To calculate an index (termed Pmusc/Eadi index) relating the pressure generated by the respiratory muscles (Pmusc) to the electrical activity of the diaphragm (Eadi), during assisted mechanical ventilation and to assess if the Pmusc/Eadi index is affected by the type and level of ventilator assistance. The Pmusc/Eadi index was also used to measure the patient's inspiratory effort from Eadi without esophageal pressure. Crossover study. One general ICU. Ten patients undergoing assisted ventilation. Pressure support and neurally adjusted ventilator assist delivered, each, at three levels of ventilatory assistance. Airways flow and pressure, esophageal pressure, and Eadi were continuously recorded. Sixty tidal volumes for each ventilator settings were analyzed off-line, at three time points during inspiration. For each time point, Pmusc/Eadi index was calculated. Pmusc/Eadi index was also calculated from airway pressure drop during end-expiratory occlusions. Pmusc/Eadi index was very variable among patients, but within one patient it was not affected by type and level of ventilator assistance. Pmusc/Eadi index decreased during the inspiration. Pmusc/Eadi index obtained during an occlusion from airway pressure swing was tightly correlated with that derived from esophageal pressure during tidal ventilation and allowed to estimate pressure time product. Pmusc is tightly related to Eadi, by a proportionality coefficient that we termed Pmusc/Eadi index, stable within each patient under different conditions of ventilator assistance. The derivation of the Pmusc/Eadi index from Eadi and airway pressure during an expiratory occlusion enables a continuous estimate of patient's inspiratory effort.

Preservation of spontaneous breathing (SB) is sometimes debated because it has potentially both negative and positive effects on lung injury in comparison with fully controlled mechanical ventilation (CMV). We wanted (1) to verify in mechanically ventilated patients if the change in transpulmonary pressure was similar between pressure support ventilation (PSV) and CMV for a similar tidal volume, (2) to estimate the influence of SB on alveolar pressure (Palv), and (3) to determine whether a reliable plateau pressure could be measured during pressure support ventilation (PSV). We studied ten patients equipped with esophageal catheters undergoing three levels of PSV followed by a phase of CMV. For each condition, we calculated the maximal and mean transpulmonary (ΔPL) swings and Palv. Overall, ΔPL was similar between CMV and PSV, but only loosely correlated. The differences in ΔPL between CMV and PSV were explained largely by different inspiratory flows, indicating that the resistive pressure drop caused this difference. By contrast, the Palv profile was very different between CMV and SB; SB led to progressively more negative Palv during inspiration, and Palv became lower than the set positive end-expiratory pressure in nine of ten patients at low PSV. Finally, inspiratory occlusion holds performed during PSV led to plateau and Δ PL pressures comparable with those measured during CMV. Under similar conditions of flow and volume, transpulmonary pressure change is similar between CMV and PSV. SB during mechanical ventilation can cause remarkably negative swings in Palv, a mechanism by which SB might potentially induce lung injury.

Purpose The soluble receptor for advanced glycation end-products (sRAGE) is a marker of lung epithelial injury and alveolar fluid clearance (AFC), with promising values for assessing prognosis and lung injury severity in acute respiratory distress syndrome (ARDS). Because AFC is impaired in most patients with ARDS and is associated with higher mortality, we hypothesized that baseline plasma sRAGE would predict mortality, independently of two key mediators of ventilator-induced lung injury. Methods We conducted a meta-analysis of individual data from 746 patients enrolled in eight prospective randomized and observational studies in which plasma sRAGE was measured in ARDS articles published through March 2016. The primary outcome was 90-day mortality. Using multivariate and mediation analyses, we tested the association between baseline plasma sRAGE and mortality, independently of driving pressure and tidal volume. Results Higher baseline plasma sRAGE [odds ratio (OR) for each one-log increment, 1.18; 95% confidence interval (CI) 1.01–1.38; P = 0.04], driving pressure (OR for each one-point increment, 1.04; 95% CI 1.02–1.07; P = 0.002), and tidal volume (OR for each one-log increment, 1.98; 95% CI 1.07–3.64; P = 0.03) were independently associated with higher 90-day mortality in multivariate analysis. Baseline plasma sRAGE mediated a small fraction of the effect of higher ΔP on mortality but not that of higher V_T. Conclusions Higher baseline plasma sRAGE was associated with higher 90-day mortality in patients with ARDS, independently of driving pressure and tidal volume, thus reinforcing the likely contribution of alveolar epithelial injury as an important prognostic factor in ARDS. Registration: PROSPERO (ID: CRD42018100241).

Acute respiratory distress syndrome is characterized by collapse of gravitationally dependent lung regions that usually diverts tidal ventilation toward nondependent regions. We hypothesized that higher positive end-expiratory pressure and enhanced spontaneous breathing may increase the proportion of tidal ventilation reaching dependent lung regions in patients with acute respiratory distress syndrome undergoing pressure support ventilation. Prospective, randomized, cross-over study. General and neurosurgical ICUs of a single university-affiliated hospital. We enrolled ten intubated patients recovering from acute respiratory distress syndrome, after clinical switch from controlled ventilation to pressure support ventilation. We compared, at the same pressure support ventilation level, a lower positive end-expiratory pressure (i.e., clinical positive end-expiratory pressure = 7 ± 2 cm H2O) with a higher one, obtained by adding 5 cm H2O (12 ± 2 cm H2O). Furthermore, a pressure support ventilation level associated with increased respiratory drive (3 ± 2 cm H2O) was tested against resting pressure support ventilation (12 ± 3 cm H2O), at clinical positive end-expiratory pressure. During all study phases, we measured, by electrical impedance tomography, the proportion of tidal ventilation reaching dependent and nondependent lung regions (Vt%dep and Vt%(nondep)), regional tidal volumes (Vt(dep) and Vt(nondep)), and antero-posterior ventilation homogeneity (Vt%nondep/Vt%dep). We also collected ventilation variables and arterial blood gases. Application of higher positive end-expiratory pressure levels increased Vt%dep and Vtdep values and decreased Vt%nondep/Vt%dep ratio, as compared with lower positive end-expiratory pressure (p < 0.01). Similarly, during lower pressure support ventilation, Vt%dep increased, Vtnondep decreased, and Vtdep did not change, likely indicating a higher efficiency of posterior diaphragm that led to decreased Vt%nondep/Vt%dep (p < 0.01). Finally, PaO2/FIO2 ratios correlated with Vt%dep during all study phases (p < 0.05). In patients with acute respiratory distress syndrome undergoing pressure support ventilation, higher positive end-expiratory pressure and lower support levels increase the fraction of tidal ventilation reaching dependent lung regions, yielding more homogeneous ventilation and, possibly, better ventilation/perfusion coupling.

Pentraxin 3 is a fluid phase receptor involved in innate immunity. It belongs to the Pentraxins family, as C-reactive protein does. Pentraxin 3 is produced by a variety of tissue cells, whereas only the liver produces C-reactive protein. Pentraxin 3 plays a unique role in the regulation of inflammation. Acute lung injury and acute respiratory distress syndrome are characterized by an important inflammatory reaction. We investigated the role of pentraxin 3 as a marker of severity and outcome predictor of acute lung injury and acute respiratory distress syndrome. We measured circulating pentraxin 3 and C-reactive protein levels within 24 hrs from intubation (day 1), after 24 hrs from the first sample, then every 3 days for the first month and then once a week, until discharge from the intensive care unit. Pentraxin 3 was also measured in bronchoalveolar lavages, performed when clinically indicated. One university medical center general intensive care unit. The study included 21 patients affected by acute lung injury and acute respiratory distress syndrome (1994 Consensus Conference criteria). None. Pentraxin 3 plasma levels were high with a peak on the first day (median 71.05 ng/mL, interquartile range 52.37-117.38 ng/mL, normal values <2 ng/mL), declining thereafter. C-reactive protein peaked later and remained at relatively high values. Out of several day 1 parameters, pentraxin 3 was the only significant difference between survivors and nonsurvivors. Pentraxin 3 levels were positively correlated with lung injury score values (p < 0.001) and number of organ failures (p < 0.001). Pentraxin 3 was present in bronchoalveolar lavages fluids (5.03 ng/mL, interquartile range 1.52-8.48 ng/mL) and bronchoalveolar lavages positive to bacterial culture were associated with significantly higher pentraxin 3 values (p < 0.05). The results presented here show that pentraxin 3 is elevated in acute lung injury and acute respiratory distress syndrome and that its levels correlate with parameters of lung injury and systemic involvement. The clinical and pathophysiological significance of pentraxin 3 in acute lung injury and acute respiratory distress syndrome deserves further scrutiny.