Fibrotic-Like Pulmonary Radiographic Patterns Are Not Associated With Adverse Outcomes in COVID-19 Chronic Critical Illness.

OBJECTIVES: Pulmonary fibrosis is a feared complication of COVID-19. To characterize the risks and outcomes associated with fibrotic-like radiographic abnormalities in patients with COVID-19-related acute respiratory distress syndrome (ARDS) and chronic critical illness. DESIGN: Single-center prospective cohort study. SETTING: We examined chest CT scans performed between ICU discharge and 30 days after hospital discharge using established methods to quantify nonfibrotic and fibrotic-like patterns. PATIENTS: Adults hospitalized with COVID-19-related ARDS and chronic critical illness (> 21 d of mechanical ventilation, tracheostomy, and survival to ICU discharge) between March 2020 and May 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We tested associations of fibrotic-like patterns with clinical characteristics and biomarkers, and with time to mechanical ventilator liberation and 6-month survival, controlling for demographics, comorbidities, and COVID-19 therapies. A total of 141 of 616 adults (23%) with COVID-19-related ARDS developed chronic critical illness, and 64 of 141 (46%) had a chest CT a median (interquartile range) 66 days (42-82 d) after intubation. Fifty-five percent had fibrotic-like patterns characterized by reticulations and/or traction bronchiectasis. In adjusted analyses, interleukin-6 level on the day of intubation was associated with fibrotic-like patterns (odds ratio, 4.40 per quartile change; 95% CI, 1.90-10.1 per quartile change). Other inflammatory biomarkers, Sequential Organ Failure Assessment score, age, tidal volume, driving pressure, and ventilator days were not. Fibrotic-like patterns were not associated with longer time to mechanical ventilator liberation or worse 6-month survival. CONCLUSIONS: Approximately half of adults with COVID-19-associated chronic critical illness have fibrotic-like patterns that are associated with higher interleukin-6 levels at intubation. Fibrotic-like patterns are not associated with longer time to liberation from mechanical ventilation or worse 6-month survival.

The Use of Extracorporeal Membrane Oxygenation for COVID-19: Lessons Learned.

The coronavirus disease 2019 (COVID-19) pandemic has seen an increase in global cases of severe acute respiratory distress syndrome (ARDS), with a concomitant increased demand for extracorporeal membrane oxygenation (ECMO). Outcomes of patients with severe ARDS due to COVID-19 infection receiving ECMO support are evolving. The need for surge capacity, practical and ethical limitations on implementing ECMO, and the prolonged duration of ECMO support in patients with COVID-19-related ARDS has revealed limitations in organization and resource utilization. Coordination of efforts at multiple levels, from research to implementation, resulted in numerous innovations in the delivery of ECMO.

Foundations of a life support equipment exchange platform.

Background: The Extracorporeal Life Support Organization Supplies Platform (https://Supplies.ELSO.org) was created out of Extracorporeal Membrane Oxygenation (ECMO) disposable product shortage prior to and during the Coronavirus Disease 2019 (COVID-19) pandemic. This novel Platform supports Centers in obtaining disposables from other Centers when alternative avenues are exhausted. Methods: Driven by the opportunity for increased patient care by using the product availability of the 962 ELSO centers worldwide was the motivation to form an efficient online supply sharing Platform. The pandemic created by COVID-19 became a catalyst to further recognize the magnitude of the supply disruption on a global scale, impacting allocations and guidelines for institutions, practice, and patient care. Conclusions: Records kept on the Platform website are helpful to the industry by providing insights into where difficulties exist in the supply chain for needed equipment. Yet, the common thread is awareness, of how critical situations can stretch resources and challenge our resolve for the best patient care. ELSO is proud to support member centers in these situations, by providing a means of attaining needed ECMO life support products to cover supply shortages.

Extracorporeal Membrane Oxygenation during Respiratory Pandemics: Past, Present, and Future.

The role of extracorporeal membrane oxygenation (ECMO) in the management of severe acute respiratory failure, including acute respiratory distress syndrome, has become better defined in recent years in light of emerging high-quality evidence and technological advances. Use of ECMO has consequently increased throughout many parts of the world. The coronavirus disease (COVID-19) pandemic, however, has highlighted deficiencies in organizational capacity, research capability, knowledge sharing, and resource use. Although governments, medical societies, hospital systems, and clinicians were collectively unprepared for the scope of this pandemic, the use of ECMO, a highly resource-intensive and specialized form of life support, presented specific logistical and ethical challenges. As the pandemic has evolved, there has been greater collaboration in the use of ECMO across centers and regions, together with more robust data reporting through international registries and observational studies. Nevertheless, centralization of ECMO capacity is lacking in many regions of the world, and equitable use of ECMO resources remains uneven. There are no widely available mechanisms to conduct large-scale, rigorous clinical trials in real time. In this critical care review, we outline lessons learned during COVID-19 and prior respiratory pandemics in which ECMO was used, and we describe how we might apply these lessons going forward, both during the ongoing COVID-19 pandemic and in the future.

Fulminant myocarditis in adults: a narrative review.

Fulminant myocarditis (FM) is an uncommon syndrome characterized by sudden and severe hemodynamic compromise secondary to acute myocardial inflammation, often presenting as profound cardiogenic shock, life-threatening ventricular arrhythmias and/or electrical storm. FM may be refractory to conventional therapies and require mechanical circulatory support (MCS). The immune system has been recognized as playing a pivotal role in the pathophysiology of myocarditis, leading to an increased focus on immunosuppressive treatment strategies. Recent data have highlighted not only the fact that FM has significantly worse outcomes than non-FM, but that prognosis and management strategies of FM are heavily dependent on histological subtype, placing greater emphasis on the role of endomyocardial biopsy in diagnosis. The impact of subtype on severity and prognosis will likewise influence how aggressively the myocarditis is managed, including whether MCS is warranted. Many patients with refractory cardiogenic shock secondary to FM end up requiring MCS, with venoarterial extracorporeal membrane oxygenation demonstrating favorable survival rates, particularly when initiated prior to the development of multiorgan failure. Among the challenges facing the field are the need to more precisely identify immunopathophysiological pathways in order to develop targeted therapies, and the need to better optimize the timing and management of MCS to minimize complications and maximize outcomes.

Extracorporeal cardiopulmonary resuscitation in adults: evidence and implications.

Rates of survival with functional recovery for both in-hospital and out-of-hospital cardiac arrest are notably low. Extracorporeal cardiopulmonary resuscitation (ECPR) is emerging as a modality to improve prognosis by augmenting perfusion to vital end-organs by utilizing extracorporeal membrane oxygenation (ECMO) during conventional CPR and stabilizing the patient for interventions aimed at reversing the aetiology of the arrest. Implementing this emergent procedure requires a substantial investment in resources, and even the most successful ECPR programs may nonetheless burden healthcare systems, clinicians, patients, and their families with unsalvageable patients supported by extracorporeal devices. Non-randomized and observational studies have repeatedly shown an association between ECPR and improved survival, versus conventional CPR, for in-hospital cardiac arrest in select patient populations. Recently, randomized controlled trials suggest benefit for ECPR over standard resuscitation, as well as the feasibility of performing such trials, in out-of-hospital cardiac arrest within highly coordinated healthcare delivery systems. Application of these data to clinical practice should be done cautiously, with outcomes likely to vary by the setting and system within which ECPR is initiated. ECPR introduces important ethical challenges, including whether it should be considered an extension of CPR, at what point it becomes sustained organ replacement therapy, and how to approach patients unable to recover or be bridged to heart replacement therapy. The economic impact of ECPR varies by health system, and has the potential to outstrip resources if used indiscriminately. Ideally, studies should include economic evaluations to inform health care systems about the cost-benefits of this therapy.

Extracorporeal membrane oxygenation for coronavirus disease 2019-related acute respiratory distress syndrome.

PURPOSE OF REVIEW: To understand the potential role of extracorporeal membrane oxygenation (ECMO) in coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS), highlighting evolving practices and outcomes. RECENT FINDINGS: The role for ECMO in COVID-19-related ARDS has evolved throughout the pandemic. Early reports of high mortality led to some to advocate for withholding ECMO in this setting. Subsequent data suggested mortality rates were on par with those from studies conducted prior to the pandemic. However, outcomes are evolving and mortality in these patients may be worsening with time. SUMMARY: ECMO has an established role in the treatment of severe forms of ARDS. Current data suggest adherence to the currently accepted algorithm for management of ARDS, including the use of ECMO. However, planning related to resource utilization and strain on healthcare systems are necessary to determine the feasibility of ECMO in specific regions at any given time. Utilization of national and local networks, pooling of resources and ECMO mobilization units are important to optimize access to ECMO as appropriate. Reported complications of ECMO in the setting of COVID-19-related ARDS have been predominantly similar to those reported in studies of non-COVID-19-related ARDS. Further high-quality research is needed.

Latent Class Analysis Reveals COVID-19-related Acute Respiratory Distress Syndrome Subgroups with Differential Responses to Corticosteroids.

Rationale: Two distinct subphenotypes have been identified in acute respiratory distress syndrome (ARDS), but the presence of subgroups in ARDS associated with coronavirus disease (COVID-19) is unknown. Objectives: To identify clinically relevant, novel subgroups in COVID-19-related ARDS and compare them with previously described ARDS subphenotypes. Methods: Eligible participants were adults with COVID-19 and ARDS at Columbia University Irving Medical Center. Latent class analysis was used to identify subgroups with baseline clinical, respiratory, and laboratory data serving as partitioning variables. A previously developed machine learning model was used to classify patients as the hypoinflammatory and hyperinflammatory subphenotypes. Baseline characteristics and clinical outcomes were compared between subgroups. Heterogeneity of treatment effect for corticosteroid use in subgroups was tested. Measurements and Main Results: From March 2, 2020, to April 30, 2020, 483 patients with COVID-19-related ARDS met study criteria. A two-class latent class analysis model best fit the population (P = 0.0075). Class 2 (23%) had higher proinflammatory markers, troponin, creatinine, and lactate, lower bicarbonate, and lower blood pressure than class 1 (77%). Ninety-day mortality was higher in class 2 versus class 1 (75% vs. 48%; P < 0.0001). Considerable overlap was observed between these subgroups and ARDS subphenotypes. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR cycle threshold was associated with mortality in the hypoinflammatory but not the hyperinflammatory phenotype. Heterogeneity of treatment effect to corticosteroids was observed (P = 0.0295), with improved mortality in the hyperinflammatory phenotype and worse mortality in the hypoinflammatory phenotype, with the caveat that corticosteroid treatment was not randomized. Conclusions: We identified two COVID-19-related ARDS subgroups with differential outcomes, similar to previously described ARDS subphenotypes. SARS-CoV-2 PCR cycle threshold had differential value for predicting mortality in the subphenotypes. The subphenotypes had differential treatment responses to corticosteroids.

Tracheostomy management in patients with severe acute respiratory distress syndrome receiving extracorporeal membrane oxygenation: an International Multicenter Retrospective Study.

BACKGROUND: Current practices regarding tracheostomy in patients treated with extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome are unknown. Our objectives were to assess the prevalence and the association between the timing of tracheostomy (during or after ECMO weaning) and related complications, sedative, and analgesic use. METHODS: International, multicenter, retrospective study in four large volume ECMO centers during a 9-year period. RESULTS: Of the 1,168 patients treated with ECMO for severe ARDS (age 48 ± 16 years, 76% male, SAPS II score 51 ± 18) during the enrollment period, 353 (30%) and 177 (15%) underwent tracheostomy placement during or after ECMO, respectively. Severe complications were uncommon in both groups. Local bleeding within 24 h of tracheostomy was four times more frequent during ECMO (25 vs 7% after ECMO, p < 0.01). Cumulative sedative consumption decreased more rapidly after the procedure with sedative doses almost negligible 48-72 h later, when tracheostomy was performed after ECMO decannulation (p < 0.01). A significantly increased level of consciousness was observed within 72 h after tracheostomy in the "after ECMO" group, whereas it was unchanged in the "during-ECMO" group. CONCLUSION: In contrast to patients undergoing tracheostomy after ECMO decannulation, tracheostomy during ECMO was neither associated with a decrease in sedation and analgesia levels nor with an increase in the level of consciousness. This finding together with a higher risk of local bleeding in the days following the procedure reinforces the need for a case-by-case discussion on the balance between risks and benefits of tracheotomy when performed during ECMO.

A randomized double-blind controlled trial of convalescent plasma in adults with severe COVID-19.

BACKGROUNDAlthough convalescent plasma has been widely used to treat severe coronavirus disease 2019 (COVID-19), data from randomized controlled trials that support its efficacy are limited.METHODSWe conducted a randomized, double-blind, controlled trial among adults hospitalized with severe and critical COVID-19 at 5 sites in New York City (USA) and Rio de Janeiro (Brazil). Patients were randomized 2:1 to receive a single transfusion of either convalescent plasma or normal control plasma. The primary outcome was clinical status at 28 days following randomization, measured using an ordinal scale and analyzed using a proportional odds model in the intention-to-treat population.RESULTSOf 223 participants enrolled, 150 were randomized to receive convalescent plasma and 73 to receive normal control plasma. At 28 days, no significant improvement in the clinical scale was observed in participants randomized to convalescent plasma (OR 1.50, 95% confidence interval [CI] 0.83-2.68, P = 0.180). However, 28-day mortality was significantly lower in participants randomized to convalescent plasma versus control plasma (19/150 [12.6%] versus 18/73 [24.6%], OR 0.44, 95% CI 0.22-0.91, P = 0.034). The median titer of anti-SARS-CoV-2 neutralizing antibody in infused convalescent plasma units was 1:160 (IQR 1:80-1:320). In a subset of nasopharyngeal swab samples from Brazil that underwent genomic sequencing, no evidence of neutralization-escape mutants was detected.CONCLUSIONIn adults hospitalized with severe COVID-19, use of convalescent plasma was not associated with significant improvement in day 28 clinical status. However, convalescent plasma was associated with significantly improved survival. A possible explanation is that survivors remained hospitalized at their baseline clinical status.TRIAL REGISTRATIONClinicalTrials.gov, NCT04359810.FUNDINGAmazon Foundation, Skoll Foundation.

Allocating scarce intensive care resources during the COVID-19 pandemic: practical challenges to theoretical frameworks.

The COVID-19 pandemic strained health-care systems throughout the world. For some, available medical resources could not meet the increased demand and rationing was ultimately required. Hospitals and governments often sought to establish triage committees to assist with allocation decisions. However, for institutions operating under crisis standards of care (during times when standards of care must be substantially lowered in the setting of crisis), relying on these committees for rationing decisions was impractical-circumstances were changing too rapidly, occurring in too many diverse locations within hospitals, and the available information for decision making was notably scarce. Furthermore, a utilitarian approach to decision making based on an analysis of outcomes is problematic due to uncertainty regarding outcomes of different therapeutic options. We propose that triage committees could be involved in providing policies and guidance for clinicians to help ensure equity in the application of rationing under crisis standards of care. An approach guided by egalitarian principles, integrated with utilitarian principles, can support physicians at the bedside when they must ration scarce resources.

Extracorporeal Membrane Oxygenation for Coronavirus Disease 2019: Crisis Standards of Care.

The coronavirus disease 2019 (COVID-19) pandemic has placed extraordinary strain on global healthcare systems. Use of extracorporeal membrane oxygenation (ECMO) for patients with severe respiratory or cardiac failure attributed to COVID-19 has been debated due to uncertain survival benefit and the resources required to safely deliver ECMO support. We retrospectively investigated adult patients supported with ECMO for COVID-19 at our institution during the first 80 days following New York City's declaration of a state of emergency. The primary objective was to evaluate survival outcomes in patients supported with ECMO for COVID-19 and describe the programmatic adaptations made in response to pandemic-related crisis conditions. Twenty-two patients with COVID-19 were placed on ECMO during the study period. Median age was 52 years and 18 (81.8%) were male. Twenty-one patients (95.4%) had severe ARDS and seven (31.8%) had cardiac failure. Fifteen patients (68.1%) were managed with venovenous ECMO while 7 (31.8%) required arterial support. Twelve patients (54.5%) were transported on ECMO from external institutions. Twelve patients were discharged alive from the hospital (54.5%). Extracorporeal membrane oxygenation was used successfully in patients with respiratory and cardiac failure due to COVID-19. The continued use of ECMO, including ECMO transport, during crisis conditions was possible even at the height of the COVID-19 pandemic.

A propósito de la contingencia COVID-19. ECMO en el adulto: Oxigenación por membrana extracorpórea. A quién, cómo y cuándo

ECMO (Extracorporeal Membrane Oxygenation) is an extracorporeal life support system in catastrophic lung failure, shock and cardiopulmonary resuscitation, in different age groups, with multiple physiologic features. When the candidate to be submitted is too unstable to be transported to a hospital with ECMO, cannulation before transfer allows stabilization and subsequent transport. The aim of this article is to review the current concepts of extracorporeal support, its indications, national and international experience, and its possible role in the SARS-Cov2 pandemic.

[With regard to COVID-19 contingency. ECMO in adults. Extracorporeal Membrane Oxygenation). To whom, how and when]. / A propósito de la contingencia COVID-19. ECMO en el adulto: Oxigenación por membrana extracorpórea. A quién, cómo y cuándo.

ECMO (Extracorporeal Membrane Oxygenation) is an extracorporeal life support system in catastrophic lung failure, shock and cardiopulmonary resuscitation, in different age groups, with multiple physiologic features. When the candidate to be submitted is too unstable to be transported to a hospital with ECMO, cannulation before transfer allows stabilization and subsequent transport. The aim of this article is to review the current concepts of extracorporeal support, its indications, national and international experience, and its possible role in the SARS-Cov2 pandemic.

Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study.

BACKGROUND: Over 40 000 patients with COVID-19 have been hospitalised in New York City (NY, USA) as of April 28, 2020. Data on the epidemiology, clinical course, and outcomes of critically ill patients with COVID-19 in this setting are needed. METHODS: This prospective observational cohort study took place at two NewYork-Presbyterian hospitals affiliated with Columbia University Irving Medical Center in northern Manhattan. We prospectively identified adult patients (aged ≥18 years) admitted to both hospitals from March 2 to April 1, 2020, who were diagnosed with laboratory-confirmed COVID-19 and were critically ill with acute hypoxaemic respiratory failure, and collected clinical, biomarker, and treatment data. The primary outcome was the rate of in-hospital death. Secondary outcomes included frequency and duration of invasive mechanical ventilation, frequency of vasopressor use and renal replacement therapy, and time to in-hospital clinical deterioration following admission. The relation between clinical risk factors, biomarkers, and in-hospital mortality was modelled using Cox proportional hazards regression. Follow-up time was right-censored on April 28, 2020 so that each patient had at least 28 days of observation. FINDINGS: Between March 2 and April 1, 2020, 1150 adults were admitted to both hospitals with laboratory-confirmed COVID-19, of which 257 (22%) were critically ill. The median age of patients was 62 years (IQR 51-72), 171 (67%) were men. 212 (82%) patients had at least one chronic illness, the most common of which were hypertension (162 [63%]) and diabetes (92 [36%]). 119 (46%) patients had obesity. As of April 28, 2020, 101 (39%) patients had died and 94 (37%) remained hospitalised. 203 (79%) patients received invasive mechanical ventilation for a median of 18 days (IQR 9-28), 170 (66%) of 257 patients received vasopressors and 79 (31%) received renal replacement therapy. The median time to in-hospital deterioration was 3 days (IQR 1-6). In the multivariable Cox model, older age (adjusted hazard ratio [aHR] 1·31 [1·09-1·57] per 10-year increase), chronic cardiac disease (aHR 1·76 [1·08-2·86]), chronic pulmonary disease (aHR 2·94 [1·48-5·84]), higher concentrations of interleukin-6 (aHR 1·11 [95%CI 1·02-1·20] per decile increase), and higher concentrations of D-dimer (aHR 1·10 [1·01-1·19] per decile increase) were independently associated with in-hospital mortality. INTERPRETATION: Critical illness among patients hospitalised with COVID-19 in New York City is common and associated with a high frequency of invasive mechanical ventilation, extrapulmonary organ dysfunction, and substantial in-hospital mortality. FUNDING: National Institute of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences, National Institutes of Health, and the Columbia University Irving Institute for Clinical and Translational Research.