Variation in survival in patients with Coronavirus Disease 2019 supported with extracorporeal membrane oxygenation: A multi-institutional analysis of 594 consecutive patients with Coronavirus Disease 2019 supported with extracorporeal membrane oxygenation at 49 hospitals within 21 states.

OBJECTIVES: We reviewed 594 consecutive patients with Coronavirus Disease 2019 supported with extracorporeal membrane oxygenation at 49 hospitals within 21 states and examined patient characteristics, treatments, and variation in outcomes over the course of the pandemic. METHODS: A multi-institutional database was used to assess all patients with Coronavirus Disease 2019 supported with and separated from extracorporeal membrane oxygenation between March 2020 and December 2021, inclusive. Descriptive analysis was stratified by 4 time categories: group A = March 2020 to June 2020, group B = July 2020 to December 2020, group C = January 2021 to June 2021, group D = July 2021 to December 2021. A Bayesian mixed-effects logistic regression was used to assess continuous trends in survival where time was operationalized as the number of days between each patient's cannulation and that of the first patient in March 2020, controlling for multiple variables and risk factors. RESULTS: At hospital discharge, of 594 patients, 221 survived (37.2%) and 373 died. Throughout the study, median age [interquartile range] declined (group A = 51.0 [41.0-60.0] years, group D = 39.0 [32.0-48.0] years, P < .001); median days between Coronavirus Disease 2019 diagnosis and intubation increased (group A = 4.0 [1.0-8.5], group D = 9.0 [5.0-14.5], P < .001); and use of medications (glucocorticoids, interleukin-6 blockers, antivirals, antimalarials) and convalescent plasma fluctuated significantly (all P < .05). Estimated odds of survival varied over the study period with a decline between April 1, 2020, and November 21, 2020 (odds ratio, 0.39, 95% credible interval, 0.18-0.87, probability of reduction in survival = 95.7%), improvement between November 21, 2020, and May 17, 2021 (odds ratio, 1.85, 95% credible interval, 0.86-4.09, probability of improvement = 93.4%), and decline between May 17, 2021, and December 1, 2021 (odds ratio, 0.49, 95% credible interval, 0.19-1.44, probability of decrease = 92.1%). CONCLUSIONS: Survival for patients with Coronavirus Disease 2019 supported with extracorporeal membrane oxygenation has fluctuated during the stages of the pandemic. Minimizing variability by adherence to best practices may refine the optimal use of extracorporeal membrane oxygenation in a pandemic response.

ECMO During COVID-19: A Society of Thoracic Surgeons/Extracorporeal Life Support Organization Survey.

Background: The Society of Thoracic Surgeons Workforce on Critical Care and the Extracorporeal Life Support Organization sought to identify how the coronavirus disease 2019 (COVID-19) pandemic has changed the practice of venoarterial (VA) and venovenous (VV) extracorporeal membrane oxygenation (ECMO) programs across North America. Methods: A 26-question survey covering 6 categories (ECMO initiation, cannulation, management, anticoagulation, triage/protocols, and credentialing) was emailed to 276 North American Extracorporeal Life Support Organization centers. ECMO practices before and during the COVID-19 pandemic were compared. Results: Responses were received from 93 (34%) programs. The percentage of high-volume (>20 cases per year) VV ECMO programs increased during the pandemic from 29% to 41% (P < .001), as did institutions requiring multiple clinicians for determining initiation of ECMO (VV ECMO, 25% to 43% [P = .001]; VA ECMO, 20% to 32% [P = .012]). During the pandemic, more institutions developed their own protocols for resource allocation (23% before to 51%; P < .001), and more programs created sharing arrangements to triage patients and equipment with other centers (31% to 57%; P < .001). Direct thrombin inhibitor use increased for both VA ECMO (13% to 18%; P = .025) and VV ECMO (12% to 24%; P = .005). Although cardiothoracic surgeons remained the primary cannulating proceduralists, VV ECMO cannulations performed by pulmonary and critical care physicians increased (13% to 17%; P = .046). Conclusions: The Society of Thoracic Surgeons/Extracorporeal Life Support Organization collaborative survey indicated that the pandemic has affected ECMO practice. Further research on these ECMO strategies and lessons learned during the COVID-19 pandemic may be useful in future global situations.

The Association of Baseline Plasma SARS-CoV-2 Nucleocapsid Antigen Level and Outcomes in Patients Hospitalized With COVID-19.

BACKGROUND: Levels of plasma SARS-CoV-2 nucleocapsid (N) antigen may be an important biomarker in patients with COVID-19 and enhance our understanding of the pathogenesis of COVID-19. OBJECTIVE: To evaluate whether levels of plasma antigen can predict short-term clinical outcomes and identify clinical and viral factors associated with plasma antigen levels in hospitalized patients with SARS-CoV-2. DESIGN: Cross-sectional study of baseline plasma antigen level from 2540 participants enrolled in the TICO (Therapeutics for Inpatients With COVID-19) platform trial from August 2020 to November 2021, with additional data on day 5 outcome and time to discharge. SETTING: 114 centers in 10 countries. PARTICIPANTS: Adults hospitalized for acute SARS-CoV-2 infection with 12 days or less of symptoms. MEASUREMENTS: Baseline plasma viral N antigen level was measured at a central laboratory. Delta variant status was determined from baseline nasal swabs using reverse transcriptase polymerase chain reaction. Associations between baseline patient characteristics and viral factors and baseline plasma antigen levels were assessed using both unadjusted and multivariable modeling. Association between elevated baseline antigen level of 1000 ng/L or greater and outcomes, including worsening of ordinal pulmonary scale at day 5 and time to hospital discharge, were evaluated using logistic regression and Fine-Gray regression models, respectively. RESULTS: Plasma antigen was below the level of quantification in 5% of participants at enrollment, and 1000 ng/L or greater in 57%. Baseline pulmonary severity of illness was strongly associated with plasma antigen level, with mean plasma antigen level 3.10-fold higher among those requiring noninvasive ventilation or high-flow nasal cannula compared with room air (95% CI, 2.22 to 4.34). Plasma antigen level was higher in those who lacked antispike antibodies (6.42 fold; CI, 5.37 to 7.66) and in those with the Delta variant (1.73 fold; CI, 1.41 to 2.13). Additional factors associated with higher baseline antigen level included male sex, shorter time since hospital admission, decreased days of remdesivir, and renal impairment. In contrast, race, ethnicity, body mass index, and immunocompromising conditions were not associated with plasma antigen levels. Plasma antigen level of 1000 ng/L or greater was associated with a markedly higher odds of worsened pulmonary status at day 5 (odds ratio, 5.06 [CI, 3.41 to 7.50]) and longer time to hospital discharge (median, 7 vs. 4 days; subhazard ratio, 0.51 [CI, 0.45 to 0.57]), with subhazard ratios similar across all levels of baseline pulmonary severity. LIMITATIONS: Plasma samples were drawn at enrollment, not hospital presentation. No point-of-care test to measure plasma antigen is currently available. CONCLUSION: Elevated plasma antigen is highly associated with both severity of pulmonary illness and clinically important patient outcomes. Multiple clinical and viral factors are associated with plasma antigen level at presentation. These data support a potential role of ongoing viral replication in the pathogenesis of SARS-CoV-2 in hospitalized patients. PRIMARY FUNDING SOURCE: U.S. government Operation Warp Speed and National Institute of Allergy and Infectious Diseases.

Cannulate, Extubate, Ambulate: Effect of a Mobility-Focused Program on Outcomes of COVID+ ECMO Patients at West Virginia University Medicine

Objective: The motto Cannulate, Extubate, Ambulate reflects the care ECMO patients receive at West Virginia University Medicine. Early mobility, crucial in our outcomes, especially with the COVID-19 population, is started with a Physical Therapist. This is followed by all team members participating in ECMO mobilization. This project examined the impact of mobilization for our COVID+ population placed on VV ECMO. Method(s): A WVU retrospective review was completed of COVID-19+ patients on ECMO between 3/2020 and 12/2021, determining survival to decannulation and discharge location. Mobility was examined for ECMOday of first active participation, first active transfer out of bed, and first ambulation. Further, PT sessions during cannulation, total PT, staff assist mobility while cannulated, and total number of sessions during admission. All patients who survived to discharge were included in survival rate, but those transferred to outside facilities for ECMO management were excluded from mobility and discharge location analyses. Result(s): Out of 91 patients, 70% successfully decannulated, and 98.4% survived to discharge. Mobilization began day 1 of ECMO, averaging 7.6 sessions/patient during their hospitalization. 88% performed their first active transfers with PT assist. Mobility sessions were also performed by Nursing/ECMO Specialists (3.6 times vs. 2.8 times). Total active mobilizations ranged 2-69 sessions, averaging 13.9 mobilizations during hospitalization. 60% of COVID-19 ECMO survivors were discharged home. Conclusion(s): Physical therapists lead mobility efforts, however, active involvement of nursing and ECMO Specialists is vital to provide continuity and repetition of mobility. Our results suggest teamwork improves patient survival and other important outcomes.

Early initiation of hemoadsorption reduces the need for organ support in critically ill COVID-19 patients on ECMO: A post-hoc analysis from the CytoSorb Therapy in COVID-19 (CTC) Registry

Objectives: Preliminary results of the CTC Registry on the first 52 patients showed survival of 69% at 90 days [1]. The current exploratory analysis aimed to examine whether the time of initiation of hemoadsorption (i.e.: early vs late) had any effect organ support requirements and survival. Method(s): We included all 100 patients recruited in the CTC Registry in 5 U.S. intensive care units (ICU). The median time from ICU admission to the start of hemoadsorption was 86.7 h. We created two post hoc groups: <=86.7 h (group-early, GE) and >86.7 h (group-late, GL) and compared outcomes with special focus on the need of mechanical ventilation (MV), vasopressor, renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO). Result(s): There was no difference between groups in baseline characteristics. 90-day survival was 78% in GE and 62% in GL (p=0.08). Patients in the GL vs GE spent longer time on ECMO (p=0.021), mechanical ventilation (p=0.02) and needed significantly longer ICU-stay (p=0.002), (Fig. 1). There was also a trend for longer vasopressor support (8 [4-21] vs 4 [1-17] days, p=0.13). There was no significant difference between the groups regarding the need of CRRT. Conclusion(s): The current analysis shows that early initiation of hemoadsorption with ECMO in critically ill COVID-19 patients is associated with shorter duration of organ support measures and shorter ICU stays.

The Impact of Morbid Obesity on Patients with COVID-19 who Develop Respiratory Failure requiring Extracorporeal Membrane Oxygenation

Background: In patients with COVID-19 and respiratory failure, class 3 obesity (body mass index > 40 kg/m2) has been associated with worse survival. Obese patients on mechanical ventilation with progressively more severe acute respiratory syndrome (ARDS) may be offered venovenous (VV) extracorporeal membrane oxygenation (ECMO) therapy. The impact of morbid obesity on the outcome of COVID-19 patients supported with VV ECMO has been underexplored. Methods: This is a multicenter, retrospective observational cohort analysis of critically ill adults with COVID-19 ARDS requiring advanced mechanical ventilation with or without VV ECMO. Data was collected from 236 international institutions forming the COVID-19 Critical Care Consortium international registry. Patients were admitted between January 2020 to December 2021. Included patients were stratified by ECMO status and a BMI threshold at 40 kg/m2. Median values with interquartile range (IQR) were used to summarize continuous variables and multi-state analysis was used to explore the effect of Class 3 obesity on the study endpoints of patient survival to discharge or death. Results: Complete data was available on 8851 of 9059 patients on mechanical ventilation, of which 767 patients required VV ECMO. For the entire study group, older age and male gender were associated with an increased risk of death. The demographics and comorbidities of the higher BMI (H >40 kg/m2) and lower BMI (L ≤40 kg/m2) cohorts were similar with the exception of age and weight. Patients with a higher BMI were younger. The median age of the H, non-ECMO cohort was 56 years (46-64), and the H, ECMO cohort was 41 years (35-51) versus the L, non-ECMO cohort of 64 years(55-71), and the L, ECMO cohort of 53years (45-60). Patients requiring VV ECMO had higher SOFA scores, experienced longer ICU and hospital lengths of stay, and a longer duration of total mechanical ventilation. Table The median time to intubation was longer in the mechanical ventilation only group (2 versus 0 days). Predictors for requiring ECMO included younger age, higher BMI and male gender. Risk factors for death included advancing age (every 10 years), male gender and increasing BMI (every 5kg/m2). The association between BMI and a higher rate of death was reduced in the mechanical ventilation only group (HR 0.92, 95% confidence interval 0.85 to 0.99). Conclusion: In patients with severe ARDS due to COVID-19 requiring mechanical ventilation, the likelihood of progressing to VV ECMO therapy or experiencing death is impacted by age, gender and higher BMI. The cohort of COVID-19 patients that ultimately required ECMO appear to be sicker at time hospital admission owing to the shorter time until mechanical ventilation. It appears the association between increasing BMI and death differs among the ECMO and mechanical ventilation alone cohorts. We would advocate for a prospective study to determine the benefit of VVECMO for the obese patient requiring VV-ECMO for COVID-19 ARDS. (Figure Presented).

2021: Perioperative and critical care year in review for the cardiothoracic surgery team.

For yet another year, our lives have been dominated by a pandemic. This year in review, we feature an expert panel opinion regarding extracorporeal support in the context of COVID-19, challenging previously held standards. We also feature survey results assessing the impact of the pandemic on cardiac surgical volume. Furthermore, we focus on a single center experience that evaluated the use of pulmonary artery catheters and the comparison of transfusion strategies in the Restrictive and Liberal Transfusion Strategies in Patients With Acute Myocardial Infarction (REALITY) trial. Additionally, we address the impact of acute kidney injury on cardiac surgery and highlight the controversy regarding the choice of fluid resuscitation. We close with an evaluation of dysphagia in cardiac surgery and the impact of prehabilitation to optimize surgical outcomes.

Early trends in ECMO mortality during the first quarters of 2019 and 2020: Could we have predicted the onset of the pandemic?

OBJECTIVE: To compare mortality trends in patients requiring Extracorporeal Membrane Oxygenation (ECMO) support between the first quarters of 2019 and 2020 and determine whether these trends might have predicted the severe acute respiratory syndrome coronavirus-2 (SARS)-Cov-2 pandemic in the United States. METHODS: We analyzed 5% Medicare claims data at aggregate, state, hospital, and encounter levels using MS-DRG (Medicare Severity-Diagnosis Related Group) codes for ECMO, combining state-level data with national census data. Necessity and sufficiency relations associated with change in mortality between the 2 years were modeled using qualitative comparative analysis (QCA). Multilevel, generalized linear modeling was used to evaluate mortality trends. RESULTS: Based on state-level data, there was a 3.36% increase in mortality between 2019 and 2020. Necessity and sufficiency evaluation of aggregate data at state and institutional levels did not identify any association or combinations of risk factors associated with this increase in mortality. However, multilevel and generalized linear models using disaggregated patient-level data to evaluate institution mortality and patient death, identified statistically significant differences between the first (p = .019) and second (p = .02) months of the 2 years, the first and second quarters (p < .001 and p = .042, respectively), and the first 6 months (p < .001) of 2019 and 2020. CONCLUSION: Mortality in ECMO patients increased significantly during the first quarter of 2020 and may have served as an early warning of the SARS-Cov-2 pandemic. Granular data shared in real-time may be used to better predict public health threats.

Surgical Triage and Timing for Patients With Coronavirus Disease: A Guidance Statement from The Society of Thoracic Surgeons.

The coronavirus disease 2019 (COVID-19) pandemic continues to disrupt the provision of cardiac procedural services due to overwhelming interval surges in COVID-19 cases and the associated crisis of cardiac intervention deferment. Despite the availability of widespread testing, highly efficacious vaccines, and intensive public health efforts, the pandemic is entering its third year, where new severe acute respiratory syndrome-coronavirus-2 variants have increased the likelihood that patients scheduled for a cardiac intervention will contract COVID-19 in the perioperative period. The Society of Thoracic Surgeons (STS) Workforce on Critical Care, the STS Workforce on Adult Cardiac and Vascular Surgery, and the Canadian Society of Cardiac Surgeons have developed this document, endorsed by the STS and affirmed by the Society of Cardiovascular Angiography and Interventions and the Canadian Association of Interventional Cardiology, to provide guidance for cardiac procedure deferment and intervention timing for preoperative patients diagnosed with COVID-19. This document is intended for the perioperative cardiac surgical team and outlines the present state of the pandemic, the impact of COVID-19 on intervention outcome, and offers a recommended algorithm for individualized cardiac procedure triage and timing.

Multi-institutional Analysis of 505 Patients With Coronavirus Disease-2019 Supported With Extracorporeal Membrane Oxygenation: Predictors of Survival.

BACKGROUND: We reviewed our experience with 505 patients with confirmed coronavirus disease-2019 (COVID-19) supported with extracorporeal membrane oxygenation (ECMO) at 45 hospitals and estimated risk factors for mortality. METHODS: A multi-institutional database was created and used to assess all patients with COVID-19 who were supported with ECMO. A Bayesian mixed-effects logistic regression model was estimated to assess the effect on survival of multiple potential risk factors for mortality, including age at cannulation for ECMO as well as days between diagnosis of COVID-19 and intubation and days between intubation and cannulation for ECMO. RESULTS: Median time on ECMO was 18 days (interquartile range, 10-29 days). All 505 patients separated from ECMO: 194 patients (38.4%) survived and 311 patients (61.6%) died. Survival with venovenous ECMO was 184 of 466 patients (39.5%), and survival with venoarterial ECMO was 8 of 30 patients (26.7%). Survivors had lower median age (44 vs 51 years, P < .001) and shorter median time interval from diagnosis to intubation (7 vs 11 days, P = .001). Adjusting for several confounding factors, we estimated that an ECMO patient intubated on day 14 after the diagnosis of COVID-19 vs day 4 had a relative odds of survival of 0.65 (95% credible interval, 0.44-0.96; posterior probability of negative effect, 98.5%). Age was also negatively associated with survival: relative to a 38-year-old patient, we estimated that a 57-year-old patient had a relative odds of survival of 0.43 (95% credible interval, 0.30-0.61; posterior probability of negative effect, >99.99%). CONCLUSIONS: ECMO facilitates salvage and survival of select critically ill patients with COVID-19. Survivors tend to be younger and have shorter time from diagnosis to intubation. Survival of patients supported with only venovenous ECMO was 39.5%.

Relationship of lung oxygenation to timing of hemoadsorption therapy initiation in COVID-19 patients requiring extracorporeal mechanical oxygenation (ECMO): an observational analysis from the CytoSorb therapy in COVID-19 (CTC) Registry

Introduction: The multicenter CTC Registry study collected patientlevel data in COVID-19 patients receiving CytoSorb therapy under FDA Emergency Use Authorization. An earlier report on the first 52 CTC patients on ECMO treated with CytoSorb showed 69% overall survival [1]. The current analysis focuses on changes in pulmonary function relative to the time of CytoSorb therapy. Methods: A total of 56 patients from 5 U.S. centers were included. Data on demographics, mechanical ventilation (MV), ECMO, and arterial blood gases during CytoSorb therapy were analyzed. Linear regression was used to evaluate the relationship between the timing of initiation of CytoSorb therapy to lung oxygenation according to changes in PaO2/FiO2 ratio. Results: In the current analysis, 71% (40/56) overall survival was observed. For these survivors, time to CytoSorb start after ICU admission, MV start, and ECMO start was 138 ± 171.3 h, 83 ± 111.0 h, and 55 ± 156.5 h, respectively, with mean duration of CytoSorb therapy of 83 ± 29.1 h. At the first 24 h following CytoSorb therapy, oxygenation was improved evidenced by decreased MV FiO2 and ECMO FdO2 requirements and an increased PaO2/FiO2 ratio (90.2 ± 58.13 mmHg to 166.3 ± 98.67 mmHg, p < 0.001, N = 21). Linear regression analysis suggested that earlier initiation of CytoSorb therapy following ICU admission may be correlated to greater improvements in PaO2/FiO2 ratio (r = -0.37, p = 0.103), however, this trend did not achieve statistical significance. Conclusions: High survival rates have been observed with adjunct CytoSorb therapy in critically ill COVID-19 patients on ECMO. The current analysis suggests that early initiation of hemoadsorption following ICU admission may contribute to earlier improvements in native lung oxygenation.

Cannulate, extubate, ambulate approach for extracorporeal membrane oxygenation for COVID-19.

OBJECTIVE: We compared outcomes in patients with severe COVID-19 versus non-COVID-19-related acute respiratory distress syndrome (ARDS) managed using a dynamic, goal-driven approach to venovenous extracorporeal membrane oxygenation (ECMO). METHODS: We performed a retrospective, single-center analysis of our institutional ECMO registry using data from 2017 to 2021. We used Kaplan-Meier plots, Cox proportional hazard models, and propensity score analyses to evaluate the association of COVID-19 status (COVID-19-related ARDS vs non-COVID-19 ARDS) and survival to decannulation, discharge, tracheostomy, and extubation. We also conducted subgroup analyses to compare outcomes with the use of extracorporeal cytoreductive techniques (CytoSorb [CytoSorbents Corp] and plasmapheresis). RESULTS: The sample comprised 128 patients, 50 with COVID-19 and 78 with non-COVID-19 ARDS. Advancing age was associated with decreased probability of survival to decannulation (P = .04). Compared with the non-COVID-19 ARDS group, patients with COVID-19 had a greater probability of survival to extubation (P < .01) and comparable survival to discharge (P = .14). CONCLUSIONS: Patients with COVID-19 managed with ECMO had comparable outcomes as patients with non-COVID ARDS. A strategy of early extubation and ambulation might be a safe and effective strategy to improve outcomes and survival, even for patients with severe COVID-19.

Multi-institutional Analysis of 200 COVID-19 Patients Treated With Extracorporeal Membrane Oxygenation: Outcomes and Trends.

BACKGROUND: The role of extracorporeal membrane oxygenation (ECMO) in the management of patients with COVID-19 continues to evolve. The purpose of this analysis is to review our multi-institutional clinical experience involving 200 consecutive patients at 29 hospitals with confirmed COVID-19 supported with ECMO. METHODS: This analysis includes our first 200 COVID-19 patients with complete data who were supported with and separated from ECMO. These patients were cannulated between March 17 and December 1, 2020. Differences by mortality group were assessed using χ2 tests for categoric variables and Kruskal-Wallis rank sum tests and Welch's analysis of variance for continuous variables. RESULTS: Median ECMO time was 15 days (interquartile range, 9 to 28). All 200 patients have separated from ECMO: 90 patients (45%) survived and 110 patients (55%) died. Survival with venovenous ECMO was 87 of 188 patients (46.3%), whereas survival with venoarterial ECMO was 3 of 12 patients (25%). Of 90 survivors, 77 have been discharged from the hospital and 13 remain hospitalized at the ECMO-providing hospital. Survivors had lower median age (47 versus 56 years, P < .001) and shorter median time from diagnosis to ECMO cannulation (8 versus 12 days, P = .003). For the 90 survivors, adjunctive therapies on ECMO included intravenous steroids (64), remdesivir (49), convalescent plasma (43), anti-interleukin-6 receptor blockers (39), prostaglandin (33), and hydroxychloroquine (22). CONCLUSIONS: Extracorporeal membrane oxygenation facilitates survival of select critically ill patients with COVID-19. Survivors tend to be younger and have a shorter duration from diagnosis to cannulation. Substantial variation exists in drug treatment of COVID-19, but ECMO offers a reasonable rescue strategy.

Perioperative Coronavirus Vaccination-Timing and Implications: A Guidance Document.

EXECUTIVE SUMMARY: Cardiothoracic surgical patients are at risk of increased coronavirus disease severity. Several important factors influence the administration of the coronavirus disease vaccine in the perioperative period. This guidance statement outlines current information regarding vaccine types, summarizes recommendations regarding appropriate timing of administration, and provides information regarding side effects in the perioperative period for cardiac and thoracic surgical patients.