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Critical care trials evaluate the effect of interventions in patients with diverse personal histories and causes of illness, often under the umbrella of heterogeneous clinical syndromes, such as sepsis or acute respiratory distress syndrome. Given this variation, it is reasonable to expect that the effect of treatment on outcomes may differ for individuals with variable characteristics. However, in randomized controlled trials, efficacy is typically assessed by the average treatment effect (ATE), which quantifies the average effect of the intervention on the outcome in the study population. Importantly, the ATE may hide variations of the treatment's effect on a clinical outcome across levels of patient characteristics, which may erroneously lead to the conclusion that an intervention does not work overall when it may in fact benefit certain patients. In this review, we describe methodological approaches for assessing heterogeneity of treatment effect (HTE), including expert-derived subgrouping, data-driven subgrouping, baseline risk modeling, treatment effect modeling, and individual treatment rule estimation. Next, we outline how insights from HTE analyses can be incorporated into the design of clinical trials. Finally, we propose a research agenda for advancing the field and bringing HTE approaches to the bedside. [ABSTRACT FROM AUTHOR]

The given text is a list of references to various scientific articles related to the topic of airway pressure release ventilation (APRV) and its effects on lung injury and respiratory mechanics. The articles discuss the preventive and therapeutic potential of APRV in conditions such as acute respiratory distress syndrome (ARDS), traumatic hemorrhagic shock, ventilator-induced lung injury, and extrapulmonary lung injury. The studies explore the physiological mechanisms and benefits of APRV, including its ability to prevent lung injury, reduce alveolar strain, improve respiratory mechanics, and minimize ventilator-associated lung injury. The articles also highlight the importance of personalized ventilation strategies and the role of dynamic alveolar physiology in minimizing lung injury. [Extracted from the article]

This document provides a summary of several randomized controlled trials (RCTs) that examine the use of airway pressure release ventilation (APRV) in patients with acute respiratory distress syndrome (ARDS) or at risk for ARDS. The trials evaluate different APRV settings and compare them to control groups using various outcomes such as ventilator-free days, mortality, and adverse events. The studies highlight the complexity of APRV settings and the need for further research to determine the optimal approach. The document also discusses potential sources of bias in interpreting the results of these trials. The article suggests that further research is needed to determine the appropriate use of APRV and to assess its potential benefits and risks. Current clinical guidelines do not recommend routine use of APRV for ARDS. [Extracted from the article]

OBJECTIVES: Mortality due to acute respiratory distress syndrome (ARDS) is a major global health problem. Knowledge of epidemiological data on ARDS is crucial to design management, treatment strategies, and optimize resources. There is ample data regarding mortality of ARDS from high-income countries; in this review, we evaluated mortality due to ARDS in Latin America. DATA SOURCES: We searched in PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and Latin American and Caribbean Health Science Literature databases from 1967 to March 2023. STUDY SELECTION: We searched prospective or retrospective observational studies and randomized controlled trials conducted in Latin American countries reporting ARDS mortality. DATA EXTRACTION: Three pairs of independent reviewers checked all studies for eligibility based on their titles and abstracts. We performed meta-analysis of proportions using a random-effects model. We performed sensitivity analyses including studies with low risk of bias and with diagnosis using the Berlin definition. Subgroup analysis comparing different study designs, time of publication (up to 2000 and from 2001 to present), and studies in which the diagnosis of ARDS was made using Pao2/Fio2 less than or equal to 200 and regional variations. Subsequently, we performed meta-regression analyses. Finally, we graded the certainty of the evidence (Grading of Recommendations Assessment, Development, and Evaluation). DATA SYNTHESIS: Of 3315 articles identified, 32 were included (3627 patients). Mortality was 52% in the pooled group (low certainty of evidence). In the sensitivity analysis (according to the Berlin definition), mortality was 46% (moderate certainty of evidence). In the subgroup analysis mortality was 53% (randomized controlled trials), 51% (observational studies), 66% (studies published up to 2000), 50% (studies after 2000), 44% (studies with Pao2/Fio2 ≤ 200), 56% (studies from Argentina/Brazil), and 40% (others countries). No variables were associated with mortality in the meta-regression. CONCLUSIONS: ARDS mortality in Latin America remains high, as in other regions. These results should constitute the basis for action planning to improve the prognosis of patients with ARDS (PROSPERO [CRD42022354035]). [ABSTRACT FROM AUTHOR]

OBJECTIVES: To describe U.S. practice regarding administration of sedation and analgesia to patients on noninvasive ventilation (NIV) for acute respiratory failure (ARF) and to determine the association of this practice with odds of intubation or death. DESIGN: A retrospective multicenter cohort study. SETTING: A total of 1017 hospitals contributed data between January 2010 and September 2020 to the Premier Healthcare Database, a nationally representative healthcare database in the United States. PATIENTS: Adult (≥ 18 yr) patients admitted to U.S. hospitals requiring NIV for ARF. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 433,357 patients on NIV of whom (26.7% [95% CI] 26.3%-27.0%) received sedation or analgesia. A total of 50,589 patients (11.7%) received opioids only, 40,646 (9.4%) received benzodiazepines only, 20,146 (4.6%) received opioids and benzodiazepines, 1.573 (0.4%) received dexmedetomidine only, and 2,639 (0.6%) received dexmedetomidine in addition to opioid and/or benzodiazepine. Of 433,357 patients receiving NIV, 50,413 (11.6%; 95% CI, 11.5-11.7%) patients underwent invasive mechanical ventilation on hospital days 2-5 or died on hospital days 2-30. Intubation was used in 32,301 patients (7.4%; 95% CI, 7.3-7.6%). Further, death occurred in 24,140 (5.6%; 95% CI, 5.5-5.7%). In multivariable analysis adjusting for relevant covariates, receipt of any medication studied was associated with increased odds of intubation or death. In inverse probability weighting, receipt of any study medication was also associated with increased odds of intubation or death (average treatment effect odds ratio 1.38; 95% CI, 1.35-1.40). CONCLUSIONS: The use of sedation and analgesia during NIV is common. Medication exposure was associated with increased odds of intubation or death. Further investigation is needed to confirm this finding and determine whether any subpopulations are especially harmed by this practice. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Nonconventional ventilators (NCVs), defined here as transport ventilators and certain noninvasive positive pressure devices, were used extensively as crisis-time ventilators for intubated patients with COVID-19. We assessed whether there was an association between the use of NCV and higher mortality, independent of other factors. DESIGN: This is a multicenter retrospective observational study. SETTING: The sample was recruited from a single healthcare system in New York. The recruitment period spanned from March 1, 2020, to April 30, 2020. PATIENTS: The sample includes patients who were intubated for COVID-19 acute respiratory distress syndrome (ARDS). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was 28-day in-hospital mortality. Multivariable logistic regression was used to derive the odds of mortality among patients managed exclusively with NCV throughout their ventilation period compared with the remainder of the sample while adjusting for other factors. A secondary analysis was also done, in which the mortality of a subset of the sample exclusively ventilated with NCV was compared with that of a propensity score-matched subset of the control group. Exclusive use of NCV was associated with a higher 28-day in-hospital mortality while adjusting for confounders in the regression analysis (odds ratio, 1.41; 95% CI [1.07-1.86]). In the propensity score matching analysis, the mortality of patients exclusively ventilated with NCV was 68.9%, and that of the control was 60.7% (p = 0.02). CONCLUSIONS: Use of NCV was associated with increased mortality among patients with COVID-19 ARDS. More lives may be saved during future ventilator shortages if more full-feature ICU ventilators, rather than NCVs, are reserved in national and local stockpiles. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Critically ill patients with tuberculosis carry high mortality. Identification of factors associated with mortality in critically ill tuberculosis patients may enable focused treatment. DATA SOURCES: An extensive literature search of PubMed (MEDLINE), Embase, the Cochrane Library, and Google Scholar was performed using Medical Subject Headings terms "tuberculosis," "critical care," "critical care outcome," and "ICU." We aimed to identify factors affecting mortality in critically ill tuberculosis patients. STUDY SELECTION: All the studies comparing factors affecting mortality between survivors and nonsurvivors in critically ill tuberculosis patients were included. The database search yielded a total of 3017 records, of which 17 studies were included in the meta-analysis. DATA EXTRACTION: Data were collected including the name of the author, year and country of publication, duration of the study, number of patients studied, type of tuberculosis, patient demography, smoking history, laboratory parameters, comorbidities, the requirement for mechanical ventilation, duration of ventilation, ICU and hospital length of stay (LOS), type of lung involvement, complications, and outcomes. DATA SYNTHESIS: The major factors that contributed to mortality in critically ill tuberculosis patients were age, platelet count, albumin, C-reactive protein (CRP), the requirement and duration of invasive mechanical ventilation, Pao2/Fio2 ratio, presence of acute respiratory distress syndrome, shock, hospital-acquired infections, renal replacement therapy, and ICU and hospital LOS. CONCLUSIONS: Patient age, platelet count, albumin and CRP levels, the requirement and duration of invasive mechanical ventilation, Pao2/Fio2 ratio, hospitalacquired infections, renal replacement therapy, and ICU LOS were variables associated with mortality. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To examine trends in utilization and outcomes among patients with the acute respiratory distress syndrome (ARDS) requiring prolonged venovenous extracorporeal membrane oxygenation (VV ECMO) support. DESIGN: Retrospective observational cohort study. SETTING: Adult patients in the Extracorporeal Life Support Organization registry. PATIENTS: Thirteen thousand six hundred eighty-one patients that required ECMO for the support of ARDS between January 2012 and December 2022. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Mortality while supported with VV ECMO and survival to hospital discharge based on ECMO duration were examined utilizing multivariable logistic regression. Among the 13,681 patients supported with VV ECMO, 4,040 (29.5%) were supported for greater than or equal to 21 days and 975 (7.1%) for greater than or equal to 50 days. Patients supported with prolonged VV ECMO were less likely to be discharged alive from the hospital compared with those with short duration of support (46.5% vs. 59.7%; p < 0.001). However, among patients supported with VV ECMO greater than or equal to 21 days, duration of extracorporeal life support was not significantly associated with mortality (odds ratio [OR], 0.99; 95% CI, 0.98-1.01; p = 0.87 and adjusted OR, 0.99; 95% CI, 0.97-1.02; p = 0.48). Even in those supported with VV ECMO for at least 120 days (n = 113), 52 (46.0%) of these patients were ultimately discharged alive from the hospital. CONCLUSIONS: Prolonged VV ECMO support of ARDS has increased and accounts for a substantial portion of cases. Among patients that survive for greater than or equal to 21 days while receiving VV ECMO support, duration is not predictive of survival to hospital discharge and clinical recovery may occur even after very prolonged VV ECMO support. [ABSTRACT FROM AUTHOR]

RATIONALE: New evidence is available examining the use of corticosteroids in sepsis, acute respiratory distress syndrome (ARDS) and community-acquired pneumonia (CAP), warranting a focused update of the 2017 guideline on critical illness-related corticosteroid insufficiency. OBJECTIVES: To develop evidence-based recommendations for use of corticosteroids in hospitalized adults and children with sepsis, ARDS, and CAP. PANEL DESIGN: The 22-member panel included diverse representation from medicine, including adult and pediatric intensivists, pulmonologists, endocrinologists, nurses, pharmacists, and clinician-methodologists with expertise in developing evidence-based Clinical Practice Guidelines. We followed Society of Critical Care Medicine conflict of interest policies in all phases of the guideline development, including task force selection and voting. METHODS: After development of five focused Population, Intervention, Control, and Outcomes (PICO) questions, we conducted systematic reviews to identify the best available evidence addressing each question. We evaluated the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach and formulated recommendations using the evidence-to-decision framework. RESULTS: In response to the five PICOs, the panel issued four recommendations addressing the use of corticosteroids in patients with sepsis, ARDS, and CAP. These included a conditional recommendation to administer corticosteroids for patients with septic shock and critically ill patients with ARDS and a strong recommendation for use in hospitalized patients with severe CAP. The panel also recommended against high dose/short duration administration of corticosteroids for septic shock. In response to the final PICO regarding type of corticosteroid molecule in ARDS, the panel was unable to provide specific recommendations addressing corticosteroid molecule, dose, and duration of therapy, based on currently available evidence. CONCLUSIONS: The panel provided updated recommendations based on current evidence to inform clinicians, patients, and other stakeholders on the use of corticosteroids for sepsis, ARDS, and CAP. [ABSTRACT FROM AUTHOR]

This document is an executive summary of guidelines on the use of corticosteroids in critically ill patients with sepsis, acute respiratory distress syndrome (ARDS), and community-acquired pneumonia (CAP). The guidelines were developed by a task force of international experts in critical care medicine and endocrinology. The summary provides updated recommendations based on new evidence and focuses on the most common diagnoses in which corticosteroids are considered. The recommendations are categorized by condition and include the strength of the recommendation and the quality of evidence. The summary also mentions that the guidelines are applicable to adult and pediatric patients, but specific recommendations for pediatric patients are limited due to a lack of available studies. [Extracted from the article]

This article discusses the potential harm caused by patient-ventilator interactions (PVIs) in patients receiving mechanical ventilation for acute hypoxemic respiratory failure. The authors conducted a study to assess the association between different types of breaths and surrogate markers of lung strain, stress, and mechanical power. They found that certain abnormal PVIs, such as double-triggered and flow-limited breaths, had the strongest potential to increase markers of lung stress and strain. However, there are limitations to the study, including the use of surrogate markers and the specific mode of ventilation used. Further research is needed to understand the impact of these interactions on clinical outcomes. [Extracted from the article]

OBJECTIVES: Ventilator dyssynchrony may be associated with increased delivered tidal volumes (V t s) and dynamic transpulmonary pressure (ΔPL,dyn), surrogate markers of lung stress and strain, despite low V t ventilation. However, it is unknown which types of ventilator dyssynchrony are most likely to increase these metrics or if specific ventilation or sedation strategies can mitigate this potential. DESIGN: A prospective cohort analysis to delineate the association between ten types of breaths and delivered V t , ΔPL,dyn, and transpulmonary mechanical energy. SETTING: Patients admitted to the medical ICU. PATIENTS: Over 580,000 breaths from 35 patients with acute respiratory distress syndrome (ARDS) or ARDS risk factors. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients received continuous esophageal manometry. Ventilator dyssynchrony was identified using a machine learning algorithm. Mixed-effect models predicted V t , ΔPL,dyn, and transpulmonary mechanical energy for each type of ventilator dyssynchrony while controlling for repeated measures. Finally, we described how V t , positive end-expiratory pressure (PEEP), and sedation (Richmond Agitation-Sedation Scale) strategies modify ventilator dyssynchrony's association with these surrogate markers of lung stress and strain. Double-triggered breaths were associated with the most significant increase in V t , ΔPL,dyn, and transpulmonary mechanical energy. However, flow-limited, early reverse-triggered, and early ventilator-terminated breaths were also associated with significant increases in V t , ΔPL,dyn, and energy. The potential of a ventilator dyssynchrony type to increase V t , ΔPL,dyn, or energy clustered similarly. Increasing set V t may be associated with a disproportionate increase in high-volume and high-energy ventilation from double-triggered breaths, but PEEP and sedation do not clinically modify the interaction between ventilator dyssynchrony and surrogate markers of lung stress and strain. CONCLUSIONS: Double-triggered, flow-limited, early reverse-triggered, and early ventilator-terminated breaths are associated with increases in V t , ΔPL,dyn, and energy. As flow-limited breaths are more than twice as common as double-triggered breaths, further work is needed to determine the interaction of ventilator dyssynchrony frequency to cause clinically meaningful changes in patient outcomes. [ABSTRACT FROM AUTHOR]

The article discusses the use of clinical trial enrichment to improve the success of trials targeting patients who receive mechanical ventilation. Enrichment involves identifying a more homogeneous population with a higher likelihood of benefiting from a potentially risky therapy. The authors propose using machine learning methods to identify patients with hypoxemic respiratory failure (HRF) who are likely to persist on mechanical ventilation, as persistent ventilation increases the risk of poor outcomes. They present a framework for utilizing machine learning methods for trial enrichment and demonstrate the potential benefits and limitations of this approach. However, it is important to consider the patients who would not be included in an enriched trial and to assess the broader population before implementing this model in clinical practice. [Extracted from the article]

OBJECTIVES: To characterize health-related quality of life (HRQL) and functional recovery trajectories and risk factors for prolonged impairments among critically ill children receiving greater than or equal to 3 days of invasive ventilation. DESIGN: Prospective cohort study. SETTING: Quaternary children's hospital PICU. PATIENTS: Children without a preexisting tracheostomy who received greater than or equal to 3 days of invasive ventilation, survived hospitalization, and completed greater than or equal to 1 postdischarge data collection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We evaluated 144 children measuring HRQL using proxy-report Pediatric Quality of Life Inventory and functional status using the Functional Status Scale (FSS) reflecting preillness baseline, PICU and hospital discharge, and 1, 3, 6, and 12 months after hospital discharge. They had a median age of 5.3 years (interquartile range, 1.1–13.0 yr), 58 (40%) were female, 45 (31%) had a complex chronic condition, and 110 (76%) had normal preillness FSS scores. Respiratory failure etiologies included lung disease (n = 49; 34%), neurologic failure (n = 23; 16%), and septic shock (n = 22; 15%). At 1-month postdischarge, 68 of 122 (56%) reported worsened HRQL and 35 (29%) had a new functional impairment compared with preillness baseline. This improved at 3 months to 54 (46%) and 24 (20%), respectively, and remained stable through the remaining 9 months of follow-up. We used interaction forests to evaluate relative variable importance including pairwise interactions and found that therapy consultation within 3 days of intubation was associated with better HRQL recovery in older patients and those with better preillness physical HRQL. During the postdischarge year, 76 patients (53%) had an emergency department visit or hospitalization, and 62 (43%) newly received physical, occupational, or speech therapy. CONCLUSIONS: Impairments in HRQL and functional status as well as health resource use were common among children with acute respiratory failure. Early therapy consultation was a modifiable characteristic associated with shorter duration of worsened HRQL in older patients. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Improving the efficiency of clinical trials in acute hypoxemic respiratory failure (HRF) depends on enrichment strategies that minimize enrollment of patients who quickly resolve with existing care and focus on patients at high risk for persistent HRF. We aimed to develop parsimonious models predicting risk of persistent HRF using routine data from ICU admission and select research immune biomarkers. DESIGN: Prospective cohorts for derivation (n = 630) and external validation (n = 511). SETTING: Medical and surgical ICUs at two U.S. medical centers. PATIENTS: Adults with acute HRF defined as new invasive mechanical ventilation (IMV) and hypoxemia on the first calendar day after ICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We evaluated discrimination, calibration, and practical utility of models predicting persistent HRF risk (defined as ongoing IMV and hypoxemia on the third calendar day after admission): 1) a clinical model with least absolute shrinkage and selection operator (LASSO) selecting Pa o 2/F io 2, vasopressors, mean arterial pressure, bicarbonate, and acute respiratory distress syndrome as predictors; 2) a model adding interleukin-6 (IL-6) to clinical predictors; and 3) a comparator model with Pa o 2/F io 2 alone, representing an existing strategy for enrichment. Forty-nine percent and 69% of patients had persistent HRF in derivation and validation sets, respectively. In validation, both LASSO (area under the receiver operating characteristic curve, 0.68; 95% CI, 0.64–0.73) and LASSO + IL-6 (0.71; 95% CI, 0.66–0.76) models had better discrimination than Pa o 2/F io 2 (0.64; 95% CI, 0.59–0.69). Both models underestimated risk in lower risk deciles, but exhibited better calibration at relevant risk thresholds. Evaluating practical utility, both LASSO and LASSO + IL-6 models exhibited greater net benefit in decision curve analysis, and greater sample size savings in enrichment analysis, compared with Pa o 2/F io 2. The added utility of LASSO + IL-6 model over LASSO was modest. CONCLUSIONS: Parsimonious, interpretable models that predict persistent HRF may improve enrichment of trials testing HRF-targeted therapies and warrant future validation. [ABSTRACT FROM AUTHOR]

A systematic review and meta-analysis of studies on acute respiratory distress syndrome (ARDS) in Latin America between 1967 and 2023 found that hospital mortality for ARDS in the region was 52% overall, with variations over time and by country. The study highlighted the need for further research to understand the factors contributing to high mortality rates in Latin America, including patient characteristics, adherence to evidence-based management strategies, and resource limitations. The study also noted the evolving definitions of ARDS and the impact of supportive care strategies on outcomes. Further data on practice patterns in Latin America is necessary to identify and address barriers to evidence-based care. [Extracted from the article]

A recent study published in Critical Care Medicine examined the association between metabolic syndrome and outcomes in patients with acute respiratory distress syndrome (ARDS). The study found that patients with metabolic syndrome had similar survival rates compared to those without the syndrome, but after adjusting for various factors, metabolic syndrome was actually associated with reduced mortality. However, the study has limitations, including potential bias and challenges in accurately classifying metabolic syndrome in critically ill patients. Further research is needed to better understand the relationship between metabolic syndrome and ARDS outcomes. The findings of the study should not impact clinicians' prognostication for ARDS patients, and more research is needed to understand the underlying mechanisms and potential subphenotypes of ARDS. [Extracted from the article]

OBJECTIVES: Metabolic syndrome is known to predict outcomes in COVID-19 acute respiratory distress syndrome (ARDS) but has never been studied in non- COVID-19 ARDS. We therefore aimed to determine the association of metabolic syndrome with mortality among ARDS trial subjects. DESIGN: Retrospective cohort study of ARDS trials' data. SETTING: An ancillary analysis was conducted using data from seven ARDS Network and Prevention and Early Treatment of Acute Lung Injury Network randomized trials within the Biologic Specimen and Data Repository Information Coordinating Center database. PATIENTS: Hospitalized patients with ARDS and metabolic syndrome (defined by obesity, diabetes, and hypertension) were compared with similar patients without metabolic syndrome (those with less than three criteria). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was 28-day mortality. Among 4288 ARDS trial participants, 454 (10.6%) with metabolic syndrome were compared with 3834 controls (89.4%). In adjusted analyses, the metabolic syndrome group was associated with lower 28-day and 90-day mortality when compared with control (adjusted odds ratio [aOR], 0.70 [95% CI, 0.55-0.89] and 0.75 [95% CI, 0.60-0.95], respectively). With each additional metabolic criterion from 0 to 3, adjusted 28-day mortality was reduced by 18%, 22%, and 40%, respectively. In subgroup analyses stratifying by ARDS etiology, mortality was lower for metabolic syndrome vs. control in ARDS caused by sepsis or pneumonia (at 28 d, aOR 0.64 [95% CI, 0.48--0.84] and 90 d, aOR 0.69 [95% CI, 0.53-0.89]), but not in ARDS from noninfectious causes (at 28 d, aOR 1.18 [95% CI, 0.70-1.99] and 90 d, aOR 1.26 [95% CI, 0.77-2.06]). Interaction p = 0.04 and p = 0.02 for 28- and 90-day comparisons, respectively. CONCLUSIONS: Metabolic syndrome in ARDS was associated with a lower risk of mortality in non-COVID-19 ARDS. The relationship between metabolic in- flammation and ARDS may provide a novel biological pathway to be explored in precision medicine-based trials. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To assess the effect of incorporating bilateral abnormalities as detected by lung ultrasound (LUS) in the Kigali modification and the New Global definition of acute respiratory distress syndrome (ARDS) on the occurrence rate of ARDS. DESIGN: Post hoc analysis of a previously published prospective cohort study. SETTING: An academic mixed medical-surgical ICU. PATIENTS: The original study included critically ill adults with any opacity on chest radiography in whom subsequent LUS was performed. Patients with ARDS according to the Berlin definition, COVID-19 patients and patients with major thorax trauma were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: LUS was performed within 24 hours of chest radiography and the presence of unilateral and bilateral abnormalities on LUS and chest radiograph (opacities) was scored. Subsequently, the Kigali modification and the New Global definition of ARDS were applied by two independent researchers on the patients with newly found bilateral opacities. Of 120 patients, 116 were included in this post hoc analysis. Thirty-three patients had bilateral opacities on LUS and unilateral opacities on chest radiograph. Fourteen of these patients had ARDS according to the Kigali modification and 12 had ARDS according to the New Global definition. The detected LUS patterns were significantly different between patients with and without ARDS (p = 0.004). An A-profile with a positive PosteroLateral Alveolar and/or Pleural Syndrome was most prevalent in patients without ARDS, whereas heterogeneous and mixed A, B, and C patterns were most prevalent in patients with ARDS. CONCLUSION: The addition of bilateral abnormalities as detected by LUS to the Kigali modification and the New Global definition increases the occurrence rate of the ARDS. The nomenclature for LUS needs to be better defined as LUS patterns differ between patients with and without ARDS. Incorporating well-defined LUS criteria can increase specificity and sensitivity of new ARDS definitions. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Concise definitive review of the use of venopulmonary arterial extracorporeal membrane oxygenation (V-PA ECMO) support in patients with cardiopulmonary failure. DATA SOURCES: Original investigations identified through a PubMed search with search terms "percutaneous right ventricular assist device," "oxy-RVAD," "V-PA ECMO," and "veno-pulmonary arterial ECMO" were reviewed and evaluated for relevance. STUDY SELECTION: Studies that included more than three patients supported with V-PA ECMO were included. DATA EXTRACTION: Clinically relevant data from included studies, including patient-important outcomes, were summarized and discussed. DATA SYNTHESIS: We identified four groups of patients where V-PA ECMO has been studied: acute respiratory distress syndrome, right ventricular dysfunction after left ventricular assist device placement, bridge to lung transplantation, and pulmonary embolism. Most identified works are small, single center, and retrospective in nature, precluding definitive conclusions regarding the efficacy of V-PA ECMO. There have been no clinical trials evaluating the efficacy of V-PA ECMO for any indication. CONCLUSIONS: V-PA ECMO is a promising form of extracorporeal support for patients with right ventricular dysfunction. Future work should focus on identifying the optimal timing and populations for the use of V-PA ECMO. [ABSTRACT FROM AUTHOR]

The article discusses the need to redefine the criteria for diagnosing acute respiratory distress syndrome (ARDS) in order to increase equity and embrace heterogeneity in the treatment of the condition. The current definition, known as the Berlin definition, has limitations in terms of its predictive validity and its applicability in low- and middle-income countries (LMICs) where resources are limited. The proposed "global" definition of ARDS aims to include patients in LMICs by incorporating additional criteria such as lung ultrasound and oxygen saturation. Expanding the definition of ARDS would allow for a more comprehensive understanding of the condition and improve patient outcomes worldwide. However, further empirical testing is needed before widespread adoption of the new definition. [Extracted from the article]

The article discusses the trade-off between the benefits and potential harm of invasive mechanical ventilation in critical care practice. The focus is on the concept of mechanical power (MP) of ventilation and its association with adverse outcomes, such as postoperative respiratory failure. The study by Tartler et al. examines the relationship between high MP and postoperative respiratory failure, independent of patients' respiratory system compliance. The authors advocate for the use of MP in titrating mechanical ventilation in the operating room and ICU. However, the study has limitations, and further research is needed to determine the ideal threshold for safe ventilation and the feasibility of integrating MP into clinical practice. [Extracted from the article]

The article discusses the process of weaning patients from venovenous extracorporeal membrane oxygenation (ECMO), a treatment used for severe acute respiratory distress syndrome (ARDS). The authors highlight the lack of standardized guidelines for weaning and the variation in practices among different ECMO centers. They present findings from a study conducted at a German ECMO center, which identified risk factors for failed weaning trials. The article also compares different weaning methods and discusses the importance of considering factors such as respiratory drive and fluid management during the weaning process. The authors emphasize the need for further research to develop optimal weaning approaches. [Extracted from the article]

This article discusses the use of extracorporeal membrane oxygenation (ECMO) as a treatment for respiratory failure in young patients. The study examines whether there are differences in outcomes between teenagers and young adults who receive ECMO. The researchers analyzed data from the International Registry of the Extracorporeal Life Support Organization and found that young adults had a higher survival rate compared to teenagers. The study also identified differences in pre-ECMO factors and management during ECMO between the two groups. The authors highlight the need for further research to determine optimal management strategies for these patients. [Extracted from the article]

OBJECTIVES: The Berlin definition of acute respiratory distress syndrome (ARDS) was constructed for patients receiving invasive mechanical ventilation (IMV) with consideration given to issues related to reliability, feasibility, and validity. Notwithstanding, patients with acute respiratory failure (ARF) may be treated with high-flow nasal oxygen (HFNO) and may not fall within the scope of the original definition. We aimed to evaluate the predictive validity of the Berlin definition in HFNO-treated patients with COVID-19-related respiratory failure who otherwise met ARDS criteria. DESIGN: Multicenter, prospective cohort study. SETTING: Five ICUs of five centers in Argentina from March 2020 to September 2021. PATIENTS: We consecutively included HFNO-treated patients older than 18 years with confirmed COVID-19-related ARF, a Pa o 2/F io 2 of less than 300 mm Hg, bilateral infiltrates on imaging, and worsening respiratory symptoms for less than 1 week. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We evaluated the predictive validity of mortality at day 28 using the area under the receiver operating characteristics curve (AUC), compared the predictive validity across subgroups, and characterized relevant clinical outcomes. We screened 1,231 patients and included 696 ARDS patients [30 (4%) mild, 380 (55%) moderate, and 286 (41%) severe]. For the study cohort, the AUC for mortality at day 28 was 0.606 (95% CI, 0.561–0.651) with the AUC for subgroups being similar to that of the overall cohort. Two hundred fifty-six patients (37%) received IMV. By day 28, 142 patients (21%) had died, of whom 81 (57%) had severe ARDS. Mortality occurred primarily in patients who were transitioned to IMV. CONCLUSIONS: The predictive validity of the Berlin ARDS definition was similar for HFNO-treated patients as compared with the original population of invasively ventilated patients. Our findings support the extension of the Berlin definition to HFNO-treated patients with ARDS. [ABSTRACT FROM AUTHOR]

The article examines the use of ChatGPT, a chatbot powered by a language model, in predicting outcomes for patients with traumatic brain injury (TBI). The study found that ChatGPT's predictions were less accurate than those of human clinicians and a validated prognostic model. The chatbot tended to overestimate the likelihood of poor outcomes, which could have negative implications for patient care. The article also discusses the limitations and ethical considerations of using AI models like ChatGPT in clinical decision-making. It references several other articles that explore the potential and limitations of AI in various medical applications, including glioma adjuvant therapy, drug information, and prognosis assessment in depression. However, caution and further research are advised when considering the use of AI in healthcare. [Extracted from the article]

This article explores the decision-making process for tracheal intubation in COVID-19 patients in the ICU. It discusses a study that examined the impact of intubation timing on mortality in critically ill COVID-19 patients. The study found that early intubation, guided by severity criteria, was associated with a lower risk of death. However, the study's design and definition of timing have limitations. The article emphasizes the importance of timely intubation in COVID-19 patients with respiratory failure to reduce mortality risk. Additionally, the article discusses a study that used ChatGPT to predict patients' functional status after 6 months, categorizing outcomes as favorable or poor based on the GOSE. The study aimed to assess the accuracy of ChatGPT in predicting these outcomes. [Extracted from the article]

OBJECTIVES: Interleukin-18 (IL-18) plasma level and latent class analysis (LCA) have separately been shown to predict prognosis and treatment response in acute respiratory distress syndrome (ARDS). IL-18 is a measure of inflammasome activation, a pathway potentially distinct from inflammation captured by biomarkers defining previously published LCA classes. We hypothesized that elevated IL-18 would identify distinct “high-risk” patients not captured by prior LCA classifications. DESIGN: Statins for acutely injured lungs from sepsis (SAILS) and hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in acute lung injury to reduce pulmonary dysfunction trial (HARP-2) are two large randomized, controlled trials in ARDS in which both LCA assignments and IL-18 levels were shown to predict mortality. We first evaluated the overlap between high IL-18 levels (≥ 800 pg/mL) with prior LCA class assignments using McNemar’s test and then tested the correlation between IL-18 and LCA biomarkers using Pearson’s exact test on log-2 transformed values. Our primary analysis was the association of IL-18 level with 60-day mortality in the hypoinflammatory LCA class, which was assessed using the Fisher exact test and Cox proportional hazards modeling adjusting for age, Acute Physiology and Chronic Health Evaluation score, and gender. Secondary analyses included the association of IL-18 and LCA with mortality within each IL-18/LCA subgroup. SETTING: Secondary analysis of two multicenter, randomized controlled clinical trials of ARDS patients. SUBJECTS: Six hundred eighty-three patients in SAILS and 511 patients in HARP-2. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We found that 33% of patients in SAILS and HARP-2 were discordant by IL-18 level and LCA class. We further found that IL-18 level was only modestly correlated (0.17–0.47) with cytokines used in the LCA assignment. A substantial subset of individuals classified as hypoinflammatory by LCA (14% of SAILS and 43% of HARP-2) were classified as high risk by elevated IL-18. These individuals were at high risk for mortality in both SAILS (42% 60-d mortality, odds ratio [OR] 3.3; 95% CI, 1.8–6.1; p < 0.001) and HARP-2 (27% 60-d mortality, OR 2.1; 95% CI, 1.2–3.8; p = 0.009). CONCLUSIONS: Plasma IL-18 level provides important additional prognostic information to LCA subphenotypes defined largely by traditional inflammatory biomarkers in two large ARDS cohorts. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Trimethoprim-sulfamethoxazole (TMP-SMX)-associated severe acute respiratory distress syndrome (ARDS) has gone underrecognized. We propose the first disease definition and clinical evaluation for a novel adverse drug reaction (ADR) based on a series of recently identified rare cases of life-threatening ADRs. DESIGN: A retrospective study was conducted. All medical records were evaluated. Available pathology samples were sent to Massachusetts General for clinical consultation. Blood samples from surviving patients were obtained and human leukocyte antigen (HLA) analysis was performed by the Children’s Mercy Hospital Genomic Center and Vanderbilt University Medical Center. SETTING: U.S. ICUs, 1996–2021. PATIENTS: Nineteen young patients (10–37) were identified. Patients were previously healthy, with no preexisting pulmonary disease, no other cause for respiratory failure, and no chronic history of smoking/vaping. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Through our retrospective analysis, we analyzed clinical characteristics associated with TMP-SMX. Pathology samples were reviewed, and HLA analysis was performed on available samples by the study team or as standard of care at treatment hospitals in some cases. In 19 critically ill patients, we identified a pattern of severe respiratory failure requiring ICU admission, mechanical ventilation, and frequent extracorporeal membrane oxygenation use. We describe the first three-part clinical diagnosis and evaluation strategy: 1) Clinical definition: Unexplained severe respiratory failure in a patient receiving greater than or equal to 6 days of TMP-SMX at treatment dose (not prophylaxis). TMP-SMX ARDS is a diagnosis of exclusion. 2) Genetic association: One hundred percent of currently available TMP-SMX respiratory failure patient genomic data, (n = 11) have been carriers of both HLA-B*07:02 and HLA-C*07:02 alleles. HLA allele evaluation could be considered in patients with suspected TMP-SMX respiratory failure. 3) Lung pathology: A unique pulmonary pathologic pattern of lung injury termed diffuse alveolar injury with delayed epithelialization has been observed in these cases. In suspected cases, surgical lung biopsy early in the clinical course could be considered. CONCLUSIONS: TMP-SMX is a commonly prescribed antibiotic. However, we find it imperative to share this relatively rare but life-threatening condition with clinicians as the mortality rate approaches 40%. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) is an advanced treatment for acute severe respiratory failure. Patients on ECMO are frequently maintained sedated and immobilized until weaning from ECMO, first, and then from mechanical ventilation. Avoidance of sedation and invasive ventilation during ECMO may have potential advantages. We performed a systematic literature review to assess efficacy and safety of awake ECMO without invasive ventilation in patients with respiratory failure. DATA SOURCES: PubMed, Web of Science, and Scopus were searched for studies reporting outcome of awake ECMO for adult patients with respiratory failure. STUDY SELECTION: We included all studies reporting outcome of awake ECMO in patients with respiratory failure. Studies on ECMO for cardiovascular failure, cardiac arrest, or perioperative support and studies on pediatric patients were excluded. Two investigators independently screened and selected studies for inclusion. DATA EXTRACTION: Two investigators abstracted data on study characteristics, rate of awake ECMO failure, and mortality. Primary outcome was rate of awake ECMO failure (need for intubation). Pooled estimates with corresponding 95% CIs were calculated. Subgroup analyses by setting were performed. DATA SYNTHESIS: A total of 57 studies (28 case reports) included data from 467 awake ECMO patients. The subgroup of patients with acute respiratory distress syndrome showed a pooled estimate for awake ECMO failure of 39.3% (95% CI, 24.0–54.7%), while in patients bridged to lung transplantation, pooled estimate was 23.4% (95% CI, 13.3–33.5%). Longest follow-up mortality was 121 of 439 (pooled estimate, 28%; 95% CI, 22.3–33.6%). Mortality in patients who failed awake ECMO strategy was 43 of 74 (pooled estimate, 57.2%; 95% CI, 40.2–74.3%). Two cases of cannula self-removal were reported. CONCLUSIONS: Awake ECMO is feasible in selected patients, although the effect on outcome remains to be demonstrated. Mortality is almost 60% in patients who failed awake ECMO strategy. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Impaired nitric oxide (NO) bioavailability may contribute to microvascular dysfunction in sepsis. Excessive plasma NO consumption has been attributed to scavenging by circulating cell-free hemoglobin. This may be a mechanism for NO deficiency in sepsis and critical illness. We hypothesized that plasma NO consumption is high in critically ill patients, particularly those with sepsis, acute respiratory distress syndrome (ARDS), shock, and in hospital nonsurvivors. We further hypothesized that plasma NO consumption is correlated with plasma cell-free hemoglobin concentration. DESIGN: Retrospective cohort study. SETTING: Adult ICUs of an academic medical center. PATIENTS AND SUBJECTS: Three hundred sixty-two critically ill patients and 46 healthy control subjects. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma NO consumption was measured using reductive chemiluminescence and cell-free hemoglobin was measured with a colorimetric assay. Mean (95% CI) plasma NO consumption (µM) was higher in critically ill patients versus healthy control subjects (3.9 [3.7– 4.1] vs 2.1 [1.8–2.5]), septic versus nonseptic patients (4.1 [3.8–4.3] vs 3.6 [3.3–3.8]), ARDS versus non-ARDS patients (4.4 [4.0–4.9] vs 3.7 [3.6–3.9]), shock vs nonshock patients (4.4 [4.0–4.8] vs 3.6 [3.4–3.8]), and hospital nonsurvivors versus survivors (5.3 [4.4–6.4] vs 3.7 [3.6–3.9]). These relationships remained significant in multivariable analyses. Plasma cell-free hemoglobin was weakly correlated with plasma NO consumption. CONCLUSIONS: Plasma NO consumption is elevated in critically ill patients and independently associated with sepsis, ARDS, shock, and hospital death. These data suggest that excessive intravascular NO scavenging characterizes sepsis and adverse outcomes of critical illness. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To assess the value of machine learning approaches in the development of a multivariable model for early prediction of ICU death in patients with acute respiratory distress syndrome (ARDS). DESIGN: A development, testing, and external validation study using clinical data from four prospective, multicenter, observational cohorts. SETTING: A network of multidisciplinary ICUs. PATIENTS: A total of 1,303 patients with moderate-to-severe ARDS managed with lung-protective ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We developed and tested prediction models in 1,000 ARDS patients. We performed logistic regression analysis following variable selection by a genetic algorithm, random forest and extreme gradient boosting machine learning techniques. Potential predictors included demographics, comorbidities, ventilatory and oxygenation descriptors, and extrapulmonary organ failures. Risk modeling identified some major prognostic factors for ICU mortality, including age, cancer, immunosuppression, PaO2/FIO2, inspiratory plateau pressure, and number of extrapulmonary organ failures. Together, these characteristics contained most of the prognostic information in the first 24 hours to predict ICU mortality. Performance with machine learning methods was similar to logistic regression (area under the receiver operating characteristic curve [AUC], 0.87; 95% CI, 0.82–0.91). External validation in an independent cohort of 303 ARDS patients confirmed that the performance of the model was similar to a logistic regression model (AUC, 0.91; 95% CI, 0.87–0.94). CONCLUSIONS: Both machine learning and traditional methods lead to promising models to predict ICU death in moderate/severe ARDS patients. More research is needed to identify markers for severity beyond clinical determinants, such as demographics, comorbidities, lung mechanics, oxygenation, and extrapulmonary organ failure to guide patient management. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Patient-ventilator asynchrony is often observed during mechanical ventilation and is associated with higher mortality. We hypothesized that patientventilator asynchrony causes lung and diaphragm injury and dysfunction. DESIGN: Prospective randomized animal study. SETTING: University research laboratory. SUBJECTS: Eighteen New Zealand White rabbits. INTERVENTIONS: Acute respiratory distress syndrome (ARDS) model was established by depleting surfactants. Each group (assist control, breath stacking, and reverse triggering) was simulated by phrenic nerve stimulation. The effects of each group on lung function, lung injury (wet-to-dry lung weight ratio, total protein, and interleukin-6 in bronchoalveolar lavage), diaphragm function (diaphragm force generation curve), and diaphragm injury (cross-sectional area of diaphragm muscle fibers, histology) were measured. Diaphragm RNA sequencing was performed using breath stacking and assist control (n = 2 each). MEASUREMENTS AND MAIN RESULTS: Inspiratory effort generated by phrenic nerve stimulation was small and similar among groups (esophageal pressure swing ≈ -2.5 cm H2O). Breath stacking resulted in the largest tidal volume (>10 mL/kg) and highest inspiratory transpulmonary pressure, leading to worse oxygenation, worse lung compliance, and lung injury. Reverse triggering did not cause lung injury. No asynchrony events were observed in assist control, whereas eccentric contractions occurred in breath stacking and reverse triggering, but more frequently in breath stacking. Breath stacking and reverse triggering significantly reduced diaphragm force generation. Diaphragmatic histology revealed that the area fraction of abnormal muscle was x2.5 higher in breath stacking (vs assist control) and x2.1 higher in reverse triggering (vs assist control). Diaphragm RNA sequencing analysis revealed that genes associated with muscle differentiation and contraction were suppressed, whereas cytokine- and chemokine-mediated proinflammatory responses were activated in breath stacking versus assist control. CONCLUSIONS: Breath stacking caused lung and diaphragm injury, whereas reverse triggering caused diaphragm injury. Thus, careful monitoring and management of patient-ventilator asynchrony may be important to minimize lung and diaphragm injury from spontaneous breathing in ARDS. [ABSTRACT FROM AUTHOR]

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

OBJECTIVES: Prone positioning for acute respiratory distress syndrome (ARDS) has historically been underused, but was widely adopted for COVID-19-associated ARDS early in the pandemic. Whether this successful implementation has been sustained over the first 3 years of the COVID-19 pandemic is unknown. In this study, we characterized proning use in patients with COVID-19 ARDS from March 2020 to December 2022. DESIGN: Multicenter retrospective observational study. SETTING: Five-hospital health system in Maryland, USA. PATIENTS: Adults with COVID-19 supported with invasive mechanical ventilation and with a PaO2/FIO2 ratio of less than or equal to 150 mm Hg while receiving FIO2 of greater than or equal to 0.6 within 72 hours of intubation. INTERVENTIONS: None. MEASUREMENTS: We extracted demographic, clinical, and positioning data from the electronic medical record. The primary outcome was the initiation of proning within 48 hours of meeting criteria. We compared proning use by year with univariate and multivariate relative risk (RR) regression. Additionally, we evaluated the association of treatment during a COVID-19 surge period and receipt of prone positioning. MAIN RESULTS: We identified 656 qualifying patients; 341 from 2020, 224 from 2021, and 91 from 2022. More than half (53%) met severe ARDS criteria. Early proning occurred in 56.2% of patients in 2020, 56.7% in 2021, and 27.5% in 2022. This translated to a 51% reduction in use of prone positioning among patients treated in 2022 versus 2020 (RR = 0.49; 95% CI, 0.33-0.72; p < 0.001). This reduction remained significant in adjusted models (adjusted RR = 0.59; 95% CI, 0.42-0.82; p = 0.002). Treatment during COVID-19 surge periods was associated with a 7% increase in proning use (adjusted RR = 1.07; 95% CI, 1.02-1.13; p = 0.01). CONCLUSIONS: The use of prone positioning for COVID-19 ARDS is declining. Interventions to increase and sustain appropriate use of this evidence-based therapy are warranted. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Acute respiratory distress syndrome (ARDS) is associated with high ventilation-perfusion heterogeneity and dead-space ventilation. However, whether the degree of dead-space ventilation is associated with outcomes is uncertain. In this systematic review and meta-analysis, we evaluated the ability of dead-space ventilation measures to predict mortality in patients with ARDS. DATA SOURCES: MEDLINE, CENTRAL, and Google Scholar from inception to November 2022. STUDY SELECTION: Studies including adults with ARDS reporting a deadspace ventilation index and mortality. DATA EXTRACTION: Two reviewers independently identified eligible studies and extracted data. We calculated pooled effect estimates using a random effects model for both adjusted and unadjusted results. The quality and strength of evidence were assessed using the Quality in Prognostic Studies and Grading of Recommendations, Assessment, Development, and Evaluation, respectively. DATA SYNTHESIS: We included 28 studies in our review, 21 of which were included in our meta-analysis. All studies had a low risk of bias. A high pulmonary dead-space fraction was associated with increased mortality (odds ratio [OR], 3.52; 95% CI, 2.22-5.58; p < 0.001; I² = 84%). After adjusting for other confounding variables, every 0.05 increase in pulmonary-dead space fraction was associated with an increased odds of death (OR, 1.23; 95% CI, 1.13-1.34; p < 0.001; I² = 57%). A high ventilatory ratio was also associated with increased mortality (OR, 1.55; 95% CI, 1.33-1.80; p < 0.001; I² = 48%). This association was independent of common confounding variables (OR, 1.33; 95% CI, 1.12-1.58; p = 0.001; I² = 66%). CONCLUSIONS: Dead-space ventilation indices were independently associated with mortality in adults with ARDS. These indices could be incorporated into clinical trials and used to identify patients who could benefit from early institution of adjunctive therapies. The cut-offs identified in this study should be prospectively validated. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To determine the impact of high doses of corticosteroids (HDCT) in critically ill COVID-19 patients with nonresolving acute respiratory distress syndrome (ARDS) who had been previously treated with dexamethasone as a standard of care. DESIGN: Prospective observational cohort study. Eligible patients presented nonresolving ARDS related to severe acute respiratory syndrome coronavirus 2 infection and had received initial treatment with dexamethasone. We compared patients who had received or not HDCT during ICU stay, consisting of greater than or equal to 1 mg/kg of methylprednisolone or equivalent for treatment of nonresolving ARDS. The primary outcome was 90-day mortality. We assessed the impact of HDCT on 90-day mortality using univariable and multivariable Cox regression analysis. Further adjustment for confounding variables was performed using overlap weighting propensity score. The association between HDCT and the risk of ventilator-associated pneumonia was estimated using multivariable causespecific Cox proportional hazard model adjusting for pre-specified confounders. SETTING: We included consecutive patients admitted in 11 ICUs of Great Paris area from September 2020 to February 2021. PATIENTS: Three hundred eighty-three patients were included (59 in the HDCT group, 324 in the no HDCT group). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: At day 90, 30 of 59 patients (51%) in the HDCT group and 116 of 324 patients (35.8%) in the no HDCT group had died. HDCT was significantly associated with 90-day mortality in unadjusted (hazard ratio [HR], 1.60; 95% CI, 1.04-2.47; p = 0.033) and adjusted analysis with overlap weighting (adjusted HR, 1.65; 95% CI, 1.03-2.63; p = 0.036). HDCT was not associated with an increased risk of ventilator-associated pneumonia (adjusted cause-specific HR, 0.42; 95% CI, 0.15-1.16; p = 0.09). CONCLUSIONS: In critically ill COVID-19 patients with nonresolving ARDS, HDCT result in a higher 90-day mortality. [ABSTRACT FROM AUTHOR]

The article discusses the use of single-site versus multisite cannulation for venovenous extracorporeal membrane oxygenation (ECMO) in patients with severe acute respiratory distress syndrome (ARDS) caused by COVID-19. The authors acknowledge the limitations of the existing evidence and emphasize the need for high-quality randomized controlled trials (RCTs) to assess patient-centered outcomes and mortality associated with blood purification techniques. They also highlight the lack of available information in the dataset used for their study, which limits the analysis of certain variables. The authors agree with the commenters that additional variables should be studied in future iterations of the dataset or other large, multicenter datasets. [Extracted from the article]

OBJECTIVES: To determine whether an under-the-nose face mask (FM) as the first-line interface strategy reduces the incidence of facial pressure sores with the same clinical improvement as the one obtained by standard over-the-nose face mask-noninvasive ventilation (FM-NIV) in patients with acute hypercapnic respiratory failure (AHRF). DESIGN: A multicenter, prospective randomized controlled study. SETTING: Two ICUs from two French tertiary hospitals. PATIENTS: A total of 108 patients needed NIV for AHRF. INTERVENTIONS: participants were randomized (1/1) to receive either the under-the-nose FM (intervention group) or the over-the-nose FM (control group). The primary endpoint was the reduction of facial pressure sores. Secondary end-points included patients outcome, NIV failure (intubation or death), arterial blood gas improvement, and interface failure (the need to switch to a total face mask). MEASUREMENTS AND MAIN RESULTS: Despite less protective dressings in the intervention group (n = 4, 5% vs n = 27, 51%; p < 0.001), pressure sores developed less frequently than in the control group (n = 3, 5% vs n = 39, 74%; p < 0.001). Similar mortality, NIV failure, and arterial blood gas improvement occurred in the two groups. However, under-the-nose FM resulted in a higher interface failure rate than conventional FM (n = 18, 33% vs n = 5, 9%; p = 0.004), mainly because of excessive unintentional air leaks (n = 15, 83% vs n = 0, 0%; p < 0.001). CONCLUSIONS: In patients with AHRF, under-the-nose FM significantly reduced the incidence of facial pressure sores compared to the most commonly used first-line interface, the standard FM. However, with this new mask, excessive unintentional air leaks more often compelled the attending clinician to switch to another interface to pursue NIV. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Early studies of venovenous extracorporeal membrane oxygenation (ECMO) in COVID-19 have revealed similar outcomes to historical cohorts. Changes in the disease and treatments have led to differences in the patients supported on venovenous ECMO in the first and second waves. We aimed to compare these two groups in both the acute and follow-up phase. DESIGN: Retrospective single-center cohort study comparing mortality at censoring date (November 30, 2021) and decannulation, patient characteristics, complications and lung function and quality of life (QOL—by European Quality of Life 5 Dimensions 3 Level Version) at first follow-up in patients supported on venovenous ECMO between wave 1 and wave 2 of the COVID-19 pandemic. SETTING: Critical care department of a severe acute respiratory failure service. PATIENTS: Patients supported on ECMO for COVID-19 between wave 1 (March 17, 2020, to August 31, 2020) and wave 2 (January 9, 2020, to May 25, 2021). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred twenty-three patients were included in our analysis. Survival at censoring date (χ2, 6.35; p = 0.012) and decannulation (90.4% vs 70.0%; p < 0.001) was significantly lower in the second wave, while duration of ECMO run was longer (12.0 d [18.0–30.0 d] vs 29.5 d [15.5–58.3 d]; p = 0.005). Wave 2 patients had longer application of noninvasive ventilation (NIV) prior to ECMO and a higher frequency of barotrauma. Patient age and NIV use were independently associated with increased mortality (odds ratio 1.07 [1.01–1.14]; p = 0.025 and 3.37 [1.12–12.60]; p = 0.043, respectively). QOL and lung function apart from transfer coefficient of carbon monoxide corrected for hemoglobin was similar at follow-up across the waves. CONCLUSIONS: Most patients with COVID-19 supported on ECMO in both waves survived in the short and longer term. At follow-up patients had similar lung function and QOL across the two waves. This suggests that ECMO has an ongoing role in the management of a carefully selected group of patients with COVID-19. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Studies have suggested intrapulmonary shunts may contribute to hypoxemia in COVID-19 acute respiratory distress syndrome (ARDS) with worse associated outcomes. We evaluated the presence of right-to-left (R-L) shunts in COVID-19 and non-COVID ARDS patients using a comprehensive hypoxemia workup for shunt etiology and associations with mortality. DESIGN: Prospective, observational cohort study. SETTING: Four tertiary hospitals in Edmonton, Alberta, Canada. PATIENTS: Adult critically ill, mechanically ventilated, ICU patients admitted with COVID-19 or non-COVID (November 16, 2020, to September 1, 2021). INTERVENTIONS: Agitated-saline bubble studies with transthoracic echocardiography/transcranial Doppler ± transesophageal echocardiography assessed for R-L shunts presence. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were shunt frequency and association with hospital mortality. Logistic regression analysis was used for adjustment. The study enrolled 226 patients (182 COVID-19 vs 42 non-COVID). Median age was 58 years (interquartile range [IQR], 47–67 yr) and Acute Physiology and Chronic Health Evaluation II scores of 30 (IQR, 21–36). In COVID-19 patients, the frequency of R-L shunt was 31 of 182 COVID patients (17.0%) versus 10 of 44 non-COVID patients (22.7%), with no difference detected in shunt rates (risk difference [RD], –5.7%; 95% CI, –18.4 to 7.0; p = 0.38). In the COVID-19 group, hospital mortality was higher for those with R-L shunt compared with those without (54.8% vs 35.8%; RD, 19.0%; 95% CI, 0.1–37.9; p = 0.05). This did not persist at 90-day mortality nor after adjustment with regression. CONCLUSIONS: There was no evidence of increased R-L shunt rates in COVID-19 compared with non-COVID controls. R-L shunt was associated with increased in-hospital mortality for COVID-19 patients, but this did not persist at 90-day mortality or after adjusting using logistic regression. [ABSTRACT FROM AUTHOR]

Objectives: Extracorporeal carbon dioxide removal (ECCO2R) devices are effective in reducing hypercapnia and mechanical ventilation support but have not been shown to reduce mortality. This may be due to case selection, device performance, familiarity, or the management. The objective of this study is to investigate the effectiveness and safety of a single ECCO2R device (Hemolung) in patients with acute respiratory failure and identify variables associated with survival that could help case selection in clinical practice as well as future research. Design: Multicenter, multinational, retrospective review. Setting: Data from the Hemolung Registry between April 2013 and June 2021, where 57 ICUs contributed deidentified data. Patients: Patients with acute respiratory failure treated with the Hemolung. The characteristics of patients who survived to ICU discharge were compared with those who died. Multivariable logistical regression analysis was used to identify variables associated with ICU survival. Interventions: None. Measurements and Main Results: Of the 159 patients included, 65 (41%) survived to ICU discharge. The survival was highest in status asthmaticus (86%), followed by acute respiratory distress syndrome (ARDS) (52%) and COVID-19 ARDS (31%). All patients had a significant reduction in Pa co 2 and improvement in pH with reduction in mechanical ventilation support. Patients who died were older, had a lower Pa o 2:F io 2 (P/F) and higher use of adjunctive therapies. There was no difference in the complications between patients who survived to those who died. Multivariable regression analysis showed non-COVID-19 ARDS, age less than 65 years, and P/F at initiation of ECCO2R to be independently associated with survival to ICU discharge (P/F 100–200 vs <100: odds ratio, 6.57; 95% CI, 2.03–21.33). Conclusions: Significant improvement in hypercapnic acidosis along with reduction in ventilation supports was noted within 4 hours of initiating ECCO2R. Non-COVID-19 ARDS, age, and P/F at commencement of ECCO2R were independently associated with survival. [ABSTRACT FROM AUTHOR]

Objectives: There has been a sustained increase in the utilization of venovenous extracorporeal membrane oxygenation (ECMO) over the last decade, further exacerbated by the COVID-19 pandemic. We set out to describe our institutional experience with extremely prolonged (> 50 d) venovenous ECMO support for recovery or bridge to lung transplant candidacy in patients with acute respiratory failure. Design: Retrospective cohort study. Setting: A large tertiary urban care center. Patients: Patients 18 years or older receiving venovenous ECMO support for greater than 50 days, with initial cannulation between January 2018 and January 2022. Interventions: None. Measurements and Main Results: One hundred thirty patients were placed on venovenous ECMO during the study period. Of these, 12 received prolonged (> 50 d) venovenous ECMO support. Eleven patients (92%) suffered from adult respiratory distress syndrome (ARDS) secondary to COVID-19, while one patient with prior bilateral lung transplant suffered from ARDS secondary to bacterial pneumonia. The median age of patients was 39 years (interquartile range [IQR], 35–51 yr). The median duration of venovenous ECMO support was 94 days (IQR, 70–128 d), with a maximum of 180 days. Median time from intubation to cannulation was 5 days (IQR, 2–14 d). Nine patients (75%) were successfully mobilized while on venovenous ECMO support. Successful weaning of venovenous ECMO support occurred in eight patients (67%); 6 (50%) were bridged to lung transplantation and 2 (17%) were bridged to recovery. Of those successfully weaned, seven patients (88%) were discharged from the hospital. All seven patients discharged from the hospital were alive 6 months post-decannulation; 83% (5/6) with sufficient follow-up time were alive 1-year after decannulation. Conclusions: Our experience suggests that extremely prolonged venovenous ECMO support to allow native lung recovery or optimization for lung transplantation may be a feasible strategy in select critically ill patients, further supporting the expanded utilization of venovenous ECMO for refractory respiratory failure. [ABSTRACT FROM AUTHOR]

OBJECTIVES: We implemented a computerized protocol for low tidal volume ventilation (LTVV) to improve management and outcomes of mechanically ventilated patients with, and without, the acute respiratory distress syndrome (ARDS). DESIGN: Pragmatic, nonrandomized stepped wedge type II hybrid implementation/effectiveness trial. SETTING: Twelve hospitals in an integrated healthcare system over a 2-year period. PATIENTS: Patients greater than or equal to 18 years old who had initiation of mechanical ventilation in the emergency department or ICU. We excluded patients who died or transitioned to comfort care on the day of admission to the ICU. We defined a subgroup of patients with ARDS for analysis. INTERVENTIONS: Implementation of ventilator protocols for LTVV in the ICU. MEASUREMENTS AND MAIN RESULTS: Our primary clinical outcome was ventilator-free days (VFDs) to day 28. Our primary process outcome was median initial set tidal volume. We included 8,692 mechanically ventilated patients, 3,282 (38%) of whom had ARDS. After implementation, set tidal volume reported as mL/kg predicted body weight decreased from median 6.1 mL/kg (interquartile range [IQR], 6.0–6.8 mL/kg) to 6.0 mL/kg (IQR, 6.0–6.6 mL/kg) (p = 0.009). The percent of patients receiving LTVV (tidal volume ≤ 6.5 mL/kg) increased from 69.8% (n = 1,721) to 72.5% (n = 1,846) (p = 0.036) after implementation. The percent of patients receiving greater than 8 mL/kg initial set tidal volume was reduced from 9.0% (n = 222) to 6.7% (n = 174) (p = 0.005) after implementation. Among patients with ARDS, day 1 positive end-expiratory pressure increased from 6.7 to 8.0 cm H2O (p < 0.001). We observed no difference in VFD (adjusted odds ratio, 1.06; 95% CI, 0.91–1.24; p = 0.44), or in secondary outcomes of length of stay or mortality, either within the main cohort or the subgroup of patients with ARDS. CONCLUSIONS: We observed improved adherence to optimal ventilator management with implementation of a computerized protocol and reduction in the number of patients receiving tidal volumes greater than 8 mL/kg. We did not observe improvement in clinical outcomes. [ABSTRACT FROM AUTHOR]