Effects of Positive End-Expiratory Pressure in "High Compliance" Severe Acute Respiratory Syndrome Coronavirus 2 Acute Respiratory Distress Syndrome.

OBJECTIVES: Clinical observation suggests that early acute respiratory distress syndrome induced by the severe acute respiratory syndrome coronavirus 2 may be "atypical" due to a discrepancy between a relatively unaffected static respiratory system compliance and a significant hypoxemia. This would imply an "atypical" response to the positive end-expiratory pressure. DESIGN: Single-center, unblinded, crossover study. SETTING: ICU of Bari Policlinico Academic Hospital (Italy), dedicated to care patients with confirmed diagnosis of novel coronavirus disease 2019. PATIENTS: Eight patients with early severe acute respiratory syndrome coronavirus 2 acute respiratory distress syndrome and static respiratory compliance higher than or equal to 50 mL/cm H2O. INTERVENTIONS: We compared a "lower" and a "higher" positive end-expiratory pressure approach, respectively, according to the intervention arms of the acute respiratory distress syndrome network and the positive end-expiratory pressure setting in adults with acute respiratory distress syndrome studies. MEASUREMENTS AND MAIN RESULTS: Patients were ventilated with the acute respiratory distress syndrome network and, subsequently, with the ExPress protocol. After 1 hour of ventilation, for each protocol, we recorded arterial blood gas, respiratory mechanics, alveolar recruitment, and hemodynamic variables. Comparisons were performed with analysis of variance for repeated measures or Friedman test as appropriate. Positive end-expiratory pressure was increased from 9 ± 3.5 to 17.7 ± 1.7 cm H2O (p < 0.01). Alveolar recruitment was 450 ± 111 mL. Static respiratory system compliance decreased from 58.3 ± 7.6 mL/cm H2O to 47.4 ± 14.5 mL/cm H2O (p = 0.018) and the "stress index" increased from 0.97 ± 0.03 to 1.22 ± 0.07 (p < 0.001). The PaO2/FIO2 ratio increased from 131 ± 22 to 207 ± 41 (p < 0.001), and the PaCO2 increased from 45.9 ± 12.7 to 49.8 ± 13.2 mm Hg (p < 0.001). The cardiac index went from 3.6 ± 0.4 to 2.9 ± 0.6 L/min/m (p = 0.01). CONCLUSIONS: Our data suggest that the "higher" positive end-expiratory pressure approach in patients with severe acute respiratory syndrome coronavirus 2 acute respiratory distress syndrome and high compliance improves oxygenation and lung aeration but may result in alveolar hyperinflation and hemodynamic alterations.

A Lower Global Lung Ultrasound Score Is Associated with Higher Likelihood of Successful Extubation in Invasively Ventilated COVID-19 Patients.

Lung ultrasound (LUS) can be used to assess loss of aeration, which is associated with outcome in patients with coronavirus disease 2019 (COVID-19) presenting to the emergency department. We hypothesized that LUS scores are associated with outcome in critically ill COVID-19 patients receiving invasive ventilation. This retrospective international multicenter study evaluated patients with COVID-19-related acute respiratory distress syndrome (ARDS) with at least one LUS study within 5 days after invasive mechanical ventilation initiation. The global LUS score was calculated by summing the 12 regional scores (range 0-36). Pleural line abnormalities and subpleural consolidations were also scored. The outcomes were successful liberation from the ventilator and intensive care mortality within 28 days, analyzed with multistate, competing risk proportional hazard models. One hundred thirty-seven patients with COVID-19-related ARDS were included in our study. The global LUS score was associated with successful liberation from mechanical ventilation (hazard ratio [HR]: 0.91 95% confidence interval [CI] 0.87-0.96; P = 0.0007) independently of the ARDS severity, but not with 28 days mortality (HR: 1.03; 95% CI 0.97-1.08; P = 0.36). Subpleural consolidation and pleural line abnormalities did not add to the prognostic value of the global LUS score. Examinations within 24 hours of intubation showed no prognostic value. To conclude, a lower global LUS score 24 hours after invasive ventilation initiation is associated with increased probability of liberation from the mechanical ventilator COVID-19 ARDS patients, independently of the ARDS severity.

Tracheostomy Timing and Outcome in Severe COVID-19: The WeanTrach Multicenter Study.

BACKGROUND: Tracheostomy can be performed safely in patients with coronavirus disease 2019 (COVID-19). However, little is known about the optimal timing, effects on outcome, and complications. METHODS: A multicenter, retrospective, observational study. This study included 153 tracheostomized COVID-19 patients from 11 intensive care units (ICUs). The primary endpoint was the median time to tracheostomy in critically ill COVID-19 patients. Secondary endpoints were survival rate, length of ICU stay, and post-tracheostomy complications, stratified by tracheostomy timing (early versus late) and technique (surgical versus percutaneous). RESULTS: The median time to tracheostomy was 15 (1-64) days. There was no significant difference in survival between critically ill COVID-19 patients who received tracheostomy before versus after day 15, nor between surgical and percutaneous techniques. ICU length of stay was shorter with early compared to late tracheostomy (p < 0.001) and percutaneous compared to surgical tracheostomy (p = 0.050). The rate of lower respiratory tract infections was higher with surgical versus percutaneous technique (p = 0.007). CONCLUSIONS: Among critically ill patients with COVID-19, neither early nor percutaneous tracheostomy improved outcomes, but did shorten ICU stay. Infectious complications were less frequent with percutaneous than surgical tracheostomy.

Markers of endothelial and epithelial pulmonary injury in mechanically ventilated COVID-19 ICU patients.

BACKGROUND: Biomarkers can be used to detect the presence of endothelial and/or alveolar epithelial injuries in case of ARDS. Angiopoietin-2 (Ang-2), soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion protein-1 (VCAM-1), P-selectin and E-selectin are biomarkers of endothelial injury, whereas the receptor for advanced glycation end-products (RAGE) reflects alveolar epithelial injury. The aims of this study were to evaluate whether the plasma concentration of the above-mentioned biomarkers was different 1) in survivors and non-survivors of COVID-19-related ARDS and 2) in COVID-19-related and classical ARDS. METHODS: This prospective study was performed in two COVID-19-dedicated Intensive Care Units (ICU) and one non-COVID-19 ICU at Ferrara University Hospital. A cohort of 31 mechanically ventilated patients with COVID-19 ARDS and a cohort of 11 patients with classical ARDS were enrolled. Ang-2, ICAM-1, VCAM-1, P-selectin, E-selectin and RAGE were determined with a bead-based multiplex immunoassay at three time points: inclusion in the study (T1), after 7 ± 2 days (T2) and 14 ± 2 days (T3). The primary outcome was to evaluate the plasma trend of the biomarker levels in survivors and non-survivors. The secondary outcome was to evaluate the differences in respiratory mechanics variables and gas exchanges between survivors and non-survivors. Furthermore, we compared the plasma levels of the biomarkers at T1 in patients with COVID-19-related ARDS and classical ARDS. RESULTS: In COVID-19-related ARDS, the plasma levels of Ang-2 and ICAM-1 at T1 were statistically higher in non-survivors than survivors, (p = 0.04 and p = 0.03, respectively), whereas those of P-selectin, E-selectin and RAGE did not differ. Ang-2 and ICAM-1 at T1 were predictors of mortality (AUROC 0.650 and 0.717, respectively). At T1, RAGE and P-selectin levels were higher in classical ARDS than in COVID-19-related ARDS. Ang-2, ICAM-1 and E-selectin were lower in classical ARDS than in COVID-19-related ARDS (all p < 0.001). CONCLUSIONS: COVID-19 ARDS is characterized by an early pulmonary endothelial injury, as detected by Ang-2 and ICAM-1. COVID-19 ARDS and classical ARDS exhibited a different expression of biomarkers, suggesting different pathological pathways. Trial registration NCT04343053 , Date of registration: April 13, 2020.

Focus on renal blood flow in mechanically ventilated patients with SARS-CoV-2: a prospective pilot study.

Mechanically ventilated patients with ARDS due to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) seem particularly susceptible to AKI. Our hypothesis was that the renal blood flow could be more compromised in SARS-CoV-2 patients than in patients with "classical" ARDS. We compared the renal resistivity index (RRI) and the renal venous flow (RVF) in ARDS patients with SARS-CoV-2 and in ARDS patients due to other etiologies. Prospective, observational pilot study performed on 30 mechanically ventilated patients (15 with SARS-COV-2 ARDS and 15 with ARDS). Mechanical ventilation settings included constant-flow controlled ventilation, a tidal volume of 6 ml/kg of ideal body weight and the PEEP level titrated to the lowest driving pressure. Ultrasound Doppler measurements of RRI and RVF pattern were performed in each patient. Patients with SARS-COV-2 ARDS had higher RRI than patients with ARDS (0.71[0.67-0.78] vs 0.64[0.60-0.74], p = 0.04). RVF was not-continuous in 9/15 patients (71%) in the SARS-COV-2 ARDS group and in and 5/15 (33%) in the ARDS group (p = 0.27). A linear correlation was found between PEEP and RRI in patients with SARS-COV-2 ARDS (r2 = 0.31; p = 0.03) but not in patients with ARDS. Occurrence of AKI was 53% in patients with SARS-COV-2 ARDS and 33% in patients with ARDS (p = 0.46). We found a more pronounced impairment in renal blood flow in mechanically ventilated patients with SARS-COV-2 ARDS, compared with patients with "classical" ARDS.