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Abstract 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.

Abstract 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.

Abstract Background Seizures, strokes, and intracranial hemorrhage are common and feared complications in children receiving extracorporeal membrane oxygenation (ECMO) support. Researchers and clinicians have proposed and deployed methods for monitoring and detecting neurologic injury, but best practices are unknown. We sought to characterize clinicians’ approach to electroencephalography (EEG) and brain imaging modalities in children supported by ECMO. Methods We performed a retrospective observational cohort study among US Children’s Hospitals participating in the Pediatric Health Information System (PHIS) from 2016 to 2021. We identified hospitalizations containing ECMO support. We stratified these admissions by pediatric, neonatal, cardiac surgery, and non-cardiac surgery. We characterized the frequency of EEG, cranial ultrasound, brain computed tomography (CT), magnetic resonance imaging (MRI), and transcranial Doppler during ECMO hospitalizations. We reported key diagnoses (stroke and seizures) and the prescription of antiseizure medication. To assess hospital variation, we created multilevel logistic regression models. Results We identified 8746 ECMO hospitalizations. Nearly all children under 1 year of age (5389/5582) received a cranial ultrasound. Sixty-two percent of the cohort received an EEG, and use increased from 2016 to 2021 (52–72% of hospitalizations). There was marked variation between hospitals in rates of EEG use. Rates of antiseizure medication use (37% of hospitalizations) and seizure diagnoses (20% of hospitalizations) were similar across hospitals, including high and low EEG utilization hospitals. Overall, 37% of the cohort received a CT and 36% received an MRI (46% of neonatal patients). Stroke diagnoses (16% of hospitalizations) were similar between high- and low-MRI utilization hospitals (15% vs 17%, respectively). Transcranial Doppler (TCD) was performed in just 8% of hospitalizations, and 77% of the patients who received a TCD were cared for at one of five centers. Conclusions In this cohort of children at high risk of neurologic injury, there was significant variation in the approach to EEG and neuroimaging in children on ECMO. Despite the variation in monitoring and imaging, diagnoses of seizures and strokes were similar across hospitals. Future work needs to identify a management strategy that appropriately screens and monitors this high-risk population without overuse of resource-intensive modalities.

Abstract Background Extracorporeal membrane oxygenation (ECMO) has been used extensively for coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS). Reports early in the pandemic suggested that mortality in patients with COVID-19 receiving ECMO was comparable to non-COVID-19-related ARDS. However, subsequent reports suggested that mortality appeared to be increasing over time. Therefore, we conducted an updated systematic review and meta-analysis, to characterise changes in mortality over time and elucidate risk factors for poor outcomes. Methods We conducted a meta-analysis (CRD42021271202), searching MEDLINE, Embase, Cochrane, and Scopus databases, from 1 December 2019 to 26 January 2022, for studies reporting on mortality among adults with COVID-19 receiving ECMO. We also captured hospital and intensive care unit lengths of stay, duration of mechanical ventilation and ECMO, as well as complications of ECMO. We conducted random-effects meta-analyses, assessed risk of bias of included studies using the Joanna Briggs Institute checklist and evaluated certainty of pooled estimates using GRADE methodology. Results Of 4522 citations, we included 52 studies comprising 18,211 patients in the meta-analysis. The pooled mortality rate among patients with COVID-19 requiring ECMO was 48.8% (95% confidence interval 44.8–52.9%, high certainty). Mortality was higher among studies which enrolled patients later in the pandemic as opposed to earlier (1st half 2020: 41.2%, 2nd half 2020: 46.4%, 1st half 2021: 62.0%, 2nd half 2021: 46.5%, interaction p value = 0.0014). Predictors of increased mortality included age, the time of final patient enrolment from 1 January 2020, and the proportion of patients receiving corticosteroids, and reduced duration of ECMO run. Conclusions The mortality rate for patients receiving ECMO for COVID-19-related ARDS has increased as the pandemic has progressed. The reasons for this are likely multifactorial; however, as outcomes for these patients evolve, the decision to initiate ECMO should include the best contextual estimate of mortality at the time of ECMO initiation.

Abstract Background Fluid overload and acute kidney injury are common and associated with poor outcomes among critically ill children. The prodrome of renal angina stratifies patients by risk for severe acute kidney injury, but the predictive discrimination for fluid overload is unknown. Methods Post-hoc analysis of patients admitted to a tertiary care pediatric intensive care unit (PICU). The primary outcome was the performance of renal angina fulfillment on day of ICU admission to predict fluid overload ≥15% on Day 3. Results 77/139 children (55%) fulfilled renal angina (RA+). After adjusting for covariates, RA+ was associated with increased odds of fluid overload on Day 3 (adjusted odds ratio (aOR) 5.1, 95% CI 1.23–21.2, p = 0.025, versus RA-). RA- resulted in a 90% negative predictive value for fluid overload on Day 3. Median fluid overload was significantly higher in RA+ patients with severe acute kidney injury compared to RA+ patients without severe acute kidney injury (% fluid overload on Day 3: 8.8% vs. 0.73%, p = 0.002). Conclusion Among critically ill children, fulfillment of renal angina was associated with increased odds of fluid overload versus the absence of renal angina and a higher fluid overload among patients who developed acute kidney injury. Renal angina directed risk classification may identify patients at highest risk for fluid accumulation. Expanded study in larger populations is warranted.

Abstract Background There are several reports of extracorporeal membrane oxygenation (ECMO) use in patients with coronavirus disease 2019 (COVID-19) who develop severe acute respiratory distress syndrome (ARDS). We conducted a systematic review and meta-analysis to guide clinical decision-making and future research. Methods We searched MEDLINE, Embase, Cochrane and Scopus databases from 1 December 2019 to 10 January 2021 for observational studies or randomised clinical trials examining ECMO in adults with COVID-19 ARDS. We performed random-effects meta-analyses and meta-regression, assessed risk of bias using the Joanna Briggs Institute checklist and rated the certainty of evidence using the GRADE approach. Survival outcomes were presented as pooled proportions while continuous outcomes were presented as pooled means, both with corresponding 95% confidence intervals [CIs]. The primary outcome was in-hospital mortality. Secondary outcomes were duration of ECMO therapy and mechanical ventilation, weaning rate from ECMO and complications during ECMO. Results We included twenty-two observational studies with 1896 patients in the meta-analysis. Venovenous ECMO was the predominant mode used (98.6%). The pooled in-hospital mortality in COVID-19 patients (22 studies, 1896 patients) supported with ECMO was 37.1% (95% CI 32.3–42.0%, high certainty). Pooled mortality in the venovenous ECMO group was 35.7% (95% CI 30.7–40.7%, high certainty). Meta-regression found that age and ECMO duration were associated with increased mortality. Duration of ECMO support (18 studies, 1844 patients) was 15.1 days (95% CI 13.4–18.7). Weaning from ECMO (17 studies, 1412 patients) was accomplished in 67.6% (95% CI 50.5–82.7%) of patients. There were a total of 1583 ECMO complications reported (18 studies, 1721 patients) and renal complications were the most common. Conclusion The majority of patients received venovenous ECMO support for COVID-19-related ARDS. In-hospital mortality in patients receiving ECMO support for COVID-19 was 37.1% during the first year of the pandemic, similar to those with non-COVID-19-related ARDS. Increasing age was a risk factor for death. Venovenous ECMO appears to be an effective intervention in selected patients with COVID-19-related ARDS. PROSPERO CRD42020192627.

Abstract Background This study outlines an image processing algorithm for accurate and consistent lung segmentation in chest radiographs of critically ill adults and children typically obscured by medical equipment. In particular, this work focuses on applications in analysis of acute respiratory distress syndrome – a critical illness with a mortality rate of 40% that affects 200,000 patients in the United States and 3 million globally each year. Methods Chest radiographs were obtained from critically ill adults (n = 100), adults diagnosed with acute respiratory distress syndrome (ARDS) (n = 25), and children (n = 100) hospitalized at Michigan Medicine. Physicians annotated the lung field of each radiograph to establish the ground truth. A Total Variation-based Active Contour (TVAC) lung segmentation algorithm was developed and compared to multiple state-of-the-art methods including a deep learning model (U-Net), a random walker algorithm, and an active spline model, using the Sørensen–Dice coefficient to measure segmentation accuracy. Results The TVAC algorithm accurately segmented lung fields in all patients in the study. For the adult cohort, an averaged Dice coefficient of 0.86 ±0.04 (min: 0.76) was reported for TVAC, 0.89 ±0.12 (min: 0.01) for U-Net, 0.74 ±0.19 (min: 0.15) for the random walker algorithm, and 0.64 ±0.17 (min: 0.20) for the active spline model. For the pediatric cohort, a Dice coefficient of 0.85 ±0.04 (min: 0.75) was reported for TVAC, 0.87 ±0.09 (min: 0.56) for U-Net, 0.67 ±0.18 (min: 0.18) for the random walker algorithm, and 0.61 ±0.18 (min: 0.18) for the active spline model. Conclusion The proposed algorithm demonstrates the most consistent performance of all segmentation methods tested. These results suggest that TVAC can accurately identify lung fields in chest radiographs in critically ill adults and children.

OBJECTIVES:. Although there is a substantial published experience of extracorporeal membrane oxygenation during the H1N1 pandemic, less is known about the use of extracorporeal membrane oxygenation in patients with other subtypes of the influenza A virus. We hypothesized that the severity of illness and survival of patients supported with extracorporeal membrane oxygenation would differ for those with H1N1 influenza A compared with other subtypes of influenza A. DESIGN, SETTING, PATIENTS:. Retrospective study of extracorporeal membrane oxygenation–supported adults (> 18 yr) with influenza A viral infection reported to the Extracorporeal Life Support Organization Registry between 2009 and 2019. We describe the frequency and compare characteristics and factors associated with in-hospital survival using a least absolute shrinkage and selection operator regression analysis. MAIN OUTCOMES AND MEASURES:. Of 2,461 patients supported with extracorporeal membrane oxygenation for influenza A, 445 had H1N1, and 2,004 had other subtypes of influenza A. H1N1 was the predominant subtype between 2009 and 2011. H1N1 patients were younger, with more severe illness at extracorporeal membrane oxygenation cannulation and higher reported extracorporeal membrane oxygenation complications than those with other influenza A subtypes. Patient characteristics including younger age and higher weight and patient management characteristics including longer ventilation duration before extracorporeal membrane oxygenation were associated with worse survival. Extracorporeal membrane oxygenation complications were associated with reduced survival. There was no difference in survival to hospital discharge according to influenza subtype after adjusting for other characteristics. CONCLUSIONS:. Patients supported with extracorporeal membrane oxygenation for H1N1 were younger, with more severe illness than those supported for other influenza A subtypes. Survival to hospital discharge was associated with patient characteristics, management characteristics, and extracorporeal membrane oxygenation complications but was not impacted by the specific influenza A subtype.

Abstract Background The Extracorporeal Life Support Organization (ELSO) Maastricht Treaty for Nomenclature in Extracorporeal Life Support (ECLS) established consensus nomenclature and abbreviations for ECLS to ensure accurate, concise communication. Methods We build on this consensus nomenclature by layering a framework of precise and efficient abbreviations for cannula configuration that describe flow direction, number of cannulae used, any additional ECLS-related catheters, and cannulation sites. This work is a consensus of international representatives of the ELSO, including those from the North American, Latin American, European, South and West Asian, and Asian-Pacific chapters of ELSO. Results The classification increases in descriptive capability by introducing a third (cannula tip position) and fourth (cannula dimension) level to those provided in the previous consensus on ECLS cannulation configuration nomenclature. This expansion offers the simplest level needed to convey cannulation information yet allows for more details when required. Conclusions A complete nomenclature for ECLS cannulation configurations accommodating future revisions was developed to facilitate ability to compare practices and results, to promote efficient communication, and to improve quality of registry data.