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

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

Validation of automated data abstraction for SCCM discovery VIRUS COVID-19 registry: practical EHR export pathways (VIRUS-PEEP).

Background: The gold standard for gathering data from electronic health records (EHR) has been manual data extraction; however, this requires vast resources and personnel. Automation of this process reduces resource burdens and expands research opportunities. Objective: This study aimed to determine the feasibility and reliability of automated data extraction in a large registry of adult COVID-19 patients. Materials and methods: This observational study included data from sites participating in the SCCM Discovery VIRUS COVID-19 registry. Important demographic, comorbidity, and outcome variables were chosen for manual and automated extraction for the feasibility dataset. We quantified the degree of agreement with Cohen's kappa statistics for categorical variables. The sensitivity and specificity were also assessed. Correlations for continuous variables were assessed with Pearson's correlation coefficient and Bland-Altman plots. The strength of agreement was defined as almost perfect (0.81-1.00), substantial (0.61-0.80), and moderate (0.41-0.60) based on kappa statistics. Pearson correlations were classified as trivial (0.00-0.30), low (0.30-0.50), moderate (0.50-0.70), high (0.70-0.90), and extremely high (0.90-1.00). Measurements and main results: The cohort included 652 patients from 11 sites. The agreement between manual and automated extraction for categorical variables was almost perfect in 13 (72.2%) variables (Race, Ethnicity, Sex, Coronary Artery Disease, Hypertension, Congestive Heart Failure, Asthma, Diabetes Mellitus, ICU admission rate, IMV rate, HFNC rate, ICU and Hospital Discharge Status), and substantial in five (27.8%) (COPD, CKD, Dyslipidemia/Hyperlipidemia, NIMV, and ECMO rate). The correlations were extremely high in three (42.9%) variables (age, weight, and hospital LOS) and high in four (57.1%) of the continuous variables (Height, Days to ICU admission, ICU LOS, and IMV days). The average sensitivity and specificity for the categorical data were 90.7 and 96.9%. Conclusion and relevance: Our study confirms the feasibility and validity of an automated process to gather data from the EHR.

Long short-term memory model identifies ARDS and in-hospital mortality in both non-COVID-19 and COVID-19 cohort.

OBJECTIVE: To identify the risk of acute respiratory distress syndrome (ARDS) and in-hospital mortality using long short-term memory (LSTM) framework in a mechanically ventilated (MV) non-COVID-19 cohort and a COVID-19 cohort. METHODS: We included MV ICU patients between 2017 and 2018 and reviewed patient records for ARDS and death. Using active learning, we enriched this cohort with MV patients from 2016 to 2019 (MV non-COVID-19, n=3905). We collected a second validation cohort of hospitalised patients with COVID-19 in 2020 (COVID+, n=5672). We trained an LSTM model using 132 structured features on the MV non-COVID-19 training cohort and validated on the MV non-COVID-19 validation and COVID-19 cohorts. RESULTS: Applying LSTM (model score 0.9) on the MV non-COVID-19 validation cohort had a sensitivity of 86% and specificity of 57%. The model identified the risk of ARDS 10 hours before ARDS and 9.4 days before death. The sensitivity (70%) and specificity (84%) of the model on the COVID-19 cohort are lower than MV non-COVID-19 cohort. For the COVID-19 + cohort and MV COVID-19 + patients, the model identified the risk of in-hospital mortality 2.4 days and 1.54 days before death, respectively. DISCUSSION: Our LSTM algorithm accurately and timely identified the risk of ARDS or death in MV non-COVID-19 and COVID+ patients. By alerting the risk of ARDS or death, we can improve the implementation of evidence-based ARDS management and facilitate goals-of-care discussions in high-risk patients. CONCLUSION: Using the LSTM algorithm in hospitalised patients identifies the risk of ARDS or death.

Decreased Utilization of Low Tidal Volume Ventilation Outside of the Intensive Care Unit as Compared to Inside.

Background: Investigations into the use of low tidal volume ventilation (LTVV) have been performed for patients in emergency departments (EDs) or intensive care units (ICUs). Practice differences between the ICU and non-ICU care areas have not been described. We hypothesized that the initial implementation of LTVV would be better inside ICUs than outside. Methods: This is a retrospective observational study of patients initiated on invasive mechanical ventilation (IMV) between January 1, 2016, and July 17, 2019. Initial recorded tidal volumes after intubation were used to compare the use of LTVV between care areas. Low tidal volume was considered 6.5 cc/kg of ideal body weight (IBW) or less. The primary outcome was the initiation of low tidal volume. Sensitivity analyses used a tidal volume of 8 cc/kg of IBW or less, and direct comparisons were performed between the ICU, ED, and wards. Results: There were 6392 initiations of IMV: 2217 (34.7%) in the ICU and 4175 (65.3%) outside. LTVV was more likely to be initiated in the ICU than outside (46.5% vs 34.2%; adjusted odds ratio [aOR] 0.62, 95% confidence interval [CI] 0.56-0.71, P < .01). The ICU also had more implementation when PaO2/FiO2 ratio was less than 300, (48.0% vs 34.6%; aOR 0.59, 95% CI 0.48-0.71, P < .01). When comparing individual locations, wards had lower odds of LTVV than the ICU (aOR 0.82, 95% CI 0.70-0.96, P = .02), the ED had lower odds than the ICU (aOR 0.55, 95% CI 0.48-0.63, P < .01), and the ED had lower odds than the wards (aOR 0.66, 95% CI 0.56-0.77, P < .01). Interpretation: Initial low tidal volumes were more likely to be initiated in the ICU than outside. This finding remained when examining only patients with a PaO2/FiO2 ratio less than 300. Care areas outside of the ICU do not employ LTVV as often as ICUs and are, therefore, a possible target for process improvement.

Resuscitation in the First 3 Hours of Sepsis-Induced Hypotension Varies by Patient and Hospital Factors.

Patient and hospital factors affects how we resuscitate patients in the first 3 hours of sepsis-induced hypotension. OBJECTIVES: To evaluate variability in compliance to the 3-hour surviving sepsis campaign (SSC) bundle and explore the association of early compliance with subsequent shock and in-hospital mortality. DESIGN: Retrospective cohort study between September 2017 and February 2018. SETTING: Thirty-four academic medical centers. PARTICIPANTS: A subgroup sepsis-induced hypotensive patients from a larger shock cohort study. MAIN OUTCOMES AND MEASURES: Compliance to SSC bundle that was defined as receiving appropriate antibiotics, 30 mL/kg of crystalloid or initiation of vasopressors, and lactate, obtained in the first 3 hours following sepsis-induced hypotension. RESULTS: We included 977 patients with septic-induced hypotension. Bundle compliance was 43.8%, with the lowest compliance to fluid or vasopressor components (56%). Patients with high Sequential Organ Failure Assessment scores and physiologic assessments were more likely to receive compliant care, as were patients with sepsis-induced hypotension onset in the emergency department (ED) or admitted to mixed medical-surgical ICUs. SSC compliance was not associated with in-hospital mortality (adjusted odds ratio, 0.72; 95% CI, 0.47-1.10). The site-to-site variability contributed to SSC compliance (intraclass correlation coefficient [ICC], 0.15; 95% CI, 0.07-0.3) but not in-hospital mortality (ICC, 0.02; 95% CI, 0.001-0.24). Most patients remained in shock after 3 hours of resuscitation (SSC compliant 81.1% and noncompliant 53.7%). Mortality was higher among patients who were persistently hypotensive after 3 hours of resuscitation for both the SSC compliant (persistent hypotension 37% vs not hypotensive 27.2%; p = 0.094) and noncompliant (30.1% vs 18.2%; p = 0.001, respectively). CONCLUSIONS AND RELEVANCE: Patients with a higher severity of illness and sepsis-induced hypotension identified in the ED were more likely to receive SSC-compliant care. SSC compliance was not associated with in-hospital mortality after adjusting for patient- and hospital-level differences. Higher mortality is seen among those who remain in shock after initial resuscitation, regardless of SSC compliance.

Assessing a standardized decision-making algorithm for blood culture collection in the intensive care unit.

PURPOSE: Blood cultures are commonly ordered for patients with low risk of bacteremia. Indications for obtaining blood cultures are often broad and ill defined, and decision algorithms for appropriate blood cultures have not been comprehensively evaluated in critically-ill populations. METHODS: We conducted a retrospective analysis to assess the frequency of inappropriate blood cultures in the ICUs at Montefiore Medical Center based on an evidence-based guidance algorithm. Blood cultures were reviewed against this algorithm to determine their appropriateness. We calculated the prevalence of inappropriate blood culture and explored the reasons for these collected cultures. RESULTS: 300 patients were randomly selected from an initial cohort of 3370 patients. 294 patients were included and of these, 167 patients had at least 1 blood culture drawn. 125 patients had one or more inappropriate blood culture. 61.4% of blood cultures drawn were assessed to be inappropriate. The most common reason for inappropriate cultures was a culture drawn as a result of isolated fever or leukocytosis. CONCLUSION: In a cohort of critically-ill patients, inappropriate blood cultures were common. The indications for blood cultures are often not evidence-based, and evidence-based algorithms to guide the collection of blood cultures may offer a way to decrease inappropriate culture orders.

SWEAT ICU-An Observational Study of Physician Workload and the Association of Physician Outcomes in Academic ICUs.

The optimal staffing model for physicians in the ICU is unknown. Patient-to-intensivist ratios may offer a simple measure of workload and be associated with patient mortality and physician burnout. To evaluate the association of physician workload, as measured by the patient-to-intensivist ratio, with physician burnout and patient mortality. DESIGN: Cross-sectional observational study. SETTING: Fourteen academic centers in the United States from August 2020 to July 2021. SUBJECTS: We enrolled ICU physicians and collected data on adult ICU patients under the physician's care on the single physician-selected study day for each physician. MEASUREMENTS and MAIN RESULTS: The primary exposure was workload (self-reported number of patients' physician was responsible for) modeled as high (>14 patients) and low (≤14 patients). The primary outcome was burnout, measured by the Well-Being Index. The secondary outcome measure was 28-day patient mortality. We calculated odds ratio for burnout and patient outcomes using a multivariable logistic regression model and a binomial mixed effects model, respectively. We enrolled 122 physicians from 62 ICUs. The median patient-to-intensivist ratio was 12 (interquartile range, 10-14), and the overall prevalence of burnout was 26.4% (n = 32). Intensivist workload was not independently associated with burnout (adjusted odds ratio, 0.74; 95% CI, 0.24-2.23). Of 1,322 patients, 679 (52%) were discharged alive from the hospital, 257 (19%) remained hospitalized, and 347 (26%) were deceased by day 28; 28-day outcomes were unknown for 39 of patients (3%). Intensivist workload was not independently associated with 28-day patient mortality (adjusted odds ratio, 1.33; 95% CI, 0.92-1.91). CONCLUSIONS: In our cohort, approximately one in four physicians experienced burnout on the study day. There was no relationship be- tween workload as measured by patient-to-intensivist ratio and burnout. Factors other than the number of patients may be important drivers of burnout among ICU physicians.

Wellness and Coping of Physicians Who Worked in ICUs During the Pandemic: A Multicenter Cross-Sectional North American Survey.

OBJECTIVES: Few surveys have focused on physician moral distress, burnout, and professional fulfilment. We assessed physician wellness and coping during the COVID-19 pandemic. DESIGN: Cross-sectional survey using four validated instruments. SETTING: Sixty-two sites in Canada and the United States. SUBJECTS: Attending physicians (adult, pediatric; intensivist, nonintensivist) who worked in North American ICUs. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We analysed 431 questionnaires (43.3% response rate) from 25 states and eight provinces. Respondents were predominantly male (229 [55.6%]) and in practice for 11.8 ± 9.8 years. Compared with prepandemic, respondents reported significant intrapandemic increases in days worked/mo, ICU bed occupancy, and self-reported moral distress (240 [56.9%]) and burnout (259 [63.8%]). Of the 10 top-ranked items that incited moral distress, most pertained to regulatory/organizational ( n = 6) or local/institutional ( n = 2) issues or both ( n = 2). Average moral distress (95.6 ± 66.9), professional fulfilment (6.5 ± 2.1), and burnout scores (3.6 ± 2.0) were moderate with 227 physicians (54.6%) meeting burnout criteria. A significant dose-response existed between COVID-19 patient volume and moral distress scores. Physicians who worked more days/mo and more scheduled in-house nightshifts, especially combined with more unscheduled in-house nightshifts, experienced significantly more moral distress. One in five physicians used at least one maladaptive coping strategy. We identified four coping profiles (active/social, avoidant, mixed/ambivalent, infrequent) that were associated with significant differences across all wellness measures. CONCLUSIONS: Despite moderate intrapandemic moral distress and burnout, physicians experienced moderate professional fulfilment. However, one in five physicians used at least one maladaptive coping strategy. We highlight potentially modifiable factors at individual, institutional, and regulatory levels to enhance physician wellness.

Review of Anti-inflammatory and Antiviral Therapeutics for Hospitalized Patients Infected with Severe Acute Respiratory Syndrome Coronavirus 2.

Severe acute respiratory syndrome coronavirus 2 infection leads to dysregulation of immune pathways. Therapies focusing on suppressing cytokine activity have some success. Current evidence supports the use of dexamethasone in hospitalized patients requiring oxygen to decrease mortality. Interleukin-6 inhibitors, like tocilizumab and sarilumab, are also beneficial in hypoxemic patients, if used early. Janus kinase inhibition in combination with glucocorticoids is emerging as a potential therapeutic option for patients with moderate to severe symptoms. Data on the role of anakinra, hyperimmune immunoglobulin/convalescent plasma, or plasma purification are limited.

Quantifying Utilitarian Outcomes to Inform Triage Ethics: Simulated Performance of a Ventilator Triage Protocol under Sars-CoV-2 Pandemic Surge Conditions.

BACKGROUND: Equitable protocols to triage life-saving resources must be specified prior to shortages in order to promote transparency, trust and consistency. How well proposed utilitarian protocols perform to maximize lives saved is unknown. We aimed to estimate the survival rates that would be associated with implementation of the New York State 2015 guidelines for ventilator triage, and to compare them to a first-come-first-served triage method. METHODS: We constructed a simulation model based on a modified version of the New York State 2015 guidelines compared to a first-come-first-served method under various hypothetical ventilator shortages. We included patients with SARs-CoV-2 infection admitted with respiratory failure requiring mechanical ventilation to three acute care hospitals in New York from 3/01/2020 and 5/27/2020. We estimated (1) survival rates, (2) number of excess deaths, (3) number of patients extubated early or not allocated a ventilator due to capacity constraints, (4) survival rates among patients not allocated a ventilator at triage or extubated early due to capacity constraints. RESULTS: 807 patients were included in the study. The simulation model based on a modified New York State policy did not decrease mortality, excess death or exclusion from ventilators compared to the first-come-first-served policy at every ventilator capacity we tested using COVID-19 surge cohort patients. Survival rates were similar at all the survival probabilities estimated. At the lowest ventilator capacity, the modified New York State policy has an estimated survival of 28.5% (CI: 28.4-28.6), compared to 28.1% (CI: 27.7-28.5) for the first-come-first-served policy. CONCLUSIONS: This simulation of a modified New York State guideline-based triage protocol revealed limitations in achieving the utilitarian goals these protocols are designed to fulfill. Quantifying these outcomes can inform a better balance among competing moral aims.

Effects of Timing of Invasive Mechanical Ventilation in Patients with Shock. An Analysis of the Multicenter Prospective Observational VOLUME-CHASERS Cohort.

Objectives: Describe the variation in practice and identify predictors of invasive mechanical ventilation (IMV) use in shock. Explore the association between the timing of IMV initiation ("Early" vs. "Delayed") on shock duration. Design: Multicenter, prospective, observational cohort study between September 2017 and February 2018 Setting: 34 hospitals in the United States and Jordan. Patients: Consecutive, adult, critically ill patients with shock, defined as a systolic blood pressure less than or equal to 90mm Hg, mean arterial pressure less than or equal to 65mm Hg, or need for a vasopressor medication. Interventions: None. Measurements and Main Results: "Early" IMV was defined as starting IMV 0-6 hours of shock onset and "Delayed" IMV was defined as starting IMV between 6 and 48 hours of shock onset. The primary outcome was shock-free days, defined as the number of days without shock after the first 48 hours of shock onset. Variation and predictors of IMV use were examined within the whole cohort as well as the subgroup of those intubated within 0-48 hours of shock onset. Mixed effects modeling with hospital site as a random effect showed that there was 7% variation by site in the use and timing of IMV in this shock cohort. In a propensity-matched model for the timing of IMV, "Early" IMV after shock onset was associated with more shock-free days when compared to "Delayed" IMV in those intubated within 0-48 hours of shock onset (Beta coefficient 0.65 days, 95% CI 0.14-1.16 days). Conclusions: Timing of IMV initiation for patients in shock has potentially important implications for patient outcomes and merits further study.

Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19.

BACKGROUND: Thrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19. METHODS: In an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. RESULTS: The trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%). The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively; adjusted odds ratio, 0.84; 95% credible interval, 0.64 to 1.11). Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis. CONCLUSIONS: In critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin did not result in a greater probability of survival to hospital discharge or a greater number of days free of cardiovascular or respiratory organ support than did usual-care pharmacologic thromboprophylaxis. (REMAP-CAP, ACTIV-4a, and ATTACC ClinicalTrials.gov numbers, NCT02735707, NCT04505774, NCT04359277, and NCT04372589.).

Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19.

BACKGROUND: Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19. METHODS: In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level. RESULTS: The trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support-free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis. CONCLUSIONS: In noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis. (ATTACC, ACTIV-4a, and REMAP-CAP ClinicalTrials.gov numbers, NCT04372589, NCT04505774, NCT04359277, and NCT02735707.).

Practice, Outcomes, and Complications of Emergent Endotracheal Intubation by Critical Care Practitioners During the COVID-19 Pandemic.

BACKGROUND: For patients with COVID-19 who undergo emergency endotracheal intubation, data are limited regarding the practice, outcomes, and complications of this procedure. RESEARCH QUESTION: For patients with COVID-19 requiring emergency endotracheal intubation, how do the procedural techniques, the incidence of first-pass success, and the complications associated with the procedure compare with intubations of critically ill patients before the COVID-19 pandemic? STUDY DESIGN AND METHODS: We conducted a retrospective study of adult patients with COVID-19 at Montefiore Medical Center who underwent first-time endotracheal intubation by critical care physicians between July 19, 2019, and May 1, 2020. The first COVID-19 patient was admitted to our institution on March 11, 2020; patients admitted before this date are designated the prepandemic cohort. Descriptive statistics were used to compare groups. A Fisher exact test was used to compare categorical variables. For continuous variables, a two-tailed Student t test was used for parametric variables or a Wilcoxon rank-sum test was used for nonparametric variables. RESULTS: One thousand two hundred sixty intubations met inclusion criteria (782 prepandemic cohort, 478 pandemic cohort). Patients during the pandemic were more likely to be intubated for hypoxemic respiratory failure (72.6% vs 28.1%; P < .01). During the pandemic, operators were more likely to use video laryngoscopy (89.4% vs 53.3%; P < .01) and neuromuscular blocking agents (86.0% vs 46.2%; P < .01). First-pass success was higher during the pandemic period (94.6% vs 82.9%; P < .01). The rate of associated complications was higher during the pandemic (29.5% vs 15.2%; P < .01), a finding driven by a higher rate of hypoxemia during or immediately after the procedure (25.7% vs 8.2%; P < .01). INTERPRETATION: Video laryngoscopy and neuromuscular blockade were used increasingly during the COVID-19 pandemic. Despite a higher rate of first-pass success during the pandemic, the incidence of complications associated with the procedure was higher.

Variation in Early Management Practices in Moderate-to-Severe ARDS in the United States: The Severe ARDS: Generating Evidence Study.

BACKGROUND: Although specific interventions previously demonstrated benefit in patients with ARDS, use of these interventions is inconsistent, and patient mortality remains high. The impact of variability in center management practices on ARDS mortality rates remains unknown. RESEARCH QUESTION: What is the impact of treatment variability on mortality in patients with moderate to severe ARDS in the United States? STUDY DESIGN AND METHODS: We conducted a multicenter, observational cohort study of mechanically ventilated adults with ARDS and Pao2 to Fio2 ratio of ≤ 150 with positive end-expiratory pressure of ≥ 5 cm H2O, who were admitted to 29 US centers between October 1, 2016, and April 30, 2017. The primary outcome was 28-day in-hospital mortality. Center variation in ventilator management, adjunctive therapy use, and mortality also were assessed. RESULTS: A total of 2,466 patients were enrolled. Median baseline Pao2 to Fio2 ratio was 105 (interquartile range, 78.0-129.0). In-hospital 28-day mortality was 40.7%. Initial adherence to lung protective ventilation (LPV; tidal volume, ≤ 6.5 mL/kg predicted body weight; plateau pressure, or when unavailable, peak inspiratory pressure, ≤ 30 mm H2O) was 31.4% and varied between centers (0%-65%), as did rates of adjunctive therapy use (27.1%-96.4%), methods used (neuromuscular blockade, prone positioning, systemic steroids, pulmonary vasodilators, and extracorporeal support), and mortality (16.7%-73.3%). Center standardized mortality ratios (SMRs), calculated using baseline patient-level characteristics to derive expected mortality rate, ranged from 0.33 to 1.98. Of the treatment-level factors explored, only center adherence to early LPV was correlated with SMR. INTERPRETATION: Substantial center-to-center variability exists in ARDS management, suggesting that further opportunities for improving ARDS outcomes exist. Early adherence to LPV was associated with lower center mortality and may be a surrogate for overall quality of care processes. Future collaboration is needed to identify additional treatment-level factors influencing center-level outcomes. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03021824; URL: www.clinicaltrials.gov.

A Case-Control Study of Prone Positioning in Awake and Nonintubated Hospitalized Coronavirus Disease 2019 Patients.

To determine the association between prone positioning in nonintubated patients with coronavirus disease 2019 and frequency of invasive mechanical ventilation or inhospital mortality. DESIGN: A nested case-matched control analysis. SETTING: Three hospital sites in Bronx, NY. PATIENTS: Adult coronavirus disease 2019 patients admitted between March 1, 2020, and April 1, 2020. We excluded patients with do-not-intubate orders. Cases were defined by invasive mechanical ventilation or inhospital mortality. Each case was matched with two controls based on age, gender, admission date, and hospital length of stay greater than index time of matched case via risk-set sampling. The presence of nonintubated proning was identified from provider documentation. INTERVENTION: Nonintubated proning documented prior to invasive mechanical ventilation or inhospital mortality for cases or prior to corresponding index time for matched controls. MEASUREMENTS AND MAIN RESULTS: We included 600 patients, 41 (6.8%) underwent nonintubated proning. Cases had lower Spo2/Fio2 ratios prior to invasive mechanical ventilation or inhospital mortality compared with controls (case median, 97 [interquartile range, 90-290] vs control median, 404 [interquartile range, 296-452]). Although most providers (58.5%) documented immediate improvement in oxygenation status after initiating nonintubated proning, there was no difference in worst Spo2/Fio2 ratios before and after nonintubated proning in both case and control (case median Spo2/Fio2 ratio difference, 3 [interquartile range, -3 to 8] vs control median Spo2/Fio2 ratio difference, 0 [interquartile range, -3 to 50]). In the univariate analysis, patients who underwent nonintubated proning were 2.57 times more likely to require invasive mechanical ventilation or experience inhospital mortality (hazard ratio, 2.57; 95% CI, 1.17-5.64; p = 0.02). Following adjustment for patient level differences, we found no association between nonintubated proning and invasive mechanical ventilation or inhospital mortality (adjusted hazard ratio, 0.92; 95% CI, 0.34-2.45; p = 0.86). CONCLUSIONS: There was no significant association with reduced risk of invasive mechanical ventilation or inhospital mortality after adjusting for baseline severity of illness and oxygenation status.