Respiratory extracorporeal membrane oxygenation : From rescue therapy to standard tool for treatment of acute respiratory distress syndrome?

BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) for patients with acute respiratory distress syndrome (ARDS) has increased substantially. With modern trials supporting its efficacy, ECMO has become an important tool in the management of severe ARDS. OBJECTIVES: The objectives of this paper are to discuss ECMO physiology and configurations used for patients with ARDS, review evidence supporting the use of ECMO for ARDS, and discuss aspects of management during ECMO. CONCLUSION: Current evidence supports the use of ECMO, combined with an ultra-lung-protective approach to mechanical ventilation, in patients with ARDS who have refractory hypoxemia or hypercapnia with severe respiratory acidosis. Furthermore, data suggest that center volume and experience are important factors in the care of patients receiving ECMO. The use of extracorporeal technologies in expanded patient populations and the optimal management of patients during ECMO remain areas of investigation. This article is freely available.

Practices surrounding antimicrobial use in patients managed with extracorporeal membrane oxygenation: An international survey.

PURPOSE: This study aimed to survey critical care clinicians and characterize their perception of antimicrobial dosing strategies in patients receiving extracorporeal membrane oxygenation (ECMO). METHODS: International, cross-sectional survey distributed to members of the Society of Critical Care Medicine in October 2022. RESULTS: Respondents were primarily physicians (45%), with 92% practicing in North America. Ninety-seven percent of respondents reported antimicrobial dosing in critically ill patients to be challenging, due to physiological derangements seen in the patient population. Eighty-seven percent reported consideration of physicochemical drug properties when dosing antimicrobials in ECMO-supported patients, with lipophilicity (83%) and degree of protein binding (74%) being the two most common. Respondents' approach to antimicrobial dosing strategies did not significantly differ in critically ill ECMO-supported patients, compared to patients with equal severity of illness not receiving ECMO support. CONCLUSION: Approaches to antimicrobial dosing strategies do not significantly differ among respondents between critically ill patients on ECMO support, compared to patients with equal severity of illness not receiving ECMO support. These findings were unexpected considering the added physiologic complexity of the ECMO circuit to critically ill adult patients and the need for well designed and adequately powered studies to inform empiric dosing guidance for ECMO-supported patients.

Age and associated outcomes among patients receiving venovenous extracorporeal membrane oxygenation for acute respiratory failure: analysis of the Extracorporeal Life Support Organization registry.

PURPOSE: Venovenous extracorporeal membrane oxygenation (VV-ECMO) can be used to support patients with refractory acute respiratory failure, though guidance on patient selection is lacking. While age is commonly utilized as a factor in establishing the potential VV-ECMO candidacy of these patients, little is known regarding its association with outcome. We studied the association between increasing patient age and outcomes among patients with acute respiratory failure receiving VV-ECMO. METHODS: In this registry-based cohort study, we used individual patient data from 144 centres. We included adult patients (≥ 18 years of age) receiving VV-ECMO from 2017 to 2022. The primary outcome was hospital mortality. Secondary outcomes included a composite of complications following initiation of VV-ECMO. We conducted Bayesian analyses to estimate the association between chronological age and outcomes. RESULTS: We included 27,811 patients receiving VV-ECMO. Of these, 11,533 (41.5%) died in hospital. For the analysis conducted using weakly informed priors, and as compared to the reference category of age 18-29, the age brackets of 30-39 (odds ratio [OR] 1.17, 95% credible interval [CrI] 1.06-1.31), 40-49 (OR 1.65, 95% CrI 1.49-1.82), 50-59 (OR 2.39, 95% CrI 2.16-2.61), 60-69 (OR 3.29, 95% CrI 2.97-3.67), 70-79 (OR 4.57, 95% CrI 3.90-5.37), and ≥ 80 (OR 8.08, 95% CrI 4.85-13.74) were independently associated with increasing hospital mortality. Similar results were found between increasing age and post-ECMO complications. CONCLUSIONS: Among patients receiving VV-ECMO for acute respiratory failure, increasing age is significantly associated with poorer outcomes, and this association emerges as early as 30 years of age.

Anticoagulation and Bleeding during Veno-Venous Extracorporeal Membrane Oxygenation: Insights from the PROTECMO Study.

Rationale: Definitive guidelines for anticoagulation management during veno-venous extracorporeal membrane oxygenation (VV ECMO) are lacking, whereas bleeding complications continue to pose major challenges. Objectives: To describe anticoagulation modalities and bleeding events in adults receiving VV ECMO. Methods: This was an international prospective observational study in 41 centers, from December 2018 to February 2021. Anticoagulation was recorded daily in terms of type, dosage, and monitoring strategy. Bleeding events were reported according to site, severity, and impact on mortality. Measurements and Main Results: The study cohort included 652 patients, and 8,471 days on ECMO were analyzed. Unfractionated heparin was the initial anticoagulant in 77% of patients, and the most frequently used anticoagulant during the ECMO course (6,221 d; 73%). Activated partial thromboplastin time (aPTT) was the most common test for monitoring coagulation (86% of days): the median value was 52 seconds (interquartile range, 39 to 61 s) but dropped by 5.3 seconds after the first bleeding event (95% confidence interval, -7.4 to -3.2; P < 0.01). Bleeding occurred on 1,202 days (16.5%). Overall, 342 patients (52.5%) experienced at least one bleeding event (one episode every 215 h on ECMO), of which 10 (1.6%) were fatal. In a multiple penalized Cox proportional hazard model, higher aPTT was a potentially modifiable risk factor for the first episode of bleeding (for 20-s increase; hazard ratio, 1.07). Conclusions: Anticoagulation during VV ECMO was a dynamic process, with frequent stopping in cases of bleeding and restart according to the clinical picture. Future studies might explore lower aPTT targets to reduce the risk of bleeding.

How I manage differential gas exchange in peripheral venoarterial extracorporeal membrane oxygenation.

Dual circulation is a common but underrecognized physiological occurrence associated with peripheral venoarterial extracorporeal membrane oxygenation (ECMO). Competitive flow will develop between blood ejected from the heart and blood travelling retrograde within the aorta from the ECMO reinfusion cannula. The intersection of these two competitive flows is referred to as the "mixing point". The location of this mixing point, which depends upon the relative strengths of the native and extracorporeal pumps, will determine which regions of the body are perfused with blood ejected from the left ventricle and which regions are perfused by reinfused blood from the ECMO circuit, effectively establishing dual circulations. Because gas exchange within these circulations is dictated by the native lungs and membrane lung, respectively, oxygenation and carbon dioxide removal may differ between regions-depending on how well gas exchange is preserved within each circulation-potentially leading to differential oxygenation or differential carbon dioxide, each of which may have important clinical implications. In this perspective, we address the identification and management of dual circulation and differential gas exchange through various clinical scenarios of venoarterial ECMO. Recognition of dual circulation, proper monitoring for differential gas exchange, and understanding the various strategies to resolve differential oxygenation and carbon dioxide may allow for more optimal patient management and improved clinical outcomes.

Mortality in Patients with Obesity and Acute Respiratory Distress Syndrome Receiving Extracorporeal Membrane Oxygenation: The Multicenter ECMObesity Study.

Rationale: Patients with obesity are at increased risk for developing acute respiratory distress syndrome (ARDS). Some centers consider obesity a relative contraindication to receiving extracorporeal membrane oxygenation (ECMO) support, despite growing implementation of ECMO for ARDS in the general population. Objectives: To investigate the association between obesity and mortality in patients with ARDS receiving ECMO. Methods: In this large, international, multicenter, retrospective cohort study, we evaluated the association of obesity, defined as body mass index ⩾ 30 kg/m2, with ICU mortality in patients receiving ECMO for ARDS by performing adjusted multivariable logistic regression and propensity score matching. Measurements and Main Results: Of 790 patients with ARDS receiving ECMO in our study, 320 had obesity. Of those, 24.1% died in the ICU, compared with 35.3% of patients without obesity (P < 0.001). In adjusted models, obesity was associated with lower ICU mortality (odds ratio, 0.63 [95% confidence interval, 0.43-0.93]; P = 0.018). Examined as a continuous variable, higher body mass index was associated with decreased ICU mortality in multivariable regression (odds ratio, 0.97 [95% confidence interval, 0.95-1.00]; P = 0.023). In propensity score matching of 199 patients with obesity to 199 patients without, patients with obesity had a lower probability of ICU death than those without (22.6% vs. 35.2%; P = 0.007). Conclusions: Among patients receiving ECMO for ARDS, those with obesity had lower ICU mortality than patients without obesity in multivariable and propensity score matching analyses. Our findings support the notion that obesity should not be considered a general contraindication to ECMO.

Gender Disparities in Presentation, Management, and Outcomes of Acute Pulmonary Embolism.

Pulmonary embolism (PE) is the third most common cause of cardiovascular death; however, gender disparities in PE remain understudied. All PE cases at a single institution between January 2013 and June 2019 were retrospectively reviewed. The clinical presentation, treatment modalities, and outcomes were compared between men and women using univariate and multivariate analyses adjusting for differences in baseline characteristics. A total of 1,345 patients were diagnosed with acute PE, of whom 56.3% were women (n = 757). Women had a significantly higher mean body mass index (29.4 vs 28.4) and a higher frequency of hypertension (53% vs 46%) and hormone use (6.6% vs 0%; all p <0.02). Men had a higher frequency of smoking (45% vs 33%, p <0.0001). Women had significantly lower PE severity index classifications (p = 0.0009). The rates of intensive care unit admission, vasopressor requirements, extracorporeal membrane oxygenation cannulation, and mechanical ventilation were similar between the genders. There was no significant difference in the treatment modality used between the genders. Although the risk factors and PE severity index class differed between the genders, there was no significant difference in resource utilization or treatment modality. Gender was also not a significant predictor of in-hospital mortality, moderate or severe bleeding, increased length of stay, or readmission in the study population.

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.

Association between Hispanic or Latino ethnicity and pulmonary embolism severity, management, and in-hospital outcomes.

BACKGROUND: Hispanic and Latino patients are under-represented in existing healthcare disparities research in pulmonary embolism (PE). The goal of this study was to determine if differences in PE severity, treatment modality, or in-hospital outcomes exist for Hispanic or Latino patients with PE. METHODS: All PE cases from 2013 to 2019 at a single institution were reviewed. Clinical characteristics, imaging findings, intervention types, and in-hospital and 30-day outcomes were collected. Two cohorts were created based on patients' self-reported ethnicity. Outcomes were compared using univariate and multivariate analysis. RESULTS: A total of 1265 patients were identified with confirmed PE; 474 (37%) identified as Hispanic or Latino. Hispanic or Latino patients presented with high-risk PE significantly less often (19% vs 25%, p = 0.03). On univariate analysis, Hispanic or Latino patients had lower rates of PE-specific intervention (15% vs 19%, p = 0.03) and similar rates of inpatient mortality (6.8% vs 7.5%, p = 0.64). On ordinal regression analysis, Hispanic or Latino ethnicity was associated with lower PE severity (OR 0.69, 95% CI 0.54-0.89, p = 0.003). In subgroup analyses of intermediate and high-risk PEs, ethnicity was not a significant predictor of receipt of PE-specific intervention or in-hospital mortality. CONCLUSIONS: At this institution, Hispanic or Latino patients were less likely to present with high-risk PE but had similar rates of inpatient mortality. Future research is needed to identify if disparities in in-hospital care are driving perceived differences in PE severity and what addressable systematic factors are driving higher-than-expected in-hospital mortality for Hispanic or Latino patients.

Transfusion practice in patients receiving VV ECMO (PROTECMO): a prospective, multicentre, observational study.

BACKGROUND: In patients receiving venovenous (VV) extracorporeal membrane oxygenation (ECMO) packed red blood cell (PRBC) transfusion thresholds are usually higher than in other patients who are critically ill. Available guidelines suggest a restrictive approach, but do not provide specific recommendations on the topic. The main aim of this study was, in a short timeframe, to describe the actual values of haemoglobin and the rate and the thresholds for transfusion of PRBC during VV ECMO. METHODS: PROTECMO was a multicentre, prospective, cohort study done in 41 ECMO centres in Europe, North America, Asia, and Australia. Consecutive adult patients with acute respiratory distress syndrome (ARDS) who were receiving VV ECMO were eligible for inclusion. Patients younger than 18 years, those who were not able to provide informed consent when required, and patients with an ECMO stay of less than 24 h were excluded. Our main aim was to monitor the daily haemoglobin concentration and the value at the point of PRBC transfusion, as well as the rate of transfusions. The practice in different centres was stratified by continent location and case volume per year. Adjusted estimates were calculated using marginal structural models with inverse probability weighting, accounting for baseline and time varying confounding. FINDINGS: Between Dec 1, 2018, and Feb 22, 2021, 604 patients were enrolled (431 [71%] men, 173 [29%] women; mean age 50 years [SD 13·6]; and mean haemoglobin concentration at cannulation 10·9 g/dL [2·4]). Over 7944 ECMO days, mean haemoglobin concentration was 9·1 g/dL (1·2), with lower concentrations in North America and high-volume centres. PRBC were transfused on 2432 (31%) of days on ECMO, and 504 (83%) patients received at least one PRBC unit. Overall, mean pretransfusion haemoglobin concentration was 8·1 g/dL (1·1), but varied according to the clinical rationale for transfusion. In a time-dependent Cox model, haemoglobin concentration of less than 7 g/dL was consistently associated with higher risk of death in the intensive care unit compared with other higher haemoglobin concentrations (hazard ratio [HR] 2·99 [95% CI 1·95-4·60]); PRBC transfusion was associated with lower risk of death only when transfused when haemoglobin concentration was less than 7 g/dL (HR 0·15 [0·03-0·74]), although no significant effect in reducing mortality was reported for transfusions for other haemoglobin classes (7·0-7·9 g/dL, 8·0-9·9 g/dL, or higher than 10 g/dL). INTERPRETATION: During VV ECMO, there was no universally accepted threshold for transfusion, but PRBC transfusion was invariably associated with lower mortality only when done with haemoglobin concentration of less than 7 g/dL. FUNDING: Extracorporeal Life Support Organization.

Extracorporeal Membrane Oxygenation Support in COVID-19 Patients: A Propensity Score Analysis.

Revised guidelines clarify indications for extracorporeal membrane oxygenation (ECMO) support in Coronavirus disease 2019 (COVID-19) patients with acute respiratory distress syndrome (ARDS). Limited data exist to compare clinical outcomes of COVID-19 ARDS patients to non-COVID-19-related ARDS patients when supported with ECMO. An observational propensity-matched study was performed to compare clinical and ECMO-related complications between COVID-19-related ARDS patients (COVID) and non-COVID-19-related ARDS (Control). COVID- patients cannulated from March 1st, 2020, through June 1st, 2021, were included and matched to patients from the historical cohort at our center from 2012 to 2020 based on age, body mass index (BMI), acute physiology and chronic health evaluation (APACHE) II score, and duration ECMO run. The primary outcome was complications during ECMO therapy. A total of 56 patients were propensity matched 1:1 with a mean age of 40.9 years, BMI 32.1 kg/m2, APACHE II score of 26.6, and duration of ECMO support of 22.6 days. In total 18 COVID-19 patients were observed to have more major bleeding complications (18 vs. 9, p = 0.03). Although not statistically significant, they also had more strokes (6 vs. 3) and required more chest tubes (13 vs. 8). Inpatient mortality was not different. ECMO support in COVID-19 patients is associated with more major bleeding complications, strokes, and chest tube placements. The use of ECMO in patients with COVID-19-related ARDS appears to be associated with an increased risk of complications.

Extracorporeal Life Support Organization Guideline for Transport and Retrieval of Adult and Pediatric Patients with ECMO Support.

DISCLAIMER: This guideline for the preparation for and undertaking of transport and retrieval of patients on extracorporeal membrane oxygenation (ECMO) is intended for educational use to build the knowledge of physicians and other health professionals in assessing the conditions and managing the treatment of patients undergoing ECLS / ECMO and describe what are believed to be useful and safe practice for extracorporeal life support (ECLS, ECMO) but these are not necessarily consensus recommendations. The aim of clinical guidelines are to help clinicians to make informed decisions about their patients. However, adherence to a guideline does not guarantee a successful outcome. Ultimately, healthcare professionals must make their own treatment decisions about care on a case-by-case basis, after consultation with their patients, using their clinical judgement, knowledge and expertise. These guidelines do not take the place of physicians' and other health professionals' judgment in diagnosing and treatment of particular patients. These guidelines are not intended to and should not be interpreted as setting a standard of care or be deemed inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results. The ultimate judgment must be made by the physician and other health professionals and the patient in light of all the circumstances presented by the individual patient, and the known variability and biological behavior of the clinical condition. These guidelines reflect the data at the time the guidelines were prepared; the results of subsequent studies or other information may cause revisions to the recommendations in these guidelines to be prudent to reflect new data, but ELSO is under no obligation to provide updates. In no event will ELSO be liable for any decision made or action taken in reliance upon the information provided through these guidelines.

Risks and Benefits of Ultra-Lung-Protective Invasive Mechanical Ventilation Strategies with a Focus on Extracorporeal Support.

Lung-protective ventilation strategies are the current standard of care for patients with acute respiratory distress syndrome in an effort to provide adequate ventilatory requirements while minimizing ventilator-induced lung injury. Some patients may benefit from ultra-lung-protective ventilation, a strategy that achieves lower airway pressures and Vt than the current standard. Specific physiological parameters beyond severity of hypoxemia, such as driving pressure and respiratory system elastance, may be predictive of those most likely to benefit. Because application of ultra-lung-protective ventilation is often limited by respiratory acidosis, extracorporeal membrane oxygenation or extracorporeal carbon dioxide removal, which remove carbon dioxide from blood, is an attractive option. These strategies are associated with hematological complications, especially when applied at low blood-flow rates with devices designed for higher blood flows, and a recent large randomized controlled trial failed to show a benefit from an extracorporeal carbon dioxide removal-facilitated ultra-lung-protective ventilation strategy. Only in patients with very severe forms of acute respiratory distress syndrome has the use of an ultra-lung-protective ventilation strategy-accomplished with extracorporeal membrane oxygenation-been suggested to have a favorable risk-to-benefit profile. In this critical care perspective, we address key areas of controversy related to ultra-lung-protective ventilation, including the trade-offs between minimizing ventilator-induced lung injury and the risks from strategies to achieve this added protection. In addition, we suggest which patients might benefit most from an ultra-lung-protective strategy and propose areas of future research.

Early Mobilization during Extracorporeal Membrane Oxygenation for Cardiopulmonary Failure in Adults: Factors Associated with Intensity of Treatment.

Rationale: Early mobilization of extracorporeal membrane oxygenation (ECMO)-supported patients is increasingly common, but it remains unknown whether there are factors predictive of achieving higher intensity mobilization among those able to participate in physical therapy. Additionally, data regarding the safety and feasibility of early mobilization with femoral cannulation, particularly ambulation, are sparse. Objectives: To determine whether there are factors associated with achieving out-of-bed versus in-bed physical therapy in ECMO-supported patients participating in physical therapy, and whether mobilization with femoral cannulation is safe and feasible. Methods: This large, single-center, retrospective study evaluated adult patients who performed active physical therapy while receiving ECMO. Mixed effects modeling was used to identify predictors of out-of-bed versus in-bed activity. Rates of mobilization with femoral cannulation and adverse events were also reported. Results: Between April 2009 and January 2020, 511 patients were supported with ECMO in a single medical intensive care unit, of whom 177 (35%) underwent active physical therapy and were included in the analysis, including 124 of 141 (88%) bridge to lung transplantation and 53 of 370 (14%) bridge to recovery. These 177 patients accounted for 2,706 active physical therapy sessions, with 138 patients (78%) achieving out-of-bed activity. In total, 108 (61%) patients ambulated (1,284 sessions), 34 of whom had femoral cannulae (250 sessions). Bridge-to-transplant (odds ratio [OR], 17.2; 95% confidence interval [CI], 4.12-72.1), venovenous ECMO (OR, 2.83; 95% CI, 1.29-6.22), later cannulation year (OR, 1.65; 95% CI, 1.37-1.98) and higher Charlson comorbidity index (OR, 1.53; 95% CI, 1.07-2.19) were associated with increased odds of achieving out-of-bed versus in-bed physical therapy, whereas invasive mechanical ventilation (OR, 0.11; 95% CI, 0.05-0.25) and femoral cannulation (OR, 0.19; 95% CI, 0.04-0.92) were associated with decreased odds of performing out-of-bed activities. Adverse events occurred in 2% of sessions. Conclusions: Several patient- and ECMO-related factors were associated with achieving higher intensity of early mobilization in patients participating in rehabilitation. Physical therapy with femoral cannulation was safe and feasible, and complications related to mobilization were uncommon.

Extracorporeal membrane oxygenation for COVID-19: evolving outcomes from the international Extracorporeal Life Support Organization Registry.

BACKGROUND: Over the course of the COVID-19 pandemic, the care of patients with COVID-19 has changed and the use of extracorporeal membrane oxygenation (ECMO) has increased. We aimed to examine patient selection, treatments, outcomes, and ECMO centre characteristics over the course of the pandemic to date. METHODS: We retrospectively analysed the Extracorporeal Life Support Organization Registry and COVID-19 Addendum to compare three groups of ECMO-supported patients with COVID-19 (aged ≥16 years). At early-adopting centres-ie, those using ECMO support for COVID-19 throughout 2020-we compared patients who started ECMO on or before May 1, 2020 (group A1), and between May 2 and Dec 31, 2020 (group A2). Late-adopting centres were those that provided ECMO for COVID-19 only after May 1, 2020 (group B). The primary outcome was in-hospital mortality in a time-to-event analysis assessed 90 days after ECMO initiation. A Cox proportional hazards model was fit to compare the patient and centre-level adjusted relative risk of mortality among the groups. FINDINGS: In 2020, 4812 patients with COVID-19 received ECMO across 349 centres within 41 countries. For early-adopting centres, the cumulative incidence of in-hospital mortality 90 days after ECMO initiation was 36·9% (95% CI 34·1-39·7) in patients who started ECMO on or before May 1 (group A1) versus 51·9% (50·0-53·8) after May 1 (group A2); at late-adopting centres (group B), it was 58·9% (55·4-62·3). Relative to patients in group A2, group A1 patients had a lower adjusted relative risk of in-hospital mortality 90 days after ECMO (hazard ratio 0·82 [0·70-0·96]), whereas group B patients had a higher adjusted relative risk (1·42 [1·17-1·73]). INTERPRETATION: Mortality after ECMO for patients with COVID-19 worsened during 2020. These findings inform the role of ECMO in COVID-19 for patients, clinicians, and policy makers. FUNDING: None.

Lung transplantation disparities based on diagnosis for patients bridging to transplant on extracorporeal membrane oxygenation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly utilized as a bridge to lung transplantation, but ECMO status is not explicitly accounted for in the Lung Allocation Score (LAS). We hypothesized that among waitlist patients on ECMO, patients with pulmonary arterial hypertension (PAH) would have lower transplantation rates. METHODS: Using United Network for Organ Sharing data, we conducted a retrospective cohort study of patients who were ≥12 years old, active on the lung transplant waitlist, and required ECMO support from June 1, 2015 through June 12, 2020. Multivariable competing risk analysis was used to examine waitlist outcomes. RESULTS: 1064 waitlist subjects required ECMO support; 40 (3.8%) had obstructive lung disease (OLD), 97 (9.1%) had PAH,138 (13.0%) had cystic fibrosis (CF), and 789 (74.1%) had interstitial lung disease (ILD). Ultimately, 671 (63.1%) underwent transplant, while 334 (31.4%) died or were delisted. The transplant rate per person-years on the waitlist on ECMO was 15.41 for OLD, 6.05 for PAH, 15.66 for CF, and 15.62 for ILD. Compared to PAH patients, OLD, CF, and ILD patients were 78%, 69%, and 62% more likely to undergo transplant throughout the study period, respectively (adjusted SHRs 1.78 p = 0.007, 1.69 p = 0.002, and 1.62 p = 0.001). The median LAS at waitlist removal for transplantation, death, or delisting were 75.1 for OLD, 79.6 for PAH, 91.0 for CF, and 88.3 for ILD (p < 0.001). CONCLUSIONS: Among patients bridging to transplant on ECMO, patients with PAH had a lower transplantation rate than patients with OLD, CF, and ILD.

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.

The Evolution of the Use of Extracorporeal Membrane Oxygenation in Respiratory Failure.

Extracorporeal membrane oxygenation (ECMO) has been used with increasing frequency to support patients with acute respiratory failure, most commonly, and severe forms of acute respiratory distress syndrome (ARDS). The marked increase in the global use of ECMO followed the publication of a large randomized trial in 2009 and the experience garnered during the 2009 influenza A (H1N1) pandemic, and has been further supported by the release of a large, randomized clinical trial in 2018, confirming a benefit from using ECMO in patients with severe ARDS. Despite a rapid expansion of ECMO-related publications, optimal management of patients receiving ECMO, in terms of patient selection, ventilator management, anticoagulation, and transfusion strategies, is evolving. Most recently, ECMO is being utilized for an expanding variety of conditions, including for cases of severe pulmonary or cardiac failure from coronavirus disease 2019 (COVID-19). This review evaluates modern evidence for ECMO for respiratory failure and the current challenges in the field.

Pulmonary Embolism Response Team utilization during the COVID-19 pandemic.

Coronavirus disease 2019 (COVID-19) may predispose patients to venous thromboembolism (VTE). Limited data are available on the utilization of the Pulmonary Embolism Response Team (PERT) in the setting of the COVID-19 global pandemic. We performed a single-center study to evaluate treatment, mortality, and bleeding outcomes in patients who received PERT consultations in March and April 2020, compared to historical controls from the same period in 2019. Clinical data were abstracted from the electronic medical record. The primary study endpoints were inpatient mortality and GUSTO moderate-to-severe bleeding. The frequency of PERT utilization was nearly threefold higher during March and April 2020 (n = 74) compared to the same period in 2019 (n = 26). During the COVID-19 pandemic, there was significantly less PERT-guided invasive treatment (5.5% vs 23.1%, p = 0.02) with a numerical but not statistically significant trend toward an increase in the use of systemic fibrinolytic therapy (13.5% vs 3.9%, p = 0.3). There were nonsignificant trends toward higher in-hospital mortality or moderate-to-severe bleeding in patients receiving PERT consultations during the COVID-19 period compared to historical controls (mortality 14.9% vs 3.9%, p = 0.18 and moderate-to-severe bleeding 35.1% vs 19.2%, p = 0.13). In conclusion, PERT utilization was nearly threefold higher during the COVID-19 pandemic than during the historical control period. Among patients evaluated by PERT, in-hospital mortality or moderate-to-severe bleeding were not significantly different, despite being numerically higher, while invasive therapy was utilized less frequently during the COVID-19 pandemic.