Lung Recruitment Assessed by Electrical Impedance Tomography (RECRUIT): A Multicenter Study of COVID-19 Acute Respiratory Distress Syndrome.

Rationale: Defining lung recruitability is needed for safe positive end-expiratory pressure (PEEP) selection in mechanically ventilated patients. However, there is no simple bedside method including both assessment of recruitability and risks of overdistension as well as personalized PEEP titration. Objectives: To describe the range of recruitability using electrical impedance tomography (EIT), effects of PEEP on recruitability, respiratory mechanics and gas exchange, and a method to select optimal EIT-based PEEP. Methods: This is the analysis of patients with coronavirus disease (COVID-19) from an ongoing multicenter prospective physiological study including patients with moderate-severe acute respiratory distress syndrome of different causes. EIT, ventilator data, hemodynamics, and arterial blood gases were obtained during PEEP titration maneuvers. EIT-based optimal PEEP was defined as the crossing point of the overdistension and collapse curves during a decremental PEEP trial. Recruitability was defined as the amount of modifiable collapse when increasing PEEP from 6 to 24 cm H2O (ΔCollapse24-6). Patients were classified as low, medium, or high recruiters on the basis of tertiles of ΔCollapse24-6. Measurements and Main Results: In 108 patients with COVID-19, recruitability varied from 0.3% to 66.9% and was unrelated to acute respiratory distress syndrome severity. Median EIT-based PEEP differed between groups: 10 versus 13.5 versus 15.5 cm H2O for low versus medium versus high recruitability (P < 0.05). This approach assigned a different PEEP level from the highest compliance approach in 81% of patients. The protocol was well tolerated; in four patients, the PEEP level did not reach 24 cm H2O because of hemodynamic instability. Conclusions: Recruitability varies widely among patients with COVID-19. EIT allows personalizing PEEP setting as a compromise between recruitability and overdistension. Clinical trial registered with www.clinicaltrials.gov (NCT04460859).

Heterogeneity of Ventilation/Perfusion Mismatch at Different Levels of PEEP and in Mechanical Phenotypes of COVID-19 ARDS.

BACKGROUND: COVID-19-related ARDS is characterized by severe hypoxemia with initially preserved lung compliance and impaired ventilation/perfusion (V̇/Q̇) matching. PEEP can increase end-expiratory lung volume, but its effect on V̇/Q̇ 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 V̇/Q̇. Respiratory mechanics measurements, shunt, and V̇/Q̇ mismatch (low V̇/Q̇ and high V̇/Q̇) were collected at 3 PEEP levels (clinical PEEP = intermediate PEEP, low PEEP [clinical - 50%], and high PEEP [clinical + 50%]). A mixed-effect model was used to evaluate the impact of PEEP on V̇/Q̇. We also investigated if PEEP might have a different effect on V̇/Q̇ 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 PaO2 /FIO2 of 141 ± 74 mm Hg were studied at low PEEP = 5.6 ± 2.2 cm H2O, intermediate PEEP = 10.6 ± 3.8 cm H2O, and high PEEP = 15 ± 5 cm H2O. Shunt, low V̇/Q̇, high V̇/Q̇, and alveolar dead space were not significantly influenced, on average, by PEEP. Respiratory system compliance decreased significantly when increasing PEEP without significant variation of PaO2 /FIO2 (P = .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 = .048). CONCLUSIONS: In subjects with COVID-related ARDS placed on invasive mechanical ventilation for > 48 h, PEEP had a heterogeneous effect on V̇/Q̇ mismatch and, on average, higher levels were not able to reduce shunt. The subject's compliance could influence the effect of PEEP on V̇/Q̇ mismatch since an increased shunt was observed in subjects with lower compliance, whereas the opposite occurred in those with higher compliance.

Effects of PEEP on regional ventilation-perfusion mismatch in the acute respiratory distress syndrome.

PURPOSE: In the acute respiratory distress syndrome (ARDS), decreasing Ventilation-Perfusion [Formula: see text] mismatch might enhance lung protection. We investigated the regional effects of higher Positive End Expiratory Pressure (PEEP) on [Formula: see text] mismatch and their correlation with recruitability. We aimed to verify whether PEEP improves regional [Formula: see text] mismatch, and to study the underlying mechanisms. METHODS: In fifteen patients with moderate and severe ARDS, two PEEP levels (5 and 15 cmH2O) were applied in random order. [Formula: see text] mismatch was assessed by Electrical Impedance Tomography at each PEEP. Percentage of ventilation and perfusion reaching different ranges of [Formula: see text] ratios were analyzed in 3 gravitational lung regions, leading to precise assessment of their distribution throughout different [Formula: see text] mismatch compartments. Recruitability between the two PEEP levels was measured by the recruitment-to-inflation ratio method. RESULTS: In the non-dependent region, at higher PEEP, ventilation reaching the normal [Formula: see text] compartment (p = 0.018) increased, while it decreased in the high [Formula: see text] one (p = 0.023). In the middle region, at PEEP 15 cmH2O, ventilation and perfusion to the low [Formula: see text] compartment decreased (p = 0.006 and p = 0.011) and perfusion to normal [Formula: see text] increased (p = 0.003). In the dependent lung, the percentage of blood flowing through the non-ventilated compartment decreased (p = 0.041). Regional [Formula: see text] mismatch improvement was correlated to lung recruitability and changes in regional tidal volume. CONCLUSIONS: In patients with ARDS, higher PEEP optimizes the distribution of both ventilation (in the non-dependent areas) and perfusion (in the middle and dependent lung). Bedside measure of recruitability is associated with improved [Formula: see text] mismatch.

Effects of Prone Position on Lung Recruitment and Ventilation-Perfusion Matching in Patients With COVID-19 Acute Respiratory Distress Syndrome: A Combined CT Scan/Electrical Impedance Tomography Study.

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 H2O 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.

Sigh in Patients With Acute Hypoxemic Respiratory Failure and ARDS: The PROTECTION Pilot Randomized Clinical Trial.

BACKGROUND: Sigh is a cyclic brief recruitment maneuver: previous physiologic studies showed that its use could be an interesting addition to pressure support ventilation to improve lung elastance, decrease regional heterogeneity, and increase release of surfactant. RESEARCH QUESTION: Is the clinical application of sigh during pressure support ventilation (PSV) feasible? STUDY DESIGN AND METHODS: We conducted a multicenter noninferiority randomized clinical trial on adult intubated patients with acute hypoxemic respiratory failure or ARDS undergoing PSV. Patients were randomized to the no-sigh group and treated by PSV alone, or to the sigh group, treated by PSV plus sigh (increase in airway pressure to 30 cm H2O for 3 s once per minute) until day 28 or death or successful spontaneous breathing trial. The primary end point of the study was feasibility, assessed as noninferiority (5% tolerance) in the proportion of patients failing assisted ventilation. Secondary outcomes included safety, physiologic parameters in the first week from randomization, 28-day mortality, and ventilator-free days. RESULTS: Two-hundred and fifty-eight patients (31% women; median age, 65 [54-75] years) were enrolled. In the sigh group, 23% of patients failed to remain on assisted ventilation vs 30% in the no-sigh group (absolute difference, -7%; 95% CI, -18% to 4%; P = .015 for noninferiority). Adverse events occurred in 12% vs 13% in the sigh vs no-sigh group (P = .852). Oxygenation was improved whereas tidal volume, respiratory rate, and corrected minute ventilation were lower over the first 7 days from randomization in the sigh vs no-sigh group. There was no significant difference in terms of mortality (16% vs 21%; P = .337) and ventilator-free days (22 [7-26] vs 22 [3-25] days; P = .300) for the sigh vs no-sigh group. INTERPRETATION: Among hypoxemic intubated ICU patients, application of sigh was feasible and without increased risk. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03201263; URL: www.clinicaltrials.gov.

Potential for Lung Recruitment and Ventilation-Perfusion Mismatch in Patients With the Acute Respiratory Distress Syndrome From Coronavirus Disease 2019.

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 H2O 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 CO2 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 FIO2 needed to obtain viable oxygenation at lower positive end-expiratory 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.