Breathing pattern, accessory respiratory muscles work, and gas exchange evaluation for prediction of NIV failure in moderate-to-severe COVID-19- associated ARDS after deterioration of respiratory failure outside ICU: the COVID-NIV observational study

Background: Data on the efficacy of non-invasive ventilation (NIV) after progression of respiratory failure in patients who have already received oxygen therapy, or CPAP outside ICU is limited. The aim of the study was to find predictors of NIV failure based on breathing pattern, gas exchange, and accessory respiratory muscles evaluation in patients who progressed to moderate-to-severe COVID-19 ARDS. Methods: : This was a prospective observational study in patients with moderate-to-severe COVID-19-ARDS on NIV (n=80) admitted to COVID-ICU of Sechenov University. Combined success rate for conventional oxygen and CPAP outside ICU was 78.6% (440 of 560 patients). The primary endpoints were intubation rate and mortality. We measured respiratory rate, exhaled tidal volume (Vte), mean peak inspiratory flow (PIF), inspiratory time (Ti), PaO 2 , SpO 2 , end-tidal carbon dioxide (P ET CO 2 ), and Patrick score, and calculated ROX index, PaO 2 /FiO 2 , ventilatory ratio, and alveolar dead space (Vdalv/Vt) on Days 1, 3, 5, 7, 10, and 14. For all significant differences between NIV success and failure groups in measured data we performed ROC-analysis. Results: : NIV failure rate in ICU after deterioration of respiratory failure outside ICU was 71.3% (n=57). Patients with the subsequent NIV failure were older at inclusion, more frail, had longer duration of disease before ICU admission, and higher rate of CPAP use outside ICU. ROC-analysis revealed that the following respiratory parameters after 48 hours of NIV can serve as a predictors for NIV failure in moderate-to-severe COVID-19-associated ARDS: PaO 2 /FiO 2 <112 mmHg (AUROC 0.90 (0.93-0.97), p<0.0001); P ET CO 2 <19.5 mmHg (AUROC 0.84 (0.73-0.94), p 0.43 (AUROC 0.78 (0.68-0.90), p<0.0001); ROX-index < 5.02 (AUROC 0.89 (0.81-0.97), p 2 points (AUROC 0.87 (0.78-0.96), p=0.006). Conclusion: In patients who progressed to moderate-to-severe COVID-19-ARDS probability of NIV success rate was about 1/3. Prediction of the NIV failure can be made after 48 hours based on ROX index<5.02, PaO 2 /FiO 2 <112 mmHg, P ET CO2=2. Trial registration: ClinicalTrials.gov identifier: NCT04667923, registered on 16/12/2020. https://clinicaltrials.gov/ct2/show/NCT04667923?term=NCT04667923&draw=2&rank=1