Objectives: Severe cases of coronavirus disease 2019 develop the acute respiratory distress syndrome, requiring admission to the ICU. This study aimed to describe specific pathophysiological characteristics of acute respiratory distress syndrome from coronavirus disease 2019. Design: Prospective crossover physiologic study. Setting: ICU of a university-affiliated hospital from northern Italy dedicated to care of patients with confirmed diagnosis of coronavirus disease 2019. Patients: Ten intubated patients with acute respiratory distress syndrome and confirmed diagnosis of coronavirus disease 2019. Interventions: We performed a two-step positive end-expiratory pressure trial with change of 10 cm H 2 O in random order. Measurements and Main Results: At each positive end-expiratory pressure level, we assessed arterial blood gases, respiratory mechanics, ventilation inhomogeneity, and potential for lung recruitment by electrical impedance tomography. Potential for lung recruitment was assessed by the recently described recruitment to inflation ratio. In a subgroup of seven paralyzed patients, we also measured ventilation-perfusion mismatch at lower positive end-expiratory pressure by electrical impedance tomography. At higher positive end-expiratory pressure, respiratory mechanics did not change significantly: compliance remained relatively high with low driving pressure. Oxygenation and ventilation inhomogeneity improved but arterial co 2 increased despite unchanged respiratory rate and tidal volume. The recruitment to inflation ratio presented median value higher than previously reported in acute respiratory distress syndrome patients but with large variability (median, 0.79 [0.53-1.08]; range, 0.16-1.40). The Fio 2 needed to obtain viable oxygenation at lower positive endexpiratory pressure was significantly correlated with the recruitment to inflation ratio (r = 0.603; p = 0.05). The ventilation-perfusion mismatch was elevated (median, 34% [32-45%] of lung units) and, in six out of seven patients, ventilated nonperfused units represented a much larger proportion than perfused nonventilated ones. Conclusions: In patients with acute respiratory distress syndrome from coronavirus disease 2019, potential for lung recruitment presents large variability, while elevated dead space fraction may be a specific pathophysiological trait. These findings may guide selection of personalized mechanical ventilation settings. (Crit

OBJECTIVES: Prone positioning allows to improve oxygenation and decrease mortality rate in COVID-19–associated acute respiratory distress syndrome (C-ARDS). However, the mechanisms leading to these effects are not fully understood. The aim of this study is to assess the physiologic effects of pronation by the means of CT scan and electrical impedance tomography (EIT). DESIGN: Experimental, physiologic study. SETTING: Patients were enrolled from October 2020 to March 2021 in an Italian dedicated COVID-19 ICU. PATIENTS: Twenty-one intubated patients with moderate or severe C-ARDS. INTERVENTIONS: First, patients were transported to the CT scan facility, and image acquisition was performed in prone, then supine position. Back to the ICU, gas exchange, respiratory mechanics, and ventilation and perfusion EIT-based analysis were provided toward the end of two 30 minutes steps (e.g., in supine, then prone position). MEASUREMENTS AND MAIN RESULTS: Prone position induced recruitment in the dorsal part of the lungs (12.5% ± 8.0%; p < 0.001 from baseline) and derecruitment in the ventral regions (–6.9% ± 5.2%; p < 0.001). These changes led to a global increase in recruitment (6.0% ± 6.7%; p < 0.001). Respiratory system compliance did not change with prone position (45 ± 15 vs 45 ± 18 mL/cm H 2 O in supine and prone position, respectively; p = 0.957) suggesting a decrease in atelectrauma. This hypothesis was supported by the decrease of a time-impedance curve concavity index designed as a surrogate for atelectrauma (1.41 ± 0.16 vs 1.30 ± 0.16; p = 0.001). Dead space measured by EIT was reduced in the ventral regions of the lungs, and the dead-space/shunt ratio decreased significantly (5.1 [2.3–23.4] vs 4.3 [0.7–6.8]; p = 0.035), showing an improvement in ventilation-perfusion matching. CONCLUSIONS: Several changes are associated with prone position in C-ARDS: increased lung recruitment, decreased atelectrauma, and improved ventilation-perfusion matching. These physiologic effects may be associated with more protective ventilation.

Personalised mechanical ventilation tailored to lung morphology versus low positive end-expiratory pressure for patients with acute respiratory distress syndrome in France (the LIVE study): a multicentre, single-blind, randomised controlled trial. Lancet Respir Med 2019;7:870-80.

BACKGROUND: COVID-19-related ARDS is characterized by severe hypoxemia with initially preserved lung compliance and impaired ventilation/perfusion (V ˙/Q ˙) matching. PEEP can increase end-expiratory lung volume, but its effect on V ˙/Q ˙mismatch in COVID-19-related ARDS is not clear. METHODS: We enrolled intubated and mechanically ventilated subjects with COVID-19 ARDS and used the automatic lung parameter estimator (ALPE) to measure V ˙/Q ˙. Respiratory mechanics measurements, shunt, and V ˙/Q ˙mismatch (low V ˙/Q ˙and high V ˙/Q ˙) were collected at 3 PEEP levels (clinical PEEP 5 intermediate PEEP, low PEEP [clinical 2 50%], and high PEEP [clinical + 50%]). A mixed-effect model was used to evaluate the impact of PEEP on V ˙/Q ˙. We also investigated if PEEP might have a different effect on V ˙/Q ˙mismatch in 2 different respiratory mechanics phenotypes, that is, high elastance/low compliance (phenotype H) and low elastance/high compliance (phenotype L). RESULTS: Seventeen subjects with COVID-related ARDS age 66 [60-71] y with a P aO 2 /F IO 2 of 141 6 74 mm Hg were studied at low PEEP 5 5.6 6 2.2 cm H 2 O, intermediate PEEP 5 10.6 6 3.8 cm H 2 O, and high PEEP 5 15 6 5 cm H 2 O. Shunt, low V ˙/Q ˙, high V ˙/Q ˙, and alveolar dead space were not significantly influenced, on average, by PEEP. Respiratory system compliance decreased significantly when increasing PEEP without significant variation of P aO 2 /F IO 2 (P 5 .26). In the 2 phenotypes, PEEP had opposite effects on shunt, with a decrease in the phenotype L and an increase in phenotype H (P 5 .048). CONCLUSIONS: In subjects with COVID-related ARDS placed on invasive mechanical ventilation for > 48 h, PEEP had a heterogeneous effect on V ˙/Q ˙mismatch and, on average, higher levels were not able to reduce shunt. The subject's compliance could influence the effect of PEEP on V ˙/Q ˙mismatch since an increased shunt was observed in subjects with lower compliance, whereas the opposite occurred in those with higher compliance.

Transpulmonary driving pressure (DPL) corresponds to the cyclical stress imposed on the lung parenchyma during tidal breathing and, therefore, can be used to assess the risk of ventilator-induced lung injury (VILI). Its measurement at the bedside requires the use of esophageal pressure (Peso), which is sometimes technically challenging. Recently, it has been demonstrated how in an animal model of ARDS, the transpulmonary pressure (PL) measured with Peso calculated with the absolute values method (PL = Paw—Peso) is equivalent to the transpulmonary pressure directly measured using pleural sensors in the central-dependent part of the lung. We hypothesized that, since the PL derived from Peso reflects the regional behavior of the lung, it could exist a relationship between regional parameters measured by electrical impedance tomography (EIT) and driving PL (DPL). Moreover, we explored if, by integrating airways pressure data and EIT data, it could be possible to estimate non-invasively DPL and consequently lung elastance (EL) and elastance-derived inspiratory PL (PI). We analyzed 59 measurements from 20 patients with ARDS. There was a significant intra-patient correlation between EIT derived regional compliance in regions of interest (ROI1) (r = 0.5, p = 0.001), ROI2 (r = −0.68, p &lt; 0.001), and ROI3 (r = −0.4, p = 0.002), and DPL. A multiple linear regression successfully predicted DPL based on respiratory system elastance (Ers), ideal body weight (IBW), roi1%, roi2%, and roi3% (R2 = 0.84, p &lt; 0.001). The corresponding Bland-Altmann analysis showed a bias of −1.4e-007 cmH2O and limits of agreement (LoA) of −2.4–2.4 cmH2O. EL and PI calculated using EIT showed good agreement (R2 = 0.89, p &lt; 0.001 and R2 = 0.75, p &lt; 0.001) with the esophageal derived correspondent variables. In conclusion, DPL has a good correlation with EIT-derived parameters in the central lung. DPL, PI, and EL can be estimated with good accuracy non-invasively combining information coming from EIT and airway pressure.