High-Flow Nasal Oxygen in Patients With COVID-19-Associated Acute Respiratory Failure

Ricard Mellado-Artigas; Bruno L. Ferreyro; Federico Angriman; Maria Hernandez-Sanz; Egoitz Arruti; Antoni Torres; Jesus Villar; Laurent Brochard; Carlos Ferrando

Disclosures

Crit Care. 2021;25(58) 

In This Article

Results

Study Population

From March 12 to August 13, 2020, 468 critically ill patients with COVID-19 patients fulfilled the inclusion criteria for the present study (Figure 1). Three-hundred and twelve (67%) patients were intubated on day 1 (37 of them after a HFNO trial). The remaining 156 patients received HFNO, of whom 49 (31%) received intubation from day 2 and onward. Baseline characteristics for the entire population (before matching) are shown in Additional file 1: e-table 2. After propensity score matching, 61 patients in each group were included. Overall, we observed adequate balance between most of baseline characteristics with the exception of baseline ROX index, systolic blood pressure, Glasgow Coma Scale, pH, inspired oxygen fraction (FiO2) and active cancer (Table 1).

Figure 1.

Study flowchart

Study Outcomes

When compared to an early intubation strategy, the use of HFNO was associated with an increase in VFDs (mean difference 8.0 days; 95% CI 4.4 to 11.7 days), and a reduction in ICU length of stay (mean difference -8.2 days; 95% CI -12.7 to -3.6 days). Intubation rate was 38% in the conservative group (compared to an expected 100% in the early intubation group). No difference was observed in all-cause in-hospital mortality between groups (OR 0.64; 95% CI 0.25 to 1.64) (Figure 2).

Figure 2.

Effect of a conservative approach (use of high-flow nasal oxygen) compared to early intubation on main outcomes of interest for patients with COVID-19 associated acute respiratory failure. Difference is expressed as mean difference for continuous variables or absolute risk difference for in-hospital mortality. In-hospital mortality in both groups expressed as cumulative incidence. CI: Confidence interval. HFNO: high-flow nasal oxygen. (1) Cumulative incidence and cumulative incidence difference (i.e., risk difference; 95% CI) reported for both groups. Results for ventilator-free days and intensive care unit length of stay were rounded up or down to the closest whole number

Sensitivity Analysis

All sensitivity analysis yielded similar results to the main estimates (Additional file 1: e-table 3). Specifically, in the complete-case analysis, the use of HFNO remained associated with an increase in VFDs (mean difference 6.8 days; 95% CI 1.5 to 12.1 days) and shorter ICU length of stay (mean difference 12.3 days; 95% CI 19.8 to 4.7). No difference was observed in all-cause hospital mortality (OR 1.64; 95% CI 0.40 to 6.66). Furthermore, after adjusting for imbalanced covariates, namely the presence of an active cancer, Glasgow Coma Scale, ROX index and FiO2, the use of HFNO remained associated with an increase in VFDs (mean difference 7.7 days; 95% CI 3.6 to 11.9) and shorter ICU length of stay (mean difference -9.4; 95% CI -14.7 to -4.0) when compared to an early intubation approach. No difference was observed in all-cause hospital mortality (OR 0.75; 95% CI 0.22 to 2.55). The estimated E-value for the primary analysis for the effects of HFNO on VFDs was 3.28 (e-Figure 2 in Additional file 1). Finally, no modification of the effects of HFNO on VFDs was evident by baseline PaO2/FiO2 ratio (Additional file 1: e-table 4).

Subgroup Analysis by the Time of Intubation

Of the 61 included patients who initially received a conservative strategy with HFNO, 23 (38%) were intubated from day 2 onward. When compared to patients intubated early in their ICU course, VFDs (median 10 vs 15 days, p = 0.88), ICU length of stay (12 vs 17 days, p = 0.41) and in-hospital mortality (26% vs 21%, p = 0.77) did not differ (Additional file 1: Table S5).

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