BACKGROUND Survival of patients with acute lung injury or the acute respiratory distress syndrome (ARDS) has been improved by ventilation with small tidal volumes and the use of positive end-expiratory pressure (PEEP); however, the optimal level of PEEP has been difficult to determine. In this pilot study, we estimated transpulmonary pressure with the use of esophageal balloon catheters. We reasoned that the use of pleural-pressure measurements, despite the technical limitations to the accuracy of such measurements, would enable us to find a PEEP value that could maintain oxygenation while preventing lung injury due to repeated alveolar collapse or overdistention. METHODS We randomly assigned patients with acute lung injury or ARDS to undergo mechanical ventilation with PEEP adjusted according to measurements of esophageal pressure (the esophageal-pressure–guided group) or according to the Acute Respiratory Distress Syndrome Network standard-of-care recommendations (the control group). The primary end point was improvement in oxygenation. The secondary end points included respiratory-system compliance and patient outcomes. RESULTS The study reached its stopping criterion and was terminated after 61 patients had been enrolled. The ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen at 72 hours was 88 mm Hg higher in the esophageal-pressure–guided group than in the control group (95% confidence interval, 78.1 to 98.3; P = 0.002). This effect was persistent over the entire follow-up time (at 24, 48, and 72 hours; P = 0.001 by repeated-measures analysis of variance). Respiratory-system compliance was also significantly better at 24, 48, and 72 hours in the esophageal-pressure–guided group (P = 0.01 by repeated-measures analysis of variance). CONCLUSIONS As compared with the current standard of care, a ventilator strategy using esophageal pressures to estimate the transpulmonary pressure significantly improves oxygenation and compliance. Multicenter clinical trials are needed to determine whether this approach should be widely adopted. (ClinicalTrials.gov number, NCT00127491.)

Background-Statins have anti-inflammatory properties that are independent of their lipid-lowering abilities. We hypothesized that statin therapy before the onset of an acute bacterial infection may have a protective effect against severe sepsis.

ARDS seems to be a common and fatal syndrome in a hospital in Rwanda, with few patients admitted to an ICU. The Berlin definition is likely to underestimate the impact of ARDS in low-income countries, where resources to meet the definition requirements are lacking. Although the Kigali modification requires validation before widespread use, we hope this study stimulates further work in refining an ARDS definition that can be consistently used in all settings.

Importance: Adjusting positive end-expiratory pressure (PEEP) to offset pleural pressure might attenuate lung injury and improve patient outcomes in acute respiratory distress syndrome (ARDS). Objective: To determine whether PEEP titration guided by esophageal pressure (PES), an estimate of pleural pressure, was more effective than empiric high PEEP-FiO2 in moderate-to-severe ARDS. Design, Setting, and Participants: Phase-II randomized clinical trial conducted at 14 hospitals in North America. Two hundred mechanically ventilated patients aged ≥ 16 years with moderate-to-severe ARDS (PaO2:FiO2 ≤ 200) were enrolled between October 31, 2012 and September 14, 2017; long-term follow-up completed July 30, 2018. Interventions: Participants were randomized to PES-guided PEEP (n = 102) or empiric high PEEP-FiO2 (n = 98). All participants received low tidal volumes. Main Outcomes and Measures: The primary outcome was a ranked composite score incorporating death and days free from mechanical ventilation among survivors through day 28. Pre-specified secondary outcomes included 28-day mortality, days free from mechanical ventilation among survivors, and need for rescue therapy. Results: Two hundred patients were enrolled (mean [SD] age 56 [16] years; 46% female) and completed 28-day follow-up. The primary composite endpoint was not significantly different between treatment groups (probability of more favorable outcome with PES-guided PEEP: 49.6% [95% CI 41.7% to 57.5%]; p = 0.92). At 28 days, 33 of 102 patients (32.4%) assigned to PES-guided PEEP and 33 of 98 patients (30.6%) assigned to empiric PEEP-FiO2 died (risk difference 1.7% [95% CI −11.1% to 14.6%]; p = 0.88). Days free from mechanical among survivors was not significantly different (22 [15-24] vs. 21 [16.5-24] days; median difference 0 [95% CI −1 to 2] days; p = 0.85). Patients assigned to PES-guided PEEP were significantly less likely to receive rescue therapy (4/102 [3.9%] vs. 12/98 [12.2%]; risk difference −8.3% [95% CI −15.8% to −0.8%]; p = 0.04). None of the seven other pre-specified secondary clinical endpoints were significantly different. Adverse events included gross barotrauma, which occurred in six patients with PES-guided PEEP and five patients with empiric PEEP-FiO2. Conclusions and Relevance: Among patients with moderate-to-severe ARDS, PES-guided PEEP, compared to empiric high PEEP-FiO2, resulted in no significant difference in death and days free from mechanical ventilation. These findings do not support PES-guided PEEP titration in ARDS. Trial Registration: ClinicalTrials.gov identifier

Increasing levels of pharmacologic acid suppression are associated with increased risks of nosocomial C difficile infection. This evidence of a dose-response effect provides further support for the potentially causal nature of iatrogenic acid suppression in the development of nosocomial C difficile infection.