Acute respiratory distress syndrome readmissions: A nationwide cross-sectional analysis of epidemiology and costs of care.

BACKGROUND: Acute Respiratory Distress Syndrome affects approximately 10% of patients admitted to intensive care units internationally, with as many as 40%-52% of patients reporting re-hospitalization within one year. RESEARCH QUESTION/AIM: To describe the epidemiology of patients with acute respiratory distress syndrome who require 30-day readmission, and to describe associated costs. STUDY DESIGN AND METHODS: A cross-sectional analysis of the 2016 Healthcare Cost and Utilization Project's Nationwide Readmission Database, which is a population-based administrative database which includes discharge data from U.S. hospitals. Inclusion criteria: hospital discharge records for adults age > 17 years old, with a diagnosis of ARDS on index admission, with associated procedure codes for endotracheal intubation and/or invasive mechanical ventilation, who were discharged alive. Primary exposure is adult hospitalization for meeting criteria as described. The primary outcome measure is 30-day readmission rate, as well as patient characteristics and time distribution of readmissions. RESULTS: Nationally, 25,170 admissions meeting criteria were identified. Index admission mortality rate was 37.5% (95% confidence interval [CI], 36.2-38.8). 15,730 records of those surviving hospitalization had complete discharge information. 30-day readmission rate was 18.4%, with 14% of total readmissions occurring within 2 calendar days of discharge; these early readmissions had higher mortality risk (odds ratio 1.82, 95% CI 1.05-6.56) compared with readmission in subsequent days. For the closest all-cause readmission within 30 days, the mean cost was $26,971, with a total national cost of over $75.6 million. INTERPRETATION: Thirty-day readmission occurred in 18.4% of patients with acute respiratory distress syndrome in this sample, and early readmission is strongly associated with increased mortality compared to late readmission. Further research is needed to clarify whether the rehospitalizations or associated mortalities are preventable.

Improved outcomes over time for adult COVID-19 patients with acute respiratory distress syndrome or acute respiratory failure.

BACKGROUND: COVID-19's pulmonary manifestations are broad, ranging from pneumonia with no supplemental oxygen requirements to acute respiratory distress syndrome (ARDS) with acute respiratory failure (ARF). In response, new oxygenation strategies and therapeutics have been developed, but their large-scale effects on outcomes in severe COVID-19 patients remain unknown. Therefore, we aimed to examine the trends in mortality, mechanical ventilation, and cost over the first six months of the pandemic for adult COVID-19 patients in the US who developed ARDS or ARF. METHODS AND FINDINGS: The Vizient Clinical Data Base, a national database comprised of administrative, clinical, and financial data from academic medical centers, was queried for patients ≥ 18-years-old with COVID-19 and either ARDS or ARF admitted between 3/2020-8/2020. Demographics, mechanical ventilation, length of stay, total cost, mortality, and discharge status were collected. Mann-Kendall tests were used to assess for significant monotonic trends in total cost, mechanical ventilation, and mortality over time. Chi-square tests were used to compare mortality rates between March-May and June-August. 110,223 adult patients with COVID-19 ARDS or ARF were identified. Mean length of stay was 12.1±13.3 days and mean total cost was $35,991±32,496. Mechanical ventilation rates were 34.1% and in-hospital mortality was 22.5%. Mean cost trended downward over time (p = 0.02) from $55,275 (March) to $18,211 (August). Mechanical ventilation rates trended down (p<0.01) from 53.8% (March) to 20.3% (August). Overall mortality rates also decreased (p<0.01) from 28.4% (March) to 13.7% (August). Mortality rates in mechanically ventilated patients were similar over time (p = 0.45), but mortality in patients not requiring mechanical ventilation decreased from March-May compared to June-July (13.5% vs 4.6%, p<0.01). CONCLUSIONS: This study describes the outcomes of a large cohort with COVID-19 ARDS or ARF and the subsequent decrease in cost, mechanical ventilation, and mortality over the first 6 months of the pandemic in the US.

Temporal changes in the epidemiology, management, and outcome from acute respiratory distress syndrome in European intensive care units: a comparison of two large cohorts.

BACKGROUND: Mortality rates for patients with ARDS remain high. We assessed temporal changes in the epidemiology and management of ARDS patients requiring invasive mechanical ventilation in European ICUs. We also investigated the association between ventilatory settings and outcome in these patients. METHODS: This was a post hoc analysis of two cohorts of adult ICU patients admitted between May 1-15, 2002 (SOAP study, n = 3147), and May 8-18, 2012 (ICON audit, n = 4601 admitted to ICUs in the same 24 countries as the SOAP study). ARDS was defined retrospectively using the Berlin definitions. Values of tidal volume, PEEP, plateau pressure, and FiO2 corresponding to the most abnormal value of arterial PO2 were recorded prospectively every 24 h. In both studies, patients were followed for outcome until death, hospital discharge or for 60 days. RESULTS: The frequency of ARDS requiring mechanical ventilation during the ICU stay was similar in SOAP and ICON (327[10.4%] vs. 494[10.7%], p = 0.793). The diagnosis of ARDS was established at a median of 3 (IQ: 1-7) days after admission in SOAP and 2 (1-6) days in ICON. Within 24 h of diagnosis, ARDS was mild in 244 (29.7%), moderate in 388 (47.3%), and severe in 189 (23.0%) patients. In patients with ARDS, tidal volumes were lower in the later (ICON) than in the earlier (SOAP) cohort. Plateau and driving pressures were also lower in ICON than in SOAP. ICU (134[41.1%] vs 179[36.9%]) and hospital (151[46.2%] vs 212[44.4%]) mortality rates in patients with ARDS were similar in SOAP and ICON. High plateau pressure (> 29 cmH2O) and driving pressure (> 14 cmH2O) on the first day of mechanical ventilation but not tidal volume (> 8 ml/kg predicted body weight [PBW]) were independently associated with a higher risk of in-hospital death. CONCLUSION: The frequency of and outcome from ARDS remained relatively stable between 2002 and 2012. Plateau pressure > 29 cmH2O and driving pressure > 14 cmH2O on the first day of mechanical ventilation but not tidal volume > 8 ml/kg PBW were independently associated with a higher risk of death. These data highlight the continued burden of ARDS and provide hypothesis-generating data for the design of future studies.

Mortality Risk Assessment in COVID-19 Venovenous Extracorporeal Membrane Oxygenation.

BACKGROUND: A life-threatening complication of coronavirus disease 2019 (COVID-19) is acute respiratory distress syndrome (ARDS) refractory to conventional management. Venovenous (VV) extracorporeal membrane oxygenation (ECMO) (VV-ECMO) is used to support patients with ARDS in whom conventional management fails. Scoring systems to predict mortality in VV-ECMO remain unvalidated in COVID-19 ARDS. This report describes a large single-center experience with VV-ECMO in COVID-19 and assesses the utility of standard risk calculators. METHODS: A retrospective review of a prospective database of all patients with COVID-19 who underwent VV-ECMO cannulation between March 15 and June 27, 2020 at a single academic center was performed. Demographic, clinical, and ECMO characteristics were collected. The primary outcome was in-hospital mortality; survivor and nonsurvivor cohorts were compared by using univariate and bivariate analyses. RESULTS: Forty patients who had COVID-19 and underwent ECMO were identified. Of the 33 patients (82.5%) in whom ECMO had been discontinued at the time of analysis, 18 patients (54.5%) survived to hospital discharge, and 15 (45.5%) died during ECMO. Nonsurvivors presented with a statistically significant higher Prediction of Survival on ECMO Therapy (PRESET)-Score (mean ± SD, 8.33 ± 0.8 vs 6.17 ± 1.8; P = .001). The PRESET score demonstrated accurate mortality prediction. All patients with a PRESET-Score of 6 or lowers survived, and a score of 7 or higher was associated with a dramatic increase in mortality. CONCLUSIONS: These results suggest that favorable outcomes are possible in patients with COVID-19 who undergo ECMO at high-volume centers. This study demonstrated an association between the PRESET-Score and survival in patients with COVID-19 who underwent VV-ECMO. Standard risk calculators may aid in appropriate selection of patients with COVID-19 ARDS for ECMO.

Prolonged Hospitalization Following Acute Respiratory Failure.

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.

CT fatty muscle fraction as a new parameter for muscle quality assessment predicts outcome in venovenous extracorporeal membrane oxygenation.

Impaired skeletal muscle quality is a major risk factor for adverse outcomes in acute respiratory failure. However, conventional methods for skeletal muscle assessment are inapplicable in the critical care setting. This study aimed to determine the prognostic value of computed tomography (CT) fatty muscle fraction (FMF) as a biomarker of muscle quality in patients undergoing extracorporeal membrane oxygenation (ECMO). To calculate FMF, paraspinal skeletal muscle area was obtained from clinical CT and separated into areas of fatty and lean muscle based on densitometric thresholds. The cohort was binarized according to median FMF. Patients with high FMF displayed significantly increased 1-year mortality (72.7% versus 55.8%, P = 0.036) on Kaplan-Meier analysis. A multivariable logistic regression model was built to test the impact of FMF on outcome. FMF was identified as a significant predictor of 1-year mortality (hazard ratio per percent FMF, 1.017 [95% confidence interval, 1.002-1.033]; P = 0.031), independent of anthropometric characteristics, Charlson Comorbidity Index, Simplified Acute Physiology Score, Respiratory Extracorporeal Membrane Oxygenation Survival Prediction Score, and duration of ECMO support. To conclude, FMF predicted 1-year mortality independently of established clinical prognosticators in ECMO patients and may have the potential to become a new muscle quality imaging biomarker, which is available from clinical CT.

A quantitative CT parameter for the assessment of pulmonary oedema in patients with acute respiratory distress syndrome.

OBJECTIVES: The aim of this study was to establish quantitative CT (qCT) parameters for pathophysiological understanding and clinical use in patients with acute respiratory distress syndrome (ARDS). The most promising parameter is introduced. MATERIALS AND METHODS: 28 intubated patients with ARDS obtained a conventional CT scan in end-expiratory breathhold within the first 48 hours after admission to intensive care unit (ICU). Following manual segmentation, 137 volume- and lung weight-associated qCT parameters were correlated with 71 clinical parameters such as blood gases, applied ventilation pressures, pulse contour cardiac output measurements and established status and prognosis scores (SOFA, SAPS II). RESULTS: Of all examined qCT parameters, excess lung weight (ELW), i.e. the difference between a patient's current lung weight and the virtual lung weight of a healthy person at the same height, displayed the most significant results. ELW correlated significantly with the amount of inflated lung tissue [%] (p<0.0001; r = -0.66) and was closely associated with the amount of extravascular lung water (EVLW) (p<0.0001; r = 0.72). More substantially than the oxygenation index (PaO2/FiO2) or any other clinical parameter it correlated with the patients' mean SOFA- (p<0.0001, r = 0.69) and SAPS II-Score (p = 0.0005, r = 0.62). Patients who did not survive intensive care treatment displayed higher values of ELW in the initial CT scans. CONCLUSIONS: ELW could serve as a non-invasive method to quantify the amount of pulmonary oedema. It might serve as an early radiological marker of severity in patients with ARDS.

Early Changes Over Time in the Radiographic Assessment of Lung Edema Score Are Associated With Survival in ARDS.

BACKGROUND: The Radiographic Assessment of Lung Edema (RALE) score is associated with the severity of ARDS, and treatments targeted at reducing pulmonary edema such as conservative fluid management cause a reduction in RALE score over time. RESEARCH QUESTION: Are early changes in RALE score over time associated with survival in patients with ARDS? STUDY DESIGN AND METHODS: Data from patients enrolled in three centers in the Lung Imaging for Ventilation sEtting in ARDS (LIVE) trial with available chest radiographs at baseline (day 0) and days 2 or 3 were used. The RALE was scored by two independent reviewers. The primary end point was death by day 90, considering RALE score both at baseline and as a time-varying covariate in a marginal Cox survival model. RESULTS: RALE was scored from 135, 64, and 88 radiographs on days 0, 2, and 3, respectively. Both baseline RALE (hazard ratio [HR] for each one-point increment, 1.04; 95% CI, 1.01-1.08; P = .006) and the change in RALE over time (HR for each one-point decrease per unit of time, 0.99; 95% CI, 0.99-0.99; P = .03) were associated with death by day 90, even after adjustment for age, sex, BMI, Simplified Acute Physiology Score II, vasopressor use, and total volume of fluids received since study entry. INTERPRETATION: The change in RALE during the first days after ARDS onset is independently associated with survival and may be useful as a surrogate end point in future clinical trials of new therapeutics in ARDS.

Association of Economic Status and Mortality in Patients with Acute Respiratory Distress Syndrome.

The high cost of treatment for acute respiratory distress syndrome (ARDS) is a concern for healthcare systems, while the impact of patients' socio-economic status on the risk of ARDS-associated mortality remains controversial. This study investigated associations between patients' income at the time of ARDS diagnosis and ARDS-specific mortality rate after treatment initiation. Data from records provided by the National Health Insurance Service of South Korea were used. Adult patients admitted for ARDS treatment from 2013 to 2017 were included in the study. Patients' income in the year of diagnosis was evaluated. A total of 14,600 ARDS cases were included in the analysis. The 30-day and 1-year mortality rates were 48.6% and 70.3%, respectively. In multivariable Cox regression model, we compared income quartiles, showing that compared to income strata Q1, the Q2 (P = 0.719), Q3 (P = 0.946), and Q4 (P = 0.542) groups of income level did not affect the risk of 30-day mortality, respectively. Additionally, compared to income strata Q1, the Q2 (P = 0.762), Q3 (P = 0.420), and Q4 (P = 0.189) strata did not affect the risk of 1-year mortality. Patient income at the time of ARDS diagnosis did not affect the risk of 30-day or 1-year mortality in the present study based on South Korea's health insurance data.

Utility of Plasma GDF-15 for Diagnosis and Prognosis Assessment of ICU-Acquired Weakness in Mechanically Ventilated Patients: Prospective Observational Study.

OBJECTIVE: To identify the clinical correlations between plasma growth differentiation factor-15 (GDF-15), skeletal muscle function, and acute muscle wasting in ICU patients with mechanical ventilation. In addition, to investigate its diagnostic value for ICU-acquired weakness (ICU-AW) and its predictive value for 90-day survival in mechanically ventilated patients. METHODS: 95 patients with acute respiratory failure, who required mechanical ventilation therapy, were randomly selected among hospitalized patients from June 2017 to January 2019. The plasma GDF-15 level was detected by ELISA, the rectus femoris cross-sectional area (RFcsa) was measured by ultrasound, and the patient's muscle strength was assessed using the British Medical Research Council (MRC) muscle strength score on day 1, day 4, and day 7. Patients were divided into an ICU-AW group and a non-ICU-AW group according to their MRC-score on the 7th day. The differences in plasma GDF-15 level, MRC-score, and RFcsa between the two groups were compared on the 1st, 4th, and 7th day after being admitted to the ICU. Then, the correlations between plasma GDF-15 level, RFcsa loss, and MRC-score on day 7 were investigated. The receiver operating characteristic curve (ROC) was used to analyze the plasma GDF-15 level, RFcsa loss, and % decrease in RFcsa on the 7th day to the diagnosis of ICU-AW in mechanically ventilated patients. Moreover, the predictive value of GDF-15 on the 90-day survival status of patients was assessed using patient survival curves. RESULTS: Based on whether the 7th day MRC-score was <48, 50 cases were included in the ICU-AW group and 45 cases in the non-ICU-AW group. The length of mechanical ventilation, ICU length of stay, and hospital length of stay were significantly longer in the ICU-AW group than in the non-ICU-AW group (all P < 0.05), while the other baseline indicators were not statistically significant between the two groups. As the treatment time increased, the plasma GDF-15 level was significantly increased, the ICU-AW group demonstrated a significant decreasing trend in the MRC-score and RFcsa, while no significant changes were found in the non-ICU-AW group. In the ICU-AW group, the plasma GDF-15 level was significantly higher than that in the non-ICU-AW group, while the RFcsa and the MRC-score were significantly lower than those in the non-ICU-AW group (GDF-15 (pg/ml): 2542.44 ± 629.38 vs. 1542.86 ± 502.86; RFcsa (cm2): 2.04 ± 0.64 vs. 2.34 ± 0.61; MRC-score: 41.22 ± 3.42 vs. 51.42 ± 2.72, all P < 0.05), while the other baseline indicators were not statistically significant between the two groups. As the treatment time increased, the plasma GDF-15 level was significantly increased, the ICU-AW group demonstrated a significant decreasing trend in the MRC-score and RFcsa, while no significant changes were found in the non-ICU-AW group. In the ICU-AW group, the plasma GDF-15 level was significantly higher than that in the non-ICU-AW group, while the RFcsa and the MRC-score were significantly lower than those in the non-ICU-AW group (GDF-15 (pg/ml): 2542.44 ± 629.38 vs. 1542.86 ± 502.86; RFcsa (cm2): 2.04 ± 0.64 vs. 2.34 ± 0.61; MRC-score: 41.22 ± 3.42 vs. 51.42 ± 2.72, all r = -0.60), while it was significantly positively correlated with the RFcsa loss (r = -0.60), while it was significantly positively correlated with the RFcsa loss (r = -0.60), while it was significantly positively correlated with the RFcsa loss (r = -0.60), while it was significantly positively correlated with the RFcsa loss (P < 0.05), while the other baseline indicators were not statistically significant between the two groups. As the treatment time increased, the plasma GDF-15 level was significantly increased, the ICU-AW group demonstrated a significant decreasing trend in the MRC-score and RFcsa, while no significant changes were found in the non-ICU-AW group. In the ICU-AW group, the plasma GDF-15 level was significantly higher than that in the non-ICU-AW group, while the RFcsa and the MRC-score were significantly lower than those in the non-ICU-AW group (GDF-15 (pg/ml): 2542.44 ± 629.38 vs. 1542.86 ± 502.86; RFcsa (cm2): 2.04 ± 0.64 vs. 2.34 ± 0.61; MRC-score: 41.22 ± 3.42 vs. 51.42 ± 2.72, all P < 0.05), while the other baseline indicators were not statistically significant between the two groups. As the treatment time increased, the plasma GDF-15 level was significantly increased, the ICU-AW group demonstrated a significant decreasing trend in the MRC-score and RFcsa, while no significant changes were found in the non-ICU-AW group. In the ICU-AW group, the plasma GDF-15 level was significantly higher than that in the non-ICU-AW group, while the RFcsa and the MRC-score were significantly lower than those in the non-ICU-AW group (GDF-15 (pg/ml): 2542.44 ± 629.38 vs. 1542.86 ± 502.86; RFcsa (cm2): 2.04 ± 0.64 vs. 2.34 ± 0.61; MRC-score: 41.22 ± 3.42 vs. 51.42 ± 2.72, all P < 0.05), while the other baseline indicators were not statistically significant between the two groups. As the treatment time increased, the plasma GDF-15 level was significantly increased, the ICU-AW group demonstrated a significant decreasing trend in the MRC-score and RFcsa, while no significant changes were found in the non-ICU-AW group. In the ICU-AW group, the plasma GDF-15 level was significantly higher than that in the non-ICU-AW group, while the RFcsa and the MRC-score were significantly lower than those in the non-ICU-AW group (GDF-15 (pg/ml): 2542.44 ± 629.38 vs. 1542.86 ± 502.86; RFcsa (cm2): 2.04 ± 0.64 vs. 2.34 ± 0.61; MRC-score: 41.22 ± 3.42 vs. 51.42 ± 2.72, all. CONCLUSION: The plasma GDF-15 concentration level was significantly associated with skeletal muscle function and muscle wasting on day 7 in ICU patients with mechanical ventilation. Therefore, it can be concluded that the plasma GDF-15 level on the 7th day has a high diagnostic yield for ICU-acquired muscle weakness, and it can predict the 90-day survival status of ICU mechanically ventilated patients.

Alive and Ventilator Free: A Hierarchical, Composite Outcome for Clinical Trials in the Acute Respiratory Distress Syndrome.

OBJECTIVES: Survival from acute respiratory distress syndrome is improving, and outcomes beyond mortality may be important for testing new treatments. The "ventilator-free days" score, is an established composite that equates ventilation on day 28 to death. A hierarchical outcome treating death as a worse than prolonged ventilation would enhance face validity, but performance characteristics and reporting of such an outcome are unknown. We therefore evaluated the performance of a novel hierarchical composite endpoint, the Alive and Ventilator Free score. DESIGN: Using data from four Acute Respiratory Distress Syndrome Network clinical trials, we compared Alive and Ventilator Free to the ventilator-free days score. Alive and Ventilator Free compares each patient with every other patient in a win-lose-tie for each comparison. Duration of mechanical ventilation is only compared if both patients survived. We evaluated power of Alive and Ventilator Free versus ventilator-free days score under various circumstances. SETTING: ICUs within the Acute Respiratory Distress Syndrome Network. PATIENTS: Individuals enrolled in four Acute Respiratory Distress Syndrome Network trials. INTERVENTIONS: None for this analysis. MEASUREMENTS AND MAIN RESULTS: Within the four trials (n = 2,410 patients), Alive and Ventilator Free and ventilator-free days score had similar power, with Alive and Ventilator Free slightly more powerful when a mortality difference was present, and ventilator-free days score slightly more powerful with a difference in duration of mechanical ventilation. Alive and Ventilator Free less often found in favor of treatments that increased mortality and increased days free of ventilation among survivors. CONCLUSIONS: A hierarchical composite endpoint, Alive and Ventilator Free, preserves statistical power while improving face validity. Alive and Ventilator Free is less prone to favor a treatment with discordant effects on survival and days free of ventilation. This general approach can support complex outcome hierarchies with multiple constituent outcomes. Approaches to interpretation of differences in Alive and Ventilator Free are also presented.

Semi-quantitative visual assessment of chest radiography is associated with clinical outcomes in critically ill patients.

BACKGROUND: Respiratory pathology is a major driver of mortality in the intensive care unit (ICU), even in the absence of a primary respiratory diagnosis. Prior work has demonstrated that a visual scoring system applied to chest radiographs (CXR) is associated with adverse outcomes in ICU patients with Acute Respiratory Distress Syndrome (ARDS). We hypothesized that a simple, semi-quantitative CXR score would be associated with clinical outcomes for the general ICU population, regardless of underlying diagnosis. METHODS: All individuals enrolled in the Registry of Critical Illness at Brigham and Women's Hospital between June 2008 and August 2018 who had a CXR within 24 h of admission were included. Each patient's CXR was assigned an opacification score of 0-4 in each of four quadrants with the total score being the sum of all four quadrants. Multivariable negative binomial, logistic, and Cox regression, adjusted for age, sex, race, immunosuppression, a history of chronic obstructive pulmonary disease, a history of congestive heart failure, and APACHE II scores, were used to assess the total score's association with ICU length of stay (LOS), duration of mechanical ventilation, in-hospital mortality, 60-day mortality, and overall mortality, respectively. RESULTS: A total of 560 patients were included. Higher CXR scores were associated with increased mortality; for every one-point increase in score, in-hospital mortality increased 10% (OR 1.10, CI 1.05-1.16, p < 0.001) and 60-day mortality increased by 12% (OR 1.12, CI 1.07-1.17, p < 0.001). CXR scores were also independently associated with both ICU length of stay (rate ratio 1.06, CI 1.04-1.07, p < 0.001) and duration of mechanical ventilation (rate ratio 1.05, CI 1.02-1.07, p < 0.001). CONCLUSIONS: Higher values on a simple visual score of a patient's CXR on admission to the medical ICU are associated with increased in-hospital mortality, 60-day mortality, overall mortality, length of ICU stay, and duration of mechanical ventilation.

Mortality and costs following extracorporeal membrane oxygenation in critically ill adults: a population-based cohort study.

PURPOSE: Extracorporeal membrane oxygenation (ECMO) is used as temporary cardiorespiratory support in critically ill patients. Little is known about population-level short- and long-term outcomes following ECMO, including healthcare use and health system cost across a wide range of sectors. METHODS: Population-based cohort study in Ontario, Canada (October 1, 2009-March 31, 2017) of adult patients (≥ 18 years) receiving ECMO for cardiorespiratory support. We captured outcomes through linkage to health administrative databases. Primary outcome was mortality during hospitalization, as well as at 7 days, 30 days, 1 year, 2 years, and 5 years following ECMO initiation. We analyzed health system costs (in Canadian dollars) in the 1 year following the date of the index admission. RESULTS: A total of 692 patients were included. Mean (standard deviation [SD]) age was 51.3 (16.0) years. Median (interquartile range [IQR]) time to ECMO initiation from date of admission was 2 (0-9) days. In-hospital mortality was 40.0%. Mortality at 1 year, 2 years, and 5 years was 45.1%, 49.0%, and 57.4%, respectively. Among survivors, 78.4% were discharged home, while 21.2% were discharged to continuing care. Median (IQR) total costs in the 1 year following admission among all patients were Canadian $130,157 (Canadian $58,645-Canadian $240,763), of which Canadian $91,192 (Canadian $38,507-Canadian $184,728) were attributed to inpatient care. CONCLUSIONS: Hospital mortality among critically ill adults receiving ECMO for advanced cardiopulmonary support is relatively high, but does not markedly increase in the years following discharge. Survivors are more likely to be discharged home than to continuing care. Median costs are high, but largely reflect inpatient hospital costs, and not costs incurred following discharge.

Assessment of Therapeutic Interventions and Lung Protective Ventilation in Patients With Moderate to Severe Acute Respiratory Distress Syndrome: A Systematic Review and Network Meta-analysis.

Importance: A number of interventions are available to manage patients with moderate to severe acute respiratory distress syndrome (ARDS). However, the associations of currently available ventilatory strategies and adjunctive therapies with mortality are uncertain. Objectives: To compare and rank different therapeutic strategies to identify the best intervention associated with a reduction in mortality in adult patients with moderate to severe ARDS. Data Sources: An electronic search of MEDLINE, MEDLINE In-Process/ePubs Ahead of Print, Embase, Cochrane Controlled Clinical Trial Register (Central), PubMed, and CINAHL was conducted, from database inception to May 29, 2019. Study Selection: Randomized clinical trials of interventions for adults with moderate to severe ARDS that used lung protective ventilation. No language restrictions were applied. Data Extraction and Synthesis: Data were independently extracted by 2 reviewers and synthesized with Bayesian random-effects network meta-analyses. Main Outcomes and Measures: The primary outcome was 28-day mortality. Barotrauma was a secondary outcome. Results: Among 25 randomized clinical trials evaluating 9 interventions, 2686 of 7743 patients (34.6%) died within 28 days. Compared with lung protective ventilation alone, prone positioning and venovenous extracorporeal membrane oxygenation were associated with significantly lower 28-day mortality (prone positioning: risk ratio, 0.69; 95% credible interval, 0.48-0.99; low quality of evidence; venovenous extracorporeal membrane oxygenation: risk ratio, 0.60; 95% credible interval, 0.38-0.93; moderate quality of evidence). These 2 interventions had the highest ranking probabilities, although they were not significantly different from each other. Among 18 trials reporting on barotrauma, 448 of 6258 patients (7.2%) experienced this secondary outcome. No intervention was superior to any other in reducing barotrauma, and each represented low to very low quality of evidence. Conclusions and Relevance: This network meta-analysis supports the use of prone positioning and venovenous extracorporeal membrane oxygenation in addition to lung protective ventilation in patients with ARDS. Moreover, venovenous extracorporeal membrane oxygenation may be considered as an early strategy for adults with severe ARDS receiving lung protective ventilation.

Ultrasound Assessment of Lung Aeration in Subjects Supported by Venovenous Extracorporeal Membrane Oxygenation.

BACKGROUND: The value of ultrasound in assessing lung aeration of patients with ARDS who require venovenous extracorporeal membrane oxygenation (ECMO) has, to our knowledge, never been studied. The objective of the study was to evaluate by using ultrasound lung aeration at ECMO initiation and withdrawal in subjects with severe ARDS supported by venovenous ECMO. METHODS: Fifty subjects were included in this pilot retrospective study. The lung ultrasound aeration score (LUS) and respiratory variables were collected at ECMO initiation (T0) and ECMO withdrawal (T1). The LUS at T0 between the subjects who survived to ICU discharge and those who died in ICU was compared. The relationship between changes in LUS and changes in PaO2 /FIO2 from T0 to T1 was assessed. RESULTS: The ICU mortality was 34%. The LUS at T0 did not differ between survivors and non-survivors (median 22 [interquartile range] {IQR} 19-26 vs median 24 [IQR, 19-28]; P = .60). From T0 to T1, the LUS decreased significantly in survivors (median 22 [IQR, 19-26] vs median 16 [IQR, 13-19]; P < .001), it decreased moderately in non-survivors who were weaned off ECMO (median 26 [24-29]) vs median 22 (IQR, 17-24), P = .031), and remained stable in those who died during ECMO (median 25 [IQR, 19-29] vs median 25 [IQR, 23-31]; P = .22). Changes in PaO2 /FIO2 were not related to changes in the LUS between T0 and T1. CONCLUSIONS: At the time of ECMO placement, the subjects who survived ARDS had aeration loss close to that observed in the subjects who did not survive. At the time of ECMO withdrawal, there was a significant improvement in lung aeration in the survivors, whereas a severe loss of lung aeration persisted in the non-survivors, although some were weaned off ECMO. Lung ultrasound provided a valuable tool for bedside assessment of lung aeration in subjects supported by ECMO.

Emerging drugs for treating the acute respiratory distress syndrome.

INTRODUCTION: The acute respiratory distress syndrome (ARDS) is a common and catastrophic condition, with a high mortality rate and economic burden on society. Despite 50 years of study, there is no specific pharmacological therapy for ARDS. Areas covered: This review outlines the definitions, epidemiology, risk factors and pathophysiology of ARDS. The priority of developing a clinically-relevant model for ARDS to test pre-clinical candidates is discussed, together with the limitations of current models. The scientific rationale of emerging therapeutic candidates is outlined in the setting of the biological mechanisms implicated in the complex pathogenesis of ARDS. Emerging therapies, currently in clinical trials, are discussed, including the pre-clinical basis for their use and the expected timeline to trial completion. Expert opinion: We highlight the necessity of improving pre-clinical models of ARDS and the design of clinical trials for the development of novel pharmacological therapies. We reflect on the most promising emerging strategies and their potential role in ARDS management.

Anticoagulation and Transfusions Management in Veno-Venous Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome: Assessment of Factors Associated With Transfusion Requirements and Mortality.

PURPOSE: We describe an approach for anticoagulation and transfusions in veno-venous-extracorporeal membrane oxygenation (VV-ECMO), evaluating factors associated with higher transfusion requirements, and their impact on mortality. METHODS: Observational study on consecutive adults supported with VV-ECMO for acute respiratory distress syndrome (ARDS). We targeted an activated partial thromboplastin time of 40 to 50 seconds and a hematocrit of 24% to 30%. Univariate and multiple analyses were done to evaluate factors associated with transfusion requirements and the influence of increasing transfusions on mortality during ECMO. RESULTS: In a cohort of 82 VV-ECMO patients (PRedicting dEath for SEvere ARDS on VV-ECMO [PRESERVE] score: 4, Interquartile range [IQR]: 3-5, Respiratory Extracorporeal Membrane Oxygenation Survival Prediction [RESP] score: 2, IQR: 2-4), 76 (92.7%) patients received at least 1 unit of packed red blood cells (PRBCs) during the intensive care unit stay related to ECMO (median PRBC/d 156 mL, IQR: 93-218; median ECMO duration 14 days, IQR: 8-22). A higher requirement of PRBC transfusions was associated with pre-ECMO hematocrit, and with the following conditions during ECMO: platelet nadir, antithrombin III (ATIII), and stage 3 of acute kidney injury (all P < .05). Sixty-two (75.6%) patients survived ECMO. Pre-ECMO hospital stay, PRBC transfusion, and septic shock were associated with mortality (all P < .05). The adjusted odds ratio for each 100mL/d increase in PRBC transfusion was 1.9 (95% confidence interval [CI]: 1.1-3.2, P = .01); for the development of septic shock it was 15.4 (95% CI: 1.7-136.8, P = .01), and for each day of pre-ECMO stay it was 1.1 (95% CI: 1-1.2, P = .04). CONCLUSION: Implementation of a comprehensive protocol for anticoagulation and transfusions in VV-ECMO for ARDS resulted in a low PRBC requirement, and an ECMO survival comparable to data in the literature. Lower ATIII emerged as a factor associated with increased need for transfusions. Higher PRBC transfusions were associated with ECMO mortality. Further investigations are needed to better understand the right level of anticoagulation in ECMO, and the factors to take into account in order to manage personalized transfusion practice in this select setting.

The Incremental Burden of Acute Respiratory Distress Syndrome: Long-term Follow-up of a Population-Based Nested Case-Control Study.

OBJECTIVE: To evaluate the long-term survival of patients at similar risk for hospital-acquired acute respiratory distress syndrome (ARDS) who did and did not develop ARDS. METHODS: We conducted long-term follow-up of a population-based nested case-control study in a consecutive cohort of adult Olmsted County, Minnesota, patients admitted from January 1, 2001, through December 31, 2010. Patients in whom ARDS developed during their hospital stay (cases) were matched to similar-risk patients without ARDS (controls) by 6 characteristics: age, sex, sepsis, high-risk surgery, ratio of oxygen saturation to fraction of inspired oxygen, and ARDS risk according to the Lung Injury Prediction Score. Hospital mortality, discharge disposition, and long-term survival were compared. RESULTS: Patients who developed hospital-acquired ARDS (n=400) had higher hospital mortality than at-risk controls (n=400) (35% vs 5%; P<.001). Among hospital survivors (252 matched pairs), ARDS cases were more likely to be discharged to rehabilitation (13% vs 4%) and long-term care (30% vs 15%) facilities, whereas more controls were discharged home (71% vs 41%). After discharge, differences in survival persisted beyond 90 days (adjusted hazard ratio [HR], 1.76; 95% CI, 1.2-2.5; P=.002) and 6 months (adjusted HR, 1.73; 95% CI, 1.2-2.6; P<.001). CONCLUSION: These results suggest that in a population-based matched case-control study of patients with similar characteristics at the time of hospital admission, those who developed hospital-acquired ARDS had worse long-term survival.

Lessons to learn from epidemiologic studies in ARDS.

PURPOSE OF REVIEW: Recent advances in our understanding of the epidemiology of ARDS has generated key insights into the incidence, risk factors, demographics, management and outcomes from this devastating clinical syndrome. RECENT FINDINGS: ARDS occurs in 10% of all ICU patients, in 23% of all mechanically ventilated patients, with 5.5 cases per ICU bed each year. Although some regional variation exists regarding ARDS incidence, this may be less than previously thought. Subphenotypes are increasingly identified within the ARDS cohort, with studies identifying a 'hyperinflammatory' or 'reactive' subgroup that has a higher mortality, and may respond differently to therapeutic interventions. Demographic factors, such as race, may also affect the therapeutic response. Although mortality in ARDS is decreasing in clinical trials, it remains unchanged at approximately 40% in major observational studies. Modifiable ventilatory management factors, including PEEP, airway pressures, and respiratory rate are associated with mortality in ARDS. Hospital and ICU organizational factors play a role in outcome, whereas socioeconomic status is independently associated with survival in patients with ARDS. The Kigali adaptation of the Berlin ARDS definition may provide useful insights into the burden of ARDS in the developing world. SUMMARY: ARDS exerts a substantial disease burden, with 40% of patients dying in hospital. Diverse factors, including patient-related factors such as age and illness severity, country level socioeconomic status, and ventilator management and ICU organizational factors each contribute to outcome from ARDS. Addressing these issues provides opportunities to improve outcome in patients with ARDS.