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Background: Mortality for patients receiving extracorporeal membrane oxygenation (ECMO) for COVID-19 has increased over time. We investigated the association between immunomodulators and mortality for patients receiving ECMO for COVID-19. Method(s): We analysed the Extracorporeal Life Support Organisation Registry from Jan 1, 2020 through Dec 31, 2021, comparing in-hospital mortality and the overall survival since ECMO initiation of patients who did and did not receive immunomodulators (selective interleukin blockers, corticosteroids, janus-kinase inhibitors, convalescent plasma, and intravenous immunoglobulins) before or during ECMO, by using logistic regression and Cox regression. We calculated the propensity scores, and applied the overlap-weightage method to account for confounding factors. We conducted sensitivity analyses including regression models using inverse propensity score weightage method, models adjusted by propensity score, and unadjusted models to ensure robustness of results. A subgroup analysis on patients receiving corticosteroids was conducted. Result(s): 7180 patients were included in the final analysis. Immunomodulators were associated with increased mortality (OR: 1.168, 95%CI: 1.059-1.289, p=0.0020) and shorter survival since ECMO (HR: 1.05, 95%- CI: 1.078, 95%CI: 1.007-1.154, p=0.031). Similarly, corticosteroids were associated with a significant increase in mortality (OR: 1.302, 95%-CI: 1.180-1.437, p<0.0001) and shorter survival (HR: 1.221, 95%-CI: 1.139- 1.308, p<0.0001). Sensitivity analyses did not significantly change the overall results. Conclusion(s): Immunomodulators and corticosteroids, in particular, were associated with a significant increase in mortality amongst patients receiving ECMO for COVID-19, even after adjusting for potential confounding variables. Further studies are required to evaluate the timing of immunomodulators and understand the possible mechanisms behind this association.
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Objective: Prone positioning for severe acute respiratory distress syndrome (ARDS) is associated with improved outcome. It is unclear whether prone positioning during Venovenous extracorporeal membrane oxygenation (VV ECMO) has survival benefit. The study investigated the impact of prone positioning on survival during VV ECMO support for COVID-19 acute respiratory failure. Methods: An observational analysis of VV ECMO patients using the COVID-19 Critical Care Consortium (COVID Critical) international registry. We used a multi-state survival model to compare the outcomes of patients treated with or without prone positioning during ECMO. Results: There were 213 COVID-19 patients at 67 participating institutions who were supported with VV ECMO from February 19, 2020, to October 31, 2020. Proning was used in 160 patients (75%) before initiation of ECMO and in 67 patients (31%) during ECMO. Prone positioning during ECMO support was associated with reduced mortality (hazard ratio 0.33, 95% CI, 0.15 to 0.73). Conclusions: Our study highlights that prone-positioning during VV ECMO support for refractory COVID- 19-related ARDS is associated with reduced mortality. Given our observational study design, a randomized controlled trial of prone positioning on VV ECMO is needed to confirm these findings.
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Objective: To identify the incidence of infections in those receiving immunomodulatory drugs for COVID- 19 during ECMO and the risk factors for infection. Methods: Deidentified data on all patients who had ECMO for COVID-19 till July 2020 were analysed from the ELSO Registry. A comparison cohort of patients who did not acquire superinfections during ECMO was used to identify risk factors for infection. Our primary outcome measure was incidence of infections pre- or on ECMO in patients receiving immunomodulatory drugs. Univariate analysis assessed potential associations between survival and various pre-ECMO/ECMOrelated factors. Variables (p< 0.1) entered a logistic regression model which identified predictors of infections in this cohort. Results: Of the 1237 patients who required ECMO for COVID-19 related complications, 911 patients (73.6%) received immunomodulatory drugs. 47% of these patients had superinfections, predominantly with gram negative bacteria (56%). Pre-ECMO factors associated with a higher odds of infection included immunodeficiency and treatment with selective cytokine blockers. ECMO complications (mechanical, renal, pulmonary, infectious and metabolic) increased the odds of infection. (Table 1) Patients who developed an infection preor on ECMO had significantly longer ECMO runs than those who did not (491.1±308.9 hours vs 293.4± 240.6hours, p< 0.001) with no mortality difference (45.7% Vs 43.4%, p = 0.45). Conclusions: Of the three quarter of patients who received immunomodulatory drugs for COVID-19 during ECMO, 47% had superinfections. Immunodeficiency and use of selective cytokine blockers were risk factors for infections pre or on ECMO in addition to ECMO related complications.
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Objective: Extracorporeal membrane oxygenation (ECMO) use in COVID-19 has been supported by major health organizations and studies, but optimal management strategies need further research. We characterize and describe the tracheostomy practice in ECMO-supported patients with acute respiratory failure related to viral pneumonia without SARS-CoV-2 in 2019 and to COVID-19 in 2020. Methods: Analysis of the Extracorporeal Life Support Organization (ELSO) Registry including patients receiving respiratory ECMO support for COVID-19 in 2020 or other viral-induced respiratory failure in 2019. We compared tracheostomy practices between the 2019 and 2020 cohorts and reported outcomes of those that receive a tracheostomy on ECMO. Results: We identified 1960 patients who received VV-ECMO support for acute respiratory failure related to COVID-19. 57% of patients received a tracheostomy during the hospitalization, and 25% had a tracheostomy placed while on ECMO. The proportion of patients receiving a tracheostomy was similar in 2019 viral disease, but tracheostomies were performed 4 days earlier in 2019 compared to 2020 (median 6.7 days [IQR 3.0- 12.0 days] vs. 11.2 days [IQR 5.8-17.0 days], p< 0.01). More patients were mobilized in 2019 than 2020, but patients who received a tracheostomy on ECMO were more likely to be mobilized in both cohorts. 8% of patients were reported as having surgical site bleeding after a tracheostomy placement on ECMO in 2020. The median ECMO duration in those who received a tracheostomy on ECMO was 23.5 days [IQR 15.8-35.3]. Hospital mortality was 45% for patients with COVID- 19 (46% for patients who received a tracheostomy on ECMO). Conclusions: Tracheostomies are commonly performed in COVID-19 patients on ECMO. The number of tracheostomies performed on ECMO in the SARS-CoV-2 pandemic is similar to other viral diseases in 2019, however, they are performed later in the ECMO run. Patients who receive a tracheostomy are more likely to achieve mobilization.
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INTRODUCTION: Coronavirus disease 2019 (COVID-19)-induced coagulopathy (CIC) has been widely reported in the literature. However, the spectrum of abnormalities associated with CIC has been highly variable. METHODS: We conducted a systematic review of the literature (until 1 June 2020) to assess CIC and disease severity during the early COVID-19 pandemic. Primary outcomes were pooled mean differences in platelet count, D-dimer level, prothrombin time, activated partial thromboplastin time (aPTT) and fibrinogen level between non-severe and severe patients, stratified by degree of hypoxaemia or those who died. The risk factors for CIC were analysed. Random-effects meta-analyses and meta-regression were performed using R version 3.6.1, and certainty of evidence was rated using the Grading of Recommendation, Assessment, Development, and Evaluation approach. RESULTS: Of the included 5,243 adult COVID-19 patients, patients with severe COVID-19 had a significantly lower platelet count, and higher D-dimer level, prothrombin time and fibrinogen level than non-severe patients. Pooled mean differences in platelet count (-19.7×109/L, 95% confidence interval [CI] -31.7 to -7.6), D-dimer level (0.8μg/mL, 95% CI 0.5-1.1), prothrombin time (0.4 second, 95% CI 0.2-0.6) and fibrinogen level (0.6g/L, 95% CI 0.3-0.8) were significant between the groups. Platelet count and D-dimer level were significant predictors of disease severity on meta-regression analysis. Older men had higher risks of severe coagulopathic disease. CONCLUSION: Significant variability in CIC exists between non-severe and severe patients, with platelet count and D-dimer level correlating with disease severity. Routine monitoring of all coagulation parameters may help to assess CIC and decide on the appropriate management.