An Update on Management of Adult Patients with Acute Respiratory Distress Syndrome: An Official American Thoracic Society Clinical Practice Guideline.

Background: This document updates previously published Clinical Practice Guidelines for the management of patients with acute respiratory distress syndrome (ARDS), incorporating new evidence addressing the use of corticosteroids, venovenous extracorporeal membrane oxygenation, neuromuscular blocking agents, and positive end-expiratory pressure (PEEP). Methods: We summarized evidence addressing four "PICO questions" (patient, intervention, comparison, and outcome). A multidisciplinary panel with expertise in ARDS used the Grading of Recommendations, Assessment, Development, and Evaluation framework to develop clinical recommendations. Results: We suggest the use of: 1) corticosteroids for patients with ARDS (conditional recommendation, moderate certainty of evidence), 2) venovenous extracorporeal membrane oxygenation in selected patients with severe ARDS (conditional recommendation, low certainty of evidence), 3) neuromuscular blockers in patients with early severe ARDS (conditional recommendation, low certainty of evidence), and 4) higher PEEP without lung recruitment maneuvers as opposed to lower PEEP in patients with moderate to severe ARDS (conditional recommendation, low to moderate certainty), and 5) we recommend against using prolonged lung recruitment maneuvers in patients with moderate to severe ARDS (strong recommendation, moderate certainty). Conclusions: We provide updated evidence-based recommendations for the management of ARDS. Individual patient and illness characteristics should be factored into clinical decision making and implementation of these recommendations while additional evidence is generated from much-needed clinical trials.

Association of Positive End-Expiratory Pressure and Lung Recruitment Selection Strategies with Mortality in Acute Respiratory Distress Syndrome: A Systematic Review and Network Meta-analysis.

Rationale: The most beneficial positive end-expiratory pressure (PEEP) selection strategy in patients with acute respiratory distress syndrome (ARDS) is unknown, and current practice is variable. Objectives: To compare the relative effects of different PEEP selection strategies on mortality in adults with moderate to severe ARDS. Methods: We conducted a network meta-analysis using a Bayesian framework. Certainty of evidence was evaluated using grading of recommendations assessment, development and evaluation methodology. Measurements and Main Results: We included 18 randomized trials (4,646 participants). Compared with a lower PEEP strategy, the posterior probability of mortality benefit from a higher PEEP without lung recruitment maneuver (LRM) strategy was 99% (risk ratio [RR], 0.77; 95% credible interval [CrI], 0.60-0.96, high certainty), the posterior probability of benefit of the esophageal pressure-guided strategy was 87% (RR, 0.77; 95% CrI, 0.48-1.22, moderate certainty), the posterior probability of benefit of a higher PEEP with brief LRM strategy was 96% (RR, 0.83; 95% CrI, 0.67-1.02, moderate certainty), and the posterior probability of increased mortality from a higher PEEP with prolonged LRM strategy was 77% (RR, 1.06; 95% CrI, 0.89-1.22, low certainty). Compared with a higher PEEP without LRM strategy, the posterior probability of increased mortality from a higher PEEP with prolonged LRM strategy was 99% (RR, 1.37; 95% CrI, 1.04-1.81, moderate certainty). Conclusions: In patients with moderate to severe ARDS, higher PEEP without LRM is associated with a lower risk of death than lower PEEP. A higher PEEP with prolonged LRM strategy is associated with increased risk of death when compared with higher PEEP without LRM.

Quality of Heart Failure Care in the Intensive Care Unit.

Patients with heart failure (HF) who are seen in an intensive care unit (ICU) manifest the highest-risk, most complex and most resource-intensive disease states. These patients account for a large relative proportion of days spent in an ICU. The paradigms by which critical care is provided to patients with HF are being reconsidered, including consideration of various multidisciplinary ICU staffing models and the development of acute-response teams. Traditional HF quality initiatives have centered on the peri- and postdischarge period in attempts to improve adherence to guideline-directed therapies and reduce readmissions. There is a compelling rationale for expanding high-quality efforts in treating patients with HF who are receiving critical care so we can improve outcomes, reduce preventable harm, improve teamwork and resource use, and achieve high health-system performance. Our goal is to answer the following question: For a patient with HF in the ICU, what is required for the provision of high-quality care? Herein, we first review the epidemiology of HF syndromes in the ICU and identify relevant critical care and quality stakeholders in HF. We next discuss the tenets of high-quality care for patients with HF in the ICU that will optimize critical care outcomes, such as ICU staffing models and evidence-based management of cardiac and noncardiac disease. We discuss strategies to mitigate preventable harm, improve ICU culture and conduct outcomes review, and we conclude with our summative vision of high-quality of ICU care for patients with HF; our vision includes clinical excellence, teamwork and ICU culture.

Lung- and Diaphragm-Protective Ventilation.

Mechanical ventilation can cause acute diaphragm atrophy and injury, and this is associated with poor clinical outcomes. Although the importance and impact of lung-protective ventilation is widely appreciated and well established, the concept of diaphragm-protective ventilation has recently emerged as a potential complementary therapeutic strategy. This Perspective, developed from discussions at a meeting of international experts convened by PLUG (the Pleural Pressure Working Group) of the European Society of Intensive Care Medicine, outlines a conceptual framework for an integrated lung- and diaphragm-protective approach to mechanical ventilation on the basis of growing evidence about mechanisms of injury. We propose targets for diaphragm protection based on respiratory effort and patient-ventilator synchrony. The potential for conflict between diaphragm protection and lung protection under certain conditions is discussed; we emphasize that when conflicts arise, lung protection must be prioritized over diaphragm protection. Monitoring respiratory effort is essential to concomitantly protect both the diaphragm and the lung during mechanical ventilation. To implement lung- and diaphragm-protective ventilation, new approaches to monitoring, to setting the ventilator, and to titrating sedation will be required. Adjunctive interventions, including extracorporeal life support techniques, phrenic nerve stimulation, and clinical decision-support systems, may also play an important role in selected patients in the future. Evaluating the clinical impact of this new paradigm will be challenging, owing to the complexity of the intervention. The concept of lung- and diaphragm-protective ventilation presents a new opportunity to potentially improve clinical outcomes for critically ill patients.

Mean Airway Pressure As a Predictor of 90-Day Mortality in Mechanically Ventilated Patients.

OBJECTIVES: To determine the association between mean airway pressure and 90-day mortality in patients with acute respiratory failure requiring mechanical ventilation and to compare the predictive ability of mean airway pressure compared with inspiratory plateau pressure and driving pressure. DESIGN: Prospective observational cohort. SETTING: Five ICUs in Lima, Peru. SUBJECTS: Adults requiring invasive mechanical ventilation via endotracheal tube for acute respiratory failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of potentially eligible participants (n = 1,500), 65 (4%) were missing baseline mean airway pressure, while 352 (23.5%) were missing baseline plateau pressure and driving pressure. Ultimately, 1,429 participants were included in the analysis with an average age of 59 ± 19 years, 45% female, and a mean PaO2/FIO2 ratio of 248 ± 147 mm Hg at baseline. Overall, 90-day mortality was 50.4%. Median baseline mean airway pressure was 13 cm H2O (interquartile range, 10-16 cm H2O) in participants who died compared to a median mean airway pressure of 12 cm H2O (interquartile range, 10-14 cm H2O) in participants who survived greater than 90 days (p < 0.001). Mean airway pressure was independently associated with 90-day mortality (odds ratio, 1.38 for difference comparing the 75th to the 25th percentile for mean airway pressure; 95% CI, 1.10-1.74) after adjusting for age, sex, baseline Acute Physiology and Chronic Health Evaluation III, baseline PaO2/FIO2 (modeled with restricted cubic spline), baseline positive end-expiratory pressure, baseline tidal volume, and hospital site. In predicting 90-day mortality, baseline mean airway pressure demonstrated similar discriminative ability (adjusted area under the curve = 0.69) and calibration characteristics as baseline plateau pressure and driving pressure. CONCLUSIONS: In a multicenter prospective cohort, baseline mean airway pressure was independently associated with 90-day mortality in mechanically ventilated participants and predicts mortality similarly to plateau pressure and driving pressure. Because mean airway pressure is readily available on all mechanically ventilated patients and all ventilator modes, it is a potentially more useful predictor of mortality in acute respiratory failure.

Searching for the optimal positive end-expiratory pressure for lung protective ventilation.

PURPOSE OF REVIEW: The optimal strategy for setting positive end-expiratory pressure (PEEP) has not been established. This review examines different approaches for setting PEEP to achieve lung-protective ventilation. RECENT FINDINGS: PEEP titration strategies commonly focus either on achieving adequate arterial oxygenation or reducing ventilator-induced lung injury from repetitive alveolar opening and closing, referred to as the open lung approach. Five recent trials of higher versus lower PEEP have not shown benefit with higher PEEP, and one of the five trials showed increased harm for patients treated with the open lung strategy. Evidence suggests that some patients may respond beneficially to higher PEEP by recruiting lung, whereas other patients do not recruit lung and merely overdistend previously open alveoli when higher PEEP is applied. A PEEP titration approach that differentiates PEEP responders from nonresponders and provides higher or lower PEEP accordingly has not been prospectively tested. SUMMARY: When compared, no method for setting PEEP has been proven superior to another. Based on recent studies, higher compared with lower PEEP has not improved clinical outcomes and worsened mortality in one study. Future research should focus on identifying feasible methods for assessing lung recruitability in response to PEEP to enrich future trials of PEEP strategies.

Performance of Critical Care Outcome Prediction Models in an Intermediate Care Unit.

BACKGROUND: Intermediate care units (IMCUs) are heterogeneous in design and operation, which makes comparative effectiveness studies challenging. A generalizable outcome prediction model could improve such comparisons. However, little is known about the performance of critical care outcome prediction models in the intermediate care setting. The purpose of this study is to evaluate the performance of the Acute Physiology and Chronic Health Evaluation version II (APACHE II), Simplified Acute Physiology Score version II (SAPS II) and version 3 (SAPS 3), and Mortality Probability Model version III (MPM0III) in patients admitted to a well-characterized IMCU. MATERIALS AND METHODS: In the IMCU of an academic medical center (July to December 2012), the discrimination and calibration of each outcome prediction model were evaluated using the area under the receiver-operating characteristic and Hosmer-Lemeshow goodness-of-fit test, respectively. Standardized mortality ratios (SMRs) were also calculated. RESULTS: The cohort included data from 628 unique IMCU admissions with an inpatient mortality rate of 8.3%. All models exhibited good discrimination, but only the SAPS II and MPM0III were well calibrated. While the APACHE II and SAPS 3 both markedly overestimated mortality, the SMR for the SAPS II and MPM0III were 0.91 and 0.91, respectively. CONCLUSIONS: The SAPS II and MPM0III exhibited good discrimination and calibration, with slight overestimation of mortality. Each model should be further evaluated in multicenter studies of patients in the intermediate care setting.

Association between hospital mortality and inspiratory airway pressures in mechanically ventilated patients without acute respiratory distress syndrome: a prospective cohort study.

BACKGROUND: Higher inspiratory airway pressures are associated with worse outcomes in mechanically ventilated patients with the acute respiratory distress syndrome (ARDS). This relationship, however, has not been well investigated in patients without ARDS. We hypothesized that higher driving pressures (ΔP) and plateau pressures (Pplat) are associated with worse patient-centered outcomes in mechanically ventilated patients without ARDS as well as those with ARDS. METHODS: Using data collected during a prospective, observational cohort study of 6179 critically ill participants enrolled in 59 ICUs across the USA, we used multivariable logistic regression to determine whether ΔP and Pplat at enrollment were associated with hospital mortality among 1132 mechanically ventilated participants. We stratified analyses by ARDS status. RESULTS: Participants without ARDS (n = 822) had lower average severity of illness scores and lower hospital mortality (27.3% vs. 38.7%; p <  0.001) than those with ARDS (n = 310). Average Pplat (20.6 vs. 23.9 cm H2O; p <  0.001), ΔP (14.3 vs. 16.0 cm H2O; p <  0.001), and positive end-expiratory pressure (6.3 vs. 7.9 cm H2O; p <  0.001) were lower in participants without ARDS, whereas average tidal volumes (7.2 vs. 6.8 mL/kg PBW; p <  0.001) were higher. Among those without ARDS, higher ΔP (adjusted OR = 1.36 per 7 cm H2O, 95% CI 1.14-1.62) and Pplat (adjusted OR = 1.42 per 8 cm H2O, 95% CI 1.17-1.73) were associated with higher mortality. We found similar relationships with mortality among those participants with ARDS. CONCLUSIONS: Higher ΔP and Pplat are associated with increased mortality for participants without ARDS. ΔP may be a viable target for lung-protective ventilation in all mechanically ventilated patients.

Risk factors for pleural effusion recurrence in patients with malignancy.

BACKGROUND AND OBJECTIVE: The main purpose of treatment in patients with malignant pleural effusion (MPE) is symptom palliation. Currently, patients undergo repeat thoracenteses prior to receiving a definitive procedure as clinicians are not aware of the risk factors associated with fluid recurrence. The primary objective of this study was to identify risk factors associated with recurrent symptomatic MPE. METHODS: Retrospective multicentre cohort study of patients who underwent first thoracentesis was performed. The primary outcome was time to fluid recurrence requiring intervention in patients with evidence of metastatic disease. We used a cause-specific hazard model to identify risk factors associated with fluid recurrence. We also developed a predictive model, utilizing Fine-Gray subdistribution hazard model, and externally validated the model. RESULTS: A total of 988 patients with diagnosed metastatic disease were included. Cumulative incidence of recurrence was high with 30% of patients recurring by day 15. On multivariate analysis, size of the effusion on chest X-ray (up to the top of the cardiac silhouette (hazard ratio (HR): 1.84, 95% CI: 1.21-2.80, P = 0.004) and above the cardiac silhouette (HR: 2.22, 95% CI: 1.43-3.46, P = 0.0004)), larger amount of pleural fluid drained (HR: 1.06, 95% CI: 1.04-1.07, P < 0.0001) and higher pleural fluid LDH (HR: 1.008, 95% CI: 1.004-1.011, P < 0.0001) were associated with increased hazard of recurrence. Negative cytology (HR: 0.52, 95% CI: 0.43-0.64, P < 0.0001) was associated with decreased hazard of recurrence. The model had low prediction accuracy. CONCLUSION: Pleural effusion size, amount of pleural fluid drained, LDH and pleural fluid cytology were found to be risk factors for recurrence.

Fifty Years of Research in ARDS. Vt Selection in Acute Respiratory Distress Syndrome.

Mechanical ventilation (MV) is critical in the management of many patients with acute respiratory distress syndrome (ARDS). However, MV can also cause ventilator-induced lung injury (VILI). The selection of an appropriate Vt is an essential part of a lung-protective MV strategy. Since the publication of a large randomized clinical trial demonstrating the benefit of lower Vts, the use of Vts of 6 ml/kg predicted body weight (based on sex and height) has been recommended in clinical practice guidelines. However, the predicted body weight approach is imperfect in patients with ARDS because the amount of aerated lung varies considerably due to differences in inflammation, consolidation, flooding, and atelectasis. Better approaches to setting Vt may include limits on end-inspiratory transpulmonary pressure, lung strain, and driving pressure. The limits of lowering Vt have not yet been established, and some patients may benefit from Vts that are lower than those in current use. However, lowering Vts may result in respiratory acidosis. Tactics to reduce respiratory acidosis include reductions in ventilation circuit dead space, increases in respiratory rate, higher positive end-expiratory pressures in patients who recruit lung in response to positive end-expiratory pressure, recruitment maneuvers, and prone positioning. Mechanical adjuncts such as extracorporeal carbon dioxide removal may be useful to normalize pH and carbon dioxide levels, but further studies will be necessary to demonstrate benefit with this technology.

Fifty Years of Research in ARDS. Setting Positive End-Expiratory Pressure in Acute Respiratory Distress Syndrome.

Positive end-expiratory pressure (PEEP) has been used during mechanical ventilation since the first description of acute respiratory distress syndrome (ARDS). In the subsequent decades, many different strategies for optimally titrating PEEP have been proposed. Higher PEEP can improve arterial oxygenation, reduce tidal lung stress and strain, and promote more homogenous ventilation by preventing alveolar collapse at end expiration. However, PEEP may also cause circulatory depression and contribute to ventilator-induced lung injury through alveolar overdistention. The overall effect of PEEP is primarily related to the balance between the number of alveoli that are recruited to participate in ventilation and the amount of lung that is overdistended when PEEP is applied. Techniques to assess lung recruitment from PEEP may help to direct safer and more effective PEEP titration. Some PEEP titration strategies attempt to weigh beneficial effects on arterial oxygenation and on prevention of cyclic alveolar collapse with the harmful potential of overdistention. One method for PEEP titration is a PEEP/FiO2 table that prioritizes support for arterial oxygenation. Other methods set PEEP based on mechanical parameters, such as the plateau pressure, respiratory system compliance, or transpulmonary pressure. No single method of PEEP titration has been shown to improve clinical outcomes compared with other approaches of setting PEEP. Future trials should focus on identifying individuals who respond to higher PEEP with recruitment and on clinically important outcomes (e.g., mortality).

The promises and problems of transpulmonary pressure measurements in acute respiratory distress syndrome.

PURPOSE OF REVIEW: The optimal strategy for assessing and preventing ventilator-induced lung injury in the acute respiratory distress syndrome (ARDS) is controversial. Recent investigative efforts have focused on personalizing ventilator settings to individual respiratory mechanics. This review examines the strengths and weaknesses of using transpulmonary pressure measurements to guide ventilator management in ARDS. RECENT FINDINGS: Recent clinical studies suggest that adjusting ventilator settings based on transpulmonary pressure measurements is feasible, may improve oxygenation, and reduce ventilator-induced lung injury. SUMMARY: The measurement of transpulmonary pressure relies upon esophageal manometry, which requires the acceptance of several assumptions and potential errors. Notably, this includes the ability of localized esophageal pressures to represent global pleural pressure. Recent investigations demonstrated improved oxygenation in ARDS patients when positive end-expiratory pressure was adjusted to target specific end-inspiratory or end-expiratory transpulmonary pressures. However, there are different methods for estimating transpulmonary pressure and different goals for positive end-expiratory pressure titration among recent studies. More research is needed to refine techniques for the estimation and utilization of transpulmonary pressure to guide ventilator settings in ARDS patients.

Designing a Bayesian adaptive clinical trial to evaluate novel mechanical ventilation strategies in acute respiratory failure using integrated nested Laplace approximations.

BACKGROUND: Adaptive trials usually require simulations to determine values for design parameters, demonstrate error rates, and establish the sample size. We designed a Bayesian adaptive trial comparing ventilation strategies for patients with acute hypoxemic respiratory failure using simulations. The complexity of the analysis would usually require computationally expensive Markov Chain Monte Carlo methods but this barrier to simulation was overcome using the Integrated Nested Laplace Approximations (INLA) algorithm to provide fast, approximate Bayesian inference. METHODS: We simulated two-arm Bayesian adaptive trials with equal randomization that stratified participants into two disease severity states. The analysis used a proportional odds model, fit using INLA. Trials were stopped based on pre-specified posterior probability thresholds for superiority or futility, separately for each state. We calculated the type I error and power across 64 scenarios that varied the probability thresholds and the initial minimum sample size before commencing adaptive analyses. Two designs that maintained a type I error below 5%, a power above 80%, and a feasible mean sample size were evaluated further to determine the optimal design. RESULTS: Power generally increased as the initial sample size and the futility threshold increased. The chosen design had an initial recruitment of 500 and a superiority threshold of 0.9925, and futility threshold of 0.95. It maintained high power and was likely to reach a conclusion before exceeding a feasible sample size. CONCLUSIONS: We designed a Bayesian adaptive trial to evaluate novel strategies for ventilation using the INLA algorithm to efficiently evaluate a wide range of designs through simulation.

Extended Versus Standard Proning Duration for COVID-19 Associated Acute Respiratory Distress Syndrome: A Target Trial Emulation Study.

RATIONALE: Prone positioning for > 16 hours in moderate-to-severe acute respiratory distress syndrome (ARDS) improves survival. However, the optimal duration of proning is unknown. OBJECTIVE: To estimate the effect of extended versus standard proning duration on patients with moderate-to-severe COVID-19 ARDS. METHODS: Data were extracted from a 5-hospital electronic medical record registry. Patients who were proned within 72 hours of mechanical ventilation were categorized as receiving extended (> 24 hours) versus standard (16-24 hours) proning based on the first proning session length. We used a target trial emulation design to estimate the effect of extended vs. standard proning on the primary outcome of 90-day mortality, and secondary outcomes of ventilator liberation and ICU discharge. Analytically we used inverse probability of treatment weighted (IPTW) Cox, or Fine and Gray regression models. RESULTS: 314 patients were included, 234 who received extended proning, and 80 who received standard duration. Extended proning patients were older, had greater comorbidity, were more often at an academic hospital, and had shorter time from admission to mechanical ventilation. After IPTW, characteristics were well balanced. Unadjusted 90-day mortality in the extended vs. standard proning groups was 39% vs 58%. In doubly-robust IPTW analyses, we found no significant effects of extended vs. standard proning duration on mortality (hazard ratio [95% CI] 0.95 [0.51-1.77]), ventilator liberation (sub-distribution hazard [sHR] 1.60, [0.97-2.64], or ICU discharge (sHR 1.31 [0.82-2.10]). CONCLUSION: Using target trial emulation, we found no significant effect of extended vs. standard proning duration on mortality, ventilator liberation, or ICU discharge. However, given the imprecision of estimates, further study is justified. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Laying the Groundwork for Physiology-Guided Precision Medicine in the Critically Ill.

Canonical critical care syndromes such as sepsis and acute respiratory distress syndrome (ARDS) include patients with markedly heterogeneous biology.1 This, paired with decades of randomized controlled trials (RCTs) that were traditionally viewed as "negative," has stalled progress in improving patient outcomes.2 However, emerging awareness of sub-phenotypes based on differences in biomarker profiles and resulting heterogeneous treatment effects have led to calls for precision medicine in which therapies are targeted to those most likely to benefit.3.

Outcomes Among Mechanically Ventilated Patients With Severe Pneumonia and Acute Hypoxemic Respiratory Failure From SARS-CoV-2 and Other Etiologies.

Importance: Early observations suggested that COVID-19 pneumonia had a higher mortality rate than other causes of pneumonia. Objective: To compare outcomes between mechanically ventilated patients with pneumonia due to COVID-19 (March 2020 to June 2021) and other etiologies (July 2016 to December 2019). Design, Setting, and Participants: This retrospective cohort study was conducted at the Johns Hopkins Healthcare System among adult patients (aged ≥18 years) with pneumonia who required mechanical ventilation in the first 2 weeks of hospitalization. Clinical, laboratory, and mechanical ventilation data were extracted from admission to hospital discharge or death. Exposures: Pneumonia due to COVID-19. Main Outcomes and Measures: The primary outcome was 90-day in-hospital mortality. Secondary outcomes were time to liberation from mechanical ventilation, hospital length of stay, static respiratory system compliance, and ventilatory ratio. Unadjusted and multivariable-adjusted logistic regression, proportional hazards regression, and doubly robust regression were used in propensity score-matched sets to compare clinical outcomes. Results: Overall, 719 patients (mean [SD] age, 61.8 [15.3] years; 442 [61.5%] were male; 460 [64.0%] belonged to a minoritized racial group and 253 [35.2%] were White) with severe COVID-19 pneumonia and 1127 patients (mean [SD] age, 60.9 [15.8] years; 586 [52.0%] were male; 459 [40.7%] belonged to a minoritized racial group and 655 [58.1%] were White) with severe non-COVID-19 pneumonia. In unadjusted analyses, patients with COVID-19 pneumonia had higher 90-day mortality (odds ratio, 1.21, 95% CI 1.04-1.41), longer time on mechanical ventilation (subdistribution hazard ratio 0.72, 95% CI 0.63-0.81), and lower compliance (32.0 vs 28.4 mL/kg PBW/cm H2O; P < .001) when compared with those with non-COVID-19 pneumonia. In propensity score-matched analyses, patients with COVID-19 pneumonia were equally likely to die within 90 days as those with non-COVID-19 pneumonia (odds ratio, 1.04; 95% CI, 0.81 to 1.35; P = .85), had similar respiratory system compliance (mean difference, 1.82 mL/cm H2O; 95% CI, -1.53 to 5.17 mL/cm H2O; P = .28) and ventilatory ratio (mean difference, -0.05; 95% CI, -0.22 to 0.11; P = .52), but had lower rates of liberation from mechanical ventilation (subdistribution hazard ratio, 0.81; 95% CI, 0.65 to 1.00) when compared with those with non-COVID-19 pneumonia. Patients with COVID-19 pneumonia had somewhat lower rates of being discharged from the hospital alive at 90 days (subdistribution hazard ratio, 0.83; 95% CI, 0.68 to 1.01) than those with non-COVID-19 pneumonia; however, this was not statistically significant. Conclusions and Relevance: In this study, mechanically ventilated patients with severe COVID-19 pneumonia had similar mortality rates as patients with other causes of severe pneumonia but longer times to liberation from mechanical ventilation. Mechanical ventilation use in COVID-19 pneumonia should follow the same evidence-based guidelines as for any pneumonia.

Assessment of Symptom, Disability, and Financial Trajectories in Patients Hospitalized for COVID-19 at 6 Months.

Importance: Individuals who survived COVID-19 often report persistent symptoms, disabilities, and financial consequences. However, national longitudinal estimates of symptom burden remain limited. Objective: To measure the incidence and changes over time in symptoms, disability, and financial status after COVID-19-related hospitalization. Design, Setting, and Participants: A national US multicenter prospective cohort study with 1-, 3-, and 6-month postdischarge visits was conducted at 44 sites participating in the National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Network's Biology and Longitudinal Epidemiology: COVID-19 Observational (BLUE CORAL) study. Participants included hospitalized English- or Spanish-speaking adults without severe prehospitalization disabilities or cognitive impairment. Participants were enrolled between August 24, 2020, and July 20, 2021, with follow-up occurring through March 30, 2022. Exposure: Hospitalization for COVID-19 as identified with a positive SARS-CoV-2 molecular test. Main Outcomes and Measures: New or worsened cardiopulmonary symptoms, financial problems, functional impairments, perceived return to baseline health, and quality of life. Logistic regression was used to identify factors associated with new cardiopulmonary symptoms or financial problems at 6 months. Results: A total of 825 adults (444 [54.0%] were male, and 379 [46.0%] were female) met eligibility criteria and completed at least 1 follow-up survey. Median age was 56 (IQR, 43-66) years; 253 (30.7%) participants were Hispanic, 145 (17.6%) were non-Hispanic Black, and 360 (43.6%) were non-Hispanic White. Symptoms, disabilities, and financial problems remained highly prevalent among hospitalization survivors at month 6. Rates increased between months 1 and 6 for cardiopulmonary symptoms (from 67.3% to 75.4%; P = .001) and fatigue (from 40.7% to 50.8%; P < .001). Decreases were noted over the same interval for prevalent financial problems (from 66.1% to 56.4%; P < .001) and functional limitations (from 55.3% to 47.3%; P = .004). Participants not reporting problems at month 1 often reported new symptoms (60.0%), financial problems (23.7%), disabilities (23.8%), or fatigue (41.4%) at month 6. Conclusions and Relevance: The findings of this cohort study of people discharged after COVID-19 hospitalization suggest that recovery in symptoms, functional status, and fatigue was limited at 6 months, and some participants reported new problems 6 months after hospital discharge.