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Studies investigating the effect of trunk inclination on respiratory mechanics in mechanically ventilated patients with ARDS have reported postural differences in partition respiratory mechanics. Compared with more upright positions, the supine-flat position provided lower lung and chest wall elastance, allowing reduced driving pressures and end-inspiratory transpulmonary pressure. However, the effect of trunk inclination on respiratory mechanics in patients with obesity and ARDS is uncertain. Does the effect of change in posture on partition respiratory mechanics differ between patients with ARDS with and without obesity? In this single-center study, patients with ARDS with and without obesity were randomized into two 15-minute steps in which trunk inclination was changed from semi-recumbent (40° head up) to supine-flat (0°), or vice versa. At the end of each step partition respiratory mechanics, airway opening pressure and arterial blood gases were measured. Paired t test was used to examine respiratory mechanics and blood gas variables in each group. Forty consecutive patients were enrolled. Twenty were obese (BMI, 38.4 [34.5-42.3]), and 20 were non-obese (BMI, 26.6 [25.2-28.5]). In the patients with obesity, lung and chest wall elastance, driving pressure, inspiratory transpulmonary pressure, Pa co 2 , and ventilatory ratio were lower supine than semi-recumbent (P <.001). Airways resistance was greater supine (P =.006). In the patients without obesity, only chest wall elastance was lower in supine vs semi-recumbent (P <.001). In mechanically ventilated patients with ARDS and obesity, supine posture provided lower lung and chest wall elastance, and better CO 2 clearance, than the semi-recumbent posture. This study was registered with Australian New Zealand Clinical Trials Registry (ACTRN12623000794606). [Display omitted] [ABSTRACT FROM AUTHOR]

In immunocompromised patients with acute respiratory failure (ARF), the clinical significance of respiratory virus detection in the nasopharynx remains uncertain. Is viral detection in nasopharyngeal swabs associated with causes and outcomes of ARF in immunocompromised patients? This preplanned post hoc analysis of a randomized controlled trial enrolled immunocompromised patients admitted to 32 ICUs for ARF between May 2016 and December 2017. Nasopharyngeal swabs sampled at inclusion were assessed for 23 respiratory pathogens using multiplex polymerase chain reaction (PCR) assay. Causes of ARF were established by managing physicians and were reviewed by three expert investigators masked to the multiplex PCR assay results. Associations between virus detection in nasopharyngeal swabs, causes of ARF, and composite outcome of day 28 mortality, invasive mechanical ventilation (IMV), or both were assessed. Among the 510 sampled patients, the multiplex PCR assay results were positive in 103 patients (20.2%), and a virus was detected in 102 samples: rhinoviruses or enteroviruses in 35.5%, coronaviruses in 10.9%, and flu-like viruses (influenza virus, parainfluenza virus, respiratory syncytial virus, human metapneumovirus) in 52.7%. The cause of ARF varied significantly according to the results of the multiplex PCR assay, especially the proportion of viral pneumonia: 50.0% with flu-like viruses, 14.0% with other viruses, and 3.6% when no virus was detected (P <.001). No difference was found in the composite outcome of day 28 mortality, IMV, or both according to positive assay findings (54.9% vs 54.7%; P =.965). In a pre-established subgroup analysis, flu-like virus detection was associated with a higher rate of day 28 mortality, IMV, or both among recipients of allogeneic hematopoietic stem cell transplantation compared with those without detected virus. In immunocompromised patients with ARF, the results of nasopharyngeal multiplex PCR assays are not associated with IMV or mortality. A final diagnosis of viral pneumonia is retained in one-third of patients with positive assay results and in one-half of the patients with a flu-like virus. [ABSTRACT FROM AUTHOR]

Diagnostic guidelines for pediatric ARDS (PARDS) were developed at the 2015 Pediatric Acute Lung Injury Consensus Conference (PALICC). Although this was an improvement in creating pediatric-specific diagnostic criteria, there remains potential for variability in identification of PARDS. What is the interrater reliability of the 2015 PALICC criteria for diagnosing moderate to severe PARDS? What clinical criteria and patient factors are associated with diagnostic disagreements? Patients with acute hypoxic respiratory failure admitted from 2016 to 2021 who received invasive mechanical ventilation were retrospectively reviewed by two pediatric ICU physicians. Reviewers evaluated whether the patient met the 2015 PALICC definition of moderate to severe PARDS and rated their diagnostic confidence. Interrater reliability was measured using Gwet's agreement coefficient. Thirty-seven of 191 encounters had a diagnostic disagreement. Interrater reliability was substantial (Gwet's agreement coefficient, 0.74; 95% CI, 0.65-0.83). Disagreements were caused by different interpretations of chest radiographs (56.8%), ambiguity in origin of pulmonary edema (37.8%), or lack of clarity if patient's current condition was significantly different from baseline (27.0%). Disagreement was more likely in patients who were chronically ventilated (OR, 4.66; 95% CI, 2.16-10.08; P <.001), had a primary cardiac admission diagnosis (OR, 3.36; 95% CI, 1.18-9.53; P =.02), or underwent cardiothoracic surgery during the admission (OR, 4.90; 95% CI, 1.60-15.00; P =.005). Reviewers were at least moderately confident in their decision 73% of the time; however, they were less likely to be confident if the patient had cardiac disease or chronic respiratory failure. The interrater reliability of the 2015 PALICC criteria for diagnosing moderate to severe PARDS in this cohort was substantial, with diagnostic disagreements commonly caused by differences in chest radiograph interpretations. Patients with cardiac disease or chronic respiratory failure were more vulnerable to diagnostic disagreements. More guidance is needed on interpreting chest radiographs and diagnosing PARDS in these subgroups. [Display omitted] [ABSTRACT FROM AUTHOR]

Limited data from low-income countries report on respiratory support techniques in COVID-19-associated ARDS. Which respiratory support techniques are used in patients with COVID-19-associated ARDS in Uganda? A multicenter, prospective, observational study was conducted at 13 Ugandan hospitals during the pandemic and included adults with COVID-19-associated ARDS. Patient characteristics, clinical and laboratory data, initial and most advanced respiratory support techniques, and 28-day mortality were recorded. Standard tests, log-rank tests, and logistic regression analyses were used for statistical analyses. Four hundred ninety-nine patients with COVID-19-associated ARDS (mild, n = 137; moderate, n = 247; and severe, n = 115) were included (ICU admission, 38.9%). Standard oxygen therapy (SOX), high-flow nasal oxygen (HFNO), CPAP, noninvasive ventilation (NIV), and invasive mechanical ventilation (IMV) was used as the first-line (most advanced) respiratory support technique in 37.3% (35.3%), 10% (9.4%), 11.6% (4.8%), 23.4% (14.4%), and 17.6% (36.6%) of patients, respectively. The first-line respiratory support technique was escalated in 19.8% of patients. Twenty-eight-day mortality was 51.9% (mild ARDS, 13.1%; moderate ARDS, 62.3%; severe ARDS, 75.7%; P <.001) and was associated with respiratory support techniques as follows: SOX, 19.9%; HFNO, 31.9%; CPAP, 58.3%; NIV 61.1%; and IMV, 83.9% (P <.001). Proning was used in 79 patients (15.8%; 59 of 79 awake) and was associated with lower mortality (40.5% vs 54%; P =.03). The oxygen saturation to F io 2 ratio (OR, 0.99; 95% CI, 0.98-0.99; P <. 001) and respiratory rate (OR, 1.07; 95% CI, 1.03-1.12; P =. 002) at admission and NIV (OR, 6.31; 95% CI, 2.29-17.37; P <. 001) or IMV (OR, 8.08; 95% CI, 3.52-18.57; P <. 001) use were independent risk factors for death. SOX, HFNO, CPAP, NIV, and IMV were used as respiratory support techniques in patients with COVID-19-associated ARDS in Uganda. Although these data are observational, they suggest that the use of SOX and HFNO therapy as well as awake proning are associated with a lower mortality resulting from COVID-19-associated ARDS in a resource-limited setting. [ABSTRACT FROM AUTHOR]

Patients often have high expectations for recovery after critical illness, but the impact of these expectations on subsequent quality of life (QoL) after serious illnesses has not been evaluated empirically. Among adult survivors of acute respiratory failure (ARF), are met vs unmet expectations for health associated with self-reported QoL 6 months after discharge? This was a prospective longitudinal cohort study enrolling consecutive adult patients with ARF managed in ICUs at five academic medical centers. At hospital discharge, we evaluated participants' expected health 6 months in the future via a visual analog scale (VAS; range, 0-100), with higher scores representing better expected health. At 6-month follow-up, perceived health was assessed using the EQ-5D VAS, and QoL was assessed using the World Health Organization Quality of Life Brief Version (WHOQOL-BREF) instrument. Participants' health expectations were categorized as having been met when perceived health at 6 months was no more than eight points lower than their expectation at study enrollment. The primary analysis compared WHOQOL-BREF domain scores (range, 0-100) at 6 months after discharge in patients with met vs unmet health expectations using the nonparametric Mann-Whitney U test. Secondary analysis modeled WHOQOL-BREF domain scores using multivariate regression, and sensitivity analyses assessed QoL using EQ-5D-5L index values. In the primary analysis, QoL was significantly better among participants with met vs unmet health expectations across all domains of the WHOQOL-BREF: physical health (estimated difference in scores: median, 19 [interquartile range (IQR), 12-15]; P <.001), psychological health (median, 12 [IQR, 6-18]; P <.001), social relationships (median, 6 [IQR, 0-13]; P =.02), and environmental health (median, 12 [IQR, 6-13]; P <.001). In multivariate regression, the difference between expected and perceived health remained associated significantly with the physical health domain score. Fulfillment of health expectations is associated with better QoL after ARF, suggesting a mechanism underpinning successful ICU recovery programs that incorporate normalization and expectation management. [Display omitted] [ABSTRACT FROM AUTHOR]

A 60-year-old man was referred to a pulmonologist evaluation with persistent dyspnea and cough 1 month after discharge for an acute respiratory failure caused by Legionella pneumophila pneumonia, which required invasive mechanical ventilation. Chest CT scan performed during hospitalization showed lobar consolidation of upper left lobe (Fig 1A). Bronchial culture revealed L pneumophila ; the patient was treated with levofloxacin and supported with invasive mechanical ventilation for 2 weeks. Chest radiograph after extubation showed almost complete resolution of infiltrates. After 1 month, the patient still complained of dyspnea and a new chest CT scan was performed: the consolidation migrated (Fig 1B; Video 1). [ABSTRACT FROM AUTHOR]

Prone positioning is an immediately accessible, readily implementable intervention that was proposed initially as a method for improvement in gas exchange > 50 years ago. Initially implemented clinically as an empiric therapy for refractory hypoxemia, multiple clinical trials were performed on the use of prone positioning in various respiratory conditions, cumulating in the landmark Proning Severe ARDS Patients trial, which demonstrated mortality benefit in patients with severe ARDS. After this trial and the corresponding meta-analysis, expert consensus and societal guidelines recommended the use of prone positioning for the management of severe ARDS. The ongoing COVID-19 pandemic has brought prone positioning to the forefront of medicine, including widespread implementation of prone positioning in awake, spontaneously breathing, nonintubated patients with acute hypoxemic respiratory failure. Multiple clinical trials now have been performed to investigate the safety and effectiveness of prone positioning in these patients and have enhanced our understanding of the effects of the prone position in respiratory failure. In this review, we discuss the physiologic features, clinical outcome data, practical considerations, and lingering questions of prone positioning. [ABSTRACT FROM AUTHOR]

National data on bronchoscopy for the evaluation of acute respiratory failure are lacking, and the limited available data suggest wide variation in use. How commonly is bronchoscopy performed among hospitalizations with acute respiratory failure? How has use changed over time and across hospitals? This was an observational cohort study of adult hospitalizations (2012-2018) treated with invasive mechanical ventilation (IMV) using the National Inpatient Sample, which represents 97% of all hospitalizations in the United States. We measured the proportion of hospitalizations treated with IMV who underwent bronchoscopy and assessed trends in bronchoscopy use over time. Multilevel linear regression models were used to quantify hospital-level variation, adjusting for differences in patient and hospital characteristics. We identified 6,101,070 IMV-treated hospitalizations (2012-2018), of whom 609,405 underwent bronchoscopy; among hospitalizations receiving bronchoscopy, mean age was 61 years, 41.8% were women, and in-hospital mortality was 30.8%. The percentage of IMV-treated hospitalizations receiving bronchoscopy increased from 9.5% (95% CI, 9.1%-9.9%) in 2012 to 10.8% (95% CI, 10.4%-11.2%) in 2018 (P <.001 for difference). In 2018, bronchoscopy use varied from 0% to 57.1% among 1,787 hospitals, and in multilevel models adjusted for patient and hospital characteristics, 16.0% of the variation was explained at the hospital level. The median OR was 2.13 (95% CI, 2.05-2.21), indicating 113% increased odds of receiving bronchoscopy if moving from a lower-use to a higher-use hospital. Bronchoscopy use among hospitalizations treated with IMV has increased over time. The large variation in use of bronchoscopy across hospitals suggests potentially unwarranted practice variation and need for further studies to clarify which patients benefit from bronchoscopy. [ABSTRACT FROM AUTHOR]

An acute exacerbation of interstitial lung disease (ILD) is an acute deterioration that can occur at any time and is associated with significant morbidity and mortality rates. We herein report three patients with ILD who experienced acute respiratory failure after SARS-CoV-2 messenger RNA vaccination. All the patients were male; the mean age was 77 years. They had a smoking history that ranged from 10 to 30 pack-years. Duration from the vaccination to the onset of respiratory failure was 1 day in two patients and 9 days in one patient. In an autopsied case, lung pathologic evidence indicated diffuse alveolar damage superimposed on usual interstitial pneumonia. In the other two cases, CT scans showed diffuse ground-glass opacities and subpleural reticulation, which suggests acute exacerbation of ILD. Two patients were treated successfully with high-dose methylprednisolone. Although benefits of vaccination outweigh the risks associated with uncommon adverse events, patients with chronic lung diseases should be observed carefully after SARS-CoV-2 vaccination. [ABSTRACT FROM AUTHOR]

Background: The inhaled vasodilators nitric oxide and epoprostenol may be initiated to improve oxygenation in mechanically ventilated patients with severe acute respiratory failure (ARF); however, practice patterns and head-to-head comparisons of effectiveness are unclear.Research Question: What are the practice patterns and comparative effectiveness for inhaled nitric oxide and epoprostenol in severe ARF?Study Design and Methods: Using a large US database (Premier Healthcare Database), we identified adult patients with ARF or ARDS who were mechanically ventilated and started on inhaled nitric oxide, epoprostenol, or both. Leveraging large hospital variation in the choice of initial inhaled vasodilator, we compared the effectiveness of inhaled nitric oxide with that of epoprostenol by limiting analysis to patients admitted to hospitals that exclusively used either inhaled nitric oxide or epoprostenol. The primary outcome of successful extubation was modeled using multivariate Fine-Grey competing risk (death or hospice discharge) time-to-event models.Results: Among 11,200 patients (303 hospitals), 6,366 patients (56.8%) received inhaled nitric oxide first, 4,720 patients (42.1%) received inhaled epoprostenol first, and 114 patients (1.0%) received both therapies on the same day. One hundred four hospitals (34.3%; 1,666 patients) exclusively used nitric oxide and 118 hospitals (38.9%; 1,812 patients) exclusively used epoprostenol. No differences were found in the likelihood of successful extubation between patients admitted to nitric oxide-only hospitals vs those admitted to epoprostenol-only hospitals (subdistribution hazard ratio, 0.97; 95% CI, 0.80-1.18). Also no differences were found in total hospital costs or death. Results were robust to multiple sensitivity analyses.Interpretation: Large variation exists in the use of initial inhaled vasodilator for respiratory failure across US hospitals. Comparative effectiveness analyses identified no differences in outcomes based on inhaled vasodilator type. [ABSTRACT FROM AUTHOR]

Background: Indeterminate randomized controlled trials (RCTs) in ARDS may arise from sample size misspecification, leading to abandonment of efficacious therapies.Research Questions: If evidence exists for sample size misspecification in ARDS RCTs, has this led to rejection of potentially beneficial therapies? Does evidence exist for prognostic enrichment in RCTs using mortality as a primary outcome?Study Design and Methods: We identified 150 ARDS RCTs commencing recruitment after the 1994 American European Consensus Conference ARDS definition and published before October 31, 2020. We examined predicted-observed sample size, predicted-observed control event rate (CER), predicted-observed average treatment effect (ATE), and the relationship between observed CER and observed ATE for RCTs with mortality and nonmortality primary outcome measures. To quantify the strength of evidence, we used Bayesian-averaged meta-analysis, trial sequential analysis, and Bayes factors.Results: Only 84 of 150 RCTs (56.0%) reported sample size estimations. In RCTs with mortality as the primary outcome, CER was overestimated in 16 of 28 RCTs (57.1%). To achieve predicted ATE, interventions needed to prevent 40.8% of all deaths, compared with the original prediction of 29.3%. Absolute reduction in mortality ≥ 10% was observed in 5 of 28 RCTs (17.9%) but was predicted in 21 of 28 RCTs (75.0%). For RCTs with mortality as the primary outcome, no association was found between observed CER and observed ATE (pooled OR: β = -0.04; 95% credible interval, -0.18 to 0.09). We identified three interventions that are not currently standard of care with a Bayesian-averaged effect size of > 0.20 and moderate strength of existing evidence: corticosteroids, airway pressure release ventilation, and noninvasive ventilation.Interpretation: Reporting of sample size estimations was inconsistent in ARDS RCTs, and misspecification of CER and ATE was common. Prognostic enrichment strategies in ARDS RCTs based on all-cause mortality are unlikely to be successful. Bayesian methods can be used to prioritize interventions for future effectiveness RCTs. [ABSTRACT FROM AUTHOR]

Background: Data assessing outcomes of patients with solid tumors demonstrating septic shock using the Third International Consensus Definitions for Sepsis and Septic Shock are scarce.Research Question: What are the independent predictors of 28-day mortality in critically ill adults with solid tumors and septic shock?Study Design and Methods: Cohort of solid tumor patients admitted to the ICU with septic shock. Demographic and clinical characteristics were gathered from the electronic health records. We developed a reduced multivariate logistics regression model to identify independent predictors of 28-day mortality and used Kaplan-Meier plots to assess survival.Results: A total of 271 patients were included. The median age was 62 years (range, 19-94 years); 57.2% were men and 53.5% were White. The most common underlying malignancies were lung (19.2%), breast (7.7%), pancreatic (7.7%), and colorectal (7.4%) cancers. Most patients (84.5%) harbored metastatic disease. Twenty-eight days after ICU admission, 188 patients (69.4%) had died. Nonsurvivors showed a higher rate of advanced cancer, longer hospital stays before ICU admission, and higher Sequential Organ Failure Assessment scores at admission and throughout the ICU stay (P < .001 for all). The multivariate analysis identified metastatic disease (OR, 3.17; 95% CI, 1.43-7.03), respiratory failure (OR, 2.34; 95% CI, 1.15-4.74), elevated lactate levels (OR, 3.19; 95% CI, 1.90-5.36), and Eastern Cooperative Oncology Group performance scores of 3 or 4 (OR, 2.72; 95% CI, 1.33-5.57) as independent predictors of 28-day mortality. Only 38 patients (14%) were discharged home without medical assistance.Interpretation: The 28-day mortality rate of patients with solid tumors and septic shock was considerably high. Factors associated with worse survival included advanced oncologic disease, poor performance status, high lactate level, and concomitant acute respiratory failure. Early goals-of-care discussions should be considered for frail patients with septic shock and advanced metastatic disease without denying access to the appropriate level of care. [ABSTRACT FROM AUTHOR]

Background: SARS-CoV-2-related ARDS is associated with endothelial dysfunction and profound dysregulation of the thrombotic-fibrinolytic pathway. Defibrotide is a polyanionic compound with fibrinolytic, antithrombotic, and antiinflammatory properties.Research Question: What is the safety and tolerability of defibrotide in patients with severe SARS-CoV-2 infections?Study Design and Methods: We report a prospective, open-label, single-center safety trial of defibrotide for the management of SARS-CoV-2-related ARDS. Eligible participants were 18 years of age or older with clinical and radiographic signs of ARDS, no signs of active bleeding, a serum D-dimer of more than twice upper limit of normal, and positive polymerase chain reaction-based results for SARS-CoV-2. Defibrotide (6.25 mg/kg/dose IV q6h) was administered for a planned 7-day course, with serum D-dimer levels and respiratory function monitored daily during therapy.Results: Twelve patients (median age, 63 years) were treated, with 10 patients receiving mechanical ventilation and 6 receiving vasopressor support at study entry. The median D-dimer was 3.25 μg/ml (range, 1.33-12.3) at study entry. The median duration of therapy was 7 days. No hemorrhagic or thrombotic complications occurred during therapy. No other adverse events attributable to defibrotide were noted. Four patients met the day 7 pulmonary response parameter, all four showing a decrease in serum D-dimer levels within the initial 72 h of defibrotide therapy. Three patients died of progressive pulmonary disease 11, 17, and 34 days after study entry. Nine patients (75%) remain alive 64 to 174 days after initiation of defibrotide. Day 30 all-cause mortality was 17% (95% CI, 0%-35%). All patients with a baseline Pao2 to Fio2 ratio of ≥ 125 mm Hg survived, whereas the three patients with a baseline Pao2 to Fio2 ratio of < 125 mm Hg died.Interpretation: The use of defibrotide for management of SARS-CoV-2-related ARDS proved safe and tolerable. No hemorrhagic or thrombotic complications were reported during therapy, with promising outcomes in a patient population with a historically high mortality rate.Trial Registry: ClinicalTrials.gov; No.: NCT04530604; URL: www.Clinicaltrials: gov. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygenation (ECMO) increasingly is being used to support acute respiratory failure and for bridging to lung transplantation. Bleeding and thrombosis are common complications in the acute setting, but the literature describing long-term ECMO complications is limited, and no previous reports have been made of delayed central venous strictures resulting from remote ECMO bridging. Herein, we describe a patient who demonstrated complete inferior vena cava obstruction resulting from venovenous ECMO bridge to lung transplantation 5 years previously. The severe stricture and secondary thrombosis were managed with inferior vena cava angioplasty, stenting, thrombectomy, and thrombolysis, leading to clinical improvement. This case highlights the need for awareness and monitoring for long-term vascular complications in a growing population of patients who have received ECMO support. [ABSTRACT FROM AUTHOR]

Background: There is no pharmacologic treatment for ARDS. Platelets play an important role in the pathophysiology of ARDS. Preclinical, observational, and clinically relevant models of ARDS indicate aspirin as a potential therapeutic option.Research Question: Is enteral aspirin (75 mg, once daily) safe and effective in improving surrogate outcomes in adult patients with ARDS?Study Design and Methods: This randomized, double-blind (patient and investigator), allocation-concealed, placebo-controlled phase 2 trial was conducted in five UK ICUs. Patients fulfilling the Berlin definition of ARDS were randomly assigned at a 1:1 ratio to receive enteral aspirin (75 mg) or placebo, for a maximum of 14 days, using a computer-generated randomization schedule, with variable block size, stratified by vasopressor requirement. The primary end point was oxygenation index (OI) on day 7. Secondary outcomes included safety parameters and other respiratory physiological markers. Analyses were by intention to treat.Results: The trial was stopped early, due to slow recruitment, after 49 of a planned 60 patients were recruited. Twenty-four patients were allocated to aspirin and 25 to placebo. There was no significant difference in day 7 OI [aspirin group: unadjusted mean, 54.4 (SD 26.8); placebo group: 42.4 (SD 25); mean difference, 12.0; 95% CI, -6.1 to 30.1; P = .19]. Aspirin did not significantly impact the secondary outcomes. There was no difference in the number of adverse events between the groups (13 in each; OR, 1.04; 95% CI, 0.56-1.94; P = .56).Interpretation: Aspirin was well tolerated but did not improve OI or other physiological outcomes; a larger trial is not feasible in its current design.Trial Registration: ClinicalTrials.gov; No.: NCT02326350; URL: www.Clinicaltrials: gov. [ABSTRACT FROM AUTHOR]

Background: ARDS is an inflammatory condition of the lungs and is a common condition in adult ICUs. The resources required and costs of care for patients with ARDS are significant because of the severity of the illness and extended ICU lengths of stay.Research Question: What are the costs associated with ARDS?Study Design and Methods: We systematically searched the literature through April 29, 2021, for articles relevant to ARDS and costs. MEDLINE, Embase, Central, and EconLit databases were searched, and articles that reported on cost data from an original publication in adult patients with ARDS were included. Two authors independently assessed articles for inclusion and extracted data elements related to costs, methodology, health care system type, economic perspective, and clinical data. Publication quality was assessed using a modified version of the Quality of Health Economic Studies Instrument.Results: Four thousand six hundred sixty-three publications were found, of which 110 were included for full-text review (κ = 0.72). A total of 22 publications (49,483 patients) were suitable for data extraction. The publications represented a broad range of health care systems, economic perspectives, costing methodology, and time frames. Mean inpatient costs ranged from $8,476 (2021 US dollars [USD]) to $547,974 (2021 USD) and were highest in publications of lower quality and in American health systems and were associated with trauma cohorts. Outpatient costs were highest in publications with higher readmission rates, longer durations of follow-up, and in American health systems.Interpretation: A wide range of costing data is available for ARDS. A comprehensive synthesis of this literature frames the reasons for this and allows estimates to reflect the context in which they were assessed. This information will be of value to researchers and administrators interested in the economics of caring for patients with ARDS.Trial Registry: PROSPERO; No.: CRD42020192487 https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=192487. [ABSTRACT FROM AUTHOR]

Case Presentation: A 19-year-old, previously healthy man presented with 3 days of cough, high-grade fevers (40 °C), and dyspnea. Apart from a resolved history of seizures not requiring medications, he had no medical or surgical history. He had no known drug allergies. He took montelukast for allergies and trimethoprim-sulfamethoxazole (TMP-SMX) for 2 weeks before admission for acne, but no other medications, including over-the-counter medications and supplements. He had animal exposures to a new puppy and a friend's bird. He had no history of smoking, vaping, or recreational drug use. His paternal grandmother had rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Background: Perceived health is one of the strongest determinants of subjective well-being, but it has received little attention among survivors of ARDS.Research Question: How well do self-reported measures of physical, emotional, and social functioning predict perceived overall health (measured using the EQ-5D visual analog scale [EQ-5D-VAS]) among adult survivors of ARDS? Are demographic features, comorbidity, or severity of illness correlated with perceived health after controlling for self-reported functioning?Study Design and Methods: We analyzed the ARDSNet Long Term Outcomes Study (ALTOS) and Improving Care of Acute Lung Injury Patients (ICAP) Study, two longitudinal cohorts with a total of 823 survivors from 44 US hospitals, which prospectively assessed survivors at 6 and 12 months after ARDS. Perceived health, evaluated using the EQ-5D-VAS, was predicted using ridge regression and self-reported measures of physical, emotional, and social functioning. The difference between observed and predicted perceived health was termed perspective deviation (PD). Correlations between PD and demographics, comorbidities, and severity of illness were explored.Results: The correlation between observed and predicted EQ-5D-VAS scores ranged from 0.68 to 0.73 across the two cohorts and time points. PD ranged from -80 to +34 and was more than the minimum clinically important difference for 52% to 55% of survivors. Neither demographic features, comorbidity, nor severity of illness were correlated strongly with PD, with |r| < 0.25 for all continuous variables in both cohorts and time points. The correlation between PD at 6- and 12-month assessments was weak (ALTOS: r = 0.22, P < .001; ICAP: r = 0.20, P = .02).Interpretation: About half of survivors of ARDS showed clinically important differences in actual perceived health vs predicted perceived health based on self-reported measures of functioning. Survivors of ARDS demographic features, comorbidities, and severity of illness were correlated only weakly with perceived health after controlling for measures of perceived functioning, highlighting the challenge of predicting how individual patients will respond psychologically to new impairments after critical illness. [ABSTRACT FROM AUTHOR]

Considering the COVID-19 pandemic where concomitant occurrence of ARDS and severe acute brain injury (sABI) has increasingly coemerged, we synthesize existing data regarding the simultaneous management of both conditions. Our aim is to provide readers with fundamental principles and concepts for the management of sABI and ARDS, and highlight challenges and conflicts encountered while managing concurrent disease. Up to 40% of patients with sABI can develop ARDS. Although there are trials and guidelines to support the mainstays of treatment for ARDS and sABI independently, guidance on concomitant management is limited. Treatment strategies aimed at managing severe ARDS may at times conflict with the management of sABI. In this narrative review, we discuss the physiological basis and risks involved during simultaneous management of ARDS and sABI, summarize evidence for treatment decisions, and demonstrate these principles using hypothetical case scenarios. Use of invasive or noninvasive monitoring to assess brain and lung physiology may facilitate goal-directed treatment strategies with the potential to improve outcome. Understanding the pathophysiology and key treatment concepts for comanagement of these conditions is critical to optimizing care in this high-acuity patient population. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has caused acute lung injury in millions of individuals worldwide. Some patients develop COVID-related acute respiratory distress syndrome (CARDS) and cannot be liberated from mechanical ventilation. Others may develop post-COVID fibrosis, resulting in substantial disability and need for long-term supplemental oxygen. In both of these situations, treatment teams often inquire about the possibility of lung transplantation. In fact, lung transplantation has been successfully employed for both CARDS and post-COVID fibrosis in a limited number of patients worldwide. Lung transplantation after COVID infection presents a number of unique challenges that transplant programs must consider. In those with severe CARDS, the inability to conduct proper psychosocial evaluation and pretransplantation education, marked deconditioning from critical illness, and infectious concerns regarding viral reactivation are major hurdles. In those with post-COVID fibrosis, our limited knowledge about the natural history of recovery after COVID-19 infection is problematic. Increased knowledge of the likelihood and degree of recovery after COVID-19 acute lung injury is essential for appropriate decision-making with regard to transplantation. Transplant physicians must weigh the risks and benefits of lung transplantation differently in a post-COVID fibrosis patient who is likely to remain stable or gradually improve in comparison with a patient with a known progressive fibrosing interstitial lung disease (fILD). Clearly lung transplantation can be a life-saving therapeutic option for some patients with severe lung injury from COVID-19 infection. In this review, we discuss how lung transplant providers from a number of experienced centers approach lung transplantation for CARDS or post-COVID fibrosis. [ABSTRACT FROM AUTHOR]

Case Presentation: A 17-year-old previously healthy Taiwanese girl presented with syncope on a background of 1 month of weakness, polyarthritis, and heliotrope rash. Her presentation and investigations, which included an elevated creatine phosphokinase level and diffuse myositis on lower limb MRI, were consistent with juvenile dermatomyositis (JDM). [ABSTRACT FROM AUTHOR]

Background: Family members of patients admitted to the ICU experience a constellation of sequelae described as postintensive care syndrome-family. The influence that an inter-ICU transfer has on psychological outcomes is unknown.Research Question: Is inter-ICU transfer associated with poor psychological outcomes in families of patients with acute respiratory failure?Study Design and Methods: Cross-sectional observational study of 82 families of patients admitted to adult ICUs (tertiary hospital). Data included demographics, admission source, and outcomes. Admission source was classified as inter-ICU transfer (n = 39) for patients admitted to the ICU from other hospitals and direct admit (n = 43) for patients admitted from the ED or the operating room of the same hospital. We used quantitative surveys to evaluate psychological distress (Hospital Anxiety and Depression Scale [HADS]) and posttraumatic stress (Post-Traumatic Stress Scale; PTSS) and examined clinical, family, and satisfaction factors associated with psychological outcomes.Results: Families of transferred patients travelled longer distances (mean ± SD, 109 ± 106 miles) compared with those of patients directly admitted (mean ± SD, 65 ± 156 miles; P ≤ .0001). Transferred patients predominantly were admitted to the neuro-ICU (64%), had a longer length of stay (direct admits: mean ± SD, 12.7 ± 9.3 days; transferred patients: mean ± SD, 17.6 ± 9.3 days; P < .01), and a higher number of ventilator days (direct admits: mean ± SD, 6.9 ± 8.6 days; transferred: mean ± SD, 10.6 ± 9.0 days; P < .01). Additionally, they were less likely to be discharged home (direct admits, 63%; transferred, 33%; P = .08). In a fully adjusted model of psychological distress and posttraumatic stress, family members of transferred patients were found to have a 1.74-point (95% CI, -1.08 to 5.29; P = .30) higher HADS score and a 5.19-point (95% CI, 0.35-10.03; P = .03) higher PTSS score than those of directly admitted family members.Interpretation: In this exploratory study, posttraumatic stress measured by the PTSS was higher in the transferred families, but these findings will need to be replicated to infer clinical significance. [ABSTRACT FROM AUTHOR]

Background: Joblessness is common after ARDS, but related risk factors are not fully understood.Research Question: What is the association between survivors' pre-ARDS workload and post-ARDS functional impairment, pain, and fatigue with their return to work (RTW) status?Study Design and Methods: The U.S. Occupational Information Network (O∗NET) was used to determine pre-ARDS workload for participants in the ARDS Network Long-Term Outcomes Study (ALTOS). Post-ARDS functional impairment was assessed using the Mini-Mental State Examination and SF-36 Physical Functioning, Social Functioning, and Mental Health sub-scales, and categorized as either no impairments, only psychosocial impairment, physical with low psychosocial impairment, or physical with high psychosocial impairment. Post-ARDS pain and fatigue were assessed using the SF-36 pain item and Functional Assessment of Chronic Illness Therapy-Fatigue Scale fatigue scale, respectively. Generalized linear mixed modeling methods were used to evaluate associations among pre-ARDS workload, post-ARDS functional impairment, and symptoms of pain and fatigue with post-ARDS RTW.Results: Pre-ARDS workload was not associated with post-ARDS RTW. However, as compared with survivors with no functional impairment, those with only psychosocial impairment (OR [CI]: 0.18 [0.06-0.50]), as well as physical impairment plus either low psychosocial impairment (0.08 [0.03-0.22]) or high psychosocial impairment (0.01 [0.003-0.05]) had lower odds of working. Pain (0.06 [0.03-0.14]) and fatigue (0.07 [0.03-0.16]) were also negatively associated with RTW.Interpretation: For previously employed survivors of ARDS, post-ARDS psychosocial and physical impairments, pain, and fatigue were negatively associated with RTW, whereas pre-ARDS workload was not associated. These findings are important for designing and implementing vocational interventions for ARDS survivors. [ABSTRACT FROM AUTHOR]

Background: Despite the frequency and cost of hospitalizations for acute respiratory failure (ARF), the literature regarding the impact of hospital safety net burden on outcomes of these hospitalizations is sparse.Research Question: How does safety net burden impact outcomes of ARF hospitalizations such as mortality, tracheostomy, and resource use?Study Design and Methods: This was a retrospective cohort study using the National Inpatient Sample 2007-2017. All patients hospitalized with a primary diagnosis of ARF were tabulated using the International Classification of Diseases 9th and 10th Revision codes, and safety net burden was calculated using previously published methodology. High- and low-burden hospitals were generated from proportions of Medicaid and uninsured patients. Trends were analyzed using a nonparametric rank-based test, whereas multivariate logistic and linear regression models were used to establish associations of safety net burden with key clinical outcomes.Results: Of an estimated 8,941,334 hospitalizations with a primary diagnosis of ARF, 33.9% were categorized as occurring at low-burden hospitals (LBHs) and 31.6% were categorized as occurring at high-burden hospitals (HBHs). In-hospital mortality significantly decreased at HBHs (22.8%-12.6%; nonparametric trend [nptrend] < .001) and LBHs (22.0%-10.9%; nptrend < .001) over the study period, as did tracheostomy placement (HBH, 5.6%-1.3%; LBH, 3.5%-0.8%; all nptrend <.001). After adjustment for patient and hospital factors, an HBH was associated with increased odds of mortality (adjusted OR [AOR], 1.11; 95% CI, 1.10-1.12) and tracheostomy use (AOR, 1.33; 95% CI, 1.29-1.37), as well as greater hospitalization costs (β coefficient, +$1,083; 95% CI, $882-$1,294) and longer lengths of stay (β coefficient, +3.3 days; 95% CI, 3.2-3.3 days).Interpretation: After accounting for differences between patient cohorts, high safety net burden was associated independently with inferior clinical outcomes and increased costs after ARF hospitalizations. These findings emphasize the need for health care reform to ameliorate disparities within these safety net centers, which treat our most vulnerable populations. [ABSTRACT FROM AUTHOR]

Patients with COVID-19 report severe respiratory symptoms consistent with ARDS. The clinical presentation of ARDS in COVID-19 is often atypical, as patients with COVID-19 exhibit a disproportionate hypoxemia compared with relatively preserved lung mechanics. This pattern is more similar to neonatal respiratory distress syndrome secondary to surfactant deficiency, which has been shown to benefit from exogenous surfactant. We present our experience with exogenous surfactant treatment in a patient with COVID-19 experiencing COVID-19-related ARDS. The patient responded with improved oxygenation, and we believe surfactant was the catalyst for the successful extubation and clinical improvement of the patient. [ABSTRACT FROM AUTHOR]

Background: Although clinical studies have evaluated dexmedetomidine as a strategy to improve noninvasive ventilation (NIV) comfort and tolerance in patients with acute respiratory failure (ARF), their results have not been summarized.Research Question: Does dexmedetomidine, when compared with another sedative or placebo, reduce the risk of delirium, mortality, need for intubation and mechanical ventilation, or ICU length of stay (LOS) in adults with ARF initiated on NIV in the ICU?Study Design and Methods: We electronically searched MEDLINE, EMBASE, and the Cochrane Library from inception through July 31, 2020, for randomized clinical trials (RCTs). We calculated pooled relative risks (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes with the corresponding 95% CIs using a random-effect model.Results: Twelve RCTs were included in our final analysis (n = 738 patients). The use of dexmedetomidine, compared with other sedation strategies or placebo, reduced the risk of intubation (RR, 0.54; 95% CI, 0.41-0.71; moderate certainty), delirium (RR, 0.34; 95% CI, 0.22-0.54; moderate certainty), and ICU LOS (MD, -2.40 days; 95% CI, -3.51 to -1.29 days; low certainty). Use of dexmedetomidine was associated with an increased risk of bradycardia (RR, 2.80; 95% CI, 1.92-4.07; moderate certainty) and hypotension (RR, 1.98; 95% CI, 1.32-2.98; moderate certainty).Interpretation: Compared with any sedation strategy or placebo, dexmedetomidine reduced the risk of delirium and the need for mechanical ventilation while increasing the risk of bradycardia and hypotension. The results are limited by imprecision, and further large RCTs are needed.Trial Registry: PROSPERO; No.: 175086; URL: www.crd.york.ac.uk/prospero/. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection causes direct lung damage, overwhelming endothelial activation, and inflammatory reaction, leading to acute respiratory failure and multi-organ dysfunction. Ongoing clinical trials are evaluating targeted therapies to hinder this exaggerated inflammatory response. Critically ill coronavirus disease 2019 (COVID-19) patients have shown heterogeneous severity trajectories, suggesting that response to therapies is likely to vary across patients.Research Question: Are critically ill COVID-19 patients biologically and immunologically dissociable based on profiling of currently evaluated therapeutic targets?Study Design and Methods: We did a single-center, prospective study in an ICU department in France. Ninety-six critically ill adult patients admitted with a documented SARS-CoV-2 infection were enrolled. We conducted principal components analysis and hierarchical clustering on a vast array of immunologic variables measured on the day of ICU admission.Results: We found that patients were distributed in three clusters bearing distinct immunologic features and associated with different ICU outcomes. Cluster 1 had a "humoral immunodeficiency" phenotype with predominant B-lymphocyte defect, relative hypogammaglobulinemia, and moderate inflammation. Cluster 2 had a "hyperinflammatory" phenotype, with high cytokine levels (IL-6, IL-1β, IL-8, tumor necrosis factor-alpha [TNF⍺]) associated with CD4+ and CD8+ T-lymphocyte defects. Cluster 3 had a "complement-dependent" phenotype with terminal complement activation markers (elevated C3 and sC5b-9).Interpretation: Patients with severe COVID-19 exhibiting cytokine release marks, complement activation, or B-lymphocyte defects are distinct from each other. Such immunologic variability argues in favor of targeting different mediators in different groups of patients and could serve as a basis for patient identification and clinical trial eligibility. [ABSTRACT FROM AUTHOR]

Background: A better understanding of the clinical features associated with prolonged hospitalization in acute respiratory failure may allow for better-informed care planning.Research Question: What are the incidence, mortality, cost, and clinical determinants of prolonged hospitalization among patients with acute respiratory failure (ARF)?Study Design and Methods: Using the National Inpatient Sample data from 2004 to 2014, we identified adults 18 years and older with International Classification of Diseases, 9th edition (ICD-9) codes for ARF requiring mechanical ventilation for at least 2 days (ICD-9 518.81 or 518.82, 96.7 or 96.04, and 96.05). Outcomes studied included incidence, in-hospital mortality, cost of hospitalization, and associated patient-level and hospital-level characteristics. Trends were assessed by logistic regression, linear regression, and general linear modeling with Poisson distribution.Results: Of the 5,539,567 patients with ARF, 77,665 (1.4%) had a prolonged length of stay (pLOS), defined as ≥ 60 days. Among those with pLOS, 52,776 (68%) survived to discharge. Over the study period, the incidence of pLOS decreased by 48%, in-patient mortality decreased by 18%, per-patient cost of care rose, but the percentage of the total cost of ARF care consumed by patients with pLOS did not significantly decrease (P = .06). Prolonged LOS was more likely to occur in urban teaching hospitals (OR, 6.8; 95% CI, 4.6-10.2; P < .001), hospitals located in the northeastern United States (OR, 3.6; 95% CI, 3.0-4.3; P < .001), and among patients with Medicaid insurance coverage (OR, 2.1; 95% CI, 1.9-2.4; P < .001).Interpretation: From 2004 to 2014, incidence and mortality decreased among patients with ARF and pLOS, and although per-patient costs rose, the percentage of total cost of care remained stable. There is substantial variation in length of stay for patients with ARF by US region, hospital teaching status, and patient insurance coverage. [ABSTRACT FROM AUTHOR]