Objectives: Effective pharmacologic treatments directly targeting lung injury in patients with the acute respiratory distress syndrome are lacking. Early treatment with inhaled corticosteroids and beta agonists may reduce progression to acute respiratory distress syndrome by reducing lung inflammation and enhancing alveolar fluid clearance. Design: Double-blind, randomized clinical trial (ClinicalTrials.gov: NCT01783821). The primary outcome was longitudinal change in oxygen saturation divided by the Fio ₂ (S/F) through day 5. We also analyzed categorical change in S/F by greater than 20%. Other outcomes included need for mechanical ventilation and development of acute respiratory distress syndrome. Setting: Five academic centers in the United States. Patients: Adult patients admitted through the emergency department at risk for acute respiratory distress syndrome. Interventions: Aerosolized budesonide/formoterol versus placebo bid for up to 5 days. Measurements and Main Results: Sixty-one patients were enrolled from September 3, 2013, to June 9, 2015. Median time from presentation to first study drug was less than 9 hours. More patients in the control group had shock at enrollment (14 vs 3 patients). The longitudinal increase in S/F was greater in the treatment group (p = 0.02) and independent of shock (p = 0.04). Categorical change in S/F improved (p = 0.01) but not after adjustment for shock (p = 0.15). More patients in the placebo group developed acute respiratory distress syndrome (7 vs 0) and required mechanical ventilation (53% vs 21%). Conclusions: Early treatment with inhaled budesonide/formoterol in patients at risk for acute respiratory distress syndrome is feasible and improved oxygenation as assessed by S/F. These results support further study to test the efficacy of inhaled corticosteroids and beta agonists for prevention of acute respiratory distress syndrome.

Purpose: Oxygen saturation to fraction of inspired oxygen ratio (SpO₂/FiO₂) has been validated as a surrogate marker for partial pressure of oxygen to fraction of inspired oxygen ratio among mechanically ventilated patients with acute respiratory distress syndrome (ARDS). The validity of SpO₂/FiO₂ measurements in predicting ARDS has not been studied. Recently, a Lung Injury Prediction Score (LIPS) has been developed to help identify patients at risk of developing ARDS. Methods: This was a secondary analysis of the LIPS-1 cohort. A multivariate logistic regression included all established variables for LIPS, Acute Physiology and Chronic Health Evaluation 2, age, and comorbid conditions that could affect SpO₂/FiO₂. The primary outcome was development of ARDS in the hospital. The secondary outcomes included hospital mortality, hospital day of ARDS development, and hospital day of death. Results: Of the 5584 patients, we evaluated all 4646 with recorded SpO₂/FiO₂ values. Median SpO₂/FiO₂ in those who did and did not develop ARDS was 254 (100, 438) and 452 (329, 467), respectively. There was a significant association between SpO₂/FiO₂ and ARDS ( P ≤ .001). The SpO₂/FiO₂ was found to be an independent predictor of ARDS in a “dose-dependent” manner; for SpO₂/FiO₂ < 100—odds ratios (OR) 2.49 (1.69-3.64, P < .001), for SpO₂/FiO₂ 100 < 200—OR 1.75 (1.16-2.58, P = .007), and for SpO₂/FiO₂ 200 < 300—OR 1.62 (1.06-2.42, P = .025). The discriminatory characteristics of the multivariable model and SpO₂/FiO₂ as a single variable demonstrated area under the curve (AUC) of 0.81 and AUC of 0.74, respectively. Conclusions: The SpO₂/FiO₂, measured within the first 6 hours after hospital admission, is an independent indicator of ARDS development among patients at risk.

Inhaled corticosteroids are commonly prescribed for patients with severe chronic obstructive pulmonary disease. Although their use improves quality of life and reduces exacerbations, it is associated with increased risk of pneumonia. Curiously, their use has not been associated with increased risk of pneumonia-related or overall mortality. We review pertinent literature to further explore the effects of inhaled corticosteroids on incident pneumonia and mortality in patients with chronic obstructive pulmonary disease. The association of use of inhaled corticosteroids and incident pneumonia is substantial and has been present in the majority of the studies on the topic. This includes both randomized controlled trials and observational studies. However, all of the studies have substantial risk of bias. Most randomized trials are limited by lack of systematic ascertainment of pneumonia; they depended on adverse event reporting. Many observational studies included proper radiographic assessment of pneumonia, but they are limited by their retrospective, observational design. The unadjusted higher risk of pneumonia is associated with longer duration of use, more potent ICS compounds, and higher doses. That implies a dose–effect relationship. Unlike pneumonia, mortality is a precise outcome. Despite the robust association of inhaled corticosteroid use with increased risk of pneumonia, all studies find either no difference or a reduction in pulmonary-related and overall mortality associated with the use of inhaled corticosteroids. These observations suggest a double effect of inhaled corticosteroids (i.e., an adverse effect plus an unexplained mitigating effect).

Limited critical care subspecialty training and experience is available in many low- and middle-income countries, creating barriers to the delivery of evidence-based critical care. We hypothesized that a structured tele-education critical care program using case-based learning and ICU management principles is an efficient method for knowledge translation and quality improvement in this setting. Weekly 45-min case-based tele-education rounds were conducted in the recently established medical intensive care unit (MICU) in Banja Luka, Bosnia and Herzegovina. The Checklist for Early Recognition and Treatment of Acute Illness (CERTAIN) was used as a platform for structured evaluation of critically ill cases. Two practicing US intensivists fluent in the local language served as preceptors using a secure two-way video communication platform. Intensive care unit structure, processes, and outcomes were evaluated before and after the introduction of the tele-education intervention. Patient demographics and acuity were similar before (2015) and 2 years after (2016 and 2017) the intervention. Sixteen providers (10 physicians, 4 nurses, and 2 physical therapists) evaluated changes in the ICU structure and processes after the intervention. Structural changes prompted by the intervention included standardized admission and rounding practices, incorporation of a pharmacist and physical therapist into the interprofessional ICU team, development of ICU antibiogram and hand hygiene programs, and ready access to point of care ultrasound. Process changes included daily sedation interruption, protocolized mechanical ventilation management and liberation, documentation of daily fluid balance with restrictive fluid and transfusion strategies, daily device assessment, and increased family presence and participation in care decisions. Less effective (dopamine, thiopental, aminophylline) or expensive (low molecular weight heparin, proton pump inhibitor) medications were replaced with more effective (norepinephrine, propofol) or cheaper (unfractionated heparin, H2 blocker) alternatives. The intervention was associated with reduction in ICU (43% vs 27%) and hospital (51% vs 44%) mortality, length of stay (8.3 vs 3.6 days), cost savings ($400,000 over 2 years), and a high level of staff satisfaction and engagement with the tele-education program. Weekly, structured case-based tele-education offers an attractive option for knowledge translation and quality improvement in the emerging ICUs in low- and middle-income countries.