Annals of the American Thoracic Society
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Randomized Controlled Trial
Driving Pressure-Limited Strategy for Patients with Acute Respiratory Distress Syndrome (ARDS): A Pilot Randomized Clinical Trial.
Rationale: Evidence from observational studies suggests that driving pressure is strongly associated with pulmonary injury and mortality, regardless of positive end-expiratory pressure (PEEP) levels, tidal volume, or plateau pressure. Therefore, it is possible that targeting driving pressure may improve the safety of ventilation strategies for patients with acute respiratory distress syndrome (ARDS). However, the clinical effects of a driving pressure-limited strategy for ARDS has not been assessed in randomized controlled trials. ⋯ We did not find statistically significant differences in the incidence of severe acidosis (pH < 7.10) within 7 days (absolute difference -12.1; 95% CI, -41.5 to -17.3) or any clinical secondary endpoint. Conclusions: In patients with ARDS, a trial assessing the effects of a driving pressure-limited strategy using very low tidal volumes versus a conventional ventilation strategy on clinical outcomes is feasible. Clinical trial registered with ClinicalTrials.gov (NCT02365038).
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Randomized Controlled Trial
Sex-Specific Differential Responses of Circulating Biomarkers in Obstructive Sleep Apnea Treatment. A Post Hoc Analysis of a Randomized Controlled Trial.
Rationale: Knowledge of sex-specific changes of cardiovascular biomarkers in response to continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea (OSA) is limited. Objectives: We hypothesized a differential sex-specific cardiovascular biomarker response with CPAP therapy for OSA. Methods: Participants with moderate-severe OSA (apnea-hypopnea index, 15 events/h) were randomized to CPAP versus sham and completed polysomnography and collection of biomarkers of inflammation (myeloperoxidase, fibrinogen, paraoxonase, interleukin [IL]-6, IL-6 soluble receptor, aryl esterase, oxidized low-density lipoprotein, lipoprotein A, plasminogen activator inhibitor 1, and F2-isoprostane urine/creatinine ratio) and vascular measures at baseline and 8 weeks of therapy with either CPAP (n = 72) or sham treatment (n = 70). ⋯ Conclusions: Differential sex-specific responses to CPAP therapy for OSA were observed for circulating inflammatory biomarkers, which persisted after adjustment for confounders. These findings set the stage for validation studies and, if confirmed, biochemical pathway elucidation to inform sex-specific personalized treatment approaches. Clinical trial registered with www.clinicaltrials.gov (NCT00607893).
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Multicenter Study Observational Study
Do Ambient Ozone or Other Pollutants Modify Effects of Controlled Ozone Exposure on Pulmonary Function?
Rationale: In a previous trial (MOSES [Multicenter Ozone Study of oldEr Subjects]), 3 hours of controlled ozone (O3) exposure caused concentration-related reductions in lung function with evidence of airway inflammation and injury, but without convincing evidence of effects on cardiovascular function. However, the subjects' exposures to indoor and outdoor air pollution in the hours and days before each controlled O3 exposure may have modified biomarker responses to the controlled O3 exposures. Objectives: We sought to determine whether personal measures of nitrogen dioxide (NO2) and O3, or ambient concentrations of O3, particulate matter ≤2.5 μm in aerodynamic diameter, NO2, carbon monoxide (CO), and sulfur dioxide (SO2) in the 72 and 96 hours before the exposure visit modified biomarker responses to controlled O3 exposure. ⋯ There was no such modification of the effect of controlled O3 exposure on any other cardiopulmonary outcome group. Conclusions: Reductions in markers of lung function, but not other pathways, by the MOSES controlled O3 exposure were modified by ambient NO2 and CO, and PES NO2, and these reductions were observed only when these pollutant concentrations were elevated in the hours and days before the pre-exposure visit. Clinical trial registered with ClinicalTrials.gov (NCT01487005).
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Rationale: Sleep-disordered breathing (SDB) occurring primarily during rapid eye movement (REM) sleep is a common clinical problem. The natural history of REM-related SDB and the associated cardiovascular sequelae of disease progression remain to be determined. Objectives: The objective of the current study was to describe the natural history of REM-related SDB, ascertain predictors of progression, and determine whether the evolution of REM-related SDB into non-REM (NREM) sleep is associated with incident cardiovascular events. ⋯ Progression of SDB into NREM sleep is associated with sex, weight, and age. SDB during REM and NREM sleep tends to develop concurrently. Finally, the development of SDB during NREM sleep is associated with incident cardiovascular events, but only in women with REM-related SDB at baseline.
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Intensive care units (ICUs) are an appropriate focus of antibiotic stewardship program efforts because a large proportion of any hospital's use of parenteral antibiotics, especially broad-spectrum, occurs in the ICU. Given the importance of antibiotic stewardship for critically ill patients and the importance of critical care practitioners as the front line for antibiotic stewardship, a workshop was convened to specifically address barriers to antibiotic stewardship in the ICU and discuss tactics to overcome these. The working definition of antibiotic stewardship is "the right drug at the right time and the right dose for the right bug for the right duration." A major emphasis was that antibiotic stewardship should be a core competency of critical care clinicians. ⋯ Instead, it should enhance care both for individual patients (by improving and individualizing their choice of antibiotic) and for the ICU population as a whole. Opportunities for antibiotic stewardship in common ICU infections, including community- and hospital-acquired pneumonia and sepsis, are discussed. Intensivists can partner with antibiotic stewardship programs to address barriers and improve patient care.