Associations of early changes in lung ultrasound aeration scores and mortality in invasively ventilated patients: a post hoc analysis.

BACKGROUND: Lung ultrasound (LUS) in an emerging technique used in the intensive care unit (ICU). The derivative LUS aeration score has been shown to have associations with mortality in invasively ventilated patients. This study assessed the predictive value of baseline and early changes in LUS aeration scores in critically ill invasively ventilated patients with and without ARDS (Acute Respiratory Distress Syndrome) on 30- and 90-day mortality. METHODS: This is a post hoc analysis of a multicenter prospective observational cohort study, which included patients admitted to the ICU with an expected duration of ventilation for at least 24 h. We restricted participation to patients who underwent a 12-region LUS exam at baseline and had the primary endpoint (30-day mortality) available. Logistic regression was used to analyze the primary and secondary endpoints. The analysis was performed for the complete patient cohort and for predefined subgroups (ARDS and no ARDS). RESULTS: A total of 442 patients were included, of whom 245 had a second LUS exam. The baseline LUS aeration score was not associated with mortality (1.02 (95% CI: 0.99 - 1.06), p = 0.143). This finding was not different in patients with and in patients without ARDS. Early deterioration of the LUS score was associated with mortality (2.09 (95% CI: 1.01 - 4.3), p = 0.046) in patients without ARDS, but not in patients with ARDS or in the complete patient cohort. CONCLUSION: In this cohort of critically ill invasively ventilated patients, the baseline LUS aeration score was not associated with 30- and 90-day mortality. An early change in the LUS aeration score was associated with mortality, but only in patients without ARDS. TRIAL REGISTRATION: ClinicalTrials.gov, ID NCT04482621.

Prognostic Value of the Radiographic Assessment of Lung Edema Score in Mechanically Ventilated ICU Patients.

INTRODUCTION: The Radiographic Assessment of Lung Edema (RALE) score provides a semi-quantitative measure of pulmonary edema. In patients with acute respiratory distress syndrome (ARDS), the RALE score is associated with mortality. In mechanically ventilated patients in the intensive care unit (ICU) with respiratory failure not due to ARDS, a variable degree of lung edema is observed as well. We aimed to evaluate the prognostic value of RALE in mechanically ventilated ICU patients. METHODS: Secondary analysis of patients enrolled in the 'Diagnosis of Acute Respiratory Distress Syndrome' (DARTS) project with an available chest X-ray (CXR) at baseline. Where present, additional CXRs at day 1 were analysed. The primary endpoint was 30-day mortality. Outcomes were also stratified for ARDS subgroups (no ARDS, non-COVID-ARDS and COVID-ARDS). RESULTS: 422 patients were included, of which 84 had an additional CXR the following day. Baseline RALE scores were not associated with 30-day mortality in the entire cohort (OR: 1.01, 95% CI: 0.98-1.03, p = 0.66), nor in subgroups of ARDS patients. Early changes in RALE score (baseline to day 1) were only associated with mortality in a subgroup of ARDS patients (OR: 1.21, 95% CI: 1.02-1.51, p = 0.04), after correcting for other known prognostic factors. CONCLUSIONS: The prognostic value of the RALE score cannot be extended to mechanically ventilated ICU patients in general. Only in ARDS patients, early changes in RALE score were associated with mortality.

Biomarkers of alveolar epithelial injury and endothelial dysfunction are associated with scores of pulmonary edema in invasively ventilated patients.

Pulmonary edema is a central hallmark of acute respiratory distress syndrome (ARDS). Endothelial dysfunction and epithelial injury contribute to alveolar-capillary permeability but their differential contribution to pulmonary edema development remains understudied. Plasma levels of surfactant protein-D (SP-D), soluble receptor for advanced glycation end products (sRAGE), and angiopoietin-2 (Ang-2) were measured in a prospective, multicenter cohort of invasively ventilated patients. Pulmonary edema was quantified using the radiographic assessment of lung edema (RALE) and global lung ultrasound (LUS) score. Variables were collected within 48 h after intubation. Linear regression was used to examine the association of the biomarkers with pulmonary edema. In 362 patients, higher SP-D, sRAGE, and Ang-2 concentrations were significantly associated with higher RALE and global LUS scores. After stratification by ARDS subgroups (pulmonary, nonpulmonary, COVID, non-COVID), the positive association of SP-D levels with pulmonary edema remained, whereas sRAGE and Ang-2 showed less consistent associations throughout the subgroups. In a multivariable analysis, SP-D levels were most strongly associated with pulmonary edema when combined with sRAGE (RALE score: ßSP-D = 6.79 units/log10 pg/mL, ßsRAGE = 3.84 units/log10 pg/mL, R2 = 0.23; global LUS score: ßSP-D = 3.28 units/log10 pg/mL, ßsRAGE = 2.06 units/log10 pg/mL, R2 = 0.086), whereas Ang-2 did not further improve the model. Biomarkers of epithelial injury and endothelial dysfunction were associated with pulmonary edema in invasively ventilated patients. SP-D and sRAGE showed the strongest association, suggesting that epithelial injury may form a final common pathway in the alveolar-capillary barrier dysfunction underlying pulmonary edema.

Latent class analysis of imaging and clinical respiratory parameters from patients with COVID-19-related ARDS identifies recruitment subphenotypes.

BACKGROUND: Patients with COVID-19-related acute respiratory distress syndrome (ARDS) require respiratory support with invasive mechanical ventilation and show varying responses to recruitment manoeuvres. In patients with ARDS not related to COVID-19, two pulmonary subphenotypes that differed in recruitability were identified using latent class analysis (LCA) of imaging and clinical respiratory parameters. We aimed to evaluate if similar subphenotypes are present in patients with COVID-19-related ARDS. METHODS: This is the retrospective analysis of mechanically ventilated patients with COVID-19-related ARDS who underwent CT scans at positive end-expiratory pressure of 10 cmH2O and after a recruitment manoeuvre at 20 cmH2O. LCA was applied to quantitative CT-derived parameters, clinical respiratory parameters, blood gas analysis and routine laboratory values before recruitment to identify subphenotypes. RESULTS: 99 patients were included. Using 12 variables, a two-class LCA model was identified as best fitting. Subphenotype 2 (recruitable) was characterized by a lower PaO2/FiO2, lower normally aerated lung volume and lower compliance as opposed to a higher non-aerated lung mass and higher mechanical power when compared to subphenotype 1 (non-recruitable). Patients with subphenotype 2 had more decrease in non-aerated lung mass in response to a standardized recruitment manoeuvre (p = 0.024) and were mechanically ventilated longer until successful extubation (adjusted SHR 0.46, 95% CI 0.23-0.91, p = 0.026), while no difference in survival was found (p = 0.814). CONCLUSIONS: A recruitable and non-recruitable subphenotype were identified in patients with COVID-19-related ARDS. These findings are in line with previous studies in non-COVID-19-related ARDS and suggest that a combination of imaging and clinical respiratory parameters could facilitate the identification of recruitable lungs before the manoeuvre.