndromic approach of cardiogenic shock., (© 2024. The Author(s).)

Competing Interests: RRL acknowledges research support outside of this work from the Clinician Scientist Development Unit, Yong Loo Lin School of Medicine, National University of Singapore. KR serves on the steering committee of the Extracorporeal Life Support Organisation, currently chairs its publication committee, and is the immediate past co-chair of the Scientific Oversight Committee. KS serves on the executive committee of the International ECMO Network.

Background: Critical care of patients on extracorporeal membrane oxygenation (ECMO) with acute brain injury (ABI) is notable for a lack of high-quality clinical evidence. Here, we offer guidelines for neurological care (neurological monitoring and management) of adults during and after ECMO support., Methods: These guidelines are based on clinical practice consensus recommendations and scientific statements. We convened an international multidisciplinary consensus panel including 30 clinician-scientists with expertise in ECMO from all chapters of the Extracorporeal Life Support Organization (ELSO). We used a modified Delphi process with three rounds of voting and asked panelists to assess the recommendation levels., Results: We identified five key clinical areas needing guidance: (1) neurological monitoring, (2) post-cannulation early physiological targets and ABI, (3) neurological therapy including medical and surgical intervention, (4) neurological prognostication, and (5) neurological follow-up and outcomes. The consensus produced 30 statements and recommendations regarding key clinical areas. We identified several knowledge gaps to shape future research efforts., Conclusions: The impact of ABI on morbidity and mortality in ECMO patients is significant. Particularly, early detection and timely intervention are crucial for improving outcomes. These consensus recommendations and scientific statements serve to guide the neurological monitoring and prevention of ABI, and management strategy of ECMO-associated ABI., (© 2024. The Author(s).)

Introduction: Myopericarditis is a rare but serious coronavirus disease 2019 (COVID-19) vaccine-related adverse event primarily affecting adolescents. Given recent approvals for childhood vaccination, we performed a meta-analysis investigating myopericarditis following messenger ribonucleic acid COVID-19 vaccination in children aged <19 years, focusing on its overall risk and high-risk subgroups., Methods: We searched MEDLINE via PubMed, Embase and Scopus from inception to 1 August 2022 for observational studies reporting myopericarditis in temporal relation to paediatric COVID-19 vaccination. We conducted random-effects meta-analyses (DerSimonian and Laird) on myopericarditis (primary outcome), myocarditis and pericarditis (secondary outcomes)., Results: Of 2115 studies, 12 (59,229,160 doses) studies were included in our analysis. There were 19.8 (95% confidence interval [CI]: 10.4-37.6) myopericarditis cases reported per million doses in children, compared to 23.7 (95% CI: 12.2-46.1) cases in adults (eight studies, 376,899,888 doses; P = 0.70). Compared to the second dose (34.4, 95% CI: 15.2-77.8), the number of cases post-first dose was significantly lower (9.1, 95% CI: 4.4-18.8; P = 0.017), while the number of cases post-third dose was not higher than that of post-second dose (28.4, 95% CI: 10.4-61.8; P = 0.57, global P = 0.031). Males were at higher risk of myopericarditis (67.4, 95% CI: 36.5-124.5) than females (6.9, 95% CI: 3.1-15.3; P < 0.0001). Finally, the number of cases was higher (overall P < 0.0001) among children aged ≥12 years (39.9, 95% CI: 24.1-66.0) than among children aged <12 years (3.0, 95% CI: 2.3-3.9)., Conclusion: Our meta-analysis showed 19.8 cases of myopericarditis per million doses among children, not significantly different from that of adults. Higher risk subgroups included adolescents, males, and those receiving their second dose of vaccination., (Copyright © 2024 Copyright: © 2024 Singapore Medical Journal.)

Purpose: Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is an integral part of the management algorithm of patients with severe respiratory failure refractory to evidence-based conventional treatments. Right ventricular injury (RVI) pertaining to abnormalities in the dimensions and/or function of the right ventricle (RV) in the context of VV-ECMO significantly influences mortality. However, in the absence of a universally accepted RVI definition and evidence-based guidance for the management of RVI in this very high-risk patient cohort, variations in clinical practice continue to exist., Methods: Following a systematic search of the literature, an international Steering Committee consisting of eight healthcare professionals involved in the management of patients receiving ECMO identified domains and knowledge gaps pertaining to RVI definition and management where the evidence is limited or ambiguous. Using a Delphi process, an international panel of 52 Experts developed Expert position statements in those areas. The process also conferred RV-centric overarching open questions for future research. Consensus was defined as achieved when 70% or more of the Experts agreed or disagreed on a Likert-scale statement or when 80% or more of the Experts agreed on a particular option in multiple-choice questions., Results: The Delphi process was conducted through four rounds and consensus was achieved on 31 (89%) of 35 statements from which 24 Expert position statements were derived. Expert position statements provided recommendations for RVI nomenclature in the setting of VV-ECMO, a multi-modal diagnostic approach to RVI, the timing and parameters of diagnostic echocardiography, and VV-ECMO settings during RVI assessment and management. Consensus was not reached on RV-protective driving pressure thresholds or the effect of prone positioning on patient-centric outcomes., Conclusion: The proposed definition of RVI in the context of VV-ECMO needs to be validated through a systematic aggregation of data across studies. Until further evidence emerges, the Expert position statements can guide informed decision-making in the management of these patients., (© 2024. Crown.)

Background: Mortality for patients receiving extracorporeal membrane oxygenation (ECMO) for COVID-19 increased over the course of the pandemic. We investigated the association between immunomodulators and mortality for patients receiving ECMO for COVID-19., Methods: We retrospectively analysed the Extracorporeal Life Support Organisation registry from 1 January, 2020, through 31 December, 2021, to compare the outcomes of patients who received no immunomodulators, only corticosteroids, only other immunomodulators (selective interleukin blockers, janus-kinase inhibitors, convalescent plasma, and intravenous immunoglobulin), and a combination of corticosteroids and other immunomodulators administered either before or during ECMO. We used Cox regression models to estimate survival time until 90 days. We estimated the propensity score of receiving different immunomodulators using multinomial regression, and incorporated these scores into the regression models., Results: We included 7181 patients in the final analysis; 6169 patients received immunomodulators either before or during ECMO. The 90-day survival was 58.1% (95%-CI 55.1-61.2%) for patients receiving no immunomodulators, 50.7% (95%-CI 49.0-52.5%) for those receiving only corticosteroids, 62.2% (95%-CI 57.4-67.0%) for those receiving other immunomodulators, and 48.5% (95%-CI 46.7-50.4%) for those receiving corticosteroids and other immunomodulators. Compared to patients without immunomodulators, patients receiving either corticosteroids alone (HR: 1.13, 95%-CI 1.01-1.28) or with other immunomodulators (HR: 1.21, 95%-CI: 1.07-1.54) had significantly shorter survival time, while patients receiving only other immunomodulators had significantly longer survival time (HR: 0.79, 95%-CI: 0.66-0.96). The receipt of immunomodulators (across all three groups) was associated with an increase in secondary infections., Conclusions: In this cohort study, we found that immunomodulators, in particular corticosteroids, were associated with significantly higher mortality amongst patients receiving ECMO for COVID-19, after adjusting for potential confounding variables and propensity score. In addition, patients receiving corticosteroids with or without other immunomodulators had longer ECMO runs, which has potential implications for resource allocation. While residual confounding likely remains, further studies are required to evaluate the timing of immunomodulators and better understand the possible mechanisms behind this association, including secondary infections., (© 2024. The Author(s).)

Background: Cerebral perfusion may change depending on arterial cannulation site and may affect the incidence of neurologic adverse events in post-cardiotomy extracorporeal life support (ECLS). The current study compares patients' neurologic outcomes with three commonly used arterial cannulation strategies (aortic vs. subclavian/axillary vs. femoral artery) to evaluate if each ECLS configuration is associated with different rates of neurologic complications., Methods: This retrospective, multicenter (34 centers), observational study included adults requiring post-cardiotomy ECLS between January 2000 and December 2020 present in the Post-Cardiotomy Extracorporeal Life Support (PELS) Study database. Patients with Aortic, Subclavian/Axillary and Femoral cannulation were compared on the incidence of a composite neurological end-point (ischemic stroke, cerebral hemorrhage, brain edema). Secondary outcomes were overall in-hospital mortality, neurologic complications as cause of in-hospital death, and post-operative minor neurologic complications (seizures). Association between cannulation and neurological outcomes were investigated through linear mixed-effects models., Results: This study included 1897 patients comprising 26.5% Aortic (n = 503), 20.9% Subclavian/Axillary (n = 397) and 52.6% Femoral (n = 997) cannulations. The Subclavian/Axillary group featured a more frequent history of hypertension, smoking, diabetes, previous myocardial infarction, dialysis, peripheral artery disease and previous stroke. Neuro-monitoring was used infrequently in all groups. Major neurologic complications were more frequent in Subclavian/Axillary (Aortic: n = 79, 15.8%; Subclavian/Axillary: n = 78, 19.6%; Femoral: n = 118, 11.9%; p < 0.001) also after mixed-effects model adjustment (OR 1.53 [95% CI 1.02-2.31], p = 0.041). Seizures were more common in Subclavian/Axillary (n = 13, 3.4%) than Aortic (n = 9, 1.8%) and Femoral cannulation (n = 12, 1.3%, p = 0.036). In-hospital mortality was higher after Aortic cannulation (Aortic: n = 344, 68.4%, Subclavian/Axillary: n = 223, 56.2%, Femoral: n = 587, 58.9%, p < 0.001), as shown by Kaplan-Meier curves. Anyhow, neurologic cause of death (Aortic: n = 12, 3.9%, Subclavian/Axillary: n = 14, 6.6%, Femoral: n = 28, 5.0%, p = 0.433) was similar., Conclusions: In this analysis of the PELS Study, Subclavian/Axillary cannulation was associated with higher rates of major neurologic complications and seizures. In-hospital mortality was higher after Aortic cannulation, despite no significant differences in incidence of neurological cause of death in these patients. These results encourage vigilance for neurologic complications and neuromonitoring use in patients on ECLS, especially with Subclavian/Axillary cannulation., (© 2024. The Author(s).)

The optimal pharmacological prophylaxis for venous thromboembolism (VTE) after hip or knee arthroplasty is uncertain. We conducted a systematic review and network meta-analysis to compare the efficacy and safety of various medications. We searched multiple databases for randomized clinical trials (RCTs) comparing medications (including factor Xa inhibitors, factor IIa inhibitor, warfarin, unfractionated heparin [UFH], low-molecular-weight heparin [LMWH], aspirin, pentasaccharide) for VTE prophylaxis post-arthroplasty. Outcomes included any postoperative VTE identified with screening, major bleeding, and death. We used LMWH as the main comparator for analysis and performed trial sequential analysis (TSA) for each pairwise comparison. Certainty of evidence was assessed using GRADE (Grading of Recommendations, Assessments, Developments and Evaluations). We analyzed 70 RCTs (55,841 participants). Factor Xa inhibitors decreased postoperative VTE significantly compared with LMWH (odds ratio [OR]: 0.55, 95% confidence interval [CI]: 0.44-0.68, high certainty). Pentasaccharides probably reduce VTE (OR: 0.61, 95% CI: 0.36-1.02, moderate certainty), while the factor IIa inhibitor dabigatran may reduce VTE (OR: 0.75, 95% CI: 0.40-1.42, low certainty). UFH probably increases VTE compared with LMWH (OR: 1.31, 95% CI: 0.91-1.89, moderate certainty), and other agents like warfarin, aspirin, placebo, and usual care without thromboprophylaxis increase VTE (high certainty). Factor Xa inhibitors may not significantly affect major bleeding compared with LMWH (OR: 1.06, 95% CI: 0.81-1.39, low certainty). No medications had a notable effect on mortality compared with LMWH (very low certainty). TSA suggests sufficient evidence for the benefit of factor Xa inhibitors over LMWH for VTE prevention. Compared with LMWH and aspirin, factor Xa inhibitors are associated with reduced VTE after hip or knee arthroplasty, without an increase in bleeding and likely no impact on mortality., Competing Interests: R.R.L. receives research support from the Clinician Scientist Development Unit, Yong Loo Lin School of Medicine, Singapore. All other authors declare no competing interests., (Thieme. All rights reserved.)

Artificial intelligence (AI) and its application in classification of blood cells in the peripheral blood film is an evolving field in haematology. We performed a rapid review of the literature on AI and peripheral blood films, evaluating the condition studied, image datasets, machine learning models, training set size, testing set size and accuracy. A total of 283 studies were identified, encompassing 6 broad domains: malaria (n = 95), leukemia (n = 81), leukocytes (n = 72), mixed (n = 25), erythrocytes (n = 15) or Myelodysplastic syndrome (MDS) (n = 1). These publications have demonstrated high self-reported mean accuracy rates across various studies (95.5% for malaria, 96.0% for leukemia, 94.4% for leukocytes, 95.2% for mixed studies and 91.2% for erythrocytes), with an overall mean accuracy of 95.1%. Despite the high accuracy, the challenges toward real world translational usage of these AI trained models include the need for well-validated multicentre data, data standardisation, and studies on less common cell types and non-malarial blood-borne parasites., Competing Interests: Declaration of Competing Interest We declare no conflicts of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) may reduce mortality and improve neurological outcomes in patients with cardiac arrest. We updated our existing meta-analysis and trial sequential analysis to further evaluate ECPR compared to conventional CPR (CCPR)., Methods: We searched three international databases from 1 January 2000 through 1 November 2023, for randomised controlled trials or propensity score matched studies (PSMs) comparing ECPR to CCPR in both out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA). We conducted an updated random-effects meta-analysis, with the primary outcome being in-hospital mortality. Secondary outcomes included short- and long-term favourable neurological outcome and survival (30 days-1 year). We also conducted a trial sequential analysis to evaluate the required information size in the meta-analysis to detect a clinically relevant reduction in mortality., Results: We included 13 studies with 14 pairwise comparisons (6336 ECPR and 7712 CCPR) in our updated meta-analysis. ECPR was associated with greater precision in reducing overall in-hospital mortality (OR 0.63, 95% CI 0.50-0.79, high certainty), to which the trial sequential analysis was concordant. The addition of recent studies revealed a newly significant decrease in mortality in OHCA (OR 0.62, 95% CI 0.45-0.84). Re-analysis of relevant secondary outcomes reaffirmed our initial findings of favourable short-term neurological outcomes and survival up to 30 days. Estimates for long-term neurological outcome and 90-day-1-year survival remained unchanged., Conclusions: We found that ECPR reduces in-hospital mortality, improves neurological outcome, and 30-day survival. We additionally found a newly significant benefit in OHCA, suggesting that ECPR may be considered in both IHCA and OHCA., (© 2024. The Author(s).)

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.)

Purpose: Cardiogenic shock is associated with high mortality. In refractory shock, it is unclear if mechanical circulatory support (MCS) devices improve survival. We conducted a network meta-analysis to determine which MCS devices confers greatest benefit., Methods: We searched MEDLINE, Embase, and Scopus databases through 27 August 2023 for relevant randomized controlled trials (RCTs) and propensity score-matched studies (PSMs). We conducted frequentist network meta-analysis, investigating mortality (either 30 days or in-hospital) as the primary outcome. We assessed risk of bias (Cochrane risk of bias 2.0 tool/Newcastle-Ottawa Scale) and as sensitivity analysis reconstructed survival data from published survival curves for a one-stage unadjusted individual patient data (IPD) meta-analysis using a stratified Cox model., Results: We included 38 studies (48,749 patients), mostly reporting on patients with Society for Cardiovascular Angiography and Intervention shock stages C-E cardiogenic shock. Compared with no MCS, extracorporeal membrane oxygenation with intra-aortic balloon pump (ECMO-IABP; network odds ratio [OR]: 0.54, 95% confidence interval (CI): 0.33-0.86, moderate certainty) was associated with lower mortality. There were no differences in mortality between ECMO, IABP, microaxial ventricular assist device (mVAD), ECMO-mVAD, centrifugal VAD, or mVAD-IABP and no MCS (all very low certainty). Our one-stage IPD survival meta-analysis based on the stratified Cox model found only ECMO-IABP was associated with lower mortality (hazard ratio, HR, 0.55, 95% CI 0.46-0.66)., Conclusion: In patients with cardiogenic shock, ECMO-IABP may reduce mortality, while other MCS devices did not reduce mortality. However, this must be interpreted within the context of inter-study heterogeneity and limited certainty of evidence., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: Declaration of Competing Interest We declare no competing interests.

Due to the paucity of longitudinal molecular studies of COVID-19, particularly those covering the early stages of infection (Days 1-8 symptom onset), our understanding of host response over the disease course is limited. We perform longitudinal single cell RNA-seq on 286 blood samples from 108 age- and sex-matched COVID-19 patients, including 73 with early samples. We examine discrete cell subtypes and continuous cell states longitudinally, and we identify upregulation of type I IFN-stimulated genes (ISGs) as the predominant early signature of subsequent worsening of symptoms, which we validate in an independent cohort and corroborate by plasma markers. However, ISG expression is dynamic in progressors, spiking early and then rapidly receding to the level of severity-matched non-progressors. In contrast, cross-sectional analysis shows that ISG expression is deficient and IFN suppressors such as SOCS3 are upregulated in severe and critical COVID-19. We validate the latter in four independent cohorts, and SOCS3 inhibition reduces SARS-CoV-2 replication in vitro. In summary, we identify complexity in type I IFN response to COVID-19, as well as a potential avenue for host-directed therapy., (© 2024. The Author(s).)

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.)

Purpose: We aimed to conduct a systematic review and meta-analysis to assess the effects of anemia and anemia severity on patient outcomes in cardiac surgery and determine whether preoperative treatments confer postoperative benefit., Source: We searched four international databases for observational and randomized studies published until 1 October 2022. Study quality was assessed via Newcastle-Ottawa scores and the Cochrane Risk-of-Bias 2 tool and certainty of evidence was rated with the Grading of Recommendations, Assessment, Development and Evaluations approach. We conducted random-effects meta-analyses for our primary outcome of mortality, for secondary outcomes including length of stay (LOS) in the hospital and intensive care unit, and for postsurgical complications. As part of a secondary analysis, we analyzed short-term preoperative anemia treatments and conducted trial sequential analysis of randomized trials to assess the efficacy of these treatment programs., Principal Findings: We included 35 studies (159,025 patients) in our primary meta-analysis. Preoperative anemia was associated with increased mortality (odds ratio [OR], 2.5; 95% confidence interval [CI], 2.2 to 2.9; P < 0.001, high certainty). Study-level meta-regression revealed lower hemoglobin levels and studies with lower proportions of male patients to be associated with increased risk of mortality. Preoperative anemia was also associated with an increase in LOS and postsurgical complications. Our secondary analysis (seven studies, 1,012 patients) revealed short-term preoperative anemia treatments did not significantly reduce mortality (OR, 1.1; 95% CI, 0.65 to 1.9; P = 0.69). Trial sequential analysis suggested that there was insufficient evidence to conclude if treatment programs yield any benefit or harm., Conclusions: Preoperative anemia is associated with mortality and morbidity after cardiac surgery. More research is warranted to test the efficacy of current anemia treatment programs., Study Registration: PROSPERO (CRD42022319431); first submitted 17 April 2023., (© 2023. Canadian Anesthesiologists' Society.)

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.)

The COVID-19 pandemic has undeniably changed the way intensivists manage acute hypoxaemic respiratory failure. Paradigms had evolved particularly in the way we support patients with respiratory failure, and the adjunctive therapies which can be used. Many questions have been answered, and many more generated, from the last few years. For example, is COVID-19 acute respiratory failure and acute respiratory distress syndrome similar to non-COVID-19? How can we personalize therapy in patients with COVID-19, and what are some new statistical tools that we can use to aid in this approach? Is intubation and invasive mechanical ventilation the only way to support patients with acute respiratory failure, or can we turn to other modalities of respiratory support? And what about patients with the most severe form of respiratory failure, how can we support them? In this chapter, we explore the lessons learnt, identifying gaps and advances in knowledge in terms of the pathophysiology of acute respiratory failure, its prognostic factors, oxygen supports, and other therapies. We also touch on how physicians treating patients can tap on international networks to create a "whole that is more than the sum of its parts", and impart clinical insights on the management of acute respiratory failure. Finally, we highlight the importance of a cautious skepticism in our approach to both clinical medicine and evidence-based medicine, highlighting how evidence in a pandemic can rapidly evolve both within an ICU, and longitudinally around the world., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Background: The use of extracorporeal membrane oxygenation (ECMO) for high-risk pulmonary embolism (HRPE) with haemodynamic instability or profound cardiogenic shock has been reported. Guidelines currently support the use of ECMO only in patients with cardiac arrest or circulatory collapse and in conjunction with other curative therapies. We aimed to characterise the mortality of adults with HRPE treated with ECMO, identify factors associated with mortality, and compare different adjunct curative therapies., Methods: We conducted a systematic review and meta-analysis, searching four international databases from their inception until 25 June 2023 for studies reporting on more than five patients receiving ECMO for HRPE. Random-effects meta-analyses were conducted. The primary outcome was in-hospital mortality. A subgroup analysis investigating the outcomes with curative treatment for HRPE was also performed. The intra-study risk of bias and the certainty of evidence were also assessed. This study was registered with PROSPERO (CRD42022297518)., Results: A total of 39 observational studies involving 6409 patients receiving ECMO for HRPE were included in the meta-analysis. The pooled mortality was 42.8% (95% confidence interval [CI]: 37.2% to 48.7%, moderate certainty). Patients treated with ECMO and catheter-directed therapy (28.6%) had significantly lower mortality ( p < 0.0001) compared to those treated with ECMO and systemic thrombolysis (57.0%). Cardiac arrest prior to ECMO initiation (regression coefficient [B]: 1.77, 95%-CI: 0.29 to 3.25, p = 0.018) and pre-ECMO heart rate (B: -0.076, 95%-CI: -0.12 to 0.035, p = 0.0003) were significantly associated with mortality. The pooled risk ratio when comparing mortality between patients on ECMO and those not on ECMO was 1.51 (95%-CI: 1.07 to 2.14, p < 0.01) in favour of ECMO. The pooled mortality was 55.2% (95%-CI: 47.7% to 62.6%), using trim-and-fill analysis to account for the significant publication bias., Conclusions: More than 50% of patients receiving ECMO for HRPE survive. While outcomes may vary based on the curative therapy used, early ECMO should be considered as a stabilising measure when treating patients with HRPE. Patients treated concurrently with systemic thrombolysis have higher mortality than those receiving ECMO alone or with other curative therapies, particularly catheter-directed therapies. Further studies are required to explore ECMO vs. non-ECMO therapies in view of currently heterogenous datasets.

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.)

Purpose: Venoarterial extracorporeal membrane oxygenation (V-A ECMO) can be used to support severely ill patients with cardiogenic shock. While age is commonly used in patient selection, little is known regarding its association with outcomes in this population. We sought to evaluate the association between increasing age and outcomes following V-A ECMO., Methods: We used individual-level patient data from 440 centers in the international Extracorporeal Life Support Organization registry. We included all adult patients receiving V-A ECMO from 2017 to 2019. The primary outcome was hospital mortality. Secondary outcomes included a composite of complications following initiation of V-A ECMO. We conducted Bayesian analyses of the relationship between increasing age and outcomes of interest., Results: We included 15,172 patients receiving V-A ECMO. Of these, 8172 (53.9%) died in hospital. For the analysis conducted using weakly informed priors, and as compared to the reference category of age 18-29, the age bracket of 30-39 (odds ratio [OR] 0.94, 95% credible interval [CrI] 0.79-1.10) was not associated with hospital mortality, but age brackets 40-49 (odds ratio [OR] 1.26, 95% CrI: 1.08-1.47), 50-59 (OR 1.78, 95% CrI: 1.55-2.06), 60-69 (OR 2.24, 95% CrI: 1.94-2.59), 70-79 (OR 2.90, 95% CrI: 2.49-3.39) and ≥ 80 (OR 4.02, 95% CrI: 3.13-5.20) were independently associated with increasing hospital mortality. Similar results were found in the analysis conducted with an informative prior, as well as between increasing age and post-ECMO complications., Conclusions: Among patients receiving V-A ECMO for cardiogenic shock, increasing age is strongly associated with increasing odds of death and complications, and this association emerges as early as 40 years of age., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Postcardiotomy extracorporeal membrane oxygenation (ECMO) can be initiated intraoperatively or postoperatively based on indications, settings, patient profile, and conditions. The topic of implantation timing only recently gained attention from the clinical community. We compare patient characteristics as well as in-hospital and long-term survival between intraoperative and postoperative ECMO., Methods: The retrospective, multicenter, observational Postcardiotomy Extracorporeal Life Support (PELS-1) study includes adults who required ECMO due to postcardiotomy shock between 2000 and 2020. We compared patients who received ECMO in the operating theater (intraoperative) with those in the intensive care unit (postoperative) on in-hospital and postdischarge outcomes., Results: We studied 2003 patients (women: 41.1%; median age: 65 years; interquartile range [IQR], 55.0-72.0). Intraoperative ECMO patients (n = 1287) compared with postoperative ECMO patients (n = 716) had worse preoperative risk profiles. Cardiogenic shock (45.3%), right ventricular failure (15.9%), and cardiac arrest (14.3%) were the main indications for postoperative ECMO initiation, with cannulation occurring after (median) 1 day (IQR, 1-3 days). Compared with intraoperative application, patients who received postoperative ECMO showed more complications, cardiac reoperations (intraoperative: 19.7%; postoperative: 24.8%, P = .011), percutaneous coronary interventions (intraoperative: 1.8%; postoperative: 3.6%, P = .026), and had greater in-hospital mortality (intraoperative: 57.5%; postoperative: 64.5%, P = .002). Among hospital survivors, ECMO duration was shorter after intraoperative ECMO (median, 104; IQR, 67.8-164.2 hours) compared with postoperative ECMO (median, 139.7; IQR, 95.8-192 hours, P < .001), whereas postdischarge long-term survival was similar between the 2 groups (P = .86)., Conclusions: Intraoperative and postoperative ECMO implantations are associated with different patient characteristics and outcomes, with greater complications and in-hospital mortality after postoperative ECMO. Strategies to identify the optimal location and timing of postcardiotomy ECMO in relation to specific patient characteristics are warranted to optimize in-hospital outcomes., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Personalized surgery is not just a new trend but rather a patient-specific approach to therapy that makes it possible to adopt a targeted approach for a specific patient and closely mirrors the approach of personalized medicine. However, the application of tailored surgery in the context of cardiovascular replacement surgery has not been systematically reviewed. The ability to customize a device is highly dependent on the collection of radiological image data for precise prosthesis modeling. These facts are essential to "tailor-made" device design for precise prosthesis implantation. According to this study, computed tomography (CT) was the most prominent imaging modality; however, transesophageal echocardiography and echocardiography were also found to be helpful. Additionally, a dynamic finite element simulation was also found to be an attractive alternative to the finite element analysis for an in-silico experiment. Nonetheless, there is a paucity of relevant publications and only sporadic evidence. More clinical studies have been warranted, notwithstanding that the derived data and results from this insight into the use of therapeutic interventions may be evidence of multiple directives in clinical practices and beyond. This study may help the integration of personalized devices for better comprehension of predicted clinical outcomes, thus leading towards enhanced performance gains.

Heart failure is a global health concern with significant implications for healthcare systems. Left ventricular assist devices (LVADs) provide mechanical support for patients with severe heart failure. However, the placement of the LVAD outflow graft within the aorta has substantial implications for hemodynamics and can lead to aortic insufficiency during long-term support. This study employs computational fluid dynamics (CFD) simulations to investigate the impact of different LVAD outflow graft locations on aortic hemodynamics. The introduction of valve morphology within the aorta geometry allows for a more detailed analysis of hemodynamics at the aortic root. The results demonstrate that the formation of vortex rings and subsequent vortices during the high-velocity jet flow from the graft interacted with the aortic wall. Time-averaged wall shear stress (TAWSS) and oscillatory shear index (OSI) indicate that modification of the outflow graft location changes mechanical states within the aortic wall and aortic valve. Among the studied geometric factors, both the height and inclination angle of the LVAD outflow graft are important in controlling retrograde flow to the aortic root, while the azimuthal angle primarily determines the rotational direction of blood flow in the aortic arch. Thus, precise positioning of the LVAD outflow graft emerges as a critical factor in optimizing patient outcomes by improving the hemodynamic environment.

Background: Although outcomes of patients after cardiac arrest remain poor, studies have suggested that extracorporeal cardiopulmonary resuscitation (ECPR) might improve survival and neurological outcomes. We aimed to investigate any potential benefits of using ECPR over conventional cardiopulmonary resuscitation (CCPR) in patients with out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA)., Methods: In this systematic review and meta-analysis, we searched MEDLINE via PubMed, Embase, and Scopus from Jan 1, 2000, to April 1, 2023, for randomised controlled trials and propensity-score matched studies. We included studies comparing ECPR with CCPR in adults (aged ≥18 years) with OHCA and IHCA. We extracted data from published reports using a prespecified data extraction form. We did random-effects (Mantel-Haenszel) meta-analyses and rated the certainty of evidence using the Grading of Recommendations, Assessments, Developments, and Evaluations (GRADE) approach. We rated the risk of bias of randomised controlled trials using the Cochrane risk-of-bias 2.0 tool, and that of observational studies using the Newcastle-Ottawa Scale. The primary outcome was in-hospital mortality. Secondary outcomes included complications during extracorporeal membrane oxygenation, short-term (from hospital discharge to 30 days after cardiac arrest) and long-term (≥90 days after cardiac arrest) survival with favourable neurological outcomes (defined as cerebral performance category scores 1 or 2), and survival at 30 days, 3 months, 6 months, and 1 year after cardiac arrest. We also did trial sequential analyses to evaluate the required information sizes in the meta-analyses to detect clinically relevant reductions in mortality., Findings: We included 11 studies (4595 patients receiving ECPR and 4597 patients receiving CCPR) in the meta-analysis. ECPR was associated with a significant reduction in overall in-hospital mortality (OR 0·67, 95% CI 0·51-0·87; p=0·0034; high certainty), without evidence of publication bias (p egger =0·19); the trial sequential analysis was concordant with the meta-analysis. When considering IHCA only, in-hospital mortality was lower in patients receiving ECPR than in those receiving CCPR (0·42, 0·25-0·70; p=0·0009), whereas when considering OHCA only, no differences were found (0·76, 0·54-1·07; p=0·12). Centre volume (ie, the number of ECPR runs done per year in each centre) was associated with reductions in odds of mortality (regression coefficient per doubling of centre volume -0·17, 95% CI -0·32 to -0·017; p=0·030). ECPR was also associated with an increased rate of short-term (OR 1·65, 95% CI 1·02-2·68; p=0·042; moderate certainty) and long-term (2·04, 1·41-2·94; p=0·0001; high certainty) survival with favourable neurological outcomes. Additionally, patients receiving ECPR had increased survival at 30-day (OR 1·45, 95% CI 1·08-1·96; p=0·015), 3-month (3·98, 1·12-14·16; p=0·033), 6-month (1·87, 1·36-2·57; p=0·0001), and 1-year (1·72, 1·52-1·95; p<0·0001) follow-ups., Interpretation: Compared with CCPR, ECPR reduced in-hospital mortality and improved long-term neurological outcomes and post-arrest survival, particularly in patients with IHCA. These findings suggest that ECPR could be considered for eligible patients with IHCA, although further research into patients with OHCA is warranted., Funding: None., Competing Interests: Declaration of interests KR is the Co-Chair of the ELSO scientific oversight committee. KR has received honoraria from Xenios for educational lectures on ECMO. RL is a Consultant for LivaNova, Medtronic, Abiomed, and Getinge (all honoraria are paid to his university to support research activities), and a member of the medical advisory board of Eurosets, Xenios, and HemoCue. GM is the President of ELSO. KS is a member of the scientific committee of the International ECMO Network and is the Chair of the research working group of ELSO education taskforce—ELSOed. KS reports receiving honoraria in relation to educational lectures on ECMO from Getinge. DB receives research support from, and consults for, LivaNova. DB has been on the medical advisory boards for Abiomed, Xenios, Medtronic, Inspira, and Cellenkos. DB is the President-elect of ELSO and the Chair of the executive committee of the International ECMO Network. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Research on fast-track recovery protocols postulates that thoracic epidural anesthesia (TEA) in cardiac surgery contributes to improved postoperative outcomes. However, concerns about TEA's safety hinder its widespread usage. We conducted a systematic review and meta-analysis to assess the benefits and risks of TEA in cardiac surgery., Methods: We searched 4 databases for randomized controlled trials (RCTs) assessing the use of TEA against only general anesthesia (GA) in adults undergoing cardiac surgery, up till June 4, 2022. We conducted random-effects meta-analyses, evaluated risk of bias using the Cochrane Risk-of-Bias 2 tool, and rated certainty of evidence via the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. Primary outcomes were intensive care unit (ICU), hospital length of stay, extubation time (ET), and mortality. Other outcomes included postoperative complications. Trial sequential analysis (TSA) was conducted on all outcomes to elicit statistical and clinical benefit., Results: Our meta-analysis included 51 RCTs (2112 TEA patients and 2220 GA patients). TEA significantly reduced ICU length of stay (-6.9 hours; 95% confidence interval [CI], -12.5 to -1.2; P = .018), hospital length of stay (-0.8 days; 95% CI, -1.1 to -0.4; P < .0001), and ET (-2.9 hours; 95% CI, -3.7 to -2.0; P < .0001). However, we found no significant change in mortality. TSA found that the cumulative Z-curve passed the TSA-adjusted boundary for ICU length of stay, hospital length of stay, and ET, suggesting a clinical benefit. TEA also significantly reduced pain scores, pooled pulmonary complications, transfusion requirements, delirium, and arrhythmia, without additional complications such as epidural hematomas, of which the risk was estimated to be <0.14%., Conclusions: TEA reduces ICU and hospital length of stay, and postoperative complications in patients undergoing cardiac surgery with minimal reported complications such as epidural hematomas. These findings favor the use of TEA in cardiac surgery and warrant consideration for use in cardiac surgeries worldwide., Competing Interests: Conflicts of Interests: See Disclosures at the end of the article., (Copyright © 2023 International Anesthesia Research Society.)

Introduction: Anticoagulation is recommended during continuous kidney replacement therapy (CKRT) to prolong the filter lifespan for optimal filter performance. We aimed to evaluate the effect of anticoagulation during CKRT on dialysis dependence and mortality within 90 days of intensive care unit (ICU) admission., Method: Our retrospective observational study evaluated the first CKRT session in critically ill adults with acute kidney injury (AKI) in Singapore from April to September 2017. The primary outcome was a composite of dialysis dependence or death within 90 days of ICU admission; the main exposure variable was anticoagulation use (regional citrate anticoagulation [RCA] or systemic heparin). Multivariable logistic regression was performed to adjust for possible confounders: age, female sex, Acute Physiology and Chronic Health Evaluation (APACHE II) score, liver dysfunction, coagulopathy (international normalised ratio[INR] >1.5) and platelet counts of less than 100,000/uL)., Results: The study cohort included 276 patients from 14 participating adult ICUs, of whom 176 (63.8%) experienced dialysis dependence or death within 90 days of ICU admission (19 dialysis dependence, 157 death). Anticoagulation significantly reduced the odds of the primary outcome (adjusted odds ratio [AOR] 0.47, 95% confidence interval [CI] 0.27-0.83, P=0.009). Logistic regression analysis using anticoagulation as a 3-level indicator variable demonstrated that RCA was associated with mortality reduction (AOR 0.46, 95% CI 0.25-0.83, P=0.011), with heparin having a consistent trend (AOR 0.51, 95% CI 0.23-1.14, P=0.102)., Conclusion: Among critically ill patients with AKI, anticoagulation use during CKRT was associated with reduced dialysis or death at 90 days post-ICU admission, which was statistically significant for regional citrate anticoagulation and trended in the same direction of benefit for systemic heparin anticoagulation. Anticoagulation during CKRT should be considered whenever possible., Competing Interests: The authors have no relevant financial or non-financial interests to disclose.

Background: With ideal mean arterial pressure (MAP) targets in resuscitated out-of-hospital cardiac arrest (OHCA) patients unknown, we performed a meta-analysis of randomised controlled trials (RCTs) to compare the effects of higher versus lower MAP targets., Methods: We searched four databases until 1 May 2023 for RCTs reporting the effects of higher MAP targets (>70 mmHg) in resuscitated OHCA patients and conducted random-effects meta-analyses. The primary outcome was mortality while secondary outcomes were neurological evaluations, arrhythmias, acute kidney injury, and durations of mechanical ventilation and ICU stay. We conducted inverse-variance weighted strata-level meta-regression against a proportion of non-survivors to assess differences between reported MAPs. We also conducted a trial sequential analysis of RCTs., Results: Four RCTs were included. Higher MAP was not associated with reduced mortality (OR: 1.09, 95%-CI: 0.84 to 1.42, p = 0.51), or improved neurological outcomes (OR: 0.99, 95%-CI: 0.77 to 1.27, p = 0.92). Such findings were consistent despite additional sensitivity analyses. Our robust variance strata-level meta-regression revealed no significant associations between mean MAP and the proportion of non-survivors (B: 0.029, 95%-CI: -0.023 to 0.081, p = 0.162), and trial sequential analysis revealed no meaningful survival benefit for higher MAPs., Conclusions: A higher MAP target was not significantly associated with improved mortality and neurological outcomes in resuscitated OHCA patients.

Competing Interests: None declared.

Background: A strategy that limits tidal volumes and inspiratory pressures, improves outcomes in patients with the acute respiratory distress syndrome (ARDS). Extracorporeal carbon dioxide removal (ECCO 2 R) may facilitate ultra-protective ventilation. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of venovenous ECCO 2 R in supporting ultra-protective ventilation in moderate-to-severe ARDS., Methods: MEDLINE and EMBASE were interrogated for studies (2000-2021) reporting venovenous ECCO 2 R use in patients with moderate-to-severe ARDS. Studies reporting ≥10 adult patients in English language journals were included. Ventilatory parameters after 24 h of initiating ECCO 2 R, device characteristics, and safety outcomes were collected. The primary outcome measure was the change in driving pressure at 24 h of ECCO 2 R therapy in relation to baseline. Secondary outcomes included change in tidal volume, gas exchange, and safety data., Results: Ten studies reporting 421 patients (PaO 2 :FiO 2 141.03 mmHg) were included. Extracorporeal blood flow rates ranged from 0.35-1.5 L/min. Random effects modelling indicated a 3.56 cmH 2 O reduction (95%-CI: 3.22-3.91) in driving pressure from baseline ( p < .001) and a 1.89 mL/kg (95%-CI: 1.75-2.02, p < .001) reduction in tidal volume. Oxygenation, respiratory rate and PEEP remained unchanged. No significant interactions between driving pressure reduction and baseline driving pressure, partial pressure of arterial carbon dioxide or PaO 2 :FiO 2 ratio were identified in metaregression analysis. Bleeding and haemolysis were the commonest complications of therapy., Conclusions: Venovenous ECCO 2 R permitted significant reductions in ∆P in patients with moderate-to-severe ARDS. Heterogeneity amongst studies and devices, a paucity of randomised controlled trials, and variable safety reporting calls for standardisation of outcome reporting. Prospective evaluation of optimal device operation and anticoagulation in high quality studies is required before further recommendations can be made.

Background: High-quality evidence for post-cardiotomy extracorporeal life support (PC-ECLS) management is lacking. This study investigated the real-world PC-ECLS clinical practices., Methods: This cross-sectional, multi-institutional, international pilot survey explored center organization, anticoagulation management, left ventricular unloading, distal limb perfusion, PC-ECLS monitoring and transfusions practices. Twenty-nine questions were distributed among 34 hospitals participating in the Post-cardiotomy Extra-Corporeal Life Support Study., Results: Of the 32 centers [16 low-volume (50%); 16 high-volume (50%)] that responded, 16 (50%) had dedicated ECLS specialists. Twenty-six centers (81.3%) reported using additional mechanical circulatory supports. Anticoagulation practices were highly heterogeneous: 24 hospitals (75%) reported using patient's bleeding status as a guide, without a specific threshold in 54.2% of cases. Transfusion targets ranged 7-10 g/dL. Most centers used cardiac venting on a case-by-case basis (78.1%) and regular distal limb perfusion (84.4%). Nineteen (54.9%) centers reported dedicated monitoring protocols including daily echocardiography (87.5%), Swan-Ganz catheterization (40.6%), cerebral near-infrared spectroscopy (53.1%) and multimodal assessment of limb ischemia. Inspection of the circuit (71.9%), oxygenator pressure drop (68.8%), plasma free hemoglobin (75%), d-dimer (59.4%), lactate dehydrogenase (56.3%) and fibrinogen (46.9%) are used to diagnose hemolysis and thrombosis., Conclusions: This study shows remarkable heterogeneity in clinical practices for PC-ECLS management. More standardized protocols and better implementation of available evidence are recommended., (This article is protected by copyright. All rights reserved.)

Competing Interests: We declare no competing interests.

Background: The high-quality evidence on managing COVID-19 patients requiring extracorporeal membrane oxygenation (ECMO) support is insufficient. Furthermore, there is little consensus on allocating ECMO resources when scarce. The paucity of evidence and the need for guidance on controversial topics required an international expert consensus statement to understand the role of ECMO in COVID-19 better. Twenty-two international ECMO experts worldwide work together to interpret the most recent findings of the evolving published research, statement formulation, and voting to achieve consensus., Objectives: To guide the next generation of ECMO practitioners during future pandemics on tackling controversial topics pertaining to using ECMO for patients with COVID-19-related severe ARDS., Methods: The scientific committee was assembled of five chairpersons with more than 5 years of ECMO experience and a critical care background. Their roles were modifying and restructuring the panel's questions and, assisting with statement formulation in addition to expert composition and literature review. Experts are identified based on their clinical experience with ECMO (minimum of 5 years) and previous academic activity on a global scale, with a focus on diversity in gender, geography, area of expertise, and level of seniority. We used the modified Delphi technique rounds and the nominal group technique (NGT) through three face-to-face meetings and the voting on the statement was conducted anonymously. The entire process was planned to be carried out in five phases: identifying the gap of knowledge, validation, statement formulation, voting, and drafting, respectively., Results: In phase I, the scientific committee obtained 52 questions on controversial topics in ECMO for COVID-19, further reviewed for duplication and redundancy in phase II, resulting in nine domains with 32 questions with a validation rate exceeding 75% (Fig. 1). In phase III, 25 questions were used to formulate 14 statements, and six questions achieved no consensus on the statements. In phase IV, two voting rounds resulted in 14 statements that reached a consensus are included in four domains which are: patient selection, ECMO clinical management, operational and logistics management, and ethics., Conclusion: Three years after the onset of COVID-19, our understanding of the role of ECMO has evolved. However, it is incomplete. Tota14 statements achieved consensus; included in four domains discussing patient selection, clinical ECMO management, operational and logistic ECMO management and ethics to guide next-generation ECMO providers during future pandemic situations., (© 2023. The Author(s).)

Background: Venovenous extracorporeal membrane oxygenation (ECMO) can be considered for patients with COVID-19-associated acute respiratory distress syndrome (ARDS) who continue to deteriorate despite evidence-based therapies and lung-protective ventilation. The Extracorporeal Life Support Organization has emphasised the importance of patient selection; however, to better inform these decisions, a comprehensive and evidence-based understanding of the risk factors associated with poor outcomes is necessary. We aimed to summarise the association between pre-cannulation prognostic factors and risk of mortality in adult patients requiring venovenous ECMO for the treatment of COVID-19., Methods: In this systematic review and meta-analysis, we searched MEDLINE and Embase from Dec 1, 2019, to April 14, 2022, for randomised controlled trials and observational studies involving adult patients who required ECMO for COVID-19-associated ARDS and for whom pre-cannulation prognostic factors associated with in-hospital mortality were evaluated. We conducted separate meta-analyses of unadjusted and adjusted odds ratios (uORs), adjusted hazard ratios (aHRs), and mean differences, and excluded studies if these data could not be extracted. We assessed the risk of bias using the Quality in Prognosis Studies tool and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. Our protocol was registered with the Open Science Framework registry, osf.io/6gcy2., Findings: Our search identified 2888 studies, of which 42 observational cohort studies involving 17 449 patients were included. Factors that had moderate or high certainty of association with increased mortality included patient factors, such as older age (adjusted hazard ratio [aHR] 2·27 [95% CI 1·63-3·16]), male sex (unadjusted odds ratio [uOR] 1·34 [1·20-1·49]), and chronic lung disease (aHR 1·55 [1·20-2·00]); pre-cannulation disease factors, such as longer duration of symptoms (mean difference 1·51 days [95% CI 0·36-2·65]), longer duration of invasive mechanical ventilation (uOR 1·94 [1·40-2·67]), higher partial pressure of arterial carbon dioxide (mean difference 4·04 mm Hg [1·64-6·44]), and higher driving pressure (aHR 2·36 [1·40-3·97]); and centre factors, such as less previous experience with ECMO (aOR 2·27 [1·28-4·05]., Interpretation: The prognostic factors identified highlight the importance of patient selection, the effect of injurious lung ventilation, and the potential opportunity for greater centralisation and collaboration in the use of ECMO for the treatment of COVID-19-associated ARDS. These factors should be carefully considered as part of a risk stratification framework when evaluating a patient for potential treatment with venovenous ECMO., Funding: None., Competing Interests: Declaration of interests RPB is Chair of the Extracorporeal Life Support Organization (ELSO) registry. GM serves on the Board of Directors for ELSO. KR reports honoraria from Baxter and Faesenius, outside of the submitted work. LJB reports research support from Medtronic and Draeger, and honoraria from Fisher Paykel, outside of the submitted work. NDF reports consulting fees from Baxter and Xenios, outside of the submitted work. ASS reports consulting fees from Baxter and Xenios, outside of the submitted work. He is the Chair of the Scientific Committee of the International ECMO Network (ECMONet). EF reports personal fees from ALung Technologies, Aerogen, Baxter, Boehringer-Ingelheim, GE Healthcare, Inspira, and Vasomune, outside of the submitted work. He is the Chair of the Data Committee of ECMONet. DB reports research support from Alung Technologies, outside of the submitted work. He has been on medical advisory boards for Abiomed, Xenios, Medtronic, LivaNova, Inspira, and Cellenkos, and is the President-Elect of ELSO and the Chair of the Executive Committee of ECMONet. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

A growing body of evidence supports the use of extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS) refractory to maximal medical therapy. ARDS may develop in a proportion of patients hospitalized for coronavirus disease 2019 (COVID-19) and ECMO may be used to manage patients refractory to maximal medical therapy to mitigate the risk of ventilator-induced lung injury and provide lung rest while awaiting recovery. The mortality of COVID-19-related ARDS was variously reassessed during the pandemic. Veno-venous (VV) ECMO was the default choice to manage refractory respiratory failure; however, with concomitant severe right ventricular dysfunction, venoarterial (VA) ECMO or mechanical right ventricular assist devices with extracorporeal gas exchange (Oxy-RVAD) were also considered. ECMO has also been used to manage special populations such as pregnant women, pediatric patients affected by severe forms of COVID-19, and, in cases with persistent and seemingly irreversible respiratory failure, as a bridge to successful lung transplantation. In this narrative review, we outline and summarize the most recent evidence that has emerged on ECMO use in different patient populations with COVID-19-related ARDS., (© 2023. The Author(s).)

Burns are among the leading causes of trauma worldwide, and acute respiratory distress syndrome (ARDS) is a common cause of death in burn patients. Some patients develop hypoxemia refractory to conventional therapies and may be initiated on extracorporeal membrane oxygenation (ECMO) as rescue therapy. We conducted a meta-analysis for studies reporting on survival rates of patients receiving ECMO for burns or inhalation injuries, which was the primary outcome. Secondary outcomes included the hospital and intensive care unit length of stay and duration of ECMO. Random-effects (DerSimonian and Laird) were conducted. The pooled survival from 10 studies was 53.6% (95% confidence interval [CI]: 37.6-69.2%, high certainty). Survival was significantly associated with age (regression coefficient [B]: -0.0088, 95% CI: -0.0155 to -0.0021, p = 0.011) and the proportion of male patients (B: -1.0137 95% CI: -1.9695 to -0.0580, p = 0.038). Patients were cannulated on ECMO for a mean of 8.4 days (95% CI: 6.1-10.7) and remained in the ICU for a mean of 40.4 days (95% CI: 11.4-69.3). Mean hospital length of stay was 45.4 days (95% CI: 31.7-59.0). In conclusion, patients with burn and inhalation injuries who develop ARDS refractory to conservative management have a survival rate of 54% when placed on ECMO., Competing Interests: Disclosure: K.R. currently serves as a co-chair of the Extracorporeal Life Support Organisation Scientific Oversight Committee. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2022.)