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BACKGROUND: The optimal strategy for initial respiratory support in patients with respiratory failure associated with COVID-19 is unclear, and the initial strategy may affect outcomes. RESEARCH QUESTION: Which initial respiratory support strategy is associated with improved outcomes in patients with COVID-19 with acute respiratory failure? STUDY DESIGN AND METHODS: All patients with COVID-19 requiring respiratory support and admitted to a large health care network were eligible for inclusion. We compared patients treated initially with noninvasive respiratory support (NIRS; noninvasive positive pressure ventilation by facemask or high-flow nasal oxygen) with patients treated initially with invasive mechanical ventilation (IMV). The primary outcome was time to in-hospital death analyzed using an inverse probability of treatment weighted Cox model adjusted for potential confounders. Secondary outcomes included unweighted and weighted assessments of mortality, lengths of stay (ICU and hospital), and time to intubation. RESULTS: Nearly one-half of the 2,354 patients (47%) who met inclusion criteria received IMV first, and 53% received initial NIRS. Overall, in-hospital mortality was 38% (37% for IMV and 39% for NIRS). Initial NIRS was associated with an increased hazard of death compared with initial IMV (hazard ratio, 1.42; 95% CI, 1.03-1.94), but also an increased hazard of leaving the hospital sooner that waned with time (noninvasive support by time interaction: hazard ratio, 0.97; 95% CI, 0.95-0.98). INTERPRETATION: Patients with COVID-19 with acute hypoxemic respiratory failure initially treated with NIRS showed an increased hazard of in-hospital death.
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Rationale: Noninvasive respiratory support modalities are common alternatives to mechanical ventilation for patients with early acute hypoxemic respiratory failure. These modalities include noninvasive positive pressure ventilation, using either continuous or bilevel positive airway pressure, and nasal high flow using a high flow nasal cannula system. However, outcomes data historically compare noninvasive respiratory support to conventional oxygen rather than to mechanical ventilation. Objectives: The goal of this study was to compare the outcomes of in-hospital death and alive discharge in patients with acute hypoxemic respiratory failure when treated initially with noninvasive respiratory support compared to patients treated initially with invasive mechanical ventilation. Methods: We used a validated phenotyping algorithm to classify all patients with eligible International Classification of Diseases codes at a large healthcare network between January 1, 2018 and December 31, 2019 into noninvasive respiratory support and invasive mechanical ventilation cohorts. The primary outcome was time-to-in-hospital death analyzed using an inverse probability of treatment weighted Cox model adjusted for potential confounders, with estimated cumulative incidence curves. Secondary outcomes included time-to-hospital discharge alive. A secondary analysis was conducted to examine potential differences between noninvasive positive pressure ventilation and nasal high flow. Results: During the study period, 3177 patients met inclusion criteria (40% invasive mechanical ventilation, 60% noninvasive respiratory support). Initial noninvasive respiratory support was not associated with a decreased hazard of in-hospital death (HR: 0.65, 95% CI: 0.35 - 1.2), but was associated with an increased hazard of discharge alive (HR: 2.26, 95% CI: 1.92 - 2.67). In-hospital death varied between the nasal high flow (HR 3.27, 95% CI: 1.43 - 7.45) and noninvasive positive pressure ventilation (HR 0.52, 95% CI 0.25 - 1.07), but both were associated with increased likelihood of discharge alive (nasal high flow HR 2.12, 95 CI: 1.25 - 3.57; noninvasive positive pressure ventilation HR 2.29, 95% CI: 1.92 - 2.74). Conclusion: These observational data from a large healthcare network show that noninvasive respiratory support is not associated with reduced hazards of in-hospital death but is associated with hospital discharge alive. There are also potential differences between the noninvasive respiratory support modalities.