Renin-Angiotensin System Modulation With Synthetic Angiotensin (1-7) and Angiotensin II Type 1 Receptor-Biased Ligand in Adults With COVID-19: Two Randomized Clinical Trials.

Importance: Preclinical models suggest dysregulation of the renin-angiotensin system (RAS) caused by SARS-CoV-2 infection may increase the relative activity of angiotensin II compared with angiotensin (1-7) and may be an important contributor to COVID-19 pathophysiology. Objective: To evaluate the efficacy and safety of RAS modulation using 2 investigational RAS agents, TXA-127 (synthetic angiotensin [1-7]) and TRV-027 (an angiotensin II type 1 receptor-biased ligand), that are hypothesized to potentiate the action of angiotensin (1-7) and mitigate the action of the angiotensin II. Design, Setting, and Participants: Two randomized clinical trials including adults hospitalized with acute COVID-19 and new-onset hypoxemia were conducted at 35 sites in the US between July 22, 2021, and April 20, 2022; last follow-up visit: July 26, 2022. Interventions: A 0.5-mg/kg intravenous infusion of TXA-127 once daily for 5 days or placebo. A 12-mg/h continuous intravenous infusion of TRV-027 for 5 days or placebo. Main Outcomes and Measures: The primary outcome was oxygen-free days, an ordinal outcome that classifies a patient's status at day 28 based on mortality and duration of supplemental oxygen use; an adjusted odds ratio (OR) greater than 1.0 indicated superiority of the RAS agent vs placebo. A key secondary outcome was 28-day all-cause mortality. Safety outcomes included allergic reaction, new kidney replacement therapy, and hypotension. Results: Both trials met prespecified early stopping criteria for a low probability of efficacy. Of 343 patients in the TXA-127 trial (226 [65.9%] aged 31-64 years, 200 [58.3%] men, 225 [65.6%] White, and 274 [79.9%] not Hispanic), 170 received TXA-127 and 173 received placebo. Of 290 patients in the TRV-027 trial (199 [68.6%] aged 31-64 years, 168 [57.9%] men, 195 [67.2%] White, and 225 [77.6%] not Hispanic), 145 received TRV-027 and 145 received placebo. Compared with placebo, both TXA-127 (unadjusted mean difference, -2.3 [95% CrI, -4.8 to 0.2]; adjusted OR, 0.88 [95% CrI, 0.59 to 1.30]) and TRV-027 (unadjusted mean difference, -2.4 [95% CrI, -5.1 to 0.3]; adjusted OR, 0.74 [95% CrI, 0.48 to 1.13]) resulted in no difference in oxygen-free days. In the TXA-127 trial, 28-day all-cause mortality occurred in 22 of 163 patients (13.5%) in the TXA-127 group vs 22 of 166 patients (13.3%) in the placebo group (adjusted OR, 0.83 [95% CrI, 0.41 to 1.66]). In the TRV-027 trial, 28-day all-cause mortality occurred in 29 of 141 patients (20.6%) in the TRV-027 group vs 18 of 140 patients (12.9%) in the placebo group (adjusted OR, 1.52 [95% CrI, 0.75 to 3.08]). The frequency of the safety outcomes was similar with either TXA-127 or TRV-027 vs placebo. Conclusions and Relevance: In adults with severe COVID-19, RAS modulation (TXA-127 or TRV-027) did not improve oxygen-free days vs placebo. These results do not support the hypotheses that pharmacological interventions that selectively block the angiotensin II type 1 receptor or increase angiotensin (1-7) improve outcomes for patients with severe COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04924660.

Quantifying Critical Care Pharmacist Interventions in COVID-19.

Purpose/Background: Pharmacists have been shown to play an important role in the medication management of critically ill patients. Pharmacist interventions in the care of critically ill patients with coronavirus disease 2019 (COVID-19) have not been quantitatively described. Methodology: A single center, retrospective, observational study was conducted at Vanderbilt University Medical Center in Nashville, Tennessee. All adult patients admitted to the COVID-19 intensive care unit (ICU) or Medical ICU with a COVID-19 diagnosis between March 1, 2020, and June 30, 2021, were included. All interventions made by pharmacists were documented electronically, collected, categorized, and analyzed. The primary outcome of this study was the median number of interventions by pharmacists per patient. The secondary outcome was the number of different types of interventions performed. Results: A total of 768 patients were included in the analysis. The median age was 63 years old; 63% of patients were male and 71% were Caucasian. Median hospital length of stay (LOS) was 12 days (interquartile range (IQR) 7-21) and ICU LOS was 5 days (IQR 1-11). The median Sequential Organ Failure Assessment score was 4 (IQR 2-7) and Charlson Comorbidity Index was 3 (IQR 2-5). Mortality at 60 days occurred in 352 patients (46%). Pharmacists performed a total of 7027 interventions for 655 patients with a median number of pharmacist interventions per patient of 6 (IQR 3-14). The most common pharmacist interventions were medication discontinuation (24%), completion of components of the ICU liberation bundle (19%), medication dose adjustment (18%), therapeutic drug monitoring (15%), and medication initiation (10%). Conclusions: Pharmacists made multiple interventions related to medication use and management in critically ill patients with COVID-19. This study adds important information of the evolving role clinical pharmacists play in the care of critical illness, specifically during the COVID-19 pandemic.

Extracorporeal Membrane Oxygenation Selection by Multidisciplinary Consensus: The ECMO Council.

Coronavirus disease 2019 (COVID-19) has increased the demand for extracorporeal membrane oxygenation (ECMO) and introduced distinct challenges to patient selection for ECMO. Standardized processes for patient selection amidst resource limitations are lacking, and data on ECMO consults are underreported. We retrospectively reviewed consecutive adult ECMO consults for acute respiratory failure received at a single academic medical center from April 1, 2020, to February 28, 2021, and evaluated the implementation of a multidisciplinary selection committee (ECMO Council) and standardized framework for patient selection for ECMO. During the 334-day period, there were 202 total ECMO consults; 174 (86.1%) included a diagnosis of COVID-19. Among all consults, 157 (77.7%) were declined and 41 (20.3%) resulted in the initiation of ECMO. Frequent reasons for decline included the presence of multiple relative contraindications (n = 33), age greater than 60 years (n = 32), and resource limitations (n = 27). The ECMO Council deliberated on every case in which an absolute contraindication was not present (n = 96) via an electronic teleconference platform. Utilizing multidisciplinary consensus together with a standardized process for patient selection in ECMO is feasible during a pandemic and may be reliably exercised over time. Whether such an approach is feasible at other centers remains unknown.

Oxygen-Saturation Targets for Critically Ill Adults Receiving Mechanical Ventilation.

BACKGROUND: Invasive mechanical ventilation in critically ill adults involves adjusting the fraction of inspired oxygen to maintain arterial oxygen saturation. The oxygen-saturation target that will optimize clinical outcomes in this patient population remains unknown. METHODS: In a pragmatic, cluster-randomized, cluster-crossover trial conducted in the emergency department and medical intensive care unit at an academic center, we assigned adults who were receiving mechanical ventilation to a lower target for oxygen saturation as measured by pulse oximetry (Spo₂) (90%; goal range, 88 to 92%), an intermediate target (94%; goal range, 92 to 96%), or a higher target (98%; goal range, 96 to 100%). The primary outcome was the number of days alive and free of mechanical ventilation (ventilator-free days) through day 28. The secondary outcome was death by day 28, with data censored at hospital discharge. RESULTS: A total of 2541 patients were included in the primary analysis. The median number of ventilator-free days was 20 (interquartile range, 0 to 25) in the lower-target group, 21 (interquartile range, 0 to 25) in the intermediate-target group, and 21 (interquartile range, 0 to 26) in the higher-target group (P = 0.81). In-hospital death by day 28 occurred in 281 of the 808 patients (34.8%) in the lower-target group, 292 of the 859 patients (34.0%) in the intermediate-target group, and 290 of the 874 patients (33.2%) in the higher-target group. The incidences of cardiac arrest, arrhythmia, myocardial infarction, stroke, and pneumothorax were similar in the three groups. CONCLUSIONS: Among critically ill adults receiving invasive mechanical ventilation, the number of ventilator-free days did not differ among groups in which a lower, intermediate, or higher Spo₂ target was used. (Supported by the National Heart, Lung, and Blood Institute and others; PILOT ClinicalTrials.gov number, NCT03537937.).

Extracorporeal membrane oxygenation circuits in parallel for refractory hypoxemia in patients with COVID-19.

OBJECTIVES: Refractory hypoxemia can occur in patients with acute respiratory distress syndrome from COVID-19 despite support with venovenous (VV) extracorporeal membrane oxygenation (ECMO). Parallel ECMO circuits can be used to increase physiologic support. We report our clinical experience using ECMO circuits in parallel for select patients with persistent severe hypoxemia despite the use of a single ECMO circuit. METHODS: We performed a retrospective cohort study of all patients with COVID-19-related acute respiratory distress syndrome who received VV-ECMO with an additional circuit in parallel at Vanderbilt University Medical Center between March 1, 2020, and March 1, 2022. We report demographic characteristics and clinical characteristics including ECMO settings, mechanical ventilator settings, use of adjunctive therapies, and arterial blood gas results after initial cannulation, before and after receipt of a second ECMO circuit in parallel, and before removal of the circuit in parallel, and outcomes. RESULTS: Of 84 patients with COVID-19 who received VV-ECMO during the study period, 22 patients (26.2%) received a circuit in parallel. The median duration of ECMO was 40.0 days (interquartile range, 31.6-53.1 days), of which 19.0 days (interquartile range, 13.0-33.0 days) were spent with a circuit in parallel. Of the 22 patients who received a circuit in parallel, 16 (72.7%) survived to hospital discharge and 6 (27.3%) died before discharge. CONCLUSIONS: In select patients, the additional use of an ECMO circuit in parallel can increase ECMO blood flow and improve oxygenation while allowing for lung-protective mechanical ventilation and excellent outcomes.

Hydroxychloroquine/chloroquine for the treatment of hospitalized patients with COVID-19: An individual participant data meta-analysis.

BACKGROUND: Results from observational studies and randomized clinical trials (RCTs) have led to the consensus that hydroxychloroquine (HCQ) and chloroquine (CQ) are not effective for COVID-19 prevention or treatment. Pooling individual participant data, including unanalyzed data from trials terminated early, enables more detailed investigation of the efficacy and safety of HCQ/CQ among subgroups of hospitalized patients. METHODS: We searched ClinicalTrials.gov in May and June 2020 for US-based RCTs evaluating HCQ/CQ in hospitalized COVID-19 patients in which the outcomes defined in this study were recorded or could be extrapolated. The primary outcome was a 7-point ordinal scale measured between day 28 and 35 post enrollment; comparisons used proportional odds ratios. Harmonized de-identified data were collected via a common template spreadsheet sent to each principal investigator. The data were analyzed by fitting a prespecified Bayesian ordinal regression model and standardizing the resulting predictions. RESULTS: Eight of 19 trials met eligibility criteria and agreed to participate. Patient-level data were available from 770 participants (412 HCQ/CQ vs 358 control). Baseline characteristics were similar between groups. We did not find evidence of a difference in COVID-19 ordinal scores between days 28 and 35 post-enrollment in the pooled patient population (odds ratio, 0.97; 95% credible interval, 0.76-1.24; higher favors HCQ/CQ), and found no convincing evidence of meaningful treatment effect heterogeneity among prespecified subgroups. Adverse event and serious adverse event rates were numerically higher with HCQ/CQ vs control (0.39 vs 0.29 and 0.13 vs 0.09 per patient, respectively). CONCLUSIONS: The findings of this individual participant data meta-analysis reinforce those of individual RCTs that HCQ/CQ is not efficacious for treatment of COVID-19 in hospitalized patients.

Pulse Oximetry and Race in Critically Ill Adults.

For critically ill adults, oxygen saturation is continuously monitored using pulse oximetry (Spo2) as a surrogate for arterial oxygen saturation (Sao2). Skin pigmentation may affect accuracy of Spo2 by introducing error from statistical bias, variance, or both. We evaluated relationships between race, Spo2, Sao2, and hypoxemia (Sao2 < 88%) or hyperoxemia (Pao2 > 150 mm Hg) among adults receiving mechanical ventilation in a medical ICU. DESIGN: Single-center, observational study. SETTING: Medical ICU at an academic medical center. PATIENTS: Critically ill adults receiving mechanical ventilation from July 2018 to February 2021, excluding patients with COVID-19, with race documented as Black or White in the electronic medical record, who had a pair of Spo2 and Sao2 measurements collected within 10 minutes of each other. INTERVENTIONS: None. MEASUREMENTS: We included 1,024 patients with 5,557 paired measurements within 10 minutes, of which 3,885 (70%) were within 1 minute. Of all pairs, 769 (14%) were from Black patients and 4,788 (86%) were from White patients. In analyses using a mixed-effects model, we found that across the range of Spo2 values of 92-98%, the associated Sao2 value was approximately 1% point lower for Black patients compared with White patients. Among patients with a Spo2 value between 92% and 96%, Black patients were more likely to have both hypoxemia (3.5% vs 1.1%; p = 0.002) and hyperoxemia (4.7% vs 2.4%; p = 0.03), compared with White patients. CONCLUSIONS: Among patients with a measured Spo2 of 92-96%, greater variation in Sao2 values at a given Spo2 resulted in a higher occurence rate of both hypoxemia and hyperoxemia for Black patients compared with White patients.

Extracorporeal Membrane Oxygenation Circuits in Parallel for Refractory Hypoxemia in COVID-19

Objectives Refractory hypoxemia can occur in patients with acute respiratory distress syndrome (ARDS) from Coronavirus disease 2019 (COVID-19) despite support with venovenous extracorporeal membrane oxygenation (VV-ECMO). Parallel ECMO circuits can be used to increase physiologic support. We report our clinical experience using ECMO circuits in parallel for select patients with persistent severe hypoxemia despite the use of a single ECMO circuit. Methods We performed a retrospective cohort study of all patients with COVID-19 related ARDS receiving VV-ECMO who received an additional circuit in parallel at Vanderbilt University Medical Center between March 1, 2020 and March 1, 2022. We report demographics, clinical characteristics including ECMO settings, mechanical ventilator settings, use of adjunctive therapies, and arterial blood gas results after initial cannulation, before and after receipt of a second ECMO circuit in parallel, and prior to removal of the circuit in parallel, and outcomes. Results Of 84 patients with COVID-19 who received VV-ECMO during the study period, 22 patients (26.2%) received a circuit in parallel. The median time on ECMO was 40.0 days (IQR, 31.6-53.1 days), of which 19.0 days (IQR, 13.0-33.0 days) were spent on a circuit in parallel. Of the 22 patients who received a circuit in parallel, 16 (72.7%) survived to hospital discharge and 6 (27.3%) died before discharge. Conclusions In select patients, addition of an ECMO circuit in parallel can increase ECMO blood flow and improve oxygenation while allowing for lung-protective mechanical ventilation and excellent outcomes.

Oxygen-Free Days as an Outcome Measure in Clinical Trials of Therapies for COVID-19 and Other Causes of New-Onset Hypoxemia.

Mortality historically has been the primary outcome of choice for acute and critical care clinical trials. However, undue reliance on mortality can limit the scope of trials that can be performed. Large sample sizes are usually needed for trials powered for a mortality outcome, and focusing solely on mortality fails to recognize the importance that reducing morbidity can have on patients' lives. The COVID-19 pandemic has highlighted the need for rapid, efficient trials to rigorously evaluate new therapies for hospitalized patients with acute lung injury. Oxygen-free days (OFDs) is a novel outcome for clinical trials that is a composite of mortality and duration of new supplemental oxygen use. It is designed to characterize recovery from acute lung injury in populations with a high prevalence of new hypoxemia and supplemental oxygen use. In these populations, OFDs captures two patient-centered consequences of acute lung injury: mortality and hypoxemic lung dysfunction. Power to detect differences in OFDs typically is greater than that for other clinical trial outcomes, such as mortality and ventilator-free days. OFDs is the primary outcome for the Fourth Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-4) Host Tissue platform, which evaluates novel therapies targeting the host response to COVID-19 among adults hospitalized with COVID-19 and new hypoxemia. This article outlines the rationale for use of OFDs as an outcome for clinical trials, proposes a standardized method for defining and analyzing OFDs, and provides a framework for sample size calculations using the OFD outcome.

Protocol and statistical analysis plan for the Pragmatic Investigation of optimaL Oxygen Targets (PILOT) clinical trial.

INTRODUCTION: Mechanical ventilation of intensive care unit (ICU) patients universally involves titration of the fraction of inspired oxygen to maintain arterial oxygen saturation (SpO2). However, the optimal SpO2 target remains unknown. METHODS AND ANALYSIS: The Pragmatic Investigation of optimaL Oxygen Targets (PILOT) trial is a prospective, unblinded, pragmatic, cluster-crossover trial being conducted in the emergency department (ED) and medical ICU at Vanderbilt University Medical Center in Nashville, Tennessee, USA. PILOT compares use of a lower SpO2 target (target 90% and goal range: 88%-92%), an intermediate SpO2 target (target 94% and goal range: 92%-96%) and a higher SpO2 target (target 98% and goal range: 96%-100%). The study units are assigned to a single SpO2 target (cluster-level allocation) for each 2-month study block, and the assigned SpO2 target switches every 2 months in a randomly generated sequence (cluster-level crossover). The primary outcome is ventilator-free days (VFDs) to study day 28, defined as the number of days alive and free of invasive mechanical ventilation from the final receipt of invasive mechanical ventilation through 28 days after enrolment. ETHICS AND DISSEMINATION: The trial was approved by the Vanderbilt Institutional Review Board. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences. TRIAL REGISTRATION NUMBER: The trial protocol was registered with ClinicalTrials.gov on 25 May 2018 prior to initiation of patient enrolment (ClinicalTrials.gov identifier: NCT03537937).

Machine Learning Prediction of Death in Critically Ill Patients With Coronavirus Disease 2019.

OBJECTIVES: Critically ill patients with coronavirus disease 2019 have variable mortality. Risk scores could improve care and be used for prognostic enrichment in trials. We aimed to compare machine learning algorithms and develop a simple tool for predicting 28-day mortality in ICU patients with coronavirus disease 2019. DESIGN: This was an observational study of adult patients with coronavirus disease 2019. The primary outcome was 28-day inhospital mortality. Machine learning models and a simple tool were derived using variables from the first 48 hours of ICU admission and validated externally in independent sites and temporally with more recent admissions. Models were compared with a modified Sequential Organ Failure Assessment score, National Early Warning Score, and CURB-65 using the area under the receiver operating characteristic curve and calibration. SETTING: Sixty-eight U.S. ICUs. PATIENTS: Adults with coronavirus disease 2019 admitted to 68 ICUs in the United States between March 4, 2020, and June 29, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The study included 5,075 patients, 1,846 (36.4%) of whom died by day 28. eXtreme Gradient Boosting had the highest area under the receiver operating characteristic curve in external validation (0.81) and was well-calibrated, while k-nearest neighbors were the lowest performing machine learning algorithm (area under the receiver operating characteristic curve 0.69). Findings were similar with temporal validation. The simple tool, which was created using the most important features from the eXtreme Gradient Boosting model, had a significantly higher area under the receiver operating characteristic curve in external validation (0.78) than the Sequential Organ Failure Assessment score (0.69), National Early Warning Score (0.60), and CURB-65 (0.65; p < 0.05 for all comparisons). Age, number of ICU beds, creatinine, lactate, arterial pH, and Pao2/Fio2 ratio were the most important predictors in the eXtreme Gradient Boosting model. CONCLUSIONS: eXtreme Gradient Boosting had the highest discrimination overall, and our simple tool had higher discrimination than a modified Sequential Organ Failure Assessment score, National Early Warning Score, and CURB-65 on external validation. These models could be used to improve triage decisions and clinical trial enrichment.

BOugie or stylet in patients UnderGoing Intubation Emergently (BOUGIE): protocol and statistical analysis plan for a randomised clinical trial.

INTRODUCTION: Intubation-related complications are less frequent when intubation is successful on the first attempt. The rate of first attempt success in the emergency department (ED) and intensive care unit (ICU) is typically less than 90%. The bougie, a semirigid introducer that can be placed into the trachea to facilitate a Seldinger-like technique of tracheal intubation and is typically reserved for difficult or failed intubations, might improve first attempt success. Evidence supporting its use, however, is from a single academic ED with frequent bougie use. Validation of these findings is needed before widespread implementation. METHODS AND ANALYSIS: The BOugie or stylet in patients Undergoing Intubation Emergently trial is a prospective, multicentre, non-blinded randomised trial being conducted in six EDs and six ICUs in the USA. The trial plans to enrol 1106 critically ill adults undergoing orotracheal intubation. Eligible patients are randomised 1:1 for the use of a bougie or use of an endotracheal tube with stylet for the first intubation attempt. The primary outcome is successful intubation on the first attempt. The secondary outcome is severe hypoxaemia, defined as an oxygen saturation less than 80% between induction until 2 min after completion of intubation. Enrolment began on 29 April 2019 and is expected to be completed in 2021. ETHICS AND DISSEMINATION: The trial protocol was approved with waiver of informed consent by the Central Institutional Review Board at Vanderbilt University Medical Center or the local institutional review board at an enrolling site. The results will be submitted for publication in a peer-reviewed journal and presented at scientific conferences. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT03928925).

Severity of illness scores at presentation predict ICU admission and mortality in COVID-19.

BACKGROUND: The COVID-19 pandemic has overwhelmed hospital systems in multiple countries and necessitated caring for patients in atypical healthcare settings. The goal of this study was to ascertain if the conventional critical care severity scores qSOFA, SOFA, APACHE-II, and SAPS-II could predict which patients admitted to the hospital from an emergency department would eventually require intensive care. METHODS: This single-center, retrospective cohort study enrolled patients admitted to Vanderbilt University Hospital from the emergency room with symptomatic, confirmed COVID-19 infection between March 8, 2020 through May 15, 2020. Clinical phenotyping was performed by chart abstraction, and the correlation of the qSOFA, SOFA, APACHE-II, and SAPS-II scores for the primary endpoint of ICU admission and secondary endpoint of in-hospital mortality was evaluated. RESULTS: During the study period, 128 patients were admitted to Vanderbilt University Hospital from the emergency room with COVID-19. Of these, 39 patients eventually required intensive care; the remaining 89 were discharged from the medical ward. All severity of illness scores demonstrated at least moderate ability to identify patients who would die or require ICU admission. Of the three severity of illness scores assessed, the APACHE-II score performed best with an AUC of 0.851 (95% CI: 0.786 to 0.917) for identifying patient that would require ICU admission. No patient with an APACHE-II score at the time of presentation less than 8 or qSOFA of 0 required intensive care unit (ICU) admission. All patients with an APACHE-II score less than 10 or qSOFA score of 0 survived to hospital discharge. CONCLUSIONS: The APACHE-II score accurately predicts the eventual need for ICU admission. This may allow for risk-stratification of patients safe to treat in alternative health care settings and prognostic enrichment to accelerate clinical trials of COVID-19 therapies.

Safety and Feasibility of a Protocolized Daily Assessment of Readiness for Liberation From Venovenous Extracorporeal Membrane Oxygenation.

BACKGROUND: Decannulation from venovenous extracorporeal membrane oxygenation (ECMO) at the earliest and safest possible time may improve outcomes and reduce cost. Yet, no prospective studies have compared weaning strategies for liberation from ECMO. RESEARCH QUESTION: Is a protocolized daily assessment of readiness to liberate from venovenous ECMO safe and feasible? STUDY DESIGN AND METHODS: We conducted a prospective, single-arm safety and feasibility study of a protocol for daily assessment of readiness to liberate from venovenous ECMO among consecutive adult patients receiving venovenous ECMO across four ICUs at a single center between June 20, 2020, and November 24, 2020. The ECMO-free protocol included three phases: (1) the safety screening, (2) non-ECMO Fio2 titration, and (3) the ECMO-free trial. Enrollment, interventions, and data collection were performed prospectively by trained study staff. RESULTS: Twenty-six patients received the ECMO-free protocol on 385 patient-days. The safety screening was passed during a total of 59 ECMO-free daily assessments (15.3%) among 20 patients. Every passed safety screening proceeded to an ECMO-free trial. Twenty-eight passed ECMO-free trials (47.5%) occurred among 16 patients (61.5%). No missed safety screenings, protocol deviations, or adverse events occurred. Of the 16 patients who passed an ECMO-free trial, 14 patients (87.5%) were decannulated. Among decannulated patients, 12 patients (85.7%) were decannulated on the same day as a passed ECMO-free trial, 6 patients (42.9%) were decannulated on the first day that they passed an ECMO-free trial, and 6 patients (42.9%) passed an ECMO-free trial at least twice consecutively before decannulation. The median time from first passed ECMO-free trial to decannulation was 2 days (interquartile range, 0-3 days). INTERPRETATION: The ECMO-free protocol is feasible and may identify patients for decannulation earlier than gradual approaches to weaning.

Multisystem Inflammatory Syndrome in an Adult With COVID-19.

Multisystem inflammatory syndrome (MIS) in children is a severe illness characterized by fever, laboratory evidence of inflammation, and multisystem organ dysfunction resulting from severe acute respiratory syndrome coronavirus 2 infection in a patient younger than 21 years. We present the case of a 39-year-old man with evidence of prior COVID-19 who seemed to meet all non-age-related criteria for MIS in children as well as criteria for the working definition of MIS in adults, and who improved after treatment with aspirin, corticosteroids, and intravenous immunoglobulin. Clinicians should be aware of this new inflammatory illness, not only in children but potentially also in adults with antecedent or concurrent COVID-19.

Extracorporeal membrane oxygenation in patients with severe respiratory failure from COVID-19.

PURPOSE: Limited data are available on venovenous extracorporeal membrane oxygenation (ECMO) in patients with severe hypoxemic respiratory failure from coronavirus disease 2019 (COVID-19). METHODS: We examined the clinical features and outcomes of 190 patients treated with ECMO within 14 days of ICU admission, using data from a multicenter cohort study of 5122 critically ill adults with COVID-19 admitted to 68 hospitals across the United States. To estimate the effect of ECMO on mortality, we emulated a target trial of ECMO receipt versus no ECMO receipt within 7 days of ICU admission among mechanically ventilated patients with severe hypoxemia (PaO2/FiO2 < 100). Patients were followed until hospital discharge, death, or a minimum of 60 days. We adjusted for confounding using a multivariable Cox model. RESULTS: Among the 190 patients treated with ECMO, the median age was 49 years (IQR 41-58), 137 (72.1%) were men, and the median PaO2/FiO2 prior to ECMO initiation was 72 (IQR 61-90). At 60 days, 63 patients (33.2%) had died, 94 (49.5%) were discharged, and 33 (17.4%) remained hospitalized. Among the 1297 patients eligible for the target trial emulation, 45 of the 130 (34.6%) who received ECMO died, and 553 of the 1167 (47.4%) who did not receive ECMO died. In the primary analysis, patients who received ECMO had lower mortality than those who did not (HR 0.55; 95% CI 0.41-0.74). Results were similar in a secondary analysis limited to patients with PaO2/FiO2 < 80 (HR 0.55; 95% CI 0.40-0.77). CONCLUSION: In select patients with severe respiratory failure from COVID-19, ECMO may reduce mortality.