As of June 16, 2020, 8 251 224 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and 445 188 coronavirus disease 2019 (COVID-19)–related deaths had been reported worldwide.¹ Among active cases, 1.6% (54 593 of 3 503 249) are in severe or critical condition.

Rationale: During acute lung injury (ALI), mechanical ventilation can aggravate inflammation by promoting alveolar distension and cyclic recruitment–derecruitment. As an estimate of the intensity of inflammation, metabolic activity can be measured by positron emission tomography imaging of [18F]fluoro-2-deoxy-D-glucose. Objectives: To assess the relationship between gas volume changes induced by tidal ventilation and pulmonary metabolic activity in patients with ALI. Methods: In 13 mechanically ventilated patients with ALI and relatively high positive end-expiratory pressure, we performed a positron emission tomography scan of the chest and three computed tomography scans: at mean airway pressure, end-expiration, and end-inspiration. Metabolic activity was measured from the [18F]fluoro-2-deoxy-D-glucose uptake rate. The computed tomography scans were used to classify lung regions as derecruited throughout the respiratory cycle, undergoing recruitment–derecruitment, and normally aerated. Measurements and Main Results: Metabolic activity of normally aerated lung was positively correlated both with plateau pressure, showing a pronounced increase above 26 to 27 cm H2O, and with regional Vt normalized by end-expiratory lung gas volume. This relationship did not appear to be caused by a higher underlying parenchymal metabolic activity in patients with higher plateau pressure. Regions undergoing cyclic recruitment–derecruitment did not have higher metabolic activity than those collapsed throughout the respiratory cycle. Conclusions: In patients with ALI managed with relatively high end-expiratory pressure, metabolic activity of aerated regions was associated with both plateau pressure and regional Vt normalized by end-expiratory lung gas volume, whereas no association was found between cyclic recruitment–derecruitment and increased metabolic activity.

Critically ill intubated patients are positioned in the semirecumbent position to prevent pneumonia. In tracheally intubated sheep, we investigated the effects of gravitational force on tracheal mucus transport and on bacterial colonization of the respiratory system. Prospective randomized animal study. Animal research facility at the National Institutes of Health. Sixteen healthy sheep. Spontaneously breathing or mechanically ventilated sheep were randomized to be positioned with the orientation of the trachea above (40 degrees, trachea-up) or below (5 degrees, trachea-down) horizontal. Tracheal mucus velocity was measured through radiographic tracking of radiopaque tantalum disks, insufflated into the trachea. After 24 hrs, sheep were euthanized, and samples from the airways and lungs were taken for microbiological analysis. The proximal trachea was colonized in all sheep. In trachea-down sheep, all mucus moved toward the glottis at a mean velocity of 2.1 +/- 1.1 mm/min. When mucus reached the endotracheal tube, it either entered the endotracheal tube or was lodged at the inflated endotracheal tube cuff. In all trachea-up sheep, abnormal tracheal mucus clearance was found. Mucus, mostly on the nondependent part of the trachea, moved toward the glottis at an average velocity of 2.2 +/- 2.0 mm/min and constantly accumulated at the inflated endotracheal tube cuff. From the proximal trachea, mucus eventually moved toward the lungs on the dependent part of the trachea, leading to an "intratracheal route" of colonization of the lungs. Pneumonia was found in 6/8 of trachea-up sheep and the same microorganisms were isolated from the lungs and the proximal trachea. No pneumonia was found in trachea-down sheep (p = .007). The study indicates that following tracheal intubation gravitational force influences tracheal mucus clearance. When the trachea is oriented above horizontal, a flow of mucus from the proximal trachea toward the lungs is highly associated with bacterial colonization of the airways and pneumonia.

Rationale: Prone positioning reduces mortality in patients with severe acute respiratory distress syndrome (ARDS). To date, no evidence supports the use of prone positioning (PP) during venovenous extracorporeal oxygenation (ECMO). Objectives: The aim of the study was to assess the feasibility, safety, and effect on oxygenation and lung mechanics of PP during ECMO. As a secondary exploratory aim, we assessed the association between PP and hospital mortality. Methods: We performed a multicenter retrospective cohort study in six Italian ECMO centers, including patients managed with PP during ECMO support (prone group; four centers) and patients managed in the supine position (control group; two centers). Physiological variables were analyzed at four time points (supine before PP, start of PP, end of PP, and supine after PP). The association between PP and hospital mortality was assessed by multivariate analysis and propensity score–matching. Results: A total of 240 patients were included, with 107 in the prone group and 133 in the supine group. The median duration of the 326 pronation cycles was 15 (12–18) hours. Minor reversible complications were reported in 6% of PP maneuvers. PP improved oxygenation and reduced intrapulmonary shunt. Unadjusted hospital mortality was lower in the prone group (34 vs. 50%; P = 0.017). After adjusting for covariates, PP remained significantly associated with a reduction of hospital mortality (odds ratio, 0.50; 95% confidence interval, 0.29–0.87). Sixty-six propensity score–matched patients were identified in each group. In this matched sample, patients who underwent pronation had higher ECMO duration (16 vs. 10 d; P = 0.0344) but lower hospital mortality (30% vs. 53%; P = 0.0241). Conclusions: PP during ECMO improved oxygenation and was associated with a reduction of hospital mortality.