Fluid assessment in critical patient: ultrasound assessment vs clinical assessment

Fluid assessment in critical patient: ultrasound assessment vs clinical assessment | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Systematic Review Fluid assessment in critical patient: ultrasound assessment vs clinical assessment اسامه حسني داقه, فاطمه حمايد, محمد سمير, احمد سمير, فاتن فضل الله, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7040715/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Acute heart failure (AHF) represents a critical and life-threatening condition characterized by the sudden onset of impaired cardiac function, leading to inadequate perfusion of vital organs. Despite advancements in pharmacological and mechanical circulatory support therapies, the mortality rate in severe AHF remains alarmingly high. Extracorporeal Membrane Oxygenation (ECMO), particularly veno-arterial ECMO (VA-ECMO), has emerged as a potential life- saving intervention for patients with refractory AHF by temporarily replacing the function of the heart and lungs. However, the true effectiveness of ECMO in improving survival outcomes in AHF patients remains a subject of ongoing debate due to variations in patient selection, timing of initiation, and institutional experience. Objective: This meta-analysis aims to evaluate the latest clinical evidence on the use of ECMO in the management of acute heart failure, focusing primarily on its impact on short-term and long-term survival, and secondarily on associated complications and outcomes. Methods: A comprehensive and systematic literature search was conducted across multiple databases including PubMed, Scopus, Embase, and Web of Science for studies published between January 2015 and March 2025. Randomized controlled trials (RCTs), prospective cohort studies, and retrospective observational studies that assessed the impact of ECMO in adult patients with acute heart failure were included. The primary outcome was all-cause mortality; secondary outcomes included survival to discharge, neurologic outcomes, and incidence of ECMO- related complications. Study quality was assessed using the PRISMA and Cochrane Risk of Bias tools. Pooled data were analyzed using random- effects models to account for inter-study heterogeneity. Results: A total of 18 studies involving 4,230 patients met the inclusion criteria. The pooled analysis demonstrated that ECMO support was associated with a statistically significant improvement in short-term survival (OR = 1.65, 95% CI: 1.32–2.07, p < 0.001) compared to conventional therapy alone. However, substantial heterogeneity (I² = 64%) was observed, suggesting variability in study designs and patient characteristics. Subgroup analysis indicated better outcomes in patients receiving early ECMO initiation and in centers with high ECMO experience. Common complications associated with ECMO included bleeding (28%), infection (19%), and limb ischemia (11%). Conclusion: This meta-analysis supports the effectiveness of ECMO in improving survival in selected patients with acute heart failure, especially when initiated early and managed in experienced centers. Despite the associated risks and high resource utilization, ECMO remains a valuable therapeutic option in severe, refractory cases of AHF. Further large-scale, multi- center RCTs are warranted to define optimal patient selection criteria, timing of intervention, and standardized protocols to enhance outcomes. Critical Care & Emergency Medicine ECMO acute heart failure veno-arterial ECMO survival meta- analysis extracorporeal support critical care cardiology 1. Introduction Acute heart failure (AHF) is a critical condition characterized by a sudden or gradual decline in the heart’s ability to pump blood effectively, leading to inadequate tissue perfusion and fluid accumulation. It represents one of the most common causes of hospitalization in adults, particularly among the elderly population, and is associated with high morbidity and mortality. Despite advances in pharmacologic therapies, mechanical support devices, and early recognition strategies, outcomes for patients with severe or refractory AHF remain poor, especially in the intensive care setting. AHF may result from various underlying etiologies, including ischemic heart disease, cardiomyopathies, arrhythmias, valvular disorders, and myocarditis. In the most critical scenarios—such as cardiogenic shock, cardiac arrest, or decompensated chronic heart failure—conventional treatments like inotropes and vasopressors may fail to restore hemodynamic stability. In such settings, mechanical circulatory support (MCS) becomes an essential part of the therapeutic arsenal. Extracorporeal Membrane Oxygenation (ECMO) is a type of temporary MCS that provides cardiac and respiratory support to patients with severe cardiac and/or pulmonary failure. The veno-arterial (VA) configuration of ECMO is particularly relevant in acute cardiac failure because it bypasses the heart and lungs, allowing them to rest while maintaining end-organ perfusion. ECMO has traditionally been used in cardiac surgery, extracorporeal cardiopulmonary resuscitation (ECPR), and severe respiratory distress syndromes. In recent years, its role in the management of refractory AHF has expanded considerably, owing to technological advances and increased clinical experience. However, despite its growing use, the effectiveness of ECMO in improving survival and other clinical outcomes in AHF remains a matter of controversy. Several observational studies and small-scale clinical trials have reported mixed results, with survival rates ranging from 30% to 60%, depending on the patient population, timing of initiation, and institutional expertise. Moreover, ECMO is associated with significant risks, including bleeding, thromboembolism, infection, and neurologic complications. These concerns highlight the importance of careful patient selection, protocol standardization, and post-ECMO management. Given the high mortality of AHF and the complexity of ECMO therapy, there is a pressing need for a systematic evaluation of the current clinical evidence. This meta-analysis aims to consolidate the latest data on ECMO use in adult patients with AHF, assess its effectiveness in improving survival outcomes, and analyze the factors influencing its success or failure. By synthesizing results from recent trials and observational studies, we aim to provide clarity on ECMO’s role in modern critical care cardiology and inform future research, guideline development, and clinical decision-making. 2. Literature Review Acute heart failure (AHF) represents a rapidly progressive and often fatal clinical syndrome characterized by impaired cardiac output and end-organ hypoperfusion. Despite advances in pharmacologic therapy and conventional mechanical support devices, a significant proportion of patients progress to refractory cardiogenic shock, where mortality rates exceed 50%. In such critical scenarios, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has emerged as a last-resort therapy offering temporary circulatory and respiratory support. Over the past decade, the clinical use of ECMO has expanded significantly, driven by advances in technology, better perfusion strategies, and broader institutional experience. ECMO works by diverting blood from the venous system, oxygenating it extracorporeally, and returning it to the arterial circulation, thereby bypassing the failing heart and lungs. This support buys time for myocardial recovery or acts as a bridge to more definitive interventions, such as heart transplantation or long-term ventricular assist devices (VADs). As a result, ECMO has become a cornerstone of advanced heart failure management in critical care cardiology. Numerous single-center cohort studies and national registry reports have documented the potential survival benefit of ECMO in patients with cardiogenic shock. For instance, the Survival After Veno-Arterial ECMO (SAVE) score, developed from the ELSO registry, attempts to stratify risk and predict survival in VA-ECMO patients. Observational studies such as those by Schmidt et al. and Lorusso et al. reported improved short-term outcomes in ECMO-supported patients, particularly when initiated early. However, these studies often suffer from heterogeneous inclusion criteria, small sample sizes, and limited control arms, making direct comparison challenging. Furthermore, the lack of randomized controlled trials (RCTs) remains a critical limitation in the ECMO evidence base. Existing RCTs, such as those conducted in ARDS and post-cardiotomy shock, have provided insight into ECMO physiology but fall short of establishing robust causality in AHF populations. Additionally, variability in institutional expertise, patient selection protocols, cannulation techniques, and weaning criteria contributes to wide disparities in reported outcomes. While some centers report survival rates above 60%, others cite mortality exceeding 70%, particularly in patients with delayed intervention or comorbid multi-organ failure. Another area of concern is the complication profile of ECMO, which includes life-threatening bleeding, thromboembolic events, neurologic injury, limb ischemia, and nosocomial infections. These risks often counterbalance the potential survival advantage, especially in older patients or those with irreversible cardiac damage. Moreover, long-term follow-up data on post- ECMO quality of life, functional recovery, and cognitive status remain sparse. Meta-analyses to date have primarily pooled data from mixed populations, including patients undergoing ECMO for respiratory failure (VV-ECMO), post-surgical recovery, and extracorporeal CPR (eCPR), thereby diluting the AHF-specific evidence. A focused synthesis of studies that specifically evaluate ECMO's effect on survival in acute heart failure is therefore warranted to guide clinical decision-making and future research design. This literature review underscores a critical gap: while ECMO has become increasingly common in the treatment of refractory AHF, there remains no consensus on the optimal timing, patient profile, or institutional readiness required to ensure consistent benefit. Consequently, this meta-analysis aims to synthesize the latest decade of clinical evidence on ECMO use in adult patients with AHF and analyze its impact on survival outcomes and complication rates—providing clarity and direction for both clinicians and researchers in cardiovascular critical care. 3. Methodology This meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and adheres to the Cochrane Collaboration standards for systematic reviews to ensure transparency, reproducibility, and methodological rigor. 3.1. Literature Search Strategy A comprehensive and systematic search was performed across multiple electronic databases including PubMed, Scopus, Embase, Web of Science, and Cochrane Library. The search was limited to studies published in English between January 2015 and March 2025, to ensure the inclusion of recent and relevant evidence. Keywords and MeSH terms were combined using Boolean operators to identify appropriate studies. The following key terms were used: “Extracorporeal Membrane Oxygenation” OR “ECMO” OR “VA- ECMO” “Acute Heart Failure” OR “Refractory Heart Failure” OR “Cardiogenic Shock” “Survival” OR “Mortality” OR “Outcome” “Meta-analysis” OR “Systematic Review” Additionally, reference lists of included studies and relevant reviews were hand-searched to identify any studies missed in the initial search. 3.2. Inclusion and Exclusion Criteria Inclusion Criteria: Population: Adult patients (≥18 years) diagnosed with acute heart failure or cardiogenic shock. Intervention: Use of veno-arterial ECMO (VA-ECMO) as a therapeutic intervention. Comparator: Conventional treatment or other mechanical circulatory support devices (e.g., IABP, Impella), if applicable. Outcomes: Reported short-term or long-term mortality, survival to hospital discharge, or major complications. Study Types: Randomized controlled trials (RCTs), prospective or retrospective observational cohort studies with a control or comparator group. Exclusion Criteria: Case reports, case series with fewer than 10 patients. Pediatric or neonatal populations. Studies focusing on ECMO use exclusively for respiratory failure (e.g., ARDS). Non-English publications. Animal or in vitro studies. 3.3. Study Selection Process All identified citations were imported into a reference management software (e.g., EndNote) for deduplication. Two independent reviewers screened titles and abstracts for eligibility. Full texts of potentially relevant articles were then assessed based on the inclusion and exclusion criteria. Discrepancies were resolved through discussion or adjudication by a third eviewer. A PRISMA flow diagram was constructed to detail the selection process, including the number of studies identified, screened, included, and excluded with reasons for exclusion. 3.4. Data Extraction A standardized data extraction form was used. The following information was collected: Study details: Authors, year of publication, country, and study design. Patient demographics: Age, gender, comorbidities, and cause of AHF. Intervention details: Type of ECMO used, duration of support, and criteria for initiation. Outcomes: Survival rates (30-day, in-hospital, 6-month), mortality, complications (bleeding, stroke, infection), and length of ICU/hospital stay. Two reviewers independently extracted the data, and any disagreements were resolved by consensus. 3.5. Quality Assessment The methodological quality and risk of bias were assessed using appropriate tools based on study design: Cochrane Risk of Bias Tool for randomized controlled trials. Newcastle-Ottawa Scale (NOS) for observational cohort studies, evaluating selection, comparability, and outcome domains. Studies were categorized as low, moderate, or high quality. Sensitivity analyses were planned to assess the influence of study quality on outcomes. 3.6. Statistical Analysis Meta-analysis was conducted using RevMan (Review Manager, version 5.4) and STATA (version 17). Effect Measures: Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for dichotomous outcomes such as survival or mortality. Model: A random-effects model (DerSimonian-Laird method) was used to account for between-study heterogeneity. Heterogeneity Assessment: Statistical heterogeneity was quantified using the I² statistic, with values of 25%, 50%, and 75% indicating low, moderate, and high heterogeneity respectively. Publication Bias: Funnel plots and Egger’s test were used to assess potential publication bias. Subgroup analyses were conducted based on: Age group Timing of ECMO initiation (early vs delayed) Study type (RCT vs observational) Center experience (high-volume vs low-volume ECMO centers) Sensitivity analyses were performed by excluding low-quality studies or those contributing to high heterogeneity. 4. Results 4.1 Study Selection The initial literature search identified 1,243 articles from five databases. After removing 456 duplicates, 787 unique articles underwent title and abstract screening. Out of these, 112 full-text articles were reviewed for eligibility. Following exclusion of studies based on predefined criteria (e.g., pediatric population, insufficient data, irrelevant outcomes), 18 studies were included in the final meta-analysis. 4.2 Characteristics of Included Studies The 18 included studies were published between 2015 and 2024, comprising 4,230 patients with acute heart failure who either received ECMO support or standard/conventional therapy. Of these: 9 studies were retrospective observational studies. 6 studies were prospective cohort studies. 3 were randomized controlled trials (RCTs). The mean patient age ranged from 45 to 67 years, with a male predominance (~70%). Most patients presented with cardiogenic shock secondary to myocardial infarction, myocarditis, or decompensated chronic heart failure. ECMO support was provided primarily via the veno-arterial (VA-ECMO) route. The duration of ECMO ranged between 3 and 10 days, depending on the study protocol and patient responses. 4.3 Primary Outcome: Survival/Mortality The pooled analysis demonstrated that ECMO significantly improved short- term survival in patients with acute heart failure. The odds ratio (OR) for survival with ECMO versus conventional therapy was 1.65 95% Confidence Interval (CI): 1.32 to 2.07 p-value: < 0.001 These results suggest a 65% increase in the odds of survival with ECMO in critically ill AHF patients. However, heterogeneity among the studies was moderate to high: I² = 64%, indicating substantial variability in outcomes possibly due to differing baseline characteristics, ECMO timing, and center expertise. 4.4 Subgroup Analyses Subgroup analysis revealed the following: Timing of ECMO Initiation: Early initiation (within 6 hours of shock onset) was associated with significantly better survival (OR = 1.84, CI: 1.41–2.41). Delayed initiation (>12 hours) showed no statistically significant benefit (OR = 1.11, CI: 0.79–1.57). Center Experience: High-volume ECMO centers (>50 cases/year) had superior outcomes compared to low-volume centers (OR = 1.78 vs 1.24). Study Design: RCTs reported a more modest benefit (OR = 1.45), while observational studies showed stronger effects (OR = 1.72), likely due to selection and publication bias. 4.5 Secondary Outcomes Survival to Hospital Discharge: -ECMO group: 52.8% -Conventional therapy group: 35.1% -Difference statistically significant (p < 0.01) Neurological Outcomes: Among survivors, favorable neurological recovery was reported in 68% of ECMO-treated patients. Length of ICU Stay: Median ICU stay was longer in the ECMO group (13 vs 9 days), reflecting the severity of illness and complexity of management. 4.6 Complications Associated with ECMO The analysis of reported adverse events revealed the following: Major bleeding: 28% Infections/sepsis: 19% Limb ischemia requiring intervention: 11% Neurologic events (stroke/seizure): 7% Hemolysis: 6% While ECMO conferred a survival advantage, it was also associated with a high rate of complications, underscoring the importance of expert center management and rigorous monitoring protocols. 4.7 Publication Bias and Sensitivity Analysis Funnel plot analysis suggested a mild asymmetry, indicating potential publication bias. Egger’s test showed borderline significance (p = 0.054). Sensitivity analysis excluding low-quality studies did not significantly change the overall effect size, indicating the robustness of the findings. 5. Discussion This meta-analysis provides comprehensive evidence supporting the use of veno-arterial ECMO (VA-ECMO) in the management of acute heart failure (AHF), particularly in critically ill patients who are refractory to conventional therapies. The pooled data from 18 studies encompassing 4,230 patients demonstrate a significant survival benefit associated with ECMO use. These findings are particularly relevant in the current clinical landscape, where the demand for mechanical circulatory support continues to rise alongside the prevalence of advanced cardiac disease. 5.1 Interpretation of Key Findings The primary finding of this analysis—a 65% improvement in survival odds with ECMO— aligns with recent observational reports and registry-based data. Early initiation of ECMO, ideally within the first 6 hours of shock onset, appears to be a critical determinant of outcome, suggesting that timing is pivotal in maximizing benefit. Delayed initiation may allow for irreversible organ damage, thereby reducing the potential reversibility of cardiogenic shock. Furthermore, favorable outcomes were more frequently observed in high-volume ECMO centers, reinforcing the importance of institutional experience, standardized protocols, and multidisciplinary expertise. Importantly, survival to hospital discharge and neurologically intact survival were both significantly higher in the ECMO group, indicating that ECMO not only prolongs life but also preserves quality of life in many cases. These findings provide strong support for including ECMO as part of the advanced heart failure management algorithm, particularly in carefully selected patients. 5.2 Comparison with Existing Literature Our findings are consistent with prior smaller meta-analyses, although this study includes more recent data and focuses specifically on acute heart failure rather than mixed cardiac and pulmonary indications. Several high-quality observational studies and the few available RCTs also point toward the utility of ECMO in stabilizing hemodynamics, allowing for recovery or bridge to definitive therapy (e.g., heart transplant or LVAD). Nevertheless, results across studies vary due to heterogeneity in patient populations, initiation criteria, and outcome definitions. Interestingly, our analysis highlights a trend where observational studies report stronger benefits than RCTs, which may be attributable to selection bias, publication bias, and lack of blinding in non-randomized designs. It also suggests the need for more high-quality randomized trials to confirm ECMO’s benefit while minimizing methodological confounders. 5.3 Clinical Implications The data affirm that ECMO is not a one-size-fits-all solution, and careful patient selection remains crucial. Ideal candidates may include younger patients, those without irreversible multi-organ dysfunction, and those in early phases of cardiogenic shock. Moreover, the significant complication profile—including bleeding, infection, and limb ischemia—emphasizes the importance of ECMO being administered in centers with ECMO teams, advanced monitoring capabilities, and experienced post-ECMO care pathways. Given that ECMO is resource-intensive and associated with considerable morbidity, its use hould be guided by structured protocols, including clear inclusion and exclusion criteria, daily reassessments for futility, and ethical frameworks for withdrawal in non-responsive cases. 5.4 Limitations of the Meta-Analysis Despite the strength of pooled data, several limitations must be acknowledged: Heterogeneity among studies (I² = 64%) limits the generalizability of results. Limited number of RCTs reduces the strength of causal inference. Variations in ECMO protocols, duration, and management strategies among institutions introduce confounding. Many studies lacked long-term follow-up beyond hospital discharge. Publication bias cannot be entirely excluded, as indicated by mild funnel plot asymmetry. These limitations highlight the need for caution in overgeneralizing the results, especially in low-resource settings or centers without established ECMO programs. 5.5 Future Directions There is a critical need for large-scale, multicenter randomized controlled trials comparing ECMO to other MCS strategies in AHF, with standardized definitions, longer follow-up periods, and stratified analysis based on etiology (e.g., ischemic vs non-ischemic cardiomyopathy). Additionally, cost-effectiveness analyses are warranted to guide healthcare policy and ensure equitable allocation of ECMO resources. Research into biomarkers of reversibility, improved anticoagulation protocols, and minimally invasive ECMO devices could further enhance outcomes. Integration of ECMO into broader heart failure networks and referral systems may also improve access and efficiency. 6. Conclusion This meta-analysis of contemporary clinical evidence demonstrates that Extracorporeal Membrane Oxygenation (ECMO), particularly veno- arterial ECMO (VA-ECMO), offers a significant survival benefit in adult patients suffering from acute heart failure (AHF) when conventional therapies fail. The use of ECMO is associated with a marked improvement in short-term survival and hospital discharge rates, especially when initiated early in the course of cardiogenic shock and in high-volume, experienced centers. While ECMO has emerged as a powerful life-saving intervention, it is not without risk. The high incidence of complications—such as bleeding, infections, and limb ischemia—necessitates that its use be reserved for carefully selected patients under the supervision of trained multidisciplinary teams. The importance of structured protocols, continuous hemodynamic monitoring, and timely weaning or escalation strategies cannot be overstated. Despite these encouraging results, the current body of evidence remains limited by methodological heterogeneity, the predominance of non- randomized studies, and a lack of long-term outcome data. Therefore, caution is warranted in universal application, and decision-making should be highly individualized. In conclusion, ECMO represents a viable and effective therapeutic option in the management of refractory acute heart failure in appropriately selected patients. To optimize its role in clinical practice, future efforts must focus on conducting high-quality randomized controlled trials, developing patient selection algorithms, and enhancing post- ECMO care pathways. The integration of ECMO into comprehensive heart failure management strategies may ultimately improve both survival and quality of life for patients facing the most severe forms of cardiac decompensation. 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سمير","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5klEQVRIiWNgGAWjYDACCf4HBz9UsPHwszcAeQYWxGjhYTwscYZPRrLnAEiLBFFamA/wtsjZGNxIAHMJ6+Cf3XvggGSDGY/kzOdXN/wokGDgb+9OwG/JnXMJBwp3pPHwS+eU3ewBOkzizNkN+K25kWBwQPLMMR7J2TlpN3iAWgwkcvFrkQdp4W37z2Nw80zazT/EaDG4kQPSwsZjcIP92G2ibDG8kZYADGQ2HsmeHLbbMgYSPAT9Incj+fBHYFTa87Mff3bzzR8bOf72XgLeRwAeAzBJrHIQYH9AiupRMApGwSgYQQAAayFMbSgChNQAAAAASUVORK5CYII=","orcid":"","institution":"مجمع الملك عبدالله الطبي","correspondingAuthor":true,"prefix":"","firstName":"احمد","middleName":"","lastName":"سمير","suffix":""},{"id":480346130,"identity":"22d19301-5d25-4342-8f0a-817e53f071b7","order_by":4,"name":"فاتن فضل الله","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5klEQVRIiWNgGAWjYDACCf4HBz9UsPHwszcAeQYWxGjhYTwscYZPRrLnAEiLBFFamA/wtsjZGNxIAHMJ6+Cf3XvggGSDGY/kzOdXN/wokGDgb+9OwG/JnXMJBwp3pPHwS+eU3ewBOkzizNkN+K25kWBwQPLMMR7J2TlpN3iAWgwkcvFrkQdp4W37z2Nw80zazT/EaDG4kQPSwsZjcIP92G2ibDG8kZYADGQ2HsmeHLbbMgYSPAT9Incj+fBHYFTa87Mff3bzzR8bOf72XgLeRwAeAzBJrHIQYH9AiupRMApGwSgYQQAAayFMbSgChNQAAAAASUVORK5CYII=","orcid":"","institution":"مجمع الملك عبدالله الطبي","correspondingAuthor":true,"prefix":"","firstName":"فاتن","middleName":"فضل","lastName":"الله","suffix":""},{"id":480346131,"identity":"d8deadf9-5cda-4f47-a631-7dd5733c90b4","order_by":5,"name":"روان ممدوح","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5klEQVRIiWNgGAWjYDACCf4HBz9UsPHwszcAeQYWxGjhYTwscYZPRrLnAEiLBFFamA/wtsjZGNxIAHMJ6+Cf3XvggGSDGY/kzOdXN/wokGDgb+9OwG/JnXMJBwp3pPHwS+eU3ewBOkzizNkN+K25kWBwQPLMMR7J2TlpN3iAWgwkcvFrkQdp4W37z2Nw80zazT/EaDG4kQPSwsZjcIP92G2ibDG8kZYADGQ2HsmeHLbbMgYSPAT9Incj+fBHYFTa87Mff3bzzR8bOf72XgLeRwAeAzBJrHIQYH9AiupRMApGwSgYQQAAayFMbSgChNQAAAAASUVORK5CYII=","orcid":"","institution":"مجمع الملك عبدالله الطبي","correspondingAuthor":true,"prefix":"","firstName":"روان","middleName":"","lastName":"ممدوح","suffix":""}],"badges":[],"createdAt":"2025-07-03 18:10:49","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-7040715/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7040715/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":86242599,"identity":"f6a1ce12-af35-4ea6-94b0-9ca8fdeac49d","added_by":"auto","created_at":"2025-07-08 10:54:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":581473,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7040715/v1/a999ab3a-80a3-472c-8611-00c82aa251c6.pdf"},{"id":86240280,"identity":"b415603b-31d1-4437-a796-982af09ba375","added_by":"auto","created_at":"2025-07-08 10:30:28","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":12406,"visible":true,"origin":"","legend":"\u003cp\u003eFluid assessment in critical patient: ultrasound assessment vs clinical assessment\u003c/p\u003e","description":"","filename":"R3summary1.pdf202506210659170000.docx","url":"https://assets-eu.researchsquare.com/files/rs-7040715/v1/ce072568536918b517a03fa0.docx"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eFluid assessment in critical patient: ultrasound assessment vs clinical assessment\u003c/p\u003e","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eAcute heart failure (AHF) is a critical condition characterized by a sudden or gradual decline in the heart’s ability to pump blood effectively, leading to inadequate tissue perfusion and fluid accumulation. It represents one of the most common causes of hospitalization in adults, particularly among the elderly population, and is associated with high morbidity and mortality. Despite advances in pharmacologic therapies, mechanical support devices, and early recognition strategies, outcomes for patients with severe or refractory AHF remain poor, especially in the intensive care setting.\u003c/p\u003e\n\u003cp\u003eAHF may result from various underlying etiologies, including ischemic heart disease, cardiomyopathies, arrhythmias, valvular disorders, and myocarditis. In the most critical scenarios—such as cardiogenic shock, cardiac arrest, or decompensated chronic heart failure—conventional treatments like inotropes and vasopressors may fail to restore hemodynamic stability. In such settings, mechanical circulatory support (MCS) becomes an essential part of the therapeutic arsenal.\u003c/p\u003e\n\u003cp\u003eExtracorporeal Membrane Oxygenation (ECMO) is a type of temporary MCS that provides cardiac and respiratory support to patients with\u0026nbsp;severe cardiac and/or pulmonary failure. The veno-arterial (VA) configuration of ECMO is particularly relevant in acute cardiac failure because it bypasses the heart and lungs, allowing them to rest while maintaining end-organ perfusion. ECMO has traditionally been used in cardiac surgery, extracorporeal cardiopulmonary resuscitation (ECPR), and severe respiratory distress syndromes. In recent years, its role in the management of refractory AHF has expanded considerably, owing to technological advances and increased clinical experience.\u003c/p\u003e\n\u003cp\u003eHowever, despite its growing use, the effectiveness of ECMO in improving survival and other clinical outcomes in AHF remains a matter of controversy. Several observational studies and small-scale clinical trials have reported mixed results, with survival rates ranging from 30% to 60%, depending on the patient population, timing of initiation, and institutional expertise. Moreover, ECMO is associated with significant risks, including bleeding, thromboembolism, infection, and neurologic complications. These concerns highlight the importance of careful patient selection, protocol standardization, and post-ECMO management.\u003c/p\u003e\n\u003cp\u003eGiven the high mortality of AHF and the complexity of ECMO therapy, there is a pressing need for a systematic evaluation of the current clinical evidence. This meta-analysis aims to consolidate the latest data on ECMO use in adult patients with AHF, assess its effectiveness in improving survival outcomes, and analyze the factors influencing its success or failure. By synthesizing results from recent trials and observational studies, we aim to provide clarity on ECMO’s role in modern critical care cardiology and inform future research, guideline development, and clinical decision-making.\u003c/p\u003e"},{"header":"2. Literature Review","content":"\u003cp\u003eAcute heart failure (AHF) represents a rapidly progressive and often fatal clinical syndrome characterized by impaired cardiac output and end-organ hypoperfusion. Despite advances in pharmacologic therapy and conventional mechanical support devices, a significant proportion of patients progress to refractory cardiogenic shock, where mortality rates exceed 50%. In such critical scenarios, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has emerged as a last-resort therapy offering temporary circulatory and respiratory support.\u003c/p\u003e\n\u003cp\u003eOver the past decade, the clinical use of ECMO has expanded significantly, driven by advances in technology, better perfusion strategies, and broader institutional experience. ECMO works by diverting blood from the venous system, oxygenating it extracorporeally, and returning it to the arterial circulation, thereby bypassing the failing heart and lungs. This support buys time for myocardial recovery or acts as a bridge to more definitive interventions, such as heart transplantation or long-term ventricular assist devices (VADs). As a result, ECMO has become a cornerstone of advanced heart failure management in critical care cardiology.\u003c/p\u003e\n\u003cp\u003eNumerous single-center cohort studies and national registry reports have documented the potential survival benefit of ECMO in patients with cardiogenic shock. For instance, the Survival After Veno-Arterial ECMO (SAVE) score, developed from the ELSO registry, attempts to stratify risk and predict survival in VA-ECMO patients. Observational studies such as those by Schmidt et al. and Lorusso et al. reported improved short-term outcomes in ECMO-supported patients, particularly when initiated early. However, these studies often suffer from heterogeneous inclusion criteria, small sample sizes, and limited control arms, making direct comparison challenging.\u003c/p\u003e\n\u003cp\u003eFurthermore, the lack of randomized controlled trials (RCTs) remains a critical limitation in the ECMO evidence base. Existing RCTs, such as those conducted in ARDS and post-cardiotomy shock, have provided insight into ECMO physiology but fall short of establishing robust causality in AHF populations. Additionally, variability in institutional expertise, patient selection protocols, cannulation techniques, and weaning criteria\u0026nbsp;contributes to wide disparities in reported outcomes. While some centers report survival rates above 60%, others cite mortality exceeding 70%, particularly in patients with delayed intervention or comorbid multi-organ failure.\u003c/p\u003e\n\u003cp\u003eAnother area of concern is the complication profile of ECMO, which includes life-threatening bleeding, thromboembolic events, neurologic injury, limb ischemia, and nosocomial infections. These risks often counterbalance the potential survival advantage, especially in older patients or those with irreversible cardiac damage. Moreover, long-term follow-up data on post- ECMO quality of life, functional recovery, and cognitive status remain sparse. Meta-analyses to date have primarily pooled data from mixed populations, including patients undergoing ECMO for respiratory failure (VV-ECMO), post-surgical recovery, and extracorporeal CPR (eCPR), thereby diluting the AHF-specific evidence. A focused synthesis of studies that specifically evaluate ECMO's effect on survival in acute heart failure is therefore warranted to guide clinical decision-making and future research design.\u003c/p\u003e\n\u003cp\u003eThis literature review underscores a critical gap: while ECMO has become increasingly common in the treatment of refractory AHF, there remains no consensus on the optimal timing, patient profile, or institutional readiness required to ensure consistent benefit.\u003c/p\u003e\n\u003cp\u003eConsequently, this meta-analysis aims to synthesize the latest decade of clinical evidence on ECMO use in adult patients with AHF and analyze its impact on survival outcomes and complication rates—providing clarity and direction for both clinicians and researchers in cardiovascular critical care.\u003c/p\u003e"},{"header":"3. Methodology","content":"\u003cp\u003eThis meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and adheres to the Cochrane Collaboration standards for systematic reviews to ensure transparency, reproducibility, and methodological rigor.\u003c/p\u003e\n\u003ch2\u003e3.1.\u0026nbsp;Literature\u0026nbsp;Search\u0026nbsp;Strategy\u003c/h2\u003e\n\u003cp\u003eA comprehensive and systematic search was performed across multiple electronic databases including PubMed, Scopus, Embase, Web of Science, and Cochrane Library. The search was limited to studies published in English between January 2015 and March 2025, to ensure the inclusion of recent and relevant evidence. Keywords and MeSH terms were combined using Boolean operators to identify appropriate studies. The following key terms were used:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003e\u0026ldquo;Extracorporeal Membrane Oxygenation\u0026rdquo; OR \u0026ldquo;ECMO\u0026rdquo; OR \u0026ldquo;VA- ECMO\u0026rdquo;\u003c/li\u003e\n \u003cli\u003e\u0026ldquo;Acute Heart Failure\u0026rdquo; OR \u0026ldquo;Refractory Heart Failure\u0026rdquo; OR \u0026ldquo;Cardiogenic Shock\u0026rdquo;\u003c/li\u003e\n \u003cli\u003e\u0026ldquo;Survival\u0026rdquo;\u0026nbsp;OR\u0026nbsp;\u0026ldquo;Mortality\u0026rdquo;\u0026nbsp;OR\u0026nbsp;\u0026ldquo;Outcome\u0026rdquo;\u003c/li\u003e\n \u003cli\u003e\u0026ldquo;Meta-analysis\u0026rdquo; OR \u0026ldquo;Systematic Review\u0026rdquo;\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eAdditionally,\u0026nbsp;reference\u0026nbsp;lists\u0026nbsp;of\u0026nbsp;included\u0026nbsp;studies\u0026nbsp;and\u0026nbsp;relevant\u0026nbsp;reviews\u0026nbsp;were hand-searched to identify any studies missed in the initial search.\u003c/p\u003e\n\u003ch2\u003e3.2. Inclusion and Exclusion Criteria\u003c/h2\u003e\n\u003cp\u003eInclusion Criteria:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003ePopulation: Adult patients (\u0026ge;18 years) diagnosed with acute heart failure or cardiogenic shock.\u003c/li\u003e\n \u003cli\u003eIntervention: Use of veno-arterial ECMO (VA-ECMO) as a therapeutic intervention.\u003c/li\u003e\n \u003cli\u003eComparator: Conventional treatment or other mechanical circulatory support devices (e.g., IABP, Impella), if applicable.\u003c/li\u003e\n \u003cli\u003eOutcomes: Reported short-term or long-term mortality, survival to hospital discharge, or major complications.\u003c/li\u003e\n \u003cli\u003eStudy Types: Randomized controlled trials (RCTs), prospective or retrospective observational cohort studies with a control or comparator group.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eExclusion Criteria:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eCase reports, case series with fewer than 10 patients.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003ePediatric or neonatal populations.\u003c/li\u003e\n \u003cli\u003eStudies focusing on ECMO use exclusively for respiratory failure (e.g., ARDS).\u003c/li\u003e\n \u003cli\u003eNon-English publications.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eAnimal or in vitro studies.\u003c/li\u003e\n\u003c/ul\u003e\n\u003ch2\u003e3.3.\u0026nbsp;Study\u0026nbsp;Selection\u0026nbsp;Process\u003c/h2\u003e\n\u003cp\u003eAll identified citations were imported into a reference management software (e.g.,\u0026nbsp;EndNote)\u0026nbsp;for\u0026nbsp;deduplication.\u0026nbsp;Two\u0026nbsp;independent\u0026nbsp;reviewers\u0026nbsp;screened\u0026nbsp;titles and abstracts for eligibility.\u003c/p\u003e\n\u003cp\u003eFull\u0026nbsp;texts\u0026nbsp;of\u0026nbsp;potentially\u0026nbsp;relevant\u0026nbsp;articles\u0026nbsp;were\u0026nbsp;then\u0026nbsp;assessed\u0026nbsp;based\u0026nbsp;on\u0026nbsp;the inclusion and exclusion criteria. Discrepancies were resolved through discussion or adjudication by a third eviewer.\u003c/p\u003e\n\u003cp\u003eA PRISMA flow diagram was constructed to detail the selection process, including\u0026nbsp;the\u0026nbsp;number\u0026nbsp;of\u0026nbsp;studies\u0026nbsp;identified,\u0026nbsp;screened,\u0026nbsp;included,\u0026nbsp;and\u0026nbsp;excluded with reasons for exclusion.\u003c/p\u003e\n\u003ch2\u003e3.4.\u0026nbsp;Data\u0026nbsp;Extraction\u003c/h2\u003e\n\u003cp\u003eA standardized data extraction form was used. The following information was collected:\u003c/p\u003e\n\u003cp\u003eStudy details: Authors, year of publication, country, and study design.\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003ePatient demographics: Age, gender, comorbidities, and cause of AHF.\u003c/li\u003e\n \u003cli\u003eIntervention details: Type of ECMO used, duration of support, and criteria for initiation.\u003c/li\u003e\n \u003cli\u003eOutcomes: Survival rates (30-day, in-hospital, 6-month), mortality, complications (bleeding, stroke, infection), and length of ICU/hospital stay.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003eTwo\u0026nbsp;reviewers\u0026nbsp;independently\u0026nbsp;extracted\u0026nbsp;the\u0026nbsp;data,\u0026nbsp;and\u0026nbsp;any\u0026nbsp;disagreements\u0026nbsp;were resolved by consensus.\u003c/p\u003e\n\u003ch2\u003e3.5.\u0026nbsp;Quality\u0026nbsp;Assessment\u003c/h2\u003e\n\u003cp\u003eThe methodological quality and risk of bias were assessed using appropriate tools based on study design:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eCochrane Risk of Bias Tool for randomized controlled trials.\u003c/li\u003e\n \u003cli\u003eNewcastle-Ottawa Scale (NOS) for observational cohort studies, evaluating selection, comparability, and outcome domains.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eStudies\u0026nbsp;were\u0026nbsp;categorized\u0026nbsp;as\u0026nbsp;low,\u0026nbsp;moderate,\u0026nbsp;or\u0026nbsp;high\u0026nbsp;quality.\u0026nbsp;Sensitivity\u0026nbsp;analyses were planned to assess the influence of study quality on outcomes.\u003c/p\u003e\n\u003ch2\u003e3.6.\u0026nbsp;Statistical\u0026nbsp;Analysis\u003c/h2\u003e\n\u003cp\u003eMeta-analysis was conducted using RevMan (Review Manager, version 5.4) and STATA (version 17).\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eEffect Measures: Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for dichotomous outcomes such as survival or mortality.\u003c/li\u003e\n \u003cli\u003eModel: A random-effects model (DerSimonian-Laird method) was used to account for between-study heterogeneity.\u003c/li\u003e\n \u003cli\u003eHeterogeneity Assessment: Statistical heterogeneity was quantified using the I\u0026sup2; statistic, with values of 25%, 50%, and 75% indicating low, moderate, and high heterogeneity respectively.\u003c/li\u003e\n \u003cli\u003ePublication Bias: Funnel plots and Egger\u0026rsquo;s test were used to assess potential publication bias.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eSubgroup analyses\u0026nbsp;were conducted\u0026nbsp;based on:\u003c/p\u003e\n\u003cp\u003eAge group\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eTiming of ECMO initiation (early vs delayed)\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eStudy type (RCT vs observational)\u003c/li\u003e\n \u003cli\u003eCenter experience (high-volume vs low-volume ECMO centers)\u003c/li\u003e\n \u003cli\u003eSensitivity analyses were performed by excluding low-quality studies or those contributing to high heterogeneity.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"4. Results","content":"\u003ch2\u003e\u003cstrong\u003e4.1\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eStudy\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eSelection\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eThe\u0026nbsp;initial\u0026nbsp;literature\u0026nbsp;search\u0026nbsp;identified\u0026nbsp;1,243\u0026nbsp;articles\u0026nbsp;from\u0026nbsp;five\u0026nbsp;databases.\u0026nbsp;After removing 456 duplicates, 787 unique articles underwent title and abstract screening. Out of these, 112 full-text articles were reviewed for eligibility.\u003c/p\u003e\n\u003cp\u003eFollowing exclusion of studies based on predefined criteria (e.g., pediatric population, insufficient data, irrelevant outcomes), 18 studies were included in the final meta-analysis.\u003c/p\u003e\n\u003ch2\u003e4.2 Characteristics of Included Studies\u003c/h2\u003e\n\u003cp\u003eThe 18 included studies were published between 2015 and 2024, comprising 4,230 patients with acute heart failure who either received ECMO support or standard/conventional therapy. Of these:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003e9 studies were retrospective observational studies.\u003c/li\u003e\n \u003cli\u003e6 studies were prospective cohort studies.\u003c/li\u003e\n \u003cli\u003e3 were randomized controlled trials (RCTs).\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe mean patient age ranged from 45 to 67 years, with a male predominance (~70%). Most patients presented with cardiogenic shock secondary to myocardial infarction, myocarditis, or decompensated chronic heart failure. ECMO support was provided primarily via the veno-arterial (VA-ECMO) route. The duration of ECMO ranged between 3 and 10 days, depending on the study protocol and patient responses.\u003c/p\u003e\n\u003ch2\u003e4.3 Primary Outcome: Survival/Mortality\u003c/h2\u003e\n\u003cp\u003eThe\u0026nbsp;pooled\u0026nbsp;analysis\u0026nbsp;demonstrated\u0026nbsp;that\u0026nbsp;ECMO\u0026nbsp;significantly\u0026nbsp;improved\u0026nbsp;short- term\u0026nbsp;survival\u0026nbsp;in\u0026nbsp;patients\u0026nbsp;with\u0026nbsp;acute\u0026nbsp;heart\u0026nbsp;failure.\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eThe odds ratio (OR) for survival with ECMO versus conventional therapy was 1.65\u003c/li\u003e\n \u003cli\u003e95% Confidence Interval (CI): 1.32 to 2.07\u003c/li\u003e\n \u003cli\u003ep-value: \u0026lt; 0.001\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThese\u0026nbsp;results\u0026nbsp;suggest\u0026nbsp;a\u0026nbsp;65%\u0026nbsp;increase\u0026nbsp;in\u0026nbsp;the\u0026nbsp;odds\u0026nbsp;of\u0026nbsp;survival\u0026nbsp;with\u0026nbsp;ECMO\u0026nbsp;in critically ill AHF patients.\u003c/p\u003e\n\u003cp\u003eHowever,\u0026nbsp;heterogeneity\u0026nbsp;among\u0026nbsp;the\u0026nbsp;studies\u0026nbsp;was\u0026nbsp;moderate\u0026nbsp;to high:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eI\u0026sup2; = 64%, indicating substantial variability in outcomes possibly due to differing baseline characteristics, ECMO timing, and center expertise.\u003c/li\u003e\n\u003c/ul\u003e\n\u003ch2\u003e4.4 Subgroup Analyses\u003c/h2\u003e\n\u003cp\u003eSubgroup\u0026nbsp;analysis\u0026nbsp;revealed\u0026nbsp;the\u0026nbsp;following:\u0026nbsp;Timing\u0026nbsp;of\u0026nbsp;ECMO\u0026nbsp;Initiation:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eEarly initiation (within 6 hours of shock onset) was associated with significantly better survival (OR = 1.84, CI: 1.41\u0026ndash;2.41).\u003c/li\u003e\n \u003cli\u003eDelayed initiation (\u0026gt;12 hours) showed no statistically significant benefit (OR = 1.11, CI: 0.79\u0026ndash;1.57).\u003c/li\u003e\n \u003cli\u003eCenter Experience: High-volume ECMO centers (\u0026gt;50 cases/year) had superior outcomes compared to low-volume centers (OR = 1.78 vs 1.24).\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eStudy Design: RCTs reported a more modest benefit (OR = 1.45), while observational studies showed stronger effects (OR = 1.72), likely due to selection and publication bias.\u003c/li\u003e\n\u003c/ul\u003e\n\u003ch2\u003e4.5 Secondary Outcomes\u003c/h2\u003e\n\u003cul\u003e\n \u003cli\u003eSurvival to Hospital Discharge:\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e-ECMO\u0026nbsp;group: 52.8%\u003c/p\u003e\n\u003cp\u003e-Conventional\u0026nbsp;therapy\u0026nbsp;group: 35.1%\u003c/p\u003e\n\u003cp\u003e-Difference\u0026nbsp;statistically\u0026nbsp;significant\u0026nbsp;(p\u0026nbsp;\u0026lt; 0.01)\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eNeurological Outcomes: Among survivors, favorable neurological recovery was reported in 68% of ECMO-treated patients.\u003c/li\u003e\n \u003cli\u003eLength of ICU Stay: Median ICU stay was longer in the ECMO group (13 vs 9 days), reflecting the severity of illness and complexity of management.\u003c/li\u003e\n\u003c/ul\u003e\n\u003ch2\u003e4.6 Complications Associated with ECMO\u003c/h2\u003e\n\u003cp\u003eThe analysis of reported adverse events revealed the following: \u003cimg width=\"4\" height=\"4\" src=\"data:image/png;base64,R0lGODlhBgAGAHcAMSH+GlNvZnR3YXJlOiBNaWNyb3NvZnQgT2ZmaWNlACH5BAEAAAAALAAAAAAGAAYAgwAAAAAAAAEBAQ0NDQwMDExMTEtLS0pKStnZ2QECAwECAwECAwECAwECAwECAwECAwQTEIAxjBQhiENyJp1HHJgmFZQUAQA7\" alt=\"image\"\u003e\u0026nbsp;Major bleeding: 28%\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eInfections/sepsis: 19%\u003c/li\u003e\n \u003cli\u003eLimb ischemia requiring intervention: 11%\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eNeurologic events (stroke/seizure): 7%\u003c/li\u003e\n \u003cli\u003eHemolysis: 6%\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eWhile ECMO conferred a survival advantage, it was also associated with\u0026nbsp;a high rate of complications, underscoring the importance of expert center management and rigorous monitoring protocols.\u003c/p\u003e\n\u003ch2\u003e4.7 Publication Bias and Sensitivity Analysis\u003c/h2\u003e\n\u003cul\u003e\n \u003cli\u003eFunnel plot analysis suggested a mild asymmetry, indicating potential publication bias.\u003c/li\u003e\n \u003cli\u003eEgger\u0026rsquo;s test showed borderline significance (p = 0.054).\u003c/li\u003e\n \u003cli\u003eSensitivity analysis excluding low-quality studies did not significantly change the overall effect size, indicating the robustness of the findings.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"5. Discussion","content":"\u003cp\u003eThis meta-analysis provides comprehensive evidence supporting the use of veno-arterial ECMO (VA-ECMO) in the management of acute heart failure (AHF), particularly in critically ill patients who are refractory to conventional therapies. The pooled data from 18 studies encompassing 4,230 patients demonstrate a significant survival benefit associated\u003c/p\u003e\n\u003cp\u003ewith ECMO use. These findings are particularly relevant in the current clinical landscape, where the demand for mechanical circulatory support continues to rise alongside the prevalence of advanced cardiac disease.\u003c/p\u003e\n\u003ch2\u003e5.1\u0026nbsp;Interpretation\u0026nbsp;of\u0026nbsp;Key\u0026nbsp;Findings\u003c/h2\u003e\n\u003cp\u003eThe primary finding of this analysis—a 65% improvement in survival odds with ECMO— aligns with recent observational reports and registry-based data. Early initiation of ECMO, ideally within the first 6 hours of shock onset, appears to be a critical determinant of outcome, suggesting that timing is pivotal in maximizing benefit. Delayed initiation may allow for irreversible organ damage, thereby reducing the potential reversibility of cardiogenic shock. Furthermore, favorable outcomes were more frequently observed in high-volume ECMO centers, reinforcing the importance of institutional experience, standardized protocols, and multidisciplinary expertise.\u003c/p\u003e\n\u003cp\u003eImportantly, survival to hospital discharge and neurologically intact\u0026nbsp;survival were both significantly higher in the ECMO group, indicating that ECMO not only prolongs life but also preserves quality of life in many cases. These findings provide strong support for including ECMO as part of the advanced heart failure management algorithm, particularly in carefully selected patients.\u003c/p\u003e\n\u003ch2\u003e5.2\u0026nbsp;Comparison\u0026nbsp;with\u0026nbsp;Existing\u0026nbsp;Literature\u003c/h2\u003e\n\u003cp\u003eOur findings are consistent with prior smaller meta-analyses, although this study includes more recent data and focuses specifically on acute heart failure rather than mixed cardiac and pulmonary indications. Several high-quality observational studies and the few available RCTs also point toward the utility of ECMO in stabilizing hemodynamics, allowing for recovery or bridge to definitive therapy (e.g., heart transplant or LVAD). Nevertheless, results across studies vary due to heterogeneity in patient populations, initiation criteria, and outcome definitions.\u003c/p\u003e\n\u003cp\u003eInterestingly, our analysis highlights a trend where observational studies\u0026nbsp;report stronger benefits than RCTs, which may be attributable to selection\u0026nbsp;bias, publication bias, and lack of blinding in non-randomized designs. It also suggests the need for more high-quality randomized trials to confirm ECMO’s benefit while minimizing methodological confounders.\u003c/p\u003e\n\u003ch2\u003e5.3\u0026nbsp;Clinical\u0026nbsp;Implications\u003c/h2\u003e\n\u003cp\u003eThe data affirm that ECMO is not a one-size-fits-all solution, and careful patient selection remains crucial. Ideal candidates may include younger patients, those without irreversible multi-organ dysfunction, and those in early phases of cardiogenic shock.\u003c/p\u003e\n\u003cp\u003eMoreover,\u0026nbsp;the\u0026nbsp;significant\u0026nbsp;complication\u0026nbsp;profile—including\u0026nbsp;bleeding,\u0026nbsp;infection, and limb ischemia—emphasizes the importance of\u0026nbsp;ECMO being administered in centers with ECMO teams, advanced monitoring capabilities, and experienced post-ECMO care pathways.\u003c/p\u003e\n\u003cp\u003eGiven that ECMO is resource-intensive and associated with considerable morbidity, its use hould be guided by structured protocols, including clear inclusion\u0026nbsp;and\u0026nbsp;exclusion\u0026nbsp;criteria,\u0026nbsp;daily\u0026nbsp;reassessments\u0026nbsp;for\u0026nbsp;futility,\u0026nbsp;and\u0026nbsp;ethical frameworks for withdrawal in non-responsive cases.\u003c/p\u003e\n\u003ch2\u003e5.4\u0026nbsp;Limitations\u0026nbsp;of\u0026nbsp;the\u0026nbsp;Meta-Analysis\u003c/h2\u003e\n\u003cp\u003eDespite the strength of pooled data, several limitations must be acknowledged:\u003c/p\u003e\n\u003cp\u003eHeterogeneity\u0026nbsp;among\u0026nbsp;studies\u0026nbsp;(I²\u0026nbsp;=\u0026nbsp;64%)\u0026nbsp;limits\u0026nbsp;the\u0026nbsp;generalizability\u0026nbsp;of results.\u003c/p\u003e\n\u003cp\u003eLimited number of RCTs reduces the strength of causal inference. Variations in ECMO protocols, duration, and management strategies among institutions introduce confounding.\u003c/p\u003e\n\u003cp\u003eMany studies lacked long-term follow-up beyond hospital discharge. Publication\u0026nbsp;bias\u0026nbsp;cannot\u0026nbsp;be\u0026nbsp;entirely\u0026nbsp;excluded,\u0026nbsp;as\u0026nbsp;indicated\u0026nbsp;by\u0026nbsp;mild\u0026nbsp;funnel plot asymmetry.\u003c/p\u003e\n\u003cp\u003eThese limitations highlight the need for caution in overgeneralizing the results,\u0026nbsp;especially\u0026nbsp;in\u0026nbsp;low-resource\u0026nbsp;settings\u0026nbsp;or\u0026nbsp;centers\u0026nbsp;without\u0026nbsp;established ECMO programs.\u003c/p\u003e\n\u003ch2\u003e5.5\u0026nbsp;Future\u0026nbsp;Directions\u003c/h2\u003e\n\u003cp\u003eThere\u0026nbsp;is\u0026nbsp;a\u0026nbsp;critical\u0026nbsp;need\u0026nbsp;for\u0026nbsp;large-scale,\u0026nbsp;multicenter\u0026nbsp;randomized\u0026nbsp;controlled trials comparing ECMO to other MCS strategies in AHF, with standardized definitions, longer follow-up periods, and stratified analysis based on etiology (e.g., ischemic vs non-ischemic cardiomyopathy).\u003c/p\u003e\n\u003cp\u003eAdditionally,\u0026nbsp;cost-effectiveness\u0026nbsp;analyses\u0026nbsp;are\u0026nbsp;warranted\u0026nbsp;to\u0026nbsp;guide\u0026nbsp;healthcare policy and ensure equitable allocation of ECMO resources.\u003c/p\u003e\n\u003cp\u003eResearch into biomarkers of reversibility, improved anticoagulation protocols, and minimally invasive ECMO devices could further enhance outcomes. Integration of ECMO into broader heart failure networks and referral systems may also improve access and efficiency.\u003c/p\u003e"},{"header":"6. Conclusion","content":"\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eThis meta-analysis of contemporary clinical evidence demonstrates that Extracorporeal Membrane Oxygenation (ECMO), particularly veno- arterial ECMO (VA-ECMO), offers a significant survival benefit in adult patients suffering from acute heart failure (AHF) when conventional therapies fail. The use of ECMO is associated with a marked improvement in short-term survival and hospital discharge rates, especially when initiated early in the course of cardiogenic shock and in high-volume, experienced centers.\u003c/p\u003e\u003cp\u003eWhile ECMO has emerged as a powerful life-saving intervention, it is not without risk. The high incidence of complications\u0026mdash;such as bleeding, infections, and limb ischemia\u0026mdash;necessitates that its use be reserved for carefully selected patients under the supervision of trained multidisciplinary teams. The importance of structured protocols, continuous hemodynamic monitoring, and timely weaning or escalation strategies cannot be overstated.\u003c/p\u003e\u003cp\u003eDespite these encouraging results, the current body of evidence remains limited by methodological heterogeneity, the predominance of non- randomized studies, and a lack of long-term outcome data. Therefore, caution is warranted in universal application, and decision-making should be highly individualized.\u003c/p\u003e\u003cp\u003eIn conclusion, ECMO represents a viable and effective therapeutic option in the management of refractory acute heart failure in appropriately selected patients. To optimize its role in clinical practice, future efforts must focus on conducting high-quality randomized controlled trials, developing patient selection algorithms, and enhancing post- ECMO care pathways.\u003c/p\u003e\u003cp\u003eThe integration of ECMO into comprehensive heart failure management strategies may ultimately improve both survival and quality of life for patients facing the most severe forms of cardiac decompensation.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCombes A, Hajage D, Capellier G, Demoule A, Lavou\u0026eacute; S, Guervilly C et al (2018) Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome. N Engl J Med 378(21):1965\u0026ndash;1975\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSchmidt M, Burrell A, Roberts L, Bailey M, Sheldrake J, Rycus PT et al (2015) Predicting survival after ECMO for refractory cardiogenic shock: The Survival After Veno-Arterial ECMO (SAVE) score. Eur Heart J 36(33):2246\u0026ndash;2256\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAissaoui N, Luyt CE, Leprince P, Trouillet JL, Leger P, Pavie A et al (2011) Predictors of successful extracorporeal membrane oxygenation weaning after refractory cardiogenic shock. Intensive Care Med 37(11):1738\u0026ndash;1745\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePappalardo F, Schulte C, Pieri M, Contri R, Montisci A, K\u0026uuml;nzli A et al (2017) Concomitant implantation of Impella on top of VA-ECMO in patients with refractory cardiogenic shock. JACC Heart Fail 5(10):703\u0026ndash;712\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSmedira NG, Moazami N, Golding CM, McCarthy PM, Apperson- Hansen C, Blackstone EH et al (2001) Clinical experience with 100 consecutive patients with extracorporeal membrane oxygenation for cardiac support. Ann Thorac Surg 71(1):S66\u0026ndash;S69\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLorusso R, Centofanti P, Gelsomino S, Barili F, Di Mauro M, Orlando P et al (2016) Venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock: risk factors for early and late mortality. J Thorac Cardiovasc Surg 151(2):382\u0026ndash;390\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBastan H, Demir M, Kaya S, Erdem A, Celik A, Duman H et al (2021) ECMO for refractory cardiogenic shock due to fulminant myocarditis: experience from a tertiary center. Perfusion 36(5):446\u0026ndash;452\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAbrams D, Combes A, Brodie D (2014) Extracorporeal membrane oxygenation in cardiopulmonary disease in adults. J Am Coll Cardiol 63(25):2769\u0026ndash;2778\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTehrani BN, Truesdell AG, Singh R, Zeymer U, De Silva R, Kar B et al (2019) A standardized team-based approach for cardiogenic shock. J Am Coll Cardiol 73(13):1659\u0026ndash;1669\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKaragiannidis C, Brodie D, Strassmann S, Stoelben E, Philipp A, Luedi MM et al (2016) Extracorporeal membrane oxygenation: evolving epidemiology and mortality. Intensive Care Med 42(5):889\u0026ndash;896\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGuglin M, Zucker MJ, Bazan VM, Bozkurt B, El Banayosy A, Estep JD et al (2019) Venoarterial ECMO for adults: JACC Scientific Expert Panel. J Am Coll Cardiol 73(6):698\u0026ndash;716\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMakdisi G, Wang IW (2015) Extra corporeal membrane oxygenation (ECMO) review of a lifesaving technology. J Thorac Dis 7(7):E166\u0026ndash;E176\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMarasco SF, Lukas G, McDonald M, McMillan J, Ihle B (2008) Review of ECMO (extra corporeal membrane oxygenation) support in critically ill adult patients. Heart Lung Circ 17(5):S41\u0026ndash;S47\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRao P, Khalpey Z, Smith R, Burkhoff D, Kociol RD (2018) Venoarterial extracorporeal membrane oxygenation for cardiogenic shock and cardiac arrest. Circ Heart Fail 11(9):e004905\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKeebler ME, Haddad EV, Choi CW, McGrane S, Zalawadiya SK, Schlendorf KH et al (2018) Venoarterial extracorporeal membrane oxygenation in cardiogenic shock. JACC Heart Fail 6(6):503\u0026ndash;516\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eShih E, DiMaio JM, Wang D, George TJ, Lee JC (2019) Veno-arterial extracorporeal membrane oxygenation in adults: An overview. J Thorac Dis 11(Suppl 6):S792\u0026ndash;803\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGaran AR, Kirtane AJ, Takayama H, Redfors B, Green P, Kapur NK et al (2019) ECMO and Impella use in acute myocardial infarction complicated by cardiogenic shock. J Am Coll Cardiol 73(5):653\u0026ndash;659\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRyu KM, Choi JH, Chang SH, Hong Y, Choi YH (2020) Predictors of survival in acute myocardial infarction complicated by cardiogenic shock requiring extracorporeal membrane oxygenation. Int J Cardiol 298:107\u0026ndash;112\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"مجمع الملك عبدالله الطبي ","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"ECMO, acute heart failure, veno-arterial ECMO, survival, meta- analysis, extracorporeal support, critical care cardiology","lastPublishedDoi":"10.21203/rs.3.rs-7040715/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7040715/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAcute heart failure (AHF) represents a critical and life-threatening condition characterized by the sudden onset of impaired cardiac function, leading to inadequate perfusion of vital organs. Despite advancements in pharmacological and mechanical circulatory support therapies, the mortality rate in severe AHF remains alarmingly high. Extracorporeal Membrane Oxygenation (ECMO), particularly veno-arterial ECMO (VA-ECMO), has emerged as a potential life- saving intervention for patients with refractory AHF by temporarily replacing the function of the heart and lungs. However, the true effectiveness of ECMO in improving survival outcomes in AHF patients remains a subject of ongoing debate due to variations in patient selection, timing of initiation, and institutional experience.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis meta-analysis aims to evaluate the latest clinical evidence on the use of ECMO in the management of acute heart failure, focusing primarily on its impact on short-term and long-term survival, and secondarily on associated complications and outcomes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA comprehensive and systematic literature search was conducted across multiple databases including PubMed, Scopus, Embase, and Web of Science for studies published between January 2015 and March 2025. Randomized controlled trials (RCTs), prospective cohort studies, and retrospective observational studies that assessed the impact of ECMO in adult patients with acute heart failure were included. The primary outcome was all-cause mortality; secondary outcomes included survival to discharge, neurologic outcomes, and incidence of ECMO- related complications. Study quality was assessed using the PRISMA and Cochrane Risk of Bias tools. Pooled data were analyzed using random- effects models to account for inter-study heterogeneity.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 18 studies involving 4,230 patients met the inclusion criteria. The pooled analysis demonstrated that ECMO support was associated with a statistically significant improvement in short-term survival (OR = 1.65, 95% CI: 1.32–2.07, p \u0026lt; 0.001) compared to conventional therapy alone. However, substantial heterogeneity (I² = 64%) was observed, suggesting variability in study designs and patient characteristics. Subgroup analysis indicated better outcomes in patients receiving early ECMO initiation and in centers with high ECMO experience. Common complications associated with ECMO included bleeding (28%), infection (19%), and limb ischemia (11%).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis meta-analysis supports the effectiveness of ECMO in improving survival in selected patients with acute heart failure, especially when initiated early and managed in experienced centers. Despite the associated risks and high resource utilization, ECMO remains a valuable therapeutic option in severe, refractory cases of AHF. Further large-scale, multi- center RCTs are warranted to define optimal patient selection criteria, timing of intervention, and standardized protocols to enhance outcomes.\u003c/p\u003e","manuscriptTitle":"Fluid assessment in critical patient: ultrasound assessment vs clinical assessment","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-08 10:30:23","doi":"10.21203/rs.3.rs-7040715/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"be12e7fb-3479-4ceb-b4c7-9cd56dca6291","owner":[],"postedDate":"July 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":51013130,"name":"Critical Care \u0026 Emergency Medicine"}],"tags":[],"updatedAt":"2025-07-08T10:30:23+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-08 10:30:23","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7040715","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7040715","identity":"rs-7040715","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}