Cardiovascular Disease and Severe Hypoxemia Are Associated with Higher Rates of Non-Invasive Respiratory Support Failure in COVID-19 Pneumonia

RATIONALE Acute hypoxemic respiratory failure (AHRF) is the major complication of coronavirus disease 2019 (COVID-19), yet optimal respiratory support strategies are uncertain. We aimed to describe outcomes with highflow oxygen delivered through nasal cannula (HFNC) and non-invasive positive pressure ventilation (NIPPV) in COVID-19 AHRF and identify individual factors associated with non-invasive respiratory support failure. METHODS We conducted a retrospective cohort study of hospitalized adults with COVID-19 within a large academic health system in New York City early in the pandemic to describe outcomes with HFNC and NIPPV. Patients were categorized into the HFNC cohort if they received HFNC but not NIPPV, whereas the NIPPV cohort included patients who received NIPPV with or without HFNC. We described rates of HFNC and NIPPV success, defined as live discharge without endotracheal intubation (ETI). Further, using Fine-Gray sub-distribution hazard models, we identified demographic and patient characteristics associated with HFNC and NIPPV failure, defined as the need for ETI and/or in-hospital mortality. RESULTS Of the 331 patients in the HFNC cohort, 154 (46.5%) patients were successfully discharged without requiring ETI. Of the 177 (53.5%) who experienced HFNC failure, 100 (56.5%) required ETI and 135 (76.3%) patients ultimately died. Among the 747 patients in the NIPPV cohort, 167 (22.4%) patients were successfully discharged without requiring ETI, and 8 (1.1%) were censored. Of the 572 (76.6%) patients who failed NIPPV, 338 (59.1%) required ETI and 497 (86.9%) ultimately died. In adjusted models, significantly increased risk of HFNC and NIPPV failure was observed among patients with co-morbid cardiovascular disease (sub-distribution hazard ratio (sHR) 1.82;95% confidence interval (CI), 1.17-2.83 and sHR 1.40;95% CI 1.06-1.84, respectively). Conversely, a higher oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2) at HFNC and NIPPV initiation was associated with reduced risk of failure (sHR, 0.32;95% CI 0.19-0.54, and sHR 0.34;95% CI 0.21-0.55, respectively). CONCLUSIONS A subset of patients with COVID-19 AHRF was effectively managed with non-invasive respiratory modalities and achieved successful hospital discharge without requiring ETI. Notably, patients with co-morbid cardiovascular disease and more severe hypoxemia experienced lower success rates with both HFNC and NIPPV. Identification of specific patient factors may help inform more selective use of non-invasive respiratory strategies, and allow for a more personalized approach to the management of COVID-19 AHRF in pandemic settings.